bluuebunny/crossref_metadata_2025_split huggingface dataset:
PRAGMATISM OF RANDOMIZED CLINICAL TRIALS ON RANIBIZUMAB FOR THE TREATMENT OF DIABETIC MACULAR EDEMA
Authors: Stewart Stephen , Yeong Jian Lee , Virgili Gianni , Azuara-Blanco Augusto , Lois Noemi 
Published: February 2019

Purpose:
To evaluate the pragmatism and generalizability of randomized clinical trials (RCTs) on ranibizumab for diabetic macular edema and determine whether clinical outcomes would differ based on whether or not patients fulfill the eligibility criteria of these RCTs.

Methods:
Pragmatism and generalizability of three RCTs on ranibizumab for diabetic macular edema (DRCRnet Protocols I and T, and RESTORE) were rated using the PRECIS-2 tool. A cohort of consecutive patients with diabetic macular edema was assessed to determine whether clinical outcomes differed based on whether or not patients met the RCT eligibility criteria. Univariable and multivariable regression analyses, adjusted for baseline best-corrected visual acuity, central retinal thickness and number of injections received, were used.

Results:
All RCTs were rated as being more pragmatic than explanatory, with DRCRnet trials being the most pragmatic. Of the 216 eyes (176 patients) included in the cohort, 63% would have met eligibility criteria for Protocol T, 61% for Protocol I, and 56% for RESTORE. When adjusted for best-corrected visual acuity, central retinal thickness, and number of ranibizumab injections received, there were no statistically significant differences in best-corrected visual acuity or central retinal thickness found between “eligible” and “ineligible” patients.

Conclusion:
Randomized clinical trials evaluating ranibizumab for diabetic macular edema were more pragmatic than explanatory. “Ineligible” patients still benefited from ranibizumab therapy.
Comparison of Medicare Claims-based Proxy Measures of Poor Function and Associations With Treatment Receipt and Mortality in Older Colon Cancer Patients
Authors: Mayer Sophie E. , Tan Hung-Jui , Peacock Hinton Sharon , Sanoff Hanna K. , Stürmer Til , Hester Laura L. , Faurot Keturah R. , Jonsson Funk Michele , Lund Jennifer L. 
Published: February 2019

Background:
Multiple claims-based proxy measures of poor function have been developed to address confounding in observational studies of drug effects in older adults. We evaluated agreement between these measures and their associations with treatment receipt and mortality in a cohort of older colon cancer patients.

Methods:
Medicare beneficiaries age 66+ diagnosed with stage II–III colon cancer were identified in the Surveillance, Epidemiology, and End Results-Medicare database (2004–2011). Poor function was operationalized by: (1) summing the total poor function indicators for each model; and (2) estimating predicted probabilities of poor function at diagnosis. Agreement was evaluated using Fleiss’ κ and Spearman’s correlation. Associations between proxy measures and: (1) laparoscopic versus open surgery; (2) chemotherapy versus none; (3) 5-fluorouracil (5FU)+oxaliplatin (FOLFOX) versus 5FU monotherapy; and (4) 1-year mortality were estimated using log-binomial regression, controlling for age, sex, stage, and comorbidity. Survival estimates were stratified by functional group, age, and comorbidity.

Results:
Among 29,687 eligible colon cancer patients, 67% were 75+ years and 45% had stage III disease. Concordance across the poor function indicator counts was moderate (κ: 0.64) and correlation of predicted probability measures varied (ρ: 0.21–0.74). Worse function was associated with lower chemotherapy and FOLFOX receipt, and higher 1-year mortality. Within age and comorbidity strata, poor function remained associated with mortality.

Conclusions:
While agreement varied across the claims-based proxy measures, each demonstrated anticipated associations with treatment receipt and mortality independent of comorbidity. Claims-based comparative effectiveness studies in older populations should consider applying one of these models to improve confounding control.
Incidence and Mortality Rates of Second Pancreatic Cancer Among Survivors of Digestive Cancers
Authors: Ahn Hyeong Sik , Kang Tae Uk , Swan Heather , Kang Min Ji , Kim Nayoung , Kim Hyun Jung , Park Seon Mee 
Published: February 2019

Objectives
We analyzed the incidence and mortality rates of second pancreatic ductal adenocarcinoma (PDAC) among survivors of digestive cancers in South Korea.

Methods
We evaluated data from the Korea National Health Insurance to identify individuals with digestive cancers in 2005 to 2015. The standardized incidence ratios (SIRs) of second PDACs and survival rates were evaluated.

Results
Among 772,534 patients with first digestive cancers, 1696 (0.22%) developed second PDACs. The incidence of second PDACs increased until 10 years since the first cancer diagnosis. Patients with biliary tract cancers (BTCs) showed a higher incidence of second PDACs than did those with gastrointestinal cancers or hepatocellular carcinoma. In ages 20 to 49 years, SIRs (95% confidence interval) were higher in survivors of hepatocellular carcinoma (3.08; 1.04–3.08), gastric cancer (3.40; 1.90–3.40), colorectal cancer (5.00; 2.75–5.00), gallbladder cancer (58.52; 11.81–58.52), intrahepatic cholangiocarcinoma (86.99; 1.73–86.99), extrahepatic cholangiocarcinoma (89.41; 27.42–89.41), and ampulla of Vater cancer (156.78; 48.08–156.78). In ages 50 to 64 years, colorectal cancer (1.42; 1.04–1.42), gastric cancer (1.66; 1.29–1.66), and BTCs revealed higher SIRs. In ages more than 65 years, SIR was increased only in BTCs. Second PDACs revealed a more favorable prognosis than first PDACs.

Conclusions
Careful surveillance for second PDACs after curative treatment of BTCs and colorectal cancers should be considered.
Desmoplasia in Lymph Node Metastasis of Pancreatic Adenocarcinoma Reveals Activation of Cancer-Associated Fibroblasts Pattern and T-helper 2 Immune Cell Infiltration
Authors: Nizri Eran , Bar-David Shoshi , Aizic Asaf , Sternbach Neta , Lahat Guy , Wolf Ido , Klausner Joseph 
Published: February 2019

Objectives
Pancreatic ductal adenocarcinoma (PDAC) is characterized by a peritumoral proliferation of fibroblasts and extracellular matrix production known as desmoplasia. We aimed to study desmoplasia in PDAC lymph node (LN) metastases.

Methods
We evaluated LNs from 66 patients with PDAC and LN metastases. We used immunohistochemistry and real-time polymerase chain reaction to phenotype the desmoplastic response.

Results
Desmoplasia was identified in 57% of patients with LN metastases (Des+). Cancer-associated fibroblasts (CAFs) in Des+ expressed α-smooth muscle actin and collagen 11A1. The latter expression was present only in CAFs but not in LN stroma or in LN metastases without desmoplasia (Des−). Desmoplasia was associated with upregulation of transforming growth factor β messenger RNA. Whereas numbers of CD8+ in tumor vicinity were not different between Des+ and Des− patients (78 [standard deviation {SD}, 57] vs 92 [SD, 52], P = 0.48, respectively), the numbers of GATA-3+ cells, a marker of T-helper 2 immune response was significantly increased (3.7 [SD, 6.3] for Des+ vs 1.3 [SD, 2.7] for Des−, P < 0.05).

Conclusions
Lymph node desmoplasia is associated with CAF pattern activation and Th2 infiltration. Therapeutic modulation of desmoplasia may be relevant in the metastatic phase and influence antitumor immune response.
A Meta-analysis of Traffic-related Air Pollution and Risk of Childhood Leukemia
Authors: Gong Zeng-Hong , Li Jian , Wang Xiao-Yong , Yu Yan , Ren Min-Min , Zhou Jian 
Published: February 2019

Background:
Many studies have analyzed the association between traffic-related air pollution and risk of childhood leukemia, but the results are inconsistent. Therefore, we performed this meta-analysis to investigate the association between traffic-related air pollution and risk of childhood leukemia.

Methods:
PubMed, Cochrane, and Embase databases were searched by the index words to identify eligible case-control studies, and relevant literature sources were also searched. The latest research was performed in September 2017. Odds ratio (OR) along with 95% confidence interval (95% CI) were used to analyzed the main outcomes.

Results:
Twenty-one case-control studies were included in the meta-analysis. The results indicated that in the studies of overall traffic density (OR: 1.01, 95% CI: 0.98-1.04), high traffic density (OR: 1.04, 95% CI: 0.91-1.17), moderate exposure to NO2 (OR: 1.02, 95% CI: 0.93-1.10), and benzene (OR: 1.04, 95% CI: 0.71-1.37), the risks of childhood leukemia incidence were higher in the case group than the control group, but no significant difference was found. In other analysis, no significant difference was observed in the risk of childhood leukemia in the 2 groups.

Conclusions:
Current evidence suggests that childhood leukemia is associated with traffic density, and moderate exposure to NO2 and benzene. However, more high-quality studies are required to confirm the conclusions.
Using a Delphi Survey to Develop Clinical Nursing Research Priorities Among Nursing Management
Authors: Sun Carolyn , Prufeta Patricia 
Published: February 2019

OBJECTIVE
The aim of this study was to identify clinical nursing research priorities among nurse managers (NMs).

BACKGROUND
Determining research priorities is the 1st step toward building a solid evidence base for clinical practice. NMs are well poised to identify research priorities, and yet, a literature review revealed a dearth of research priorities as determined by clinical NMs.

METHODS
Using a Delphi survey, 38 NMs were queried at a large, urban hospital regarding critical priorities for nursing research.

RESULTS
Critical priorities for clinical nursing research included nursing workforce/nursing workflow and communication (categorized as critical by 68% and 53% of NMs, respectively). Other important priorities focused on falls/patient safety/hospital-acquired infections, patient/family satisfaction, emergency preparedness, patient outcomes, and collaboration/interdisciplinary research.

CONCLUSIONS
Because NMs are positioned to direct clinical research agendas, the results provide a critical guide for policy development surrounding nursing research. Directing research toward these identified topics will help build a solid evidence base for nurses and ultimately improve patient outcomes.
Distributing Local Resources for Public Health Preparedness Grants: A Data-Driven Approach
Authors: Zamboni Lucila M. , Martin Erika G. 
Published: February 2019

Objectives:
To simulate allocations of Public Health Emergency Preparedness funds to counties using alternative metrics of need, minimum allocation amounts, and the proportion earmarked for discretionary considerations.

Design:
We developed a county-level community resilience index of 57 New York State counties using publicly available indicators, which we incorporated into an interactive spreadsheet of 8 hypothetical allocation formulas with different combinations of population size, the index and its 5 domains, and population density. Simulations were compared with the 2013-2014 fiscal year grant allocation.

Results:
New York allocated $6.27 million to counties outside New York City, with a median allocation of $78 038, ranging from $50 825 to $556 789. These allocations would vary under different strategies, with the largest changes among sparsely populated counties that currently receive a minimum allocation of $50 825. Allocations were sensitive to changes in minimum allocation, amount earmarked for discretionary allocation, and need indicator.

Conclusions:
Population-based approaches are commonly used but ignore important dimensions of need. It is feasible to include robust local community resilience measures in formulas, and interactive spreadsheet models can help stakeholders evaluate the consequences of alternative funding strategies.
Incentivizing Healthy Snacks During Out-of-School Time Through Grocery Store Partnerships
Authors: Anzman-Frasca Stephanie , Folta Sara C. , Angstrom Heather M. , Brown Clarissa M. , Beets Michael W. , Finley Anna Marie , Nelson Miriam E. , Economos Christina D. 
Published: February 2019

Context:
Volunteer-led out-of-school-time (OST) programs, such as 4-H, scouting, and youth sports, reach a large population of children and are positioned to offer opportunities for healthy eating. However, cost is a barrier to providing healthy snacks such as fruits and vegetables (FVs) during OST.

Objective:
Offering discounts through grocery store partnerships has shown promise in addressing this barrier in structured, staff-led after-school programs. We tested this model in volunteer-led OST programs and evaluated it using mixed methods.

Design/Setting:
The Snack It Up (SIU) intervention was designed to promote FV snacks to volunteer-led OST programs through weekly $5 grocery store discounts. Participation was limited to 1 leader per program.

Participants:
Thirty-five of 36 recruited OST program leaders completed the study; 16 were enrolled in SIU and 19 in a comparison group.

Main Outcome Measures:
We assessed the following: (1) discount redemption among SIU leaders; (2) snacks served by SIU and comparison group leaders via photographs from 3 to 4 OST program sessions during SIU implementation; and (3) SIU leader perspectives using key informant interviews before and after implementation.

Results:
SIU leaders saved an average of $48.75 on FV snacks throughout the intervention ($2.90 per week, more than one-fifth of typical self-reported spending on snacks). SIU leaders also served a greater frequency (100% of sessions vs 75%, P < .001) and variety of FVs (an average of 3.5 types per session vs 1.3, P < .001) and fewer salty/sweet snacks (0.0 vs 1.3 types per session, P < .001) than those in the comparison group and expressed positive impressions of SIU.

Conclusions:
Partnerships between OST programs and grocery stores are a promising avenue for promoting healthier snacks during OST.
Inframammary Fold Reconstruction in the Previously Reconstructed Breast: A Comprehensive Review
Authors: Kraft Casey T. , Rendon Juan L. , Koutz Cynthia A. , Miller Michael J. 
Published: February 2019

Summary:
The inframammary fold presents a reconstructive challenge once disrupted during total mastectomy or inadequately restored during breast reconstruction. Various methods of recreating the inframammary fold have been proposed, but reports are generally based on small sample sizes and lack long-term analyses and patient-reported outcomes. The authors herein review the literature on inframammary fold anatomy and reconstructive techniques, highlighting the need for more critical analysis of methodology to develop more predictable and durable outcomes.
The Use of the Restricted Mean Survival Time as a Treatment Measure in HIV/AIDS Clinical Trial: Reanalysis of the ACTG A5257 Trial
Authors: Abulizi Xianmixikemaier , Ribaudo Heather J. , Flandre Philippe 
Published: February 2019

Background:
The restricted mean survival time (RMST) measures have not been used as primary measure of efficacy in HIV/AIDS clinical trials. In this work, we aim to compare analysis based on the difference in RMST (Δ-RMST) measure and 2 other treatment-effect measures in a recent HIV equivalence trial, and to investigate the performance and characteristics of Δ-RMST–based analysis in a simulation study.

Setting and Methods:
We reanalyzed a recent HIV equivalence trial (ACTG A5257 trial) with hazard ratio and Δ-RMST, and then compared the results with the original analysis based on risk difference estimated by Kaplan–Meier curves (RDKM). In a simulation study, we investigated the performance and operating characteristics of Δ-RMST–based analysis in the setting of non-proportional hazards (PH) ratio.

Results:
In the ACTG A5257 trial, analyses based on Δ-RMST globally led to similar conclusions as the published finding based on RDKM. By contrast, analyses based on hazard ratio provided some discordant equivalence conclusions compared both with the initial analyses based on RDKM and the Δ-RMST. Results of simulation study indicate that the violation of the PH assumption has an impact on Δ-RMST–based analysis regarding the probability of declaring equivalence.

Conclusions:
Although the RMST-based analysis is an alternative measure of efficacy in HIV/AIDS, clinical trials such an analysis can be strongly impacted by departures from the PH assumption.
High Plasma Soluble CD163 During Infancy Is a Marker for Neurocognitive Outcomes in Early-Treated HIV-Infected Children
Authors: Benki-Nugent Sarah F. , Martopullo Ira , Laboso Tony , Tamasha Nancy , Wamalwa Dalton C. , Tapia Kenneth , Langat Agnes , Maleche-Obimbo Elizabeth , Marra Christina M. , Bangirana Paul , Boivin Michael J. , John-Stewart Grace C. 
Published: February 2019

Background:
Monocyte activation may contribute to neuronal injury in aviremic HIV-infected adults; data are lacking in children. We examined the relation between monocyte activation markers and early and long-term neurodevelopmental outcomes in early-treated HIV-infected children.

Setting:
Prospective study of infant and child neurodevelopmental outcomes nested within a randomized clinical trial (NCT00428116) and extended cohort study in Kenya.

Methods:
HIV-infected infants (N = 67) initiated antiretroviral therapy (ART) at age <5 months. Plasma soluble (s) CD163 (sCD163), sCD14, and neopterin were measured before ART (entry) and 6 months later. Milestone attainment was ascertained monthly during 24 months, and neuropsychological tests were performed at 5.8–8.2 years after initiation of ART (N = 27). The relationship between neurodevelopment and sCD163, sCD14, and neopterin at entry and 6 months after ART was assessed using Cox proportional hazards models and linear regression.

Results:
Infants with high entry sCD163 had unexpected earlier attainment of supported sitting (5 vs 6 months; P = 0.006) and supported walking (10 vs 12 months; P = 0.02) with trends in adjusted analysis. Infants with high 6-month post-ART sCD163 attained speech later (17 vs 15 months; P = 0.006; adjusted hazard ratio, 0.47; P = 0.02), threw toys later (18 vs 17 months; P = 0.01; adjusted hazard ratio, 0.53; P = 0.04), and at median 6.8 years after ART, had worse neuropsychological test scores (adj. mean Z-score differences, cognition, −0.42; P = 0.07; short-term memory, −0.52; P = 0.08; nonverbal test performance, −0.39, P = 0.05).

Conclusions:
Before ART, monocyte activation may reflect transient neuroprotective mechanisms in infants. After ART and viral suppression, monocyte activation may predict worse short- and long-term neurodevelopment outcomes.
18F-FDG PET/CT Demonstrates Renal Cell Cancer in a Transplant With Synchronous Intestinal Infection
Authors: Kavanal Anwin Joseph , Bharati Joyita , Vadi Shelvin Kumar , Gupta Krishan Lal , Kumar Rajender , Mittal Bhagwant Rai 
Published: February 2019

Abstract
We present a case of a 22-year-old man with history of allogenic renal transplantation on immunosuppression, who underwent 18F-FDG-PET/CT to characterize a lesion in the transplanted kidney on ultrasonogram and contrast-enhanced computed tomography imaging. PET/CT revealed FDG avid lesion in the transplanted kidney and mural thickening involving the distal ileum, ileocecal junction, and ileocolic lymph nodes. Subsequent histopathological examination from the renal lesion revealed renal cell carcinoma in the transplanted kidney. Additionally, endoscopic biopsy from the ileal thickening revealed granulomatous inflammation, suggesting tuberculosis, which was missed on both ultrasonogram and contrast-enhanced CT imaging.
Oral immunization with a probiotic cholera vaccine induces broad protective immunity againstVibrio choleraecolonization and disease in mice
Authors: Sit Brandon , Zhang Ting , Fakoya Bolutife , Akter Aklima , Biswas Rajib , Ryan Edward T. , Waldor Matthew K. 
Published: February 2019

AbstractOral cholera vaccines (OCVs) are being increasingly employed, but current killed formulations generally require multiple doses and lack efficacy in young children. We recently developed a new live-attenuated OCV candidate (HaitiV) derived from aVibrio choleraestrain isolated during the 2010 Haiti cholera epidemic. HaitiV exhibited an unexpected probiotic-like activity in infant rabbits, preventing intestinal colonization and disease by wild-typeV. choleraebefore the onset of adaptive immunity. However, it remained unknown whether HaitiV would behave similarly to other OCVs to stimulate adaptive immunity againstV. cholerae.Here, we orally immunized adult germ-free female mice to test HaitiV’s immunogenicity. HaitiV safely and stably colonized vaccinated mice and induced known adaptive immune correlates of cholera protection within 14 days of administration. Pups born to immunized mice were protected against lethal challenges of both homologous and heterologousV. choleraestrains. Cross-fostering experiments revealed that protection was not dependent on vaccine colonization in or transmission to the pups. These findings demonstrate the protective immunogenicity of HaitiV and support its development as a new tool for limiting cholera.Author summaryVaccines for cholera are gaining acceptance as public health tools for prevention of cholera and curtailing the spread of outbreaks. However, current killed vaccines provide minimal protection in young children, who are especially susceptible to this diarrheal disease, and do not stimulate immunity against antigens that may only be expressed by live bacteria during infection. We recently developed HaitiV, an extensively engineered live-attenuated oral cholera vaccine candidate, derived from a clinical isolate from the Haiti cholera outbreak. Here, we found that the HaitiV induces immunological correlates of protection against cholera in germ free mice and leads to protection against disease in their offspring. Protection in this model was dependent on passively acquired factors in the milk of immunized dams and not transmission or colonization of HaitiV. Coupling the immunogenicity data presented here with our previous observation that HaitiV can protect from cholera prior to the induction of adaptive immunity, suggests that HaitiV may provide both rapid-onset short-term protection from disease while eliciting stable and long-lasting immunity against cholera.