bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimality criteria for futility stopping boundaries for group sequential designs with a continuous endpoint
Authors: Li Xieran , Herrmann Carolin , Rauch Geraldine 
Published: November 2020

AbstractBackgroundIn clinical trials with fixed study designs, statistical inference is only made when the trial is completed. In contrast, group sequential designs allow an early stopping of the trial at interim, either for efficacy when the treatment effect is significant or for futility when the treatment effect seems too small to justify a continuation of the trial. Efficacy stopping boundaries based on alpha spending functions have been widely discussed in the statistical literature, and there is also solid work on the choice of adequate futility stopping boundaries. Still, futility boundaries are often chosen with little or completely without theoretical justification, in particular in investigator initiated trails. Some authors contributed to fill this gap. In here, we rely on an idea of Schüler et al. (2017) who discuss optimality criteria for futility boundaries for the special case of trials with (multiple) time-to-event endpoints. Their concept can be adopted to define “optimal” futility boundaries (with respect to given performance indicators) for continuous endpoints.MethodsWe extend Schülers’ definition for “optimal” futility boundaries to the most common study situation of a single continuous primary endpoint compared between two groups. First, we introduce the analytic algorithm to derive these futility boundaries. Second, the new concept is applied to a real clinical trial example. Finally, the performance of a study design with an “optimal” futility boundary is compared to designs with arbitrarily chosen futility boundaries.ResultsThe presented concept of deriving futility boundaries allows to control the probability of wrongly stopping for futility, that means stopping for futility even if the treatment effect is promizing. At the same time, the loss in power is also controlled by this approach. Moreover, “optimal” futility boundaries improve the probability of correctly stopping for futility under the null hypothesis of no difference between two groups.ConclusionsThe choice of futility boundaries should be thoroughly investigated at the planning stage. The sometimes met, arbitrary choice of futility boundaries can lead to a substantial negative impact on performance. Applying futility boundaries with predefined optimization criteria increases efficiency of group sequential designs. Other optimization criteria than proposed in here might be incorporated.
Effect of complementary feeding behavior change communication delivered through community-level actors on the time of initiation of complementary foods in rural communities of West Gojjam zone, Northwest Ethiopia: a cluster-randomized controlled trial
Authors: Abiyu Chalachew , Belachew Tefera 
Published: November 2020

AbstractBackgroundAttaining the recommended level of complementary feeding practices remains a serious challenge in many developing countries. Complementary foods are usually untimely initiated, which has adverse consequences on the growth, development, and survival of infants. The focus of most studies conducted worldwide seemed to be on the effect of behavior change interventions on the adequacy of complementary diets; but not on the timing of initiations. Moreover, many of the interventions targeted only mothers/caregivers of infants, and studies that engaged the family members are scarce. This study aimed to evaluate the effectiveness of complementary feeding behavior change communication delivered through women development army leaderson the time of initiation of complementary foods.MethodsWe conducted a cluster-randomized controlled trial in rural communities of West Gojjam Zone, Northwest Ethiopia from February 2017 to March 2018. A total of 16 geographic clusters were selected. Trial participants in the intervention group received complementary feeding behavior change intervention for 9 months whereas those in the control group received only the usual health care. Trained women development army leaders delivered the intervention. A pre-tested, structured interviewer-administered questionnaire was used for data collection. Generalized estimated equation (GEE) regression and survival analyses were used to test differences in time of initiation of complementary food between the study groups.ResultsThe intervention significantly improved the likelihood of timely initiation of complementary food by 22 percentage points [RR: 2.6; 95% CI: 1.78–5.86], and reduced the risk of late initiations by 19 percentage points [RR: 2.8; 95% CI: 1.83–4.37]. The complementary food initiation survival curve for the control group after 6 months was constantly above the curve than for the intervention group. The median age at the introduction of complementary food for infants was 6 months in the intervention group, and 6.7 months in the control group and the difference was statistically significant (P-value < 0.001).ConclusionsComplementary feeding behavior change communication improved the rate of timely initiation of complementary foods and reduced the risk of late initiations.Trial registrationClinicalTrials.gov,NCT03488680. Registered 5 April 2018-Retrospectively registered,https://clinicaltrials.gov/ct2/show/NCT03488680.
A new fluoroscopic view for evaluation of anteromedial cortex reduction quality during cephalomedullary nailing for intertrochanteric femur fractures: the 30° oblique tangential projection
Authors: Chen Shi-Yi , Chang Shi-Min , Tuladhar Rujan , Wei Zhen , Xiong Wen-Feng , Hu Sun-Jun , Du Shou-Chao 
Published: November 2020

AbstractBackgroundAnteromedial cortex-to-cortex reduction is a key parameter for stable reconstruction of the fracture fragments during the intertrochanteric fracture fixation. This paper introduces the oblique fluoroscopic projection as a novel method to evaluate the quality of anteromedial cortical apposition.MethodsThree proximal femur specimens were marked with steel wires along five anatomic landmarks: Greater trochanter, Lesser trochanter, Intertrochanteric line, Anterolateral tubercle and the Anteromedial cortical line. After obtaining the standard femoral neck AP and lateral fluoroscopic images, the C-arm was rotated by every 5°increments until a clear tangential view of the antero-medial-inferior corner cortex was observed. 98 cases of intertrochanteric hip fractures were enrolled from April 2018 to October 2019. After fixation with the nails, the intra-operative anteromedial cortex reduction quality was evaluated from the AP, the true lateral, and the new anteromedial oblique fluoroscopic images. The fluoroscopic results were compared with the post-operative 3D-CT reconstruction images.ResultsThe specimen study showed that internal rotation of the C-arm to approximately 30 ° can remove all the obscure shadows and clearly display the antero-medial-inferior cortical tangent line. Clinically,the positive, neutral and negative apposition of different cortices via intra-operative fluoroscopic images showed79, 19 and 0 cases of medial cortical apposition in AP views; 2, 68 and 28 cases of anterior cortices in lateral views;and 22, 51 and 25cases of anteromedial cortical apposition in oblique views respectively. The post-operative 3D-CT reconstruction images revealed that the final anteromedial cortical contact was noted in 62 cases (63.3%), and lost in 36 cases (36.7%). The overall coincidence rate between intra-operative fluoroscopy and post-operative 3D-CT was 63.3% (62/98) in AP view,79.6% (78/98) in lateral view, and 86.7% (85/98) in oblique view(p < 0.001). Negative cortical apposition in oblique view was highly predictive of a final loss of cortical support on 3D CT (24/25 cases, 96%).And non-negative cortical apposition in oblique view was highly associated with true cortical support on 3D CT images (61/73 cases, 83.6%) (p < 0.001).ConclusionsBesides the AP and lateral projections, an anteromedial oblique view of 30° certifies to be a very useful means for evaluation of the fracture reduction quality of anteromedial cortical apposition.
Quality of recovery after total hip and knee arthroplasty in South Africa: a national prospective observational cohort study
Authors: Plenge Ulla , Parker Romy , Davids Shamiela , Davies Gareth L. , Fullerton Zahnne , Gray Lindsay , Groenewald Penelope , Isaacs Refqah , Kauta Ntambue , Louw Frederik M. , Mazibuko Andile , North David M. , Nortje Marc , Nunes Glen M. , Pebane Neo , Rajah Chantal , Roos John , Ryan Paul , September Winlecia V. , Shanahan Heidi , Siebritz Ruth E. , Smit Rian W. , Sombili Simon , Torborg Alexandra , van der Merwe Johan F. , van der Westhuizen Nico , Biccard Bruce 
Published: November 2020

Abstract

Background
Encouraged by the widespread adoption of enhanced recovery protocols (ERPs) for elective total hip and knee arthroplasty (THA/TKA) in high-income countries, our nationwide multidisciplinary research group first performed a Delphi study to establish the framework for a unified ERP for THA/TKA in South Africa. The objectives of this second phase of changing practice were to document quality of patient recovery, record patient characteristics and audit standard perioperative practice.

Methods
From May to December 2018, nine South African public hospitals conducted a 10-week prospective observational study of patients undergoing THA/TKA. The primary outcome was ‘days alive and at home up to 30 days after surgery’ (DAH30) as a patient-centred measure of quality of recovery incorporating early death, hospital length of stay (LOS), discharge destination and readmission during the first 30 days after surgery. Preoperative patient characteristics and perioperative care were documented to audit practice.

Results
Twenty-one (10.1%) out of 207 enrolled patients had their surgery cancelled or postponed resulting in 186 study patients. No fatalities were recorded, median LOS was 4 (inter-quartile-range (IQR), 3–5) days and 30-day readmission rate was 3.8%, leading to a median DAH30 of 26 (25–27) days. Forty patients (21.5%) had pre-existing anaemia and 24 (12.9%) were morbidly obese. In the preoperative period, standard care involved assessment in an optimisation clinic, multidisciplinary education and full-body antiseptic wash for 67 (36.2%), 74 (40.0%) and 55 (30.1%) patients, respectively. On the first postoperative day, out-of-bed mobilisation was achieved by 69 (38.1%) patients while multimodal analgesic regimens (paracetamol and Non-Steroid-Anti-Inflammatory-Drugs) were administered to 29 patients (16.0%).

Conclusion
Quality of recovery measured by a median DAH30 of 26 days justifies performance of THA/TKA in South African public hospitals. That said, perioperative practice, including optimisation of modifiable risk factors, lacked standardisation suggesting that quality of patient care and postoperative recovery may improve with implementation of ERP principles. Notwithstanding the limited resources available, we anticipate that a change of practice for THA/TKA is feasible if ‘buy-in’ from the involved multidisciplinary units is obtained in the next phase of our nationwide ERP initiative.

Trial registration
The study was registered with ClinicalTrials.gov (NCT03540667).
Association between coarse particulate matter and inflammatory and hemostatic markers in a cohort of midlife women
Authors: Davis Emilie , Malig Brian , Broadwin Rachel , Ebisu Keita , Basu Rupa , Gold Ellen B. , Qi Lihong , Derby Carol A. , Park Sung Kyun , Wu Xiangmei (May) 
Published: November 2020

Abstract

Background
Exposure to particulate matter air pollution has been associated with cardiovascular disease (CVD) morbidity and mortality; however, most studies have focused on fine particulate matter (PM2.5) exposure and CVD. Coarse particulate matter (PM10–2.5) exposure has not been extensively studied, particularly for long-term exposure, and the biological mechanisms remain uncertain.

Methods
We examined the association between ambient concentrations of PM10–2.5 and inflammatory and hemostatic makers that have been linked to CVD. Annual questionnaire and clinical data were obtained from 1694 women (≥ 55 years old in 1999) enrolled in the longitudinal Study of Women’s Health Across the Nation (SWAN) at six study sites from 1999 to 2004. Residential locations and the USEPA air monitoring network measurements were used to assign exposure to one-year PM10–2.5, as well as co-pollutants. Linear mixed-effects regression models were used to describe the association between PM10–2.5 exposure and markers, including demographic, health and other covariates.

Results
Each interquartile (4 μg/m3) increase in one-year PM10–2.5 exposure was associated with a 5.5% (95% confidence interval [CI]: 1.8, 9.4%) increase in levels of plasminogen activator inhibitor-1 (PAI-1) and 4.1% (95% CI: − 0.1, 8.6%) increase in high-sensitivity C-creative Protein (hs-CRP). Stratified analyses suggested that the association with PAI-1 was particularly strong in some subgroups, including women who were peri-menopausal, were less educated, had a body mass index lower than 25, and reported low alcohol consumption. The association between PM10–2.5 and PAI-1 remained unchanged with adjustment for PM2.5, ozone, nitrogen dioxide, and carbon monoxide.

Conclusions
Long-term PM10–2.5 exposure may be associated with changes in coagulation independently from PM2.5, and thus, contribute to CVD risk in midlife women.
Projecting supply and demand for pharmacists in pharmacies based on the number of prescriptions and system dynamics modeling
Authors: Morii Yasuhiro , Furuta Seiichi , Ishikawa Tomoki , Fujiwara Kensuke , Yamashina Hiroko , Ogasawara Katsuhiko 
Published: November 2020

Abstract

Background
Pharmacists play an important role in promoting people’s health in Japan, which has an aging population. Hence, it is necessary that the distribution of pharmacists meets the population’s needs in each region. This study projects the future supply and demand for pharmacists in pharmacies to consider an optimal distribution of pharmacists.

Methods
The future supply of pharmacists working in pharmacies in Hokkaido is projected using system dynamics modeling, according to their career path. The demand is projected based on the number of prescriptions, sourced from publicly available sources. The analysis period is 2015–2040. The estimated demand is converted into the number of pharmacists and the sufficiency is evaluated using sufficiency ratio (supply/demand ratio). Sensitivity analyses of the sufficiency ratio were conducted to estimate the effects of changes in parameters such as national exam pass rate, enrollments, attrition rates, the number of prescriptions per pharmacist, and diffusion of newly licensed pharmacists.

Results
The projected supply, in 2025 and 2040, is 1.24 and 1.56 times, respectively, as that in 2015 and the demand is 1.11 and 0.98 times, respectively. In 2015, although the sufficiency ratio in Hokkaido overall is 1.19, the ratios are higher in urban medical areas and lower than 1 in rural medical areas, such as Minamihiyama, Emmon, and Nemuro. By 2040, the sufficiency ratios are greater than 1 for all areas except for Emmon and higher than 2 in some areas. The sensitivity analyses found that the sufficiency ratio was most sensitive to diffusion of newly licensed pharmacists and the number of prescriptions per pharmacist.

Conclusion
Optimal distribution should be considered, as the results reveal a possible shortage in the number of pharmacists in rural medical areas in 2015–2025. Conversely, as the demand is projected to decrease after 2025 with a population decrease, future supply should be determined in order not to cause an oversupply after 2025. Refinements of the projection model should be conducted since the related factors such as the roles of pharmacists will change over time.
Discernment between candidate mechanisms for KRAS G13D colorectal cancer sensitivity to EGFR inhibitors
Authors: McFall Thomas , Schomburg Noah K. , Rossman Kent L. , Stites Edward C. 
Published: November 2020

Abstract
Phase three clinical trial evidence suggests that colorectal cancers with the KRAS G13D mutation may benefit from EGFR inhibitors, like cetuximab, in contrast to the other most common KRAS mutations. A mechanism to explain why this mutation behaves differently from other KRAS mutations had long been lacking. Two recent studies have reproduced KRAS G13D specific sensitivity to cetuximab in cellular models, and both have implicated the tumor suppressor NF1 as a critical variable in determining sensitivity and resistance. One study proposes a mechanism that focuses on the inhibition of active, GTP-bound wild-type RAS, which is proposed to occur to a greater extent in KRAS G13D tumors due to the inability of KRAS G13D to bind NF1 well. The other study suggests NF1 can convert GTP-bound KRAS G13D to inactive, GDP-bound KRAS G13D. Here, we report an inability to reproduce cellular and biophysical studies that suggested NF1 has strong GTPase activity on KRAS G13D. We also report additional data that further suggests only WT RAS-GTP levels are reduced with EGFR inhibition and that KRAS G13D is impaired in binding to NF1. These new experiments further support a mechanism in which cetuximab inhibits wild-type (HRAS and NRAS) signals in KRAS G13D colorectal cancers.
Consecutive intra-gingival injections of lipopolysaccharide and butyric acid to mice induce abnormal behavior and changes in cytokine concentrations
Authors: Tsukahara Takamitsu , Toyoda Atsushi , Kawase Takahiro , Nakamura Shin-ichi , Ochiai Kuniyasu 
Published: November 2020

AbstractBackgroundPeriodontopathic bacteria such asPorphyromonas gingivalisproduce several metabolites, including lipopolysaccharide (LPS) andn-butyric acid (BA). Past work suggested that periodontal infection may cause cognitive impairment in mice.AimsTo elucidate the mechanisms by which metabolites such as LPS and BA, resulting fromPorphyromonas gingivalisactivity, induce immunological and physiological abnormalities in mice.MethodsIn the present work, 28 male ICR mice were placed in an open-field arena and the total distance (cm/600 s) they covered was recorded. Based on their moving distances, mice were divided into 4 groups (n= 7) and injected the following substances into their gingival tissues for 32 consecutive days: saline (C), 5 mmol/L of BA (B), 1 μg/mouse of LPS (L), and BA-LPS (BL) solutions. Distances covered by mice were also measured on days 14 and 21, with their habituation scores considered as “(moving distance on day 14 or 21)/(moving distance on day 0)”. Afterwards, mice were dissected, and hippocampal gene expression and the concentrations of short-chain fatty acids, neurotransmitters and cytokines in their blood plasma and brains were analyzed. In addition, mouse brain and liver tissues were fixed and visually assessed for histopathological abnormalities.ResultsGroup BL had significantly higher habituation scores than C and B on day 14. LPS induced higher habituation scores on day 21. LPS induced significant decreases in the mRNA levels of interleukin (IL)-6 and brain-derived neurotrophic factors, and an increase in neurotrophic tyrosine kinase receptor type 2. In both plasma and brain, LPS induced a significant acetate increase. Moreover, LPS significantly increased acetylcholine in brain. In plasma alone, LPS and BA significantly decreased monocyte chemoattractant protein 1 (MCP-1). However, while LPS significantly decreased tyrosine, BA significantly increased it. Lastly, LPS significantly decreased IL-6 and tumor necrosis factor in plasma. No histopathological abnormalities were detected in liver or brain tissues of mice.ConclusionWe showed that injections of LPS and/or BA induced mice to move seemingly tireless and that both LPS and BA injections strongly induced a reduction of MCP-1 in blood plasma. We concluded that LPS and BA may have been crucial to induce and/or aggravate abnormal behavior in mice.
Pediatric craniospinal irradiation with a short partial-arc VMAT technique for medulloblastoma tumors in dosimetric comparison
Authors: Pollul Gerhard , Bostel Tilman , Grossmann Sascha , Akbaba Sati , Karle Heiko , Stockinger Marcus , Schmidberger Heinz 
Published: November 2020

Abstract

Background
This study aimed to contrast four different irradiation methods for pediatric medulloblastoma tumors in a dosimetric comparison regarding planning target volume (PTV) coverage and sparing of organs at risk (OARs).

Methods
In sum 24 treatment plans for 6 pediatric patients were realized. Besides the clinical standard of a 3D-conformal radiotherapy (3D-CRT) treatment plan taken as a reference, volumetric modulated arc therapy (VMAT) treatment plans (“VMAT_AVD” vs. “noAVD” vs. “FullArc”) were optimized and calculated for each patient. For the thoracic and abdominal region, the short partial-arc VMAT_AVD technique uses an arc setup with reduced arc-length by 100°, using posterior and lateral beam entries. The noAVD uses a half 180° (posterior to lateral directions) and the FullArc uses a full 360° arc setup arrangement. The prescription dose was set to 35.2 Gy.

Results
We identified a more conformal dose coverage for PTVs and a better sparing of OARs with used VMAT methods. For VMAT_AVD mean dose reductions in organs at risk can be realized, from 16 to 6.6 Gy, from 27.1 to 8.7 Gy and from 8.0 to 1.9 Gy for the heart, the thyroid and the gonads respectively, compared to the 3D-CRT treatment method. In addition we have found out a superiority of VMAT_AVD compared to the noAVD and FullArc trials with lower exposure to low-dose radiation to the lungs and breasts.

Conclusions
With the short partial-arc VMAT_AVD technique, dose exposures to radiosensitive OARS like the heart, the thyroid or the gonads can be reduced and therefore, maybe the occurrence of late sequelae is less likely. Furthermore the PTV conformity is increased. The advantages of the VMAT_AVD have to be weighed against the potentially risks induced by an increased low dose exposure compared to the 3D-CRT method.
Mandibular involvement in SAPHO syndrome: a retrospective study
Authors: Wang Mu , Li Yueting , Cao Yihan , Lu Xinyu , Liu Yuchen , Zhao Jizhi , Zhang Wen , Li Chen 
Published: November 2020

Abstract

Background
Mandible osteomyelitis can occur in synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome, a rare chronic inflammatory disease; however, few studies have explored its characteristics and management.

Methods
We reviewed the medical records of consecutive SAPHO patients with mandible involvement diagnosed in Peking Union Medical College Hospital from September 2014 to July 2019. Demographic, clinical, laboratory, and imaging data were collected at baseline. Prescription data and follow-up magnetic resonance imaging (MRI) and cone beam computed tomography (CBCT) images were collected from the hospital information system. An electronic questionnaire was distributed to all patients to obtain their latest symptoms.

Results
A total of 26 SAPHO patients with mandibular involvement were involved, all of whom responded to the questionnaire (38.5% male; median age, 28 years; median follow-up duration, 2.1 years). Ten patients (38.5%) had undergone an oral procedure 1 month before the onset of mandibular symptoms. All 14 of the patients who underwent a surgical intervention relapsed within a median duration of 2 months (range 0.25–4.0 months), and 24 patients (92.3%) achieved improvement with conservative treatment. Following bisphosphonate treatment, remission of bone marrow oedema and osteolysis was observed on MRI and CBCT, and 5 patients receiving bisphosphonates with follow-up CBCT after remission did not relapse in 5.4 months (mean 6.0, range 3.2–9.9 months).

Conclusion
Mandibular involvement of SAPHO syndrome predominantly occurs in young women. Dental procedures are a possible risk factor. Conservative treatment, especially intravenous bisphosphonates, can lead to oral improvement.