Intrauterine growth restriction in piglets modulates postnatal immune function and hepatic transcriptional responses independently of energy intake.

Introduction: Insufficient prenatal nutrition can affect fetal development and lead to intrauterine growth restriction (IUGR). The aim of this study was to investigate hepatic transcriptional responses and innate immune function in piglets suffering from IUGR compared to normal-sized piglets at 3 days of age and explore whether the provision of an energy-rich supplement at birth could modulate these parameters. Methods: A total of 68 piglets were included in the study. Peripheral blood mononuclear cells were harvested for LPS stimulation, and organs were harvested post-mortem to quantify relative weights. Liver tissue was utilized for RNA sequencing coupled with gene-set enrichment analysis. Results: IUGR resulted in increased expression of genes such as PDK4 and substantial alterations in transcriptional pathways related to metabolic activity (e.g., citric acid and Krebs cycles), but these changes were equivalent in piglets given an energy-rich supplement or not. Transcriptomic analysis and serum biochemistry suggested altered glucose metabolism and a shift toward oxidation of fatty acids. IUGR piglets also exhibited suppression of genes related to innate immune function (e.g., CXCL12) and pathways related to cell proliferation (e.g., WNT and PDGF signaling). Moreover, they produced less IL-1ß in response to LPS stimulation and had lower levels of blood eosinophils than normal-sized piglets. Discussion: Taken together, our results indicate that IUGR results in early-life alterations in metabolism and immunity that may not be easily restored by the provision of exogenous energy supplementation.

The motivation of breast cancer patients to participate in a national randomized control trial.

PURPOSE: Clinical trials are essential for development of better cancer care. Therefore, patient willingness to participate in these trials is important. The aim of this study was to assess motivation and thoughts of breast cancer patients concerning participation in a clinical trial. METHODS: Twenty-one patients participated in two semi-structed interviews about participating in a clinical trial testing the efficacy of cryotherapy for the prevention of chemotherapy-induced peripheral neuropathy in breast cancer patients treated with paclitaxel. The interviews took place before and after the intervention and were coded and categorized following the steps in Braun & Clarke's thematic analysis to identify motivational factors and experiential themes. RESULTS: Four overarching themes were identified: (1) reasons to participate in the trial, (2) personal resources, (3) safety, and (4) experience of the randomization. The most frequent reason for participating in the trial was to support research and help others, but many also participated hoping to receive the intervention treatment. The study showed that a surplus of personal resources played an important role when the patients decided to participate in the trial. Differences were found between patients belonging to the intervention and the control group in relation to these themes. Finally, both groups experienced the extra examinations received during the trial as an additional source of safety. CONCLUSION: This qualitative study found different factors influencing the experience of participating in a clinical trial, e.g., intervention-status, personal resources, and safety. This knowledge can be valuable when planning future clinical trials involving breast cancer patients.

An increased weaning age and liquid feed enhances weight gain compared to piglets fed dry feed pre-weaning.

Increasing age and providing liquid creep feed could potentially increase the solid feed intake in pre-weaning piglets, which may in turn promote gut maturation and post-weaning feed intake, possibly lessening the severity of the growth-check associated with the suckling-to-weaning transition. Therefore, this study aimed to investigate if feeding dry- versus liquid creep feed (DF vs. LF) and weaning in week 4 or 5 (4W or 5W) could accelerate maturational changes to the small intestines of pre-weaning piglets by increasing digestive and absorptive capacity. In a 2 × 2 factorial study the effect of weaning age (WA) and feeding strategy (FS) on weaning weight, pre-weaning accumulated gain (AG), and average daily gain was measured for 12 923 piglets. A subpopulation of 15 piglets from each treatment group (4WDF, 4WLF, 5WDF and 5WLF; n = 60) were sacrificed to assess the effects of WA and FS on weight of digestive organs, activity of maltase, lactase and sucrase, and gene expression level of sodium-glucose linked transporter 1 (SGLT-1), glucose transporter 2 (GLUT2) and peptide transporter 1 (PepT1) in the proximal part of the small intestine (SI). No interactions were found but average weaning weight was affected by WA (P < 0.001) and FS (P < 0.001), where 5W were heavier than 4W and LF were heavier than DF. Correspondingly, the average daily gain (ADG) was affected by both WA (P = 0.003) and FS (P < 0.001). Only WA affected the relative weight of the digestive organs, where stomach weight, weight of SI and colon weight were heavier in 5W piglets compared to 4W. Lactase activity tended to decrease with age (P = 0.061), but there was no difference in the activity of maltase or sucrase between any of the treatment groups. Similarly, there was no differences in gene expression level of SGLT1, GLUT2 or PepT1 between neither the two ages nor feeding strategies. In conclusion, both WA and FS affect weaning weight and weight gain of piglets in the pre-weaning period.

Monocyte secretory profiling in a clinical and MEFV genotype-characterized cohort of Danish familial Mediterranean fever patients: diagnostic potential of CCL1 and CXCL1.

OBJECTIVE: The autoinflammatory disease familial Mediterranean fever (FMF), characterized by recurrent attacks of sterile fever, serosal, and/or synovial inflammation, is caused by variants in the Mediterranean fever gene, MEFV, coding for the pyrin inflammasome sensor. The diagnosis of FMF is mainly based on clinical symptoms and confirmed by detection of disease-associated MEFV variants. However, the diagnosis is challenging among patients carrying variants of uncertain clinical significance (VUS). In this study, we aimed to identify potential FMF discriminatory diagnostic markers in a cohort of clinically characterized FMF patients. METHOD: We established a cohort of clinically and MEFV genotype-characterized FMF patients by enrolling patients from major Danish hospitals (n = 91). The secretory profile of pyrin inflammasome-activated monocytes from healthy donors (HDs) and MEFV-characterized FMF patients (n = 28) was assessed by analysing cell supernatants for a custom-designed panel of 23 cytokines, chemokines, and soluble tumour necrosis factor receptors associated with monocyte and macrophage function. RESULTS: MEFV genotypes in Danish FMF patients were associated with age at symptom onset (p < 0.05), FMF among relatives (p < 0.01), proportion of patients in colchicine treatment (p < 0.01), and treatment response (p < 0.05). Secretion of chemokines CCL1 and CXCL1 from pyrin-activated FMF monocytes was significantly decreased compared to HDs (p < 0.05), and could discriminate FMF patients with 'non-confirmatory' MEFV genotypes from HDs with 80.0% and 70.0% sensitivity for CCL1 and CXCL1, respectively (p < 0.05). CONCLUSION: Our data suggest that a functional diagnostic assay based on CCL1 or CXCL1 levels in pyrin-activated patient monocytes may contribute to FMF diagnosis in patients with VUS.

Screening Tools for Depression and Anxiety in Patients with Chronic Obstructive Pulmonary Disease - A Systematic Review.

The diagnosis of depression or anxiety is often difficult to establish in patients with Chronic Obstructive Pulmonary Disease (COPD) as many physical symptoms are shared. There is no consensus on a screening tool for depression and anxiety in patients with COPD. The aim of this systematic review is to review screening tools for depression and anxiety suitable for application among patients with COPD in the clinical setting. A systematic review was made using predefined search terms and eligibility criteria. Of 274 initially screened articles, seven studies were found eligible. Three depression screening tools (BASDEC, BDI-II and HADS-D) had a sensitivity of 100% and a specificity >85%. The best performing anxiety screening tool (GAI) had a sensitivity of 86% and a specificity of 78%. Three screening tools had acceptable psychometric properties according to sensitivity and specificity to detect depression among patients with COPD, but the screening tools for anxiety were of less quality. Further research in and validation of the screening tools is needed to recommend one specific tool.

The burden of non-communicable diseases and mortality in people living with HIV (PLHIV) in the pre-, early- and late-HAART era.

OBJECTIVES: To estimate the burden of non-communicable diseases (NCDs) and mortality among PLHIV in the pre-, early- and late-HAART (highly active antiretroviral therapy) era. METHODS: We conducted a cohort study using population-based Danish medical registries including all adult HIV-infected residents of the Central Denmark Region during 1985-2017. For each HIV patient, we selected 10 comparisons from the background population matched by age, sex and municipality of residence. Based on hospital-related diagnoses we estimated the prevalence and incidence of specific NCD at diagnosis and at 5 and 10 years. RESULTS: We identified 1043 PLHIV and 10 430 matched comparisons. PLHIV had lower socioeconomic status and more were born outside western Europe. At HIV diagnosis, 21.9% of PHLIV vs. 18.2% of non-HIV individuals had at least one NCD, increasing to 42.2% vs. 25.9% after 10 years. PLHIV had higher prevalence and cumulative incidence of alcohol abuse, chronic obstructive pulmonary disease (COPD), ischaemic heart disease, mental disorders, renal and liver disease, but no increased risk of diabetes mellitus. Only PLHIV in the age groups 41-50 and > 51 years had an increased incidence of osteoporosis. From the pre- to the late-HAART era, 10-year mortality among PLHIV decreased from 45.5% to 9.4% but continued at more than twice that of uninfected comparisons. However, in the late-HAART era, the mortality of PLHIV who were alive 2 years after HIV diagnosis was approaching that of comparisons. CONCLUSIONS: Even in the late-HAART era, PLHIV have an excess mortality, which may be attributable to several NCDs being more prevalent among PLHIV. The prevalence rates of ischaemic heart disease, diabetes, osteoporosis and renal disease tend to increase over calendar time. Therefore, improvement of survival and quality of life of PLHIV neets strategies to reduce the risk of developing NCDs, including avoiding toxic antiretroviral therapy and lifestyle changes.

A reduced CP level without medicinal zinc oxide does not alter the intestinal morphology in weaned pigs 24 days post-weaning.

The use of medicinal zinc oxide (ZnO) to prevent diarrhoea post-weaning will be banned in the EU from 2022. Therefore, new alternatives are needed to avoid an increase in diarrhoea and higher antibiotic use. A low dietary CP level has shown to lower the frequency of diarrhoea in pigs, due to lower microbial protein fermentation in the colon as well as improved conditions in the small intestine after weaning. The objective of this study was to examine the effect of decreased CP levels post-weaning as an alternative to medicinal ZnO on gut morphology and histopathology. Five hundred and sixty pigs were randomly assigned into one of six groups receiving a two-phase diet from 5.5 to 15 kg: positive control group (PC) with medicinal ZnO and standard levels of protein (19.1-18.4% CP), negative control group (NC) without medicinal ZnO and standard levels of protein (19.1-18.4% CP). The remaining four low protein groups were a low-standard (LS) CP level (16.6-18.4% CP), a low-low (LL) CP level (16.6-16.2% CP), a very low-high (VLH) CP level (14-19.3% CP) and a very low-medium (VLM) CP level (14-17.4% CP). Individual BW was recorded at day 0, 10 and 24 post-weaning, and all antibiotic treatments were recorded. Tissue samples from the small intestine (mid-jejunum) for morphological and histopathologic analysis, organ weights, blood and urine samples were collected at day 10 and 24 post-weaning from a total of 90 sacrificed weaners. The results demonstrated no differences in intestinal morphology between groups, but the histopathology showed a damaged brush border score in VLM and VLH pigs . In addition, a lower blood urea nitrogen in VLM pigs at 24 days was found. The LL and VLM pigs had a significantly decreased average daily gain in the overall trial period compared to PC and NC pigs. Conclusively, intestinal brush border was damaged by the very low protein diet at 24 days post-weaning, but intestinal morphology was unaffected by dietary strategy.

Convergent Validity of Suffering and Quality of Life as Measured by The Hidradenitis Suppurativa Quality of Life.

BACKGROUND: Hidradenitis suppurativa (HS) is a painful chronic, recurrent inflammatory skin disease with great impact on health-related quality of life (HRQOL). Recently, Hidradenitis SuppuraTiva cORe outcomes set International Collaboration (HISTORIC) established HRQOL as a core domain set for HS clinical trials and developed the Hidradenitis Suppurativa Quality of Life (HiSQOL) as a validated outcome measurement instrument. OBJECTIVES: To provide further convergent validity of HiSQOL by comparing it to Dermatology Life Quality Index (DLQI) and Pictorial Representation of Illness and Self Measure-Revised 2 (PRISM-R2). METHODS: In this cross-sectional study, 103 participants completed HiSQOL, PRISM-R2 and DLQI. PRISM-R2 is an instrument designed to measure suffering and reports the two measures, Illness Perception Measure (IPM) and Self-Illness Separation (SIS). Correlation analyses were performed including a sub-analysis for a subgroup of patients with high scores in the HS-specific domains of HiSQOL. RESULTS: A very strong correlation was found between HiSQOL and DLQI (ρ = 0.93, P < 2.2 × 10-16 , (95% CI: 0.89;0.95)), and moderately strong correlations were found between HiSQOL and SIS (ρ = -0.73, P < 2.2 × 10-16 , (95% CI: -0.81; -0.62)) and DLQI and SIS (ρ = -0.70, P < 2.2 × 10-16 , (95% CI: -0.79; -0.59)). IPM was positively associated with HiSQOL and DLQI and negatively with SIS. CONCLUSIONS: HiSQOL is a valid measure of quality of life for HS patients, and we suggest that HiSQOL can be used as a measure of suffering as well.

Prognostic utility of the assessment of diastolic function in patients undergoing cardiac resynchronization therapy.

Conflicting data exist about the relationship between cardiac resynchronization therapy (CRT) and diastolic function. Aims of the study are to assess diastolic patterns in patients undergoing CRT according to the 2016 recommendations of the American Society of Echocardiography/European Association of Cardiovascular Imaging and to evaluate the prognostic value of diastolic dysfunction (DD) in CRT candidates. METHODS AND RESULTS: One-hundred ninety-three patients (age: 67 ± 11 years, QRS width: 167 ± 21 ms) were included in this multicentre prospective study. Mitral filling pattern, mitral tissue Doppler velocity, tricuspid regurgitation velocity, and indexed left atrial volume were used to classify DD from grade I to III. CRT-response, defined as a reduction of left ventricular (LV) end-systolic volume > 15% at 6-month follow-up (FU), occurred in 132 (68%) patients. The primary endpoint was a composite of heart transplantation, LV assisted device implantation, or all-cause death during FU and occurred in 29 (15%) patients. CRT was associated with a degradation of DD in non-responders. At multivariable analysis corrected for clinical variables, QRS duration, mitral regurgitation, CRT-response and LV dyssynchrony, grade I DD was associated with a better outcome (HR 0.37, 95% CI: 0.14-0.96). Non-responders with grade II-III DD had the worse prognosis (HR 4.36, 95%CI: 2.10-9.06). CONCLUSIONS: The evaluation of DD in CRT candidates allows the prognostic stratification of patients, independently from CRT-response.

Characteristics of patients with familial Mediterranean fever in Denmark: a retrospective nationwide register-based cohort study.

Objectives: To investigate epidemiology, demography, and genetic and clinical characteristics of patients with familial Mediterranean fever (FMF) in Denmark. Method: In this population-based, cross-sectional cohort study, we identified FMF patients from discharge diagnoses using ICD-10 codes in the Danish National Patient Register, and linked data from the Danish Civil Registration System and laboratory databases for results of MEFV gene variant screening. Results: We identified 495 FMF patients (prevalence 1:11 680) with a median age of 29 years and a female ratio of 51%. The median age at diagnosis of FMF was 13 (IQR 7-22) years, with an estimated median diagnostic delay of 3 (IQR 0.7-6.9) years. The predominant ethnicities were Turkish (41.8%), Lebanese (15.8%), Syrian (6.5%), South-West Asian (7.9%), and South-East Asian (3.0%). The MEFV genotype distribution was 18.7% homozygous, 21.2% compound heterozygous, 32.0% heterozygous, 11.0% with complex alleles or unresolved zygosity, and 17.1% with no detected variants. M694V was the most prevalent variant in the overall cohort (32.5%). Homozygous or compound heterozygous MEFV exon 10 variants were associated with younger age at diagnosis (p < 0.001) and reduced number of hospital contacts before diagnosis (p = 0.008). The Charlson Comorbidity Index was ≥ 2 in 8.1% of patients. The prevalence of amyloidosis was 1.0%. Conclusions: FMF in Denmark is rare and patients are mainly of Eastern Mediterranean ethnicity. Diagnostic delay was long but patients with exon 10 MEFV variants were diagnosed at a younger age. Prolonged diagnostic delay is probably caused by lack of FMF awareness in the Danish healthcare system.

Managers attitude towards implementing workplace health promotion programmes to employees in eldercare: a cross-sectional study.

Objectives: To determine the attitudes of eldercare services managers to the potential health benefits of workplace health promotion programmes (WHPPs), including physical exercise during working hours and the feasibility of implementing a WHPP at the workplace. Study design: A cross-sectional study. Methods: Respondents filled out a 14-item questionnaire on attitudes towards the potential health benefits of WHPPs and the feasibility of implementing WHPPs. Differences between groups were analysed using the Kruskal-Wallis test. The significance level was set to p â€‹= â€‹0.05. Bonferroni's correction was used in the setting of multiple comparisons. A content analysis was performed exploring answers provided in the optional comment section in the questionnaire. Results: 695 eldercare services managers in Denmark were contacted by email, 393 replied, and 382 respondents were included in the analysis (54.7%). The survey revealed that 89.8% of the respondents believed that WHPPs would increase health, 89.6% believed that it would increase well-being and 87.6% believed that WHPPs would increase workability among workers. 87.7% expressed a willingness towards implementing WHPPs and believed 'it to be a good idea'. Respondents with a negative attitude to the feasibility of implementing WHPPs, were more likely to hold negative attitudes to the potential health benefits of WHPPs (p â€‹< â€‹0.001). Organisational issues were the most frequently stated barrier to implementation. Conclusions: The majority of eldercare managers expressed a positive attitude to the benefits of WHPPs and their implementation. Addressing organisational issues and ensuring management support in the planning stage of a WHPP is highly important.

Gut microbiota composition during a 12-week intervention with delayed-release dimethyl fumarate in multiple sclerosis - a pilot trial.

INTRODUCTION: Patients with multiple sclerosis may have a distinct gut microbiota profile. Delayed-release dimethyl fumarate is an orally administered drug for relapsing-remitting multiple sclerosis, which has been associated with gastrointestinal side-effects in some patients. OBJECTIVES: The purpose of this study was to determine if dimethyl fumarate alters the abundance and diversity of commensal gut bacteria, and if these changes are associated with gastrointestinal side-effects. METHODS: Thirty-six patients with relapsing-remitting multiple sclerosis received either dimethyl fumarate (n = 27) or an injectable multiple sclerosis disease-modifying therapy (glatiramer acetate or interferons, n = 9) for 12 weeks. Stool samples were collected at baseline, two and 12 weeks. We included 165 healthy individuals as controls. RESULTS: At baseline, 16 microbial genera were altered in multiple sclerosis patients compared with healthy controls. In the dimethyl fumarate-treated patients (n = 21) we observed a trend of reduced Actinobacteria (p = 0.03, QFDR = 0.24) at two weeks, mainly driven by Bifidobacterium (p = 0.06, QFDR = 0.69). At 12 weeks, we observed an increased abundance of Firmicutes (p = 0.02, QFDR = 0.09), mostly driven by Faecalibacterium (p = 0.01, QFDR = 0.48). CONCLUSIONS: This pilot study did not detect a major effect of dimethyl fumarate on the gut microbiota composition, but we observed a trend towards normalization of the low abundance of butyrate-producing Faecalibacterium after 12 weeks treatment. The study was underpowered to link microbiota to gastrointestinal symptoms.

Feasibility and efficacy of a novel technology-based approach to harness social networks for weight loss: the NETworks pilot randomized controlled trial.

OBJECTIVE: Harnessing social support from existing social ties represents a key weight control practice. This trial evaluated an intervention that provided health-promoting technologies for leveraging the influence of existing social ties. METHODS: Volunteers (N = 36) with a body mass index between 25 and 55 kg m-2 were randomized to a 16-week, in-person, technology-supported behavioural weight-loss treatment (standard behavioural treatment) or the same programme supplemented by providing self-selected members of participants' social networks with a digital body-weight scale and Fitbit Zip physical activity tracker (ENHANCED). RESULTS: Average weight losses from baseline to 16 weeks did not significantly differ between groups (standard behavioural treatment, 5.30%, SD =3.93%; ENHANCED, 5.96%, SD = 5.19%, p = 0.63). By the 1-year follow-up, standard behavioural treatment had lost 5.63%, SD = 8.14% of baseline weight versus 4.73%, SD = 9.43% for ENHANCED (p = 0.82). ENHANCED reported self-weighing on more days than did standard behavioural treatment (p = 0.03). Most participants reported high programme satisfaction. Similar improvements were observed in perceived social support for diet and exercise from baseline to 16 weeks in both groups (ps < 0.05) but regressed by 1 year (ps < 0.01). CONCLUSION: Although feasible to implement, this technology-based, social support approach failed to enhance outcomes of a face-to-face, group-based behavioural weight-loss treatment.

Effect of ADHD medication in male C57BL/6J mice performing the rodent Continuous Performance Test.

RATIONALE: The rodent Continuous Performance Test (rCPT) is a novel rodent paradigm to assess attention and impulsivity that resembles the human CPT. This task measures the rodents' ability to discriminate between target and non-target stimuli. The effect of attention-deficit/hyperactivity disorder (ADHD) medication on rCPT performance in mice remains to be fully characterized. OBJECTIVE: To investigate the predictive validity of the mouse rCPT by studying the effects of ADHD medication methylphenidate, atomoxetine, amphetamine, guanfacine, and modafinil in four behavioral subgroups based on performance and impulsivity levels. METHODS: Two cohorts of male C57BL/6J mice were used, and the effect of treatment was tested in a variable stimulus duration probe. Performance and impulsive subgroups were made based on discriminability and percentage premature responses, respectively. RESULTS: Methylphenidate, atomoxetine, and amphetamine improved performance in the low-performing animals, with no effect in the high-performers. These improvements were a result of increased hit rate and/or decreased false-alarm rate. Furthermore, these drugs decreased percentage premature responses in the high-impulsive group. Methylphenidate, guanfacine, and modafinil increased premature responses in the low-impulsive group. Modafinil impaired performance in the high-performers by increasing false-alarm rate. CONCLUSION: The effect of ADHD treatment was dependent on baseline, as seen by increases in performance for the low-performers and decreases in impulsivity for the high-impulsive animals. These results agree with clinical data and may support the inverted U-shaped arousal-performance theory. The rCPT combined with behavioral separation into subgroups has high predictive validity, and our study is a step forward towards establishing the clinical translatability of the rCPT.

Postpartum depression and child growth in Tanzania: a cohort study.

OBJECTIVE: To examine the association between postpartum depression and child growth in a Tanzanian birth cohort. DESIGN: Prospective cohort study. SETTING: Moshi, Tanzania. POPULATION: Pregnant women over the age of 18 who sought antenatal care at two health clinics in Moshi, and the children they were pregnant with, were assessed for inclusion in this study. METHODS: The women were interviewed twice during pregnancy and three times after birth, the final follow up taking place 2-3 years postpartum. Signs of postpartum depression were assessed approximately 40 days postpartum with the Edinburgh Postnatal Depression Scale. MAIN OUTCOME MEASURES: Child growth was assessed with anthropometric measurements at 2-3 years of age and expressed as mean z-scores. RESULTS: In all, 1128 mother-child pairs were followed throughout the duration of the study. In total, 12.2% of the mothers showed signs of postpartum depression. Adjusted mean height-for-age z-score (HAZ) was significantly lower at 2-3 years follow up for children of mothers with postpartum depression than for children of mothers without (difference in HAZ: -0.32, 95% CI-0.49 to -0.15). Adjusted mean weight-for-height z-score (WHZ) was significantly increased for the children exposed to postpartum depression (difference in WHZ: 0.21, 95% CI 0.02-0.40), whereas there was no significant difference in adjusted weight-for-age z-score (WAZ; difference in WAZ: -0.04, 95% CI -0.20 to 0.12). CONCLUSIONS: We found that postpartum depressive symptoms predicted decreased linear height in children at 2-3 years of age and slightly increased weight-for-height. TWEETABLE ABSTRACT: Postpartum depression in Tanzanian mothers is associated with impaired child growth at 2-3 years of age.

Does a 2-Week Sexual Health in Rehabilitation Course Lead to Sustained Change in Students' Attitudes?-A Pilot Study.

This pilot study aimed to explore if healthcare professional students participating in a 2-week elective course, Sexual Health in Rehabilitation (SHR), led to significant and sustained change in experienced competence and attitudes towards addressing sexual health in their future professions, when measured with the Students' Attitudes towards Sexual Health-Danish version (SA-SH-D). Comparison-group design, using the SA-SH-D at baseline, after the 2 weeks course and 3 months after completing the course. Participation in the SHR course significantly changed the students' attitudes; decreasing their fears of offending the patients and increasing their feelings of comfort in communicating about sexual health, and the results sustained during the follow-up period of 3 months. The results of the intervention suggest that a 2-week elective SHR course leads to sustained change healthcare students' attitudes towards addressing sexual health in their future profession. Sexual health education positively changed the students' attitudes, decreased their fears of offending the patients and increased their feelings of comfort in communicating about sexual health. The SA-SH-D is a useful tool to measure results of educational interventions aiming to change healthcare students' attitudes towards addressing sexual health in their future profession. Future research is recommended regarding students' attitudes towards addressing sexual health with persons living with disabilities. There is also a need to further research the effect of elective versus compulsory sexual health education in healthcare programs, to lessen the risk that healthcare students in their future profession will not be able to give equal care due to variation in competence and attitude.

Posttransplant reduction in preexisting donor-specific antibody levels after belatacept- versus cyclosporine-based immunosuppression: Post hoc analyses of BENEFIT and BENEFIT-EXT.

BENEFIT and BENEFIT-EXT were phase III studies of cytotoxic T-cell crossmatch-negative kidney transplant recipients randomized to belatacept more intense (MI)-based, belatacept less intense (LI)-based, or cyclosporine-based immunosuppression. Following study completion, presence/absence of HLA-specific antibodies was determined centrally via solid-phase flow cytometry screening. Stored sera from anti-HLA-positive patients were further tested with a single-antigen bead assay to determine antibody specificities, presence/absence of donor-specific antibodies (DSAs), and mean fluorescent intensity (MFI) of any DSAs present. The effect of belatacept-based and cyclosporine-based immunosuppression on MFI was explored post hoc in patients with preexisting DSAs enrolled to BENEFIT and BENEFIT-EXT. In BENEFIT, preexisting DSAs were detected in 4.6%, 4.9%, and 6.3% of belatacept MI-treated, belatacept LI-treated, and cyclosporine-treated patients, respectively. The corresponding values in BENEFIT-EXT were 6.0%, 5.7%, and 9.2%. In both studies, most preexisting DSAs were of class I specificity. Over the first 24 months posttransplant, a greater proportion of preexisting DSAs in belatacept-treated versus cyclosporine-treated patients exhibited decreases or no change in MFI. MFI decline was more apparent with belatacept MI-based versus belatacept LI-based immunosuppression in both studies and more pronounced in BENEFIT-EXT versus BENEFIT. Although derived post hoc, these data suggest that belatacept-based immunosuppression decreases preexisting DSAs more effectively than cyclosporine-based immunosuppression.

De novo donor-specific antibodies in belatacept-treated vs cyclosporine-treated kidney-transplant recipients: Post hoc analyses of the randomized phase III BENEFIT and BENEFIT-EXT studies.

Donor-specific antibodies (DSAs) are associated with an increased risk of antibody-mediated rejection and graft failure. In BENEFIT and BENEFIT-EXT, kidney-transplant recipients were randomized to receive belatacept more intense (MI)-based, belatacept less intense (LI)-based, or cyclosporine-based immunosuppression for up to 7 years (84 months). The presence/absence of HLA-specific antibodies was determined at baseline, at months 6, 12, 24, 36, 48, 60, and 84, and at the time of clinically suspected episodes of acute rejection, using solid-phase flow-cytometry screening. Samples from anti-HLA-positive patients were further tested with a single-antigen bead assay to determine antibody specificities, presence/absence of DSAs, and mean fluorescence intensity (MFI) of any DSAs present. In BENEFIT, de novo DSAs developed in 1.4%, 3.5%, and 12.1% of belatacept MI-treated, belatacept LI-treated, and cyclosporine-treated patients, respectively. The corresponding values in BENEFIT-EXT were 3.8%, 1.1%, and 11.2%. Per Kaplan-Meier analysis, de novo DSA incidence was significantly lower in belatacept-treated vs cyclosporine-treated patients over 7 years in both studies (P < .01). In patients who developed de novo DSAs, belatacept-based immunosuppression was associated with numerically lower MFI vs cyclosporine-based immunosuppression. Although derived post hoc, these data suggest that belatacept-based immunosuppression suppresses de novo DSA development more effectively than cyclosporine-based immunosuppression.

The negative impact of HBV/HCV coinfection on cirrhosis and its consequences.

BACKGROUND: Hepatitis B virus (HBV)/hepatitis C virus (HCV) confection has been rarely studied in nonasian series. AIM: To compare the characteristics of HBV/HCV coinfected patients to those of HBV- or HCV-monoinfected patients in the ANRS CO22 HEPATHER cohort study. PATIENTS AND METHODS: Of the 20 936 included patients, 95 had HBV/HCV coinfection (hepatitis B surface antigen, anti-HCV antibody and HCV RNA positive) and were matched with 375 HBV- and 380 HCV-monoinfected patients on age, gender and time since HBV or HCV diagnosis. RESULTS: F3-F4 fibrosis was more frequent in coinfected patients (58%) than in HBV- (32%, P < .0001), but similar in HCV-monoinfected patients (52%, P = .3142). Decompensated cirrhosis was more frequent in coinfected patients (11%) than in HBV- (2%, P = .0002) or HCV- (4%, P = .0275) monoinfected patients. Past excessive alcohol use was more frequent in coinfected patients (26%) than in HBV (12%, P = .0011), but similar in HCV monoinfected patients (32%, P = .2868). Coinfected patients had a higher proportion with arterial hypertension (42%) than HBV- (26%) or HCV-monoinfected patients (25%) (P < .003). Multivariable analysis confirmed the association between F3-F4 fibrosis and HCV infection in HBV-infected patients (OR = 3.84, 95% CI 1.99-7.43) and the association between decompensated cirrhosis and coinfection in HBV infected (OR = 5.58, 95% CI 1.42-22.0) or HCV infected patients (OR = 3.02, 95% CI 1.22-7.44). CONCLUSIONS: HCV coinfection harmfully affects liver fibrosis in HBV patients, while decompensated cirrhosis is increased in coinfected patients compared with HBV- or HCV-monoinfected patients. HCV treatment is as safe and effective in coinfected as monoinfected patients and should be considered following the same rules as HCV monoinfected patients.