Examining the dynamics of Epstein-Barr virus shedding in the tonsils and the impact of HIV-1 coinfection on daily saliva viral loads.

Epstein-Barr virus (EBV) is transmitted by saliva and is a major cause of cancer, particularly in people living with HIV/AIDS. Here, we describe the frequency and quantity of EBV detection in the saliva of Ugandan adults with and without HIV-1 infection and use these data to develop a novel mathematical model of EBV infection in the tonsils. Eligible cohort participants were not taking antiviral medications, and those with HIV-1 infection had a CD4 count >200 cells/mm3. Over a 4-week period, participants provided daily oral swabs that we analysed for the presence and quantity of EBV. Compared with HIV-1 uninfected participants, HIV-1 coinfected participants had an increased risk of EBV detection in their saliva (IRR = 1.27, 95% CI = 1.10-1.47) and higher viral loads in positive samples. We used these data to develop a stochastic, mechanistic mathematical model that describes the dynamics of EBV, infected cells, and immune response within the tonsillar epithelium to analyse potential factors that may cause EBV infection to be more severe in HIV-1 coinfected participants. The model, fit using Approximate Bayesian Computation, showed high fidelity to daily oral shedding data and matched key summary statistics. When evaluating how model parameters differed among participants with and without HIV-1 coinfection, results suggest HIV-1 coinfected individuals have higher rates of B cell reactivation, which can seed new infection in the tonsils and lower rates of an EBV-specific immune response. Subsequently, both these traits may explain higher and more frequent EBV detection in the saliva of HIV-1 coinfected individuals.

A scoping review of non-specific predictors, moderators, and mediators of family-based treatment for adolescent anorexia and bulimia nervosa: a summary of the current research findings.

PURPOSE: This scoping review presents an up-to-date synthesis of the current evidence base for non-specific predictors, moderators, and mediators of family-based treatment (FBT) for adolescent anorexia and bulimia nervosa. METHODS: We identify ways in which end-of-treatment outcomes have been shown to differ based upon baseline clinical features and person-specific factors and explore psychological mechanisms that may explain differences in treatment response. We draw from this evidence base to outline recommendations for clinical practice, as well as directions for future clinical eating disorder research. RESULTS: Noted findings from review include that early response in weight gain and parental criticism may be particularly influential in treatment for anorexia nervosa. Further, for adolescents with either anorexia or bulimia nervosa, eating-related obsessionality may be a key intervention target to improve outcomes. CONCLUSION: In addition to highlighting a need for attention to specific patient- and caregiver-level factors that impact treatment response, recommendations for research and clinical practice include testing whether certain targeted treatments (e.g., exposure-based approaches) may be suitable within the context of FBT for eating disorders. LEVEL OF EVIDENCE: Level I: Evidence obtained from: at least one properly designed randomized controlled trials; experimental studies.

Effects of spatiotemporal HSV-2 lesion dynamics and antiviral treatment on the risk of HIV-1 acquisition.

Patients with Herpes Simplex Virus-2 (HSV-2) infection face a significantly higher risk of contracting HIV-1. This is thought to be due to herpetic lesions serving as entry points for HIV-1 and tissue-resident CD4+ T cell counts increasing during HSV-2 lesional events. We have created a stochastic and spatial mathematical model describing the dynamics of HSV-2 infection and immune response in the genital mucosa. Using our model, we first study the dynamics of a developing HSV-2 lesion. We then use our model to quantify the risk of infection with HIV-1 following sexual exposure in HSV-2 positive women. Untreated, we find that HSV-2 infected women are up to 8.6 times more likely to acquire HIV-1 than healthy patients. However, when including the effects of the HSV-2 antiviral drug, pritelivir, the risk of HIV-1 infection is predicted to decrease by up to 35%, depending on drug dosage. We estimate the relative importance of decreased tissue damage versus decreased CD4+ cell presence in determining the effectiveness of pritelivir in reducing HIV-1 infection. Our results suggest that clinical trials should be performed to evaluate the effectiveness of pritelivir or similar agents in preventing HIV-1 infection in HSV-2 positive women.

The association between medication non-adherence and adverse health outcomes in ageing populations: A systematic review and meta-analysis.

AIMS: The aim of this systematic review and meta-analysis was to synthesise the evidence relating to medication non-adherence and its association with health outcomes in people aged ≥50 years. METHODS: Seven databases were searched up to February 2019 for observational studies that measured medication (non-)adherence as a predictor of the following health outcomes in adults aged ≥50 years: healthcare utilisation (hospitalisation, emergency department visits, outpatient visits and general practitioner visits), mortality, adverse clinical events and quality of life. Screening and quality assessment using validated criteria were completed by 2 reviewers independently. Random effects models were used to generate pooled estimates of association using adjusted study results. The full methodological approach was published on PROSPERO (ID: CRD42017077264). RESULTS: Sixty-six studies were identified for qualitative synthesis, with 11 of these studies eligible for meta-analyses. A meta-analysis including 3 studies measuring medication non-adherence in adults aged ≥55 years showed a significant association with all-cause hospitalisation (adjusted odds ratio 1.17, 95% confidence interval [CI] 1.12, 1.21). A meta-analysis including 2 studies showed that medication non-adherence was not significantly associated with an emergency department visit (adjusted odds ratio 1.05, 95% CI 0.90, 1.22). Good adherence was associated with a 21% reduction in long-term mortality risk in comparison to medication non-adherence (adjusted hazard ratio 0.79, 95% CI 0.63, 0.98). CONCLUSION: Medication non-adherence may be significantly associated with all-cause hospitalisation and mortality in older people. Medication adherence should be monitored and addressed in this cohort to minimise hospitalisation, improve clinical outcomes and reduce healthcare costs.

Identifying Adverse Drug Events in Older Community-Dwelling Patients.

PURPOSE: To evaluate a patient-report instrument for identifying adverse drug events (ADEs) in older populations with multimorbidity in the community setting. METHODS: This was a retrospective cohort study of 859 community-dwelling patients aged ≥70 years treated at 15 primary care practices. Patients were asked if they had experienced any of a list of 74 symptoms classified by physiologic system in the previous 6 months and if (1) they believed the symptom to be related to their medication, (2) the symptom had bothered them, (3) they had discussed it with their family physician, and (4) they required hospital care due to the symptom. Self-reported symptoms were independently reviewed by 2 clinicians who determined the likelihood that the symptom was an ADE. Family physician medical records were also reviewed for any report of an ADE. RESULTS: The ADE instrument had an accuracy of 75% (95% CI, 77%-79%), a sensitivity of 29% (95% CI, 27%-31%), and a specificity of 93% (95% CI, 92%-94%). Older people who reported a symptom had an increased likelihood of an ADE (positive likelihood ratio [LR+]: 4.22; 95% CI, 3.78-4.72). Antithrombotic agents were the drugs most commonly associated with ADEs. Patients were most bothered by muscle pain or weakness (75%), dizziness or lightheadedness (61%), cough (53%), and unsteadiness while standing (52%). On average, patients reported 39% of ADEs to their physician. Twenty-six (3%) patients attended a hospital outpatient clinic, and 32 (4%) attended an emergency department due to ADEs. CONCLUSION: Older community-dwelling patients were often not correct in recognizing ADEs. The ADE instrument demonstrated good predictive value and could be used to differentiate between symptoms of ADEs and chronic disease in the community setting.

Population pharmacokinetics of total and unbound concentrations of intravenous posaconazole in adult critically ill patients.

BACKGROUND: The population pharmacokinetics of total and unbound posaconazole following intravenous administration has not yet been described for the critically ill patient population. The aim of this work was, therefore, to describe the total and unbound population pharmacokinetics of intravenous posaconazole in critically ill patients and identify optimal dosing regimens. METHODS: This was a prospective observational population pharmacokinetic study in critically ill adult patients with presumed/confirmed invasive fungal infection. A single dose of 300 mg posaconazole was administered intravenously as an add-on to standard antifungal therapy, and serial plasma samples were collected over 48 h. Total and unbound posaconazole concentrations, measured by chromatographic method, were used to develop a population pharmacokinetic model and perform dosing simulations in R using Pmetrics. RESULTS: From eight patients, 93 pairs of total and unbound concentrations were measured. A two-compartment linear model with capacity-limited plasma protein binding best described the concentration-time data. Albumin and body mass index (BMI) were included as covariates in the final model. Mean (SD) parameter estimates for the volume of the central compartment (V) and the elimination rate constant were 72 (43) L and 42.1 (23.7) h-1, respectively. Dosing simulations showed that high BMI was associated with a reduced probability of achieving target total and unbound posaconazole concentrations. Low serum albumin concentration was associated with a reduced probability of attaining target total but not unbound posaconazole concentrations. CONCLUSIONS: An important clinical message of this study is that critically ill patients with increased BMI may require larger than approved loading doses of intravenous posaconazole when considering currently recommended dosing targets. Variability in plasma albumin concentration appears unlikely to affect dosing requirements when the assessment is based on unbound concentrations. Where available, therapeutic drug monitoring of unbound concentrations may be useful.

Impact of drug burden index on adverse health outcomes in Irish community-dwelling older people: a cohort study.

BACKGROUND: The Drug Burden Index (DBI) quantifies exposure to medications with anticholinergic and/or sedative effects. A consensus list of DBI medications available in Ireland was recently developed for use as a DBI tool. The aim of this study was to validate this DBI tool by examining the association of DBI score with important health outcomes in Irish community-dwelling older people. METHODS: This was a cohort study using data from The Irish Longitudinal Study on Ageing (TILDA) with linked pharmacy claims data. Individuals aged ≥65 years participating in TILDA and enrolled in the General Medical Services scheme were eligible for inclusion. DBI score was determined by applying the DBI tool to participants' medication dispensing data in the year prior to outcome assessment. DBI score was recoded into a categorical variable [none (0), low (> 0 and < 1), and high (≥1)]. Outcome measures included any Activities of Daily Living (ADL) impairment, any Instrumental Activities of Daily Living (IADL) impairment, any self-reported fall in the previous 12 months, any frailty criterion met (Fried Phenotype measure), quality of life (QoL) score (CASP-19 [Control Autonomy Self-realisation Pleasure] measure), and healthcare utilisation (any hospital admission and any emergency department (ED) visit) in the previous 12 months. Statistical analyses included multivariate logistic and linear regression models controlling for potential confounders. RESULTS: 61.3% (n = 1946) of participants received at least one DBI prescription in the year before their outcome assessment. High DBI exposure (DBI score ≥ 1) vs none was significantly associated with impaired function (ADL impairment adjusted OR 1.89, 95% CI 1.25, 2.88; IADL impairment adjusted OR 2.97, 95% CI 1.91, 4.61), self-reported falls (adjusted OR 1.50, 95%CI 1.03, 2.18), frailty (adjusted OR 1.74, 95% CI 1.14, 2.67), and reduced QoL (ß = - 1.84, 95%CI -3.14, - 0.54). There was no significant association between DBI exposure and healthcare utilisation. CONCLUSIONS: The findings validate the use of the DBI tool for predicting risk of functional impairment, falls, frailty and reduced QoL in older people in Ireland, and may be extended to other European countries. Integration of this tool into routine practice may be an appropriate step forward to improve outcomes in older people.

Long- and short-term outcomes in renal allografts with deceased donors: A large recipient and donor genome-wide association study.

Improvements in immunosuppression have modified short-term survival of deceased-donor allografts, but not their rate of long-term failure. Mismatches between donor and recipient HLA play an important role in the acute and chronic allogeneic immune response against the graft. Perfect matching at clinically relevant HLA loci does not obviate the need for immunosuppression, suggesting that additional genetic variation plays a critical role in both short- and long-term graft outcomes. By combining patient data and samples from supranational cohorts across the United Kingdom and European Union, we performed the first large-scale genome-wide association study analyzing both donor and recipient DNA in 2094 complete renal transplant-pairs with replication in 5866 complete pairs. We studied deceased-donor grafts allocated on the basis of preferential HLA matching, which provided some control for HLA genetic effects. No strong donor or recipient genetic effects contributing to long- or short-term allograft survival were found outside the HLA region. We discuss the implications for future research and clinical application.

Population pharmacokinetics of total and unbound teicoplanin concentrations and dosing simulations in patients with haematological malignancy.

Objectives: To develop a pharmacokinetic model describing total and unbound teicoplanin concentrations in patients with haematological malignancy and to perform Monte Carlo simulations to evaluate target attainment of unbound trough concentrations with various dose regimens. Methods: This was a hospital-based clinical trial (EudraCT 2013-004535-72). The dosing regimen was 600/800 mg q12h for three doses then 600/800 mg daily. Serial total and unbound teicoplanin concentrations were collected. Maximum protein binding was estimated from serum albumin concentration. Population pharmacokinetic analyses and Monte Carlo simulations were conducted using Pmetrics®. Target total and unbound trough concentrations were ≥20 and ≥1.5 mg/L, respectively. Results: Thirty adult patients were recruited with a mean (SD) bodyweight of 69.1 (15.8) kg, a mean (SD) CLCR of 72 (41) mL/min and a median (IQR) serum albumin concentration of 29 (4) g/L. A three-compartment complex binding pharmacokinetic model best described the concentration-time data. Total and unbound teicoplanin concentrations were related by serum albumin concentration and a dissociation constant. CLCR and bodyweight were supported as covariates for CL and volume of the central compartment, respectively. Dosing simulations showed that high CLCR was associated with reduced probability of achieving target total and unbound trough concentrations. Low serum albumin concentration was associated with a reduced probability of attaining target total but not unbound trough concentrations. A method to estimate the unbound teicoplanin concentration from the measured total concentration at different serum albumin concentration was demonstrated. Conclusions: Standard teicoplanin dosing regimens should be used with caution in patients with haematological malignancy. Bodyweight, CLCR and serum albumin concentration are important considerations for appropriate dosing.

Using bivariate latent basis growth curve analysis to better understand treatment outcome in youth with anorexia nervosa.

OBJECTIVE: This study explored the relation between eating-related obsessionality and weight restoration utilizing bivariate latent basis growth curve modelling. Eating-related obsessionality is a moderator of treatment outcome for adolescents with anorexia nervosa (AN). This study examined the degree to which the rate of change in eating-related obsessionality was associated with the rate of change in weight over time in family-based treatment (FBT) and individual therapy for AN. METHOD: Data were drawn from a 2-site randomized controlled trial that compared FBT and adolescent focused therapy for AN. Bivariate latent basis growth curves were used to examine the differences of the relations between trajectories of body weight and symptoms associated with eating and weight obsessionality. RESULTS: In the FBT group, the slope of eating-related obsessionality scores and the slope of weight were significantly (negatively) correlated. This finding indicates that a decrease in overall eating-relating obsessionality is significantly associated with an increase in weight for individuals who received FBT. However, there was no relation between change in obsessionality scores and change in weight in the adolescent focused therapy group. DISCUSSION: Results suggest that FBT has a specific impact on both weight gain and obsessive compulsive behaviour that is distinct from individual therapy.

Negative urgency and expectancies increase vulnerability to binge eating in bulimia nervosa.

Negative urgency (NU), the tendency to act impulsively when distressed, is associated with binge eating. Women who believe that eating alleviates negative affect are also more likely to binge eat. Thus, it is hypothesized that the individuals with high levels of NU, and who endorse these eating expectancies, will binge eat the following acute distress. This study tested these hypotheses using ecological momentary assessment. Sixteen women with the symptoms of BN completed clinical assessments, and were asked to report on distress and binges multiple times daily for two weeks. NU moderated the temporal relationship of negative affect to binges, such that women with lower scores on NU experienced a sharper increase in affect prior to binges. Individual differences in eating expectancies also moderated the relationship of affect to binge eating. Results suggest that women with high levels of NU and expectancy endorsement are triggered to binge by smaller shifts in negative affect than women who do not endorse these traits.

Variability in Trough Total and Unbound Teicoplanin Concentrations and Achievement of Therapeutic Drug Monitoring Targets in Adult Patients with Hematological Malignancy.

The objective of this study was to explore the following aspects of teicoplanin use in patients with hematological malignancy: early attainment of target trough concentrations with current high-dose teicoplanin regimens, variability in unbound teicoplanin fractions, factors associated with observed total and unbound trough concentrations, efficacy and toxicity, and renal function estimation. This was a single-center, prospective study. Samples for determination of trough concentrations were taken on days 3, 4, 7, and 10. Total and unbound teicoplanin concentrations were determined using validated high-performance liquid chromatography methods. Regression analyses were used to identify the factors associated with the trough concentration. Thirty teicoplanin-treated adults with hematological malignancy were recruited. Despite the use of dosages higher than the conventional dosages, the proportions of patients with a trough concentration of ≥20 mg/liter at 48 h and at 72 h were 16.7% and 37.9%, respectively. Renal function was significantly negatively associated with total trough concentrations at 48 h and 72 h (P < 0.05). For an average hematological malignancy patient (creatinine clearance = 70 ml/min), sequential loading doses of at least 12 mg/kg of body weight may be needed to achieve early adequate exposure. In the absence of measured creatinine clearance, estimates obtained using the Cockcroft-Gault (total body weight) equation could prove to be an acceptable surrogate. The unbound fractions of teicoplanin were highly variable (3.4 to 18.8%). Higher unbound fractions were observed in patients with low serum albumin concentrations. Teicoplanin was well tolerated. Teicoplanin loading doses higher than those in current use appear to be necessary. Increased dosing is needed in patients with increased renal function. The high variability in protein binding supports the contention for therapeutic drug monitoring of unbound teicoplanin concentrations. (This study has been registered with EudraCT under registration no. 2013-004535-72.).

High-risk prescribing in an Irish primary care population: trends and variation.

AIMS: The aims of the present study were to examine the prevalence of high-risk prescribing (HRP) in community-dwelling adults in Ireland from 2011-2015 using consensus-validated indicators, factors associated with HRP, and the variation in HRP between general practitioners (GPs) and in the dispensing of high-risk prescriptions between pharmacies. METHODS: A repeated cross-sectional national pharmacy claims database study was conducted. Prescribing indicators were based on those developed in formal consensus studies and applicable to pharmacy claims data. Multilevel logistic regression was used to examine factors associated with HRP and dispensing. RESULTS: There were significant reductions in the rates of most indicators over time (P < 0.001). A total of 66 022 of 300 906 patients at risk in 2011 [21.9%, 95% confidence interval (CI) 21.8, 22.1%], and 42 109 of 278 469 in 2015 (15.1%, 95% CI 15.0, 15.3%), received ≥1 high-risk prescription (P < 0.001). In 2015, indicators with the highest rates of HRP were prescription of a nonsteroidal anti-inflammatory drug (NSAID) without gastroprotection in those ≥75 years (37.2% of those on NSAIDs), coprescription of warfarin and an antiplatelet agent or high-risk antibiotic (19.5% and 16.2% of those on warfarin, respectively) and prescription of digoxin ≥250 µg day-1 in those ≥65 years (14.0% of those on digoxin). Any HRP increased significantly with age and number of chronic medications (P < 0.001). a) After controlling for patient variables, the variation in the rate of HRP between GPs was significant (P < 0.05); and b) after controlling for patient variables and the prescribing GP, the variation in the rate of dispensing of high-risk prescriptions between pharmacies was significant (P < 0.05). CONCLUSIONS: HRP in Ireland has declined over time, although some indicators persist. The variation between GPs and pharmacies suggests the potential for improvement in safe medicines use in community care, particularly in vulnerable older populations.

Utilizing Telehealth to deliver family-based treatment for adolescent anorexia nervosa.

OBJECTIVE: The purpose of this study was to test the feasibility and preliminary effect size on the main outcome measure (weight gain) of family-based treatment (FBT) for adolescents with anorexia nervosa (AN) and their families delivered via a Telehealth platform (i.e., an HIPAA compliant videoconferencing format). METHOD: Ten adolescents, mean age of 16.08 years (SD = 1.99), meeting DSM-5 criteria for AN or atypical AN, were enrolled in the study and offered FBT via a Telehealth platform. Feasibility and acceptability were evaluated by rates of recruitment and retention. Treatment outcome was determined utilizing percent median body mass index (%mBMI), the eating disorder examination (EDE), and measures for depression and self-esteem. RESULTS: Recruitment target was achieved within allotted time, and all participants were retained for the course of treatment. Percent mBMI improved significantly from baseline to the end-of-treatment (p = .013) and from baseline to the 6-month follow-up (p = .032). Similar results were achieved for the EDE Global Score (p = .002 and .001, respectively). DISCUSSION: These findings provide preliminary evidence that it is feasible to deliver FBT via Telehealth and that satisfactory clinical outcomes are achievable.

An exploratory examination of patient and parental self-efficacy as predictors of weight gain in adolescents with anorexia nervosa.

OBJECTIVE: To determine whether increases in adolescent or parental self-efficacy predicted subsequent weight gain in two different therapies for adolescent anorexia nervosa (AN). METHOD: Participants were 121 adolescents with AN (M = 14.4 years, SD = 1.6), from a two-site randomized clinical trial for family-based treatment (FBT) and individual adolescent focused therapy (AFT). Both adolescent and parental self-efficacy were assessed at baseline and sessions 2, 4, 6, and 8. Adolescent self-efficacy was assessed using a generic measure of self-efficacy, while parental self-efficacy was assessed using a measure specific to the recovery of an eating disorder. Weight was assessed at baseline, sessions 1 through 8, and end of treatment. Mixed-effects models were used to evaluate the relation between patient and parent self-efficacy and subsequent weight gain, controlling for weight at the previous time point. RESULTS: For families who received FBT, greater within-treatment increases in parental self-efficacy predicted greater subsequent adolescent weight gain compared to those who received FBT with lesser change in parental self-efficacy and those who received AFT. Interestingly, adolescent self-efficacy did not significantly predict subsequent weight gain. DISCUSSION: Greater increases in parental self-efficacy predicted significantly greater subsequent weight gain for adolescents who received FBT, but the same was not true for adolescents who received AFT. Neither overall level nor change in adolescent self-efficacy significantly predicted subsequent weight gain in either treatment group. These findings emphasize the importance of increasing parental self-efficacy in FBT in order to impact adolescent weight outcomes.

Picking and nibbling in children and adolescents with eating disorders.

OBJECTIVE: Picking and nibbling (P&N), defined as eating in an unplanned and repetitious way between meals and snacks, is prevalent among adults with eating disorders (EDs), but unexamined among youth with EDs. This study sought to assess the prevalence of P&N in youth with EDs and its association with ED and comorbid pathology. METHOD: Youth (N = 515; ages 7-18) who presented to one outpatient ED research-clinical program were assessed for ED and comorbid pathology. RESULTS: Two-fifths (n = 214, 41.6%) of youth endorsed P&N. These individuals were older (p < .001) and had a higher percent expected body weight (p = .006) than those who denied P&N. Controlling for age and percent expected body weight, P&N was only associated with global ED pathology in youth with anorexia nervosa (AN) or atypical AN (p = .007). P&N was not associated with ED diagnosis, ED pathology in youth with bulimia nervosa or subclinical bulimia nervosa, binge eating, compensatory behaviors, secret eating, or the presence of a mood or anxiety disorder (p's > .05). DISCUSSION: Consistent with research in adults, P&N is prevalent but not significantly associated with ED pathology, except for global ED pathology in youth with AN/atypical AN, or comorbid disorders.

Eating patterns in youth with restricting and binge eating/purging type anorexia nervosa.

OBJECTIVE: To describe eating patterns in youth with restricting and binge/purge type anorexia nervosa (AN) and to examine whether eating patterns are associated with binge eating or purging behaviors. METHOD: Participants included 160 children and adolescents (M = 15.14 ± 2.17 years) evaluated at The University of Chicago Eating Disorders Program who met criteria for DSM-5 restrictive type AN (AN-R; 75%; n = 120) or binge eating/purging type AN (AN-BE/P; 25%; n = 40). All participants completed the eating disorder examination on initial evaluation. RESULTS: Youth with AN-R and AN-BE/P differed in their eating patterns, such that youth with AN-R consumed meals and snacks more regularly relative to youth with AN-BE/P. Among youth with AN-BE/P, skipping dinner was associated with a greater number of binge eating episodes (r = -.379, p < .05), while skipping breakfast was associated with a greater number of purging episodes (r = -.309, p < .05). DISCUSSION: Youth with AN-R generally follow a regular meal schedule, but are likely consuming insufficient amounts of food across meals and snacks. In contrast, youth with AN-BE/P tend to have more irregular eating patterns, which may play a role in binge eating and purging behaviors. Adults monitoring of meals may be beneficial for youth with AN, and particularly those with AN-BE/P who engage in irregular eating patterns.

Subjective and objective binge eating in relation to eating disorder symptomatology, depressive symptoms, and self-esteem among treatment-seeking adolescents with bulimia nervosa.

This study investigated the importance of the distinction between objective (OBE) and subjective binge eating (SBE) among 80 treatment-seeking adolescents with bulimia nervosa. We explored relationships among OBEs, SBEs, eating disorder (ED) symptomatology, depression, and self-esteem using two approaches. Group comparisons showed that OBE and SBE groups did not differ on ED symptoms or self-esteem; however, the SBE group had significantly greater depression. Examining continuous variables, OBEs (not SBEs) accounted for significant unique variance in global ED pathology, vomiting, and self-esteem. SBEs (not OBEs) accounted for significant unique variance in restraint and depression. Both OBEs and SBEs accounted for significant unique variance in eating concern; neither accounted for unique variance in weight/shape concern, laxative use, diuretic use, or driven exercise. Loss of control, rather than amount of food, may be most important in defining binge eating. Additionally, OBEs may indicate broader ED pathology, while SBEs may indicate restrictive/depressive symptomatology.

Modestly protective cytomegalovirus vaccination of young children effectively prevents congenital infection at the population level.

A vaccine to prevent congenital cytomegalovirus infection (cCMV) is a public health priority. cCMV results from maternal primary or non-primary CMV infection (reinfection, or reactivation of chronic infection) during pregnancy. Young children are a major source of transmission to pregnant women because they shed CMV at high viral loads for prolonged periods. CMV vaccines evaluated in clinical trials so far have demonstrated only approximately 50% efficacy against maternal primary infection. None of these have been approved, as higher levels of vaccine efficacy are assumed to be required to substantially reduce cCMV prevalence. Here, we designed a mathematical model to capture the relationship between viral shedding by young children and maternal CMV infections during pregnancy. Using this model, we were able to quantify the impact of CMV post-infection immunity on protecting against reinfection and viral shedding. There was a 36% reduction in the risk of infection to a seropositive person with post-infection immunity (reinfection) versus a seronegative person without this immunity (primary infection), given the same exposure. Viral shedding following reinfection was only 34% the quantity of that following primary infection. Our model also predicted that a vaccine that confers the equivalent of post-infection immunity, when given to young children, would markedly reduce both CMV transmission to pregnant women and the prevalence of cCMV. Thus, we predict that existing vaccine candidates that have been shown to be only modestly protective may in fact be highly effective at preventing cCMV by interrupting child-to-mother transmission.

Joubert syndrome diagnosed renally late.

Joubert syndrome is a genetically heterogeneous multisystem disorder typically diagnosed in childhood. Nephronophthisis is the most common renal pathology in Joubert syndrome, and renal failure usually occurs in childhood or in young adults. We report a 61-year-old female diagnosed with AHI1-related oculorenal Joubert syndrome, who presented initially with decline in renal function in her 50s. Our report describes exceptionally late presentation of renal disease in Joubert syndrome and highlights the importance of continued renal function monitoring in older adults with Joubert syndrome.