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Length of hospital stay (LOS) is considered a vital component for successful colorectal surgery treatment. Evidence of an association between hospital surgery volume and LOS has been mixed. Data modelling techniques may give inconsistent results that adversely impact conclusions. This study applied techniques to overcome possible modelling drawbacks. An additive quantile regression model formulated to isolate hospital contextual effects was applied to every colorectal surgery for cancer conducted in Victoria, Australia, between 2005 and 2015, involving 28,343 admissions in 90 Victorian hospitals. The model compared hospitals’ operational efficiencies regarding LOS. Hospital LOS operational efficiencies for colorectal cancer surgery varied markedly between the 90 hospitals and were independent of volume. This result was adjusted for pertinent patient and hospital characteristics. No evidence was found that higher annual surgery volume was associated with lower LOS for patients undergoing colorectal cancer surgery. Our model showed strong evidence that differences in LOS efficiency between hospitals was driven by hospital contextual effects that were not predicted by provider volume. Further study is required to elucidate these inherent differences between hospitals. Our model indicated improved efficiency would benefit the patient and medical system by lowering LOS and reducing expenditure by more than $3 million per year.

Background: The Centers for Medicare and Medicaid Services (CMS) promulgated regulations commencing October 1, 2008, which deny payment for selected conditions occurring during the hospital stay and are not present on admission. Three of the 10 hospital-acquired conditions covered by the new CMS policy involve healthcare-associated infections, which are a common, expensive, and often preventable cause of inpatient morbidity and mortality. Objective: To outline a research agenda on the impact of CMS's payment policy on the healthcare system and the prevention of healthcare-associated infections. Methods: An invitational daylong conference was convened in April 2009. Including the planning committee and speakers there were 41 conference participants who were national experts and senior researchers. Results: Building upon a behavioral model and organizational theory and management research a conceptual framework was applied to organize the wide range of issues that arose. A broad array of research topics was identified. Thirty-two research agenda items were organized in the areas of incentives, environmental factors, organizational factors, clinical outcomes, staff outcomes, and financial outcomes. Methodological challenges are also discussed. Conclusions: This policy is a first significant step to move output-based inpatient funding to outcome-based funding, and this agenda is applicable to all hospital-acquired conditions. Studies beginning soon will have the best hope of capturing data for the years preceding the policy change, a key element in nonexperimental research. The CMS payment policy offers an excellent opportunity to understand and influence the use of financial incentives for improving patient safety.

In 2008 Medicare stopped reimbursing hospitals for treating eight avoidable hospital-acquired conditions. Using 2006 California data, we modeled the financial impact of this policy on six such conditions. Hospital-acquired conditions were present in 0.11 percent of acute inpatient Medicare discharges; only 3 percent of these were affected by the policy. Payment reductions were negligible (0.001 percent, or $0.1 million-equivalent to $1.1 million nationwide) and are unlikely to encourage providers to improve quality. Options to strengthen the incentives include further payment modifications for hospital-acquired conditions or expanding the hospital-acquired condition policy to exclude payment for consequences, additional procedures, and readmissions. [PUBLICATION ABSTRACT]

Understanding the use of invasive procedures (IPs) at the end of life (EoL) is important to avoid undertreatment and overtreatment, but epidemiologic analysis is hampered by limited methods to define treatment intent and EoL phase. This study applied novel methods to report IPs at the EoL using a colorectal cancer case study. An English population-based cohort of adult patients diagnosed between 2013 and 2015 was used with follow-up to 2018. Procedure intent (curative, noncurative, diagnostic) by cancer site and stage at diagnosis was classified by two surgeons independently. Joinpoint regression modeled weekly rates of IPs for 36 subcohorts of patients with incremental survival of 0–36 months. EoL phase was defined by a significant IP rate change before death. Zero-inflated Poisson regression explored associations between IP rates and clinical/sociodemographic variables. Of 87,731 patients included, 41,972 (48%) died. Nine thousand four hundred ninety two procedures were classified by intent (inter-rater agreement 99.8%). Patients received 502,895 IPs (1.39 and 3.36 per person year for survivors and decedents). Joinpoint regression identified significant increases in IPs 4 weeks before death in those living 3–6 months and 8 weeks before death in those living 7–36 months from diagnosis. Seven thousand nine hundred eight (18.8%) patients underwent IPs at the EoL, with stoma formation the most common major procedure. Younger age, early-stage disease, men, lower comorbidity, those receiving chemotherapy, and living longer from diagnosis were associated with IPs. Methods to identify and classify IPs at the EoL were developed and tested within a colorectal cancer population. This approach can be now extended and validated to identify potential undertreatment and overtreatment.

Little is known about the health-related quality of life (HRQOL) of men living with advanced prostate cancer. We report population-wide functional outcomes and HRQOL in men with all stages of prostate cancer and identify implications for health-care delivery. For this population-based study, men in the UK living 18–42 months after diagnosis of prostate cancer were identified through cancer registration data. A postal survey was administered, which contained validated measures to assess functional outcomes (urinary incontinence, urinary irritation and obstruction, bowel, sexual, and vitality and hormonal function), measured with the Expanded Prostate Cancer Index Composite short form (EPIC-26), plus questions about use of interventions for sexual dysfunction) and generic HRQOL (assessed with the 5-level EuroQol five dimensions questionnaire [EQ-5D-5L] measuring mobility, self-care, usual activities, pain or discomfort, and anxiety or depression, plus a rating of self-assessed health). Log-linear and binary logistic regression models were used to compare functional outcomes and HRQOL across diagnostic stages and self-reported treatment groups. Each model included adjustment for age, socioeconomic deprivation, and number of other long-term conditions. 35 823 (60·8%) of 58 930 men responded to the survey. Disease stage was known for 30 733 (85·8%) of 35 823 men; 19 599 (63·8%) had stage I or II, 7209 (23·4%) stage III, and 3925 (12·8%) stage IV disease. Mean adjusted EPIC-26 domain scores were high, indicating good function, except for sexual function, for which scores were much lower. Compared with men who did not receive androgen deprivation therapy, more men who received the therapy reported moderate to big problems with hot flushes (30·7% [95% CI 29·8–31·6] vs 5·4% [5·0–5·8]), low energy (29·4% [95% CI 28·6–30·3] vs 14·7% [14·2–15·3]), and weight gain (22·5%, 21·7–23·3) vs 6·9% [6·5–7·3]). Poor sexual function was common (81·0%; 95% CI 80·6–81·5), regardless of stage, and more than half of men (n=18 782 [55·8%]) were not offered any intervention to help with this condition. Overall, self-assessed health was similar in men with stage I–III disease, and although slightly reduced in those with stage IV cancer, 23·5% of men with metastatic disease reported no problems on any EQ-5D dimension. Men diagnosed with advanced disease do not report substantially different HRQOL outcomes to those diagnosed with localised disease, although considerable problems with hormonal function and fatigue are reported in men treated with androgen deprivation therapy. Sexual dysfunction is common and most men are not offered helpful intervention or support. Service improvements around sexual rehabilitation and measures to reduce the effects of androgen deprivation therapy are required. The Movember Foundation, in partnership with Prostate Cancer UK.

ObjectivesTo explore whether a James Lind Alliance Priority Setting Partnership could provide insights on knowledge translation within the field of degenerative cervical myelopathy (DCM).DesignSecondary analysis of a James Lind Alliance Priority Setting Partnership process for DCM.Participants and settingDCM stake holders, including spinal surgeons, people with myelopathy and other healthcare professionals, were surveyed internationally. Research suggestions submitted by stakeholders but considered answered were identified. Sampling characteristics of respondents were compared with the overall cohort to identify subgroups underserved by current knowledge translation.ResultsThe survey was completed by 423 individuals from 68 different countries. A total of 22% of participants submitted research suggestions that were considered ‘answered’. There was a significant difference between responses from different stakeholder groups (p<0.005). Spinal surgeons were the group which was most likely to submit an ‘answered’ research question. Respondents from South America were also most likely to submit ‘answered’ questions, when compared with other regions. However, there was no significant difference between responses from different stakeholder regions (p=0.4).ConclusionsKnowledge translation challenges exist within DCM. This practical approach to measuring knowledge translation may offer a more responsive assessment to guide interventions, complementing existing metrics.

PARP‐1 holds major functions on chromatin, DNA damage repair and transcriptional regulation, both of which are relevant in the context of cancer. Here, unbiased transcriptional profiling revealed the downstream transcriptional profile of PARP‐1 enzymatic activity. Further investigation of the PARP‐1‐regulated transcriptome and secondary strategies for assessing PARP‐1 activity in patient tissues revealed that PARP‐1 activity was unexpectedly enriched as a function of disease progression and was associated with poor outcome independent of DNA double‐strand breaks, suggesting that enhanced PARP‐1 activity may promote aggressive phenotypes. Mechanistic investigation revealed that active PARP‐1 served to enhance E2F1 transcription factor activity, and specifically promoted E2F1‐mediated induction of DNA repair factors involved in homologous recombination (HR). Conversely, PARP‐1 inhibition reduced HR factor availability and thus acted to induce or enhance “BRCA‐ness”. These observations bring new understanding of PARP‐1 function in cancer and have significant ramifications on predicting PARP‐1 inhibitor function in the clinical setting. Synopsis By integrating data generated in model systems and human tissues, and in silico analyses of cancer patient‐derived data, this study reveals that PARP‐1 affects the expression of DNA repair factors through E2F1. Co‐targeting PARP‐1 and the cell cycle machinery could be a novel treatment strategy. PARP‐1 enzymatic and transcriptional regulatory functions are elevated as a function of prostate cancer (PCa) progression. PARP‐1 impacts the transcriptional activity of E2F1, including regulation of cell cycle and DDR gene expression. HR factors are frequently transcriptionally deregulated in PCa, which is enriched in PCa progression. Transcriptional regulation of DNA repair factor expression by PARP‐1 impacts the response to PARPi. Graphical Abstract By integrating data generated in model systems and human tissues, and in silico analyses of cancer patient‐derived data, this study reveals that PARP‐1 affects the expression of DNA repair factors through E2F1. Co‐targeting PARP‐1 and the cell cycle machinery could be a novel treatment strategy.

ABSTRACT The introduction of aquatic non‐native species into novel systems may have negative impacts on native biodiversity. Introduced species can predate native species, compete for resources, transmit diseases, hybridise and degrade habitat. To minimise impacts on aquatic biota, management efforts are needed to reduce invasive species abundance. However, eradication or reduction efforts require information about the source of introductions and the biology and ecology of the organism. Therefore, the objective of this study was to quantify population dynamics, natal origins and dispersal characteristics of the introduced Weather Loach Misgurnus anguillicaudatus, which was recently discovered in Georgia, USA waters. Sagittal otoliths were extracted and aged to determine dynamic rate functions, and we performed microchemical analysis on a subset of otoliths to quantify dispersal and introduction events. Sampled Weather Loach consisted of a wide range of ages and lengths, indicating that natural reproduction and recruitment have been occurring for multiple years. The change in otolith microchemistry seen in some fish reveals that they have dispersed from their introduction or reproduction sites into different areas, while others have likely remained in the same system since hatching. Overall, our findings indicate that the Weather Loach populations in Georgia are disjunct, likely stemming from multiple introductions. These results will be used to develop management strategies as well as aid in the effort to continue and enhance outreach regarding the release of unwanted aquarium fish. We used otoliths to determine population dynamics and performed microchemical analysis to quantify dispersal and introduction events of the recently introduced Weather Loach. Results indicate this species was a cryptic invader and has been reproducing and dispersing into connected waters.

ABSTRACT Aquatic invasive species have negative impacts on native biodiversity and pose a significant threat to overall ecosystem health. Successfully established non‐native species possess life history traits that are advantageous for colonization and expansion into novel environments. The reproductive traits and strategies of fish are often good predictors of invasion success. Thus, understanding reproductive dynamics of non‐native species in their introduced environments is an important component for predicting expansion and effectively managing invasive populations. The Weather Loach Misgurnus anguillicaudatus is a recently discovered introduced species in Georgia, USA, and little is known about its life history attributes where it is not native. Thus, the objectives of this study were to: (1) estimate mean batch fecundity of female Weather Loach; (2) determine timing and periodicity of spawning; and (3) evaluate whether the gonadosomatic index (GSI) is a reliable indicator of reproductive status in this species. Based on observed peaks in eggs larger than 500 µm, we identified the presumed spawning season for Weather Loach to be occurring from April through August. The highest average fecundity observed was during July (10,539 eggs) and the lowest average fecundity observed was during April (3083 eggs). The GSI was a strong predictor of fecundity and tracked the number of mature eggs present in each month of the year. Our estimates of batch fecundity and determination of the annual spawning season can help managers better understand reproductive dynamics and develop predictive population models aimed at evaluating management activities.

Changes in connective tissues of the skeletal muscle-tendon unit (MTU) of aging animal muscles have been associated with increased passive viscoelastic properties. This study examined whether similar changes in the viscoelastic properties were present in short calf MTUs of older women in vivo. Fifteen women 68-87 years of age with short calf MTUs, as represented by limited active dorsiflexion (DF) range of motion (ROM) of < or =5 degrees, and 15 women 20-26 years of age without decreased DF ROM participated. A Kin-Com dynamometer stretched the MTU from plantarflexion to maximal DF at the slow velocity of 5 degrees s(-1) (0.087 rad s(-1)) and the fast velocity of 120 degrees s(-1) (2.094 rad s(-1)) with minimal surface electromyogram activity in the soleus, gastrocnemius, and tibialis anterior muscles. Two-way analysis of variance (ANOVA) tests for repeated measures (Velocity x Group) indicated that all women showed greater passive torque, average passive elastic stiffness, and total absorbed passive elastic energy for the fast stretch than for the slow stretch (P < 0.001). The older women had greater percent increases for the average passive torque (30%) and total absorbed passive elastic energy (26%) for the fast stretch than the younger women (P < 0.05), who had 17.5 and 13% increases, respectively. The older women had less maximal and average passive torque (Nm) and total absorbed passive elastic energy (degrees Nm), but greater average passive elastic stiffness (Nm degrees (-1)) at both stretch velocities (P < 0.001). The results indicated that short calf MTUs of older women have increased passive viscoelastic properties that could have implications for balance and ambulatory function.