• McPherson Gibson opublikował 5 miesięcy, 1 tydzień temu

    The protein level of the adverse prognostic biomarker mitochondrial aldehyde dehydrogenase (ALDH2) showed a similar significant upregulation both in elderly low-risk and elderly high-risk patients. Our results suggest that molecular mechanisms associated with cellular aging influence chemoresistance of AML cells, and especially the cytoskeleton function may then influence cellular hallmarks of aging, e.g. mitosis, polarity, intracellular transport and adhesion.Genetic, dietary, and environmental factors concurrently shape the aging process. The aryl hydrocarbon receptor (AhR) was discovered as a dioxin-binding transcription factor involved in the metabolism of different environmental toxicants in vertebrates. Since then, the variety of pathophysiological processes regulated by the AhR has grown, ranging from immune response, metabolic pathways, and aging. Many modulators of AhR activity may impact on aging and age-associated pathologies, but, whether their effects are AhR-dependent has never been explored. Here, using Caenorhabditis elegans, as an elective model organism for aging studies, we show for the first time that lack of CeAHR-1 can have opposite effects on health and lifespan in a context-dependent manner. Using known mammalian AhR modulators we found that, ahr-1 protects against environmental insults (benzo(a)pyrene and UVB light) and identified a new role for AhR-bacterial diet interaction in animal lifespan, stress resistance, and age-associated pathologies. We narrowed down the dietary factor to a bacterially extruded metabolite likely involved in tryptophan metabolism. This is the first study clearly establishing C. elegans as a good model organism to investigate evolutionarily conserved functions of AhR-modulators and -regulated processes, indicating it can be exploited to contribute to the discovery of novel information about AhR in mammals.The Edmonton Frail Scale (EFS) is an index employed to measure alterations related to frailty. The main objective in this research was to develop the EFS short-form (EFS-SF) and to evaluate its validity, reliability, and sensitivity to predict frailty disability outcomes in elderly patients with foot disabilities.

    Exploratory factor analysis (EFA) of the EFS-SF revealed the presence of three components, as in the original EFA. There were significant differences (

    < 0.05) in the study population for several of the EFS and 5-item FRAIL scale indicators. The highest correlation (Pearson

    = 0.871;

    < 0.001) was found for the first component of the EFS-SF. Finally, the Cronbach alpha was 0.864 which indicated a high level of internal consistency.

    The EFS-SF is a reliable and valid instrument to measure frailty in patients with and without foot disabilities.

    A cross sectional descriptive study was carried out. The study population was aged over 60 years (

    = 66) and comprised 29 men and 37 women. gical status, thus revealing that the EFS-SF comprised three components, a reduction compared to the nine in the original EFS.Inequalities in older adults’ health rarely consider life-course aspects of socioeconomic status (SES). We examined the association between lifelong SES and old-age health trajectories, and explored the role of lifestyle factors and depressive symptoms in this association. We followed 2760 adults aged 60+ from the Swedish National Study on Care and Aging, Kungsholmen. SES groups were derived using latent class analysis incorporating seven socioeconomic measures spanning childhood, midlife, and late life. We measured health using the Health Assessment Tool, which combines gait speed, cognition, multimorbidity, and disability. Linear mixed models were used to estimate health trajectories. Four SES groups were identified High (34.9%), Middle (40.2%), Low (21.2%), and Mixed (3.8%). The Mixed group reported greater financial difficulties in childhood and older age, but varying SES attainment in midlife. Baseline health scores indicated that Mixed SES experienced substantial cognitive and physical deficits 12 years earlier than the High SES group. Compared to the High SES group, the Mixed SES group had the fastest health deterioration (β×time=-0.07, 95% CI-0.11,-0.02); other groups followed a gradient (High>Middle>Low). Lifestyle factors and depressive symptoms attenuated the gradient but did not explain Mixed group’s health disadvantage. Life-long SES measures are crucial for understanding older adults’ health inequalities.We describe a 58-year-old Chinese man with schizophrenia who presented with an elevated clozapine level suspected to be related to acute infection.

    To explore caregivers’ perspective on factors affecting the recovery of their family members diagnosed with schizophrenia.

    A qualitative grounded theory approach was used. A convenience sample of seven male and eleven female family caregivers of patients with schizophrenia were invited from outpatient (n = 6), inpatient (n = 7), and psychiatric rehabilitation (n = 5) services in an Indian mental health institute to participate in semi-structured interviews. Interviews were recorded, transcribed, and analysed. Similar themes were grouped and the main themes identified.

    Caregivers’ perspectives on factors affecting recovery from schizophrenia were categorised to two themes facilitators and barriers. The nine facilitators were (1) getting into a precise treatment regimen and sticking to it, (2) developing some personal attributes, (3) exercising family’s role diametrically, (4) paying attention to basic needs, (5) sharing with the Almighty, (6) adapting to a supportive lifestyle, (7) not being idle… engagee patients after regaining insight can be helpful.

    To validate the Social Media Disorder scale in Nigerian adolescents by determining its unidimensional structure, reliability, sensitivity, specificity, and criterion validity.

    A total of 516 and 1213 pre-university students in two universities were randomly recruited and assessed using the 9-item Social Media Scale and the 12-item General Health Questionnaire (in the second survey only).

    46.3% and 56.3% of respondents in the first and second surveys met the criteria for social media disorder, respectively. Factor loading of items on the latent factor (addiction) was moderate. The model yielded a fairly acceptable fit in both samples. The averaged measure for intra-class correlation was acceptable (0.612). The internal consistency (Cronbach’s alpha) was good (0.713 for sample 1 and 0.724 for sample 2). The test-retest reliability among the 113 respondents was good (r=0.696, p<0.001). The item-total correlations were all significant. Sensitivity of each item ranged from 67.7% (tolerance) to 91.3% (escape); specificity of each item ranged from 41.2% (escape) to 87.6% (displacement). For criterion validity, the total Social Media Disorder scale score correlated with General Health Questionnaire items that assess self-esteem, depression, and mood, as well as the total score.

    The 9-item Social Media Disorder scale is acceptable for screening social media disorder in pre-university students in Nigeria. The high prevalence of social media disorder should be of concern to counsellors, teachers, and mental health practitioners. Strategies for public health education on social media use are needed in Nigeria.

    The 9-item Social Media Disorder scale is acceptable for screening social media disorder in pre-university students in Nigeria. The high prevalence of social media disorder should be of concern to counsellors, teachers, and mental health practitioners. Strategies for public health education on social media use are needed in Nigeria.

    To examine perceived stigma and its correlates in remitted patients with mental illnesses and their caregivers.

    In patients with mental illnesses, their perceived stigma (Perceived Devaluation Discrimination Scale), endorsed secrecy (Secrecy scale), self-esteem (Rosenberg Self-Esteem Scale), functioning (Work Social Adjustment Scale), and emotional wellbeing (Well Being Index) were assessed. In caregivers, their perceived stigma towards patients (Devaluation of Consumer Scale) and families (Devaluation of Consumer Families Scale), emotional wellbeing (Well Being Index), and depressive symptoms (Centre for Epidemiological Studies-Depression scale) were assessed. Differences between diagnoses were examined using ANOVA. Correlation between perceived stigma among patients and caregivers was studied.

    Of 152 patients with mental illnesses, 76.3% and 85.53 % reported moderate-to-high levels of perceived stigma and endorsed secrecy, respectively. Of 152 caregivers, 40.13% and 25.65% reported moderate-to-high leheir quality of life. The stigma associated with substance use disorder merits special attention.

    To examine associations between severe mental illness (SMI), general health symptoms, mental wellbeing, and different activity levels in patients with SMI.

    Consecutive patients with SMI referred for occupational therapy were prospectively included. Their hours of activities per day during hospital stay were recorded as <1 hour, 1-3 hours, and >3 hours in three categories basic self-care activities, interest-based activities, and role-specific activities. Patients were free to join or decline any activities. Patients’ somatic and mental health were measured at admission, discharge, and 1 month after discharge using the Brief Psychiatric Rating Scale (BPRS), Patient Health Questionnaire-15 (PHQ-15), Pittsburgh Sleep Quality Index (PSQI), Chinese version of Short Warwick Edinburgh Mental Wellbeing Scale (C-SWEMWBS), and Chinese version of General Activity Motivation Measure (GAMM).

    84 patients (35 men and 49 women) aged 16 to 63 years were assessed at the three timepoints. The mean length of hospitalubjective wellbeing. Outdoor soccer has added effect on patients’ somatic health. The beneficial effects are maintained at 1 month after discharge. Daily participation of activity meaningful to patients can be a non-pharmacological treatment for patients with SMI to improve somatic and mental health.

    AWARE study assesses disease activity, patient’s quality of life (QoL) and treatment patterns in chronic urticaria (CU) patient’s refractory to H1-antihistamines (H1-AH) in clinical practice during the first year of the study.

    Observational, prospective (24 months), international, multicenter study. Patients ≥18 years with H1-AH-refractory CU diagnosis (>2 months). At each visit, patients completed questionnaires to assess disease burden (Urticaria Control Test [UCT]), disease activity (7 day-Urticaria Activity Score [UAS7]), QoL (Dermatology Life Quality index [DLQI], Chronic Urticaria Quality of Life Questionnaire [CU-Q2oL], Angioedema Quality of Life [AE-QoL]). We present Spanish data.

    270 evaluable patients included (73.3% female, mean age [SD] 48.9 [14.7] years). At baseline, 89.3% were prescribed a CU treatment. After 1-year, first/second line treatments tended to decrease and third line to increase. 47.0% patients experienced angioedema at baseline, being 11.8% at 1-year. Mean (SD) AE-QoL went from 45.2 (28.7) to 24.0 (25.8). Mean (SD) UCT went from 7.0 (4.5) to 12.1 (4.1). According to UAS7, 38.2% patients reported absence of wheals and itch in the last 7 days at 1-year versus 8.3% at baseline. Mean (SD) DLQI went from 8.0 (7.4) to 2.8 (4.6). At 1-year visit, the percentage of patients reporting high/very high QoL impact went from 29.9% to 9.6%.

    Spanish H1-AH-refractory CU patients present a lack of symptomatology control with an important impact in their QoL. Continuous follow-up of chronic spontaneous urticaria patients and third line therapies have shown a tendency to reduce the burden of the disease and to improve patients’ QoL.

    Spanish H1-AH-refractory CU patients present a lack of symptomatology control with an important impact in their QoL. Continuous follow-up of chronic spontaneous urticaria patients and third line therapies have shown a tendency to reduce the burden of the disease and to improve patients’ QoL.After one-month of oral treatment with traditional Chinese medicine decoction, without using other drugs, the lung inflammatory exudate, pulmonary fibrosis and quality of life of a 61-year-old female patient with corona virus disease 2019 (COVID-19) were significantly improved. No recurrence or deterioration of the patient’s condition was found within seven weeks of treatment and follow-up, and no adverse events occurred, indicating that oral Chinese medicine decoction was able to improve the pulmonary inflammation and fibrosis in a patient recovering from COVID-19, but further research is still needed.The processing of Chinese herbal medicine is a form of pharmaceutical technology developed over thousands of years, in order to increase efficiency and decrease toxicity of herbs in traditional Chinese medicine (TCM). Herbal processing is essential for safe and effective application of TCM in clinical practice, as it alters the active chemical components and therefore the functions of herbal medicines. Alkaloid-rich herbal medicines in TCM are commonly processed by cleansing, cutting, processing by dry stir-frying, stir-frying with liquid adjuvants, and processing by water decoction. In addition, commonly used adjuvants for processing alkaloid-rich herbal medicines are river sand, wine, vinegar, brine, honey and herbal juice. For alkaloid-rich herbal medicines, the main chemical reactions that occur during processing include hydrolysis, oxidation, replacement, decomposition and condensation. This paper aimed to summarize the processing methods and mechanisms for alkaloid-rich Chinese herbal medicines, and provide much-needed theoretical support and scientific evidence for understanding those mechanisms and effects. Information on processing methods for alkaloid-rich herbal medicines was collected from classic books of herbal medicine, PhD and MSc dissertations, online scientific databases including PubMed, SciFinder, Scopus, Web of Science, Baidu Scholar and Google Scholar. This paper should help to advance our knowledge of the processing mechanisms and aid in the development of processing methods for alkaloid-rich Chinese herbal medicines.

    SC-E3 is a polyherbal formula that contains five medicinal herbs used frequently in traditional herbal medicine. In our previous study, we demonstrated the antioxidant and anti-inflammatory effects of SC-E3. The present study examined the effects of SC-E3 in a mouse model of type-II collagen-induced arthritis (CIA).

    In vivo, male DBA/1J mice were immunized by intradermal injection of bovine type-II collagen and complete or incomplete Freund’s adjuvant, to induce arthritis. SC-E3 was orally administered daily for 23days. In vitro, bone marrow-derived macrophages (BMMs) were treated with macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-κB ligand (RANKL) in the absence or presence of SC-E3.

    Administrations of SC-E3 were found to have anti-arthritic effects in the joints of CIA mice, as evidenced by reduced paw swelling, bone erosion and deformation, inflammatory cell infiltration, and inflammation in synovial membrane. SC-E3 also reduced serum levels of tumor necrosis factor-α, interleukin-1β, aspartate aminotransferase and alanine aminotransferase. Furthermore, tartrate-resistant acid phosphatase-positive osteoclast numbers in the joints were significantly lower in SC-E3-treated CIA mice than in CIA mice. In addition, the differentiations of BMMs to multinucleated osteoclasts induced by M-CSF and RANKL stimulation were dose-dependently reduced by SC-E3.

    These results suggest that SC-E3 possesses substantial anti-arthritic activity because it inhibits pro-inflammatory cytokines and osteoclastogenesis, and that SC-E3 has potential therapeutic use for the treatment of rheumatoid arthritis.

    These results suggest that SC-E3 possesses substantial anti-arthritic activity because it inhibits pro-inflammatory cytokines and osteoclastogenesis, and that SC-E3 has potential therapeutic use for the treatment of rheumatoid arthritis.

    Pancreatic ductal adenocarcinoma (PDAC) has the worst prognosis of all malignant tumors due to unavailable screening methods, late diagnosis with a low proportion of resectable tumors and resistance to systemic treatment. Complete tumor resection remains the cornerstone of modern multimodal strategies aiming at long-term survival. This study was performed to investigate the overall rate of long-term survival (LTS) and its contributing factors.

    This was a retrospective single-center analysis of consecutive patients undergoing pancreaticoduodenectomy (PD) for PDAC between 2007 and 2014 at the St. Josef Hospital, Ruhr University Bochum, Germany. Clinical and laboratory parameters were assessed and evaluated for prediction of LTS with Cox regression analysis.

    The overall rate of LTS after PD for PDAC was 20.4% (34/167). Median survival was 24 months regardless of adjuvant treatment. Carbohydrate antigen 19-9 levels, tumor grade, lymph vessel invasion, perineural invasion and reduced general condition were significantly associated with LTS in univariate analysis (P<0.05). Serum levels of carbohydrate antigen 19-9, American Joint Committee on Cancer stage, tumor grade, abdominal pain, male, exocrine pancreatic insufficiency and duration of postoperative hospital stay were independent predictors of cancer survival in multivariable analysis.

    Cancer related characteristics are associated with LTS in multimodally treated patients after curative PDAC surgery.

    Cancer related characteristics are associated with LTS in multimodally treated patients after curative PDAC surgery.

    The Barcelona Clinic Liver Cancer (BCLC) system has been endorsed by international guidelines as a staging algorithm of hepatocellular carcinoma. This analysis was performed to assess the outcome of liver transplantation in patients treated against the BCLC recommendations.

    The data of 198 patients who underwent liver transplantation for hepatocellular carcinoma were extracted from a prospectively maintained database to classify the patients according to the BCLC system.

    BCLC staging was as follows 0, n=5; A, n=77; B, n=41; C, n=53; and D, n=22. Accordingly, liver transplantation was performed in the majority of patients against BCLC recommendations. Surgery (n=16), radiofrequency ablation (n=15) and transarterial chemoembolization (n=151) preceded liver transplantation in 182 patients. Sixteen patients were transplanted without pretreatment. The1-, 5- and 10-year survival rates were 83.8%, 62.4% and 45.9%, and 1-, 5-, and 10-year recurrence rates were 7.7%, 22.7% and 26.7%. The BCLC classification did neither impact survival (P=0.796) nor recurrence (P=0.693). In the Cox analysis, RECIST tumor progression and initial alpha fetoprotein were independent predictors of outcome.

    Neither the oncological nor the functional stratification imposed by the BCLC system was of importance for outcome. Lack of flexibility and disregard of biological parameters hamper its clinical applicability in liver transplantation.

    Neither the oncological nor the functional stratification imposed by the BCLC system was of importance for outcome. Lack of flexibility and disregard of biological parameters hamper its clinical applicability in liver transplantation.

    Liver fibrosis is a hallmark determinant of morbidity in biliary atresia (BA) even in successfully operated cases. Responsible factors for this rapid progression of fibrosis are not completely defined. Aberrant expression of the transcription factor SOX9 and hepatic progenitor cells (HPCs) proliferation have roles in fibrogenesis in cholestatic disorders. However, they were not investigated sufficiently in BA. We aimed to delineate the relation of SOX9 and HPCs to fibrosis and its progression in BA.

    Forty-eight patients with BA who underwent an initial diagnostic liver biopsy (LB) and consequent intraoperative LB were recruited and compared to 28 cases with non-BA cholestasis that had an LB in their diagnostic workup. Liver fibrosis, tissue SOX9 and HPC expressions were studied in both BA and non-BA-cholestasis cases. Liver fibrosis, SOX9, and HPCs’ dynamic changes in BA cases were assessed. Relation of fibrosis and its progression to SOX9 and HPCs in BA was assessed.

    SOX9 and HPCs in ductular reaction (DR) form were expressed in 100% of BA and their grades increased significantly in the second biopsy. The rapidly progressive fibrosis in BA, represented by fibrosis grade of the intraoperative LB, correlated significantly to SOX9-DR and HPC-DR at the diagnostic (r=0.420, P=0.003 and r=0.405, P=0.004, respectively) and the intraoperative (r=0.460, P=0.001 and r=0.467, P=0.001, respectively) biopsy. On the other hand, fibrosis, SOX9-DR, and HPC-DR were significantly lower in non-BA cases at a comparable age (P<0.001, P=0.006, and P=0.014, respectively).

    Fibrosis in BA is rapidly progressive within a short time and is significantly correlated to SOX9 and HPCs. Assessment of targeting SOX9 and HPCs on fibrosis progression is warranted.

    Fibrosis in BA is rapidly progressive within a short time and is significantly correlated to SOX9 and HPCs. Assessment of targeting SOX9 and HPCs on fibrosis progression is warranted.

    Considering the evolving diagnostic criteria of polycythemia vera (PV), we analyzed the utility of serum erythropoietin (EPO) as a predictive marker for differentiating polycythemia vera (PV) from other etiologies of erythrocytosis.

    We conducted a retrospective study after a review of electronical medical records from January 2005 to December 2016 with diagnosis of erythrocytosis using International Classification of Disease-specific codes. To evaluate the diagnostic performance of EPO levels and JAK2-V617F mutation, we constructed a receiver-operated characteristic curve of sensitivity versus 1-specificity for serum EPO levels and JAK2-V617F mutation as predictive markers for differentiating PV from other causes of erythrocytosis.

    We surveyed 577 patients with erythrocytosis. Median patient age was 59.2 years, 57.72% (n= 329) were male, 86.3% (n= 491) were white, and only 3.3% (n= 19) were African American. A total of 80.88% (n= 351) of those diagnosed with PV had a JAK2-V617F mutation compared to only 1.47% (n= 2) whose primary diagnosis was secondary polycythemia. When comparing JAK2-V617 mutation to the EPO level, the area under the curve of JAK2-V617 (0.8970) was statistically larger than that of EPO test (0.6765). Therefore, the PV diagnostic methodology using JAK2-V617 is better than the EPO test. An EPO level of< 2 mIU/mL was > 99% specific to predict PV but was only 12% sensitive.

    In the appropriate clinical setting, cytogenetic and molecular studies such as JAK2 mutation status prevail as the most useful tools for PV case identification. The use of isolated EPO to screen patients with erythrocytosis is not a good diagnostic approach.

    In the appropriate clinical setting, cytogenetic and molecular studies such as JAK2 mutation status prevail as the most useful tools for PV case identification. The use of isolated EPO to screen patients with erythrocytosis is not a good diagnostic approach.

    Anti-interleukin-5 (IL-5) therapy has been proposed as a novel treatment option for patients with chronic obstructive pulmonary disease (COPD). However, its efficacy for preventing COPD exacerbation remains unclear.

    A literature review was conducted to August 26th 2019. Only randomized controlled trials (RCTs) that investigated the clinical efficacy and adverse effects of anti-IL-5 therapy were included in the meta-analysis. The primary outcome was the risk of COPD exacerbation.

    A total of 3 articles containing 5 RCTs were included in the study. Overall, 2837 and 1442 patients received anti-IL-5 therapy (mepolizumab, n=865; benralizumab, n=1972) and placebo, respectively. In the pooled analysis, anti-IL-5 therapy was associated with a lower risk of COPD exacerbation compared with the placebo (rate ratio, 0.92; 95% CI, 0.86-0.97, I

    =0%). In addition, no significant differences in the changes in SGRQ scores and FEV

    from baseline were found between the anti-IL-5 therapy and placebo (SGRQ, mean difference, -0.86, 95% CI, -1.92 – 0.19, I

    =0%; FEV

    , mean difference, 0.01, 95% CI, -0.01 – 0.03, I

    =0%). Anti-IL-5 therapy had a similar risk of any adverse event (risk ratio, 1.02; 95% CI, 0.99-1.05), an event leading to treatment discontinuation (risk ratio, 1.04; 95% CI, 0.72-1.48) and any serious adverse events (risk ratio, 0.93; 95% CI, 0.85-1.01) when compared with the placebo.

    Anti-IL-5 therapy was associated with a lower rate of COPD exacerbation compared with placebo. In addition, anti-IL-5 therapy was well tolerated for COPD patients.

    Anti-IL-5 therapy was associated with a lower rate of COPD exacerbation compared with placebo. In addition, anti-IL-5 therapy was well tolerated for COPD patients.

    Human herpesvirus type 8 (HHV-8) can be transmitted through unprotected sex as HIV. We aimed to investigate the seroincidence of HHV-8 and associated factors among people living with HIV (PLWH).

    From 2014 to 2018, blood samples of PLWH on the first date of HIV care were determined for antibodies against HHV-8. Individuals testing HHV-8-seronegative at baseline were followed for at least four months to estimate the annual seroconversion rate. To identify the factors associated with HHV-8 seroconversion, we compared the clinical characteristics between seroconverters and non-seroconverters who were matched for observation duration.

    The HHV-8 seroprevalence increased from 8.1% in 2014 to 20.0% in 2018. HHV-8 seroconversion occurred in 154 (14.7%) PLWH after a total of 2652.16 person-years of follow-up (PYFU), resulting in an overall incidence rate of 5.62 per 100 PYFU, which increased from 3.20 to 6.84 per 100 PYFU during the study period. HHV-8 seroconverters were less likely to have chronic hepatitis B virus (HBV) infection (1.9% vs 10.6%) and more likely to be antiretroviral-naïve on entry into care (87.7% vs 75.4%) (both p<0.05). In multivariate logistic analysis, men who have sex with men (MSM) (adjusted odds ratio [aOR], 2.22; 95% CI, 1.01-4.86), being antiretroviral-naïve (aOR, 2.91; 95% CI, 1.27-6.67), and chronic HBV infection (aOR, 0.13; 95% CI, 0.03-0.61) at baseline were associated with HHV-8 seroconversion.

    An increasing trend of HHV-8 infection was observed among PLWH in Taiwan between 2014 and 2018. MSM and being antiretroviral-naïve were associated with higher risk for HHV-8 seroconversion.

    An increasing trend of HHV-8 infection was observed among PLWH in Taiwan between 2014 and 2018. MSM and being antiretroviral-naïve were associated with higher risk for HHV-8 seroconversion.

    To explore variation in general practitioners’ (GPs’) performance of six recommended procedures in type 2 diabetes patients <75 years without cardiovascular disease.

    Cross-sectional study of quality of diabetes care in Norway based on electronic health records from 2014. GPs (clustered in practices) were divided in quintiles based on a composite measure of performance of six processes of care. We fitted a multilevel partial ordinal regression model to identify GP factors associated with being in quintiles with better performance.

    We identified 6015 type 2 diabetes patients from 275 GPs in 77 practices. The GPs performed on average 63.4% of the procedures; on average 46% in the poorest quintile to 81% in the best quintile with a larger range in individual GPs. After adjustments, use of a structured follow-up form was associated with GPs being in upper three quintiles (OR 12.4 (95% CI 2.37-65.1). Routines for reminders were associated with being in a better quintile (OR 2.6 (1.37-4.92). GPs’ age >60 years and heavier workload were associated with poorer performance.

    We found large variations in GPs’ performance of processes of care. Factors reflecting structure and workload were strongly associated with performance.

    We found large variations in GPs’ performance of processes of care. Factors reflecting structure and workload were strongly associated with performance.

    China has achieved near-universal health coverage (UHC) for 95 percent of its population (>1.3 billion lives) as a result of healthcare reforms that began in 2009. However, one of many remaining issues in the Chinese healthcare system is the need to better optimize the allocation and use of healthcare resources in order to meet growing healthcare demands.

    The goals are to highlight the components of the China Guidelines for Pharmacoeconomic Evaluations (CGPE) 2020 Edition and discuss its future development for UHC in China.

    We review the development process of the CGPE 2020 edition, discuss the contemporary practice of the CGPE for UHC in China, describe new opportunities and challenges to the CGPE, and provide suggestions on the future development of the CGPE based on the current state of the healthcare system in China.

    Pharmacoeconomics provides tools to evaluate the health returns and economic costs of pharmaceutical products in a scientific way for the optimal allocation of healthcare resourcesacoeconomic evaluation research and enhance the value and efficiency of UHC in China.A literature review was conducted to determine norms for practice in neonatal intensive care units (NICU) around the world, given the harmful risks associated with radiation exposure at a very young age; risk of radiation-induced harm later in life increases with every X-ray image taken, more so for younger premature babies. Empirical studies including a measurement of radiation dose in a NICU, published after the year 2000 in a peer-reviewed journal, were collected. Measured doses to patients or X-ray phantoms, number of X-rays per stay and conclusions with recommendations made in response to these values were compared for 25 studies from around the world. The number of X-rays a patient underwent during a NICU stay ranged from 0 to 159. Younger, lower birth weight patients consistently had the greatest number of X-rays per stay. Recommended action based on measured dose ranged from extensive (to minimize risk to neonates) to minimal (to reduce risk) to none (because imaging benefits outweigh patient risk), with no consistent pattern linking recommended action with dose quantity. This demonstrates a broad range of interpretations of the As Low As Reasonably Achievable (ALARA) concept. These findings indicate a disparity in the response to neonatal X-ray dose concerns on a global scale, posing a public health risk to this particular neonatal population. More up-to-date imaging protocols and dose limits specifically for the NICU environment with standardized dose monitoring would help minimize this risk to achieve the public health goals of prevention and harm reduction.

    Examine differences in skin carotenoid status (SCS) based on time, age, and sex of preschool-aged children enrolled in Head Start (HS) in North Carolina.

    Data were collected using surveys from participating families. preschool-aged children’s SCS were measured 3 times over a 6-month period.

    Three HS centers in North Carolina.

    One hundred twelve children aged 3-5 years, enrolled in HS.

    Differences in SCS assessed using the Veggie Meter (Longevity Link, Salt Lake City, UT) based on time, sex, and age.

    One-way ANOVA to assess SCS at time 1 between sex and age (n = 112). Repeated measures ANOVA with a Greenhouse-Geisser correction for assessment of SCS over time (n = 45) using Bonferroni correction.

    On average, children were aged 4 years, African American (81.3%), male (57%), and had a mean SCS of 266 (SD = 82.9). Skin carotenoid status (Veggie Meter units) were significantly different over time (P < 0.001). Significant differences were observed between ages (P = 0.01) and sex (P < 0.01).

    The Veggie Meter is a promising tool to assess fruit and vegetable intake but needs to be validated in preschool-aged children as it has been in adults. Sex and age are potential confounders which should be assessed in future studies using the Veggie Meter.

    The Veggie Meter is a promising tool to assess fruit and vegetable intake but needs to be validated in preschool-aged children as it has been in adults. Sex and age are potential confounders which should be assessed in future studies using the Veggie Meter.

    To determine the prevalence of food insecurity and the factors associated with it among health sciences graduate students.

    A cross-sectional web-based survey conducted in 2019 on an urban health sciences campus of a large, public northeastern university among health sciences graduate students. Food security status was assessed using the US Department of Agriculture validated 6-item short-form food security module.

    Of the 302 respondents (response rate, 8.8%), the mean age ± SD was 28.8 ± 7.30 years; 28.5% were food insecure. After adjusting for other covariates, receiving loans was independently associated with higher odds of being food insecure (P < 0.001).

    Universities may consider screening graduate students for food insecurity risk, especially those receiving student loans. Future research on this topic with graduate students and program administrators in other universities may help identify potential interventions. The impacts of the coronavirus disease 2019 pandemic on food insecurity among graduate students merit exploration to develop context-specific interventions.

    Universities may consider screening graduate students for food insecurity risk, especially those receiving student loans. Future research on this topic with graduate students and program administrators in other universities may help identify potential interventions. The impacts of the coronavirus disease 2019 pandemic on food insecurity among graduate students merit exploration to develop context-specific interventions.

    To assess the effectiveness of food-based science, technology, engineering, arts, and mathematics (STEAM) learning activities on preschoolers’ liking of 9 target vegetables and objectively-assessed fruit and vegetable (FV) intake.

    Seven hands-on, food-based STEAM learning activities were implemented to expose children to 9 target vegetables in 3 Head Start preschools (11 classrooms) across North Carolina. Child-reported vegetable liking scores and skin carotenoid status (SCS) were dependent variables collected at baseline, midpoint, and posttest. Adjusted repeated-measures ANOVA was used to examine intervention impact.

    A total of 113 children (intervention = 49; comparison = 64) participated. Children were an average age of 3.7 ± 0.57 years at baseline. Mean target vegetable liking scores for the intervention and comparison groups, respectively, were 3.2 ± 0.19 and 3.2 ± 0.17 at baseline, 2.9 ± 0.17 and 3.1 ± 0.15 at midpoint, and 2.8 ± 0.15 and 3.1 ± 0.13 at posttest. A time × group interaction was notlong-term impact this approach may have on children’s’ dietary quality.

    Food-based STEAM learning activities may present a unique opportunity to affect FV intake while meeting academic standards. More research is needed to understand how liking for familiar FV changes over time and its relationship with consumption. In addition, more implementation research featuring larger sample sizes, teachers as the interventionist, and a longer study duration is needed to confirm the outcomes of food-based STEAM learning observed in the current study and the long-term impact this approach may have on children’s’ dietary quality.

    CACNA1A-related disorders present with persistent progressive and non-progressive cerebellar ataxia and paroxysmal events epileptic seizures and non-epileptic attacks. These phenotypes overlap and co-exist in the majority of patients.

    To describe phenotypes in infantile onset CACNA1A-related disorder and to explore intra-familial variations and genotype-phenotype correlations.

    This study was a multicenter international collaboration. A retrospective chart review of CACNA1A patients was performed. Clinical, radiological, and genetic data were collected and analyzed in 47 patients with infantile-onset disorder.

    Paroxysmal non-epileptic events (PNEE) were observed in 68% of infants, with paroxysmal tonic upward gaze (PTU) noticed in 47% of infants. Congenital cerebellar ataxia (CCA) was diagnosed in 51% of patients including four patients with developmental delay and only one neurological sign. PNEEs were found in 63% of patients at follow-up, with episodic ataxia (EA) in 40% of the sample. Cerebellar at. There were no genotype-phenotype correlations found.

    The spine is the most common site of bone metastasis from cancer and can be divided into 5 locational subsections, varying in mobility. The purpose of this research was to determine if the mobility of the metastases-bearing vertebral segment influenced pre-treatment pain intensity or health-related quality of life (HR-QoL) for patients about to receive palliative radiation therapy for painful spine metastasis.

    This study was a retrospective chart review of patients referred to the Palliative Radiation Oncology Program, about to receive radiation therapy for vertebral metastasis between January 2014 and June 2016. The main variables included patient-reported Edmonton Symptom Assessment Score pain intensity, the EQ-5D score for HR-QoL and the location of the vertebral metastasis (categorized using the SINS mobility score (mobile, junctional, semi-rigid, or rigid)). Various patient, disease and treatment characteristics were also collected, and entered into a multivariate analysis.

    The eligible sample inclatment pain than those with metastases in junctional segments. Although further corroboration is needed, our results suggest that the mobility of the metastasis-bearing spinal section could be added to the existing list of predictors that aid clinicians in identifying patients that will benefit from closer follow-up or early intervention.

    Patients referred to an RT clinic for the treatment of painful spinal metastases have a different distribution of disease throughout the spine compared to those referred for surgery or SBRT. Those with metastases in mobile spine segments were more likely to experience severe pre-treatment pain than those with metastases in junctional segments. Although further corroboration is needed, our results suggest that the mobility of the metastasis-bearing spinal section could be added to the existing list of predictors that aid clinicians in identifying patients that will benefit from closer follow-up or early intervention.

    The human gut microbiota has emerged as a key factor in the development of obesity. Certain probiotic strains have shown anti-obesity effects. The objective of this study was to investigate whether Bifidobacterium longum APC1472 has anti-obesity effects in high-fat diet (HFD)-induced obese mice and whether B. longum APC1472 supplementation reduces body-mass index (BMI) in healthy overweight/obese individuals as the primary outcome. B. longum APC1472 effects on waist-to-hip ratio (W/H ratio) and on obesity-associated plasma biomarkers were analysed as secondary outcomes.

    B. longum APC1472 was administered to HFD-fed C57BL/6 mice in drinking water for 16 weeks. In the human intervention trial, participants received B. longum APC1472 or placebo supplementation for 12 weeks, during which primary and secondary outcomes were measured at the beginning and end of the intervention.

    B. longum APC1472 supplementation was associated with decreased bodyweight, fat depots accumulation and increased glucose tolerance me Ireland and by a research grant from Cremo S.A.

    Discordant data have been reported on the prognosis of myocardial infarction with nonobstructive coronary arteries (MINOCA). Moreover, few data are available on the impact of angiographic subtypes. The objectives of this study were to assess the prognostic impact on the long-term follow-up of the diagnosis of MINOCA and its angiographic subtypes.

    We included 591 consecutive patients with non-ST-segment elevation myocardial infarction (NSTEMI) who underwent coronary angiography. MINOCA was classified according to angiographic findings as smooth coronary arteries, mild irregularities (< 30% stenosis), and moderate atherosclerosis (30%-49% stenosis). The primary endpoint was a composite of mortality, nonfatal myocardial infarction, and revascularization (MACE) at a median of 5 years of follow-up.

    A total of 121 patients (20.5%) showed no obstructive lesions. MINOCA was associated with a lower occurrence of MACE (P=.014; HR, 0.63; 95%CI, 0.44-0.91) and was confirmed as an independent factor in the multivariate analysis (P=.018; HR, 0.63; 95%CI, 0.43-0.92). On analysis of the separate components of the main endpoint, MINOCA was significantly associated with a lower rate of myocardial infarction and revascularization, but not with mortality. Analysis of angiographic subtypes among MINOCA patients showed that smooth coronary arteries were a statistically significant protective factor on both univariate and multivariate analysis, while mild irregularities and 30% to 49% plaques were associated with a higher risk of MACE.

    MINOCA is associated with a lower rate of MACE, driven by fewer reinfarctions and revascularizations. Within the angiographic subtypes of MINOCA, smooth arteries were independently associated with a lower number of MACE.

    MINOCA is associated with a lower rate of MACE, driven by fewer reinfarctions and revascularizations. Within the angiographic subtypes of MINOCA, smooth arteries were independently associated with a lower number of MACE.

    Drug shortages affect health systems worldwide. Research in community pharmacy has focused on the nature, extent and impact of these shortages on patients and pharmacists. However, pharmacists’ moral reasoning in situations of drug shortages has not been addressed.

    To explore the moral reasoning perspectives of Dutch community pharmacists in situations of drug shortages.

    An electronic survey was developed around three drug shortage scenarios with a varying impact on patient outcomes a Contraceptive, a Parkinson’s and an Osteoporosis scenario. Pharmacists rated the likelihood of nine handling options and rated and ranked 13 considerations that may have played a role therein. The considerations represented three moral reasoning perspectives (MRPs) a business orientation (BO), a rules and regulations (RR), and a professional ethics (PE) MRP. Principle component analysis (PCA) was used to investigate construct validity of the MRPs. MRP rating and MRP ranking scores measured the relative importance of the di, this perspective can be compromised when the drug shortage is perceived to have a lower impact on patient outcomes and when alternative drugs or therapy are expensive.Despite routine supplementation, vitamin D insufficiency is often seen in cystic fibrosis (CF) patients on account of pancreatic insufficiency. Vitamin D is a crucial component of bone health and affects nearly all cells of the immune system. However, clinical benefits or harms associated with supplementation are poorly documented. In this systematic review, we included randomized controlled trials (RCTs) that compared vitamin D supplementation with placebo (i.e. 'non-increased dose’) in CF patients. Analysing the 8 included RCTs, the intervention group had significantly higher serum 25-hydroxyvitamin D (se25OHD) levels, but there were no significant differences found in the quantitative synthesis of clinical outcomes, including bone disease-, respiratory status- and immunological status-related outcomes. Based on our current results, while a higher vitamin D dose elevates se25OHD, it does not seem to influence clinical outcomes. Future RCTs should include outcomes of past studies and apply longer follow-up periods to document long-term patient-important outcomes.

    Increased (abnormal) ventilation inhomogeneity in individuals with mild Cystic Fibrosis (CF) lung disease may become a treatable trait for small-molecule therapeutics improving Cystic Fibrosis Transmembrane Regulator (CFTR) function. The relationship between CFTR function and ventilation inhomogeneity is unknown. We aimed to identify and quantify increased ventilation inhomogeneity in relation to CFTR function.

    This was an international, multi-center, cross-sectional study. We collated data from individuals aged 3-25 years with minimal (CFTR-MF) or residual (CFTR-RF) function of a variety of CFTR genotypes and FEV

    ≥ 70% predicted. We measured lung function using nitrogen multiple-breath washout and spirometry. We compared lung clearance index (LCI) and FEV

    between individuals with CFTR-MF vs CFTR-RF using a mixed effects multi-variable linear regression model to account for study differences and a logistic model based on propensity-score matching to adjust for possible confounding.

    We included 141 with CFTR-MF and 35 with CFTR-RF. LCI (> 1.96 z-score) was elevated in 71.6% individuals with CFTR-MF and in 40.0% with CFTR-RF. FEV

    (< -1.96 z-score) was reduced in 11.3% individuals with CFTR-MF and in 5.7% with CFTR-RF. The mean difference (95% CI) of LCI and FEV

    between CFTR-MF and CFTR-RF was 3.71 (1.63 to 5.79) and -0.40 (-0.83 to 0.02) z-score. The LCI differences were similar after adjustment for confounders and in individuals with normal FEV

    .

    Increased ventilation inhomogeneity is associated with less CFTR function. In individuals with mild CF lung disease, LCI can identify and quantify increased ventilation inhomogeneity, a candidate treatable trait.

    Increased ventilation inhomogeneity is associated with less CFTR function. In individuals with mild CF lung disease, LCI can identify and quantify increased ventilation inhomogeneity, a candidate treatable trait.The Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) global pandemic significantly impacted CF clinical research within the Cystic Fibrosis Foundation Therapeutics Development Network (CFF TDN). A Research Electronic Data Capture (REDCap) survey was developed and sent to network sites to monitor and understand the impact on research teams, ongoing and anticipated clinical research, and specific clinical and research procedures. Key findings indicated an early impact on participant enrollment, research team stability, and procedures such as spirometry and sputum induction. These trends steadily improved over the months as research activities began to recover across the TDN. While SARS-CoV-2 created a significant challenge it also highlights new opportunities to expand CF research with greater focus on data collection outside of research centers and increased access for remote participation.Compared to other neurodegenerative diseases, Parkinson’s disease (PD) is distinctive in terms of marked symptomatic variability and prognosis, as well as for the wide variety of symptomatic treatment options. Despite several decades of advances in medications and neurosurgical approaches, there remains an unmet need for symptomatic motor control. Better control of tremor, gait and balance, posture, dexterity, and communication skills are major challenges for better therapeutics of the PD movement disorder. Non-motor symptoms (NMS), which often precede motor impairments, add complexity to the burden of PD and its management. Recognized by James Parkinson MD two centuries ago, and despite 21st century neurological advances, a range of NMS plague the patient’s journey, from prodromal to palliative stages. Characterizing the clinical phenotype of the entire non-motor profile of PD is challenging. Further research and understanding are needed for discovering biomarkers of certain NMS, such as dementia, fatigue, pain, sleep, and apathy. More work is needed to gather a robust evidence base for guiding treatment of troubling NMS, which exert a major impact on quality of life for people with PD and their caregivers.Laboratory and clinical experience have pointed to the value of targeting motor pathways emerging from the striatum to treat problems arising in advanced Parkinson’s disease (PD). These pathways are selectively populated with a subtype of adenosine binding sites (A2A receptors) that offer a target for improving PD symptomatology. Several compounds were developed that possess high selectivity and potency for blocking this receptor. Three of these compounds – istradefylline, preladenant, and tozadenant – were chosen for clinical development programs that culminated in Phase 3 multicenter randomized clinical trials. Each of these drugs exert virtually no off-target neurochemical effects. Clinical trials with these drugs focused upon reducing OFF time when administered adjunctly to levodopa and other antiparkinsonian medications. Despite promising Phase 2 data, preladenant did not show efficacy when tested in a randomized placebo-controlled Phase 3 clinical trial. Reports of hematological toxicity necessitated ceasing an ongoing Phase 3 investigation of tozadenant. Following a challenging approval process, based on the results of randomized clinical trials carried out in the U.S. and Japan, istradefylline received approval in these countries for treatment of OFF episodes.The adenosine A2A receptor is a major target of caffeine, the most widely used psychoactive substance worldwide. Large epidemiological studies have long shown caffeine consumption is a strong inverse predictor of Parkinson’s disease (PD). In this review, we first examine the epidemiology of caffeine use vis-à-vis PD and follow this by looking at the evidence for adenosine A2A receptor antagonists as potential neuroprotective agents. There is a wealth of accumulating biological, epidemiological and clinical evidence to support the further investigation of selective adenosine A2A antagonists, as well as caffeine, as promising candidate therapeutics to fill the unmet need for disease modification of PD.While Parkinson’s disease (PD) is traditionally characterized by dopaminergic neuron degeneration, several neurotransmitters and neuromodulators besides dopamine are also involved in the onset and progression of the disease and its symptoms. The other principal neurotransmitters/neuromodulators known to control basal ganglia functions and, in particular, motor functions, are GABA, glutamate, serotonin (5-HT), noradrenaline, acetylcholine, adenosine and endocannabinoids. Among these, adenosine is the most relevant, acting through its adenosine A2A receptor. Work in experimental models of PD has established the effects of A2A receptor antagonists, including the alleviation of disrupted dopamine functions and improved efficacy of dopamine replacement therapy. Moreover, positive interactions between A2A receptor antagonists and both D2 and D1 receptor agonists have been described in vitro at the receptor-receptor level or in more complex in vivo models of PD, respectively. In addition, the interactions between A2A receptor antagonists and glutamate ionotropic GluN2B-containing N-Methyl-d-aspartic acid receptors, or metabotropic glutamate (mGlu) receptors, including both mGlu5 receptor inhibitors and mGlu4 receptor activators, have been reported in both in vitro and in vivo animal models of PD, as have positive interactions between A2A and endocannabinoid CB1 receptor antagonists.

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