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Transgender persons have an increased vulnerability to HIV infection yet have not been well-represented in past clinical trials for pre-exposure prophylaxis (PrEP). Because of this, there are few data available to understand whether gender-affirming hormone concentrations are influenced by PrEP agents in transgender men (TM) and transgender women (TW). The objective of this study was to compare gender-affirming hormone concentrations with versus without emtricitabine (F, FTC)-tenofovir disoproxil fumarate (TDF). TM and TW without HIV, aged 15-24 years, were enrolled for 1 month of directly observed daily F/TDF. Participants were required to be receiving a stable hormone dose (estradiol or testosterone) for at least 1 month or three consecutive doses, whichever was longer, before enrollment and willing to continue the same dose. Intensive pharmacokinetic (PK) sampling for gender-affirming hormones was collected before and 2-3 weeks after daily F/TDF. Serum estradiol and total testosterone were determined by liquid chromatography-tandem mass spectrometry; free testosterone by equilibrium dialysis. Maximum concentrations (C

The transgender community has expressed concerns regarding drug-drug interactions between HIV-pre-exposure prophylaxis (PrEP) and gender-affirming hormones. In this study, we evaluated emtricitabine (F, FTC)/tenofovir (TFV) disoporoxil fumarate (TDF) pharmacokinetics (PK) among adolescent and young adult transgender persons receiving gender-affirming hormone therapy (GAHT). This was a prospective, observational study among transgender women (TW) and men (TM) without HIV, 15-24 years of age, receiving GAHT (estradiol with/without spironolactone, or testosterone). Participants received 1 month of directly observed daily F/TDF. Weekly convenience blood samples were collected for plasma TFV and FTC, and intracellular TFV-diphosphate (TFV-DP) and FTC-triphosphate (FTC-TP) in peripheral blood mononuclear cells (PBMC) and dried blood spots (DBS). After 2-3 weeks of F/TDF dosing, intensive PK sampling was conducted. PK parameters were estimated using noncompartmental methods. Data were log-transformed and compared between TM and TW, and to historical data among cisgender adults. Plasma TFV exposures were similar between TM and TW [geometric mean ratio (GMR); confidence interval (95% CI): 1.06 (0.89-1.28)], whereas FTC plasma exposures were 21% higher in TM versus TW (95% CI: 1.07-1.38). TFV-DP in PBMC and DBS and FTC-TP in DBS did not differ between TM versus TW after controlling for creatinine clearance (CrCl), but FTC-TP in PBMC remained 46% (95% CI: 1.15-1.86) higher in TM versus TW. All PK exposures were within expected ranges based on historical studies. TM had higher FTC exposures compared with TW, but overall plasma and intracellular exposures for both drugs were within the range of historical studies, suggesting high PrEP efficacy will be retained in adolescent and young adult transgender persons. Registered at ClinicalTrials.gov (NCT03652623).

ObjectiveTo gain a better understanding of uncertainty regarding the illness experienced by parents of children with juvenile idiopathic arthritis (JIA).MethodsParents/guardians of a child or young person (aged less than 18 years) diagnosed JIA were recruited in the United Kingdom via the National Rheumatoid Arthritis Society JIA group. Semistructured telephone interviews were conducted with the parents.ResultsTwenty parents took part, including 19 mothers and one father. Their children with JIA were mostly female (n = 15; 75%) with polyarticular arthritis (n = 12; 60%), averaged 8 years of age, and had been diagnosed for a mean of 3.7 (SD 2.3) years. Parents expressed uncertainty in the following five key domains: diagnosis, cause, symptoms, and prognosis; medical management; impact; parenting uncertainty; and awareness of JIA. All participants expressed uncertainty in at least four of the five domains. Although parents’ uncertainty in the early stages of the disease related to lack of information and understanding of JIA, much uncertainty could not be resolved by receipt of information. These included concerns about their child’s future and a lack of support with managing the emotional aspects of living with JIA.ConclusionWe found that parents’ experiences of uncertainty went beyond dealing with the purely medical aspects of JIA. Provision of information about JIA, although essential, is not sufficient to help parents manage the considerable uncertainty they experience about many aspects of their child’s JIA. Identifying ways to incorporate support for coping with uncertainty into routine care will be an important way of supporting parents to care for their child with JIA.

Background Diabetes self-management education programmes are effective in improving health outcomes in the general population with diabetes. However, it is not known if these programmes include people who also have a severe mental illness (SMI) and, if so, what their outcomes are. The aim of this review was to examine if evaluations of diabetes self-management education programmes included people with SMI, and if so, whether the interventions were beneficial for this population. Methods The inclusion criteria for this systematic review, defined by PICOS criteria, were: Population - Adults with type 2 diabetes; Intervention - self-management education programme; Comparator – another active intervention or usual care; Outcomes of interest – inclusion of people with SMI and the clinical, behavioural and psychosocial outcomes in this population; Study design - randomised controlled trials. The following bibliographic databases were searched from January 2004 to April 2018: Cochrane Library, Medline, Embase, PsychINFO, Allied and Complimentary Medicine Database, Health Technology Assessment, NHS Economic Evaluations Database and CINAHL. Data were extracted on study characteristics, inclusion and exclusion criteria, participant and intervention characteristics, number of participants with SMI, and outcomes for people with SMI, if reported. Authors were contacted by email for missing data. Results A total of 410 trials were included. At least 42% of trials did not recruit any participants with SMI. Only nine confirmed inclusion of participants with SMI, of which six provided data on the number recruited. These six trials recruited a total of 1009 participants, of whom 31 (3.1%) had SMI. It was not possible to assess intervention effectiveness for people with SMI as none of the trials reported outcomes for these participants. Conclusions This systematic review confirms that people with SMI are often excluded from trials of diabetes self-management education, resulting in a lack of an evidence base on which to base treatment paths for this vulnerable population. It cannot be assumed that programmes developed for the general diabetes population meet the needs of people with SMI. Future research needs to examine if and how these programmes could be adapted for people with SMI or if new programmes are required.

Successful treatment of erectile dysfunction (ED) is associated with improvements in quality of life; however, treatment utilisation is sub-optimal. The aim of this systematic review was to identify the rates of ED treatment utilisation and the barriers and enablers men experience when using treatment. \ud \ud We searched: MEDLINE®, Embase, the Cochrane library; AMED; HMIC; HTA; CINAHL; PsychARTICLES; PsychINFO up to August 2018. Data on rates of treatment utilisation and barriers and enablers of utilisation were extracted and summarised. \ud \ud Fifty studies were included. Discontinuation rates ranged from 4.4-76% for phosphodiesterase type 5 inhibitors, 18.6-79.9% for intracavernosal injections, 32-69.2% for urethral suppositories. In relation to those with a penile prosthesis; 30% discontinued having sex due to e.g. device complications, lack of partner or a loss of sexual interest.\ud Most research included in the current review examined barriers to treatment utilisation and therefore focussed on reasons for discontinuing treatment. However, a small number explored factors that men found helpful with regards to treatment utilisation. The most prevalent barriers to utilisation were treatment ineffectiveness, side-effects, the quality of men’s intimate relationships and treatment costs. With regards to treatment enablers, the most salient finding was that men who reported side-effects to a health care profesionals (HCPs) were significantly less likely to discontinue treatment. There were limitations in methodology in that the studies did not use validated measures of treatment utilisation or barriers and enablers and no study used psychological theory to inform the examination of factors that influenced treatment utilisation.\ud \ud This review identifies a number of influential factors relating to ED treatment utilisation and highlights the importance of men’s beliefs with regards to ED and its treatment. Beliefs are potentially modifiable and therefore the findings of this review highlight important considerations for health care professionals with regards to supporting men to make better use of treatment.

Elevated levels of triglyceride-rich lipoproteins (TRLs), both fasting and postprandial, are associated with increased risk for atherosclerosis. However, guidelines for treatment are defined solely by fasting lipid levels, even though postprandial lipids may be more informative. In the postprandial state, circulating lipids consist of dietary fat transported from the intestine in chylomicrons (CMs; containing ApoB48) and fat transported from the liver in VLDL (containing ApoB100). Research into the roles of endogenous versus dietary fat has been hindered because of the difficulty in separating these particles by ultracentrifugation. CM fractions have considerable contamination from VLDL (purity, 10%). To separate CMs from VLDL, we produced polyclonal antibodies against ApoB100 and generated immunoaffinity columns. TRLs isolated by ultracentrifugation of plasma were applied to these columns, and highly purified CMs were collected (purity, 90–94%). Overall eight healthy unmedicated adult volunteers (BMI, 27.2 ± 1.4 kg/m(2); fasting triacylglycerol, 102.6 ± 19.5 mg/dl) participated in a feeding study, which contained an oral stable-isotope tracer (1-(13)C acetate). We then used this technique on plasma samples freshly collected during an 8 h human feeding study from a subset of four subjects. We analyzed fractionated lipoproteins by Western blot, isolated and derivatized triacylglycerols, and calculated fractional de novo lipogenesis. The results demonstrated effective separation of postprandial lipoproteins and substantially improved purity compared with ultracentrifugation protocols, using the immunoaffinity method. This method can be used to better delineate the role of dietary sugar and fat on postprandial lipids in cardiovascular risk and explore the potential role of CM remnants in atherosclerosis.

Objectives Juvenile Dermatomyositis (JDM) is a rare, chronic autoimmune condition of childhood, with known psychosocial implications. In this study, we sought to establish current psychological support for children and young people across the UK with rheumatic conditions, with a specific focus on those with JDM. Methods Electronic surveys were distributed to the 15 centres that belong to the JDM Research Group in the UK, collecting responses from health-care professionals in the fields of medicine, nursing and psychology. Results One hundred per cent of professionals from medicine and nursing replied from all 15 centres. Of these, 7 (47%) did not have a named psychologist as part of their rheumatology team, despite the majority [13 (87%)] having >200 paediatric rheumatology patients. Of the remaining centres, hospital psychology provision varied considerably. When rating their service, only 3 (8%) of 40 professionals scored their service as five (where one is poor and five is excellent); there were wide discrepancies in these scores. Many challenges were discussed, including limited psychology provision, lack of time and difficulties in offering support across large geographical areas. Conclusion Many of the challenges discussed are applicable to other centres worldwide. Suggestions have been proposed that might help to improve the situation for children and young people with rheumatic conditions, including JDM. Based on these findings, we suggest that rheumatology teams maximize use of these data to advocate and work toward more comprehensive psychology provision and support in their individual centres.

Human immunodeficiency virus–seronegative men aged 15–22 years who lost bone mineral density (BMD) during tenofovir disoproxil fumarate/emtricitabine preexposure prophylaxis (PrEP) showed BMD recovery 48 weeks following PrEP discontinuation. Lumbar spine and whole body BMD z-scores remained below baseline 48 weeks off PrEP in participants aged 15–19 years.Clinical Trials Registration. NCT01772823 (ATN 110) and NCT01769456 (ATN 113).

Author(s): Erkin-Cakmak, Ayca; Bains, Yasmin; Caccavello, Russell; Noworolski, Susan M; Schwarz, Jean-Marc; Mulligan, Kathleen; Lustig, Robert H; Gugliucci, Alejandro | Abstract: ObjectiveTo investigate the link between dietary sugar consumption and two separate pathogenetic mechanisms associated with metabolic syndrome: de novo lipogenesis (DNL) and nonenzymatic glycation.Design and participantsWe assessed changes in serum d-lactate (the detoxification end-product of methylglyoxal) concentration in response to 9 days of isocaloric fructose restriction in 20 children with obesity and metabolic syndrome, and examined correlations with changes in DNL, liver fat, insulin sensitivity, and other metrics of hepatic metabolism.InterventionsNine days of dietary sugar restriction, with substitution of equal amounts of refined starch.Main outcome measuresOn days 0 and 10, children had laboratory evaluation of d-lactate levels and other analytes, and underwent oral glucose tolerance testing, magnetic resonance spectroscopy to quantify fat depots, and 13C-acetate incorporation into triglyceride (TG) to measure DNL.Resultsd-Lactate was associated with baseline liver fat fraction (P l 0.001) and visceral adipose tissue (P l 0.001) but not with subcutaneous adipose tissue. At baseline, d-lactate was positively correlated with DNL-area under the curve (AUC) (P = 0.003), liver fat fraction (P = 0.02), TG (P = 0.004), and TG/high-density lipoprotein ratio (P = 0.002). After 9 days of isocaloric fructose restriction, serum d-lactate levels reduced by 50% (P l 0.0001), and changes in d-lactate correlated with both changes in DNL-AUC and measures of insulin sensitivity.ConclusionBaseline correlation of d-lactate with DNL and measures of insulin sensitivity and reduction in d-lactate after 9 days of isocaloric fructose restriction suggest that DNL and nonenzymatic glycation are functionally linked via intermediary glycolysis in the pathogenesis of metabolic syndrome and point to fructose as a key dietary substrate that drives both pathways.

Pressure ulcer reduction is a healthcare priority. Good clinical guidelines have the potential to transform pressure ulcer prevention and management practices. However, evidence suggests these guidelines are inconsistently utilised. The aim of this study was to explore health practitioners' perceived barriers and enablers to the implementation of evidence-based pressure ulcer prevention and management recommendations in an integrated community care setting. The study used a qualitative exploratory design. It took place in a community Trust in London, England. Semi-structured interviews were conducted with a purposive sample of registered nurses and allied healthcare professionals (AHPs). The Theoretical Domains Framework (TDF) informed both data collection and data analysis. Analysis followed a five-step process including deductive coding of the transcripts and inductive generation of specific belief statements. Nine nurses and four AHPs took part in the study. Six TDF domains were identified as most relevant to the implementation of best practice in pressure ulcer prevention and management: Goals, Knowledge, Skills, Beliefs about capabilities, Environmental context and resources and Social influences. All participants felt it was important to prevent pressure ulcers and were motivated to do so. Key enablers to the implementation of evidence-based practice included high levels of self-reported pressure ulcer knowledge and skills (nurses), responsive community equipment provision, the introduction of novel Pressure Ulcer Implementation Facilitator roles and integrated team working. Barriers included self-reported deficits in knowledge and skills (AHPs), worries about inspecting intimate anatomical locations (AHPs), difficulties initiating conversations with patients about risk and behaviour change, high workloads and clutter in the home. Family members and mobile working solutions were identified as both enablers and barriers. Potential routes to addressing implementation challenges are identified and recommendations made for future research.

Introduction: Delayed postprandial triglyceride-rich lipoprotein (TRL) metabolism is associated with increased atherogenic risk. Dietary fructose is a preferred lipogenic substrate which contributes to NAFLD and dyslipoproteinemia. Hypothesis: Isocaloric fructose restriction reduces postprandial TRL excursions in part by affecting the modulation of lipoprotein lipase (LPL) activity and peripheral clearance rates. Methods: We determined the effect of 9 days of isocaloric fructose restriction on fasting and postprandial TRL metabolism markers in obese Latino and African American children (9-18 years old; n=30) with high habitual sugar consumption (>50 g/d). Metabolic assessments were performed on day 0 and day 10 of isocaloric fructose restriction (starch substituted for sugar, same macronutrient composition). To follow postprandial TRL metabolism, after an initial double-sized meal, single-sized meals (providing 67% of daily calories, 15% protein, 35% fat, 50% carbohydrate) were fed every 30 minutes, with blood sampled every hour for 8 hours. Fructose content of meals reduced from 12% on day 0 to 4% on day 10. Paired t-tests compared change from day 0 to day 10 within each child. Results: Fasting TG, apoCIII, and ANGPTL3 reduced by 25%, 28% and 26% respectively (p Conclusions: Short-term isocaloric fructose restriction improved postprandial chylomicron and VLDL metabolism in children with obesity. Specific and selective improvements in ANGPTL3 and apoCIII suggest differential modulation of LPL activity as a putative mechanism that deserves further exploration.

Background\ud Self-management of inflammatory bowel disease is complex. Children and adolescents (CA) with inflammatory bowel disease (IBD) often have difficulty with managing aspects of their condition, resulting in treatment non-adherence and impaired psychosocial function. Self-management interventions are developed to help support patients and their parents/carers to effectively self-manage. The aim of this systematic review was to evaluate the efficacy of self-management interventions in children and adolescents with IBD. \ud \ud Methods\ud The review was conducted in accordance with PRISMA guidelines. A systematic literature search of the following databases; Medline, Embase, Cochrane, CINAHL and PsychINFO was conducted to identify controlled trials of interventions aiming to enhance IBD self-management in CA. Two reviewers screened articles for inclusion. \ud \ud Results\ud Nine trials (eleven articles) met the inclusion criteria. Most were underpowered with seven recruiting fewer than 50 participants. The interventions aimed to enhance psychological wellbeing (n=5), medication adherence (n=3) or calcium intake (n=1). There was considerable heterogeneity in intervention content and outcomes assessment. Some benefits were reported in disease activity, adherence and psychological well-being but findings were inconsistent. \ud \ud Conclusions\ud Self-management is difficult for CA with IBD, however this review identified only a small number of interventions to support self-management, most of which were under-powered and only one that was conducted outside the US. Clinical consensus is required on which self-management activities should be recommended to patients and targeted in interventions and which core outcomes should be assessed. Adequately powered trials of interventions are required to identify how best to support self-management in CA with IBD.

To review recent evidence for the role of dietary carbohydrate in de novo lipogenesis (DNL) and nonalcoholic fatty liver disease (NAFLD).A large body of evidence suggests that increased hepatic DNL is a significant pathway contributing to the development of NAFLD. Dietary carbohydrates, in particular, fructose, have been shown to stimulate DNL and increase liver fat, although it is debated whether this is due to excess energy or fructose per se. Recent dietary intervention studies conducted in energy balance show that high-fructose diets increase DNL and liver fat, whereas fructose restriction decreases DNL and liver fat.The association of high-carbohydrate and high-sugar diets with NAFLD may in part be explained by the effect of sugar on increasing hepatic DNL.

Introduction Gynecologic malignancies are an increasingly common proportion of central nervous system metastatic disease. As genetic sequencing technology improves and becomes more accessible, mutations associated with CNS metastasis are easier to elucidate. The aims of this case series and systematic literature review are to describe the patient population with CNS metastatic disease from a gynecologic primary, and to investigate why the proportion of CNS metastasis from gynecologic malignancies is increasing. Ultimately, we hope to improve understanding of this subset of metastatic CNS malignancies and improve management strategies. Methods A literature review of articles describing patients from 1990–2020 who were diagnosed with CNS metastasis from a known gynecologic primary malignancy was performed. Demographics, cancer type, mutation characteristics, management for metastatic disease, progression free survival, number of CNS metastases, and location of metastatic disease were assessed. Inclusion criteria were age>18 years, diagnosis of primary ovarian, uterine, or cervical cancer with confirmed metastatic disease to the CNS, including brain parenchyma, leptomeninges, or intradural spinal cord or dural metastases. Exclusion criteria included pediatric population and bony metastases (e.g., bony spine metastases without evidence of meningeal/parenchymal invasion). Results Our review showed that patients with gynecological metastasis to the CNS generally have worse outcomes regarding overall survival, progression free survival, and quality of life than patients without CNS metastasis. Discussion Our results infer that the reported increase in incidence of CNS metastasis from gynecologic malignancies is a reflection of improvement of detection given advances in technology, improved patient follow up, and increased overall survival of patients with gynecologic malignancies. Further characterization of mutations from gynecologic malignancies associated with brain metastasis could result in development of more treatment options for patients in the future and help determine factors that contribute to developing metastasis to the CNS of various degrees, thus, potentially inform treatment strategies.

Background Tenofovir disoproxil fumarate (TDF) decreases bone mineral density (BMD). We hypothesized that vitamin D3 (VITD3) would increase BMD in youth receiving TDF. Methods This was a randomized, double-blind, placebo-controlled trial of directly observed VITD3 vs placebo every 4 weeks for 48 weeks in youth aged 16-24 years with HIV, RNA load

Epidemiologic studies suggest a link between excess sugar consumption and obesity, fatty liver disease, metabolic syndrome, and type 2 diabetes mellitus. One important pathway that may link these metabolic diseases to sugar consumption is hepatic conversion of sugar to fat, a process known as de novo lipogenesis (DNL). Mechanistic studies have shown that diets high in simple sugars increase both DNL and liver fat. Importantly, removal of sugar from diets of children with obesity for only 9 days consistently reduced DNL and liver fat and improved glucose and lipid metabolism. Although the sugar and beverage industries continue to question the scientific evidence linking high-sugar diets to metabolic diseases, major health organizations now make evidence-based recommendations to limit consumption of simple sugars to no more than 5% to 10% of daily intake. Clear recommendation about moderating sugar intake to patients may be an important nonpharmacologic tool to include in clinical practice.

Pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) reduces bone mineral density in HIV-uninfected men who have sex with men (MSM). We hypothesized that PrEP with TDF-FTC would increase bone turnover markers (BTMs) at week 24 and that vitamin D supplementation from weeks 24 to 48 would blunt this increase. Participants were from a cohort of 398 MSM and transgender women who received daily TDF-FTC for PrEP. At week 24, a prospective intervention group initiated vitamin D3 4,000 IU daily. Concurrent controls were selected from the cohort who took ≤400 IU/day of vitamin D3 matched by age, race, and body mass index. The primary endpoint was the change in procollagen-I N-terminal propeptide (P1NP) from weeks 24 to 48. Paired t-tests were used to compare changes in BTMs between intervention and controls. Among 48 intervention-control pairs, median age was 33 years. At baseline, 68.9% of the intervention group and 77.3% of controls were vitamin D sufficient (≥20 ng/mL, p = .94). P1NP, C-telopeptide, parathyroid hormone (PTH), and 25-OH vitamin D3 did not increase significantly at week 24. P1NP fell by a mean ± SD of -27.6 ± 49.9 pg/mL from weeks 24 to 48 with vitamin D and -2.5 ± 40.2 pg/mL in controls (p = .01). There were no significant between-group differences in the weeks 24-48 change in C-telopeptide, PTH, or 25-OH vitamin D3. Vitamin D3 supplementation with 4,000 IU/day resulted in a significant reduction in the BTM P1NP compared with controls, suggesting that this intervention has potential to improve bone health during PrEP.

Introduction: Elevated fasting and postprandial triglyceride-rich lipoproteins (TRL) are associated with increased risk for atherosclerosis. In the postprandial state circulating lipids consist of dietary fat transported from the intestine, by chylomicrons (containing ApoB48) and fat transported from the liver, in very low-density lipoproteins (VLDL, containing ApoB100). Research into the roles of endogenous versus dietary fat has been hindered because current methods are inadequate to fully separate these particles. Specifically, chylomicron fractions have considerable contamination from VLDL. Hypothesis: We hypothesized that the generation of resin crosslinked to specific ApoB100 antibodies unique to VLDL would allow purification of chylomicron particles. Proof-of-principle experiments will determine: 1) individual contributions of newly synthesized fatty acids (de novo lipogenesis (DNL)), to triglycerides found in VLDL and chylomicrons; and 2) the proportion of labeled acetyl-CoA (precursor-pool value (PPV)) used to synthesize new palmitate. A difference in DNL and PPV for the purified VLDL and chylomicron fractions will confirm the successful separation of these particles. Methods: Polyclonal antibodies were produced against the C-terminus of the ApoB100 protein and crosslinked to resin generating ApoB100-specific affinity columns. To yield purified chylomicron and VLDL particles we used this technique in conjunction with stable-isotope tracer methodology in a human feeding study. Two healthy volunteers consumed a standardized diet accompanied by oral dosing of 1- 13 C-acetate every 30 minutes for 8 hours. Plasma collected hourly was used for the isolation of TRL, which was applied to the affinity resin and purified chylomicrons and VLDL collected. Triglycerides were isolated and derivatized. The enrichment of methyl-palmitate was measured by GC/MS and Mass Isotopomer Distribution Analysis was used to calculate DNL and PPV. Results: Western blots confirmed the separation of chylomicrons and VLDL by the described method. From the purified TRL fractions, the DNL-AUC (%DNL x 5 hours) values for subject 1 were chylomicron 4% and VLDL 34%, an 88% difference, and for subject 2 were chylomicron 8% and VLDL 83%, a 90% difference. The PPV calculated for each fraction in subject 1 were chylomicron 10% and VLDL 13% and in subject 2 were chylomicron 10%, VLDL 12%. On average, the PPV in the chylomicron fraction were 18% less than the VLDL fraction. Conclusions: In conclusion, results demonstrate that the immunoaffinity method effectively separated postprandial lipoproteins showing fractionated particles carry unique information regarding tissue of origin . Future applications include investigating the respective contribution of fat and sugar to atherosclerosis risk.

We examined associations of 25-hydroxy vitamin D (25-OHD), tenofovir disoproxil fumarate (TDF), and bone toxicity. We studied TDF/emtricitabine (FTC) HIV pre-exposure prophylaxis (PrEP) in young men who have sex with men (YMSM). Bone toxicity was predefined using bone mineral density/content change from baseline to week 48. Baseline serum 25-OHD was dichotomized as 700 fmol/punch (protective against HIV acquisition) versus ≤700. Associations were examined by univariate and multivariable logistic regression, reporting crude and adjusted odds ratios (ORs), with 95% confidence intervals (CIs). Of 101 enrolled, 69 had complete bone assessments and 25-OHD; of these, 59 had week 48 TFV-DP data. Median (Q1-Q3) age was 20 (18-21) years; 54% were black/African American. In univariate analysis, participants with baseline 25-OHD 700 (OR = 11.5; 95% CI = 1.4-169.6), 25-OHD 700 (OR = 32.3; 95% CI = 3.3-653.6) had greater odds of bone toxicity after adjusting for race. In multivariable models, 25-OHD insufficiency, protective TFV-DP concentrations, and black race were significantly associated with bone toxicity after 48 weeks of TDF/FTC PrEP in YMSM. Clinical Trials Registration: NCT01769469.

Objectives: Juvenile Dermatomyositis is a rare, potentially life-threatening condition with no known cure. There is no published literature capturing how children and young people feel about their condition, from their perspective. This study was therefore unique in that it asked children and young people what is it like to live with Juvenile Dermatomyositis. Methods: Data were obtained from fifteen young people with Juvenile Dermatomyositis, between eight and nineteen years of age from one Paediatric Rheumatology department using audio-recorded interpretive phenomenology interviews. Data were analyzed phenomenologically, using a process that derives narratives from transcripts resulting in a collective composite of participants shared experiences, called a ‘phenomenon’. Results: The overarching metaphor of a rollercoaster captures the phenomenon of living with Juvenile Dermatomyositis as a young person, with the ups and downs at different time points clearly described by those interviewed. The five themes plotted on the rollercoaster, began with confusion; followed by feeling different, being sick, steroidal and scared from the medications; uncertainty; and then ended with acceptance of the disease over time. Conclusion: Young people were able to talk about their experiences about having Juvenile Dermatomyositis. Our findings will aid clinicians in their practice by gaining a deeper understanding of what daily life is like and highlighting ways to enhance psychosocial functioning. Hopefully, this study and any further resulting studies, will raise understanding of Juvenile Dermatomyositis worldwide and will encourage health care professionals to better assess psychosocial needs in the future.

Background and aimsDietary fructose may play a role in the pathogenesis of metabolic syndrome (MetS). In a recently published study of obese children with MetS, we showed that isocaloric fructose restriction reduced fasting triglyceride (TG) and LDL-cholesterol (LDL-C). In these ancillary analyses, we tested the hypothesis that these effects were also accompanied by improved quantitative and qualitative changes in LDL and HDL subclasses and their apolipoproteins; as well as change in VLDL, particularly apoC-III.MethodsObese children with MetS (n=37) consumed a diet that matched self-reported macronutrient composition for nine days, with the exception that dietary fructose was reduced from 11.7±4.0% to 3.8±0.5% of daily calories and substituted with glucose (in starch). Participants underwent fasting biochemical analyses on Days 0 and 10. HDL and LDL subclasses were analyzed using the Lipoprint HDL and LDL subfraction analysis systems from Quantimetrix.ResultsSignificant reductions in apoB (78±24 vs. 66±24mg/dl) apoC-III (8.7±3.5 vs. 6.5±2.6mg/dl) and apoE (4.6±2.3 vs. 3.6±1.1mg/dl), all p&nbsp

Objective: To ascertain the prevalence of erectile dysfunction (ED), how it is perceived and the percentage seeking treatment for the condition in a population of men with cardiovascular disease (CVD) attending a cardiac rehabilitation programme in East London, United Kingdom (UK). Participants: 100 male participants aged between 30 and 88 years attending a cardiac rehabilitation centre in East London. Methods: An audit of men attending a cardiac rehabilitation programme was conducted. Participants completed the International Index of Erectile Function (IIEF-5) to ascertain the severity of ED; adapted ‘bother score’ item from the International Prostate Symptom Score (IPSS) to investigate the extent to which participants were bothered by the symptoms of their ED and questions related to both ED treatment-seeking and beliefs about the impact of cardiac medication on ED. Demographic and clinical data were also collected. The audit was carried out between January and September 2014. Results: Out of 117 male participants, 100 were audited (85.5% uptake). Prevalence of ED in this cohort was 80% and 38% were suffering with moderate or severe ED. Older men had significantly higher levels of ED and participants with severe ED were significantly more bothered by their condition. Those of Asian or British Asian descent reported significantly higher levels of ED severity than men from white ethnic backgrounds. 65% of men with ED had never spoken to a health care professional (HCP) about the condition and 35 % believed that their medication had a deleterious effect on erectile function. Conclusion: High incidences of ED remain undetected in this patient population. The study stresses the importance for HCPs to discuss ED with patients within primary care and cardiac rehabilitation programmes, which in turn could reduce mortality in those at risk of a future cardiac event, as well as facilitate access to ED treatment.

Background:Having a child with JIA presents many challenges. Many parents experience considerable stress. Parental distress and functioning have been found to be related to child outcomes (Cousino, 2013), therefore interventions that help parents to manage their child’s illness are important for both parents and child. We developed a website for parents of children with newly diagnosed JIA to help increase parental confidence in managing their child’s arthritis and reduce parenting stress.Objectives:To evaluate the efficacy of a web-based tool ‘WebParC’ for parents of children with JIA.Methods:Design:Multi-centre randomised controlled trial conducted in 16 tertiary paediatric rheumatology centres in England.Participants:Parent(s) of children aged ≤12 years, diagnosed with JIA within the previous six months.Procedures:Parents were enrolled when they attended the rheumatology service and were randomised by household to either the intervention arm (I) who were given access to the website in addition to their child’s standard care or the control arm (C) who received standard care alone.The primary outcome was parenting stress, measured with the Pediatric Inventory for Parents (PIP) (Streisand, 2001), which parents completed prior to randomisation and at 4-months and 12-months post randomisation.Website content was developed by a multidisciplinary team including rheumatology, physiotherapy, ophthalmology, social work, podiatry, occupational therapy, clinical and health psychology along with parents of children with JIA. It includes information about JIA and its treatment plus a ‘toolkit’ for parents. The toolkit is based on cognitive-behavioural principles to develop skills for managing JIA-related issues.Analysis:We conducted linear mixed models to examine the main effect of trial arm (I vs C), main effect of time (between 4M and 12M scores), and interaction between trial arm and time on PIP scores, after controlling for baseline scores.Results:A total of 220 parents (183 mothers, 37 fathers) of 203 children were randomised, 106 intervention and 114 controls. Parents mean (SD) age was 36.5 (6.5). Their children with JIA were mostly female (137/203, 67.5%), mean (SD) age of 6.1 (3.4) years. There were 107 (52.7%) with oligoarthritis, 65 (32%) polyarthritis, 8 (3.9%) systemic and 23 (11.3%) other JIA subtypes. Seventy (34.5%) were prescribed methotrexate.Trial arms did not differ significantly at baseline except for parent education, which was higher in the intervention group and was controlled for in the analysis.Follow-up assessments were completed by 133 (I60, C73) at 4M and 124 (I58, C66) at 12M.We found significant main effects of trial arm on PIP Difficulty (p=0.022, Control (Mean=93.62, SE=2.717) > Intervention (Mean=84.23, SE=3.025)) and PIP Frequency (p= 0.008, Control (Mean=95.78, SE=2.400) > Intervention (Mean=86.23, SE=2.622), with Controls reporting significantly greater frequency and difficulty of stressful events than the Intervention group (Fig 1).Conclusion:This trial found that a website for parents of children with JIA can help to reduce parenting stress.References:[1]Cousino MK, Hazen RA. J Pediatr Psychol 2013; 38(8):809-28[2]Streisand R, Braniecki S, Tercyak KP, Kazak AE. J Pediatr Psychol 2001; 26(3):155-62.Acknowledgments:We thank all parent participants, the health professionals and parents who developed website content and the clinical teams who supported recruitment.Funded by NIHR RfPB.Disclosure of Interests:Kathleen Mulligan: None declared, Shashivadan Hirani: None declared, Sally Clarke: None declared, Neil Evans: None declared, Chris Flood: None declared, Jo Taylor: None declared, Lucy Wedderburn Speakers bureau: Pfizer, Stanton Newman Grant/research support from: Yes Baxter Healthcare Educational Grants not in relation to rheumatology, Speakers bureau: Yes Baxter Healthcare and Merke Sharp and Dome

Background Tenofovir disoproxil fumarate (TDF) increases serum parathyroid hormone (PTH) and 1,25 dihydroxy vitamin D (1,25-(OH)2D), and decreases bone mineral density (BMD). Optimal treatment of TDF-associated BMD loss requires an understanding of the primary cause of these abnormalities. Methods Secondary review of data from two studies of TDF use in youth, comparing the relationship of PTH, 25-hydroxy vitamin D (25-OHD) and 1,25-(OH)2D in three groups with varying exposures to TDF: youth without HIV enrolled in a trial of TDF/emtricitabine (FTC) for HIV pre-exposure prophylaxis (PrEP) at baseline (no TDF exposure) and after 12 weeks of TDF (short-term TDF exposure); and youth with HIV treated with TDF-containing combination antiretroviral therapy (cART) for at least 6 months at study entry (long-term TDF exposure). Relationships were evaluated by correlation analyses. Results Participants ranged in age from 17 to 24 years and >50% were Black/African American. In persons not treated with TDF, PTH had the physiologically appropriate negative correlation with 25-OHD (r=-0.3504, P=0.004). Correlations between PTH and 25-OHD in groups treated with TDF were weaker or absent. With longer term TDF treatment in persons with HIV, 25-OHD and 1,25-(OH)2D had the positive correlation similar to that found in vitamin D deficiency. Conclusions TDF changes the relationship of 25-OHD to PTH, suggesting that in persons using TDF for PrEP or cART, a higher than usual target for serum 25-OHD concentration might be needed to reduce PTH and optimize bone health. Clinical trials registration: NCT01751646 (ATN 109) and NCT01769469 (ATN 117).

Background People with severe mental illnesses (SMI) such as schizophrenia and bipolar disorder have an increased risk of developing type 2 diabetes and have poorer health outcomes than those with diabetes alone. To maintain good diabetes control, people with diabetes are advised to engage in several self-management behaviours. The aim of this study was to identify barriers or enablers of diabetes self-management experienced by people with SMI. Methods Adults with type 2 diabetes and SMI were recruited through UK National Health Service organisations and mental health and diabetes charities. Participants completed an anonymous survey consisting of: Summary of Diabetes Self-Care Activities (SDSCA); CORE-10 measure of psychological distress; a measure of barriers and enablers of diabetes self-management based on the Theoretical Domains Framework; Diabetes UK care survey on receipt of 14 essential aspects of diabetes healthcare. To identify the strongest explanatory variables of SDSCA outcomes, significant variables (p

Author(s): Alba, Diana L; Wu, Lucy; Cawthon, Peggy M; Mulligan, Kathleen; Lang, Thomas; Patel, Sheena; King, Nicole J; Carter, Jonathan T; Rogers, Stanley J; Posselt, Andrew M; Stewart, Lygia; Shoback, Dolores M; Schafer, Anne L | Abstract: ContextBariatric surgery results in reduced muscle mass as weight is lost, but postoperative changes in muscle strength and performance are incompletely understood.ObjectiveTo examine changes in body composition, strength, physical activity, and physical performance following Roux-en-Y gastric bypass (RYGB).Design, participants, outcomesIn a prospective cohort of 47 adults (37 women, 10 men) aged 45 ± 12 years (mean ± SD) with body mass index (BMI) 44 ± 8 kg/m2, we measured body composition by dual-energy X-ray absorptiometry, handgrip strength, physical activity, and physical performance (chair stand time, gait speed, 400-m walk time) before and 6 and 12 months after RYGB. Relative strength was calculated as absolute handgrip strength/BMI and as absolute strength/appendicular lean mass (ALM).ResultsParticipants experienced substantial 12-month decreases in weight (-37 ± 10 kg or 30% ± 7%), fat mass (-48% ± 12%), and total lean mass (-13% ± 6%). Mean absolute strength declined by 9% ± 17% (P l 0.01). In contrast, relative strength increased by 32% ± 25% (strength/BMI) and 9% ± 20% (strength/ALM) (P l 0.01 for both). There were clinically significant postoperative improvements in all physical performance measures, including mean improvement in gait speed of g0.1 m/s (P l 0.01) and decrease in 400-m walk time of nearly a full minute.ConclusionsIn the setting of dramatic weight loss, lean mass and absolute grip strength declined after RYGB. However, relative muscle strength and physical function improved meaningfully and are thus noteworthy positive outcomes of gastric bypass.

Background: Antiretroviral drugs have been associated with changes in fat metabolism including lipids, fat mass and fat distribution. In HIV treatment, tenofovir disoproxil fumarate (TDF) has been shown to have a more favorable metabolic profile than other drugs in its class. However, the metabolic effects of TDF used as PrEP have not been reported. Methods: We evaluated the effects of TDF/FTC on lipids and body composition in participants in a blinded placebo controlled PrEP trial. Participants enrolled in a metabolic subcohort (N=251, TDF/FTC; N=247, placebo) consented to fasting lipid panels, dual-energy X-ray absorptiometry (DXA) scans for body composition and pharmacologic testing of plasma and intracellular tenofovir diphosphate levels at baseline and every 24 weeks thereafter. Results: Lean body mass was stable and unaffected by TDF/FTC. Body weight increased in both groups but was lower on TDF/FTC through week 72. This difference was explained by lower fat accumulation on TDF/FTC. The net median percent difference (SE, p-value) for TDF/FTC v. placebo at week 24 was -0.8% (0.4%, p=0.02), +0.3% (0.4%, p=0.46), -3.8% (1.4%, p=0.009) for total, lean and fat mass, respectively. There was no apparent differential regional fat accumulation on TDF/FTC. Decreases in cholesterol, but not triglycerides, were seen in TDF/FTC participants with detectable drug levels compared with placebo. Conclusions: TDF/FTC for PrEP showed cholesterol reductions and appeared to transiently suppress the accumulation of weight and body fat, compared to placebo. There was no evidence of altered fat distribution or lipodystrophy during daily oral TDF/FTC PrEP.