bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring bi-directional impacts of Lisdexamfetamine dimesylate on psychological comorbidities and quality of life in people with Binge Eating Disorder
Authors: Griffiths Kristi R. , Boulet Stephanie , Barakat Sarah , Touyz Stephen , Hay Phillipa , Maguire Sarah , Kohn Michael R.
Published: June 2024

Background

Lisdexamfetamine dimesylate (LDX) has demonstrated safety and efficacy for treatment of Binge Eating Disorder (BED). However, to date, trials have not included participants with co-occurring psychiatric disorders. This study explores how LDX affects eating disorder psychopathology, symptoms of common psychiatric comorbidities of BED (ADHD, depression, anxiety), and psychological quality of life, in people with moderate to severe BED.

Methods

These are secondary analyses of an open-label LDX trial conducted in 41 adults (18–40 years) over eight-weeks. Participants received LDX titrated to 50 or 70 mg. Clinical assessments and self-report questionnaires were conducted at baseline and 8-week follow-up.

Results

Eating disorder psychopathology and psychological quality of life improved after 8-weeks of LDX. No significant group-level changes in depression, anxiety or ADHD severity scores were observed. However, the majority within the small subsets with elevated depression and ADHD symptoms experienced reduced depressive and inattentive symptom severity, respectively.

Conclusions

We provide proof-of-concept evidence that LDX may provide broader psychological benefits to individuals with BED, beyond reducing their BE frequency. Effects of LDX on anxiety should be monitored closely by clinicians. Early indications suggest that LDX may be effectively used in people with BED, with and without co-occurring psychiatric conditions, however tolerability may be lower in highly complex cases.

Trial registration: Australian and New Zealand Clinical Trials Registry (anzctr.org.au) #ACTRN12618000623291.
Biocontrol potential of epiphytic bacteria against Xanthomonas citri pathotypes A and A*
Authors: Fathi Zahra , Rezaei Rasool , Charehgani Habiballah , Ghaderi Fariba , Ghalavoz Maryam Ghalamzan
Published: June 2024

Background

Citrus canker caused by the bacterium Xanthomonas citri (Hasse 1915) is known as a dangerous disease that has serious economic impacts on citrus production in many tropical and subtropical countries. In Iran, Citrus canker disease has caused significant damage to various citrus fruits, particularly limes. Nowadays, employing antagonistic bacteria as an effective and environmentally friendly method for plant disease management has gained special importance.

Results

Citrus leaf samples were collected from different regions of Iran, and after isolating epiphytic bacteria, ex planta and in planta investigations concerning antagonistic activities of the isolates against Xanthomonas citri pathotypes A and A* were performed. A total of 94 epiphytic bacterial isolates were isolated from citrus aerial parts. Based on biochemical, physiological, morphological, and genotypic tests, it was determined that these bacteria belong to the Bacillus and Staphylococcus genera. The highest inhibition activity against the pathogenic bacterium was related to isolates D4 and D5. Using the molecular method and the resulting dendrogram, it was found that these isolates were most similar to Bacillus amyloliquefaciens. The present findings demonstrated that pathogenicity test on key lime leaves infected with X. citri pathotypes A and A*, along with the application of the biocontrol strain B. amyloliquefaciens, resulted in a significant reduction in the number of canker lesions.

Conclusion

The results strongly suggested that the identified antagonistic bacterial isolates hold promising potential as biocontrol agents for managing citrus bacterial canker disease.
Phase IIA study of high-affinity TCR-T (TAEST16001) targeting NY-ESO-1 in soft tissue sarcoma.
Authors: Liu Jiayong , Gao Tian , Pan Qiuzhong , Bai Chujie , Han Zhaosheng , Tan Zhichao , Peng Ruiqing , Xu Bushu , Wen Xizhi , Cen Huafang , Yan Chaoxian , Lau Johnson Yiu-Nam , Zeng Lun , Wu Xueyun , Ou Yusheng , Gong Haiping , Huang Yingjie , Fan Zhengfu , Zhang Xing
Published: June 2024

11548

Background: TAEST16001 cells are genetically engineered autologous T cells expressing high-affinity NY-ESO-1-specific T-cell receptor (TCR) targeting NY-ESO-1 (expressed in a wide range of tumors) positive soft tissue sarcoma (STS) in the context of HLA-A*02:01. A phase I study of in patients with advanced STS (NCT04318964) demonstrated safety and preliminary indication of efficacy at ASCO 2022. Here, we will present our encouraging phase IIa results. Methods: This is an open-labeled, single arm study to evaluate efficacy and safety of TAEST16001 cells in patients with advanced STS (NCT05549921). Enrolled patients underwent apheresis, their isolated T cells expanded in vitro after transduction with a lentiviral vector expressing high affinity NY-ESO-1 TCR. Patients received 3-day lymphodepleting chemotherapy (cyclophosphamide 15 mg/kg/day and fludarabine 20 mg/m2/day). TAEST16001 cells were administered at 1.2 × 1010± 30% cells (determined through our phase I data) and they also received 14-day IL-2 s.c. injection. Target efficacy ( per RECIST 1.1) was set at overall response rate (ORR) =25% for the first stage cohort of 12 patients. Results: As of January 2024, 8 patients were enrolled (M:F 4: 4; mean age: 40 yrs.; median prior regimens: 3 (range:2-5)). TAEST16001 cells demonstrated a manageable safety profile consistent with previous phase I study. The common (n>1) reported grade (G) 3 adverse events were lymphocytopenia (n=8), decreased WBC count (n=7), neutropenia (n=6), elevated γ-GT (n=3), hypokalemia (n=2). Six patients had cytokine release syndrome (CRS) (G3: 1; G2: 1; G1: 4), and 2 patients also experienced G1 ICANS, all resolved completely after symptomatic treatment. Importantly, after at least two tumor assessments, 4 had confirmed partial response, 3 had stable disease, and 1 had progressive disease. The ORR at cut-off date was 50%. The median time to initial response was 1.1 months (1.1 to 2.2) and median duration of response was 5.0 months (1.5 to 8.8). Most patients are still being follow-up. When pooling the data for the same dose in phase I part, ORR at dose of 1.2 × 1010 was 54.5% (6/11). Conclusions: TAEST16001 demonstrated an acceptable safety profile. The encouraging efficacy data (ORR=50%) exceeded our pre-specified target efficacy (ORR=25%). The review committee has recommended TAEST16001 to proceed early to the next stage of clinical development. Clinical trial information: NCT05549921 .
Phase 2a results of SQ3370, a doxorubicin-based click chemistry therapeutic in patients with advanced STS: Planned interim analysis.
Authors: Bui Nam , Kwatra Vineet , Ryan Christopher W. , Gordon Erlinda Maria , Aleckovic Masa , Srinivasan Sangeetha , Nguyen Tri-Hung , Mejia Oneto Jose Manuel , Abella-Dominicis Esteban , Chawla Sant P.
Published: June 2024

11555

Background: Shasqi is a clinical stage biotech that uses click chemistry, a Nobel Prize winning technology, to selectively activate cancer treatments at the tumor. The Click Activated Protodrugs Against Cancer (CAPAC) platform comprises of 1) tumor targeting agents, which carry an activator, and 2) attenuated cancer drugs, which are selectively activated at the tumor by the targeting agent through click chemistry, maximizing therapeutic index and minimizing toxicities. We have demonstrated clinical proof of concept with SQ3370, which uses an intratumorally injected SQL70 biopolymer (bp) with a doxorubicin (Dox) protodrug (SQP33) injected systemically. As previously reported RP2D of SQP33=12x Dox. (NCT04106492). Methods: Dox naïve patients (pts) received 10/20 mL bp and protodrug IV QD x 3 or 5. Key eligibility: locally advanced or metastatic soft tissue sarcomas (STS). The objective was to explore bp dose and schedule of the RDP2 (same dose per cycle) in advanced or metastatic STS. Results: Fourteen patients with predominantly metastatic (11/14) STS, all unresectable, were enrolled at the 1st interim analysis. Median age 58 years (32-89), ECOG=1 (11/14). Therapy was well tolerated. The most common TEAE was nausea and fatigue (all grade ≤ 2), with 1 subject in each group having a manageable grade ≤ 3 TEAE-related discontinuations. The majority of subjects did not suffer clinical myelosuppression grade ≤ 1 neutropenia (10/14), anemia (13/14), or thrombocytopenia (13/14), with DCR 71% (CI 95% 44-92%) and ORR 14.3% (CI 95%1.7-40%). Detailed PK, immune assessment and safety findings will be presented. Conclusions: SQ3370 is the first clinical click chemistry-based cancer therapy, and this is the 1st clinical trial to explore doses greater than 3x Dox in STS patients. The results show that the bp activates protodrug, which is not a vesicant, and releases Dox in patients. Click chemistry favorably alters PK and safety of the Dox payload. At 12x Dox, using the commonly administered 3-week schedule, Dox was very well tolerated. Click-chemistry maintains expected clinical activity, and preliminary data suggest enhanced safety (reduced myelosuppression) as well as unlocking immunological effects (intratumoral and systemic), without the myelosuppressive effects typically seen with Dox. Clinical trial information: NCT04106492 . [Table: see text]
Efficacy of nirogacestat in participants with poor prognostic factors for desmoid tumors: Analyses from the randomized phase 3 DeFi study.
Authors: Vincenzi Bruno , Bui Nam , Dileo Palma , Federman Noah , Riedel Richard F. , Van Tine Brian Andrew , Amoruccio Vincent , Lim Allison , Oton Ana B. , Kasper Bernd
Published: June 2024

11556

Background: Desmoid tumors (DT) are rare, locally aggressive, soft-tissue tumors with a highly unpredictable natural course and substantial patient burden, including pain and functional limitations. Prognosis of DT is potentially dependent on multiple factors, including tumor location, size, patient’s age, mutational status, and presence of pain. Nirogacestat (niro), a targeted gamma secretase inhibitor, is the only treatment approved in the US for adults with progressing DT. In the phase 3 DeFi study, niro demonstrated significant and clinically meaningful improvement vs placebo (pbo) in the primary and key secondary endpoints of progression-free survival (PFS: HR, 0.29 [95% CI: 0.15-0.55]; P<.001), objective response rate (ORR: 41% vs 8%; P<.001), and patient-reported outcomes (pain, DT-specific symptom burden, physical and role functioning, and overall quality of life; P≤0.01, all). The objective of this analysis was to determine the effect of niro in patient subgroups that have been associated with poor prognosis (larger tumor size, younger age, CTNNB1 mutation types, and pain). Methods: DeFi (NCT03785964) was a global, multicenter, double-blind study to determine the efficacy, safety, and tolerability of niro in adults with progressing DT. Patients were randomized 1:1 to niro 150 mg (n=70) or pbo (n=72), taken twice-daily in 28-day cycles. Post hoc analyses of PFS and ORR were conducted in individuals stratified by patient- and tumor-related prognostic factors. Results: PFS and ORR improvement favored niro vs pbo regardless of the patient subgroup, including: baseline tumor size (≤10 cm, >10 cm); age (≤30 y, >30 y); CTNNB1 mutation type (S45F, T41A); and baseline pain (uncontrolled, controlled) (Table). Across the subgroups analyzed, PFS hazard ratio ranged from 0.18 to 0.39, with values <1 favoring niro over pbo. ORR risk difference (niro – pbo) ranged from 18.1% to 56.0%, with values >0 favoring niro. Conclusions: Niro demonstrated consistent improvement in PFS and ORR vs pbo in patients with characteristics implicated as poor prognostic factors for DT—including larger tumor size, younger age, CTNNB1 mutation types, and pain. These results indicate that niro can provide substantial benefit across the subgroups analyzed. Clinical trial information: NCT03785964 . [Table: see text]
Active surveillance in patients with extra-abdominal desmoid-type fibromatosis: A combined analysis of three prospective observational studies.
Authors: Colombo Chiara , Hakkesteegt Stefanie , Le Cesne Axel , Barretta Francesco , Blay Jean-Yves , Grunhagen Dirk J. , Penel Nicolas , Lam Laurent , Fiore Marco , Palassini Elena , Grignani Giovanni , Tolomeo Francesco , Collini Paola , Merlini Alessandra , Perrone Federica , Stacchiotti Silvia , Verhoef Cornelis , Bonvalot Sylvie , Gronchi Alessandro
Published: June 2024

11573

Background: Three observational studies on active surveillance (AS) in patients with extra-abdominal desmoid-type fibromatosis (DTF) provided prospective evidence supporting AS as frontline approach. Identification of prognostic factors for failure of AS will help determine the appropriate treatment strategy. The aim of this study was to confirm previous findings and investigate the prognostic impact of clinical and molecular variables on a larger series. Methods: Data available on January 31st 2024 from 3 prospective observational studies in Italy, the Netherlands and France in which DTF patients were followed for ≥3 years during an initial AS approach were merged. Patients ≥18 years, with primary extra-abdominal sporadic DTF (abdominal wall, extremity, head & neck, trunk) and with CTNNB1 mutation (T41A, S45F, S45P, WT, “other”) available were eligible for the analyses. The primary study endpoint was treatment-free survival (TFS). Secondary endpoints included incidence of RECIST progression, spontaneous RECIST regression and regression post-RECIST progression. Results: Two hundred and eighty-two patients (n= 282) with median follow up of 53 months (IQ, 39-63) were included. Three-year and five-year TFS and crude cumulative incidences (CCI) of RECIST progression, RECIST regression and regression post-RECIST progression were 69% (64-75%) and 66% (61-73), 34% (95% CI 28-40) and 35% (30-41), 26% (95% CI 21-32) and 34% (29-41), and 35% (95% CI 26-47) and 40% (30-52), respectively. Larger initial tumour size (P=0.031), CTNNB1 mutation (S45F and “other” mutation P=0.049), and head/neck and extremity tumour locations (P=0.032) were associated with worse TFS at multivariable analysis (Table 1). Consistently smaller size and abdominal wall were associated with higher probability of initial spontaneous RECIST regression and a specular trend for mutation was also seen (Table). Conclusions: This study confirms that spontaneous regression occurs in a significant proportion of patients and two third are treatment free at 5 years. Initial size, CTNNB1 mutation and location should be factored in the initial decision-making process. [Table: see text]
Seven year update on SOC-1702: A phase 2 study using trabectedin (T) in combination with ipilimumab (I), nivolumab (N) and trabectedin (T) in previously untreated patients with advanced soft tissue sarcoma.
Authors: Gordon Erlinda Maria , Chawla Sant P. , Omelchenko Nadezhda , Jeffrey Samantha , Agarwal Anmol Dia , Kumar Vaishali , Chawla Neal Shiv , Chua Victoria , Quon Doris V. , Moradkhani Ania , Federman Noah
Published: June 2024

11577

Background: Advanced soft tissue sarcoma is most often associated with a fatal outcome. This report is an update on the results of the SOC-1702 Phase 2 study for previously untreated STS. Methods: Objectives, Primary: Evaluate best response rate by RECIST v1.1; Secondary: Assess progression-free survival (PFS) at 6 months and overall survival. Patients and Methods: Eligible patients for this Phase 2 study are males or females ≥ 18 years of age with locally advanced unresectable or metastatic soft tissue sarcoma, previously untreated, with measurable disease by RECIST v1.1. Treatment protocol: (I) 1 mg/kg i.v. q 12 wks, (N) 3 mg/kg i.v. q 2 wks, (T) 1.2 mg/m2 CIV q 3 wks. Results: Efficacy: Ninety-one patients were evaluated for efficacy. These subjects completed at least two treatment cycles and had at least one follow-up CT scan. The best responses were 9CR, 14PR, 54SD and 14PD with 25% ORR, 85% DCR. PFS rate at 6 months was 56%; Median PFS was 7.4 (95% CI: 5.6-9.2) months; Median OS was 32.0 (95% CI: 19.8-44.2) months. The best responders (CR and PR) were patients with LMS, UPS, LPS, synovial sarcoma, myxofibrosarcoma, endometrial stromal sarcoma, clear cell sarcoma, DSRCT, and chondrosarcoma. Notably, out of the 91 patients who participated in the study between 2017 and 2022, 23 (25%) patients are still alive as of January 1, 2024, the data cut-off date. Safety: Grade 3/4 TRAEs related to Trabectedin include both hematologic and non-hematologic toxicities: fatigue, nausea, vomiting, fever, exhaustion, dehydration, asthenia, cellulitis of port, anemia, neutropenia, thrombocytopenia, transaminitis, elevated CK. There were no hematologic toxicities related to Nivolumab or Ipilimumab. Grade 3/4 TRAEs include decreased TSH, increased T4, increased TSH, transaminitis, hyponatremia, dehydration, pruritus, and psoriasis. Conclusions: Taken together we have confirmed that (1) Trabectedin in combination with Ipilimumab and Nivolumab is a safe and effective regimen for previously untreated advanced STS, and (2) Randomized studies are needed to confirm whether this regimen is superior to standard first line therapy for advanced soft tissue sarcoma. Clinical trial information: NCT03138161 .
A signal-finding study of nivolumab and relatlimab in patients with advanced chordoma.
Authors: Burkenroad Aaron , Singh Arun S. , Chmielowski Bartosz , Brackert Sandra , Federman Noah , Hagopian Anahis , Glaspy John A , Kendal Joseph , Wessel Lauren E , Hornicek Francis J. , Bernthal Nicholas M.
Published: June 2024

11578

Background: Chordomas are derived from notochordal remnants and are typically treated with surgery and radiation therapy. For advanced chordomas, there are no approved systemic therapies. Preclinical evidence and anecdotal reports have indicated that the immune system is active in chordomas and that there may be a role for immunomodulation in treating this disease. Methods: This study is a single-arm, signal-finding trial in patients with advanced chordoma treated with the anti PD-1 antibody nivolumab (480 mg Q4 weeks up to 2 years) and the anti-LAG3 antibody relatlimab (160 mg Q4 weeks up to 2 years). The primary objective of this study was to assess the safety of nivolumab and relatlimab in subjects with progressive metastatic or locally advanced/unresectable chordoma. Secondary objectives were to ascertain the median progression free survival (PFS), response rate (RR), and the 4- and 6-month PFS by RECIST 1.1. Results: Out of a planned enrollment of 20 patients, 10 patients (8 Male, 2 Female) were consented and treated on trial. Enrolled patients had the following sites of involvement: 5 clival/c-spine, 4 sacral, and 1 thoracic. Nine had conventional subtype chordoma and 1 had chondroid subtype. Eight of the 10 patients had previous surgery, 6 had previous radiation therapy and 5 had 1-2 lines of prior systemic therapy, including one who received pembrolizumab. Pretreatment biopsies were obtained from 9 out of 10 patients and blood has been collected on all patients. Nine patients were evaluable for study outcomes. A total of 64 AEs (Grades 1-4) have been noted to date, with 6 events being classified as grade 3-4: nausea, facial pain, headache, and pulmonary embolism. Five serious adverse events (SAEs) were noted in patients on treatment: headache (2), asthma (1), myocarditis (1), and sepsis (1). The median PFS of the 9 evaluable patients was 21.4 weeks. At 4 months, 7 out of 9 patients were progression free (77.7%). At 6 months, 4 out of 9 patients remained progression free (44.4%) and had continued progression-free survival at 1 year. One out of 9 (9.1%) patients had a PR via RECIST 1.1. One patient discontinued treatment due to an adverse event (grade 1 myocarditis). Conclusions: This signal-finding study indicated that some patients with advanced chordomas can receive benefit with relatlimab in combination with nivolumab. The combination was well-tolerated and no new safety signals were found in this rare patient population. Correlative studies are ongoing. The study was closed for slow accrual. Clinical trial information: NCT03623854 .
Factors associated with sexual function and sexual satisfaction in young women with breast cancer.
Authors: Ferrigno Guajardo Ana , Fonseca Alan , Miaja Melina , Cruz-Ramos Marlid , Vaca-Cartagena Bryan , Mesa-Chavez Fernanda , Platas Alejandra , Rodriguez Ana Laura , Cabrera-Galeana Paula Anel , Mohar Alejandro , Villarreal-Garza Cynthia
Published: June 2024

12062

Background: Young women with breast cancer (YWBC) are vulnerable to sexual dysfunction and dissatisfaction due to age-specific psychosocial concerns and treatment side effects. This study aimed to identify factors associated with sexual health in a prospective cohort of YWBC. Methods: Patients aged ≤40 yrs with non-metastatic BC from 3 referral centers completed emotional health, quality of life (QoL), and sexual health assessments at baseline, 6 mos, 1 yr, 2-3 yrs, and 4-5 yrs post-diagnosis. Sexual activity was defined as having had intercourse in the 4 wks preceding each assessment. Female sexual dysfunction (FSD) was defined as a total score <26.55 in the Female Sexual Function Index (FSFI), while hypoactive sexual desire disorder (HSDD) was defined as a score <5 in the desire subscale. Sexual enjoyment was classified with the Sexual Satisfaction Index (SSI), with <110 indicating dissatisfaction. Results: A total of 474 patients with a median age of 36 yrs were included, of which most were married/in a domestic partnership (65%), unemployed (61%), and had an educational level <high school (51%). Most had stage II (49%) or III (39%) disease. The most common molecular subtype was HR+/HER2- (53%), followed by HR-/HER- (26%) and HR+/HER2+ (14%). The prevalence of relevant outcomes at each assessment are shown in the Table. Factors associated with being sexually inactive were low educational level (χ2=7.7), being single (χ2=112.6), having children (χ2=8.12), and higher treatment side effects burden ( p=0.002). Factors associated with worse sexual function were being single (χ2=13.8), amenorrhea (χ2=40.8), HADS-D ≥8 (χ2=11.7), and HADS-A ≥8 (χ2=13.9). Factors associated with lower sexual satisfaction were low educational level (χ2=10.3), being single (χ2=15.5), having undergone bilateral oophorectomy (χ2=5.74), amenorrhea (χ2=8.48), HADS-D ≥8 (χ2=14.98,), and HADS-A ≥8 (χ2=13.91). Additionally, both FSFI and SSI scores directly correlated with QoL (QLQ SumScore) and body image (QLQ-BRBI), and inversely correlated with systemic therapy side effects (QLQ-BRST) ( p<0.001). When analyzing sexual health outcomes according to type of treatment (total vs partial mastectomy, chemotherapy vs no, hormone therapy vs no, anti-HER2 agent vs no), no significant differences were found. Conclusions: Sexual dysfunction and dissatisfaction are highly prevalent in YWBC the first 5 yrs post-diagnosis. As poor sexual health correlates with inferior QoL, patients at an increased risk might benefit from early targeted interventions. [Table: see text]
Trends and racial disparities in palliative care utilization among patients with prostate cancer: A ten-year retrospective study.
Authors: Ozogbo Stanley , Olafimihan Ayobami Gbenga , Jackson Inimfon , Nwachukwu Chiamaka Elsie , Olatunji Gbolahan , Kokori Emmanuel , Aderinto Nicholas , Nzeako Tochukwu , Kim James J.
Published: June 2024

12068

Background: Due to improvements in cancer therapies and treatment strategies, survivorship among patients with prostate cancer continues to increase, thus necessitating the utilization of palliative care services for symptom management. We examined the prevalence, trends and predictors of palliative care utilization among hospitalized prostate cancer patients in the US. Methods: A retrospective longitudinal study using the Nationwide Inpatient Sample (NIS) database (2010-2019) was conducted. Using join point regression and multivariable logistic regression, trends and factors associated with palliative care receipt were assessed. Results: The overall prevalence of palliative care utilization in the cohort of over 2 million admissions with prostate cancer, was 5.3%. Over the decade, there was a significant increase in palliative care consultations from 2,970 to 7,509 per 100,000 prostate cancer hospitalizations (p-trend <0.001) with an average annual percentage change of 7.7% over the study period. Individuals ≥70 years with prostate cancer had higher odds (aOR): 1.06; 95% CI: 1.01-1.12) of receiving palliative care relative to those < 70 years. Compared to non-Hispanic whites, non-Hispanic blacks were less likely to receive palliative care services (aOR: 0.93; 95% CI: 0.88-0.98). Patients on Medicaid (aOR: 1.51; 95% CI: 1.38-1.65), private insurance (aOR: 1.3; 95% CI: 1.23-1.38) and other insurance types (aOR: 2.2; 95% CI: 1.85-2.55) had higher odds of palliative care utilization when compared to those on Medicare. Prostate cancer patients discharged to facilities or with home health care were more likely (aOR: 6.4; 95% CI: 6.03-6.8) to receive palliative care. Other factors associated with palliative care receipt were non-elective admissions, admission to urban, large and teaching facilities. Furthermore, longer length of hospital stays (≥5 days vs <5 days) was associated with higher utilization of palliative care (aOR: 1.08; 95% CI: 1.05-1.13). Conclusions: Though the trends in palliative care utilization have improved over the years, it remains suboptimal. Additionally, black patients were less likely to receive palliative care. Further studies are needed to explain these disparities and generate interventions to narrow the identified gaps. Addressing the highlighted sociodemographic and hospital-level disparities will ensure optimal utilization of palliative care in this patient population.[Table: see text]
Comparative analysis of efficacy and safety profiles between conventional pegfilgrastim and its biosimilar agents in patients receiving cytotoxic chemotherapy: A systemic review and meta-analysis.
Authors: Nasir Saad , Ali Insia , Naviwala Mohammad Saad Salim , Alidina Zayan , Idrees Hiba , Moosajee Munira
Published: June 2024

12115

Background: While pegfilgrastim forms the cornerstone in chemotherapy-induced neutropenia prophylaxis, its newer biosimilar agents show potential as compelling options. However, despite head-to-head randomized clinical trials (RCTs) demonstrating comparable efficacy between these biosimilar agents of pegfilgrastim and the conventional pegfilgrastim, a lack of evidence exists to suggest definite clinical benefit. This could be attributed to the low statistical power in the clinical trials. Our systemic review and meta-analysis aim to pool the available evidence and provide a comprehensive understanding of the landscape in the prevention of chemotherapy-induced neutropenia. Methods: A literature search was conducted on online databases including, MEDLINE (PubMed), Embase, SCOPUS, and the Cochrane CENTRAL from their inception to October 2023 to identify phase II or III RCTs comparing the efficacy and safety profiles of the conventional pegfilgrastim and its biosimilar agents. Included studies reported at least one key outcome: the duration of severe neutropenia (DSN) in days after the first cycle of chemotherapy (primary outcome), incidence of febrile neutropenia (FN), and bone pain. Pooled risk ratios (RR) and weighted mean difference (WMD) with 95% confidence interval (CI) were calculated using a random-effects model. Heterogeneity was assessed using I2 statistics. Results: We identified 10 RCTs involving 2237 patients. Our analysis showed a statistically significant and favorable outcome for biosimilar agents in reducing DSN (WMD -0.08 days, 95% CI, -0.15, -0.01, P=0.03, I2=0%). No significant differences were observed in the incidence of FN (RR: 0.98, 95% CI, 0.62, 1.53, I2=0%) or bone pain (RR: 0.98, 95% CI, 0.82, 1.17, I2=0%). In the subgroup analysis based on the subtype of biosimilar agents, eflapegrastim had a statistically significant impact in decreasing DSN compared to the conventional pegfilgrastim (WMD -0.13 days, 95% CI -0.24, -0.03, P=0.01, I2=0%). Conclusions: Growing evidence supports cost-effective biosimilars of pegfilgrastim as comparable in efficacy and safety. Eflapegrastim emerges as a promising alternative, demonstrating a clinically meaningful benefit over the conventional pegfilgrastim.
Frequency of certain germline polymorphisms among ethnicities and adverse drug reaction risk associated with colorectal cancer therapies.
Authors: Jennissen Cathryn , Walker Jason , Elnashar Ghada , England Julie , Hawe Annmarie , Jhun Ellie H. , Tam Victor , Twist Greyson , Kasi Pashtoon Murtaza , Kelley James Michael
Published: June 2024

12119

Background: Chemotherapy regimens used to treat colorectal cancer (CRC) often include a combination of a fluoropyrimidine (i.e., fluorouracil or capecitabine), folinic acid, irinotecan, and/or oxaliplatin as first-line therapy in metastatic disease. Adverse drug reactions (ADRs) related to these regimens, such as neutropenia, severe diarrhea, and mucositis, can be severe or even life-threatening. Fluoropyrimidine (FP) and irinotecan-related toxicities in CRC are associated with certain germline polymorphisms in DPYD (*2A, *13, HapB3, and c.2846A>T) and UGT1A1 (*28 allele), respectively. Clinically actionable recommendations are available per the FDA and the Clinical Pharmacogenetics Implementation Consortium (CPIC) for DPYD poor metabolizers (PMs) and intermediate metabolizers (IMs) due to increased risk for FP-induced ADRs. The FDA also provides dosing guidance for UGT1A1PMs in an effort to minimize irinotecan-induced toxicities. The objective of this research was to observe the frequency of DPYDvariants (*2A, *13, HapB3, c.2846A>T, c.557A>G), UGT1A1 variants (*6, *28), and associated phenotypes in various racial and ethnic groups. Methods: A retrospective analysis of 8,640 samples genotyped for DPYD and UGT1A1 was conducted (OneOme, Minneapolis, MN). Phenotype and carrier frequencies were analyzed and stratified by self-reported ethnicity and race. Results: DPYD variants with reduced or no function were observed in 6% of all samples tested where 6% of patients having clinically actionable IM or PM status. UGT1A1 carrier frequency was 56% with 12% of patients with clinically actionable PM status. Conclusions: A significant proportion of patients carry DPYD and/or UGT1A1 variants that result in decreased metabolism of FPs and irinotecan, respectively. In this large sample size, a 6% DPYD risk variant carrier frequency is significantly more than an estimated 2%, as previously reported. The FDA and CPIC provide clinically actionable recommendations for these commonly used colorectal and other gastrointestinal cancer therapies in an effort to avoid severe and even life-threatening toxicities that may be potentiated by these germline variations. [Table: see text]
Clinical Decision Support as a Prevention Tool for Medication Errors in the Operating Room: A Retrospective Cross-Sectional Study
Authors: Amici Lynda D. , van Pelt Maria , Mylott Laura , Langlieb Marin , Nanji Karen C.
Published: June 2024

BACKGROUND:

Medication errors in the operating room have high potential for patient harm. While electronic clinical decision support (CDS) software has been effective in preventing medication errors in many nonoperating room patient care areas, it is not yet widely used in operating rooms. The purpose of this study was to determine the percentage of self-reported intraoperative medication errors that could be prevented by CDS algorithms.

METHODS:

In this retrospective cross-sectional study, we obtained safety reports involving medication errors documented by anesthesia clinicians between August 2020 and August 2022 at a 1046-bed tertiary care academic medical center. Reviewers classified each medication error by its stage in the medication use process, error type, presence of an adverse medication event, and its associated severity and preventability by CDS. Informational gaps were corroborated by retrospective chart review and disagreements between reviewers were resolved by consensus. The primary outcome was the percentage of errors that were preventable by CDS. Secondary outcomes were preventability by CDS stratified by medication error type and severity.

RESULTS:

We received 127 safety reports involving 80 medication errors, and 76/80 (95%) of the errors were classified as preventable by CDS. Certain error types were more likely to be preventable by CDS than others (P < .001). The most likely error types to be preventable by CDS were wrong medication (N = 36, 100% rated as preventable), wrong dose (N = 30, 100% rated as preventable), and documentation errors (N = 3, 100% rated as preventable). The least likely error type to be preventable by CDS was inadvertent bolus (N = 3, none rated as preventable).

CONCLUSIONS:

Ninety-five percent of self-reported medication errors in the operating room were classified as preventable by CDS. Future research should include a randomized controlled trial to assess medication error rates and types with and without the use of CDS.
Afterword: Primitivism under Erasure
Authors: Gikandi Simon
Published: June 2024

Of all the terms that came to define the making of culture and art in the long twentieth century, there was perhaps none as necessary and troublesome as primitivism and the tropes associated with it. This afterword is a reflection on the collection of articles in this special issue struggling with the question of how to work with disputed terms such as primitivism, and to consider the possibilities and limits of the aesthetic ideology of modernism and its alternative iterations.
Demand-side barriers and economic burden in accessing Human Papillomavirus screening for cervical cancer prevention in rural India: Evidence from a cross-sectional study
Authors: Sriram Shyamkumar , Jayakumar Arun Daniel , Gollapalli Pavan Kumar , Chandrasekar Swetha
Published: June 2024

Introduction Cervical cancer is a significant global health concern, especially in low- and middle-income countries with limited access to preventive healthcare. India’s vast rural population amplifies the challenge, demanding immediate action. Despite advancements, cervical cancer remains prevalent among underserved rural communities, hindered by barriers to Human Papillomavirus (HPV) screening uptake, including socioeconomic and financial constraints. This study aims to evaluate the economic challenges encountered by rural women when accessing HPV screening. Methods A cross-sectional survey was conducted among 1502 women aged 30 to 45 in Pondicherry, India, utilizing the Andersen Model as a conceptual framework. Household questionnaires gathered data on HPV screening expenses, including patient travel costs, productivity loss, and companion costs. The analysis utilized regression models, to identify the factors impacting the economic challenges associated with accessing HPV screening. Results Employment status and higher education significantly increase total costs by 73.483 (p < 0.001) and 90.169 units (p < 0.001) respectively. Income level, though with a minimal coefficient (B = 0.000), shows a significant effect (p = 0.019) on total costs. Longer travel hours raise costs by 5.129 units (p < 0.001), while having a companion increases costs by 106.095 units (p = 0.004). Prolonged patient time at Primary Health Center (PHC) contributes to a 2.357-unit increase in costs (p < 0.001). Conclusions The study highlights the multifaceted economic challenges faced by rural populations accessing HPV screening for cervical cancer prevention in India. Notwithstanding diverse demographics and varying proximity to healthcare facilities, individuals encounter significant barriers such as travel time and associated costs. Addressing these challenges necessitates targeted interventions to reduce socioeconomic disparities and improve healthcare accessibility for vulnerable populations, thereby advancing cervical cancer prevention efforts and promoting health equity in rural communities.
The role of sonication in microbiology culture yield of the explanted infected implants post fracture fixation: A systematic review
Authors: Mkochi Vincent Lewis , Dimock Richard , Schade Alexander Thomas
Published: June 2024

Objective To evaluate the role of sonication in cases of postoperative infection following fracture fixation. Methods A systematic review of studies comparing peri-implant tissue culture (PTC) and sonication fluid culture (SFC) from implants removed due to fracture-related infection was conducted. The inclusion criteria were: published in English, human studies, implants from fracture-related infection, and tests comparing the culture of deep tissue and sonication fluid. The quality of studies was assessed using the Critical Appraisal Skill Program (CASP) tool. The sensitivity, specificity, implant preservation mechanism to avoid contamination, cost, and duration of incubation for PTC and SFC were extracted and compared using descriptive statistics. Results Nine studies with a total of 1,144 participants were included. The overall mean sensitivity of SFC and PTC was 88.9% (95% CI: 84.6-92.4%) and 67.8% (95% CI: 60.9-74.2%), respectively. While the specificity of SFC and PTC was 96.2% (95% CI: 94.7-97.4%) and 98.5% (95% CI: 97.7-99.0%), respectively. However, the cost-effectiveness of sonication as a diagnostic method for sonication remains unclear, as only one study estimated the price of sonication to be $228.00 per test, similar to PTC. Conclusions Sonication fluid culture might improve sensitivity in diagnosing postoperative infection following fracture fixation. This technique can potentially enhance the microbiological output and provide valuable guidance to healthcare professionals in treating infection after fracture fixation. However, more high-quality trials are needed to establish its optimal use, especially cost-effectiveness. Registration The study protocol was registered on PROSPERO (CRD42022338190; 18 June 2022).
The genome sequence of the tree-moss, Climacium dendroides (Hedw.) F.Weber & D.Mohr (Climaciaceae)
Authors: Bell David , Long David G. ,   Royal Botanic Garden Edinburgh Genome Acquisition Lab,   Plant Genome Sizing collective,   Darwin Tree of Life Barcoding collective,   Wellcome Sanger Institute Tree of Life Management, Samples and Laboratory team,   Wellcome Sanger Institute Scientific Operations: Sequencing Operations,   Wellcome Sanger Institute Tree of Life Core Informatics team,   Tree of Life Core Informatics collective,   Darwin Tree of Life Consortium
Published: June 2024

We present a genome assembly from an individual Climacium dendroides gametophyte (the tree-moss; Bryophyta; Bryopsida; Leucodontales; Climaciaceae). The genome sequence is 413.1 megabases in span. Most of the assembly is scaffolded into 11 chromosomal pseudomolecules. The mitochondrial and plastid genome assemblies have lengths of 104.86 kilobases and 124.96 kilobases in length, respectively.
Drugie wydanie Wielkiego słownika frazeologicznego języka polskiego. Pomoc dla piszących, Warszawa 2022
Authors: Müldner-Nieckowski Piotr , Müldner-Nieckowski Łukasz
Published: June 2024

The first edition of the Great Phraseological Dictionary of the Polish Language was published in 2003 and contained 200 000 phraseological units of the language. It was the largest collection of Polish phraseology in history. It was prepared privately in a team of several people. After twenty years, at the end of 2022, the second edition of this dictionary was published, prepared on the basis of the same database, but modernized and adapted to the current Polish language. The article presents information on how the ways of writing various types of phraseological units have changed, and also on how new methods of defining the semantics of individual language units and methods of developing examples of the use of these units in texts were used. Thanks to them, the dictionary is more adapted to the needs of people who speak and write in Polish, and strictly implements the concepts and scientific recommendations regarding Polish phraseology developed by the authors. Information methods inside the dictionary have also been improved, which has significantly improved the searchability of the printed dictionary as well as its network (internet) version.
Obraz pór roku utrwalony we frazematyce gwarowej pogranicza małopolsko-mazowieckiego
Authors: Karpeta Paulina
Published: June 2024

This article is a review of phrases related to the seasons, recorded in dialect phrases, which the author collected in several villages on the border of the Lesser Poland-Masovian borderland. This approach concerns the comprehensively recognized cultural and moral sphere by the community and its specifications. As the basic order of the author’s material sources, divided into topics, which allows us to distinguish conceptual categories characteristic of the rural linguistic and cultural community. Research of ancient customs and folk rituals – with the use of socio-economic changes – is a bridge connecting the present with the past.
Frazeologizmy z komponentami šajse, šajs, šajsa w hornjoserbskim katolskim regionje. Hornjoserbski katolski region a ertne wužiwanje serbšćiny w nim
Authors: Kaulfürst Fabian
Published: June 2024

The article highlights the high frequency of loanwords from German, such as šajse and šajs (< Scheiße, Scheiß), in the oral varieties of Upper Sorbian. These words have not yet been described lexicographically for Sorbian. Additionally, a newer variant, šajsa, is gaining popularity. The article focuses on the (currently) most widely used Upper Sorbian oral variety, which is spoken by the Sorbs in the Catholic region of Upper Lusatia for their daily communication. The article aims to present multi-word lexical units of German origin that contain the components šajse, šajs (and šajsa). Lexicographical works on Sorbian have not yet included such units. The components discussed are often tabooed in printed texts, resulting in a lack of corresponding phraseological units in published literature, with few exceptions. Therefore, a specific questionnaire was created for this paper. The data suggests that individuals from the Catholic region primarily use the presented phraseologisms actively in oral communication, or are at least familiar with them. In this way, differences in the spread of certain phraseological units become apparent.
Фраземи на позначення поняття ‘ніколи’ в українській мові
Authors: Коваленко Наталія
Published: June 2024

In Ukrainian dialectology, researchers pay special attention to the identification of phraseological units, their component composition, types of ethnocultural information they accumulate, comparison and interpretation of localised phrase contexts. On the basis of studying the use and spatial distribution of phrasemes denoting the concept of ‘never’, on the material of narratives and dictionaries, it has been determined that the sphere of human life associated with the understanding of the fluidity and cyclicality of life, the impossibility or unreality of certain events, phenomena, abstract concepts is very complex, multidimensional and often encoded. Realised in different linguistic conditions, phraseological units metaphorically nominate the concept of ‘never’ in different ways: natural, physiological, historical, religious and folklore. The application of the method of structural-semantic and semantic modelling of phrases made it possible to determine the main ways of motivating their internal form (figurative specifiers for domestic animals, birds, relief, somatisms, etc.), to identify the ethno-cultural connotation of the units.
Adaptive Seamless Dose-Finding Trials
Authors: Chen Ningyuan , Khademi Amin
Published: June 2024

Problem definition: We study early-stage dose-finding clinical trials with simultaneous consideration of efficacy and toxicity without parametric assumptions on the forms of the unknown dose-efficacy and dose-toxicity curves. We propose algorithms that adaptively allocate doses based on patient responses, in order to maximize the efficacy for the patients during the trial while minimizing the toxicity. Methodology/results: We leverage online learning to design the clinical trial and propose two algorithms. The first one follows dose-escalation principles and analyzes the efficacy and toxicity simultaneously. The second one uses bisection search to identify a safe dose range and then applies upper confidence bound algorithms within the safe range to identify efficacious doses. We show the matching upper and lower bounds for the regret of both algorithms. We find that observing the dose-escalation principle is costly, as the optimal regret of the first algorithm is in the order of [Formula: see text], worse than the optimal regret of the second algorithm, which is in the order of [Formula: see text]. We test our proposed algorithms with three benchmarks commonly used in practice on synthetic and real data sets, and the results show that they are competitive with or significantly outperform the benchmarks. Managerial implications: We provide a novel insight that following the dose-escalation principle inevitably leads to higher regret. The first proposed algorithm is suitable to use when little information about the dose-toxicity profile is available, whereas the second one is appealing when more information is available about the toxicity profile.

Funding: This work was supported by the National Science Foundation [Grant 1651912].

Supplemental Material: The online appendix is available at https://doi.org/10.1287/msom.2023.0246 .
Hepatitis C:the infected blood inquiry
Authors: Hill Rebekah
Published: June 2024

Rebekah Hill discuses the infected blood inquiry final report, as well as looking at the impact nurses can have on patients with hepatitis C and HIV
Inequities in UK Kidney Transplant Access
Authors: Wong Esther ,   UK Renal Registry
Published: June 2024

The UK Renal Registry (UKRR) has released a comprehensive report evaluating access to kidney transplantation waiting lists, uncovering significant disparities across several demographics. This report, compiled as part of the Registry's ongoing assessment of kidney care in the UK, highlights the critical need for equitable access to life-saving transplantation procedures.
Rus Tüccarlarının Osmanlı Sularında Yaşadığı Zorluklar: Deniz Kazaları Sonrası Gasp ve El Koyma Olayları (1750-1800)
Authors: Ertaş Fatih
Published: June 2024

Osmanlı Devleti ile Rus Çarlığı arasındaki savaşlar ve diplomatik ilişkiler iki ülke arasındaki ticarî ilişkileri şekillendirmiştir. Özellikle güç dengelerinin Ruslar lehinde değişmesi ve Osmanlı egemenliğinde bulunan denizlerin Rus ticaret gemilerine açılması, ticarî ilişkilere farklı bir boyut kazandırmıştır. 18. yüzyılın ikinci yarısında Osmanlı sularında seyreden Rus tüccar ve gemileri, deniz kazaları sonrası gasp ve el koyma olaylarına maruz kalmıştır. Bu durum, Osmanlı-Rus ticarî ilişkilerini olumsuz yönde etkilemiştir. Cumhurbaşkanlığı Devlet Arşivleri’nde bulunan Rusya Ahkâm Defterleri, bu olaylara dair önemli bilgiler sunmaktadır. Defterlerde yer alan ve 18. yüzyılın ikinci yarısında meydana gelen 45 deniz kazasının %40’ında gasp veya el koyma vakası görülmüştür. Osmanlı Devleti, bu tür olayları antlaşmalara aykırı ve haksız bulmuştur. Mağdurların haklarını korumak ve iki devlet arasındaki iyi ilişkileri sürdürmek için gerekli adımları atmıştır. Bu çalışma, deniz kazaları sonrası gasp ve el koyma olaylarını ve Osmanlı Devleti’nin bu olaylara yönelik çözüm arayışlarını incelemektedir. Böylece, Osmanlı-Rus ticarî ilişkileri ve denizcilik tarihinin daha iyi anlaşılmasına katkıda bulunulması amaçlanmıştır.