bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association Between Oncology Clinical Pathway Utilization and Toxicity and Cost Outcomes in Patients With Metastatic Solid Tumors
Authors: Liu Ying , Mullangi Samyukta , Debono David , Chen Xiaoxue , Pham Timothy , Fisch Michael J. , Gordon Aliza S. , Hershman Dawn L. 
Published: June 2023

PURPOSE This retrospective observational study compared cancer care toxicity and cost outcomes for patients with metastatic cancer with nine different cancer types prescribed on- versus off-pathway regimens. METHODS This study used claims and authorization data from a national insurer between January 1, 2018, and October 31, 2021. Participants included adults with metastatic breast, lung, colorectal, pancreatic, melanoma, kidney, bladder, gastric, or uterine cancer, who were prescribed first-line anticancer regimens. Multivariable regressions were used to assess outcomes including counts of emergency room visits or hospitalizations, use of supportive care medications, immune-related adverse events (IRAEs), and health care costs. RESULTS Of the 8,357 patients in the study, 5,453 (65.3%) were prescribed on-pathway regimens. The on-pathway proportion trended downward, from 74.3% in 2018 to 59.8% in 2021. The on- and off-pathway groups had a similar proportion of patients with treatment-related hospitalization (adjusted odds ratio [aOR], 1.080; P = .201) and IRAEs (aOR, 0.961; P = .497). More all-cause hospitalizations (aOR, 1.679; P = .013) were observed among patients with melanoma treated on-pathway. The on-pathway group had higher use of supportive care drugs in bladder cancer (aOR, 4.602; P < .001) and colorectal cancer (aOR, 4.465; P < .001), and lower use in breast (aOR, 0.668; P = .001) and lung cancer (aOR, 0.550; P < .001). On average, on-pathway patients incurred $17,589 less total health care cost ( P < .001), and $22,543 lower chemotherapy cost ( P < .001) than those from the off-pathway group. CONCLUSION Our findings suggest that use of on-pathway regimens was associated with significant cost savings. Toxicity outcomes were variable by disease, but overall, there were similar numbers of treatment-related hospitalizations and IRAEs compared to off-pathway regimens. This cross-institutional study provides evidence to support the use of clinical pathway regimens for patients with metastatic cancer.
Prognostic Value of Neurotrophic Tyrosine Receptor Kinase Gene Fusions in Solid Tumors for Overall Survival: A Systematic Review and Meta-Analysis
Authors: Lassen Ulrik , Bokemeyer Carsten , Garcia-Foncillas Jesus , Italiano Antoine , Vassal Gilles , Paracha Noman , Marian Marisca , Chen Yuxian , Linsell Louise , Abrams Keith 
Published: June 2023

PURPOSE Evidence suggests that neurotrophic tyrosine receptor kinase ( NTRK) gene fusions in solid tumors are predictive biomarkers for targeted inhibition across a number of adult and pediatric tumor types. However, despite robust clinical response to tyrosine receptor kinase (TRK) inhibitors, the natural history and prognostic implications of NTRK fusions in solid tumors are poorly understood. It is important to evaluate their prognostic significance on survival to provide some context to the clinical effectiveness observed in clinical trials of TRK-targeted therapies. METHODS A systematic literature review was conducted in Medline, Embase, Cochrane, and PubMed to identify studies comparing the overall survival (OS) of patients with NTRK fusion–positive ( NTRK+) versus NTRK fusion–negative ( NTRK–) tumors. Five retrospective matched case-control studies published before 11 August 2022 were assessed for inclusion, and three were selected for the meta-analysis (sample size: 69 NTRK+, 444 NTRK–). Risk of bias was assessed using the Risk of Bias Assessment tool for Non-randomized Studies tool. The pooled hazard ratio (HR) was estimated using a Bayesian random-effects model. RESULTS In the meta-analysis, the median follow-up ranged from 2 to 14 years and the median OS was between 10.1 and 12.7 months (where reported). Comparing patients with tumors NTRK+ and NTRK–, the pooled HR estimate for OS was 1.51 (95% credible interval, 1.01 to 2.29). The patients analyzed had no previous or current exposure to TRK inhibitors. CONCLUSION In patients not treated with TRK inhibitor therapies, those with NTRK+ solid tumors have a 50% increased risk of mortality within 10 years from diagnosis or the start of standard therapy compared with those with NTRK– status. Although this is the most robust estimate of the comparative survival rate to date, further studies are required to reduce uncertainty.
Integration of Biorelevant Pediatric Dissolution Methodology into PBPK Modeling to Predict In Vivo Performance and Bioequivalence of Generic Drugs in Pediatric Populations: a Carbamazepine Case Study
Authors: Pawar Gopal , Wu Fang , Zhao Liang , Fang Lanyan , Burckart Gilbert J. , Feng Kairui , Mousa Youssef M. , Al Shoyaib Abdullah , Jones Marie-Christine , Batchelor Hannah K. 
Published: June 2023

AbstractThis
study investigated the impact of gastro-intestinal fluid volume and bile salt (BS) concentration on the dissolution of carbamazepine (CBZ) immediate release (IR) 100 mg tablets and to integrate these in vitro biorelevant dissolution profiles into physiologically based pharmacokinetic modelling (PBPK) in pediatric and adult populations to determine the biopredictive dissolution profile. Dissolution profiles of CBZ IR tablets (100 mg) were generated in 50–900 mL biorelevant adult fasted state simulated gastric and intestinal fluid (Ad-FaSSGF and Ad-FaSSIF), also in three alternative compositions of biorelevant pediatric FaSSGF and FaSSIF medias at 200 mL. This study found that CBZ dissolution was poorly sensitive to changes in the composition of the biorelevant media, where dissimilar dissolution (F2 = 46.2) was only observed when the BS concentration was changed from 3000 to 89 μM (Ad-FaSSIF vs Ped-FaSSIF 50% 14 BS). PBPK modeling demonstrated the most predictive dissolution volume and media composition to forecast the PK was 500 mL of Ad-FaSSGF/Ad-FaSSIF media for adults and 200 mL Ped-FaSSGF/FaSSIF media for pediatrics. A virtual bioequivalence simulation was conducted by using Ad-FaSSGF and/or Ad-FaSSIF 500 mL or Ped-FaSSGF and/or Ped-FaSSIF 200 mL dissolution data for CBZ 100 mg (reference and generic test) IR product. The CBZ PBPK models showed bioequivalence of the product. This study demonstrates that the integration of biorelevant dissolution data can predict the PK profile of a poorly soluble drug in both populations. Further work using more pediatric drug products is needed to verify biorelevant dissolution data to predict the in vivo performance in pediatrics.
Graphical Abstract
ARPC5 deficiency leads to severe early-onset systemic inflammation and mortality
Authors: Sindram Elena , Caballero-Oteyza Andrés , Kogata Naoko , Chor Mei Huang Shaina , Alizadeh Zahra , Gámez-Díaz Laura , Fazlollhi Mohammad Reza , Peng Xiao , Grimbacher Bodo , Way Michael , Proietti Michele 
Published: June 2023

ABSTRACT
The Arp2/3 complex drives the formation of branched actin networks that are essential for many cellular processes. In humans, the ARPC5 subunit of the Arp2/3 complex is encoded by two paralogous genes (ARPC5 and ARPC5L) with 67% identity. Through whole-exome sequencing, we identified a biallelic ARPC5 frameshift variant in a female child who presented with recurrent infections, multiple congenital anomalies, diarrhea and thrombocytopenia, and suffered early demise from sepsis. Her consanguineous parents also had a previous child who died with similar clinical features. Using CRISPR/Cas9-mediated approaches, we demonstrate that loss of ARPC5 affects actin cytoskeleton organization and function in vitro. Homozygous Arpc5−/− mice do not survive past embryonic day 9 owing to developmental defects, including loss of the second pharyngeal arch, which contributes to craniofacial and heart development. Our results indicate that ARPC5 is important for both prenatal development and postnatal immune signaling, in a non-redundant manner with ARPC5L. Moreover, our observations add ARPC5 to the list of genes that should be considered when patients present with syndromic early-onset immunodeficiency, particularly if recessive inheritance is suspected.
Development of High-Temperature Superconducting Coil for Solid-State NMR Experiments
Authors: Yamada Kazuhiko , Takahashi Masato , Tritrakarn Techit , Kato Shota , Okamura Tetsuji , Irie Kotaro , Hoshi Haruki , Saito Atsushi 
Published: June 2023

Abstract
A high-temperature superconducting (HTS) coil, in which YBa2Cu3O7-δ is vapor-deposited on the surface of a sapphire plane, has been developed to increase signal-to-noise ratios (SNR) in solid-state nuclear magnetic resonance (NMR) measurements. The Q-factor of the NMR probe is found to be 16,125 at the resonant frequency of 38.525 MHz. A single sharp signal, full width at half maximum of 20 ppm, can be detected by the HTS coil in a stationary solid-state 79Br NMR spectrum of a polycrystalline potassium bromide at the temperature of 9 K. Compared with the results for an isomorphic copper coil, an improvement of a factor of 6.6 is obtained for SNR, indicating that accumulation time of NMR experiments can be reduced to 1/44.
The COVID-19 pandemic and its impacts on diet quality and food prices in sub-Saharan Africa
Authors: Ismail Abbas , Madzorera Isabel , Apraku Edward A. , Tinkasimile Amani , Dasmane Dielbeogo , Zabre Pascal , Ourohire Millogo , Assefa Nega , Chukwu Angela , Workneh Firehiwot , Mapendo Frank , Lankoande Bruno , Hemler Elena , Wang Dongqing , Abubakari Sulemana W. , Asante Kwaku P. , Baernighausen Till , Killewo Japhet , Oduola Ayoade , Sie Ali , Soura Abdramane , Vuai Said , Smith Emily , Berhane Yemane , Fawzi Wafaie W. 
Published: June 2023

Background
Sub-Saharan Africa faces prolonged COVID-19 related impacts on economic activity, livelihoods and nutrition, with recovery slowed down by lagging vaccination progress.

Objective
This study investigated the economic impacts of COVID-19 on food prices, consumption and dietary quality in Burkina Faso, Ethiopia, Ghana, Nigeria, and Tanzania.

Methods
We conducted a repeated cross-sectional study using a mobile platform to collect data from July-December, 2021 (round 2). We assessed participants’ dietary intake of 20 food groups over the previous seven days and computed the primary outcome, the Prime Diet Quality Score (PDQS), and Dietary Diversity Score (DDS), with higher scores indicating better quality diets. We used generalized estimating equation (GEE) linear regression models to assess factors associated with diet quality during COVID-19.

Results
Most of the respondents were male and the mean age was 42.4 (±12.5) years. Mean PDQS (±SD) was low at 19.4(±3.8), out of a maximum score of 40 in this study. Respondents (80%) reported higher than expected prices for all food groups. Secondary education or higher (estimate: 0.73, 95% CI: 0.32, 1.15), medium wealth status (estimate: 0.48, 95% CI: 0.14, 0.81), and older age were associated with higher PDQS. Farmers and casual laborers (estimate: -0.60, 95% CI: -1.11, -0.09), lower crop production (estimate: -0.87, 95% CI: -1.28, -0.46) and not engaged in farming (estimate: -1.38, 95% CI: -1.74, -1.02) were associated with lower PDQS.

Conclusion
Higher food prices and lower diet quality persisted during the COVID-19 pandemic. Economic and social vulnerability and reliance on markets (and lower agriculture production) were negatively associated with diet quality. Although recovery was evident, consumption of healthy diets remained low. Systematic efforts to address the underlying causes of poor diet quality through transforming food system value chains, and mitigation measures, including social protection programs and national policies are critical.
Pharmacists’ communication skills with deaf and hard of hearing patients: A needs assessment
Authors: Al Aloola Noha , Alanazi Maram , Alotaibi Norah , Alwhaibi Monira 
Published: June 2023

Objectives
Assess the Saudi pharmacists’ perceptions of their responsibilities toward deaf and hard-of-hearing (DHH) patients, their current practices, and their need for communication skills training.

Study design
A prospective cross-sectional study.

Methods
Pharmacist and deaf communication questionnaire (PDCQ), a newly structured, validated, pilot-tested, and self-administered online questionnaire, was used to collect data. A total of 303 pharmacists working in the Saudi community and outpatient pharmacies participated in the study. Data were analyzed using SPSS and descriptive statistics were used to describe the study findings. These included Mean ± standard deviation (SD), frequency, and Chi-square tests.

Results
Most pharmacists perceived that DHH patients had difficulty correctly understanding their medication instructions. Writing was the most common method used for communication, whereas the unavailability of interpreters and the low reading levels of these patients were the highest barriers to communication. Moreover, most pharmacists believed that they should be skilled at communicating with DHH patients. However, many pharmacists felt that they are not well prepared to communicate with these patients.

Conclusion
This research highlights the poor skills, low confidence and low knowledge Saudi pharmacists have about their legal obligations towards DHH patients. In addition, there is paucity of sufficient resources to help pharmacists improve their communication with such patients.
Systemic pro- and anti-inflammatory profiles in acute non-specific low back pain: An exploratory longitudinal study of the relationship to six-month outcome
Authors: Chang Wei-Ju , Jenkins Luke C. , Humburg Peter , Wasinger Valerie , Walton David M. , Schabrun Siobhan M. 
Published: June 2023

ObjectivesPro-inflammatory molecules are thought to underpin the development of chronic low back pain (LBP). Although research has begun to explore the association between pro-inflammatory molecules in acute LBP and long-term outcome, no study has explored the role of anti-inflammatory molecules. We aimed to explore whether levels of systemic pro- and anti-inflammatory molecules 1) changed over a period of six months from the onset of acute LBP; 2) differed between people who were recovered (N = 11) and unrecovered (N = 24) from their episode of LBP at six months; 3) baseline psychological factors were related to inflammatory molecule serum concentrations at baseline, three and six months.MethodsWe retrospectively included participants with acute LBP included from a larger prospective trial and examined blood samples for the measurement of pro- and anti-inflammatory molecules and measures of pain, disability, and psychological factors at baseline, three and six months.ResultsThe serum concentrations of pro- and anti-inflammatory molecules did not differ over time when compared between participants who recovered and those who did not recover at six-month follow-up. At three months, the unrecovered group had higher interleukin (IL)-8 and IL-10 serum concentrations than the recovered group. Baseline psychological factors were not related to inflammatory molecules at any time point.DiscussionThis exploratory study showed that levels of systemic inflammatory molecules did not change over the course of LBP, irrespective of whether people were recovered or unrecovered at six months. There was no relationship between acute-stage psychological factors and systemic inflammatory molecules. Further investigation is needed to elucidate the contribution of pro- and anti-inflammatory molecules to long-term LBP outcome.
Minimum acceptable dietary intake among children aged 6–23 months in Ethiopia: A systematic review and meta-analysis
Authors: Kassie Gizachew Ambaw , Gebrekidan Amanuel Yosef , Enaro Eskinder Yilma , Asgedom Yordanos Sisay 
Published: June 2023

Background
In the absence of minimum acceptable diet, children aged 6–23 months are vulnerable to malnutrition. Not feeding at least the minimum acceptable diet is a major global problem, particularly in developing countries. Even though many studies have been conducted in Ethiopia there are inconsistencies. Therefore, this review aimed to estimate the pooled prevalence of a minimum acceptable diet in Ethiopia.

Methods
Published articles from various electronic databases, such as PubMed/MEDLINE, EMBASE, Google Scholar, and Science Direct were systematically searched. All cross-sectional studies conducted on the minimum acceptable diet of children aged 6–24 months and published up to October 30/2021 were included in this review. Data were extracted using an Excel spreadsheet and analyzed using STATA version 14.1. The random-effects model was used to estimate the pooled prevalence, and a subgroup analysis was performed to identify the possible source of heterogeneity. Begg’s and Egger’s tests were used to identify possible publication bias.

Results
Nine cross-sectional studies involving 4,223 participants were included. Significant heterogeneity was observed across the studies (I2 = 99.4%). The pooled prevalence of minimum acceptable diet in Ethiopia was found to be 25.69% (95% CI: 11.96, 39.41)

Conclusion
This review revealed that the minimum acceptable dietary intake among children aged 6–23 months in Ethiopia was relatively low; only 1 in 4 of children met the minimum acceptable diet. This indicates that the government should promote child feeding practices according to guidelines to increase the proportion of children with a minimum acceptable diet.
Measuring implementation outcomes in the context of scaling up possible serious bacterial infection guidelines: Implications for measurement and programs
Authors: Abuya Timothy , Odwe George , Ndwiga Charity , Okondo Chantalle , Liambila Wilson , Mungai Samuel , Mwaura Peter , K’Oduol Kezia , Natecho Alice , Gitaka Jesse , Warren Charlotte E. 
Published: June 2023

Background
Reducing the burden of neonatal sepsis requires timely identification and initiation of suitable antibiotic treatment in primary health care (PHC) settings. Countries are encouraged to adopt simplified antibiotic regimens at the PHC level for treating sick young infants (SYI) with signs of possible serious bacterial infection (PSBI). As countries implement PSBI guidelines, more lessons on effective implementation strategies and outcome measurements are needed. We document pragmatic approaches used to design, measure and report implementation strategies and outcomes while adopting PSBI guidelines in Kenya.

Methods
We designed implementation research using longitudinal mixed methods embedded in a continuous regular systematic learning and adoption of evidence in the PHC context. We synthesized formative data to co-create with stakeholders, implementation strategies to incorporate PSBI guidelines into routine service delivery for SYIs. This was followed by quarterly monitoring for learning and feedback on the effect of implementation strategies, documented lessons learned and tracked implementation outcomes. We collected endline data to measure the overall effect on service level outcomes.

Results
Our findings show that characterizing implementation strategies and linking them with implementation outcomes, helps illustrate the pathway between the implementation process and outcomes. Although we have demonstrated that it is feasible to implement PSBI in PHC, effective investment in continuous capacity strengthening of providers through blended approaches, efficient use of available human resources, and improving the efficiency of service areas for managing SYIs optimizes timely identification and management of SYI. Sustained provision of commodities for management of SYI facilitates increased uptake of services. Strengthening facility-community linkages supports adherence to scheduled visits. Enhancing the caregiver’s preparedness during postnatal contacts in the community or facility will facilitate the effective completion of treatment.

Conclusion
Careful design, and definition of terms related to the measurement of implementation outcomes and strategies enable ease of interpretation of findings. Using the taxonomy of implementation outcomes help frame the measurement process and provides empirical evidence in a structured way to demonstrate causal relationships between implementation strategies and outcomes. Using this approach, we have illustrated that the implementation of simplified antibiotic regimens for treating SYIs with PSBI in PHC settings is feasible in Kenya.
Feasibility of a patient-oriented navigation programme for patients with lung cancer or stroke in Germany: Protocol of the CoreNAVI study
Authors: Gödde Kathrin , Fügemann Hella , Goerling Ute , Grittner Ulrike , Kohl Raphael , Meisel Andreas , Reinhold Thomas , Schnitzer Susanne , Deckert P. Markus , Frost Nikolaj , Schreiber Stephan J. , Rieckmann Nina , Holmberg Christine 
Published: June 2023

Background
Patient navigation programmes were introduced in the United States and recently gained interest in Germany, where the health care system is fragmented. Navigation programmes aim to decrease barriers to care for patients with age-associated diseases and complex care paths. Here we describe a feasibility study to evaluate a patient-oriented navigation model that was developed in a first project phase by integrating data about barriers to care, vulnerable patient populations and existing support services.

Methods
We designed a mixed-methods feasibility study that consists of two two-arm randomized controlled trials aligned with observational cohorts. The intervention group of the RCTs gets support by personal navigators for 12 months. The control group receives a brochure with regional support offers for patients and caregivers. The feasibility of the patient-oriented navigation model for two prototypic age-associated diseases, lung cancer and stroke, is evaluated with regard to its acceptance, demand, practicality and efficacy. This investigation includes process evaluation measures with detailed documentation of the screening and recruitment process, questionnaires about satisfaction with navigation, observant participation and qualitative interviews. Estimates of efficacy for patient-reported outcomes are obtained at three follow-up time points including satisfaction with care and health-related quality of life. Furthermore, we analyze health insurance data from patients of the RCT insured at a large German health insurance (AOK Nordost) to investigate heath care utilization, costs and cost effectiveness.

Trial registration
The study is registered at the German Clinical Trial Register (DRKS-ID: DRKS00025476).