bluuebunny/crossref_metadata_2025 huggingface dataset:
Durvalumab consolidation therapy following chemoradiotherapy among patients with unresectable stage III non-small cell lung cancer (NSCLC) treated in a U.S. community oncology network.
Authors: Waterhouse David Michael , Yong Candice , Robert Nicholas J. , Aguilar Kathleen M. , Ndukum Juliet , Xie Yiqiong , Seal Brian S. , Cotarla Ion
Published: September 2021

295

Background: While the introduction of durvalumab consolidation therapy shifted the treatment paradigm for unresectable stage III NSCLC, few studies have examined real-world use of durvalumab in this patient population. Methods: This was a retrospective study of adult patients diagnosed with unresectable Stage III NSCLC between 8/1/2017-2/29/2020 who received chemoradiotherapy (CRT) followed by durvalumab consolidation therapy in The US Oncology Network. Structured electronic health record (EHR) data was used to screen for potentially eligible patients who received durvalumab consolidation. Through a targeted chart review, patients’ eligibility was verified. Study variables on patient demographics, clinical characteristics, CRT and durvalumab treatment patterns were sourced from structured and unstructured EHR data. Results: Among 1,626 patients who received CRT during the study observation period and were screened through structured records, 851 (52.3%) of these patients received durvalumab. Through chart review, 528 patients were verified to be eligible for this analysis (median age 70 years, 51.5% male, 18% Eastern Cooperative Oncology Group performance status [ECOG PS] score of 0, 59% with an ECOG PS score of 1). Across the study population, 73.9% received a total radiation dose between 54 and 66 Gy, with the rest receiving higher doses (6.5%), lower doses (3.2%) or doses not documented (15.8%). The mean and median time from end of radiation to post-CRT scan were 41 and 36 days, respectively; the mean and median time from end of radiation to durvalumab initiation were 58 and 47 days, respectively, with 57% of patients initiating durvalumab > 42 days. At the end of study observation period (median follow-up duration of 46.9 weeks), 173 of 528 patients (32.7%) were still actively receiving durvalumab treatment, 98 (18.6%) had completed planned treatment and 257 (48.7%) had discontinued treatment due to progression (18.2%), adverse events (17.2%), death (5.3%) or other reasons (8%). Conclusions: These results provide insights into real-world use of the PACIFIC regimen in a community setting with an older and more fragile population. Radiation therapy doses administered during CRT were largely consistent with the PACIFIC trial. There were delays in time to post-CRT scan and durvalumab initiation, with more than half of patients starting durvalumab > 42 days after CRT. These findings highlight opportunities for quality improvement measures in this population.
Real-world EGFR testing patterns among U.S. patients with advanced NSCLC.
Authors: Vanderpoel Julie , Pericone Chris , He Jinghua
Published: September 2021

298

Background: Guidelines recommend mutation testing prior to initiating first-line therapy (L1) for patients with advanced non-small cell lung cancer (aNSCLC), including testing for epidermal growth factor receptor (EGFR) mutations. Guidelines also recommend further testing after patients progress on targeted therapy to identify possible resistance mutations and inform selection of subsequent treatment. The present study characterized real-world (RW) EGFR testing patterns in aNSCLC patients. Methods: This retrospective observational cohort study evaluated an aNSCLC cohort (stage IIIB or higher) from the Flatiron Health database. Eligible patients were newly diagnosed, ≥18 years old, and received at least one line of therapy (LOT) during 2015-2020. Patients were followed to last activity, death, or end of the study period, whichever came first. Results: The final study cohort included a total of 22,726 patients. Of these, 17,165 (75.5%) had ≥1 EGFR test and 2,611 (15.2% of the tested study population) tested positive for EGFR mutations at any time during the study. The proportion of aNSCLC patients receiving EGFR testing prior to L1 initiation increased from 45.2% in 2015 to 56.6% in 2020. Among 11,791 patients who had an EGFR test prior to initiation of L1, 1,944 (16.5%) had positive results. Of these, the cumulative proportion of patients receiving a second EGFR test prior to L2, L3, and L4 (contingent on receiving the following LOT) was 36.3% (322 out of 888), 55.4% (241 out of 435), and 67.0% (146 out of 218), respectively. From 2015-2020, the median time from sample collection to EGFR test results decreased from 26 to 16 days for next generation sequencing (NGS) tests and from 17.5 to 12 days for polymerase chain reaction (PCR) tests. During this same period, the proportion of NGS EGFR tests increased from 27.6% to 75.0%. In addition, use of plasma samples for EGFR tests increased substantially (6.3% to 36.5%). Conclusions: The proportion of aNSCLC patients tested for EGFR mutations has increased over time (2015-2020). Median time to available EGFR test result has decreased for both NGS and PCR tests. NGS testing has become increasingly more common as has use of plasma samples. However, opportunities for improvement exist, including further increasing the proportion of patients tested prior to initiation of L1 therapy, as well as testing prior to the selection of subsequent therapy when indicated. As more targeted therapies emerge and resistance mutations to current therapies are further characterized, continued refinement of RW testing practices is required to optimize patient care.
Assessing the representativeness of trial populations for contemporary real-world cancer patients: A case study of adjuvant chemotherapy for colon cancer.
Authors: Lund Jennifer Leigh , Webster-Clark Michael , Bratton Emily W.
Published: September 2021

306

Background: Randomized controlled trials are the gold standard for assessing the efficacy of new cancer therapies and are required for marketing approval. However, participants enrolled into trials are often not representative of the more diverse populations in whom treatment will ultimately be delivered. Real-world data can be used to potentially bridge this gap by evaluating the effectiveness and safety of therapies in more generalizable populations. In this study, we describe differences in demographic and clinical characteristics between participants enrolled in a phase III trial of adjuvant chemotherapy for colon cancer and a contemporary comparator cohort using structured oncology electronic medical records (EMR) data. Methods: We drew upon publications from the Multicenter International Study of Oxaliplatin/5 Fluorouracil/Leucovorin in the Adjuvant Treatment of Colon Cancer (MOSAIC) recruiting patients primarily from Western Europe with stage II or III colon cancer from October 1998-January 2001. This trial established FOLFOX (oxaliplatin + 5-FU) as the standard of care over 5FU alone in treating stage III colon cancer and led to US marketing approval. For comparison, we identified patients diagnosed with stage II or III colon cancer (September 2014-2020) who received FOLFOX in the IQVIA US Oncology EMR database via E360, IQVIA’s Real World Discovery and Analytics platform. In the two populations, we described distributions of prognostic factors including age, sex, stage of disease, body mass index (BMI), and Eastern Cooperative Group (ECOG) performance status. Results: The MOSAIC trial included 2,246 participants; we identified 4,566 patients starting FOLFOX in the EMR comparator. Median age was similar: 61 versus 62 years, but the range differed (19-75 years versus 18-85 years) in the trial and EMR comparator, respectively. Female sex was similar at 44% and 48%, while the proportion of patients with stage III disease differed considerably at 60% and 84% for trial and EMR comparator, respectively. Half (51%) of all EMR patients were missing ECOG status; among those with a reported ECOG status, 96% had a score of 0-1, while 87% of trial participants had an ECOG of 0-1. BMI was missing in 34% of patients in the EMR comparator; among those with a reported BMI, 28% had a BMI < 25, while 54% of trial participants had a BMI < 25. Conclusions: Colon cancer patients receiving FOLFOX in an EMR comparator had a similar age and sex distribution as MOSAIC trial participants, but were more likely to have stage III disease. Missing ECOG and BMI data were common in the EMR comparator, which limited comparisons. Structured oncology EMR data represent an important resource for generating real-world evidence; future data enrichment efforts focused on critical patient-level variables via unstructured EMR extraction may improve data completeness and quality.
Use of formative evaluation surveying and tailored digital education to identify and address knowledge and competency gaps in upper tract urothelial carcinoma (UTUC) care.
Authors: Ackbarali Tariqa , Turell Wendy , del Nido Elizabeth L. , Shore Neal D. , Pierorazio Phillip M.
Published: September 2021

307

Background: Upper tract urothelial carcinoma (UTUC) treatment poses a unique challenge for clinicians, due to the complexity in diagnosis, risk stratification, and a lack of treatment options, leading to a lower patient quality of life. However, recent advances in kidney sparing treatment options have created an opportunity for clinicians to integrate newer therapies into practice and improve function for UTUC patients. To address these needs, a serial educational initiative was designed for the uro-oncology team. Methods: A 2-part CE activity was launched in partnership with Large Urology Group Practice Association live-online in June and December, 2020, and remains on-demand through December, 2021 at UroCareLive.com and OMedLive.com. The first activity focused on diagnosis, risk stratification, and newer treatments. Formative evaluation was applied to obtain feedback from the 1st activity through an in-depth survey to clinician learners, the results of which were used to shape the content of the 2nd activity. Formative evaluation survey results revealed gaps in recognizing disease progression (48%), risk stratification (with difficulty obtaining tissue from upper urinary tract noted as the most common barrier; 57%), and experience with newer agents leading to a lack of their use in practice (62%). Only 23% rated their team’s training on patient education as “Very Good” or “Excellent.” Additionally, knowledge and competence questions were administered pre-, immediate post-activity, and at 2-months follow-up. Data from these questions were analyzed to determine engagement and remaining gaps. Results: To date, 788 clinicians participated in the activity. All 8 pre/post-test questions demonstrated statistically significant improvements in knowledge and competence concerning risk stratification, treatment applications, and adverse event management. At 2-mos. follow-up, 75% reported improved behavioral impact on clinical practice and 55% reported impact on patient experience and outcomes. Learners provided write-in examples detailing changes such as improved confidence and understanding of newer treatment options, patient experience, and increased use of kidney-sparing treatments including mitomycin gel. Conclusions: The activity was successful in demonstrating sustained knowledge advances in critical areas such as tumor categorizing and risk stratification, the use of emerging treatment options, and management of adverse events in practice. Use of formative evaluation surveying allowed identification of practice gaps and barriers to change, providing an opportunity for tailored education addressing these needs. Learners also reported strong post-activity improvements in clinical practice and patient outcomes, illustrating the importance of serial education for the uro-oncology team.
Factors associated with failure to receive oral anticancer drugs.
Authors: Doshi Sahil D , Lichtenstein Morgan RL , Beauchemin Melissa Parsons , Raghunathan Rohit R. , Law Cynthia , Accordino Melissa Kate , Wright Jason Dennis , Elkin Elena B. , Hershman Dawn L.
Published: September 2021

41

Background: Oral anti-cancer drugs (OACDs) have become increasingly prescribed over the last 10 years and require a significant amount of care coordination. Preliminary administrative database studies have shown that 10-15% of prescriptions are never received by the patient, but the reasons behind this are poorly understood. In this study, we prospectively identified failure to receive (FR) cases in which OACD prescriptions were never received by patients, examined underlying reasons for FR, and assessed clinical and process-related factors associated with FR. Methods: We prospectively collected data on new OACD prescriptions for adult oncology patients at a large, urban academic cancer center from 1/1/2018 to 12/31/2019. We collected patient demographic, clinical, and insurance data, OACD delivery date, and interactions with payers and financial assistance groups. FR was defined as failure to receive a prescribed OACD. Reasons for FR were confirmed by manual chart review and classified into seven categories: clinical deterioration, financial access, provider-driven clinical decision making, patient-directed change, transfer of care, lost to follow up, and other. We calculated the relative proportion of each FR category and used multivariable logistic regression to identify factors associated with FR, including initiation of a prior authorization and drug class. Results: The cohort included 1,080 patients who were prescribed 1,269 new OACDs. Of these prescriptions, 13% (N=163) were categorized as FR. Among the 158 patients with FR, average patient age was 66 years, 55% identified as non-Hispanic white, 61% had any Medicare plan, 11% had Medicaid only, and 25% had commercial insurance. Overall, 18% of FR cases were attributed to clinical deterioration, 13% to financial access, 29% to provider-driven clinical decision making, 17% to patient-directed change, 13% to transfer of care, and 5% were lost to follow up. Univariate analysis showed that FR was less likely in cases where prior authorization was initiated (p < 0.001) and multivariate analysis confirmed this result (OR 0.47 [CI 0.33-0.66], p < 0.001). Conclusions: Though the majority of oncology patients prescribed OACDs received the drug, 13% of patients in our study experienced FR. FR is associated with a lack of prior authorization initiation, which may reflect barriers to access, a change in clinical decision-making, or patient choice. Ultimately, FR is multifactorial and may be appropriate in some cases. More work is needed to determine whether improved access would increase uptake in some patients. [Table: see text]
Survival in the real world: A national analysis of patients treated for early-stage breast cancer.
Authors: Franks Jeffrey , Gidwani Risha , Enogela Ene Mercy , Caston Nicole E. , Williams Courtney , Aswani Monica S. , Azuero Andres , Rocque Gabrielle Betty
Published: September 2021

75

Background: Many patient population groups are not proportionally represented in clinical trials, including patients of color, at age extremes, or with comorbidities. It is unclear how treatment outcomes may differ for these patients compared to those well represented in trials. Methods: This retrospective cohort study included women diagnosed with early-stage (I-III) breast cancer (EBC) between 2005-2015 in the CancerLinQ Discovery electronic medical record-based dataset. Patients with comorbidities or concurrent cancer were considered unrepresented in clinical trials. Non-White patients and/or those aged <45 or ≥70 years were considered underrepresented. Patients who were White and aged 45-69 were considered well represented. Overall and EBC subtype-stratified Cox proportional hazards models estimated hazard ratios (HR) and 95% confidence intervals (CI) for five-year mortality by representation group. The overall model was adjusted for cancer stage, subtype, chemotherapy intensity, and year of EBC diagnosis. Stratified models were adjusted for cancer stage, individual treatment regimen (due to lack of chemotherapy intensity variation within subtype), and year of EBC diagnosis. Results: Of 11,770 patients, most were aged 45-69 (71%), White (72%), diagnosed with stage II (51%), or HR+HER2- EBC (56%). Unrepresented patients (7%) were categorized due to comorbidities (76%), concurrent cancer (22%), or both (2%). Underrepresented patients (45%) were categorized based on age (44%), race/ethnicity (39%), or both (17%). The remaining patients were well represented in trials (48%). In adjusted models, unrepresented patients had almost three times the hazard of death than well-represented patients (HR 2.71, 95% CI 2.08-3.52; Table). The hazard of death for underrepresented versus well-represented patients was similar (HR 1.19, 95% CI 0.98-1.45). Comparable results were seen in EBC subtype-specific models. Conclusions: Over half of patients in this study would be considered underrepresented or unrepresented in clinical trials due to age, comorbidity, or race/ethnicity. Patients considered unrepresented in trials experienced poorer survival compared to those well-represented. Trialists should ensure study participants reflect the real-world disease population to support evidence-based decision making for all individuals with cancer.[Table: see text]
Exclusion criteria of breast cancer research protocols: A descriptive analysis.
Authors: Wan Clara , Caston Nicole E. , Ingram Stacey A. , Rocque Gabrielle Betty
Published: September 2021

82

Background: Clinical trials play an important role in advancing cancer treatments. Unfortunately, only about 3% of adults with cancer are enrolled in a clinical trial in the United States due to various barriers to enrollment. This includes restrictive eligibility criteria, which currently have no standard guidelines. The purpose of this study is to evaluate the variability of eligibility criteria. Methods: This descriptive analysis utilized all therapeutic breast protocols offered at the University of Alabama at Birmingham (UAB) between 2004-2020. Exclusion criteria (e.g., laboratory values and comorbidities) were extracted from protocols using OnCore, an online dataset used to manage clinical trials, and ClinicalTrials.gov. Laboratory values or vital signs analyzed included liver function tests, hematologic labs, Eastern Cooperative Oncology Group (ECOG) performance status, and hypertension. Comorbid conditions included congestive heart failure, cardiovascular disease, presence of central nervous system (CNS) metastases, and history of prior cancer. Comorbid conditions were further analyzed by amount of time protocols required participants to be from initial diagnosis or exacerbation-free. Results: There were a total of 102 eligible protocols. Substantial heterogeneity was observed in exclusion criteria across liver/hematologic laboratory values and demographic/comorbidity variables. Among liver laboratory values, most protocols included an upper limit of acceptable for bilirubin (78%): 9% used the institutional upper limit of normal (ULN), 2% used 1.2xULN, 3% used 1.25xULN, 56% used 1.5xULN, 6% used 2xULN, and 2% used 3xULN. Similar variability was observed in protocols that included alanine transaminase and aspartate transaminase. Among hematological labs, 82% of protocols defined a lower limit of acceptable absolute neutrophil count: 1% 500mcL, 11% used 1,000mcL, 4% used 1,200mcL, 1% used 1,250mcL, 64% used 1,500mcL, and 1% used 1,800mcL. Of the comorbid conditions, exclusion criteria varied for congestive heart failure (49%), an acute exacerbation of cardiovascular disease (80%), CNS metastases (59%) and a prior cancer (66%). While most protocols included cardiovascular disease, the allowable timeframe varied between protocols: 4% did not allow an acute exacerbation within the previous 3 months, 32% did not allow within the previous 6 months, 5% did not allow within the previous 12 months, and 38 % did not specify a time frame. Protocols including history of a prior cancer as a criterion similarly had varied definitions based on timeline. Conclusions: Substantial heterogeneity was observed among clinical trial protocols. While exclusion criteria are necessary for patient safety, there is lack of evidence for current parameters. Future research should focus on defining standardized eligibility criteria while allowing for deviation based on drug specificity.
Fertility preservation in young breast cancer patients: A population-based study.
Authors: Nguyen Diana , Jamjoum Ghader , Meguerditchian Ari N.
Published: September 2021

90

Background: Treatment-related infertility is an important cause of distress in young women with breast cancer (YWBC) that is preventable by fertility preservation (FP) prior to initiating therapy. This study assesses FP service use by YWBC in Quebec (Canada). Methods: Administrative claims for women ≤ 40 diagnosed between 01-04-2012 and 31-03-2018 were identified using Quebec’s universal health services database (RAMQ). Access to and use of FP services were ascertained by identifying claims for a visit with an obstetrician/gynecologist (OB/GYN) ≤ 90 days of diagnosis, followed by claims for ovarian stimulation, ovule harvesting or artificial insemination. Patient, disease and treatment-related predictors were estimated using logistic regression. Results: 1 616 YWBC were treated. Mean age was 36 (SD 4.1), 72.1% had a CCI = 0, 84.5% were urban residents, and 72.2% experienced some form of socioeconomical disadvantages. Stage distribution was: 0.93%, 68.8, and 30.3% for stages 0, 1-2, and 3 respectively. 53.0% had a mastectomy, 40.8% received chemotherapy (CT), 70.7% received radiotherapy, 20.9% initiated anti-estrogen therapy. 387 YWBC consulted an OB/GYN within 90 days of diagnosis and 155 subsequently received FP services. Predictors associated with FP use included: decreased age (OR= 0.82, 95CI = 0.79-0.86), type of surgery (OR = 0.46, CI = 0.22-0.97), social isolation (OR =1.39, 95CI = 0.99-1.96) and receipt of chemotherapy (OR = 1.74, 95CI = 1.10-2.76). Conclusions: Only 23.9% of eligible YWBC in Quebec accessed FP specialists. Of these, 40.1% chose to move forward with FP. These findings raise important questions on how to optimize access to FP expertise. [Table: see text]
Health Care-Related Economic Burden of Polycystic Ovary Syndrome in the United States: Pregnancy-Related and Long-Term Health Consequences
Authors: Riestenberg Carrie , Jagasia Anika , Markovic Daniela , Buyalos Richard P , Azziz Ricardo
Published: September 2021

Context

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder of reproductive-aged women, affecting approximately 5% to 20% of women of reproductive age. The economic burden of PCOS was previously estimated at approximately $3.7 billion annually in 2020 USD when considering only the costs of the initial diagnosis and of reproductive endocrine morbidities, without considering the costs of pregnancy-related and long-term morbidities.

Objective

This study aimed to estimate the excess prevalence and economic burden of pregnancy-related and long-term health morbidities attributable to PCOS.

Methods

PubMed, EmBase, and Cochrane Library were searched, and studies were selected in which the diagnosis of PCOS was consistent with the Rotterdam, National Institutes of Health, or Androgen Excess and PCOS Society criteria, or that used electronic medical record diagnosis codes, or diagnosis based on histopathologic sampling. Studies that included an outcome of interest and a control group of non-PCOS patients who were matched or controlled for body mass index were included. Two investigators working independently extracted data on study characteristics and outcomes. Data were pooled using random effects meta-analysis. The I2 statistic was used to assess inter-study heterogeneity. The quality of selected studies was assessed using the Newcastle-Ottawa Scale.

Results

The additional total healthcare-related economic burden of PCOS due to pregnancy-related and long-term morbidities in the United States is estimated to be $4.3 billion annually in 2020 USD.

Conclusion

Together with our prior analysis, the economic burden of PCOS is estimated at $8 billion annually in 2020 USD.
Nerve Blocks for Postoperative Pain Management in Children Receiving Subcutaneous Implantable Cardioverter-Defibrillators: A Case Series
Authors: Koller Michael P. , Cortez Daniel , Kim Tae W.
Published: September 2021

Subcutaneous implantable cardioverter-defibrillator (S-ICD) placement may cause significant postoperative pain. Limited research exists on regional anesthesia for pediatric S-ICD placement. This case series examined transversus thoracic plane blocks (TTPBs), pectointercostal fascial plane blocks (PIFBs), pectoralis nerve I and II blocks, paravertebral, serratus anterior plane, and erector spinae plane blocks (ESPBs) in 10 children receiving S-ICDs. Parasternal nerve blocks consisting of TTPB or PIFB and left ESPB appeared to provide adequate pain control. These children had reduced opioid consumption, lower mean pain scores, longer delay in first postoperative analgesic, and no complications. Regional anesthesia may reduce pain after pediatric S-ICD implantation.
PCMD-1 bridges the centrioles and the pericentriolar material scaffold in C. elegans
Authors: Stenzel Lisa , Schreiner Alina , Zuccoli Elisa , Üstüner Sim , Mehler Judith , Zanin Esther , Mikeladze-Dvali Tamara
Published: September 2021

Correct cell division relies on the formation of a bipolar spindle. In animal cells, microtubule nucleation at the spindle poles is facilitated by the pericentriolar material (PCM), which assembles around a pair of centrioles. Although centrioles are essential for PCM assembly, the proteins that anchor the PCM to the centrioles are less known. Here, we investigate the molecular function of PCMD-1 in bridging the PCM and the centrioles in Caenorhabditis elegans. We demonstrate that the centrosomal recruitment of PCMD-1 is dependent on the outer centriolar protein SAS-7. The most C-terminal part of PCMD-1 is sufficient to target it to the centrosome, and the coiled-coil domain promotes its accumulation by facilitating self-interaction. We reveal that PCMD-1 interacts with the PCM scaffold protein SPD-5, the mitotic kinase PLK-1 and the centriolar protein SAS-4. Using an ectopic translocation assay, we show that PCMD-1 can selectively recruit downstream PCM scaffold components to an ectopic location in the cell, indicating that PCMD-1 is able to anchor the PCM scaffold proteins at the centrioles. Our work suggests that PCMD-1 is an essential functional bridge between the centrioles and the PCM.
Dental health status of community-dwelling adults aged 50 years and over in Ireland. A cross-sectional analysis of the Wave 3 TILDA cohort.
Authors: Naseer Amara , McLoughlin Jacinta , Donoghue Orna A. , Kenny Rose Anne , O'Connell Brian
Published: September 2021

Background: Little is known about the current oral health status of adults in Ireland. The aim of this study was to assess the dental health of community-dwelling adults aged 50 years and over in Ireland and to compare the current status to previous national surveys. 

Methods: The Irish Longitudinal Study on Ageing (TILDA) Wave 3 assessed the dental health of a subset of participants. Respondents attending for health assessments were offered a dental examination. The World Health Organization examination criteria were used.

Results:Of the 3111 people who were offered the dental assessment, 2525 were examined. Adults below 50 years of age and respondents whose dental health data were unavailable at the time of analysis were omitted, giving a final sample of 2504.  Among the dental assessment sample, 9.9% (249) were edentate. Of those aged 65 years and older, 15.6% were edentate while for the same age group 40.9% were edentate in the 2000-02 national survey. The mean number of teeth present in those aged 65 years or older was 14.9 for males and 14.2 for females, whereas in 2000-02 it was 9.9 and 7.4, respectively.  56.8% of the dentate sample had 10 or more tooth contacts. The mean DMFT of those aged 50 years or more was 18.5 and the Root Caries Index was 6.3. Between 2000-02 and 2014-5 (this study) in adults aged 65 years and over, the mean DMFT decreased from 25.9 to 20.1 and the Root Caries Index decreased from 11.6 to 9.1.

Conclusion: The results indicate improvements in the dental health of community-dwelling adults aged 50 years and over in Ireland as compared to the previous survey of 2000-02. These improvements mean a change in the treatment needs of this age group and will require policy and service adjustments to meet these needs
The WHO guideline on drugs to prevent COVID-19: small numbers- big conclusions
Authors: Schilling William HK , Callery James J. , Chandna Arjun , Hamers Raph L , Watson James A , White Nicholas J
Published: September 2021

The World Health Organization (WHO) living guideline on drugs to prevent COVID-19 has recently advised that ongoing trials evaluating hydroxychloroquine in chemoprophylaxis should stop. The WHO guideline cites “high certainty” evidence from randomised controlled trials (RCTs) that hydroxychloroquine prophylaxis does not reduce mortality and does not reduce hospital admission, and “moderate certainty” evidence of poor tolerability because of a significantly increased rate of adverse events leading to drug discontinuation. Yet there is no such evidence. In the three pre-exposure chemoprophylaxis RCTs evaluated in the guideline there were no deaths and only two COVID-19-related hospital admissions, and there was a mistake in the analysis of the number of discontinuations (after correction there is no longer a statistically significant difference between those taking the drug and the controls). Guidelines on the prevention and treatment of COVID-19 should be based on sufficient verified evidence, understanding of the disease process, sound statistical analysis and interpretation, and an appreciation of global needs. The WHO living guideline on the prevention of COVID-19 should retract the advice to stop research on hydroxychloroquine chemoprophylaxis, should correct its errors, and should revise its guidance.
The extent of formal tobacco cessation training received by student health professionals and the prevalence of tobacco use among them: a cross-sectional study
Authors: Parthasarathi Ashwaghosha , Kumar Raj , Undela Krishna , Biligere Siddaiah Jayaraj , Mahesh Padukudru Anand
Published: September 2021

Background: Advice from health care professionals (HCPs) is critical for tobacco prevention and cessation efforts. The academic curricula for health care professional students (HCS) lack comprehensive training in assisting patients in tobacco cessation. Tobacco use among HCP’s deters them from giving proper tobacco prevention and cessation guidance. The objective of this study was to determine the prevalence and determinants of tobacco consumption in third-year students of four health care disciplines (medical, dental, pharmacy, and nursing) and to assess their undergraduate education on tobacco control and cessation.

Methods:  A web-based survey (response rate 84.4%) employing the Global Health Professions Student Survey (GHPSS) questionnaire; n= 838; [20.89 (SD± 0.94) years] was conducted in Mysore, India. A descriptive, comparative and multivariate analysis was performed.

Results: The number of students who received formal training in smoking cessation approaches was only 14.04%. In total, two-thirds of medical students, compared to 38.9% of dental, 29.7% of pharmacy, and 11.40 % of nursing students, learned “the reasons why people smoke” as a part of their formal training. However, only less than a quarter of the study population were aware of the role of antidepressants in nicotine cessation medications. The total prevalence of tobacco use was 28.9%. A total of 37.72% wanted to quit smoking, while a mere 1.2% had sought any professional help to do so.

Conclusions: Tobacco use in HCS, apart from personal health risks to themselves, may potentially affect their future commitment to support patients in tobacco cessation. There is a need for further research into tobacco prevention and cessation programs tailored to the needs of student groups. There is a need for an updated curriculum for tobacco cessation strategies and more research into better cessation strategies.
Reported exposure to SARS-CoV-2 and relative perceived importance of different settings for SARS-CoV-2 acquisition in England and Wales: Analysis of the Virus Watch Community Cohort
Authors: Beale Sarah , Byrne Thomas , Fragaszy Ellen , Kovar Jana , Nguyen Vincent , Aryee Anna , Fong Wing Lam Erica , Geismar Cyril , Patel Parth , Shrotri Madhumita , Patni Nicholas , Braithwaite Isobel , Navaratnam Annalan , Johnson Anne M , Aldridge Robert W. , Hayward Andrew C ,   Virus Watch Collaborative
Published: September 2021

We aimed to assess the relative importance of different settings for SARS-CoV-2 transmission in a large community cohort based on perceived location of infection for self-reported confirmed SARS-COV-2 cases. We demonstrate the importance of home, work and education as perceived venues for transmission. In children, education was most important and in older adults essential shopping was of high importance.  Our findings support public health messaging about infection control at home, advice on working from home and restrictions in different venues.
Topological stability and shadowing of dynamical systems from measure theoretical viewpoint
Authors: Yin Jiandong , Dong Meihua
Published: September 2021

In this paper it is proved that a topologically stable invariant measure has no sinks or sources in its support; an expansive homeomorphism is topologically stable if it exhibits a topologically stable nonatomic Borel support measure and a continuous map has the shadowing property if there exists an invariant measure with the shadowing property such that each almost periodic point is contained in the support of the invariant measure.
JANOS: An Integrated Predictive and Prescriptive Modeling Framework
Authors: Bergman David , Huang Teng , Brooks Philip , Lodi Andrea , Raghunathan Arvind U.
Published: September 2021

Business research practice is witnessing a surge in the integration of predictive modeling and prescriptive analysis. We describe a modeling framework JANOS that seamlessly integrates the two streams of analytics, allowing researchers and practitioners to embed machine learning models in an end-to-end optimization framework. JANOS allows for specifying a prescriptive model using standard optimization modeling elements such as constraints and variables. The key novelty lies in providing modeling constructs that enable the specification of commonly used predictive models within an optimization model, have the features of the predictive model as variables in the optimization model, and incorporate the output of the predictive models as part of the objective. The framework considers two sets of decision variables: regular and predicted. The relationship between the regular and the predicted variables is specified by the user as pretrained predictive models. JANOS currently supports linear regression, logistic regression, and neural network with rectified linear activation functions. In this paper, we demonstrate the flexibility of the framework through an example on scholarship allocation in a student enrollment problem and provide a numeric performance evaluation.

Summary of Contribution. This paper describes a new software tool, JANOS, that integrates predictive modeling and discrete optimization to assist decision making. Specifically, the proposed solver takes as input user-specified pretrained predictive models and formulates optimization models directly over those predictive models by embedding them within an optimization model through linear transformations.
Template-Based Minor Embedding for Adiabatic Quantum Optimization
Authors: Serra Thiago , Huang Teng , Raghunathan Arvind U. , Bergman David
Published: September 2021

Quantum annealing (QA) can be used to quickly obtain near-optimal solutions for quadratic unconstrained binary optimization (QUBO) problems. In QA hardware, each decision variable of a QUBO should be mapped to one or more adjacent qubits in such a way that pairs of variables defining a quadratic term in the objective function are mapped to some pair of adjacent qubits. However, qubits have limited connectivity in existing QA hardware. This has spurred work on preprocessing algorithms for embedding the graph representing problem variables with quadratic terms into the hardware graph representing qubits adjacencies, such as the Chimera graph in hardware produced by D-Wave Systems. In this paper, we use integer linear programming to search for an embedding of the problem graph into certain classes of minors of the Chimera graph, which we call template embeddings. One of these classes corresponds to complete bipartite graphs, for which we show the limitation of the existing approach based on minimum odd cycle transversals (OCTs). One of the formulations presented is exact and thus can be used to certify the absence of a minor embedding using that template. On an extensive test set consisting of random graphs from five different classes of varying size and sparsity, we can embed more graphs than a state-of-the-art OCT-based approach, our approach scales better with the hardware size, and the runtime is generally orders of magnitude smaller.

Summary of Contribution: Our work combines classical and quantum computing for operations research by showing that integer linear programming can be successfully used as a preprocessing step for adiabatic quantum optimization. We use it to determine how a quadratic unconstrained binary optimization problem can be solved by a quantum annealer in which the qubits are coupled as in a Chimera graph, such as in the quantum annealers currently produced by D-Wave Systems. The paper also provides a timely introduction to adiabatic quantum computing and related work on minor embeddings.
Does Congestion Always Hurt? Managing Discount Under Congestion in a Game-Theoretic Setting
Authors: Saha Rajib L. , Singha Sumanta , Kumar Subodha
Published: September 2021

Many firms buy cloud services from cloud vendors, such as Amazon Web Services to serve end users. One of the key factors that affect the quality of cloud services is congestion. Congestion leads to a potential loss of end users, resulting in lower demand for cloud services. Although discount can stimulate demand, its effect under congestion is ambiguous; a higher discount leads to higher demand, but it can further lead to higher congestion, thereby lowering demand. We explore how congestion moderates both cloud vendor pricing and the buyer’s fulfillment decisions. We seek to answer how the congestion sensitivity of the end users and the cost of technology impact buyer profitability and the cloud vendor’s choice of discount. We also examine how the cost of technology determines the buyer’s willingness to pass on savings to end users. Our results show that the buyer is not necessarily worse off even when the end users are more intolerant to congestion. In fact, when end users are more congestion sensitive, the demand for cloud services can sometimes increase, and the discount offered by the vendor can decrease. We also observe that a lower cost of technology can sometimes hurt the buyer, and the buyer can pass on lower benefits to end users.
Hedge Fund Manager Skill and Style-Shifting
Authors: Jiang George J. , Liang Bing , Zhang Huacheng
Published: September 2021

Using a novel style identification procedure, we show that style-shifting is a dynamic strategy commonly used by hedge fund managers. Three quarters of hedge funds shifted their investment styles at least once over the period from January 1994 to December 2013. We perform empirical tests of two hypotheses for the motivations of hedge fund style-shifting, namely backward-looking and forward-looking hypotheses. We find no evidence that style-shifting funds are backward-looking. Instead, we show evidence that managers of style-shifting funds exhibit both style-timing ability and the skill of generating abnormal returns in new styles. The new styles that hedge funds shift to on average outperform their old styles by 0.76% and style-shifting funds on average outperform their new style benchmark by 1.10% over the subsequent 12-month horizon. Finally, we show that small funds, winner funds, and funds with net inflows are more likely to shift styles.

This paper was accepted by David Simchi-Levi, finance.
The Effect of Role-Based Product Representations on Individual and Team Coordination Practices: A Field Study of a Globally Distributed New Product Development Team
Authors: Mattarelli Elisa , Bertolotti Fabiola , Prencipe Andrea , Gupta Amar
Published: September 2021

The investigation of the appealing indication that a modular product architecture is best associated to a loosely coupled organizational structure—that is, the mirroring hypothesis—has produced contradictory evidence, especially in the dynamic and ambiguous context of new product development. By integrating modularity theory and product-representation theories, we investigate how individual agency affects coordination in teams developing modular products. We conducted a field study of Flower-Net, a globally distributed team in a major IT company, engaged with the development of a modular software using agile practices. Our grounded model shows that, whereas top managers defined the product as modular and coordinated work accordingly, individuals developed different representations of the product’s architecture and conflicting individual coordination practices. We traced the individual development of product architecture representations back to the individual interpretations of organizational roles as more or less “segmented.” Conflicting individual practices, associated to different role-based product representations, were not addressed by the team—that developed a state of illusory concordance—and impaired the functioning of the team. This study contributes to the literature on modularity and the mirroring hypothesis by proposing individual role-based representations as an underexplored level of analysis for the matching between product and organizational modularity (Mirroring Hypothesis II). It also contributes to the debate on how representations affect team coordination, by detailing how role-based product representations can influence team members’ divergence and sustain illusory concordance.
Integration of Learning Management System as an Aid in Teaching: An Assessment
Authors: Garcia Rizaldy E. , Abaratigue Anjo M. , Alcantara Nida V.
Published: September 2021

The research delved into the assessment of integrating Learning Management System as an aid in teaching. Data were collected from 26 students at Rizal Technological University-College of Education, Philippines, through pretest-posttest quasi-experimental and normative survey design of research. Data were statistically tested using the frequency, percentage, mean, standard deviation, t-test for dependent and independent samples, and paired t-test. Results of the research indicate that the respondents have optimistic attitudes towards the integration of learning management system in teaching. The respondents performed poorly in the pretest examination but performed very satisfactorily in the posttest examination. Furthermore, the research found out that there is no significant difference between the performances of the experimental group and control group in pretest and posttest, moreover, there is a significant difference between the pretest and posttest scores of the experimental group and the pretest and posttest scores of the control group.
Fostering Tertiary Student Professional Mobility Skills via Convergence of the Professional Training and Foreign Language Learning
Authors: Bobrytska Valentyna I. , Luzik Elvira V. , Skyrda Tetiana S. , Tereminko Larysa H. , Hurska Olena O.
Published: September 2021

The purpose of the study was to identify how the instructional model that converges professional training and foreign language learning can influence the students’ professional mobility and students’ readiness to build their careers. The study used the methods of a quantitative kind for the evaluation study and descriptive research. The variables for the study were as follows: levels of student professional mobility skills proficiency that included students’ competence in their professional field, foreign language proficiency, students’ networking skills, personality qualities, and sampled students’ satisfaction with the reshaped course. The field phase of the study found that the Erasmus and Work-and-Travel programmes contributed to the former students’ adaptability and flexibility, the experience of work abroad, and practical specialism-related experience gained during study. The students developed their abilities to project a positive social image, ability to build and maintain relationships, foreign language proficiency, proficiency in presenting and negotiating, and theoretical knowledge. The English Language-delivered Professional Mobility course brought shifts in the levels of students’ professional mobility skills. The experimental group students reported that they improved their competence in their professional field, foreign language proficiency, networking skills, and personality qualities. The experimental group students’ judgements concerning the quality of the course were complimentary.
Effect of pupil matching of cold shield on the fringe contrast of long-wave infrared spatial heterodyne spectroscopy
Authors: Han Bin , Feng Yutao , Zhang Zhaohui , Wu Junqiang , Wu Yang , Sun Jian , Wang Pengchong , Chang Chenguang , Li Juan , Zhao Yudi , Hu Bingliang
Published: September 2021

Matching the cold shield with the exit pupil of the fringe-imaging system of long-wave infrared (LWIR) spatial heterodyne spectroscopy (SHS) damages illumination uniformity of the interferogram and affects the fringe contrast, which is a significant parameter for LWIR SHS. The optical models of the fringe-imaging system considering and not considering the pupil matching of the cold shield are built to illustrate the effect on the fringe contrast. Simulations based on the optical design software ASAP are conducted to verify the fringe contrast loss for field-widened LWIR SHS. The result shows that the pupil matching of the cold shield decreases the fringe contrast of LWIR SHS and field-widened LWIR SHS by 0.049% and 0.053%, respectively, and the fringe contrast loss increases with the degree of deviation from the telecentric condition of the fringe-imaging system.
Ultrawide bandwidth dual sakura hollow-core antiresonant fiber polarization beam splitter
Authors: Jia Haoqiang , Wang Xin , Benson Trevor M. , Gu Shuai , Lou Shuqin , Sheng Xinzhi
Published: September 2021

A dual sakura hollow-core antiresonant fiber (DSHC-ARF) is proposed for developing an ultrawide-bandwidth polarization beam splitter (PBS). An air gap is introduced into the fiber between dual sakura hollow cores acting as a mode-coupling channel, which determines the implementation of a DSHC-ARF-based PBS. We demonstrate the wavelength dependence of coupling length can be reduced by introducing nested tubes and investigate their impact on single-mode operation further. Through optimizing the fiber, a high-performance PBS based on a 4.42 cm long DSHC-ARF can be obtained with an ultrawide bandwidth of 460 nm ranging from 1400 to 1860 nm, good single-mode operation with a higher-order mode extinction ratio above 100, and a low fundamental mode loss below 0.543 dB.