bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Transfusion on Mortality and Other Adverse Events Among Critically Ill Septic Patients: An Observational Study Using a Marginal Structural Cox Model*
Authors: Dupuis Claire , Garrouste-Orgeas Maité , Bailly Sébastien , Adrie Christophe , Goldgran-Toledano Dany , Azoulay Elie , Ruckly Stéphane , Marcotte Guillaume , Souweine Bertrand , Darmon Michael , Cohen Yves , Schwebel Carole , Lacave Guillaume , Bouadma Lila , Timsit Jean-Francois 
Published: September 2017

Objectives:
RBC transfusion is often required in patients with sepsis. However, adverse events have been associated with RBC transfusion, raising safety concerns. A randomized controlled trial validated the 7 g/dL threshold, but previously transfused patients were excluded. Cohort studies led to conflicting results and did not handle time-dependent covariates and history of treatment. Additional data are thus warranted to guide patient’s management.

Design:
To estimate the effect of one or more RBC within 1 day on three major outcomes (mortality, ICU-acquired infections, and severe hypoxemia) at day 30, we used marginal structural models. A trajectory modeling, based on hematocrit evolution pattern, allowed identification of subgroups. Secondary analyses were performed into each of them.

Setting:
A prospective French multicenter database.

Patients:
Patients with sepsis at admission. Patients with hemorrhagic shock at admission were excluded.

Interventions:
None.

Measurements and Main Results:
Overall, in our cohort of 6,016 patients, RBC transfusion was not associated with death (hazard ratio, 1.07; 95% CI, 0.88–1.30; p = 0.52). However, RBC transfusion was associated with increased occurrence of ICU-acquired infections (hazard ratio, 2.77; 95% CI, 2.33–3.28; p < 0.01) and of severe hypoxemia (hazard ratio, 1.29; 95% CI, 1.14–1.47; p < 0.01). A protective effect from death by the transfusion was found in the subgroup with the lowest hematocrit level (26 [interquartile range, 24–28]) (hazard ratio, 0.72; 95% CI, 0.55–0.95; p = 0.02).

Conclusions:
RBC transfusion did not affect overall mortality in critically ill patients with sepsis. Increased occurrence rate of ICU-acquired infection and severe hypoxemia are expected outcomes from RBC transfusion that need to be weighted with its benefits in selected patients.
Patient Characteristics and Prevalence of Unplanned Postoperative Pediatric Intensive Care Unit Admissions
Authors: McHenry Amy , Forbes Michael , Brown Mira 
Published: September 2017

Objectives:
The aim of this study was to identify the prevalence of unplanned postoperative pediatric intensive care unit (PICU) admissions (UPPAs) and associated patient characteristics.

Design:
A retrospective, descriptive study at a single institution was conducted from January 1, 2011, to December 31, 2014. Trauma, medical, and weekend admissions were excluded. In addition, cardiac, orthopedic, and urology surgical admissions were excluded. A derived disability level was calculated using the baseline Pediatric Overall and Cognitive Performance Criteria. Mortality risk and acuity scores were compared between UPPAs and planned PICU admissions (PPAs). Outcomes as a function of patient origin (operating room [OR], postanesthesia care unit [PACU], and acute care floor [ACF]) and surgical services were compared.

Setting:
This study was conducted in a free-standing, tertiary care children's hospital.

Patients:
Patients admitted to the PICU within 24 hours following an operative procedure.

Measurements and Main Results:
There were 158 (34%) UPPAs. Compared with postoperative PPAs, UPPAs had higher acuity and mortality scores (p < .05). UPPAs were highest from the OR (58%), followed by those from the PACU (PACU-UPPA, 27%) and ACF (13%). There was no difference in the odds of UPPAs from the OR among surgical services. There was increased odds of PACU-UPPA after otolaryngology (odds ratio = 1.15, p < .0001) and pediatric surgery (odds ratio = 2.19, p < .0001) and the presence of disability (odds ratio = 3.67, p = .011). None of the variables were associated with UPPAs from the ACF.

Conclusions:
This study identified surgical services and moderate disability as independent risk factors for UPPA. PACU-UPPA may represent an improvement opportunity. It is feasible to derive a risk stratification model for UPPA.
Two Innovative Cancer Care Programs Have Potential to Reduce Utilization and Spending
Authors: Colligan Erin M. , Ewald Erin , Keating Nancy L. , Parashuram Shriram , Spafford Michelle , Ruiz Sarah , Moiduddin Adil 
Published: September 2017

Background:
Cancer patients often present to the emergency department (ED) and hospital for symptom management, but many of these visits are avoidable and costly.

Objective:
We assessed the impact of 2 Health Care Innovation Awards that used an oncology medical home model [Community Oncology Medical Home (COME HOME)] or patient navigation model [Patient Care Connect Program (PCCP)] on utilization and spending.

Methods:
Participants in COME HOME and PCCP models were matched to similar comparators using propensity scores. We analyzed utilization and spending outcomes using Medicare fee-for-service claims with unadjusted and adjusted difference-in-differences models.

Results:
In the adjusted models, both COME HOME and PCCP were associated with fewer ED visits than a comparison group (15 and 22 per 1000 patients/quarter, respectively; P<0.01). In addition, COME HOME had lower spending ($675 per patient/quarter; P<0.01), and PCCP had fewer hospitalizations (11 per 1000 patients/quarter; P<0.05), relative to the comparison group. Among patients undergoing chemotherapy, fewer COME HOME and PCCP patients had ED visits (18 and 28 per 1000 patients/quarter, respectively; P<0.01) and fewer PCCP patients had hospitalizations (13 per 1000 patients/quarter; P<0.05), than comparison patients.

Conclusions:
The oncology medical home and patient navigator programs both showed reductions in spending or utilization. Adoption of such programs holds promise for improving cancer care.
Quality of Care in the United States Territories, 1999–2012
Authors: Nuti Sudhakar V. , Wang Yun , Masoudi Frederick A. , Nunez-Smith Marcella , Normand Sharon-Lise T. , Murugiah Karthik , Rodríguez-Vilá Orlando , Ross Joseph S. , Krumholz Harlan M. 
Published: September 2017

Background:
Millions of Americans live in the US territories, but health outcomes and payments among Medicare beneficiaries in these territories are not well characterized.

Methods:
Among Fee-for-Service Medicare beneficiaries aged 65 years and older hospitalized between 1999 and 2012 for acute myocardial infarction (AMI), heart failure (HF), and pneumonia, we compared hospitalization rates, patient outcomes, and inpatient payments in the territories and states.

Results:
Over 14 years, there were 4,350,813 unique beneficiaries in the territories and 402,902,615 in the states. Hospitalization rates for AMI, HF, and pneumonia declined overall and did not differ significantly. However, 30-day mortality rates were higher in the territories for all 3 conditions: in the most recent time period (2008–2012), the adjusted odds of 30-day mortality were 1.34 [95% confidence interval (CI), 1.21–1.48], 1.24 (95% CI, 1.12–1.37), and 1.85 (95% CI, 1.71–2.00) for AMI, HF, and pneumonia, respectively; adjusted odds of 1-year mortality were also higher. In the most recent study period, inflation-adjusted Medicare in-patient payments, in 2012 dollars, were lower in the territories than the states, at $9234 less (61% lower than states), $4479 less (50% lower), and $4403 less (39% lower) for AMI, HF, and pneumonia hospitalizations, respectively (P<0.001 for all).

Conclusions and Relevance:
Among Medicare Fee-for-Service beneficiaries, in 2008–2012 mortality rates were higher, or not significantly different, and hospital reimbursements were lower for patients hospitalized with AMI, HF, and pneumonia in the territories. Improvement of health care and policies in the territories is critical to ensure health equity for all Americans.
Secondary Loss of Response to Infliximab in Pediatric Crohn Disease
Authors: Bolia Rishi , Rosenbaum Jeremy , Schildkraut Vered , Hardikar Winita , Oliver Mark , Cameron Donald , Alex George 
Published: September 2017

ABSTRACTObjectives:A significant proportion of children with Crohn disease develop a secondary loss of response (LOR) to infliximab. Our aim was to study the impact of initial treatment strategies on secondary LOR.Methods:We reviewed the medical records of children with Crohn disease who received scheduled maintenance infliximab therapy for at least 12 months. We compared children who developed LOR with those who did not; with regards to their clinical and laboratory parameters, disease phenotype, and treatment strategy before developing LOR.Results:A total of 73 children (median age at diagnosis 11 (2–16) years, 41 boys) who had received a median duration of 33 (13–110) months of infliximab therapy were included in the final analysis. LOR was seen in 25(34.2%). Demographic variables, disease phenotype (age, disease location, and behavior), inflammatory parameters, and pediatric Crohn disease activity index at induction with infliximab were similar between both groups. Children with LOR had a significantly greater number of flares of the disease when compared to those who did not have LOR (4 [1–8] vs 2 [1–5] P = 0.03). The choice of the concomitant immunomodulator—methotrexate (11/29 [37.9%]) versus azathioprine (11/36 [30.5%]) (P = 0.6) did not affect LOR rates. The median time‐lag between diagnosis and induction with infliximab was significantly longer in children with LOR as compared to those who did not have an LOR (28 [4–90] months vs 12.5 [1–121] months, P = 0.004).Conclusion:Early use of infliximab in pediatric Crohn disease is associated with a decrease in secondary LOR. The type of concomitant immunomodulator used does not make a difference to LOR rates.
Early Warning Scores to Predict Noncritical Events Overnight in Hospitalized Medical Patients: A Prospective Case Cohort Study
Authors: Bittman Jesse , Nijjar Aman P. , Tam Penny , Khan Nadia 
Published: September 2017

Background
Physicians are often called to evaluate patients overnight with varying levels of clinical deterioration. Early warning scores predict critical clinical deterioration in patients; however, it is unknown whether they are able to reliably predict which patients will need to be seen overnight and whether these patients will require further resource use.

Methods
A prospective case cohort study of 522 patient nights in a single tertiary care hospital in Vancouver, British Columbia, Canada, was conducted to assess the ability of Modified Early Warning Score (MEWS) and National Early Warning Score (NEWS) to predict patients who will need to be seen overnight by physicians and will require other healthcare resources. Prediction ability was assessed using area under the receiver operating characteristic curve and logistic regression models.

Results
The MEWS and NEWS both significantly predicted which patients needed to be seen overnight, and area under the receiver operating characteristic curves (95% confidence interval) for MEWS and NEWS were 0.72 (0.66–0.78) and 0.69 (0.63–0.76), respectively. Odds ratios (95% confidence interval) for MEWS and NEWS predicting need to be seen overnight were 1.52 (1.34–1.73) and 1.22 (1.14–1.31), respectively.

Conclusions
Both MEWS and NEWS have fair ability to predict patients who will need to be seen overnight. This may be useful for improving handover and resource allocation for overnight care.
Effect of Schooling on Age-Disparate Relationships and Number of Sexual Partners Among Young Women in Rural South Africa Enrolled in HPTN 068
Authors: Stoner Marie C. D. , Edwards Jessie K. , Miller William C. , Aiello Allison E. , Halpern Carolyn T. , Julien Aimée , Selin Amanda , Hughes James P. , Wang Jing , Gomez-Olive Francesc Xavier , Wagner Ryan G. , MacPhail Catherine , Kahn Kathleen , Pettifor Audrey 
Published: September 2017

Background:
Attending school may have a strong preventative association with sexually transmitted infections among young women, but the mechanism for this relationship is unknown. One hypothesis is that students who attend school practice safer sex with fewer partners, establishing safer sexual networks that make them less exposed to infection.

Setting:
We used longitudinal data from a randomized controlled trial of young women aged 13–20 years in the Bushbuckridge district, South Africa, to determine whether the percentage of school days attended, school dropout, and grade repetition are associated with having a partner 5 or more years older (age–disparate) and with the number of sexual partners in the previous 12 months.

Methods:
Risks of having an age-disparate relationship and number of sexual partners were compared using inverse probability of exposure weighted Poisson regression models. Generalized estimating equations were used to account for repeated measures.

Results:
Young women who attended fewer school days (<80%) and who dropped out of school were more likely to have an age–disparate relationship (risk difference 9.9%, 95% confidence interval [CI]: 3.9% to 16.0%; risk difference (%) dropout 17.2%, 95% CI: 5.4% to 29.0%) and those who dropped out reported having fewer partners (count difference dropout 0.343, 95% CI: 0.192 to 0.495). Grade repetition was not associated with either behavior.

Conclusion:
Young women who less frequently attend school or who drop out are more likely to have an age-disparate relationship. Young women who drop out have overall more partners. These behaviors may increase the risk of exposure to HIV infection in young women out of school.
Detection Rate, Anatomic Sites, and Pathologic Types of Colorectal Cancer During Colonoscopy Procedures
Authors: Liu Lan , Zhu Kongxi , Yu Weihua , Zhang Shanyan , Teng Guoxin , Guo Jianqiang 
Published: September 2017

Purpose:
This study aims to help physicians obtain the detection rate and colonoscopic information of colorectal cancer (CRC) among patients in a city in China.

Methods:
A total of 15,189 participants who underwent total colonoscopy between January 2000 and December 2015 were studied. A total of 1022 CRCs were diagnosed. We analyzed the detection rate, anatomic sites, and pathologic types among different sex, age, and decade groups. Moreover, we investigated the corresponding relationships between the anatomic sites and the pathologic types.

Results:
Colonoscopic examinations revealed that the risk for CRC between men and women showed no significant difference (6.97% vs. 6.42%). The detection rate of CRC significantly increased with age (2.08% vs. 5.95% vs. 15.09%). The proportion of poorly differentiated adenocarcinoma among the youth group was significantly higher than that in the other age groups (25.0% vs. 11.54% vs. 8.33%). However, the numbers of cases with well-differentiated and moderately differentiated adenocarcinoma observed in the old-aged group were higher than other age groups. This finding demonstrated that the differentiation degree of adenocarcinoma increased with the age. Neuroendocrine tumor was mainly located in the rectum (95.0%), and appeared more frequently among the youth group (7.5% vs. 1.48% vs. 1.06%).

Conclusions:
We found the detection rate of CRC varied in terms of sex and decade. The CRC cases in the youth group exhibited a high malignant degree. The most common anatomic site was rectum, so we should focus more on digital rectal examination.
Microbiota and neurodegenerative diseases
Authors: Marizzoni Moira , Provasi Stefania , Cattaneo Annamaria , Frisoni Giovanni B. 
Published: September 2017

Purpose of review
Despite the extensive research carried out in the past decades, the current pathophysiological notions of neurodegenerative disease as well as effective treatments to reduce their progression are largely unknown. Alterations of the human microbiota, the plethora of different microscopic organisms that our body hosts, have been linked to neurodegenerative disease risk, onset and progression. This review summarizes the current knowledge on the possible role of microbiota in neurodegenerative disorders and briefly discusses strategies to restore microbiota homeostasis.

Recent findings
Preclinical evidences and human cross-sectional studies posit the gut microbiota as a key actor in the Parkinson's disease onset and progression, reporting the presence of a specific gut microbiota profile in association with the modulation of disease and symptoms. Gut microbiota alterations have been correlated with brain disease and peripheral inflammation also in Alzheimer's patients.

Summary
The interaction between the microbiota and the host is promising to answer clinical questions that have so far escaped clarification with the current pathophysiological notions of health and disease. However, human longitudinal studies starting in the earlier disease phases are needed to understand the causative relation between microbiota and the hallmarks of these neurodegenerative disorders and to develop innovative treatments aimed at preventing or slowing brain damages.
Tumour virus epidemiology
Authors: Lunn Ruth M. , Jahnke Gloria D. , Rabkin Charles S. 
Published: September 2017

A viral etiology of cancer was first demonstrated in 1911 by Peyton Rous who injected cell-free filtrate from a chicken sarcoma into healthy chickens and found it induced a tumour. Since the discovery over 50 years ago of the Epstein-Barr virus as the cause of Burkitt lymphoma, seven other human viruses or groups of viruses—hepatitis B virus, hepatitis C virus, human immunodeficiency virus type 1, some human papillomaviruses, human T-cell lymphotropic virus type 1, Kaposi sarcoma-associated herpesvirus and Merkel cell polyomavirus—have been linked to human cancer. Collectively, these eight viruses cause over 20 different types of cancer and contribute to 10–12% of all cancer, with a greater burden in low- and middle-income countries. For many viruses, immunosuppression greatly increases the risks of persistent infection, development of chronic sequelae and cancer. Although several viruses share similar routes of transmission (especially sexual activity, injection drug use and mother-to-child transmission), the predominant route of transmission varies across viruses, and for the same virus can vary by geographical location. In general, vulnerable populations at the greatest risk for viral infections and their associated diseases include people, especially children, living in low- to middle-income countries, men who have sex with men, people who use injection drugs and female sex workers.
This article is part of the themed issue ‘Human oncogenic viruses’.
Tumour virus vaccines: hepatitis B virus and human papillomavirus
Authors: Stanley Margaret 
Published: September 2017

Two of the most important human oncogenic viruses are hepatitis B virus (HBV) and human papillomavirus (HPV). HBV infection has been preventable by vaccination since 1982; vaccination of neonates and infants is highly effective, resulting already in decreased rates of new infections, chronic liver disease and hepato-cellular carcinoma. Nonetheless, HBV remains a global public health problem with high rates of vertical transmission from mother to child in some regions. Prophylactic HPV vaccines composed of virus-like particles (VLPs) of the L1 capsid protein have been licensed since 2006/2007. These target infection by the oncogenic HPVs 16 and 18 (the cause of 70% of cervical cancers); a new vaccine licensed in 2014/2015 additionally targets HPVs 31, 33, 45, 52, 58. HPV vaccines are now included in the national immunization programmes in many countries, with young adolescent peri-pubertal girls the usual cohort for immunization. Population effectiveness in women is now being demonstrated in countries with high vaccine coverage with significant reductions in high-grade cervical intra-epithelial neoplasia (a surrogate for cervical cancer), genital warts and vaccine HPV type genoprevalence. Herd effects in young heterosexual men and older women are evident. Cancers caused by HBV and HPV should, in theory, be amenable to immunotherapies and various therapeutic vaccines for HPV in particular are in development and/or in clinical trial.
This article is part of the themed issue ‘Human oncogenic viruses’.
Take your PIKK: tumour viruses and DNA damage response pathways
Authors: Pancholi Neha J. , Price Alexander M. , Weitzman Matthew D. 
Published: September 2017

Viruses regulate cellular processes to facilitate viral replication. Manipulation of nuclear proteins and pathways by nuclear replicating viruses often causes cellular genome instability that contributes to transformation. The cellular DNA damage response (DDR) safeguards the host to maintain genome integrity, but DNA tumour viruses can manipulate the DDR to promote viral propagation. In this review, we describe the interactions of DNA tumour viruses with the phosphatidylinositol 3-kinase-like protein kinase (PIKK) pathways, which are central regulatory arms of the DDR. We review how signalling through the ataxia telangiectasia mutated (ATM), ataxia telangiectasia and Rad3 related (ATR), and DNA-dependent protein kinases (DNA-PK) influences viral life cycles, and how their manipulation by viral proteins may contribute to tumour formation.This article is part of the themed issue ‘Human oncogenic viruses’.
Epstein–Barr virus infection and nasopharyngeal carcinoma
Authors: Tsao Sai Wah , Tsang Chi Man , Lo Kwok Wai 
Published: September 2017

Epstein–Barr virus (EBV) is associated with multiple types of human cancer, including lymphoid and epithelial cancers. The closest association with EBV infection is seen in undifferentiated nasopharyngeal carcinoma (NPC), which is endemic in the southern Chinese population. A strong association between NPC risk and the HLA locus at chromosome 6p has been identified, indicating a link between the presentation of EBV antigens to host immune cells and NPC risk. EBV infection in NPC is clonal in origin, strongly suggesting that NPC develops from the clonal expansion of a single EBV-infected cell. In epithelial cells, the default program of EBV infection is lytic replication. However, latent infection is the predominant mode of EBV infection in NPC. The establishment of latent EBV infection in pre-invasive nasopharyngeal epithelium is believed to be an early stage of NPC pathogenesis. Recent genomic study of NPC has identified multiple somatic mutations in the upstream negative regulators of NF-κB signalling. Dysregulated NF-κB signalling may contribute to the establishment of latent EBV infection in NPC. Stable EBV infection and the expression of latent EBV genes are postulated to drive the transformation of pre-invasive nasopharyngeal epithelial cells to cancer cells through multiple pathways.
This article is part of the themed issue ‘Human oncogenic viruses’.
Epstein–Barr virus-associated lymphomas
Authors: Shannon-Lowe Claire , Rickinson Alan B. , Bell Andrew I. 
Published: September 2017

Epstein–Barr virus (EBV), originally discovered through its association with Burkitt lymphoma, is now aetiologically linked to a remarkably wide range of lymphoproliferative lesions and malignant lymphomas of B-, T- and NK-cell origin. Some occur as rare accidents of virus persistence in the B lymphoid system, while others arise as a result of viral entry into unnatural target cells. The early finding that EBV is a potent B-cell growth transforming agent hinted at a simple oncogenic mechanism by which this virus could promote lymphomagenesis. In reality, the pathogenesis of EBV-associated lymphomas involves a complex interplay between different patterns of viral gene expression and cellular genetic changes. Here we review recent developments in our understanding of EBV-associated lymphomagenesis in both the immunocompetent and immunocompromised host.This article is part of the themed issue ‘Human oncogenic viruses’.