bluuebunny/crossref_metadata_2025_split huggingface dataset:
Short-Term Organ Dysfunction Is Associated With Long-Term (10-Yr) Mortality of Septic Shock
Authors: Linder Adam , Lee Terry , Fisher Jane , Singer Joel , Boyd John , Walley Keith R. , Russell James A. 
Published: July 2016

Objectives:
As mortality of septic shock decreases, new therapies focus on improving short-term organ dysfunction. However, it is not known whether short-term organ dysfunction is associated with long-term mortality of septic shock.

Design:
Retrospective single-center.

Setting:
Mixed medical-surgical ICU.

Patients:
One thousand three hundred and thirty-one patients with septic shock were included from 2000-2004. To remove the bias of 28-day nonsurvivors’ obvious association with long-term mortality, we determined the associations of days alive and free of ventilation, vasopressors and renal replacement therapy in 28-day and 1-year survivors with 1-, 5- and 10-year mortality in unadjusted analyses and analyses adjusted for age, gender, Acute Physiology and Chronic Health Evaluation II and presence of chronic comorbidities.

Interventions:
None.

Measurements and Main Results:
Days alive and free of ventilation, vasopressors, and renal replacement therapy were highly significantly associated with 1-, 5-, and 10-year mortality (p < 0.0001). In 28-day survivors, using Bonferroni-corrected multiple logistic regression, days alive and free of ventilation (p < 0.0001, p = 0.0002, and p = 0.001), vasopressors (p < 0.0001, p < 0.0001, and p = 0.0004), and renal replacement therapy (p = 0.0008, p = 0.0008, and p = 0.0002) were associated with increased 1-, 5-, and 10-year mortality, respectively. In 1-year survivors, none of the acute organ support and dysfunction measures were associated with 5- and 10-year mortality.

Conclusions:
Days alive and free of ventilation, vasopressors, and renal replacement therapy in septic shock in 28-day survivors was associated with 1-, 5-, and 10-year mortality. These associations are nullified in 1-year survivors in whom none of the acute organ support measures were associated with 5- and 10-year mortality. This suggests that therapies that decrease short-term organ dysfunction could also improve long-term outcomes of 28-day survivors of septic shock.
Current-day precision oncology: from cancer prevention, screening, drug development, and treatment – have we fallen short of the promise?
Authors: Morgan Gilberto , Aftimos Philippe , Awada Ahmad 
Published: July 2016

Purpose of review
Precision oncology has been a strategy of prevention, screening, and treatment. Although much has been invested, have the results fallen so far short of the promise? The advancement of technology and research has opened new doors, yet a variety of pitfalls are present. This review presents the successes, failures, and opportunities of precision oncology in the current landscape.

Recent findings
The use of targeted gene sequencing and the overwhelming results of superresponders have generated much excitement and support for precision oncology from the medical community. Despite notable successes, many challenges still pave the way of precision oncology: intratumoral heterogeneity, the need for serial biopsies, availability of treatments, target prioritization, ethical issues with germline incidental findings, medical education, clinical trial design, and costs.

Summary
Precision oncology shows much potential through the use of next-generation sequencing and molecular advances, but does this potential warrant the investment? There are many obstacles on the way of this technology that should make us question if the investment (both monetary and man-hours) will live up to the promise. The review aims to not criticize this technology, but to give a realistic view of where we are, especially regarding cancer treatment and prevention.
Low-cost Design and Manufacturing of Surgical Guides for Mandibular Reconstruction Using a Fibula
Authors: Numajiri Toshiaki , Nakamura Hiroko , Sowa Yoshihiro , Nishino Kenichi 
Published: July 2016

Background:
Surgical cutting guides are used in mandibular reconstruction involving osteotomy of the mandible and fibula. Cutting guides produced using computer-aided design (CAD) and computer-aided manufacturing (CAM) technologies have been reported recently. These guides aim to increase the benefits to patients by improving the accuracy, shortening the operating time, and correcting occlusion. However, the availability of these advanced technologies is limited in some regions of the world. To test whether we could produce low-cost surgical cutting guides, we made surgical guides and investigated their accuracy.

Methods:
Using free CAD software, we designed surgical cutting guides for the mandible and fibula and used these to perform virtual mandibular segmental osteotomies and fibula transplants in 12 model surgeries. The cutting guides were printed on a 3-dimensional (3D) printer. The model surgeries were performed using 3D mandibular models and cutting guides to check their accuracy. Deviations between the virtually simulated plan and the actual model surgery were investigated.

Results:
CAD and CAM technologies were used to design and 3D print the cutting guides and models. The guided surgeries were performed. The deviations were about 1.3 mm for mandibular osteotomy, less than 1 mm for fibular osteotomy, and within 2.4 mm for reconstructions of the mandible.

Conclusions:
Without using expensive software or products, we were able to design surgical cutting guides for the mandible and fibula and used these to perform virtual simulation of mandibular segmental osteotomy and fibular reconstruction. Model surgeries using 3D-printed surgical guides showed that the accuracy of reconstruction was within a 3-mm deviation. In circumstances where commercial CAD/CAM guides are not available, it may be possible to use CAD/CAM surgical guides in the clinic if doctors are willing to volunteer their time for the design and printing.
The Opposite Expected Effect of p38 Inhibitors on Fat Graft Survival
Authors: Filson Simon A. , Keren Aviad , Goldstein Nyra , Ullmann Yehuda 
Published: July 2016

Background:
Fat grafting is an increasingly popular method of augmentation/reconstruction of soft tissue defects. However, the clinical unpredictability and high resorption rates of the grafts remain problematic. Cellular stress from the harvest and the ensuing ischemic episode may be the cause of this. Cellular stress activates the p38 mitogen–activated protein kinase (MAPK) signaling pathway. In response to cellular stress, the p38 pathway can lead to apoptosis and can negatively regulate cell proliferation. Inhibition of p38 in ex vivo experiments has been shown to promote the expansion of human cord blood hematopoietic stem cell and improve the adipogenesis process through its upstream regulator, Shp2. Because of its wide-ranging cell regulation and antiinflammatory properties, large-scale clinical trials using p38 inhibitors are also currently being performed, especially for therapeutic effect in chronic obstructive pulmonary disease and asthma. The rationale for our study was that the treatment of fat grafts with p38 inhibitor would (a) prevent apoptosis of adipose-derived stem cells in the fat grafts, (b) increase adipose-derived stem cells proliferation, and (c) stimulate the release of several angiogenic factors and promote revascularization.

Methods:
Clinical and histological testing was performed on 5 fat-transplanted (1 mL) CD-1 nude mice compared with the test group of 5 mice, which were injected with a p38 MAPK inhibitor at 1, 3, 6, and 9 days after the fat transplantation.

Results:
The weights and volumes of the control group grafts were significantly higher than those of the p38 MAPK inhibitor–treated grafts. Average volume resorption was 36% in the control group and 92% in the test group. Histological evaluation of the grafts revealed significantly improved integration, with a significant reduction of fibrosis and inflammation in the control group versus the treated group.

Conclusions:
This preliminary study suggests that as opposed to our hypothesis, inhibition of p38 significantly increases fat graft resorption. The dramatic effects observed in our study may suggest that p38 may act differently on the numerous cell types that constitute the fat graft, and further investigation is necessary.
Association Between Depressive Symptoms and Exercise Capacity in Patients With Heart Disease
Authors: Papasavvas Theodoros , Alhashemi Mohammad , Micklewright Dominic 
Published: July 2016

Purpose:
Depression and reduced exercise capacity are risk factors for poor prognosis in patients with heart disease, but the relationship between the 2 is unclear. We assessed the relationship between depressive symptoms and exercise capacity in patients with heart disease.

Methods:
PubMed, Cochrane Library, Google Scholar, and ProQuest databases were browsed for English-language studies published from January 2000 to September 2013. Studies including adult patients with coronary artery disease, heart failure, congenital heart disease, and implantable cardioverter defibrillator, reporting correlation between a depression scale and exercise capacity (

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2peak, peak watts, estimated metabolic equivalents, and incremental shuttle walk test distance), as well as studies from which such a correlation could be calculated and provided by the authors, were included. Correlation coefficients (CCs) were converted to Fischer z values, and the analysis was performed using a random-effects model. Then, summary effects and 95% CIs were converted back to CCs.

Results:
Fifty-nine studies (25 733 participants) were included. Depressive symptoms were inversely correlated to exercise capacity (CC = −0.15; 95% CI, −0.17 to −0.12). Heterogeneity was significant (I
2 = 64%; P < .001). There was no evidence of publication bias (Fail-safe N = 4681; Egger test: P = .06; Kendall test: P = .29).

Conclusions:
Patients with heart disease and elevated depressive symptoms may tend to have reduced exercise capacity, and vice versa. This finding has clinical and prognostic implications. It also encourages research on the effects of improving depression on exercise capacity, and vice versa. The effects of potential moderators need to be explored.
Pulmonary Rehabilitation Utilization in Older Adults With Chronic Obstructive Pulmonary Disease, 2003 to 2012
Authors: Nishi Shawn P. E. , Zhang Wei , Kuo Yong-Fang , Sharma Gulshan 
Published: July 2016

PURPOSE:
To assess the trends in pulmonary rehabilitation (PR) utilization and factors associated with its use in older adults with chronic obstructive pulmonary disease (COPD).

METHODS:
We examined data for Medicare beneficiaries with COPD who received PR from January 1, 2003, to December 31, 2012. Persons with COPD were identified by (1) ≥2 outpatient visits >30 days apart within 1 year with an encounter diagnosis of COPD or (2) an acute care hospitalization with COPD as the primary diagnosis or a primary diagnosis of acute respiratory failure with a secondary discharge diagnosis of COPD. PR utilization was the study outcome identified by health care common procedure coding system codes G0237, G0238, G0239, and G0424 (after year 2010) or current procedural terminology codes (97001, 97003, 97110, 97116, 97124, 97139, 97150, 97530, 97535, and 97537) in a calendar year.

RESULTS:
Patients with COPD who received PR increased from 2.6% in 2003 to 3.7% in 2012 (P = .001). In a multivariable analysis, factors associated with receipt of PR were younger age, non-Hispanic white race, high socioeconomic status, multiple comorbidities (OR = 1.20; 95% CI = 1.13-1.27), and evaluation by a pulmonary physician (OR = 2.23; 95% CI = 2.13-2.33). Increased use of PR was attributed to prior users rather than new users of PR.

CONCLUSIONS:
Utilization of PR during the study period increased only 1.1% in these Medicare beneficiaries with COPD and remained low.
An intraorganizational model for developing and spreading quality improvement innovations
Authors: Kellogg Katherine C. , Gainer Lindsay A. , Allen Adrienne S. , O'Sullivan Tatum , Singer Sara J. 
Published: July 2016

Background:
Recent policy reforms encourage quality improvement (QI) innovations in primary care, but practitioners lack clear guidance regarding spread inside organizations.

Purpose:
We designed this study to identify how large organizations can facilitate intraorganizational spread of QI innovations.

Methodology/Approach:
We conducted ethnographic observation and interviews in a large, multispecialty, community-based medical group that implemented three QI innovations across 10 primary care sites using a new method for intraorganizational process development and spread. We compared quantitative outcomes achieved through the group’s traditional versus new method, created a process model describing the steps in the new method, and identified barriers and facilitators at each step.

Findings:
The medical group achieved substantial improvement using its new method of intraorganizational process development and spread of QI innovations: standard work for rooming and depression screening, vaccine error rates and order compliance, and Pap smear error rates. Our model details nine critical steps for successful intraorganizational process development (set priorities, assess the current state, develop the new process, and measure and refine) and spread (develop support, disseminate information, facilitate peer-to-peer training, reinforce, and learn and adapt). Our results highlight the importance of utilizing preexisting organizational structures such as established communication channels, standardized roles, common workflows, formal authority, and performance measurement and feedback systems when developing and spreading QI processes inside an organization. In particular, we detail how formal process advocate positions in each site for each role can facilitate the spread of new processes.

Practice Implications:
Successful intraorganizational spread is possible and sustainable. Developing and spreading new QI processes across sites inside an organization requires creating a shared understanding of the necessary process steps, considering the barriers that may arise at each step, and leveraging preexisting organizational structures to facilitate intraorganizational process development and spread.
The role of health information technology in advancing care management and coordination in accountable care organizations
Authors: Wu Frances M. , Shortell Stephen M. , Rundall Thomas G. , Bloom Joan R. 
Published: July 2016

Background:
To be successful, accountable care organizations (ACOs) must effectively manage patient care. Health information technology (HIT) can support care delivery by providing various degrees of coordination. Few studies have examined the role of HIT functionalities or the role of different levels of coordination enabled by HIT on care management processes.

Purposes:
We examine HIT functionalities in ACOs, categorized by the level of coordination they enable in terms of information and work flow, to determine which specific HIT functionalities and levels of coordination are most strongly associated with care management processes.

Methodology/Approach:
Retrospective cross-sectional analysis was done using 2012 data from the National Survey of Accountable Care Organizations. HIT functionalities are categorized into coordination levels: information capture, the lowest level, which coordinates through standardization; information provision, which supports unidirectional activities; and information exchange, which reflects the highest level of coordination allowing for bidirectional exchange. The Care Management Process index (CMP index) includes 13 questions about the extent to which care is planned, monitored, and supported by providers and patients. Multiple regressions adjusting for organizational and ACO contractual factors are used to assess relationships between HIT functionalities and the CMP index.

Findings:
HIT functionality coordinating the most complex interdependences (information exchange) was associated with a 0.41 standard deviation change in the CMP index (β = .41, p < .001), but the associations for information capture (β = −.01, p = .97) and information provision (β = .15, p = .48) functionalities were not significant.

Implications:
The current study has shed some light on the relationship between HIT and care management processes by specifying the coordination roles that HIT may play and, in particular, the importance of information exchange functionalities. Although these represent early findings, further research can help policy makers and clinical leaders understand how to prioritize HIT development given resource constraints.
Expose or protect? A randomized controlled trial of exposure in vivo vs pain-contingent treatment as usual in patients with complex regional pain syndrome type 1
Authors: den Hollander Marlies , Goossens Mariëlle , de Jong Jeroen , Ruijgrok Joop , Oosterhof Jan , Onghena Patrick , Smeets Rob , Vlaeyen Johan W. S. 
Published: July 2016

Abstract
Complex regional pain syndrome type I (CRPS-I) highly affects patients' ability to perform daily life activities. Pain-related fear might be a key target to reduce disability in chronic pain. Current treatments aiming at reducing pain show little improvements on pain and disability, whereas novel exposure-based treatments targeting pain-related fears have shown to be promising. We conducted a randomized controlled trial (N = 46) comparing exposure in vivo (EXP) with pain-contingent treatment as usual (TAU), for CRPS-I patients with at least moderate levels of pain-related fear. Primary outcome is self-reported disability, for upper and lower extremity, respectively. Secondary outcomes are self-reported pain-intensity, pain-catastrophizing, perceived harmfulness of physical activity, and health-related quality of life. Pretreatment to posttreatment and pretreatment to 6-month follow-up change scores were tested using randomization-based inference. EXP was superior to TAU in reducing upper extremity disability from pretreatment to posttreatment (between-group difference, 1.082; 95% confidence interval [CI], 0.563-1.601; P < 0.001) and from pretreatment to 6-month follow-up (1.303; 95% CI, 0.917-1.690; P < 0.001). EXP was superior in reducing lower extremity disability from pretreatment to 6-month follow-up (3.624; 95% CI, 0.467-6.781; P = 0.02), but not from pretreatment to posttreatment (3.055; 95% CI, −0.018 to 6.128; P = 0.054). All secondary outcomes significantly favored EXP pretreatment to posttreatment, as well as pretreatment to 6-month follow-up. Exposure to daily activities shows to be more effective than a protective pain-contingent TAU in reducing self-reported disability in daily life of CRPS-I patients with at least moderate levels of pain-related fear.
Ethnicity-dependent influence of innate immune genetic markers on morphine PCA requirements and adverse effects in postoperative pain
Authors: Somogyi Andrew A. , Sia Alex T. , Tan Ene-Choo , Coller Janet K. , Hutchinson Mark R. , Barratt Daniel T. 
Published: July 2016

AbstractAlthough several genetic factors have been associated with postsurgical morphine requirements, those involving the innate immune system and cytokines have not been well investigated. The aim of this study was to investigate the contribution of genetic variability in innate immune signalling pathways to variability in morphine dosage after elective caesarean section under spinal anaesthesia in 133 Indian, 230 Malay, and 598 Han Chinese women previously studied. Twenty single nucleotide polymorphisms in 14 genes involved in glial activation (TLR2,TLR4,MYD88,MD2), inflammatory signalling (IL2, IL6, IL10, IL1B, IL6R, TNFA,TGFB1, CRP, CASP1), and neuronal regulation (BDNF) were newly investigated, in addition toOPRM1,COMT, andABCB1genetic variability identified previously. Postsurgical patient-controlled analgesia morphine use (mg/24 hours) was binned into 6 normally distributed groups and scored 0 to 5 to facilitate step-down multiple linear regression analysis of genetic predictors, controlling for ethnicity and nongenetic variables. Ethnicity,OPRM1rs1799971 (increased),TLR2rs3804100 (decreased), and an interaction between ethnicity andIL1Brs1143634 (increased), predicted 9.8% of variability in morphine use scores in the entire cohort. In the Indian cohort, 14.5% of the variance in morphine use score was explained byIL1Brs1143634 (increased) andTGFB1rs1800469 (decreased). In Chinese patients, the incidence of postsurgical pain was significantly higher in variantCOMTrs4680 genotypes (P= 0.0007) but not in the Malay or Indian cohorts. Innate immune genetics may contribute to variability in postsurgical opioid requirements in an ethnicity-dependent manner.
Chronic physical illness in early life and risk of chronic widespread and regional pain at age 68: evidence from the 1946 British birth cohort
Authors: Muthuri Stella G. , Kuh Diana , Bendayan Rebecca , Macfarlane Gary J. , Cooper Rachel 
Published: July 2016

Abstract
This study aimed to examine the associations between serious illness in earlier life and risk of pain in old age using data from a large nationally representative British birth cohort, the Medical Research Council (MRC) National Survey of Health and Development (NSHD). Serious illness was defined as any experience of illness before age 25 requiring hospital admission of ≥28 days. Pain was self-reported at age 68, with chronic widespread pain (CWP) defined according to American College of Rheumatology criteria. Multinomial logistic regression was used to test associations of serious illness in early life with CWP, chronic regional pain (CRP), and other pain, with no pain as the referent category. Adjustment was made for sex, socioeconomic position, adult health status, health behaviours, and psychosocial factors. Of 2401 NSHD participants with complete data, 10.5% reported CWP (13.2% of women and 7.7% of men), 30.2% reported CRP, and 14.8% other pain. Compared with those with no history of serious illness, those who experienced serious illness in early life had a higher likelihood of CWP (relative risk ratio [RRR] = 1.62 [95% CI: 1.21-2.17]) and of CRP (RRR = 1.25 [95% CI: 1.01-1.54]) after adjusting for sex. In fully adjusted models, serious illness in early life remained associated with CWP (RRR = 1.43 [95% CI: 1.05-1.95]), but associations with CRP were attenuated (RRR = 1.19 [95% CI: 0.96-1.48]). There were no associations with other pain. These findings suggest that those who have experienced serious illness in earlier life may require more support than others to minimise their risk of CWP in later life.