AM-301, a barrier-forming nasal spray, versus saline spray in seasonal allergic rhinitis: A randomized clinical trial.

RATIONALE: Saline nasal sprays are frequently used in the management of seasonal allergic rhinitis (SAR) for the cleansing and clearing of aeroallergens from the nasal cavity. Also using a drug-free approach, AM-301 nasal spray is forming a thin film barrier on the nasal mucosa to prevent contact with allergens, trap them, and facilitate their discharge. A clinical trial compared the efficacy, safety, and tolerability of AM-301 and saline spray in SAR. METHODS: A total of 100 patients were randomized 1:1 to self-administer AM-301 or saline 3 × daily for 2 weeks. Primary efficacy endpoint: reduction in mean daily reflective Total Nasal Symptom Score (rTNSS). Secondary efficacy endpoints: reduction in mean instantaneous TNSS and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), global impression of efficacy. Safety and tolerability: adverse events, relief medication use, symptom-free days, global impression of tolerability. RESULTS: AM-301-treated patients achieved a significantly lower rTNSS than the saline group (LS square means difference -1.1, 95% CI -1.959 to -0.241, p = .013) with improvement observed across all individual nasal symptoms. Likewise, all secondary endpoints showed statistical significance in favor of AM-301; for example, quality of life was significantly improved overall (p < .001) as well as for each individual RQLQ domain. Both treatments showed similarly good safety and tolerability. With AM-301, fewer patients used relief medication and more enjoyed symptom-free days compared to saline treatment. CONCLUSIONS: AM-301 was more effective than saline in improving SAR nasal symptoms and related quality of life while offering similar tolerability, demonstrating the benefits of a barrier approach.

An Exploration Into Patients' Experiences That Make Them Feel Safe During Hospitalization: A Qualitative Study.

BACKGROUND: Patient safety is a crucial indicator of health care quality. It is necessary to check the subjective perception of patient safety from the patient's point of view as a consumer of healthcare services. To identify patients' experiences of safety and the themes that constitute the patients' feeling of safety during hospitalization. METHODS: A qualitative study, comprising five focus group discussions (seven people each), was conducted in South Korea between May and July 2018. Patients who were hospitalized for at least three days within one year were included. Researchers analyzed the transcribed script, and a content analysis was performed to describe patients' hospitalized experiences of safety. RESULTS: A total of 35 patients with an average age of 45.4 years participated in the study, and had experience of hospitalization for up to 32 days. The findings revealed four core themes and 14 sub-themes. Patients wanted to take initiative in controlling his/her reception of information and wanted healthcare providers to make the patient feel safe. Patients felt safe when hospitals provided unstinted and generous support. Also, public sentiment about national healthcare and safety made an effect on patient safety sentiment. CONCLUSION: Patients felt safe during hospitalization not only because of the explanation, attitude, and professionalism of the healthcare providers but also because of the support, system, and procedure of the medical institution. Healthcare providers and medical institutions should strive to narrow the gap in patient safety awareness factors through activities with patients. Furthermore, the government and society should make an effort to create a safe medical environment and social atmosphere.

Understanding Physicians' and Nurses' Adaption of National-Leading Patient Safety Culture Policy: A Qualitative Study in Tertiary and General Hospitals in Korea.

BACKGROUND: In Korea, the safety culture is led by national policy. How the policy ensures a patient safety culture needs to be investigated. This study aimed to examine the way in which physicians and nurses regard, understand, or interpret the patient safety-related policy in the hospital setting. METHODS: In this qualitative study, we conducted four focus group interviews (FGIs) with 25 physicians and nurses from tertiary and general hospitals in South Korea. FGIs data were analyzed using thematic analysis, which was conducted in an inductive and interpretative way. RESULTS: Three themes were identified. The healthcare providers recognized its benefits in the forms of knowledge, information and training at least although the policy implemented by the law forcibly and temporarily. The second theme was about the interaction of the policy and the Korean context of healthcare, which makes a "turning point" in the safety culture. The final theme was about some strains and conflicts resulting from patient safety policy. CONCLUSION: To provide a patient safety culture, it is necessary to develop a plan to improve the voluntary participation of healthcare professionals and their commitment to safety. Hospitals should provide more resources and support for healthcare professionals.

A cross-sectional survey of musculoskeletal disorder hazard exposures and self-reported discomfort among on-shore wind turbine service technicians.

BACKGROUND: Servicing and maintaining wind turbines may expose wind turbine technicians (wind techs) to musculoskeletal disorder (MSD) hazards. We aimed to characterise MSD hazard exposures and identify work elements that should be prioritised for MSD prevention efforts. METHODS: A cross-sectional online survey methodology gathered data from 144 wind techs based on a convenience, non-probability sampling approach. The survey was developed using resources from the Ontario MSD Prevention Guideline, where cognitive interviewing yielded wind tech specific modifications. RESULTS: Climbing was the most physically demanding task, followed by torqueing/tensioning and manual materials handling (MMH). However, working in awkward and constrained postures emerged as the task most likely to cause or aggravate discomfort. CONCLUSIONS: Injecting ergonomic and human factors principles into wind turbine design should be a high priority. Re-engineering tools like torque tensioning devices may reduce MSD hazard exposures associated with tasks including torqueing/tensioning and MMH. PRACTITIONER SUMMARY: We know little about musculoskeletal disorder (MSD) hazards associated with green jobs. By surveying wind turbine technicians, we learned that MSD hazards exists, and can be addressed by better considering human factors/ergonomics principles in the design of wind turbines and the tools required for service and maintenance operations.Abbreviations: MSD: musculoskeletal disorder; MMH: manual materials handling; Wind techs: wind turbine technicians; CRE-MSD: centre of research expertise for the prevention of musculoskeletal disorders; CanWEA: Canadiarn wind energy association; HFE: human factors/ergonomics; ASME: American Society of Mechanical Engineers; CSA: Canadian Standards Association.

Comparing proton pump inhibitors with histamin-2 receptor blockers regarding the risk of osteoporotic fractures: a nested case-control study of more than 350,000 Korean patients with GERD and peptic ulcer disease.

BACKGROUND: Patients with peptic ulcer disease (PUD) and gastroesophageal reflux disease (GERD) are more likely to receive long-term therapy with proton pump inhibitors (PPIs). This study aimed to investigate the risk of osteoporotic fractures in PPI users compared to histamine-2 receptor antagonist (H2RA) users and the association between fractures and the duration and regular use of PPI. METHODS: A population-based, nationwide nested case-control study from January 2006 to December 2015 was performed using Korean National Health Insurance Service claims data. We included patients ≥50 years of age, without previous fractures, newly prescribed with PPI or H2RA, and diagnosed with PUD or GERD from 2006 to 2015. Patients with osteoporotic fracture (n = 59,240) were matched with the non-fracture control group (n = 296,200) at a 1:5 ratio based on sex, age, cohort entry date, follow-up duration, and bisphosphonate use. The osteoporotic fractures were defined using the diagnostic codes of claims data (M80, M81, M82, M484, M485, S220, S221, S320, S327, S422, S423, S525, S526, S72). RESULTS: The higher the cumulative use of PPIs, the higher the osteoporotic fracture risk (P for trend < 0.001). The risk of osteoporotic fracture in the patients whose cumulative use of PPI was more than 1 year was higher than that of others (OR: 1.42, 95% CI: 1.32-1.52). Patients who regularly used PPI in the recent 1 year had a higher risk of osteoporotic fracture than exclusive H2RA users (OR: 1.37, 95% CI: 1.26-1.50). CONCLUSIONS: The risk of osteoporotic fracture increased with the duration of PPI use, especially when PPI was used for ≥1 year and regularly in the recent 1 year.

Outcomes After Use of Standard- and Low-Dose Non-Vitamin K Oral Anticoagulants in Asian Patients With Atrial Fibrillation.

Background and Purpose- Limited data are available describing the relative effectiveness, safety, and optimal dosing of non-vitamin K antagonist oral anticoagulants (NOACs) for treatment of nonvalvular atrial fibrillation in East Asian patients. We tried to compare effectiveness and safety outcomes of standard- and low-dose NOACs and warfarin in this population. Methods- Using nationwide administrative claims-based datasets from the Korean National Health Insurance Service Database (July 1, 2015, to December 31, 2016), this study comprised 56 504 anticoagulation-naive nonvalvular atrial fibrillation patients with high thromboembolic risk (CHA2DS2-VASc score, ≥2) treated with oral anticoagulants. Main study outcomes included thromboembolic events (ischemic stroke or systemic embolism), major bleeding, and mortality. Results- Among the study patients, 10 409 (18.4%) received warfarin and 46 095 (81.6%) were treated with NOACs: dabigatran (n=12 593; 22.3%), rivaroxaban (n=21 000; 37.2%), and apixaban (n=12 502; 22.1%). Low-dose NOAC (75.1% dabigatran, 59.7% rivaroxaban, and 62.7% apixaban) was more frequently used than standard-dose NOAC. During median follow-up of 15.0 months, each NOAC was associated with significantly lower risk of thromboembolic events (hazard ratio [HR], 0.76; 95% CI, 0.75-0.81 for dabigatran; HR, 0.74; 95% CI, 0.65-0.83 for rivaroxaban; and HR, 0.68; 95% CI, 0.59-0.78 for apixaban). Regarding safety outcomes, dabigatran (HR, 0.81; CI, 0.69-0.95) and apixaban (HR, 0.67; CI, 0.56-0.79) were associated with lower risk of major bleeding but not with rivaroxaban (HR, 0.96; CI, 0.84-1.11). Among adults <75 years of age without chronic kidney disease, use of low-dose apixaban did not demonstrate clinical benefit over warfarin with respect to thromboembolic events (HR, 0.99; CI, 0.76-1.28) and mortality (HR, 0.85; CI, 0.62-1.16). Conclusions- In this cohort of East Asian patients with nonvalvular atrial fibrillation, NOACs were associated with better effectiveness and safety outcomes versus warfarin. Lower NOAC doses were more often used, but an unjustified underdosing of apixaban seems to result in lower clinical benefit.

Assessing high-intensity focused ultrasound treatment of prostate cancer with hyperpolarized 13 C dual-agent imaging of metabolism and perfusion.

The goal of the study was to establish early hyperpolarized (HP) 13 C MRI metabolic and perfusion changes that predict effective high-intensity focused ultrasound (HIFU) ablation and lead to improved adjuvant treatment of partially treated regions. To accomplish this a combined HP dual-agent (13 C pyruvate and 13 C urea) 13 C MRI/multiparametric 1 H MRI approach was used to measure prostate cancer metabolism and perfusion 3-4 h, 1 d, and 5 d after exposure to ablative and sub-lethal doses of HIFU within adenocarcinoma of mouse prostate tumors using a focused ultrasound applicator designed for murine studies. Pathologic and immunohistochemical analysis of the ablated tumor demonstrated fragmented, non-viable cells and vasculature consistent with coagulative necrosis, and a mixture of destroyed tissue and highly proliferative, poorly differentiated tumor cells in tumor tissues exposed to sub-lethal heat doses in the ablative margin. In ablated regions, the intensity of HP 13 C lactate or HP 13 C urea and dynamic contrast-enhanced (DCE) MRI area under the curve images were reduced to the level of background noise by 3-4 h after treatment with no recovery by the 5 d time point in either case. In the tissues that received sub-lethal heat dose, there was a significant 60% ± 12.4% drop in HP 13 C lactate production and a significant 30 ± 13.7% drop in urea perfusion 3-4 h after treatment, followed by recovery to baseline by 5 d after treatment. DCE MRI Ktrans showed a similar trend to HP 13 C urea, demonstrating a complete loss of perfusion with no recovery in the ablated region, while having a 40%-50% decrease 3-4 h after treatment followed by recovery to baseline values by 5 d in the margin region. The utility of the HP 13 C MR measures of perfusion and metabolism in optimizing focal HIFU, either alone or in combination with adjuvant therapy, deserves further testing in future studies.

The relationship between FSH receptor polymorphism status and IVF cycle outcome: a retrospective observational study.

RESEARCH QUESTION: What is the association between FSH receptor (FSHR) gene polymorphism at position 680 and live birth in women undergoing IVF and intracytoplasmic sperm injection (ICSI). DESIGN: In this retrospective cohort study, data were collected from the Electronic Patient Database of the VU University Medical Centre, Amsterdam, The Netherlands. Women undergoing their first IVF/ICSI cycle between January 2008 and March 2012, of whom the FSHR genotype was determined, were included. The main outcome was live birth rate. Secondary outcomes were ongoing pregnancy, total number of follicles, oocytes and embryos. RESULTS: The FSHR genotype distribution was as follows: 334 women in the Asn/Asn group (28.2%), 617 in the Asn/Ser group (52.1%) and 234 in the Ser/Ser group (19.7%). Basal FSH concentration was highest in the Ser/Ser group (P = 0.006). The number of oocytes (P = 0.01) and number of embryos (P = 0.02) were lowest in the Ser/Ser group. The Asn/Asn group showed a significantly lower live birth rate. Live birth rates were 21.9% versus 31.1% and 27.6% (P = 0.009), for Asn/Asn, Asn/Ser and Ser/Ser, respectively. Logistic regression analysis, however, showed no significant difference on cumulative live birth rate between the three genotypes either unadjusted or when adjusted for age. CONCLUSION: The homozygous Ser/Ser genotype of FSHR polymorphism at position 680 is associated with a reduced ovarian response to ovarian stimulation in IVF/ICSI. No difference in cumulative live birth rate was found.

Gastric Cancer Screening in Common Variable Immunodeficiency.

Individuals with common variable immunodeficiency (CVID) have an increased risk of gastric cancer, and gastrointestinal lymphoma, yet screening for premalignant gastric lesions is rarely offered routinely to these patients. Proposed screening protocols are not widely accepted and are based on gastric cancer risk factors that are not applicable to all CVID patients. Fifty-two CVID patients were recruited for screening gastroscopy irrespective of symptoms or blood results and were compared to 40 controls presenting for gastroscopy for other clinical indications. Overall, 34% of CVID patients had intestinal metaplasia (IM), atrophic gastritis or moderate to severe non-atrophic gastritis, which can increase the risk of gastric cancer, compared to 7.5% of controls (p < 0.01). Focal nodular lymphoid hyperplasia, a precursor lesion for gastrointestinal lymphoma, was seen in eight CVID patients (16%), one of whom was diagnosed with gastrointestinal lymphoma on the same endoscopy. High-risk gastric pathology was associated with increased time since diagnosis of CVID, smoking, Helicobacter pylori, a low-serum pepsinogen I concentration, and diarrhea, but not pepsinogen I/II ratio, iron studies, vitamin B12 levels or upper gastrointestinal symptoms. There was a lower rate of detection of IM when fewer biopsies were taken, and IM and gastric atrophy were rarely predicted by the endoscopist macroscopically, highlighting the need for standardized biopsy protocols. The prevalence of premalignant gastric lesions in patients with CVID highlights the need for routine gastric screening. We propose a novel gastric screening protocol to detect early premalignant lesions and reduce the risk of gastric cancer and gastric lymphoma in these patients.

Mammary collective cell migration involves transient loss of epithelial features and individual cell migration within the epithelium.

Normal mammary morphogenesis involves transitions between simple and multilayered epithelial organizations. We used electron microscopy and molecular markers to determine whether intercellular junctions and apico-basal polarity were maintained in the multilayered epithelium. We found that multilayered elongating ducts had polarized apical and basal tissue surfaces both in three-dimensional culture and in vivo. However, individual cells were only polarized on surfaces in contact with the lumen or extracellular matrix. The basolateral marker scribble and the apical marker atypical protein kinase C zeta localized to all interior cell membranes, whereas PAR3 displayed a cytoplasmic localization, suggesting that the apico-basal polarity was incomplete. Despite membrane localization of E-cadherin and ß-catenin, we did not observe a defined zonula adherens connecting interior cells. Instead, interior cells were connected through desmosomes and exhibited complex interdigitating membrane protrusions. Single-cell labeling revealed that individual cells were both protrusive and migratory within the epithelial multilayer. Inhibition of Rho kinase (ROCK) further reduced intercellular adhesion on apical and lateral surfaces but did not disrupt basal tissue organization. Following morphogenesis, segregated membrane domains were re-established and junctional complexes re-formed. We observed similar epithelial organization during mammary morphogenesis in organotypic culture and in vivo. We conclude that mammary epithelial morphogenesis involves a reversible, spatially limited, reduction in polarity and intercellular junctions and active individualistic cell migration. Our data suggest that reductions in polarity and adhesion during breast cancer progression might reflect partial recapitulation of a normal developmental program.

The effects of supplemental dietary chitosan on broiler performance and myopathic features of white striping.

White striping (WS) is a common myopathy seen in fast-growing broilers. Studies have demonstrated that chitosan is effective as an antioxidant and has antiobesity and fat-absorption reduction properties. We hypothesized that the dietary supplementation of chitosan would have similar effects when fed to fast-growing broilers and would thus lower WS incidence and improve meat quality. One hundred twenty-six broilers were fed corn-soy diets. The grower and finisher diets contained either 0, 0.2, or 0.4% chitosan. After a 6 wk growth period, birds were euthanized, and then WS and gross pathology scores were assessed. Pectoralis major tissues were collected to evaluate cook loss, drip loss, histopathology scores, and the gene expression of CCR7, LECT2, CD36, PPARG, and PTGS2. There were no significant differences between the broiler weights, thus chitosan did not appear to compromise the overall growth of the broilers. Female broilers fed 0.4% chitosan had the lowest WS incidence, while male broiler fed 0.4% chitosan had the least cook loss. However, gene expression analyses did not offer insight into any grossly or histologically visualized differences in the muscles. Thus, while we can postulate that chitosan could have some positive effect in reducing WS incidence and improving meat quality, further studies are required to better scrutinize the mechanisms by which chitosan affects WS and other such myopathies in fast-growing broilers.

A RE-AIM Evaluation of a Visualization-Based Electronic Patient-Reported Outcome System.

OBJECTIVES: Health care systems are primarily collecting patient-reported outcomes (PROs) for research and clinical care using proprietary, institution- and disease-specific tools for remote assessment. The purpose of this study was to conduct a Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) evaluation of a scalable electronic PRO (ePRO) reporting and visualization system in a single-arm study. METHODS: The "mi.symptoms" ePRO system was designed using gerontechnological design principles to ensure high usability among older adults. The system enables longitudinal reporting of disease-agnostic ePROs and includes patient-facing PRO visualizations. We conducted an evaluation of the implementation of the system guided by the RE-AIM framework. Quantitative data were analyzed using basic descriptive statistics, and qualitative data were analyzed using directed content analysis. RESULTS: Reach-the total reach of the study was 70 participants (median age: 69, 31% female, 17% Black or African American, 27% reported not having enough financial resources). Effectiveness-half (51%) of participants completed the 2-week follow-up survey and 36% completed all follow-up surveys. Adoption-the desire for increased self-knowledge, the value of tracking symptoms, and altruism motivated participants to adopt the tool. Implementation-the predisposing factor was access to, and comfort with, computers. Three enabling factors were incorporation into routines, multimodal nudges, and ease of use. Maintenance-reinforcing factors were perceived usefulness of viewing symptom reports with the tool and understanding the value of sustained symptom tracking in general. CONCLUSION: Challenges in ePRO reporting, particularly sustained patient engagement, remain. Nonetheless, freely available, scalable, disease-agnostic systems may pave the road toward inclusion of a more diverse range of health systems and patients in ePRO collection and use.

Crystal structure of a methyl benzoate quadruple-bonded dimolybdenum complex.

Quadruple-bond dimolybdenum complexes provide invaluable insight into the two-electron bond, with structural chemistry providing a foundation for examination of bond properties. The synthesis and solid-state structure of the quadruple-bonded dimolybdenum(II) complex tetra-kis-(µ-4-methyl-benzoato-κ 2 O:O')bis[(tetra-hydro-furan-κO)molybdenum(II)] tetra-hydro-furan disolvate, [Mo2(C8H7O2)4(C4H8O)2]·2C4H8O, are presented. This complex crystallizes in a triclinic cell with low-symmetry space group P . The dimolybdenum paddlewheel structure comprises four methyl-benzoate ligands and two axial THF ligands. The dimolybdenum bond distance of 2.1012 (4) Šis exemplary of this class of compounds.

Techniques for extensor mechanism reconstruction after total knee arthroplasty: Is there a clear winner?

Extensor mechanism (EM) disruption after total knee arthroplasty (TKA) is rare, but can result in devastating outcomes for patients including inability to ambulate. Disruption can occur at the quadriceps tendon, patella, or patellar tendon. This complication can be traumatic, but is often atraumatic from an iatrogenic or degenerative etiology. Primary repair for treatment of EM disruption has led to poor results with high failure rates and has mostly been abandoned. Most commonly accepted techniques center around Achilles tendon allograft reconstruction, synthetic mesh reconstruction, or other smaller options. However, to date, there is still no consensus for the optimal EM reconstructive technique due to the heterogeneity and small sample sizes of published studies. The need to identify a consistent and effective surgical technique is paramount to restore quality of life to patients who suffer from EM disruption after TKA. The purpose of this review is to describe the osteology, vasculature, and EM of the knee, identify risk factors associated with EM disruption after TKA, outline the considerations for surgical management, as well as compare and analyze the latest contributions to the literature, in particular allograft versus synthetic mesh, in the reconstruction of the EM after TKA.

Adherence to follow-up examination after positive fecal occult blood test results affects colorectal cancer mortality: A Korea population-based cohort study.

BACKGROUND: The impact of adherence to follow-up examination after a fecal occult blood test (FOBT) remains ill-defined. AIM: To evaluate the impact of adherence to the follow-up examination on clinical outcomes in individuals with positive FOBT results. METHODS: This was a retrospective cohort study involving Korean individuals aged 50 years or older who participated in the National Cancer Screening Program for CRC from 2009 to 2010. Individuals who underwent a confirmative examination within a year after positive FOBT results were included in compliant group, and those who did not were included in non-compliant group. The incidence and stage of CRC, and 5-year survival were compared between two groups. RESULTS: 5,914 were diagnosed with CRC in the compliant group and 2,973 in the non-compliant group. The proportion of advanced-stage CRC was significantly higher in the non-compliant group (localized CRC 44.6% vs. 36.7% and distant CRC 8.7% vs. 12.5%, p< 0.0001). The survival probability within 5 years was 71.0% in the non-compliant group and 85.9% in the compliant group (hazard ratio 1.70, 95% CI, 1.52-1.90, p< 0.001). CONCLUSION: Individuals who underwent follow-up examination 1 year or more after positive FOBT had a lower survival rate compared with that in those who underwent examination within 1 year.

Pattern and Impact of Off-label Underdosing of Non-Vitamin K Antagonist Oral Anticoagulants in Patients With Atrial Fibrillation Who are Indicated for Standard Dosing.

With safety concerns about increasing bleeding, off-label underdosing of non-vitamin K antagonist anticoagulants (NOACs) is common in East Asian patients with atrial fibrillation (AF). We tried to investigate the pattern of NOAC underdosing and associated clinical outcomes in patients with AF who are indicated for standard dosing. Using the Korean National Health Insurance Service database, we evaluated 16,568 patients with a new prescription of NOAC who are indicated for standard NOAC dosing and compared 4,536 patients with warfarin with respect to thromboembolic events (ischemic stroke or systemic embolization), all-cause mortality and major bleeding. Of the 16,568 patients indicated for standard NOAC dosing, 8,549 (51.9%) received off-label underdosing (50.6% rivaroxaban, 53.0% apixaban). During a median follow up of 15.0 months, as compared with warfarin, underdosing of rivaroxaban was associated with lower risks of major thromboembolic events (hazard ratio [HR]: 0.53; 95% confidence interval [CI]: 0.41 to 0.69) and all-cause mortality (HR 0.57, 95% CI: 0.41 to 0.82), and a similar risk of major bleeding (HR 1.10, 95% CI: 0.82 to 1.46). However, underdosing of apixaban was associated with similar risks of major thromboembolic events (HR: 0.90; 95% CI: 0.70 to 1.16), all-cause mortality (HR 0.94, 95 CI: 0.71 to 1.24) and major bleeding (HR 0.84, 95% CI: 0.61 to 1.17). In conclusion, in this Korean population with AF who are indicated for standard NOAC dosing, off-label underdosing is common and its clinical benefit over warfarin was inconsistent according to types of NOAC. Notably, apixaban underdosing provides no benefit in effectiveness compared with warfarin.

Clinical Factors Associated with Adherence to the Follow-Up Examination after Positive Fecal Occult Blood Test in National Colorectal Cancer Screening.

Background: The compliance with the follow-up examination after a positive fecal occult blood test (FOBT) is lower than expected. We aimed to evaluate the adherence rate to the follow-up examination in patients with a positive FOBT and to identify the clinical factors associated with this adherence. METHODS: The study population comprised adults aged ≥50 years who participated in the National Cancer Screening Program for colorectal cancer (CRC) in 2013. Compliance was defined as undergoing follow-up examination within 1 year of a positive FOBT. RESULTS: From 214,131 individuals with a positive FOBT, 120,911 (56.5%) were in the compliance group and 93,220 (43.5%) were in the non-compliance group. On multivariate analysis, good compliance was associated with men (odds ratio (OR) = 1.12, 95% confidence interval (CI) (1.09-1.15)), younger ages (70-79 years, OR = 2.19 (2.09-2.31); 60-69 years, OR = 3.29 (3.13-3.46); 50-59 years, OR = 3.57 (3.39-3.75) vs. >80 years), previous experience of CRC screening (a negative FOBT, OR = 1.18 (1.15-1.21); a positive FOBT, OR = 2.42 (2.31-2.54)), absent previous experience of colonoscopy or barium enema (OR = 2.06 (1.99-2.13)), higher economic income (quartile, 75%, OR = 1.14 (1.11-1.17); 100%, OR = 1.22 (1.19-1.25)), current smokers (OR = 1.12 (1.09-1.15)), alcohol intake (OR = 1.03 (1.01-1.05)), active physical activity (≥3 times/week, OR = 1.13 (1.11-1.15)), depression (OR = 1.11 (1.08-1.14)), and present comorbidities (Charlson Comorbidity Index, ≥1). CONCLUSION: This study identified clinical factors, namely, male, younger ages, prior experience of fecal test, absent history of colonoscopy or double-contrast barium enema (DCBE) within 5 years, and high socioeconomic status to be associated with good adherence to the follow-up examination after a positive FOBT.

Simultaneous Metabolic and Perfusion Imaging Using Hyperpolarized 13C MRI Can Evaluate Early and Dose-Dependent Response to Radiation Therapy in a Prostate Cancer Mouse Model.

PURPOSE: To investigate use of a novel imaging approach, hyperpolarized (HP) 13C magnetic resonance imaging (MRI) for simultaneous metabolism and perfusion assessment, to evaluate early and dose-dependent response to radiation therapy (RT) in a prostate cancer mouse model. METHODS AND MATERIALS: Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) mice (n = 18) underwent single-fraction RT (4-14 Gy steep dose across the tumor) and were imaged serially at pre-RT baseline and 1, 4, and 7 days after RT using HP 13C MRI with combined [1-13C]pyruvate (metabolic active agent) and [13C]urea (perfusion agent), coupled with conventional multiparametric 1H MRI including T2-weighted, dynamic contrast-enhanced, and diffusion-weighted imaging. Tumor tissues were collected 4 and 7 days after RT for biological correlative studies. RESULTS: We found a significant decrease in HP pyruvate-to-lactate conversion in tumors responding to RT, with concomitant significant increases in HP pyruvate-to-alanine conversion and HP urea signal; the opposite changes were observed in tumors resistant to RT. Moreover, HP lactate change was dependent on radiation dose; tumor regions treated with higher radiation doses (10-14 Gy) exhibited a greater decrease in HP lactate signal than low-dose regions (4-7 Gy) as early as 1 day post-RT, consistent with lactate dehydrogenase enzyme activity and expression data. We also found that HP [13C]urea MRI provided assessments of tumor perfusion similar to those provided by 1H dynamic contrast-enhanced MRI in this animal model. However, apparent diffusion coefficien , a conventional 1H MRI functional biomarker, did not exhibit statistically significant changes within 7 days after RT. CONCLUSION: These results demonstrate the ability of HP 13C MRI to monitor radiation-induced physiologic changes in a timely and dose-dependent manner, providing the basic science premise for further clinical investigation and translation.

The Role of Lactate Metabolism in Prostate Cancer Progression and Metastases Revealed by Dual-Agent Hyperpolarized 13C MRSI.

This study applied a dual-agent, 13C-pyruvate and 13C-urea, hyperpolarized 13C magnetic resonance spectroscopic imaging (MRSI) and multi-parametric (mp) ¹H magnetic resonance imaging (MRI) approach in the transgenic adenocarcinoma of mouse prostate (TRAMP) model to investigate changes in tumor perfusion and lactate metabolism during prostate cancer development, progression and metastases, and after lactate dehydrogenase-A (LDHA) knock-out. An increased Warburg effect, as measured by an elevated hyperpolarized (HP) Lactate/Pyruvate (Lac/Pyr) ratio, and associated Ldha expression and LDH activity were significantly higher in high- versus low-grade TRAMP tumors and normal prostates. The hypoxic tumor microenvironment in high-grade tumors, as measured by significantly decreased HP 13C-urea perfusion and increased PIM staining, played a key role in increasing lactate production through increased Hif1α and then Ldha expression. Increased lactate induced Mct4 expression and an acidic tumor microenvironment that provided a potential mechanism for the observed high rate of lymph node (86%) and liver (33%) metastases. The Ldha knockdown in the triple-transgenic mouse model of prostate cancer resulted in a significant reduction in HP Lac/Pyr, which preceded a reduction in tumor volume or apparent water diffusion coefficient (ADC). The Ldha gene knockdown significantly reduced primary tumor growth and reduced lymph node and visceral metastases. These data suggested a metabolic transformation from low- to high-grade prostate cancer including an increased Warburg effect, decreased perfusion, and increased metastatic potential. Moreover, these data suggested that LDH activity and lactate are required for tumor progression. The lactate metabolism changes during prostate cancer provided the motivation for applying hyperpolarized 13C MRSI to detect aggressive disease at diagnosis and predict early therapeutic response.

Effectiveness of adaptive seating on sitting posture and postural control in children with cerebral palsy.

PURPOSE: We reviewed research on the effect of adaptive seating on sitting posture/postural control in children with cerebral palsy. Second, we examined whether changes in postural control related to changes in other aspects of functioning. METHODS: Electronic database/hand searches were undertaken to locate studies published in English. Reviewers screened studies for inclusion criteria, extracted data, indexed outcomes to the International Classification of Functioning, Disability and Health, assigned levels of evidence, and assessed study quality. RESULTS: Thirteen of 14 articles used group designs and the other a single-subject design. Conflicting findings were reported for saddle seats and optimal seat/back angle for improving sitting posture/postural control. Significant improvements were reported with seat inserts, external supports, and modular seating systems. Evidence supporting effects of postural control on functional abilities was limited. CONCLUSIONS: Future studies on the effects of adaptive seating should describe participants with standardized classification systems and employ stronger research designs.