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Background: Renal replacement therapy (RRT) remains the key rescue therapy for critically ill patients with severe acute kidney injury (AKI). However, there are currently no tools available to predict successful liberation from RRT. Biomarkers may allow for risk stratification and individualization of treatment strategies. Proenkephalin A 119-159 (penKid) has been suggested as a promising marker of kidney function in the context of AKI, but has not yet been evaluated for RRT liberation in critically ill patients with AKI.Methods: This post hoc analysis included 210 patients from the randomized clinical ELAIN trial and penKid levels were measured in the blood of these patients. Competing risk time-to-event analyses were performed for pre-RRT penKid at initiation of RRT and in a landmark analysis at day 3 after initiation of RRT. Competing risk endpoints were successful liberation from RRT or death without prior liberation from RRT.Results: Low pre-RRT penKid levels (penKid ≤ 89 pmol/l) at RRT initiation were associated with early and successful liberation from RRT compared to patients with high pre-RRT penKid levels (subdistribution hazard ratio (sHR) 1.83, 95%CI 1.26-2.67, p = 0.002, estimated 28d-cumulative incidence function (28d-CIF) of successful liberation from RRT 61% vs. 45%, p = 0.022). This association persisted in the landmark analysis on day 3 of RRT (sHR 1.78, 95%CI 1.17-2.71, p = 0.007, 28d-CIF of successful liberation from RRT 67% vs. 47%, p = 0.018). For both time points, no difference in the competing event of death was detected.Conclusions: In critically ill patients with RRT-dependent AKI, plasma penKid appears to be a useful biomarker for the prediction of shorter duration and successful liberation from RRT and may allow an individualized approach to guide strategies of RRT liberation in critically ill patients with RRT-dependent AKI.Trial Registration: The ELAIN trial was prospectively registered at the German Clinical Trial Registry (Identifier: DRKS00004367) on 28th of May 2013. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease is a long-term, complex health condition. To improve or maintain quality of life, people with Parkinson's can have an active involvement in their care through self-management techniques. Given the complexity and individualization of self-management, people with Parkinson's will need support and encouragement from their healthcare professionals (HCPs). Despite the key role HCPs have in this, research has seldom explored their perspectives and understanding of self-management for people with Parkinson's.Methods: Multi-disciplinary teams providing care for people with Parkinson's across London, Coventry and Hertfordshire were approached and took part in either one of four focus groups or individual interviews. Forty-two HCPs, including a range of specialist doctors, general practitioners, allied health professionals, nurses, and social workers, took part in this study. Interviews were transcribed and analysed using thematic analysis to identify themes.Results: Four themes were developed from the data: 1) Empowerment of patients through holistic care and being person-centred; 2) Maximising motivation and capability for patients, for example using asset based approaches and increasing opportunities; 3) importance of empowerment of carers to support self-management and 4) contextual barriers to self-management such as the social context.Conclusions: This study is the first to explore the perspectives of HCPs on self-management in people with Parkinson's. Our findings have identified important considerations surrounding empowerment, motivation, carers and contextual barriers to better understand how we enable effective self-management techniques in people with Parkinson's. Research should build on these findings on to develop acceptable and effective self-management tools for use in practice with people affected by Parkinson's. [ABSTRACT FROM AUTHOR]

Background: Over the past decades, remarkable advancements in systemic drug therapy have improved the prognosis of patients with bone metastases. Individualization is required in external beam radiotherapy (EBRT) for bone metastases according to the patient's prognosis. To establish individualized EBRT for bone metastases, we investigated factors that affect the local control (LC) of bone metastases.Methods: Between January 2010 and December 2019, 536 patients received EBRT for 751 predominantly osteolytic bone metastases. LC at EBRT sites was evaluated with a follow-up computed tomography. The median EBRT dose was biologically effective dose (BED10) (39.0) (range of BED10: 14.4-71.7 Gy).Results: The median follow-up time and median time of computed tomography follow-up were 11 (range 1-123) months and 6 (range 1-119) months, respectively. The 0.5- and 1-year overall survival rates were 73% and 54%, respectively. The 0.5- and 1-year LC rates were 83% and 79%, respectively. In multivariate analysis, higher age (≥ 70 years), non-vertebral bone metastases, unfavorable primary tumor sites (esophageal cancer, colorectal cancer, hepatobiliary/pancreatic cancer, renal/ureter cancer, sarcoma, melanoma, and mesothelioma), lower EBRT dose (BED10 < 39.0 Gy), and non-administration of bone-modifying agents (BMAs)/antineoplastic agents after EBRT were significantly unfavorable factors for LC of bone metastases. There was no statistically significant difference in the LC between BED10 = 39.0 and BED10 > 39.0 Gy.Conclusions: Regarding tumor-related factors, primary tumor sites and the sites of bone metastases were significant for the LC. As for treatment-related factors, lower EBRT doses (BED10 < 39.0 Gy) and non-administration of BMAs/antineoplastic agents after EBRT were associated with poor LC. Dose escalation from BED10 = 39.0 Gy did not necessarily improve LC. [ABSTRACT FROM AUTHOR]

Objectives: This study evaluated the impact of self-management interventions based on the COM-B model on peri-implant conditions in older adults with periodontitis. Materials and methods: The patients were randomly divided into two groups: Group 1 (control group) received only an oral health education (OHE) pamphlet. Group 2 (test group) performed a self-management intervention based on the COM-B model. Each patient was examined for the most inflammatory implant. The measurement parameters included self-efficacy, self-management ability, and clinical indicators such as probing depth (PD), bleeding on probing (BOP), modified gingival index (mGI), modified plaque index (mPI), and peri-implant mucositis severity score (PMSS). The data was collected at baseline, 4, 8, and 12 weeks. Results: 42 patients underwent testing for 3 months. After 12 weeks, the improvement of self-efficacy, self-management ability, and the reduction of BOP, mPI, and PMSS in the test group was significantly higher than in the control group. Conclusion: The study suggests that self-management interventions based on the COM-B model can enhance the self-management ability of older adults with periodontitis and reduce peri-implant inflammation. This method is more effective than distributing OHE pamphlets. Trial registration: The randomized controlled clinical trial was registered on Chinese Clinical Trial Registry (No. ChiCTR2400082660, Date: 03/04/2024). [ABSTRACT FROM AUTHOR]

Background: The aim of the randomized controlled clinical trial study was to evaluate the effectiveness in reducing pathologically increased pocket probing depths (PPD > 3 mm) using the Guided Biofilm Therapy (GBT) protocol (adapted to the clinical conditions in non-surgical periodontal therapy (NSPT): staining, air-polishing, ultrasonic scaler, air-polishing) compared to conventional instrumentation (staining, hand curettes/sonic scaler, polishing with rotary instruments) both by less experienced practitioners (dental students). Methods: All patients were treated according to a split-mouth design under supervision as diseased teeth of quadrants I/III and II/IV randomly assigned to GBT or conventional treatment. In addition to the treatment time, periodontal parameters such as PPD and bleeding on probing (BOP) before NSPT (T0) and after NSPT (T1: 5 ± 2 months after T0) were documented by two calibrated and blinded examiners (Ethics vote/ Trial-register: Kiel-D509-18/ DRKS00026041). Results: Data of 60 patients were analyzed (stage III/IV: n = 36/ n = 24; grade A/ B/ C: n = 1/ n = 31/ n = 28). At T1, a PPD reduction of all diseased tooth surfaces was observed in 57.0% of the GBT group and 58.7% of the control group (p = 0.067). The target endpoint (PPD ≤ 4 mm without BOP) was achieved in 11.5% for GBT (conventional treatment: 11.2%; p = 0.714). With the exception for number of sites with BOP, which was at T1 15.9% in the GBT group and 14.3% in the control group (p < 0.05) no significant differences between the outcomes of the study were found. At 30.3(28.3) min, the treatment time was significantly shorter in GBT than in the control group at 34.6(24.5) min (p < 0.001). Conclusions: With both protocols (GBT/ conventional instrumentation) comparably good clinical treatment results can be achieve in NSPT in stage III-IV periodontitis patients. Trial registration: The study was registered before the start of the study and can be found under the number DRKS00026041 in the German Clinical Trials Register. The registration date was 19/08/2021. [ABSTRACT FROM AUTHOR]

Background: Affective responses are increasingly recognized as potentially effective intervention targets that may facilitate exercise and physical activity behavior change. While emerging correlational evidence suggests that more pleasant affective responses are associated with higher participation and adherence, experimental evidence remains scarce. In light of this, we conducted a preregistered, pragmatic, single-blinded, superiority randomized controlled trial with two parallel groups, with the goal of determining the impact of an individualized exercise-intensity prescription targeting pleasure on exercise frequency. Methods: Forty-seven non-regular exercisers were randomized into two groups. For both groups, the intervention consisted of three exercise sessions based on the Frequency-Intensity-Time-Type (FITT) principle. However, the experimental group also received an individualized intensity prescription based on prior assessment of preference for and tolerance of exercise intensity, as well as instructions emphasizing the promotion of pleasure as a basis for self-regulating exercise intensity. The primary outcome was gymnasium attendance over an eight-week follow-up period. Secondary outcomes were affective valence and arousal, post-exercise enjoyment, core affective exercise experiences, and anticipated and remembered affect. Results: Forty-six participants were retained for analysis (Mage = 32.00; SD = 8.62 years; 56.5% female). Compared to the control group, the experimental group exhibited 77% higher session attendance (14.35 vs. 8.13 sessions) over the eight-week follow-up period (group main effect p =.018, η2p =.120; Cohen's d ranged from 0.28 to 0.91 during follow-up). Also, the experimental group reported higher levels of pleasure during the intervention sessions (for all group main effects, p <.001, η2p from.33 to.37) and higher levels of remembered pleasure (group main effect p =.021, η2p =.116) and anticipated pleasure (group main effect p =.022, η2p =.114). No harm was detected. Conclusions: These results demonstrate the practicality and effectiveness of an intervention aimed at enhancing affective responses to exercise in improving short-term session attendance. Trial registration: ClinicalTrial.gov NCT05416593. [ABSTRACT FROM AUTHOR]

Background: For more than a decade, the Patient-Centered Medical Home model has been a guiding vision for the modernization of primary care systems. In Canada, Ontario's Family Health Teams (FHTs) were designed in the mid-2000s with the medical home model in mind. These primary care clinics aim to provide accessible, comprehensive, and person-centered primary care services to communities across Ontario. Their services typically include mental health care for people experiencing common mental disorders, such as depression and anxiety disorders. It remains unclear, however, whether the mental health care delivered within FHTs is consistent with person-centered care approaches. In the current study, we aimed to explore the perspectives of FHT providers on the care delivered to people with common mental disorders to determine whether, and to what extent, they believed this care was person-centered. Methods: We conducted a qualitative grounded theory study involving interviews with 65 health professionals and administrators from 18 FHTs across Ontario. Transcripts were coded using a three-step process of initial, focused, and axial coding that mixed inductive and deductive approaches informed by sensitizing concepts on person-centeredness. Results: Practices and challenges associated with the delivery of mental health care in a person-centered way were captured by several themes regrouped into five domains: (1) patient as unique person, (2) patient-provider relationship, (3) sharing power and responsibility, (4) connecting to family and community, and (5) creating person-centered care environments. FHT providers perceived that they delivered person-centered care by delivering mental health care that was responsive, flexible, and consistent with biopsychosocial approaches. They emphasized the importance of creating long-lasting relationships with patients grounded in empathy and trust. Their challenges included being able to ensure continuity of care, adequately prioritizing patients' mental health issues, and meaningfully engaging patients and families as partners in care. Conclusions: Our findings suggest that FHT providers have adopted a range of person-centered practices for people with common mental disorders. However, greater attention to practices such as shared decision making, supporting self-management, and involving families in care would strengthen person-centeredness and bring teams closer to the Patient-Centered Medical Home vision. [ABSTRACT FROM AUTHOR]

Objective: Türkiye is the leading country that has been applying the MPOWER criteria of the World Health Organization for years. However, the prevalence of smoking among nurses appears to be high, according to the literature. Therefore, we aimed to determine the prevalence, addiction levels, and dynamics of tobacco smoking among nurses in Türkiye. Method: In this descriptive cross-sectional study, a questionnaire (prepared in cooperation with the "World Health Organization") and the Fagerström Test for Nicotine Dependence were administered to 529 nurses working at a tertiary-care university hospital in 2020. Logistic regression was performed to determine factors predicting smoking. Results: The prevalence of smoking among nurses was 32.7% (n = 173). The mean Fagerström test score indicated a "low dependence" level (score: 3 ± 2.6). Both results were higher for males. A relationship was found between trying smoking cigarette and hookah. Of the "current smokers" group, 102 (60.4%) stated that they wanted to quit smoking. Only 21 (27.6%) of the nurses who have tried to quit smoking thus far have received professional help. Conclusion: The prevalence of smoking among nurses working at a tertiary-care university hospital was relatively low compared to that among nurses in Türkiye. While females are normally expected to smoke less, the high prevalence of smoking among nurses (most of them female) raises the question of the professional basis of this situation. However, the low rate of receiving professional help reveals the lack of promotion and accessibility of smoking cessation outpatient clinics in the faculty environment. Finally, the perception that hookah is an alternative tobacco product leads to cigarette smoking. The good news was that nurses had a low dependency rate. [ABSTRACT FROM AUTHOR]

Background: Despite the context of individualization of public policies and promotion of independent living, residential care facilities (RCFs) (called "établissements medico-sociaux" in France) still represent the main system used by disabled people. Through a study of their daily mobility, this article proposes a geographical approach to the examination of factors influencing the social participation of disabled persons with motor impairments who live in residential care facilities.Methods: The data were collected in three stages from several sources. We first carried out 24 semi-directive interviews among supervisory staff in all the institutions in two regions of France (Greater Paris and Upper Normandy) to better understand the nature of services offered by medico-social facilities. We next did field work in greater detail in 10 of these institutions. We selected residents by random sampling. These first stages then allowed us to study the mobility of residents and record their perceptions. We conducted participant observation and interviews with 81 disabled residents within the 10 RCF. Data analysis enabled consideration not only of the role of the residential environment in people's daily mobility, but the role of the institutions as well.Results: We identified three typical profiles of mobility practices depending on the facilities: "the islanders", living in isolated facilities far from public transportation, or in so-called "difficult" neighborhoods; people who alternate individual and group mobility in a more or less large area; and "the navigators" who have high mobility over a very large area, often living in facilities located in urban areas. The study also enabled an analysis of the obstacles and facilitators inside and outside the residential facilities. These place restrictions on social participation by disabled adults. However, possibilities for individual negotiation may enable bypassing some obstacles.Conclusions: The three ideal-type profiles of mobility analyzed constitute adaptations to the environment by residents and the institution. The research techniques used and the presentation of data (in the form of diagrams) enabled a better understanding of the mobility of severely disabled adults living in an institution, a population that is rarely studied. [ABSTRACT FROM AUTHOR]

Background: Current treatments for chronic hepatitis B (CHB) include pegylated interferon alpha (PEG-IFN-α) which is an immune modulator, and nucleos(t)ide analogs (NAs) which directly inhibit HBV DNA polymerase. With the limited efficacy of PEG-IFN-α and prolonged treatment periods associated with NAs, there is an urgent need for novel therapeutic strategies, especially for patients with a poor early response to anti-viral therapy.Methods: In this study, 178 patients with chronic hepatitis B (n = 131) and compensated (n = 47) HBV-induced cirrhosis were enrolled, 120 patients with HBeAg (+). All the patients were treated for 12 weeks with PEG-IFN-α. Among them, a total of 138 patients with a poor virological response after 12 weeks were treated for an additional 48 weeks with Peg-IFNα-2a (control) (n = 43), with Peg-IFNα-2a + entecavir (ETV) (n = 49), or Peg-IFNα-2a + adefovir dipivoxil (ADV) (n = 46), and were followed for 48 weeks after therapy. Early virological response was defined as undetectable HBV DNA after anti-viral therapy for 12 weeks. Sustained virological response (SVR) was defined as no change in therapeutic effectiveness after 6 months follow-up, and no recurrence.Therapeutic efficacy was determined by evaluating HBV DNA levels, serum and liver HBsAg levels, liver function tests and liver histology.Results: Patients in the Peg-IFNα-2a + ETV and Peg-IFNα-2a + ADV groups showed a significantly greater decrease in HBV DNA levels over time, and a significantly higher SVR compared to patients receiving Peg-INFα-2a monotherapy (both P values <0.05). Although patients receiving combination therapy had a significantly higher change in serum HBsAg levels compared to the monotherapy group, there was no significant difference in liver HBsAg levels between the three treatment groups.Conclusion: This study demonstrated that in patients with a poor virological response after 12 weeks of treatment with Peg-IFNα-2a alone, addition of ADV or ETV significantly reduced HBV DNA levels, serum HBsAg levels, and increased SVR. Individualization of anti-viral therapy would ensure that only patients who do not respond to Peg-IFNα-2a would receive combination therapy. Our data have important implications for the treatment of CHB patients who fail to show an early response to Peg-IFNα-2a monotherapy.Trial Registration: This trial was retrospectively registered on 2012 May 24 at the China Clinical Trials Registry (ChiCTR-OCC-12002196). [ABSTRACT FROM AUTHOR]

Background: In light of the growing emphasis on individualization in healthcare, it is vital to take the diversity of inhabitants and users into consideration. Thus, identifying shared perceptions among group members may be important in improving healthcare that is relevant to the particular group, but also perceptions of the staff with whom interactions take place. This study investigates how motherhood is perceived among three groups: Somali-born mothers; Swedish-born mothers; and nurses at Swedish child health centers. Inequities in terms of access and satisfaction have previously been identified at the health centers. Methods: Participants in all three groups were asked to finalize two statements about motherhood; one statement about perfect motherhood, another about everyday motherhood. The responses were analyzed using qualitative coding and categorization to identify differences and similarities among the three groups. Results: The responses to both statements by the three groups included divergences as well as convergences. Overall, biological aspects of motherhood were absent, and respondents focused almost exclusively on social matters. Working life was embedded in motherhood, but only for the Somali-born mothers. The three groups put emphasis on different aspects of motherhood: Somali-born mothers on the community; the Swedish-born mothers on the child; and the nurses on the mother herself. The nurses -- and to some extent the Swedish-born mothers -- expected the mother to ask for help with the children when needed. However, the Somali-born mothers responded that the mother should be independent, not asking for such help. Nurses, more than both groups of mothers, largely described everyday motherhood in positively charged words or phrases. Conclusion: The findings of this paper suggest that convergences and divergences in perceptions of motherhood among three groups may be important in equitable access and utilization of healthcare. Individualized healthcare requires nuance and should avoid normative or stereotypical encounters by recognizing social context and needs that are relevant to specific groups of the population. [ABSTRACT FROM AUTHOR]

Background: Painful spinal metastases have been treated with conventional radiotherapy for decades, but one-third of the patients have insufficient pain relief after treatment and one-fifth need retreatment. Stereotactic radiotherapy is a method to increase the dose in the spinal metastases with a potentially longer lasting palliative effect without increasing the side effects of the treatment and thereby is expected to improve the quality of life significantly.Methods/design: This study is a multicenter prospective randomized clinical trial comparing conventional radiotherapy (1 x 8 Gy) with stereotactic radiotherapy (1 x 20 Gy) for pain reduction and quality of life in patients with painful spinal metastases. A total of 386 patients will be randomized between the two treatment groups. Besides pain measured by the Dutch Brief Pain Inventory, quality of life and cost-effectiveness also will be measured. The primary outcome is pain reduction at 6 weeks after treatment. Secondary outcomes will be the time to pain response, duration of pain relief, health-related quality of life and toxicity, as well as cost-effectiveness.Discussion: This study investigates whether stereotactic radiotherapy with dose escalation for symptomatic spinal metastases can lead to improved pain reduction as compared to conventional radiotherapy without an increase of treatment-related side effects. These results will contribute to the optimization and individualization of the treatment for the patient.Trial Registration: ClinicalTrials.gov identifier NCT02407795 (March 31, 2015). [ABSTRACT FROM AUTHOR]

Background: Low back pain is one of the most common disabling pathologies in humanity worldwide. Physical exercises have been used in recent decades to reduce the pain, improve the functionality of the lumbar spine and avoid relapses. The purpose of the study is to analyze the effect of a program based on re-education exercises involving preactivation of the abdominal transverse muscle compared to conventional treatment in adults with chronic nonspecific low back pain. Methods: A two-arm, single-blind randomized control trial with 35 primary care patients with chronic nonspecific low back pain. Both groups received a 4-week intervention. Data were collected at baseline and at the end of the intervention. Sixteen patients participated in the intervention group, and 19 patients in the control group. Results: For the experimental group, the outcomes of disability and activation of the abdominal transverse muscle decreased significantly (MD -2.9; CI 95% -5.6 to -0.35; η2 = 0.14; p = 0.028) and (MD 2.3; CI 95% 0.91 to 3.67; η2 = 0.25; p = 0.002) respectively, with a large effect size, compared to the control group. There were no differences between the groups in pain intensity, thickness, and resistance of the transverse abdominal muscle. Conclusion: A 4-week specific program based on re-education exercises of the preactivation of the abdominal transverse muscle is more effective than conventional treatment for reducing disability and increasing the activation of the abdominal transverse muscle measured by VAS scale and PBU. Trial registration: Clinicaltrials.gov identifier: NCT03097497. Date of registration: 31/03/2017. [ABSTRACT FROM AUTHOR]

Background: Patients with developmental dysplasia of the hip (DDH) have complex proximal femoral deformities, and orthopedic surgery lacks objectivity. Expectations for surgical outcomes are often not achieved, and postoperative problems are common. Using 3D-printed technology in orthopedics offers a novel approach to precise and individualized treatment in modern orthopedics. The aim of this study was to investigate the value of the application of 3D-printed osteotomy guide plates in femoral osteotomy. The clinical indices of femoral osteotomy in children with DDH using 3D-printed osteotomy guide plates were compared with those of traditional osteotomy. Methods: The clinical data of children with DDH who underwent open reduction and Salter pelvic osteotomy combined with femoral osteotomy from September 2010 to September 2020 were retrospectively collected and analyzed. Based on the inclusion and exclusion criteria, a total of 36 patients were included in the study: 16 in the guide plate group and 20 in the conventional group. Operation time (total), operation time (femoral side), X-ray fluoroscopy times (total), X-ray fluoroscopy times (femoral side) and intraoperative blood loss were analyzed and compared between the two groups. Comparison of treatment-related indicators such as postoperative neck-shaft angle, postoperative anteversion angle, hospitalization time, and hospitalization expenses is made between the two groups. The two groups of patients were evaluated at the last follow-up using the McKay clinical evaluation criteria. Results: Between the two groups, there were significant differences in operation time (total), operation time (femoral side), X-ray fluoroscopy times (total), X-ray fluoroscopy times (femoral side) and intraoperative blood loss (P < 0.05). The postoperative neck-shaft angle, postoperative anteversion angle, hospitalization time and hospitalization expenses did not differ significantly (P > 0.05). The MacKay clinical evaluation did not significantly differ at the most recent follow-up (P > 0.05). Conclusions: Children with DDH undergoing proximal femoral osteotomy using 3D-printed osteotomy guide plates benefit from a simpler surgical procedure, shorter operative time, less bleeding and less radiation exposure during surgery. This technique is of great clinical value. [ABSTRACT FROM AUTHOR]

Background: In recent years, there have been many reports on the pregnancy outcomes of fresh blastocyst transfer (BT) and frozen-thawed BT, but the conclusions are controversial and incomplete. To compare the pregnancy outcomes, maternal complications and neonatal outcomes of fresh and frozen-thawed BT in the context of in vitro fertilization or intracytoplasmic sperm injection (IVF/ICSI) cycles, we conducted a meta-analysis.Methods: A meta-analysis was conducted by searching the PubMed, Embase, and Cochrane Library databases through May 2020. Data were extracted independently by two authors.Results: Fifty-four studies, including 12 randomized controlled trials (RCTs), met the inclusion criteria. Fresh BT was associated with a lower implantation rate, pregnancy rate, ongoing pregnancy rate, and clinical pregnancy rate and higher ectopic pregnancy rate than frozen-thawed BT according to the results of the RCTs. The risks of moderate or severe ovarian hyperstimulation syndrome, placental abruption, placenta previa and preterm delivery were higher for fresh BT than for frozen-thawed BT. The risk of pregnancy-induced hypertension and pre-eclampsia was lower for fresh BT; however, no significant differences in risks for gestational diabetes mellitus and preterm rupture of membrane were found between the two groups. Compared with frozen-thawed BT, fresh BT appears to be associated with small for gestational age and low birth weight. No differences in the incidences of neonatal mortality or neonatal malformation were observed between fresh and frozen-thawed BT.Conclusions: At present there is an overall slight preponderance of risks in fresh cycles against frozen, however individualization is required and current knowledge does not permit to address a defintive response. [ABSTRACT FROM AUTHOR]

Background: Despite its established association with chronic kidney disease (CKD) the role of myosin-9 (MYH9) gene variation on transplanted kidney function remains unknown. This study aimed at evaluating the effect of donor MYH9 nephrogenic variants on renal allograft function within the first post transplantation year.Methods: In the longitudinal kidney transplant study 207 deceased donors were genotyped for previously known risk MYH9 single nucleotide polymorphisms (SNPs). The predictor was MYH9 high-risk variants status. The primary outcome was mean eGFR found in low vs. high risk MYH9 genotypes between third and twelfth post-transplant month, the secondary outcome was the risk of proteinuria.Results: Distribution of genotypes remained in Hardy-Weinberg equilibrium. The T allele of rs3752462 (dominant model, TT or TC vs. CC) was associated with higher filtration rate (P = 0.05) in a multivariate analysis after adjusting for delayed graft function and donor sex. Two G alleles of rs136211 (recessive model, GG vs. GA or AA) resulted in doubling the risk of proteinuria (OR = 2.22; 95% CI = 1.18-4.37, P = 0.017) after adjusting for donor and recipient sex.Conclusion: Deceased donor kidneys of European descent harboring MYH9 SNPs rs3752462 T allele show significantly superior estimated filtration rate while those of rs136211 GG genotype excessive risk of proteinuria. These findings, if replicated, may further inform and improve individualization of allocation and treatment policies. [ABSTRACT FROM AUTHOR]

Background and aim: The role of dietary protein and glycemic index on insulin resistance (based on TyG index) within a nutritional program for weight loss and weight maintenance was examined. Methods: This study analyzed 744 adults with overweight/obesity within the DIOGenes project. Patients who lost at least 8% of their initial weight (0–8 weeks) after a low-calorie diet (LCD) were randomly assigned to one of five ad libitum diets designed for weight maintenance (8–34 weeks): high/low protein (HP/LP) and high/low glycemic index (HGI/LGI), plus a control. The complete nutritional program (0–34 weeks) included both LCD plus the randomized diets intervention. The TyG index was tested as marker of body mass composition and insulin resistance. Results: In comparison with the LP/HGI diet, the HP/LGI diet induced a greater BMI loss (p < 0.05). ∆TyG was positively associated with resistance to BMI loss (β = 0.343, p = 0.042) during the weight maintenance stage. In patients who followed the HP/LGI diet, TyG (after LCD) correlated with greater BMI loss in the 8–34 weeks period (r = −0.256; p < 0.05) and during the 0–34 weeks intervention (r = −0.222, p < 0.05) periods. ΔTyG1 value was associated with ΔBMI2 (β = 0.932; p = 0.045) concerning the HP/LGI diet. Conclusions: A HP/LGI diet is beneficial not only for weight maintenance after a LCD, but is also related to IR amelioration as assessed by TyG index changes. Registration Clinical Trials NCT00390637. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to establish and validate a clinical prediction model for assessing the risk of metastasis and patient survival in Ewing's sarcoma (ES).Methods: Patients diagnosed with ES from the Surveillance, Epidemiology and End Results (SEER) database for the period 2010-2016 were extracted, and the data after exclusion of vacant terms was used as the training set (n=767). Prediction models predicting patients' overall survival (OS) at 1 and 3 years were created by cox regression analysis and visualized using Nomogram and web calculator. Multicenter data from four medical institutions were used as the validation set (n=51), and the model consistency was verified using calibration plots, and receiver operating characteristic (ROC) verified the predictive ability of the model. Finally, a clinical decision curve was used to demonstrate the clinical utility of the model.Results: The results of multivariate cox regression showed that age, , bone metastasis, tumor size, and chemotherapy were independent prognostic factors of ES patients. Internal and external validation results: calibration plots showed that the model had a good agreement for patient survival at 1 and 3 years; ROC showed that it possessed a good predictive ability and clinical decision curve proved that it possessed good clinical utility.Conclusions: The tool built in this paper to predict 1- and 3-year survival in ES patients ( https://drwenleli0910.shinyapps.io/EwingApp/ ) has a good identification and predictive power. [ABSTRACT FROM AUTHOR]

BACKGROUND | OBJECTIVE: To evaluate the implementation of three intervention elements to reduce hospitalizations in nursing home residents.Design: Convergent mixed-method design within a hybrid type-2 effectiveness-implementation study.Setting: Eleven nursing homes in the German-speaking region of Switzerland.Participants: Quantitative data were collected from 573 care workers; qualitative data were collected from 108 care workers and the leadership from 11 nursing homes.Intervention: Three intervention elements targeting care workers were implemented to reduce unplanned hospitalizations: (1) the STOP&WATCH instrument for early recognition of changes in resident condition; (2) the ISBAR instrument for structured communication; and (3) specially-trained INTERCARE nurses providing on-site geriatric support. Multifaceted implementation strategies focusing both on the overall nursing home organization and on the care workers were used.Methods: The quantitative part comprised surveys of care workers six- and twelve-months post-intervention. The intervention's acceptability, feasibility and uptake were assessed using validated and self-developed scales. Qualitative data were collected in 22 focus groups with care workers, then analyzed using thematic analysis methodology. Data on implementation processes were collected during implementation meetings with nursing home leadership and were analyzed via content analysis. Findings were integrated using a complementary approach.Results: The ISBAR instrument and the INTERCARE nurse role were considered acceptable, feasible, and taken up by > 70% of care workers. The STOP&WATCH instrument showed the lowest acceptance (mean: 68%), ranging from 24 to 100% across eleven nursing homes. A combination of factors, including the amount of information received, the amount of support provided in daily practice, the users' perceived ease of using the intervention and its adaptations, and the intervention's usefulness, appeared to influence the implementation's success. Two exemplary nursing homes illustrated context-specific implementation processes that serve as either barriers or facilitators to implementation.Conclusions: Our findings suggest that, alongside the provision of information shortly before intervention start, constant daily support is crucial for implementation success. Ideally, this support is provided by designated and trained individuals who oversee implementation at the organizational and unit levels. Leaders who seek to implement interventions in nursing homes should consider their complexity and their consequences for workflow to optimize implementation processes accordingly.Trial Registration: This study was registered at clinicaltrials.gov ( NCT03590470 ) on the 18/06/2018. [ABSTRACT FROM AUTHOR]

Background: Patient-centeredness (PC) aims to adapt health care to the individual needs and preferences of patients. An existing integrative model of PC comprises several dimensions of PC which have not yet been investigated from the patients' perspective. Older patients with multimorbidity represent a target group for patient-centered care, as their care needs are particularly complex and should be addressed individually. We aimed to assess the perspective that older patients with multimorbidity have of patient-centered care and to examine the transferability of the integrative model of PC to this specific population.Method: We performed 4 guided focus group interviews with a total of 20 older individuals with multimorbidity. The focus group interviews were audio-recorded and transcribed verbatim. Patients' statements were content-analyzed applying an a priori designed system of categories that included the dimensions of PC from the integrative model and the additional category 'prognosis and life expectancy', which had emerged from an initial literature search on aspects of PC specific to the multimorbid elderly.Results: The new category 'prognosis and life expectancy' was confirmed and expanded to 'individual care needs related to aging and chronic disesase'. All dimensions of our integrative PC model were confirmed for older patients with multimorbidity. Among these, we found that eight dimensions (individual care needs related to aging and chronic disease, biopsychosocial perspective, clinician-patient communication, essential characteristics of the clinician, clinician-patient-relationship, involvement of family and friends, coordination and continuity of care, access to care) were complemented by aspects specific to this target population.Conclusions: The integrative PC model is applicable to the population of older patients with multimorbidity. For a population-specific adaptation, it might be complemented by the dimension 'individual care needs in aging and chronic disease', in conjunction with age-specific aspects within existing dimensions. Together with corresponding results from a Delphi survey, our adapted PC model will serve as the basis for a subsequent systematic review of instruments measuring PC in older patients with multimorbidity.Trial Registration: PROSPERO ( https://www.crd.york.ac.uk/prospero; CRD42018084057; 2018/02/01), German Clinical Trials Register ( www.drks.de ; DRKS00013309; 2018/01/23). [ABSTRACT FROM AUTHOR]

Background: Participatory research offers a promising approach to addressing health inequities and improving the social determinants of health for diverse populations of adolescents. However, little research has systematically explored factors influencing the implementation of participatory health interventions targeting health disparities.Objective: This study examined the utility of the Consolidated Framework for Implementation Research (CFIR) in identifying and comparing barriers and facilitators influencing implementation of participatory research trials by employing an adaptation of the CFIR to assess the implementation of a multi-component, urban public school-based participatory health intervention.Methods: We collected qualitative data over a one-year period through weekly team meeting observational field notes and regular semi-structured interviews with five community-based participatory researchers, one school-based partner, and four school principals involved in implementing a participatory intervention in five schools. Adapted CFIR constructs guided our largely deductive approach to thematic data analysis. We ranked each of the three intervention components as high or low implementation to create an overall implementation effectiveness score for all five schools. Cross-case comparison of constructs across high and low implementation schools identified constructs that most strongly influenced implementation.Results: Ten of 30 assessed constructs consistently distinguished between high and low implementation schools in this participatory intervention, with five strongly distinguishing. Three additional constructs played influential, though non-distinguishing, roles within this participatory intervention implementation. Influential constructs spanned all five domains and fit within three broad themes: 1) leadership engagement, 2) alignment between the intervention and institutional goals, priorities, demographics, and existing systems, and 3) tensions between adaptability and complexity within participatory interventions. However, the dynamic and collaborative nature of participatory intervention implementation underscores the artificial distinction between inner and outer settings in participatory research and the individual behavior change focus does not consider how relationships between stakeholders at multiple levels of participatory interventions shape the implementation process.Conclusions: The CFIR is a useful framework for the assessment of participatory research trial implementation. Our findings underscore how the framework can be readily adapted to further strengthen its fit as a tool to examine project implementation in this context. [ABSTRACT FROM AUTHOR]

Background: Locating technologies are a subtype of assistive technology that aim to support persons with dementia by helping manage spatial orientation impairments and provide aid to care partners by intervening when necessary. Although a variety of locating devices are commercially available, their adoption has remained low in the past years. Several studies have explored barriers to the adoption of assistive technologies from the perspective of professional stakeholders, but in-depth explorations for locating technologies are sparse. Additionally, the inputs of business professionals are lacking. The aim of this study was to expand knowledge on barriers to the adoption of locating technologies from a multi-stakeholder professional perspective, and to explore strategies to optimize adoption.Methods: In total, 22 professionals working in business (n = 7), healthcare (n = 6) and research (n = 9) fields related to gerontology and gerontechnology participated in our focus group study. Perceptions on the value of using locating technologies for dementia care, barriers to their adoption, as well as salient services and information dissemination strategies were explored. After verbatim transcription, transcripts were analysed following an inductive data-driven content analysis approach in MAXQDA.Results: Six key adoption barriers centering on: (1) awareness-, (2) technological-, (3) product characteristic- and (4) capital investment-based limitations, (5) unclear benefits, as well as (6) ethical concerns emerged. The interplay between barriers was high. Five core themes on services and information dissemination strategies centering on: (1) digital autonomy support, (2) emergency support, (3) information dissemination actors, (4) product acquisition, and (5) product advertising were extracted.Conclusions: Our study with interdisciplinary stakeholders expands knowledge on barriers to the adoption of locating technologies for dementia care, and reinforces recommendations that an interdisciplinary strategy is needed to optimize adoption. Also, our findings show that focusing on services to increase digital autonomy and on information dissemination strategies has been largely overlooked and may be particularly effective. [ABSTRACT FROM AUTHOR]

Background: Physicians who include complementary medicine in their practice are thought to have an understanding of health and disease different from that of colleagues practicing conventional medicine. The aim of this study was to identify and compare the thoughts and concepts concerning infectious childhood diseases (measles, mumps, rubella, chickenpox, pertussis and scarlet fever) of physicians practicing homeopathic, anthroposophic and conventional medicine. Methods: This qualitative study used semistructured interviews. Participating physicians were either general practitioners or pediatricians. Data collection and analysis were guided by a grounded theory approach. Results: Eighteen physicians were interviewed (6 homeopathic, 6 anthroposophic and 6 conventional). All physicians agreed that while many classic infectious childhood diseases such as measles, mumps and rubella are rarely observed today, other diseases, such as chickenpox and scarlet fever, are still commonly diagnosed. All interviewed physicians vaccinated against childhood diseases. A core concern for physicians practicing conventional medicine was the risk of complications of the diseases. Therefore, it was considered essential for them to advise their patients to strictly follow the vaccination schedule. Homeopathic-oriented physicians viewed acute disease as a biological process necessary to strengthen health, fortify the immune system and increase resistance to chronic disease. They tended to treat infectious childhood diseases with homeopathic remedies and administered available vaccines as part of individual decision-making approaches with parents. For anthroposophic-oriented physicians, infectious childhood diseases were considered a crucial factor in the psychosocial growth of children. They tended to treat these diseases with anthroposophic medicine and underlined the importance of the family's resources. Informing parents about the potential benefits and risks of vaccination was considered important. All physicians agreed that parent-delivered loving care of a sick child could benefit the parent-child relationship. Additionally, all recognized that existing working conditions hindered parents from providing such care for longer durations of time. Conclusions: The interviewed physicians agreed that vaccines are an important aspect of modern pediatrics. They differed in their approach regarding when and what to vaccinate against. The different conceptual understandings of infectious childhood diseases influenced this decision-making. A survey with a larger sample would be needed to verify these observations. [ABSTRACT FROM AUTHOR]

Background: Family involvement for persons with psychotic disorders is under-implemented in mental health care, despite its firm scientific, economic, legal and moral basis. This appears to be the case in Norway, despite the presence of national guidelines providing both general recommendations on family involvement and support in the health- and care services, and specific guidance on family interventions for patients with psychotic disorders. The aim of this project is to improve mental health services and the psychosocial health of persons with psychotic disorders and their relatives, by implementing selected recommendations from the national guidelines in community mental health centres, and to evaluate this process.Methods: The trial is cluster randomised, where 14 outpatient clusters from community mental health centres undergo stratified randomisation with an allocation ratio of 1:1. The seven intervention clusters will receive implementation support for 18 months, whereas the control clusters will receive the same support after this implementation period. The intervention consists of: 1. A basic level of family involvement and support. 2. Family psychoeducation in single-family groups. 3. Training and guidance of health care personnel. 4. A family coordinator and 5. Other implementation measures. Fidelity to the intervention will be measured four times in the intervention arm and two times in the control arm, and the differences in fidelity changes between the arms constitute the primary outcomes. In each arm, we aim to include 161 patients with psychotic disorders and their closest relative to fill in questionnaires at inclusion, 6 months and 12 months, measuring psychosocial health and satisfaction with services. Clinicians will contribute clinical data about patients at inclusion and 12 months. Use of health and welfare services and work participation, for both patients and relatives, will be retrieved from national registries. We will also perform qualitative interviews with patients, relatives, health care personnel and leaders. Finally, we will conduct a cost-effectiveness analysis and a political economy analysis.Discussion: This project, with its multilevel and mixed methods approach, may contribute valuable knowledge to the fields of family involvement, mental health service research and implementation science.Trial Registration: ClinicalTrials.gov Identifier NCT03869177 . Registered 11.03.19. [ABSTRACT FROM AUTHOR]

Background: Individualized fluid management (IFM) has been shown to be useful to improve the postoperative outcome of patients undergoing major abdominal surgery. A limited number of clinical studies have been done in orthopaedic patients and have yielded conflicting results. We designed the present study to investigate the clinical impact of IFM in patients undergoing major spine surgery. Methods: This is a before-after study done in 300 patients undergoing posterior spine arthrodesis. Postoperative outcomes were compared between control group implementing standard fluid management (n = 150) and IFM group (n = 150) guided by fluid protocol based on continuous stroke volume monitoring and optimization. The primary outcome measure was the proportion of patients who developed one or more complications within 30 days following surgery. Results: During surgery, patients received on average the same volume of crystalloids (7.4 vs 7.2 ml/kg/h) and colloids (1.6 vs 1.6 ml/kg/h) before and after the implementation of IFM. During 30 days following surgery, the proportion of patients who developed one or more complications was lower in the IFM group (32 vs 48%, p < 0.01). This difference was mainly explained by a significant decrease in post-operative nausea and vomiting (from 38 to 19%, p < 0.01), urinary tract infections (from 9 to 1%, p < 0.01) and surgical site infections (from 5 to 1%, p < 0.05). Median hospital length of stay was not affected by the implementation of IFM. Conclusion: In patients undergoing major spine surgery, the implementation of IFM was associated with a significant decrease in postoperative morbidity. Trial registration: ClinicalTrials.gov Identifier: NCT02470221. Prospectively registered on June 12, 2015. [ABSTRACT FROM AUTHOR]

Background: Despite public focus on the importance of physical activity and findings showing the benefits of such activity, research has shown that people with dementia are less physically active and have more sedentary behaviour compared to others in similar age groups. In Norway, there is a focus on day care services as a means to allow people with dementia to experience social, physical and cultural activities. Farm based services have been highlighted as an innovative and customized day care service, but little research has been done on physical activity and such services. This study therefor aims to investigate the potential of farm-based day care services as services that can promote physical activity for people with dementia.Methods: Actigraphy data from people with dementia attending farm-based day care services (n = 29) and people with dementia attending regular day care services (n = 107) was used to assess levels of physical activity in each group and to compare the two groups.Results: People attending farm-based day care had significantly higher levels of moderate activity, approximately 23 min each day, compared with persons attending ordinary day care (p = 0.048). Time spent in sedentary or light activity were similar for both groups. For the group attending farm-based day care services, days at the service, were significantly associated with less time spent in sedentary activity (p = 0.012) and more time spent in light (p < 0.001) and moderate activity (p = 0.032), and in taking more steps (p = 0.005) compared to days not at the service.Conclusion: The findings indicate that participants in farm-based day care for people with dementia have higher levels of physical activity compared to ordinary day care and that farm-based day care increases levels of physical activity for its attendees. Farm based day care services has the potential to help their participants reach or maintain recommended levels of physical activity. Further research is needed to investigate what facilitates this increase in activity and how such knowledge could be used in all types of day care services. [ABSTRACT FROM AUTHOR]

Background: Falls are the leading cause of injuries among older adults. Perturbation-based balance training (PBT) is an innovative approach to fall prevention that aims to improve the reactive balance response following perturbations such as slipping and tripping. Many of these PBT studies have targeted reactive balance after slipping or tripping, despite both contributing to a large proportion of older adult falls. The goal of this randomized controlled trial was to evaluate the effects of PBT targeting slipping and tripping on laboratory-induced slips and trips. To build upon prior work, the present study included: 1) a control group; 2) separate training and assessment sessions; 3) PBT methods potentially more amenable for use outside the lab compared to methods employed elsewhere, and 4) individualized training for older adult participants.Methods: Thirty-four community-dwelling, healthy older adults (61-75 years) were assigned to PBT or a control intervention using minimization. Using a parallel design, reactive balance (primary outcome) and fall incidence were assessed before and after four sessions of BRT or a control intervention involving general balance exercises. Assessments involved exposing participants to an unexpected laboratory-induced slip or trip. Reactive balance and fall incidence were compared between three mutually-exclusive groups: 1) baseline participants who experienced a slip (or trip) before either intervention, 2) post-control participants who experienced a slip (or trip) after the control intervention, and 3) post-PBT participants who experienced a slip (or trip) after PBT. Neither the participants nor investigators were blinded to group assignment.Results: All 34 participants completed all four sessions of their assigned intervention, and all 34 participants were analyzed. Regarding slips, several measures of reactive balance were improved among post-PBT participants when compared to baseline participants or post-control participants, and fall incidence among post-PBT participants (18%) was lower than among baseline participants (80%). Regarding trips, neither reactive balance nor fall incidence differed between groups.Conclusions: PBT targeting slipping and tripping improved reactive balance and fall incidence after laboratory-induced slips. Improvements were not observed after laboratory-induced trips. The disparity in efficacy between slips and trip may have resulted from differences in dosage and specificity between slip and trip training.Trial Registration: Name of Clinical Trial Registry: clinicaltrials.gov Trial Registration number: NCT04308239. Date of Registration: March 13, 2020 (retrospectively registered). [ABSTRACT FROM AUTHOR]

Background: The rational use of antibiotics is one of the main strategies to limit the development of bacterial resistance. We therefore sought to evaluate the effectiveness of a C-reactive protein-based protocol in reducing antibiotic treatment time in critically ill patients.Methods: A randomized, open-label, controlled clinical trial conducted in two intensive care units of a university hospital in Brazil. Critically ill infected adult patients were randomly allocated to (i) intervention to receive antibiotics guided by daily monitoring of CRP levels and (ii) control to receive antibiotics according to the best practices for rational use of antibiotics.Results: One hundred thirty patients were included in the CRP (n = 64) and control (n = 66) groups. In the intention-to-treat analysis, the median duration of antibiotic therapy for the index infectious episode was 7.0 (5.0-8.8) days in the CRP and 7.0 (7.0-11.3) days in the control (p = 0.011) groups. A significant difference in the treatment time between the two groups was identified in the curve of cumulative suspension of antibiotics, with less exposure in the CRP group only for the index infection episode (p = 0.007). In the per protocol analysis, involving 59 patients in each group, the median duration of antibiotic treatment was 6.0 (5.0-8.0) days for the CRP and 7.0 (7.0-10.0) days for the control (p = 0.011) groups. There was no between-group difference regarding the total days of antibiotic exposure and antibiotic-free days.Conclusions: Daily monitoring of CRP levels may allow early interruption of antibiotic therapy in a higher proportion of patients, without an effect on total antibiotic consumption. The clinical and microbiological relevance of this finding remains to be demonstrated.Trial Registry: ClinicalTrials.gov Identifier: NCT02987790. Registered 09 December 2016. [ABSTRACT FROM AUTHOR]

Background: Guidelines on modifiable risk factors regarding cardiological patients are poorly implemented in clinical practice perhaps due to low health literacy. Several digital tools for improving lifestyle and behavioural intervention were developed. Our primary aim is to evaluate the effectiveness of a digital exercise prescription tool on the adherence to physical activity recommendations among patients with cardiovascular diseases.Methods: A randomized controlled trial will be realized in cooperation with Cardiovascular Health Centres in Eastern Slovakia. Patients recruited through their cardiologists, will be randomised at 1:1 ratio to the three-months' experimental condition or control condition. The experimental group will receive standard lifestyle consultation leading to individually optimized prescription of physical activity. The control group will receive standard, usual-cardio-care lifestyle counselling, also in the domain of physical activity. The digital system will be used for optimized exercise prescription. The primary outcome is a change in the patient's adherence to exercise recommendations. Data will be collected in both groups prior to consultation and after 3 months.Discussion: This study protocol presents background and design of a randomized control trial to investigate the effectiveness of a digital system-provide exercise prescription tool on the adherence to physical activity recommendations. An optimized exercise prescription that better reflects patient's diagnosis, comorbidities and medication can have a significant impact on secondary prevention of cardiovascular disease. This trial can provide important evidence about the effectiveness of digital exercise guidance in everyday practice of cardiovascular healthcare.Trial Registration: The study was registered on 1st November, 2017 and is available online at ClinicalTrials.gov (ID: NCT03329053 ). [ABSTRACT FROM AUTHOR]

Background: Neuroblastoma is a paediatric cancer that despite multimodal therapy still has a poor outcome for many patients with high risk tumours. Retinoic acid (RA) promotes differentiation of some neuroblastoma tumours and cell lines, and is successfully used clinically, supporting the view that differentiation therapy is a promising strategy for treatment of neuroblastoma. To improve treatment of a wider range of tumour types, development and testing of novel differentiation agents is essential. New pre-clinical models are therefore required to test therapies in a rapid cost effective way in order to identify the most useful agents.Methods: As a proof of principle, differentiation upon ATRA treatment of two MYCN-amplified neuroblastoma cell lines, IMR32 and BE2C, was measured both in cell cultures and in tumours formed on the chick chorioallantoic membrane (CAM). Differentiation was assessed by 1) change in cell morphology, 2) reduction in cell proliferation using Ki67 staining and 3) changes in differentiation markers (STMN4 and ROBO2) and stem cell marker (KLF4). Results were compared to MLN8237, a classical Aurora Kinase A inhibitor. For the in vivo experiments, cells were implanted on the CAM at embryonic day 7 (E7), ATRA treatment was between E11 and E13 and tumours were analysed at E14.Results: Treatment of IMR32 and BE2C cells in vitro with 10 μM ATRA resulted in a change in cell morphology, a 65% decrease in cell proliferation, upregulation of STMN4 and ROBO2 and downregulation of KLF4. ATRA proved more effective than MLN8237 in these assays. In vivo, 100 μM ATRA repetitive treatment at E11, E12 and E13 promoted a change in expression of differentiation markers and reduced proliferation by 43% (p < 0.05). 40 μM ATRA treatment at E11 and E13 reduced proliferation by 37% (p < 0.05) and also changed cell morphology within the tumour.Conclusion: Differentiation of neuroblastoma tumours formed on the chick CAM can be analysed by changes in cell morphology, proliferation and gene expression. The well-described effects of ATRA on neuroblastoma differentiation were recapitulated within 3 days in the chick embryo model, which therefore offers a rapid, cost effective model compliant with the 3Rs to select promising drugs for further preclinical analysis. [ABSTRACT FROM AUTHOR]

Background: Systemic morphine has evidence to support its use for reducing breathlessness in patients with severe chronic obstructive pulmonary disease (COPD). The effectiveness of the nebulized route, however, has not yet been confirmed. Recent studies have shown that opioid receptors are localized within epithelium of human trachea and large bronchi, a target site for a dosimetric nebulizer. The aim of this study was to compare any clinical or statistical differences in breathlessness intensity between nebulized 2.0% morphine and 0,9% NaCl in patients with very severe COPD.Methods: The study was a double-blind, controlled, cross-over trial. Participants received morphine or NaCl during two 4-day periods. Sequence of periods was randomized. The primary outcome measure was reduction of breathlessness intensity now by ≥20 mm using a 100 mm visual analogue scale (VAS) at baseline, 15, 30, 60, 120, 180 and 240 min after daily administration, during normal activities.Results: Ten of 11 patients included completed the study protocol. All patients experienced clinically and statistically significant (p < 0.0001) breathlessness reduction during morphine nebulization. Mean VAS changes for morphine and 0.9% NaCl periods were 25.4 mm (standard deviation (SD): 9.0; median: 23,0; range: 14.0 to 41,5; confidence interval (CI): 95%) and 6.3 mm (SD: 7.8; median: 6.8; range: -11,5 to 19,5; CI: 95%), respectively. No treatment emergent adverse effects were noted.Discussion: Our study showed superiority of dosimetrically administered nebulized morphine compared to NaCl in reducing breathlessness. This may have been achieved through morphine's direct action on receptors in large airways, although a systemic effect from absorption through the lungs cannot be excluded.Trial Registration: Retrospectively registered (07.03.2017), ISRCTN14865597. [ABSTRACT FROM AUTHOR]

Background: Associations of eating behaviors and psychological profile between mothers and daughters with eating disorders exist, but it is important to dissect the influence of the mother in each specific disorder since all eating disorders must be seen or treated not as one entity. The aim of the present study was to evaluate the association of eating behavior and psychological profile between mothers and daughters with different eating disorders and a control group.Methods: The study group included young girls with anorexia nervosa (AN, n = 30), bulimia nervosa (BN, n = 30), binge eating disorder (BED, n = 19), and a control group of women (Non-ED, n = 54) together with their mothers. BMI was calculated for dyads and Eating Disorder Inventory, Beck Depression Inventory, Beck Anxiety Inventory, Toronto Alexithymia Scale and Three-Factor Eating Questionnaire were applied. The differences between dyads were tested by Student's t test and Pearson's correlation was used to study the association between BMI, variables of eating behavior and psychological profile in each dyad.Results: The study found significant inverse correlations between the AN dyad; some correlations between the BN dyad, and the highest positive correlations exist in BED dyad, especially in eating behavior. Finally, between the control dyads, low but significant correlations were found in the majority of cases.Conclusions: The study concluded that the associations between mothers and daughters with distinct eating disorders varied depending on the specific diagnosis of the daughter, indicating it is necessary to analyze them individually, given that there may be different implications for treatment. [ABSTRACT FROM AUTHOR]

Background: Racial disparities exist in the care provided to advanced cancer patients. This article describes an investigation designed to advance the science of healthcare disparities by isolating the effects of patient race and patient activation on physician behavior using novel standardized patient (SP) methodology.Methods/design: The Social and Behavioral Influences (SBI) Study is a National Cancer Institute sponsored trial conducted in Western New York State, Northern/Central Indiana, and lower Michigan. The trial uses an incomplete randomized block design, randomizing physicians to see patients who are either black or white and who are "typical" or "activated" (e.g., ask questions, express opinions, ask for clarification, etc.). The study will enroll 91 physicians.Discussion: The SBI study addresses important gaps in our knowledge about racial disparities and methods to reduce them in patients with advanced cancer by using standardized patient methodology. This study is innovative in aims, design, and methodology and will point the way to interventions that can reduce racial disparities and discrimination and draw links between implicit attitudes and physician behaviors.Trial Registration: https://clinicaltrials.gov/ , #NCT01501006, November 30, 2011. [ABSTRACT FROM AUTHOR]

Background: Therapy that combines repetitive training with non-invasive brain stimulation is a potential avenue to enhance upper limb recovery after stroke. This study aimed to investigate the feasibility of transcranial Random Noise Stimulation (tRNS), timed to coincide with the generation of voluntary motor commands, during reaching training.Methods: A triple-blind pilot RCT was completed. Four stroke survivors with chronic (6-months to 5-years) and severe arm paresis, not taking any medications that had the potential to alter cortical excitability, and no contraindications to tRNS or MRI were recruited. Participants were randomly allocated to 12 sessions of reaching training over 4-weeks with active or sham tRNS delivered over the lesioned hemisphere motor representation. tRNS was triggered to coincide with a voluntary movement attempt, ceasing after 5-s. At this point, peripheral nerve stimulation enabled full range reaching. To determine feasibility, we considered adverse events, training outcomes, clinical outcomes, corticospinal tract (CST) structural integrity, and reflections on training through in-depth interviews from each individual case.Results: Two participants received active and two sham tRNS. There were no adverse events. All training sessions were completed, repetitive practice performed and clinically relevant improvements across motor outcomes demonstrated. The amount of improvement varied across individuals and appeared to be independent of group allocation and CST integrity.Conclusion: Reaching training that includes tRNS timed to coincide with generation of voluntary motor commands is feasible. Clinical improvements were possible even in the most severely affected individuals as evidenced by CST integrity.Trial Registration: This study was registered on the Australian and New Zealand Clinical Trials Registry (ANZCTR) http://www.ANZCTR.org.au/ACTRN12614000952640.aspx . Registration date 4 September 2014, first participant date 9 September 2014. [ABSTRACT FROM AUTHOR]

Background: The key mechanisms underlying socioeconomic inequalities in dietary intake are still poorly understood, hampering the development of interventions. An important, but sparsely mentioned mechanism is that of 'social distinction', whereby those in a higher socioeconomic position adopt dietary patterns by which they can distinguish themselves from lower socioeconomic groups. We investigated the importance of distinction as a mechanism, by testing the socioeconomic gradient in the consumption of so-called 'superfoods' and the contribution of a well-established indicator of distinction, cultural participation. Methods: Data from participants (25-75 years) of the 2014 survey of the Dutch population-based GLOBE study were used (N = 2812). Multivariable regression models were used to analyse the association between education, income and cultural participation (e.g. visits to museums, opera, theatre, concerts) and the consumption of superfoods (spelt, quinoa and goji berries, chia seeds or wheatgrass). Results: The consumption of superfoods is far more prevalent among higher socioeconomic groups. Adjusting for cultural participation strongly attenuated the educational and income gradient in superfoods consumption, whereas cultural participation remained strongly associated with superfoods consumption. Those in the highest quintile of cultural participation reported the highest consumption of spelt products (OR = 2.97, 95% CI = 2.10;4.18), quinoa (OR = 3.50, 95% CI = 2.12;5.79) and goji berries, chia seeds or wheatgrass (OR = 2.69, 95% CI = 1.73;4.17). Conclusions: The associations between socioeconomic position and the consumption of 'superfoods' seem to be partially driven by a process of social distinction. These findings suggest that distinction may be an important, but currently neglected mechanism in generating socioeconomic inequalities in dietary intake. It deserves a more prominent role in interventions to reduce these inequalities. [ABSTRACT FROM AUTHOR]

Background: Clinical prediction rules (CPRs) represent a method of determining individual patient risk to help providers make more accurate decisions at the point of care. Well-validated CPRs are underutilized but may decrease antibiotic overuse for acute respiratory infections. The integrated clinical prediction rules (iCPR) study builds on a previous single clinic study to integrate two CPRs into the electronic health record and assess their impact on practice. This article discusses study design and implementation of a multicenter cluster randomized control trial of the iCPR clinical decision support system, including the tool adaptation, usability testing, staff training, and implementation study to disseminate iCPR at multiple clinical sites across two health care systems.Methods: The iCPR tool is based on two well-validated CPRs, one for strep pharyngitis and one for pneumonia. The iCPR tool uses the reason for visit to trigger a risk calculator. Provider completion of the risk calculator provides a risk score, which is linked to an order set. Order sets guide evidence-based care and include progress note documentation, tests, prescription medications, and patient instructions. The iCPR tool was refined based on interviews with providers, medical assistants, and clinic managers, and two rounds of usability testing. "Near live" usability testing with simulated patients was used to ensure that iCPR fit into providers' clinical workflows. Thirty-three Family Medicine and General Internal Medicine primary care clinics were recruited at two institutions. Clinics were randomized to academic detailing about strep pharyngitis and pneumonia diagnosis and treatment (control) or academic detailing plus use of the iCPR tool (intervention). The primary outcome is the difference in antibiotic prescribing rates between the intervention and control groups with secondary outcomes of difference in rapid strep and chest x-ray ordering. Use of the components of the iCPR will also be assessed.Discussion: The iCPR study uses a strong user-centered design and builds on the previous initial study, to assess whether CPRs integrated in the electronic health record can change provider behavior and improve evidence-based care in a broad range of primary care clinics.Trial Registration: Clinicaltrials.gov ( NCT02534987 ). [ABSTRACT FROM AUTHOR]

Background: Standard of care primary treatment of carcinoma of locally advanced squamous cell head and neck cancer (LAHNSCC) consists of platinum-based concomitant chemo-irradiation. Despite progress in the treatment of LAHNSCC using modern radiotherapy techniques the outcome remains still poor. Using IMRT with SIB the escalation of total dose to the GTV is possible with the aim to improve clinical outcome. This study tests the hypothesis if radiation dose escalation to the GTV improves 2-year-LRC and -OS after concomitant chemo-irradiation.Methods: The ESCALOX trial is a prospective randomized phase III study using cisplatin chemo-irradiation and the SIB-IMRT concept in patients with LAHNSCC of the oral cavity, oropharynx or hypopharynx to escalate the total dose to the GTV up to 80.5 Gy. Chemotherapy is planned either in the 1st and 5th week (cisplatin 20 mg/m2/d d 1-5 and d 29-33) or weekly (cisplatin 40 mg/m2/d) during RT. RT is delivered as SIB with total doses of 80.5 Gy/70.0 Gy/56.0 Gy with 2.3 Gy/2.0 Gy and 1.6 Gy in the experimental arm and in the control arm with 70.0 Gy/56.0 Gy with 2.0 Gy and 1.6 Gy. A pre-study with dose escalation up to 77.0 Gy/70.0 Gy/56.0 Gy with 2.2 Gy/2.0 Gy and 1.6 Gy is demanded by the German federal office of radiation protection (BfS). In the translational part of the trial 100 of the randomised patients will be investigated by 18-F-FMiso-PET-CT for the presence and behaviour of tumor hypoxia twice in the week before treatment start.Discussion: The primary endpoint of the pre-study is acute radiation induced toxicity. Primary endpoint of the main trial is 2-year-LRC. By using the dose escalation up to 80.5 Gy to the GTV of the primary tumor and lymph nodes > 2 cm a LRC benefit of 15% at 2 years should be expected. The ESCALOX trial is supported by Deutsche Forschungsgemeinschaft (DFG); Grant No.: MO-363/4-1.Trial Registration: ClinicalTrials.gov Identifier: NCT 01212354 , EudraCT-No.: 2010-021139-15. [ABSTRACT FROM AUTHOR]

Background: Older adults living in long term care (LTC) homes are nutritionally vulnerable, often consuming insufficient energy, macro- and micronutrients to sustain their health and function. Multiple factors are proposed to influence food intake, yet our understanding of these diverse factors and their interactions are limited. The purpose of this paper is to fully describe the protocol used to examine determinants of food and fluid intake among older adults participating in the Making the Most of Mealtimes (M3) study.Methods: A conceptual framework that considers multi-level influences on mealtime experience, meal quality and meal access was used to design this multi-site cross-sectional study. Data were collected from 639 participants residing in 32 LTC homes in four Canadian provinces by trained researchers. Food intake was assessed with three-days of weighed food intake (main plate items), as well as estimations of side dishes, beverages and snacks and compared to the Dietary Reference Intake. Resident-level measures included: nutritional status, nutritional risk; disease conditions, medication, and diet prescriptions; oral health exam, signs of swallowing difficulty and olfactory ability; observed eating behaviours, type and number of staff assisting with eating; and food and foodservice satisfaction. Function, cognition, depression and pain were assessed using interRAI LTCF with selected items completed by researchers with care staff. Care staff completed a standardized person-directed care questionnaire. Researchers assessed dining rooms for physical and psychosocial aspects that could influence food intake. Management from each site completed a questionnaire that described the home, menu development, food production, out-sourcing of food, staffing levels, and staff training. Hierarchical regression models, accounting for clustering within province, home and dining room will be used to determine factors independently associated with energy and protein intake, as proxies for intake. Proportions of residents at risk of inadequate diets will also be determined.Discussion: This rigorous and comprehensive data collection in a large and diverse sample will provide, for the first time, the opportunity to consider important modifiable factors associated with poor food intake of residents in LTC. Identification of factors that are independently associated with food intake will help to develop effective interventions that support food intake.Trial Registration: ClinicalTrials.gov ID: NCT02800291 , retrospectively registered June 7, 2016. [ABSTRACT FROM AUTHOR]

Background: After stroke, patients who suffer from hemiparesis tend to suppress the use of the affected extremity, a condition called learned non-use. Consequently, the lack of training may lead to the progressive deterioration of motor function. Although Constraint-Induced Movement Therapies (CIMT) have shown to be effective in treating this condition, the method presents several limitations, and the high intensity of its protocols severely compromises its adherence. We propose a novel rehabilitation approach called Reinforcement-Induced Movement Therapy (RIMT), which proposes to restore motor function through maximizing arm use. This is achieved by exposing the patient to amplified goal-oriented movements in VR that match the intended actions of the patient. We hypothesize that through this method we can increase the patients self-efficacy, reverse learned non-use, and induce long-term motor improvements.Methods: We conducted a randomized, double-blind, longitudinal clinical study with 18 chronic stroke patients. Patients performed 30 minutes of daily VR-based training during six weeks. During training, the experimental group experienced goal-oriented movement amplification in VR. The control group followed the same training protocol but without movement amplification. Evaluators blinded to group designation performed clinical measurements at the beginning, at the end of the training and at 12-weeks follow-up. We used the Fugl-Meyer Assessment for the upper extremities (UE-FM) (Sanford et al., Phys Ther 73:447-454, 1993) as a primary outcome measurement of motor recovery. Secondary outcome measurements included the Chedoke Arm and Hand Activity Inventory (CAHAI-7) (Barreca et al., Arch Phys Med Rehabil 6:1616-1622, 2005) for measuring functional motor gains in the performance of Activities of Daily Living (ADLs), the Barthel Index (BI) for the evaluation of the patient's perceived independence (Collin et al., Int Disabil Stud 10:61-63, 1988), and the Hamilton scale (Knesevich et al., Br J Psychiatr J Mental Sci 131:49-52, 1977) for the identification of improvements in mood disorders that could be induced by the reinforcement-based intervention. In order to study and predict the effects of this intervention we implemented a computational model of recovery after stroke.Results: While both groups showed significant motor gains at 6-weeks post-treatment, only the experimental group continued to exhibit further gains in UE-FM at 12-weeks follow-up (p<.05). This improvement was accompanied by a significant increase in arm-use during training in the experimental group.Conclusions: Implicitly reinforcing arm-use by augmenting visuomotor feedback as proposed by RIMT seems beneficial for inducing significant improvement in chronic stroke patients. By challenging the patients' self-limiting believe system and perceived low self-efficacy this approach might counteract learned non-use.Trial Registration: Clinical Trials NCT02657070 . [ABSTRACT FROM AUTHOR]

Background: Subcutaneous administration of Ig (SCIg) has gained popularity as an alternative route of administration but has never been rigorously examined in chronic inflammatory demyelinating polyneuropathy (CIDP).Methods/design: The primary objective of the PATH study (Polyneuropathy and Treatment with Hizentra) is to determine the efficacy of two different doses of SCIg IgPro20 (0.2 g/kg bw or 0.4 g/kg bw) in a 24-week maintenance treatment of CIDP in comparison to placebo. The primary efficacy endpoint will be the proportion of patients who show CIDP relapse (1-point deterioration on the adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability score) or are withdrawn within 24 weeks after randomization for any reason. IVIg-dependent adult patients with definite or probable CIDP according to the European Federation of Neurological Societies/Peripheral Nerve Society who fulfil the inclusion and exclusion criteria will be eligible. Based on sample-size calculation and relapse assumptions in the three arms, a sample size of 58 is needed per arm (overall sample size will be 350, of which 174 will be randomized). All eligible patients will progress through three study periods: an IgG dependency period (≤12 weeks) to select those who are Ig dependent; an IVIg restabilization period (10 or 13 weeks), which will be performed using the 10 % IgPro10 product; and an SC treatment period (24 weeks, followed by a 1-week completion visit after last follow-up). Patients showing IVIg restabilization will be randomized to demonstrate the efficacy of SCIg IgPro20 maintenance treatment over placebo. After completing the study, subjects are eligible to enter a long-term, open-label, extension study of 1 year or return to their previous treatment. In case of CIDP relapse during the 24-week SC treatment period, IgPro10 rescue medication will be offered. Safety, tolerability, and patients' preference of Ig administration route will be examined.Discussion: The PATH trial, which started in March 2012, is expected to finish at the end of 2016. The results will increase knowledge about the efficacy, safety, and tolerability of SCIg in maintenance management of CIDP patients.Trial Registration: ClinicalTrials.gov, NCT01545076 . Registered on 1 March 2012. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to evaluate the psychometric properties of the Brazilian version of the Oral Anticoagulation Knowledge (OAK) Test.Methods: This study, conducted in an anticoagulation clinic, included 201 Brazilian participants aged over 18 years, who had been using warfarin for more than two months. The reliability of the instrument was evaluated by assessing internal consistency (Kuder-Richardson coefficient) and reproducibility (test-retest reliability). The validity was evaluated by hypothesizing that there would be a positive correlation of moderate to strong intensity between the correctness levels of the OAK Test and time within therapeutic range (TTR) values, which is a measure used to evaluate the quality of oral anticoagulation.Results: The instrument exhibited good psychometric properties. The total a Kuder-Richardson coefficient value was 0.818 and intraclass correlation coefficient was 0.967. The validity revealed a strong positive correlation between the values of the level of knowledge, as measured by the OAK Test and the TTR values (rs = 0.780).Conclusion: The instrument proved to be a reliable and valid tool for evaluating the knowledge of Brazilian patients on oral anticoagulation therapy with warfarin. This instrument may be incorporated into the practice of health care for substantiating the structuring of educational activities to ensure the improvement of knowledge about the use of warfarin, thereby increasing the effectiveness and safety of treatment. [ABSTRACT FROM AUTHOR]

Background: At present a majority of older people remain in their ordinary homes. Research has generated knowledge about home and health dynamics and increased the awareness of the complexity of housing as related to ageing. As this knowledge is based mainly on research on very old, single-living people in ordinary housing there is a need to study other sub-groups of the ageing population. Thus, the aim of the present descriptive study was to compare a younger old cohort with a very old cohort living in ordinary housing in Sweden in order to shed new light on home and health dynamics in different sub-groups of the ageing population.Methods: Cross-sectional study of two population-based cohorts: one aged 67-70 years (n = 371) and one aged 79-89 years (n = 397) drawn from existing Swedish databases. Structured interviews and observations were conducted to collect data about socio-demographics, aspects of home, and symptoms. Besides descriptive statistics we computed tests of differences using the Chi-squared test and Mann-Whitney U-test.Results: Accessibility was significantly lower in the very old cohort compared to the younger old cohort even though the former were objectively assessed to have fewer environmental barriers. Those in the very old cohort perceived aspects of their housing situation as worse and were more dependent on external influences managing their housing situation. Although a larger proportion of the very old cohort had more functional limitations 22% were independent in ADL. In the younger old cohort 17% were dependent in ADL.Conclusions: Keeping in mind that there were cohort differences beyond that of age, despite fewer environmental barriers in their dwellings the very old community-living cohort lived in housing with more accessibility problems compared to those of the younger old cohort, caused by their higher prevalence of functional limitations. Those in the very old cohort perceived themselves in a less favourable situation, but still as satisfied with housing as those in the younger old cohort. This kind of knowledge is indicative for prevention and intervention in health care and social services as well as for housing provision and societal planning. Further studies based on truly comparable cohorts are warranted. [ABSTRACT FROM AUTHOR]

Background: Adequate circadian timing of cancer treatment schedules (chronotherapy) can enhance tolerance and efficacy several-fold in experimental and clinical situations. However, the optimal timing varies according to sex, genetic background and lifestyle. Here, we compute the individual phase of the Circadian Timing System to decipher the internal timing of each patient and find the optimal treatment timing.Methods: Twenty-four patients (11 male; 13 female), aged 36 to 77 years, with advanced or metastatic gastro-intestinal cancer were recruited. Inner wrist surface Temperature, arm Activity and Position (TAP) were recorded every 10 min for 12 days, divided into three 4-day spans before, during and after a course of a set chronotherapy schedule. Pertinent indexes, I < O and a new biomarker, DI (degree of temporal internal order maintenance), were computed for each patient and period.Results: Three circadian rhythms and the TAP rhythm grew less stable and more fragmented in response to treatment. Furthermore, large inter- and intra-individual changes were found for T, A, P and TAP patterns, with phase differences of up to 12 hours among patients. A moderate perturbation of temporal internal order was observed, but the administration of fixed chronomodulated chemotherapy partially resynchronized temperature and activity rhythms by the end of the study.Conclusions: The integrated variable TAP, together with the asynchrony among rhythms revealed by the new biomarker DI, would help in the personalization of cancer chronotherapy, taking into account individual circadian phase markers. [ABSTRACT FROM AUTHOR]

Background: Metronomic oral vinorelbine is effective in metastatic NSCLC and malignant pleural mesothelioma, but all the studies published thus far were based upon a variety of empirical and possibly suboptimal schedules, with inconsistent results. Mathematical modelling showed by simulation that a new metronomic protocol could lead to a better safety and efficacy profile.Design: This phase Ia/Ib trial was designed to confirm safety (phase Ia) and evaluate efficacy (phase Ib) of a new metronomic oral vinorelbine schedule. Patients with metastatic NSCLC or malignant pleural mesothelioma in whom standard treatments failed and who exhibited ECOG performance status 0-2 and adequate organ function will be eligible. Our mathematical PK-PD model suggested an alternative weekly D1, D2 and D4 schedule (named Vinorelbine Theoretical Protocol) with a respective dose of 60, 30 and 60 mg. Trial recruitment will be two-staged, as 12 patients are planned to participate in phase Ia to confirm safety and consolidate the calibration of the model parameters. Depending on the phase Ia results and after a favourable decision from a consultative committee, the extension phase (phase Ib) will be an efficacy study including 20 patients who will receive the Optimal Vinorelbine Theoretical Protocol. The primary endpoint is the tolerance (assessed by CTC v4.0) for the phase Ia and the objective response according to RECIST 1.1 for phase Ib. An ancillary study on circulating angiogenesis biomarkers will be a subproject of the trial.Discussion: This ongoing trial is the first to prospectively test a mathematically optimized schedule in metronomic chemotherapy. As such, this trial can be considered as a proof-of-concept study demonstrating the feasibility to run a computational-driven protocol to ensure an optimal efficacy/toxicity balance in patients with cancer.Trial Registration: EudraCT N°: 2015-000138-31. [ABSTRACT FROM AUTHOR]

Background: The cardiovascular risk in renal transplant patients is increased in patients who continue to smoke after transplantation. The aim of the study is to measure the effectiveness of exhaled carbon monoxide (CO) measurement plus brief advisory sessions, in comparison to brief advice, to reduce smoking exposure and smoking behavior in kidney transplant recipients who smoke. The effectiveness will be measured by: (1) abandonment of smoking, (2) increase in motivation to stop smoking, and (3) reduction in the number of cigarettes smoked per day.Methods/design: Design: a randomized, controlled, open clinical trial with blinded evaluation.Scope: A Coruña Hospital (Spain), reference to renal transplantation in the period 2012-2015.Inclusion Criteria: renal transplant patients who smoke in the precontemplation, contemplation or preparation stages according to the Prochaska and DiClemente's Stages of Change model, and who give their consent to participate.Exclusion Criteria: smokers attempting to stop smoking, patients with terminal illness or mental disability that prevents them from participating.Randomization: patients will be randomized to the control group (brief advisory session) or the intervention group (brief advisory session plus measuring exhaled CO). The sample target size is n = 112, with 56 patients in each group. Allowing for up to 10 % loss to follow-up, this would provide 80 % power to detect a 13 % difference in attempting to give up smoking outcomes at a two-tailed significance level of 5 %.Measurements: sociodemographic characteristics, cardiovascular risk factors, treatment, rejection episodes, infections, self-reported smoking habit, drug use, level of dependence (the Fagerström test), stage of change (Prochaska and DiClemente's Stages of Change model), and motivation to giving up smoking (the Richmond test).Response: the effectiveness will be evaluated every 3, 6, 9 and 12 months as: pattern of tobacco use (self-reported tobacco use), smoking cessation rates, carbon monoxide (CO) levels in exhaled air measured by CO-oximetry, urinary cotinine tests, nicotine dependence (Fagerström test), motivational stages of change (Prochaska and DiClemente's stages) and motivation to stop smoking (the Richmond test).Analysis: descriptive statistics and linear/logistic multiple regression models will be performed. Clinical relevance will be measured as relative risk reduction, absolute risk reduction and the number needed to treat.Ethics: informed consent of the patients and Ethical Review Board was obtained (code 2011/061).Discussion: Tobacco is a modifiable risk factor that increase the risk of morbidity and mortality in kidney transplant recipients. If effectiveness of CO-oximetry is confirmed to reduce tobacco exposure, we would have an intervention that is easy to use, low cost and with great implications about cardiovascular risk prevention in these patients.Trial Registration: Current Controlled Trials ISRCTN16615772 . EudraCT number: 2015-002009-12. [ABSTRACT FROM AUTHOR]

Background: The diagnostic and prognostic significance of increased cathepsin B (CTSB) and cathepsin D (CTSD) concentration in the serum of cancer patients were evaluated for some tumor types. High expression of CTSD and CTSB was detected in biopsy tissues from nasopharyngeal carcinoma (NPC). However, whether CTSD and CTSB serve as diagnostic and prognostic markers of NPC remains unclear.Methods: Serum samples were collected from 40 healthy volunteers and 80 NPC patients enrolled in the study. CTSB and CTSD in the serum samples were detected using enzyme-linked immunosorbent assay (ELISA). Concomitantly, the relationship between CTSB and CTSD concentrations and clinicopathological prognosis was assessed. The sensitivity and specificity of the two components in the diagnosis of NPC were evaluated in 80 NPC patients.Results: ELISA analysis showed that in the sera obtained from NPC patients, the CTSB concentration was 12.5 ± 3.5 mg/L (median, 12.4 mg/L), and the CTSD concentration was 15.7 ± 8.7 mg/L (median, 14.7 mg/L). CTSB and CTSD levels were significantly higher in the NPC patient population compared to the healthy control population (p = 0.001; p = 0.001, respectively). The presence of CTSB and CTSD in the serum of the patients with NPC correlated with the tumor node metastasis (TNM) scores (p = 0.001). Other parameters were not identified to be of significance. Receiver operating characteristic (ROC) analysis showed that a cut off CTSB concentration of 12.4 mg/L had 61.9% sensitivity and 63.2% specificity in the prediction of progression-free survival (Area under the curve (AUC) = 0.525; 95% CI, 39.7-65.2; p = 0.704); whereas a cut off CTSD concentration of 14.7 mg/L had 66.7% sensitivity, and 58.5% specificity (AUC = 0.552; 95% CI, 42.3-68.1; p = 0.42).Conclusions: Serum CTSB and CTSD concentrations were found to have a diagnostic value in NPC. However, the CTSB and CTSD serum levels had no prognostic role for the outcome in NPC patients. [ABSTRACT FROM AUTHOR]

Background: Cognitive dysfunction is a major feature of bipolar disorder with psychosis and is strongly associated with functional outcomes. Computer-based cognitive remediation has shown promise in improving cognition in patients with schizophrenia. However, despite similar neurocognitive deficits between patients with schizophrenia and bipolar disorder, few studies have extended neuroscience-based cognitive remediation programs to this population. Methods/design: The Treatment to Enhance Cognition in Bipolar Disorder study is an investigator-initiated, parallel group, randomized, blinded clinical trial of an Internet-based cognitive remediation protocol for patients with bipolar disorder I with psychosis (n = 100). We also describe the development of our dose-matched active control paradigm. Both conditions involve 70 sessions of computer-based activities over 24 weeks. The control intervention was developed to mirror the treatment condition in dose and format but without the neuroplasticity-based task design and structure. All participants undergo neuropsychological and clinical assessment at baseline, after approximately 25 hours of study activities, post treatment, and after 6 months of no study contact to assess durability. Neuroimaging at baseline and post treatment are offered in an "opt-in" format. The primary outcomes are scores on the MATRICS battery; secondary and exploratory outcomes include measures of clinical symptoms, community functioning, and neuroimaging changes. Associations between change in cognitive measures and change in community functioning will be assessed. Baseline predictors of treatment response will be examined. Discussion: The present study is the first we are aware of to implement an Internet-based cognitive remediation program in patients with bipolar disorder with psychosis and to develop a comparable web-based control paradigm. The mixed online and study-site format allows accessible treatment while providing weekly staff contact and bridging. Based on user-provided feedback, participant blinding is feasible. Trial Registration: ClinicalTrials.gov NCT01470781 ; 11 July 2011. [ABSTRACT FROM AUTHOR]

Background: A prospective clinical trial was conducted to evaluate the feasibility of a novel approach to the treatment of patients with high risk prostate cancer (HRPC) through the use of a nomogram to tailor radiotherapy target volumes.Methods: Twenty seven subjects with HRPC were treated with a mildly hypofractionated radiotherapy regimen using image-guided IMRT technique between Jun/2013-Jan/2015. A set of validated prognostic factors were inputted into the Memorial-Sloan-Kettering Cancer Center (MSKCC) prostate cancer nomogram to estimate risk of loco-regional spread (LRS). The nomogram risk estimates for extra-capsular extension (ECE), seminal vesicles involvement (SVI), and pelvic lymph nodes involvement (LNI) were used to adapt radiotherapy treatment volumes based on a risk threshold of ≥15 % in all cases. A planning guide was used to delineate target volumes and organs at risk (OAR). Up to three dose levels were administered over 28 fractions; 70Gy for gross disease in the prostate +/- seminal vesicles (2.5Gy/fraction), 61.6Gy for subclinical peri-prostatic disease (2.2Gy/fraction) and 50.4Gy to pelvic nodes (1.8Gy/fraction). Data regarding protocol adherence, nomogram use, radiotherapy dose distribution, and acute toxicity were collected.Results: Nomogram use 100 % of patients were treated for ECE, 88.9 % for SVI, and 70.4 % for LNI. The three areas at risk of LRS were appropriately treated according to the study protocol in 98.8 % cases. The MSKCC nomogram estimates for LRS differed significantly between the time of recruitment and analysis. Contouring protocol compliance Compliance with the trial contouring protocol for up to seven target volumes was 93.0 % (159/171). Compliance with protocol for small bowel contouring was poor (59.3 %). Dose constraints compliance Compliance with dose constraints for target volumes was 97.4 % (191/196). Compliance with dose constraints for OAR was 88.2 % (285/323). Acute toxicity There were no grade 3 acute toxicities observed. 20/27 (74.1 %) and 6/27 (22.2 %) patients experienced a grade 2 genitourinary and gastrointestinal toxicity respectively.Conclusions: We have demonstrated the feasibility of this novel risk-adapted radiation treatment protocol for HRPC. This study has identified key learning points regarding this approach, including the importance of standardization and updating of risk quantification tools, and the utility of an observer to verify their correct use.Trial Registration: ClincialTrials.gov identifier NCT01418040 . Hunter New England Human Research Ethics Committee (HNEHREC) reference number 12/08/15/4.02. [ABSTRACT FROM AUTHOR]

Background Implementation of practice change is difficult and large scale implementation is particularly difficult. Among the challenges facing the healthcare system in general and healthcare organizations is the overuse of low value care. Improving medication safety also constitutes an attempt to reduce low value or potentially harmful care. Critical issues of overuse of low value practices and medication safety intersect in overtreatment of diabetes. Specifically, (over)intensive glycemic control increases hypoglycemia risk and morbidity without providing meaningful benefit. Our work indicates that among patients with diabetes who are at high risk for hypoglycemia, potential overtreatment is common. The Choosing Wisely Initiative to reduce low value care led by the American Board of Internal Medicine Foundation recommends not to treat most persons over 65 years of age with medications to reduce the A1c<7.5%. For most physicians this involves a change in practice. We will study the implementation of the Veterans Health Administration's Choosing Wisely Initiative (which includes hypoglycemic safety as a targeted condition) with three specific aims: (1) to assess the overall impact, both intended and unintended, of the Choosing Wisely Initiative to reduce overtreatment of diabetes in especially vulnerable populations; (2) to assess the impact of commitment to quality, teaching intensity, and safety culture on likelihood of overtreatment; and (3) to identify configurations of the implementation strategy, provider characteristics and organizational level factors that are associated with successful reduction of overtreatment rates by comparing high and low performers. Because focus on this initiative could have the unintended consequence of paying less attention to poor glycemic control (A1c>9%), we will also assess undertreatment. Methods/Design We will take advantage of a natural experiment and use a Type III Hybrid Design that focuses on study of implementation while at the same time observing and gathering information on clinical interventions and outcomes. This mixed methods study will use longitudinal data and qualitative methods including Qualitative Comparative Analyses. Discussion Our multi-paradigm approach to examining potential mechanisms to explain the variation in reduction of rates of overtreatment will contribute to a better understanding of implementation of national dissemination projects and multi-component interventions in complex systems. [ABSTRACT FROM AUTHOR]

Background Methylentetrahydrofolate reductase (MTHFR) plays a major role in folate metabolism and consequently could be an important factor for the efficacy of a treatment with 5-fluorouracil. Our aim was to evaluate the prognostic and predictive value of two well characterized constitutional MTHFR gene polymorphisms for primarily resected and neoadjuvantly treated esophagogastric adenocarcinomas. Methods 569 patients from two centers were analyzed (gastric cancer: 218, carcinoma of the esophagogastric junction (AEG II, III): 208 and esophagus (AEG I): 143). 369 patients received neoadjuvant chemotherapy followed by surgery, 200 patients were resected without preoperative treatment. The MTHFR C677T and A1298C polymorphisms were determined in DNA from peripheral blood lymphozytes. Associations with prognosis, response and clinicopathological factors were analyzed retrospectively within a prospective database (chi-square, log-rank, cox regression). Results Only the MTHFR A1298C polymorphisms had prognostic relevance in neoadjuvantly treated patients but it was not a predictor for response to neoadjuvant chemotherapy. The AC genotype of the MTHFR A1298C polymorphisms was significantly associated with worse outcome (p = 0.02, HR 1.47 (1.06-2.04). If neoadjuvantly treated patients were analyzed based on their tumor localization, the AC genotype of the MTHFR A1298C polymorphisms was a significant negative prognostic factor in patients with gastric cancer according to UICC 6th edition (gastric cancer including AEG type II, III: HR 2.0, 95% CI 1.3-2.0, p = 0.001) and 7th edition (gastric cancer without AEG II, III: HR 2.8, 95% CI 1.5-5.7, p = 0.003), not for AEG I. For both definitions of gastric cancer the AC genotype was confirmed as an independent negative prognostic factor in cox regression analysis. In primarily resected patients neither the MTHFR A1298C nor the MTHFR C677T polymorphisms had prognostic Conclusions The MTHFR A1298C polymorphisms was an independent prognostic factor in patients with neoadjuvantly treated gastric adenocarcinomas (according to both UICC 6th or 7th definitions for gastric cancer) but not in AEG I nor in primarily resected patients, which confirms the impact of this enzyme on chemotherapy associated outcome. [ABSTRACT FROM AUTHOR]