bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictors of DAPSA28 remission in patients with psoriatic arthritis initiating a first TNF inhibitor: results from 13 European registries
Authors: Linde Louise , Ørnbjerg Lykke M , Georgiadis Stylianos , H. Rasmussen Simon , Lindström Ulf , Askling Johan , Michelsen Brigitte , Di Giuseppe Daniela , Wallman Johan K , Gudbjornsson Bjorn , Love Thorvardur Jon , Nordström Dan C , Yli-Kerttula Timo , Nekvindová Lucie , Vencovský Jiří , Iannone Florenzo , Cauli Alberto , Loft Anne Gitte , Glintborg Bente , Laas Karin , Rotar Ziga , Tomšič Matija , Macfarlane Gary J , Möller Burkhard , van de Sande Marleen , Codreanu Catalin , Nissen Michael J , Birlik Merih , Erten Sukran , Santos Maria J , Vieira-Sousa Elsa , Hetland Merete L , Østergaard Mikkel
Published: June 2023

Objectives

In bio-naïve patients with PsA initiating a TNF inhibitor (TNFi), we aimed to identify baseline predictors of Disease Activity index for PsA in 28 joints (DAPSA28) remission (primary objective) and DAPSA28 moderate response at 6 months, as well as drug retention at 12 months across 13 European registries.

Methods

Baseline demographic and clinical characteristics were retrieved and the three outcomes investigated per registry and in pooled data, using logistic regression analyses on multiply imputed data. In the pooled cohort, selected predictors that were either consistently positive or negative across all three outcomes were defined as common predictors.

Results

In the pooled cohort (n = 13 369), 6-month proportions of remission, moderate response and 12-month drug retention were 25%, 34% and 63% in patients with available data (n = 6954, n = 5275 and n = 13 369, respectively). Five common baseline predictors of remission, moderate response and 12-month drug retention were identified across all three outcomes. The odds ratios (95% CIs) for DAPSA28 remission were: age, per year: 0.97 (0.96–0.98); disease duration, years (<2 years as reference): 2–3 years: 1.20 (0.89–1.60), 4–9 years: 1.42 (1.09–1.84), ≥10 years: 1.66 (1.26–2.20); men vs women: 1.85 (1.54–2.23); CRP of >10 vs ≤10 mg/l: 1.52 (1.22–1.89) and 1 mm increase in patient fatigue score: 0.99 (0.98–0.99).

Conclusion

Baseline predictors of remission, response and adherence to TNFi therapy were identified, of which five were common for all three outcomes, indicating that the predictors emerging from our pooled cohort may be considered generalizable from country level to disease level.
Legislating Through Policy Statements: The Authority of National Visions in the Arabian Gulf
Authors: Bantekas Ilias
Published: June 2023

National Visions are policy instruments characterized by an outlook that is constitutional in nature, while also appealing to a country’s external relations, as well as its citizens. They are unique to the law and policy of Gulf States and set out decade-long policy aims that are subsequently translated into legislation or/and foreign policy objectives. This article examines the sports-related dimension of the Qatari National Vision, which was the basis for the country’s bid for the 2022 FIFA World Cup. It is demonstrated that the constitutional nature of the sports dimension of the Vision helped to shape social attitudes in Qatar, as well as facilitate a rapid legislative reform in the field of labor relations, such that would have been unthinkable in the absence of strong sports-oriented policy underpinning the entire nation. National Visions should therefore be viewed as accelerators of social change and drivers of rapid legislative reform, even if they themselves do not outward display normative qualities.
The Vulnerability of Cuban Banana Production to Fusarium Wilt Caused by Tropical Race 4
Authors: Martínez de la Parte Einar , Pérez-Vicente Luis , García-Bastidas Fernando , Bermúdez-Caraballoso Idalmis , Schnabel Sabine , Meijer Harold J. G. , Kema Gert H. J.
Published: June 2023

Bananas are major agricultural commodities in Cuba. One of the main constraints of banana production worldwide is Fusarium wilt of banana. Recent outbreaks in Colombia, Perú, and Venezuela have raised widespread concern in Latin America due to the potential devastating impact on the sustainability of banana production, food security, and livelihoods of millions of people in the region. Here, we phenotyped 18 important Cuban banana and plantain varieties with two Fusarium strains—Tropical Race 4 (TR4) and Race 1—under greenhouse conditions. These varieties represent 72.8% of the national banana acreage in Cuba and are also widely distributed in Latin America and the Caribbean region. A broad range of disease responses from resistant to very susceptible was observed against Race 1. On the contrary, not a single banana variety was resistant to TR4. These results underscore that TR4 potentially threatens nearly 56% of the contemporary Cuban banana production area, which is planted with susceptible and very susceptible varieties, and call for a preemptive evaluation of new varieties obtained in the national breeding program and the strengthening of quarantine measures to prevent the introduction of TR4 into the country.
Management of anesthetic complications outside the operating room
Authors: Hardman Bailor , Karamchandani Kunal
Published: June 2023

Purpose of review

Nonoperating room anesthesia (NORA) procedures have seen a significant growth over the years along with an increase in the complexity and severity of cases. Providing anesthesia care in these often-unfamiliar locations is risky, and complications are common. This review aims to report the most recent updates regarding managing anesthesia-related complications in patients undergoing procedures in non-operating room locations.

Recent findings

Surgical innovations, advent of new technology, and the economics of a healthcare environment that strives to improve value by decreasing costs, has expanded the indications for and complexity of NORA cases. In addition, an aging population with increasing comorbidity burden, requirements for deeper levels of sedation have all increased the risk of complications in NORA environments. In such a situation, improvement in monitoring and oxygen delivery techniques, better ergonomics of NORA sites and development of multidisciplinary contingency plans are likely to improve our management of anesthesia-related complications.

Delivery of anesthesia care in out-of-operating room locations is associated with significant challenges. Meticulous planning, close communication with the procedural team, establishing protocols and pathways for help, along with interdisciplinary teamwork can facilitate safe, efficient, and cost-effective procedural care in the NORA suite.
Pharmacokinetic and pharmacodynamic drug display and simulation systems in anesthesia practice
Authors: Kennedy R Ross
Published: June 2023

Purpose of review

This review explores the use of tools and displays based on pharmacokinetic and pharmacodynamic (PK/PD) modelling of drugs used in anesthesia. The primary focus is on those tools designed to illustrate the interactions between two or more drugs, or classes of drugs, and in particular, their use in a real-time clinical support role. Off-line, educational tools are also explored.

Recent findings

Despite initial promise and encouraging supporting data, the use of real-time display of PK/PD is not common except in target-controlled infusion (TCI) pumps.

PK/PD simulation is a useful tool for exposition of the relationship between drug dosing and effect. The initial promise of real-time tools has yet to be realized in routine clinical practice.
DHCR7 Expression Predicts Poor Outcomes and Mortality From Sepsis
Authors: Guirgis Faheem W. , Jacob Vinitha , Wu Dongyuan , Henson Morgan , Daly-Crews Kimberly , Hopson Charlotte , Black Lauren Page , DeVos Elizabeth L. , Sulaiman Dawoud , Labilloy Guillaume , Brusko Todd M. , Shavit Jordan A. , Bertrand Andrew , Feldhammer Matthew , Baskovich Brett , Graim Kiley , Datta Susmita , Reddy Srinivasa T.
Published: June 2023

IMPORTANCE:

This is a study of lipid metabolic gene expression patterns to discover precision medicine for sepsis.

OBJECTIVES:

Sepsis patients experience poor outcomes including chronic critical illness (CCI) or early death (within 14 d). We investigated lipid metabolic gene expression differences by outcome to discover therapeutic targets.

DESIGN, SETTING, AND PARTICITPANTS:

Secondary analysis of samples from prospectively enrolled sepsis patients (first 24 hr) and a zebrafish endotoxemia model for drug discovery. Patients were enrolled from the emergency department or ICU at an urban teaching hospital. Enrollment samples from sepsis patients were analyzed. Clinical data and cholesterol levels were recorded. Leukocytes were processed for RNA sequencing and reverse transcriptase polymerase chain reaction. A lipopolysaccharide zebrafish endotoxemia model was used for confirmation of human transcriptomic findings and drug discovery.

MAIN OUTCOMES AND MEASURES:

The derivation cohort included 96 patients and controls (12 early death, 13 CCI, 51 rapid recovery, and 20 controls) and the validation cohort had 52 patients (6 early death, 8 CCI, and 38 rapid recovery).

RESULTS:

The cholesterol metabolism gene 7-dehydrocholesterol reductase (DHCR7) was significantly up-regulated in both derivation and validation cohorts in poor outcome sepsis compared with rapid recovery patients and in 90-day nonsurvivors (validation only) and validated using RT-qPCR analysis. Our zebrafish sepsis model showed up-regulation of dhcr7 and several of the same lipid genes up-regulated in poor outcome human sepsis (dhcr24, sqlea, cyp51, msmo1, and ldlra) compared with controls. We then tested six lipid-based drugs in the zebrafish endotoxemia model. Of these, only the Dhcr7 inhibitor AY9944 completely rescued zebrafish from lipopolysaccharide death in a model with 100% lethality.

CONCLUSIONS:

DHCR7, an important cholesterol metabolism gene, was up-regulated in poor outcome sepsis patients warranting external validation. This pathway may serve as a potential therapeutic target to improve sepsis outcomes.
E3 Ubiquitin Ligases in Endothelial Dysfunction and Vascular Diseases: Roles and Potential Therapies
Authors: Wang Yihan , Zhan Yixiong , Wang Linsiqi , Huang Xuan , Xin Hong-Bo , Fu Mingui , Qian Yisong
Published: June 2023

Ubiquitin E3 ligases are a structurally conserved family of enzymes that exert a variety of regulatory functions in immunity, cell death, and tumorigenesis through the ubiquitination of target proteins. Emerging evidence has shown that E3 ubiquitin ligases play crucial roles in the pathogenesis of endothelial dysfunction and related vascular diseases. Here, we reviewed the new findings of E3 ubiquitin ligases in regulating endothelial dysfunction, including endothelial junctions and vascular integrity, endothelial activation, and endothelial apoptosis. The critical role and potential mechanism of E3 ubiquitin ligases in vascular diseases, such as atherosclerosis, diabetes, hypertension, pulmonary hypertension, and acute lung injury, were summarized. Finally, the clinical significance and potential therapeutic strategies associated with the regulation of E3 ubiquitin ligases were also proposed.
Using Prior Knowledge on Systems Through PBPK to Gain Further Insight into Routine Clinical Data on Trough Concentrations: The Case of Tacrolimus in Chronic Kidney Disease
Authors: El-Khateeb Eman , Chinnadurai Rajkumar , Al Qassabi Jokha , Scotcher Daniel , Darwich Adam S. , Kalra Philip A. , Rostami-Hodjegan Amin
Published: June 2023

Background:

Routine therapeutic drug monitoring (TDM) relies heavily on measuring trough drug concentrations. Trough concentrations are affected not only by drug bioavailability and clearance, but also by various patient and disease factors and the volume of distribution. This often makes interpreting differences in drug exposure from trough data challenging. This study aimed to combine the advantages of top-down analysis of therapeutic drug monitoring data with bottom-up physiologically-based pharmacokinetic (PBPK) modeling to investigate the effect of declining renal function in chronic kidney disease (CKD) on the nonrenal intrinsic metabolic clearance (CL

int
) of tacrolimus as a case example.

Methods:

Data on biochemistry, demographics, and kidney function, along with 1167 tacrolimus trough concentrations for 40 renal transplant patients, were collected from the Salford Royal Hospital's database. A reduced PBPK model was developed to estimate CL

int
for each patient. Personalized unbound fractions, blood-to-plasma ratios, and drug affinities for various tissues were used as priors to estimate the apparent volume of distribution. Kidney function based on the estimated glomerular filtration rate (eGFR) was assessed as a covariate for CL

int
using the stochastic approximation of expectation and maximization method.

Results:

At baseline, the median (interquartile range) eGFR was 45 (34.5–55.5) mL/min/1.73 m2. A significant but weak correlation was observed between tacrolimus CL

int
and eGFR (r = 0.2, P < 0.001). The CL

int
declined gradually (up to 36%) with CKD progression. Tacrolimus CL

int
did not differ significantly between stable and failing transplant patients.

Conclusions:

Kidney function deterioration in CKD can affect nonrenal CL

int
for drugs that undergo extensive hepatic metabolism, such as tacrolimus, with critical implications in clinical practice. This study demonstrates the advantages of combining prior system information (via PBPK) to investigate covariate effects in sparse real-world datasets.
Effect of Tacrolimus Time in Therapeutic Range on Postoperative Recurrence in Patients Undergoing Liver Transplantation for Liver Cancer
Authors: Lao Qianying , Wu Xuanyu , Zheng Xinxin , Hu Jinwei , Huang Siqi , Li Danying , Du Yao , Yang Na , Zhu Huaijun
Published: June 2023

Background and Objective:

Liver cancer is the second highest cause of cancer-related deaths worldwide. It is commonly treated with liver transplantation, where tacrolimus is typically used as an antirejection immunosuppressant. The purpose of this study was to evaluate the effect of tacrolimus time in therapeutic range (TTR) on liver cancer recurrence in liver transplant recipients and to compare the performance of TTRs calculated according to the target ranges recommended in published guidelines.

Methods:

A total of 84 patients who underwent liver transplantation for liver cancer were retrospectively included. Tacrolimus TTR was calculated using linear interpolation from the date of transplantation until recurrence or the last follow-up according to target ranges recommended in the Chinese guideline and international expert consensus.

Result:

Twenty-four recipients developed liver cancer recurrence after liver transplantation. The CTTR (TTR calculated according to the Chinese guideline) for the recurrence group was significantly lower than that of the nonrecurrence group (26.39% vs. 50.27%, P < 0.001), whereas the ITTR (TTR calculated according to the international consensus) was not significantly different between the two groups (47.81% vs. 56.37%, P = 0.165). Multivariate survival analysis revealed that age, microvascular invasion, hepatocellular carcinoma, CTTR, and mean tacrolimus trough concentration were independent predictors of liver cancer recurrence after liver transplantation.

Conclusions:

TTR predicts liver cancer recurrence in liver transplant recipients. The range of tacrolimus concentrations recommended in the Chinese guideline was more beneficial than that recommended in the international consensus for Chinese patients undergoing liver transplantation for liver cancer.
The Value of Case Reports in Plastic Surgery: An Analysis of 68,444 Articles across Six Major Plastic Surgery Journals
Authors: Ormseth Benjamin H. , Sarac Benjamin A. , Westvik Tormod S. , Janis Jeffrey E.
Published: June 2023

Background:

Case reports provide a salient contribution to the field of plastic surgery through the timely dissemination of knowledge on previously underreported topics. Once a time-honored hallmark of the surgical literature, the perceived value of case reports has decreased with the ongoing prioritization of higher levels of evidence. In this study, we aimed to assess long-term trends in case report publication rates and discuss the continued merits of case reports in the modern-day landscape.

Methods:

A PubMed search was used to identify articles published in six prominent plastic surgery journals since 1980. Articles were separated as case reports versus all other publication types. The total number of articles published by group was tracked, and citation rates were compared across groups. Additionally, the most cited articles from each journal were identified for both groups.

Results:

A total of 68,444 articles were included for analysis. In 1980, there were 181 case reports published compared with 413 other articles across all six journals. In 2022, there were 188 case reports published compared with 3343 other articles. When comparing citations per year of case reports versus other article types across all journals since 1980, case reports were found to be cited significantly less frequently (P < 0.001).

Conclusions:

Case reports have been published and cited less frequently than other types of literature over the last 42 years. However, despite these trends, they have demonstrated significant historical contributions and provide continued value as an impactful forum for highlighting novel clinical entities.
Low-dose supplementation with retinol improves retinal function in eyes with age-related macular degeneration but without reticular pseudodrusen
Authors: Pfau Kristina , Jeffrey Brett G. , Cukras Catherine A.
Published: June 2023

Aims:

To determine the functional impact of oral Vitamin A supplementation in patients with intermediate age-related macular degeneration (iAMD) with and without reticular pseudodrusen (RPD) demonstrating dysfunction in dark adaptation (DA).

Methods:

Five patients with iAMD and without RPD (AMD group; mean ± SD age 78.0 ± 4.7 years) and seven with RPD (RPD group; age 74.1 ± 11.2 years) were supplemented with 16,000 IU of Vitamin A palmitate for 8 weeks. Assessment at baseline, 4, 8 and 12 weeks included scotopic thresholds, dark adaptation, best-corrected and low luminance visual acuities and the low-luminance quality of life questionnaire.

Results:

In the linear mixed model, RIT improved significantly in the AMD group (mean[95% CI] change -1.1 min [-1.8; -0.5] after 4 weeks (p<0.001) and -2.2 min[-2.9; 1.6] after 8 weeks of Vitamin A supplementation (p<0.001). The DA cone plateau also significantly improved (i.e. more sensitive cone threshold) at 4 and 8 weeks (p=0.026 and p=0.001). No other parameters improved in the AMD group and there was no significant improvement in any parameter in the RPD group despite significantly elevated serum Vitamin A levels measurable in both groups after supplementation (p=0.024 and p=0.013).

Conclusions:

Supplementation with 16,000IU Vitamin A, a lower dose than used in previous studies, partially overcomes the pathophysiologic functional changes in AMD eyes. The lack of improvement in the RPD group may indicate structural impediments to increasing vitamin A availability in these patients, and/or may reflect the higher variability observed in the functional parameters for this group.
Pure Red Cell Aplasia Caused by Parvovirus B19 in Patients with Human Immunodeficiency Virus Infection: A Series of Four Cases
Authors: Xu Feilong , Wang Yulong , Fan Linjin , He Yaozu , Chen Xiejie , Ye Pengfei , Liu Linna , Qian Jun , Li Linghua
Published: June 2023

Parvovirus B19 (B19V) infection can cause pure red cell aplasia (PRCA) in patients with human immunodeficiency virus (HIV) infection. Intravenous immunoglobulin (IVIG) is a preferred treatment option. From July 2019 to March 2022, four patients with HIV infection were admitted to Guangzhou Eighth People’s Hospital with dizziness and fatigue and were diagnosed with PRCA. Blood investigations revealed severe anemia and the B19V genome. Therefore, the four patients were diagnosed with B19V-induced PRCA. All four patients received red blood cell transfusion in the setting of antiretroviral therapy, and two of the four patients received intravenous immunoglobulin (IVIG). After 3–7 months of treatment, all four patients recovered, although two did not receive IVIG. This suggests that IVIG is not always necessary for the treatment of PRCA in patients with HIV infection and that effective antiretroviral therapy and immunological reconstitution play an important role in the eradication of parvovirus.
Influence of Refractive Error on Circumpapillary Structure–Function Versus Vessel Density–Function Relationships in Open Angle Glaucoma
Authors: Emoto Yoshinobu , Hollό Gábor , Kita Yoshiyuki , Saito Tsunehiro , Kita Ritsuko
Published: June 2023

Précis:

In Japanese open angle glaucoma (OAG) eyes correlation of 30-degree visual field mean deviation (MD) and visual field index (VFI) with circumpapillary vessel density is systematically stronger than that with circumpapillary retinal nerve fiber layer thickness (RNFLT), and is preserved in myopia and high myopia.

Purpose:

The purpose of this study was to investigate the influence of refractive error on the relationship between circumpapillary retinal nerve fiber layer thickness (cpRNFLT) and circumpapillary vessel density (cpVD), respectively, and global visual field parameters in Japanese open angle glaucoma (OAG) eyes.

Material and Methods:

One eye of 81 Japanese OAG patients (spherical equivalent refractive error: +3.0 to −9.0 D) underwent 360-degree cpRNFLT and cpVD measurements with Cirrus HD 5000-AngioPlex optical coherence tomography and 30-2 Humphrey visual field testing for mean deviation (MD) and visual field index (VFI) within 1 month. Correlations were determined for the whole population and each refractive error subgroups, separately: emmetropia/hyperopia (n=24), mild (n=18), moderate (n=20), and high myopia (n=19).

Results:

For the total population, significant strong to very strong correlations were found between MD, VFI, and both cpRNFLT and cpVD, respectively, with consistently higher r-values for cpVD (highest r-values: 0.532 for cpRNFLT, P<0.001; 0.722 for cpVD, P<0.001). Of the refractive subgroups, statistically significant correlations between cpRNFLT and the visual field parameters were maintained only in the hyperopia/emmetropia and moderate myopia groups. In contrast, statistically significant, strong to very strong correlations between cpVD and both MD and VFI, always exceeding the corresponding r-values found for cpRNFLT were found in all refractive subgroups, with r-values ranging between 0.548 (P=0.005) and 0.841 (P<0.001).

Conclusions:

Our results suggest that in Japanese OAG eyes the relationship of MD and VFI with cpVD is strong. It is systematically stronger than that with cpRNFLT and preserved in each conventional refractive error category including high myopia.
Treatment outcomes of radium-223 in patients with metastatic castration-resistant prostate cancer: An experience before National Health Insurance reimbursement in Taiwan
Authors: Yu Ping-Hsuan , Wei Tony Tzu-Chun , Chang Yen-Hwa , Chung Hsiao-Jen , Huang Eric Yi-Hsiu , Lin Tzu-Ping , Huang William J.
Published: June 2023

Background:

Radium-223 (Ra-223), an α–particle-emitting isotope, inhibits bony metastases and prevents patients from skeletal-related events in metastatic castration-resistant prostate cancer (mCRPC). We retrospectively reviewed the treatment response, predictive factors, and adverse events (AEs) of Ra-223 before the National Health Insurance reimbursement in a Taiwanese tertiary institute.

Methods:

Patients treated with Ra-223 before January 2019 were enrolled and categorized into progressive disease (PD) and clinical benefits (CB) groups. Laboratory data before and after the treatment were collected, and spider plots concerning percentage changes of alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and prostate-specific antigen (PSA) were prepared and calculated statistically. CB/PD, baseline ALP, LDH, and PSA levels were also adopted as stratification factors for overall survival (OS).

Results:

Among 19 patients included, 5 (26.3%) and 14 (73.4%) belonged to the PD and CB groups, respectively, with no significant difference observed in the baseline laboratory data. The percentage changes in ALP, LDH, and PSA levels after Ra-223 treatment were statistically significant among the two groups (ALP: CB 54.3 ± 21.4% vs PD 77.6 ± 11.8%, p = 0.044; LDH: CB 88.2 ± 22.8% vs PD 138.3 ± 49.0%, p = 0.046; PSA: CB 97.8 ± 61.7% vs PD 277.0 ± 101.1%, p = 0.002). The trends of LDH between the two groups in spider plot were separated significantly. There were no differences in the AEs between the two groups. CB had a longer median OS than the PD group (20.50 months vs 9.43 months, p = 0.009). Patients with LDH <250 U/L at baseline tended to have longer OS but without significance.

Conclusion:

The CB rate of Ra-223 was 73.7%. No predictive factor for treatment response was obtained from pretreatment data. The mean percentage changes in ALP, LDH, and PSA levels compared with baseline significantly differed between the CB and PD groups, especially the LDH levels. The CB and PD groups showed different OS, with LDH levels exhibiting the potential to predict OS.
Adherence to Psychotropic Medication Before and During COVID-19
Authors: Froese Brandon , Aquino Gian , Valencia Eunice , Tan Qier , Yogendran Marina , Katz Cara , Bolton James M. , Falk Jamie , Kowalec Kaarina , Chateau Dan , Delaney Joseph C. , Logsetty Sarvesh , Spiwak Rae , Enns Murray W. , Sareen Jitender , Alessi-Severini Silvia , Olafson Kendiss , Eltonsy Sherif , Leong Christine
Published: June 2023

Background

The coronavirus disease 2019 (COVID-19) pandemic and associated public health measures have shifted the way people access health care. We aimed to study the effects of the COVID-19 pandemic on psychotropic medication adherence.

Methods

A retrospective cohort study using administrative data from the Manitoba Centre for Health Policy Manitoba Population Research Data Repository was conducted. Outpatients who received at least 1 prescription for an antidepressant, antipsychotic, anxiolytic/sedative-hypnotic, cannabinoid, lithium, or stimulants from 2015 to 2020 in Manitoba, Canada, were included. Adherence was measured using the proportion of individuals with a mean possession ratio of ≥0.8 over each quarter. Each quarter of 2020 after COVID-19–related health measures were implemented was compared with the expected trend using autoregression models for time series data plus indicator variables. Odds ratio of drug discontinuation among those previously adherent in 2020 was compared with each respective quarter of 2019.

Results

There were 1,394,885 individuals in the study population in the first quarter of 2020 (mean [SD] age, 38.9 [23.4] years; 50.3% female), with 36.1% having a psychiatric diagnosis in the preceding 5 years. Compared with the expected trend, increases in the proportions of individuals adherent to antidepressants and stimulants were observed in the fourth quarter (October–December) of 2020 (both P < 0.001). Increases in the proportions of individuals with anxiolytic and cannabinoid adherence were observed in the third quarter (July–September) of 2020 (both P < 0.05), whereas a decrease was seen with stimulants in the same quarter (P < 0.0001). No significant changes were observed for antipsychotics. All drug classes except lithium had decreases in drug discontinuation in previously adherent patients during the pandemic compared with 2019.

Conclusions

Improved adherence to most psychotropic medications in the 9 months after public health restrictions were enacted was observed. Patients who were already adherent to their psychotropic medications were less likely to discontinue them during the pandemic.
Hematologic Malignancy Episodes Exceed Target Price in Oncology Care Model
Authors: Nguyen Jennifer , Maio Vittorio , Walsh Karen , Handley Nathan , Patel Shivangi , Keith Scott W. , Csik Valerie P.
Published: June 2023

The current study evaluated whether total cost of care (TCOC) and target price were aligned in Oncology Care Model (OCM) hematologic malignancy episodes and identified factors associated with episodes exceeding target price. Hematologic malignancy episodes from OCM performance period 1–4 reconciliation reports were identified from a large academic medical center. Of the 516 hematologic malignancies episodes included in the analysis, 283 (54.8%) exceeded the target price. Episode characteristics found to be statistically significantly associated with exceeding target price were Medicare Part B drug use and Part D drug use, novel therapy use, home health agency, and >730 days from last chemotherapy. The mean TCOC was $85 374 (± $26 342) for the episodes that exceeded target price while the mean target price was $56 106 (±$16 309). The results found a substantial misalignment between the TCOC and target price for hematologic malignancy episodes, adding to the existing evidence on the lack of adequate adjustment to the OCM target price.
Hospital Characteristics Associated With Clinically Integrated Network Participation
Authors: Hague Emily L. , Brown Timothy T. , Brewster Amanda , Shortell Stephen M. , Rodriguez Hector P.
Published: June 2023

Background:

Increased integration of physician organizations and hospitals into health systems has not necessarily improved clinical integration or patient outcomes. However, federal regulators have issued favorable opinions for clinically integrated networks (CINs) as a way to pursue coordination between hospitals and physicians. Hospital organizational affiliations, including independent practice associations (IPA), physician-hospital organizations (PHOs), and accountable care organizations (ACOs), may support CIN participation. No empirical evidence, however, exists about factors associated with CIN participation.

Methods:

Data from the 2019 American Hospital Association survey (n = 4405) were analyzed to quantify hospital CIN participation. Multivariable logistic regression models were estimated to examine whether IPA, PHO, and ACO affiliations were associated with CIN participation, controlling for market factors and hospital characteristics.

Results:

In 2019, 34.6% of hospitals participated in a CIN. Larger, not-for-profit, and metropolitan hospitals were more likely to participate in CINs. In adjusted analyses, hospitals participating in CINs were more likely to have an IPA (9.5% points, P < 0.001), a PHO (6.1% points, P < 0.001), and ACO (19.3% points, P < 0.001) compared with hospitals not participating in a CIN.

Conclusions:

Over one-third of hospitals participate in a CIN, despite limited evidence about their effectiveness in delivering value. Results suggest that CIN participation may be a response to integrative norms. Future work should attempt to better define CIN participation and strive to disentangle overlapping organizational participation.
Central Nervous System Tumor With BCL6 Corepressor Internal Tandem Duplication: Treatment Course of a Long-term Survivor
Authors: Bakkar Mohamad , Altinok Deniz , Kupsky William J. , Marupudi Neena I. , Chiang Jason , Gorsi Hamza S.
Published: June 2023

Central nervous system (CNS) tumor with BCL6 corepressor (BCOR) internal tandem duplication (ITD) is a newly described CNS tumor, characterized by in-frame ITDs of the BCOR gene. There is no standard practice regarding the management of this tumor. We report the clinical course of a 6-year-old boy who presented to the hospital with worsening headaches. Computed tomography scan showed a large right-sided parietal supratentorial mass and brain magnetic resonance imaging confirmed a 6×8×6.7 cm lobulated, solid but heterogeneous mass in the right parieto-occipital region. While initial pathology suggested a WHO grade 3 anaplastic meningioma, additional investigation with molecular analysis confirmed the diagnosis of high-grade neuroepithelial tumor with BCOR exon 15 ITD. This diagnosis was renamed CNS tumor with BCOR ITD in the 2021 WHO CNS tumor classification. The patient received 54 Gy of focal radiation and has no evidence of disease recurrence after 48 months from the end of treatment. As this is a newly discovered entity with only a few previous reports in the scientific literature, this report presents a unique treatment for this CNS tumor compared with those previously described.
Prosthesis nonuse and discontinuation in United States veterans with major limb amputation: Results of a national survey
Authors: Webster Joseph , Borgia Matthew , Resnik Linda
Published: June 2023

Background:

Prosthesis use in persons with amputation can improve mobility and functional independence. Better understanding of the reasons for and outcomes associated with prosthesis nonuse is important to optimize function and long-term health in persons with amputation.

Objectives:

Study objectives were to describe the rate, reasons for, and factors associated with never using or discontinuing prosthesis use in United States (US) veterans with amputation.

Study Design:

Cross-sectional study design.

Methods:

The study used an online survey to assess prosthesis use and satisfaction in veterans with upper-limb and lower-limb amputation. Survey participation invitations were distributed by email, text message, and mail to 46,613 potential participants.

Results:

The survey response rate was 11.4%. After exclusions, an analytic sample of 3,959 respondents with a major limb amputation was identified. The sample was 96.4% male; 78.3% White, with mean age of 66.9; and mean of 18.2 years since amputation. The rate of never using a prosthesis was 8.2%, and the rate of prosthesis discontinuation was 10.5%. Functionality (62.0%), undesirable prosthesis characteristics (56.9%), and comfort (53.4%) were the most common reasons for discontinuation. After controlling for the amputation subgroup, the odds of prosthesis discontinuation were higher for those with unilateral upper-limb amputation, female gender, White race (compared with Black race), diabetes, above-knee amputation, and lower prosthesis satisfaction. Prosthesis satisfaction and quality of life were highest for current prosthesis users.

Conclusions:

This study adds new understanding regarding the rate and reasons for prosthesis nonuse in veterans and highlights the important relationship between prosthesis discontinuation and prosthesis satisfaction, quality of life, and satisfaction with life.
A Feasibility Study on Deep Learning Reconstruction to Improve Image Quality With PROPELLER Acquisition in the Setting of T2-Weighted Gynecologic Pelvic Magnetic Resonance Imaging
Authors: Saleh Mohammed , Virarkar Mayur , Javadi Sanaz , Mathew Manoj , Vulasala Sai Swarupa Reddy , Son Jong Bum , Sun Jia , Bayram Ersin , Wang Xinzeng , Ma Jingfei , Szklaruk Janio , Bhosale Priya
Published: June 2023

Objectives

Evaluate deep learning (DL) to improve the image quality of the PROPELLER (Periodically Rotated Overlapping Parallel Lines with Enhanced Reconstruction technique) for 3 T magnetic resonance imaging of the female pelvis.

Methods

Three radiologists prospectively and independently compared non-DL and DL PROPELLER sequences from 20 patients with a history of gynecologic malignancy. Sequences with different noise reduction factors (DL 25%, DL 50%, and DL 75%) were blindly reviewed and scored based on artifacts, noise, relative sharpness, and overall image quality. The generalized estimating equation method was used to assess the effect of methods on the Likert scales. Quantitatively, the contrast-to-noise ratio and signal-to-noise ratio (SNR) of the iliac muscle were calculated, and pairwise comparisons were performed based on a linear mixed model. P values were adjusted using the Dunnett method. Interobserver agreement was assessed using the κ statistic. P value was considered statistically significant at less than 0.05.

Results

Qualitatively, DL 50 and DL 75 were ranked as the best sequences in 86% of cases. Images generated by the DL method were significantly better than non-DL images (P < 0.0001). Iliacus muscle SNR on DL 50 and DL 75 was significantly better than non-DL images (P < 0.0001). There was no difference in contrast-to-noise ratio between the DL and non-DL techniques in the iliac muscle. There was a high percent agreement (97.1%) in terms of DL sequences' superior image quality (97.1%) and sharpness (100%) relative to non-DL images.

Conclusion

The utilization of DL reconstruction improves the image quality of PROPELLER sequences with improved SNR quantitatively.
FDG PET (and MRI) for Monitoring Immunotherapy in Alzheimer Disease
Authors: Høilund-Carlsen Poul F. , Revheim Mona-Elisabeth , Alavi Abass , Barrio Jorge R.
Published: June 2023

Passive immunotherapy for Alzheimer disease has been tried for over 10 years without success. However, in 2021 and most recently in January 2023, the US Food and Drug Administration granted accelerated approval of 2 antibodies for this purpose, aducanumab and lecanemab. In both cases, the approval was based on a presumed therapy-related removal of amyloid deposits from the brain and, in the case of lecanemab, also some delay in cognitive decline. We question the validity of the evidence for the removal of amyloid in particular as assessed by amyloid PET imaging, believing that what is observed is more likely a large nonspecific amyloid PET signal in the white matter that diminishes during immunotherapy—in line with dose-dependent increases in amyloid-related imaging abnormalities and increased loss of cerebral volume in treated compared with placebo patients. To investigate this further, we recommend repeat FDG PET and MRI in all future immunotherapy trials.
Immediate use cryoprecipitate products provide lasting organ protection in a rodent model of trauma/hemorrhagic shock and prolonged hypotensive resuscitation
Authors: Zeineddin Ahmad , Wu Feng , Cao Sereena , Corash Laurence , Pati Shibani , Kozar Rosemary Ann
Published: June 2023

BACKGROUND

Cryoprecipitate (CP) can augment hemostasis after hemorrhagic shock (HS). Similar to fresh frozen plasma (FFP), CP may provide short-term endothelial protection. We tested a new 5-day postthaw CP (5-day pathogen-reduced cryoprecipitate [5PRC]) and lyophilized pathogen-reduced cryoprecipitate (LPRC) to overcome challenges of early administration and hypothesized that 5PRC and LPRC would provide lasting organ protection in a rodent model of HS.

METHODS

Mice underwent trauma/HS (laparotomy then HS), mean arterial pressure (MAP) 35 × 90 minutes, and then 6 hours of hypotensive resuscitation (MAP, 55–60 mm Hg) with lactated Ringer's solution (LR), FFP, CP, 5PRC, or LPRC and compared with shams. Animals were followed for 72 hours. Organs and blood were collected. Data are presented as mean ± SD and analysis of variance with Bonferroni post hoc.

RESULTS

Mean arterial pressure was comparable between experimental groups at baseline, preresuscitation, and 6 hours per protocol. However, volume needed to resuscitate to target MAP over 6 hours was less than half for CP, 5PRC, LPRC, and FFP compared with LR, suggesting that CP products can serve as effective resuscitative agents. Mean arterial pressure at 72 hours was also significantly higher in the CP, 5PRC, and FFP groups compared with LR. Resuscitation with CP, 5PRC, and LPRC provided lasting protection from gut injury and enhanced syndecan immunostaining comparable with FFP, while LR mice demonstrated persistent organ dysfunction. Sustained endothelial protection was demonstrated by lessened lung permeability, while cystatin C was an indicator of kidney function, and liver aspartate aminotransferase and alanine transaminase returned to sham levels in all groups.

CONCLUSION

Cryoprecipitate products can provide lasting organ protection comparable with FFP in a sustained rodent model of trauma/HS and hypotensive resuscitation. The availability of 5PRC and LPRC will allow for investigation into the immediate use of cryoprecipitate for severely injured patients. As lyophilized products such as cryoprecipitate become available clinically, their use has important implications for prehospital, rural, and battlefield usage.
Injury-induced endotheliopathy: What you need to know
Authors: Cardenas Jessica C. , Dong Jing Fei , Kozar Rosemary Ann
Published: June 2023

The endotheliopathy of trauma involves a complex interplay between the glycocalyx, von Willebrand factor, and platelets that leads to abnormalities in coagulation, inflammation, and endothelial cell (EC) function. The current review presents a synopsis of EC function under homeostatic conditions, the structure and function of the endothelial glycocalyx; mechanisms of EC injury and activation after trauma; pathological consequences of the EoT at the cellular level; and clinical implications of the EoT. Recent evidence is presented that links the EoT to extracellular vesicles and hyperadhesive ultralarge von Willebrand factor multimers through their roles in coagulopathy. Lastly, potential therapeutics to mitigate the EoT are discussed. Most research to date has focused on blood products, primarily plasma, and its contribution to restoring postinjury EC dysfunction. Additional therapeutic adjuvants that target the glycocalyx, ultralarge von Willebrand factor, low ADAMTS-13, and pathologic extracellular vesicles are reviewed. Much of the pathobiology of EoT is known, but a better mechanistic understanding can help guide therapeutics to further repair the EoT and improve patient outcomes.
Large Discrepancies in Dementia Mortality Reported in Vital Statistics
Authors: Adair Tim , Li Hang , Temple Jeromey , Anstey Kaarin J.
Published: June 2023

Purpose:

There is limited understanding of the intercountry comparability of dementia mortality data. This study compares reported dementia mortality in national vital statistics between countries and over time. In countries with low dementia reporting, this study identifies other causes to which dementia may be misclassified.

Methods:

Using the World Health Organization (WHO) Mortality Database, we calculated the ratio of reported to expected (Global Burden of Disease estimated) age-standardized dementia death rates in 90 countries from 2000 to 2019. Other causes to which dementia may be misclassified were identified as having relatively high cause fractions compared with other countries.

Patients:

No patients were involved.

Results:

There is a large intercountry variation in reported dementia mortality rates. The ratio of reported to expected dementia mortality exceeded 100% in high-income countries but was below 50% in other super regions. In countries with low reported dementia mortality, cardiovascular diseases, ill-defined causes, and pneumonia have relatively high cause fractions and may be misclassified from dementia.

Discussion:

Large discrepancies in dementia mortality reporting between countries, including often implausibly low reported mortality, makes comparison extremely difficult. Improved guidance for and training of certifiers and the use of multiple cause-of-death data can help strengthen the policy utility of dementia mortality data.
Political repression motivates anti-government violence
Authors: Bartusevičius Henrikas , van Leeuwen Florian , Petersen Michael Bang
Published: June 2023

We examined whether political repression deters citizens from engaging in anti-government behaviour (its intended goal) or in fact motivates it. Analyses of 101 nationally representative samples from three continents (
N
= 139 266) revealed a positive association between perceived levels of repression and intentions to engage in anti-government violence. Additional analyses of fine-grained data from three countries characterized by widespread repression and anti-government violence (
N
= 2960) identified a positive association between personal experience with repression and intentions to engage in anti-government violence. Randomized experiments revealed that thoughts about repression also motivate participation in anti-government violence. These results suggest that political repression, aside from being normatively abhorrent, motivates anti-repressor violence.
Role of time-dependent foreign molecules bonding in the degradation mechanism of polymer field-effect transistors in ambient conditions
Authors: Zohaib Muhammad , Afzal Tahmina , Zahir Iqbal M. , Almutairi Badriah S. , Ali Raza Mohsin , Maqsood Muhammad Faheem , Raza M. Akram , Riaz Saira , Naseem Shahzad , Iqbal M. Javaid
Published: June 2023

Long-standing research efforts have enabled the widespread introduction of organic field-effect transistors (OFETs) in next-generation technologies. Concurrently, environmental and operational stability is the major bottleneck in commercializing OFETs. The underpinning mechanism behind these instabilities is still elusive. Here we demonstrate the effect of ambient air on the performance of p-type polymer field-effect transistors. After exposure to ambient air, the device showed significant variations in performance parameters for around 30 days, and then relatively stable behaviour was observed. Two competing mechanisms influencing environmental stability are the diffusion of moisture and oxygen in the metal–organic interface and the active organic layer of the OFET. We measured the time-dependent contact and channel resistances to probe which mechanism is dominant. We found that the dominant role in the degradation of the device stability is the channel resistance rather than the contact resistance. Through time-dependent Fourier transform infrared (FTIR) analysis, we systematically prove that moisture and oxygen cause performance variation in OFETs. FTIR spectra revealed that water and oxygen interact with the polymer chain and perturb its conjugation, thus resulting in degraded performance of the device upon prolonged exposure to ambient air. Our results are important in addressing the environmental instability of organic devices.
Non-natural amino acids into LfcinB-derived peptides: effect in their (i) proteolytic degradation and (ii) cytotoxic activity against cancer cells
Authors: Insuasty-Cepeda Diego Sebastián , Barragán-Cárdenas Andrea Carolina , Ardila-Chantre Natalia , Cárdenas-Martínez Karen Johanna , Rincón-Quiñones Isabella , Vargas-Casanova Yerly , Ochoa-Zarzosa Alejandra , Lopez-Meza Joel Edmundo , Parra-Giraldo Claudia Marcela , Ospina-Giraldo Luis Fernando , Fierro-Medina Ricardo , García-Castañeda Javier Eduardo , Rivera-Monroy Zuly Jenny
Published: June 2023

The dimeric peptide
26
[F]: (RRWQWR
F
KKLG)
2
-K-Ahx has exhibited a potent cytotoxic effect against breast cancer cell lines, with position 26 (F) being the most relevant for anti-cancer activity. In this investigation, six analogues of the
26
[F] peptide were synthesized in which the 26th position was replaced by non-natural hydrophobic amino acids, finding that some modifications increased the resistance to proteolytic degradation exerted by trypsin or pepsin. Additionally, these modifications increased the cytotoxic effect against breast cancer cells and generated cell death mediated by apoptosis pathways, activating caspases 8 and 9, and did not compromise the integrity of the cytoplasmic membrane. Finally, it was found that the modified peptides have a broad spectrum of action, since they also have a cytotoxic effect against the HeLa human cervical cancer cell line. Peptide
26
[F] was inoculated in mice by ip administration and the lethal dose 50 (LD
50
) was between 70 and 140 mg kg
−1
. While for the
26
[1-Nal]: (RRWQWR-1-Nal-KKLG)
2
-K-Ahx peptide, a dose-response test was performed, and the survival rate was 100%. These results suggested that these peptides are safe in this animal model and could be considered as promissory to develop a treatment against breast cancer.