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OBJECTIVE: The StRONG trial demonstrated the safety and efficacy of higher calorie refeeding (HCR) in hospitalized adolescents and young adults with malnutrition secondary to restrictive eating disorders. Here we compare refeeding outcomes in patients with atypical anorexia nervosa (atypical AN) versus anorexia nervosa (AN) and examine the impact of caloric dose. METHOD: Patients were enrolled upon admission and randomized to meal-based HCR, beginning 2000 kcal/day and advancing 200 kcal/day, or lower calorie refeeding (LCR), beginning 1400 kcal/day and advancing 200 kcal every other day. Atypical AN was defined as %median BMI (mBMI) > 85. Independent t-tests compared groups; multivariable linear and logistic regressions examined caloric dose (kcal/kg body weight). RESULTS: Among n = 111, mean ± SD age was 16.5 ± 2.5 yrs; 43% had atypical AN. Compared to AN, atypical AN had slower heart rate restoration (8.7 ± 4.0 days vs. 6.5 ± 3.9 days, p = .008, Cohens d = -.56), less weight gain (3.1 ± 5.9%mBMI vs. 5.4 ± 2.9%mBMI, p

The Alaskan Layered Pollution And Chemical Analysis (ALPACA) field experiment was a collaborative study designed to improve understanding of pollution sources and chemical processes during winter (cold climate and low-photochemical activity), to investigate indoor pollution, and to study dispersion of pollution as affected by frequent temperature inversions. A number of the research goals were motivated by questions raised by residents of Fairbanks, Alaska, where the study was held. This paper describes the measurement strategies and the conditions encountered during the January and February 2022 field experiment, and reports early examples of how the measurements addressed research goals, particularly those of interest to the residents. Outdoor air measurements showed high concentrations of particulate matter and pollutant gases including volatile organic carbon species. During pollution events, low winds and extremely stable atmospheric conditions trapped pollution below 73 m, an extremely shallow vertical scale. Tethered-balloon-based measurements intercepted plumes aloft, which were associated with power plant point sources through transport modeling. Because cold climate residents spend much of their time indoors, the study included an indoor air quality component, where measurements were made inside and outside a house to study infiltration and indoor sources. In the absence of indoor activities such as cooking and/or heating with a pellet stove, indoor particulate matter concentrations were lower than outdoors; however, cooking and pellet stove burns often caused higher indoor particulate matter concentrations than outdoors. The mass-normalized particulate matter oxidative potential, a health-relevant property measured here by the reactivity with dithiothreiol, of indoor particles varied by source, with cooking particles having less oxidative potential per mass than pellet stove particles.

The burden of cervical cancer is disproportionately distributed globally, with the vast majority of cases occurring in low- and middle-income countries. Women with human immunodeficiency virus (HIV) (WWH) are at increased risk of human papillomavirus (HPV) infection and cervical cancer as compared to HIV-negative individuals. HPV vaccination remains a priority in regions with a high burden of cervical cancer and high HIV prevalence. With HPV vaccines becoming more accessible, optimal use beyond the initial World Health Organization-recommended target population of 9 to 14-year-old girls is an important question. In March 2022, a group of experts in epidemiology, immunology, and vaccinology convened to discuss the state-of-the-science of HPV vaccination in WWH. This report summarizes the proceedings: review of HIV epidemiology and its intersection with cervical cancer burden, immunology, HPV vaccination including reduced-dose schedules and experience with other vaccines in people with HIV (PWH), HPV vaccination strategies and knowledge gaps, and outstanding research questions. Studies of HPV vaccine effectiveness among WWH, including duration of protection, are limited. Until data from ongoing research is available, the current recommendation for WWH remains for a multi-dose HPV vaccination regimen. A focus of the discussion included the potential impact of HIV acquisition following HPV vaccination. With no data currently existing for HPV vaccines and limited information from non-HPV vaccines, this question requires further research. Implementation research on optimal HPV vaccine delivery approaches for WWH and other priority populations is also urgently needed.

Introduction Over 265 000 women are living with HIV in the USA, but limited research has investigated the physical, mental and behavioural health outcomes among women living with HIV of reproductive age. Health status during the reproductive years before, during and after pregnancy affects pregnancy outcomes and long-term health. Understanding health outcomes among women living with HIV of reproductive age is of substantial public health importance, regardless of whether they experience pregnancy. The Health Outcomes around Pregnancy and Exposure to HIV/Antiretrovirals (HOPE) study is a prospective observational cohort study designed to investigate physical and mental health outcomes of young women living with HIV as they age, including HIV disease course, engagement in care, reproductive health and choices and cardiometabolic health. We describe the HOPE study design, and characteristics of the first 437 participants enrolled as of 1 January 2024.Methods and analysis The HOPE study seeks to enrol and follow 1630 women living with HIV of reproductive age, including those with perinatally-acquired HIV, at 12 clinical sites across 9 US states and Puerto Rico. HOPE studies multilevel dynamic determinants influencing physical, mental and social well-being and behaviours of women living with HIV across the reproductive life course (preconception, pregnancy, post partum, not or never-pregnant), informed by the socioecological model. Key research areas include the clinical course of HIV, relationship of HIV and antiretroviral medications to reproductive health, pregnancy outcomes and comorbidities and the influence of racism and social determinants of health. HOPE began enrolling in April 2022.Ethics and dissemination The HOPE study received approval from the Harvard Longwood Campus Institutional Review Board, the single institutional review board of record for all HOPE sites. Results will be disseminated through conference presentations, peer-reviewed journals and lay summaries.

BackgroundUnderstanding the natural history of anal high-risk human papillomavirus (hrHPV) infection is key for designing anal cancer prevention programs but has not been systematically characterized.MethodsWe reanalyzed data from 34 studies including 16 164 individuals in 6 risk groups defined by human immunodeficiency virus (HIV) status, sex, and male sexuality: men who have sex with men (MSM) and people with HIV (MSMWH), HIV-negative MSM, women with HIV (WWH), HIV-negative women, men who have sex with women (MSW) with HIV (MSWWH), and HIV-negative MSW. We used Markov models to estimate incidence and clearance of 13 hrHPV types and their determinants.ResultsHuman papillomavirus (HPV) 16 had the highest incidence-clearance ratio of the hrHPV types. MSMWH had the highest hrHPV incidence (eg, 15.5% newly HPV-16 infected within 2 years), followed by HIV-negative MSM (7.5%), WWH (6.6%), HIV-negative women (2.9%), MSWWH (1.7%), and HIV-negative MSW (0.7%). Determinants of HPV-16 incidence included HIV status and number of sexual partners for MSM, women, and MSW, and anal sex behavior for MSM only. HPV-16 clearance was lower for people with HIV (PWH) and lower for prevalent than incident infection. Among MSM, increasing age was associated with lower clearance of prevalent, but not incident, HPV-16 infection.ConclusionsThis robust and unifying analysis of anal hrHPV natural history is essential to designing and predicting the impact of HPV vaccination and HPV-based screening programs on anal cancer prevention, particularly in MSM and PWH. Importantly, it demonstrates the higher carcinogenic potential of longstanding anal prevalent hrHPV infection than more recent incident infection.

BackgroundAge-specific data on anal, and corresponding cervical, human papillomavirus (HPV) infection are needed to inform female anal cancer prevention.MethodsWe centrally reanalyzed individual-level data from 26 studies reporting HPV prevalence in paired anal and cervical samples by human immunodeficiency virus (HIV) status and age. For women with HIV (WWH) with anal high-grade squamous intraepithelial lesions or worse (HSIL+), we also investigated concurrent cervical cytopathology.ResultsIn HIV-negative women, HPV16 prevalence decreased significantly with age, both at anus (4.3% at 15-24 years to 1.0% at ≥55 years; ptrend = 0.0026) and cervix (7.4% to 1.7%; ptrend < 0.0001). In WWH, HPV16 prevalence decreased with age at cervix (18.3% to 7.2%; ptrend = 0.0035) but not anus (11.5% to 13.9%; ptrend = 0.5412). Given anal HPV16 positivity, concurrent cervical HPV16 positivity also decreased with age, both in HIV-negative women (ptrend = 0.0005) and WWH (ptrend = 0.0166). Among 48 WWH with HPV16-positive anal HSIL+, 27 (56%) were cervical high-risk HPV-positive, including 8 with cervical HPV16, and 5 were cervical HSIL+.ConclusionsAge-specific shifts in HPV16 prevalence from cervix to anus suggest that HPV infections in the anus persist longer, or occur later in life, than in the cervix, particularly in WWH. This is an important consideration when assessing the utility of cervical screening results to stratify anal cancer risk.

Cervical cancer has killed millions of women over the past decade. In 2019 the World Health Organization launched the Cervical Cancer Elimination Strategy, which included ambitious targets for vaccination, screening, and treatment. The COVID-19 pandemic disrupted progress on the strategy, but lessons learned during the pandemic - especially in vaccination, self-administered testing, and coordinated mobilization on a global scale - may help with efforts to achieve its targets. However, we must also learn from the failure of the COVID-19 response to include adequate representation of global voices. Efforts to eliminate cervical cancer will only succeed if those countries most affected are involved from the very start of planning. In this article we summarize innovations and highlight missed opportunities in the COVID response, and make recommendations to leverage the COVID experience to accelerate the elimination of cervical cancer globally.

BACKGROUND: Hormonal changes during the menstrual cycle play a key role in shaping immunity in the cervicovaginal tract. Cervicovaginal fluid contains cytokines, chemokines, immunoglobulins, and other immune mediators. Many studies have shown that the concentrations of these immune mediators change throughout the menstrual cycle, but the studies have often shown inconsistent results. Our understanding of immunological correlates of the menstrual cycle remains limited and could be improved by meta-analysis of the available evidence. METHODS: We performed a systematic review and meta-analysis of cervicovaginal immune mediator concentrations throughout the menstrual cycle using individual participant data. Study eligibility included strict definitions of the cycle phase (by progesterone or days since the last menstrual period) and no use of hormonal contraception or intrauterine devices. We performed random-effects meta-analyses using inverse-variance pooling to estimate concentration differences between the follicular and luteal phases. In addition, we performed a new laboratory study, measuring select immune mediators in cervicovaginal lavage samples. RESULTS: We screened 1570 abstracts and identified 71 eligible studies. We analyzed data from 31 studies, encompassing 39,589 concentration measurements of 77 immune mediators made on 2112 samples from 871 participants. Meta-analyses were performed on 53 immune mediators. Antibodies, CC-type chemokines, MMPs, IL-6, IL-16, IL-1RA, G-CSF, GNLY, and ICAM1 were lower in the luteal phase than the follicular phase. Only IL-1α, HBD-2, and HBD-3 were elevated in the luteal phase. There was minimal change between the phases for CXCL8, 9, and 10, interferons, TNF, SLPI, elafin, lysozyme, lactoferrin, and interleukins 1β, 2, 10, 12, 13, and 17A. The GRADE strength of evidence was moderate to high for all immune mediators listed here. CONCLUSIONS: Despite the variability of cervicovaginal immune mediator measurements, our meta-analyses show clear and consistent changes during the menstrual cycle. Many immune mediators were lower in the luteal phase, including chemokines, antibodies, matrix metalloproteinases, and several interleukins. Only interleukin-1α and beta-defensins were higher in the luteal phase. These cyclical differences may have consequences for immunity, susceptibility to infection, and fertility. Our study emphasizes the need to control for the effect of the menstrual cycle on immune mediators in future studies.

Mobility technologies, since the discovery of the uniaxial wheel, have strongly shaped the forms and times of cities and buildings and their interiors. The paper explores how newly developed flying transports, such as drones, may in the future reshape and alter the interiors of the buildings we inhabit. Utopias about cities with flying cars are a literature full of examples and theories, such as Andrea Branzi/Archizoom’s No Stop City and Instant City and others, but also even more extensive cinematography such as Christopher Nolan’s movie Inception and Stanley Kubrick’s 2001: A Space Odyssey. In fact, the flying vehicles, by which people as well as goods will soon move, introduce a fourth dimension (time) and will allow access to buildings from the roof and facades. They will recover the distributional logic of an iconic and historical typology of Milanese architecture, that of the edificio a ballatoio, in which the distribution of spaces followed a private/public logic that would lend itself perfectly to the buildings of the drone city. The article will explore the transformations in plans, materials, facades, ways of living, and relationships that, this coming revolution, will introduce into the interior spaces of buildings and our existences.

Abstract Background Pressure Injuries are not exclusively an adult phenomenon; various risk factors contribute to a high prevalence rate of 43% in the neonatal and pediatric intensive care population. Effective preventive measures in this population are limited. Methods We performed a pilot study to analyze the distribution and localization of support surface interface pressures in neonates in a pediatric intensive care unit (PICU). The hypothesis was that pressure redistribution by a novel air mattress would reduce pressure peaks in critical neonates. The measurements were conducted in a 27-bed level III PICU between November and December 2020. This included measuring pressure distribution and pressure peaks for five neonates positioned on either a state-of-the-art foam mattress or a new prototype air mattress. Results We confirmed that the pressure peaks were significantly reduced using the prototype air mattress, compared with the state-of-the-art foam mattress. The reduction of mean pressure values was 9–29%, while the reduction of the highest 10% of pressure values was 23–41%. Conclusions The journey to an effective, optimal, and approved product for severely ill neonates to reduce Pressure Injuries is challenging. However, a crucial step was completed by this pilot study with the first pressure measurements in a real-world setting and the successful realization of a decrease in pressure peaks obtained using a prototype air mattress.

Introduction: Spheroids are spherical aggregates of cells that mimic the three-dimensional (3D) architecture of tissues more closely than traditional two dimensional (2D) cultures. Spheroids of adipose stem cells (SASCs) show special features such as high multilineage differentiation potential and immunomodulatory activity. These properties have been attributed to their secreted factors, such as cytokines and growth factors. Moreover, a key role is played by the extracellular vesicles (EVs), which lead a heterogeneous cargo of proteins, mRNAs, and small RNAs that interfere with the pathways of the recipient cells. Purpose: The aim of this work was to characterize the composition of the secretome and exosome from SASCs and evaluate their regenerative potential. Materials and Methods: SASCs were extracted from adipose samples of healthy individuals after signing informed consent. The exosomes were isolated and characterized by Dinamic Light Scattering (DLS), Scanning Electron Microscopy (SEM), and Western blotting analyses. The expression of mRNAs and miRNAs were evaluated through real-time PCR. Lastly, a wound-healing assay was performed to investigate their regenerative potential on different cell cultures. Results: The SASCs’ exosomes showed an up-regulation of NANOG and SOX2 mRNAs, typical of stemness maintenance, as well as miR126 and miR146a, related to angiogenic and osteogenic processes. Moreover, the exosomes showed a regenerative effect. Conclusions: The SASCs’ secretome carried paracrine signals involved in stemness maintenance, pro-angiogenic and pro-osteogenic differentiation, immune system regulation, and regeneration.

PurposeCurrent cervical cancer screening guidelines recommend 3-year screening intervals, in contrast to the previous recommendation of annual screening, to prevent over screening and overtreatment. We evaluated the impact of viewing a tablet-based educational tool prior to seeing a clinician on young women's knowledge and understanding of cervical cancer screening, HPV vaccination follow-up of abnormal pap smears, and comfort in communicating with their providers.MethodsThis cross-sectional study was part of a cluster-randomized study of fourteen primary care clinics from January 2015 to December 2016. We developed the cervical cancer education tool in English and Spanish using a community-based approach that included formative work and cognitive interviewing. Clinics were randomized to use the intervention (tablet-based patient education tool) or to participate as a control group. We administered surveys to a convenience sample of 229 English- or Spanish-speaking women aged 19 to 35 years in these clinics. We used descriptive analyses and logistic regression models with cluster-robust standard errors to compare differences among the two groups.ResultsCompared to women seen in control clinics, women seen in intervention clinics demonstrated greater knowledge regarding human papilloma virus (HPV (p = 0.004) and understanding (p

IntroductionCasting is an essential treatment for neuro-orthopedic conditions in children with cognitive, sensory, and communicational disabilities. However, a main side-effect is the development of pressure injuries resulting in additional (wound) therapies and prolongation of the hospital stay. The primary aim of our study was to investigate the potential of objective pressure measurements in casts to assess the risk for pressure injury development.MethodsFive pediatric healthy participants were included in this study. We measured the global and the local compression force at body sites prone to pressure injury development for different body positions and the transfer in-between in a cast equipped with pressure sensors. These conditions resulted in partial or full body weight loading.Results and discussionThe global maximum compression force was affected significantly by body postures with partial and full loading of the cast and during transfer. The local compression force significantly correlated with the global compression force at the heel and instep area. In conclusion, the integration of sensing technologies into casts bears a high potential for early recognition of critical conditions inside the cast and inducing preventive measures in the at-risk population.

Although great strides have been made to tackle hospital-acquired pressure ulcers (HAPUs), there is a need for greater recognition of device-related pressure ulcers (DRPUs), including their causes, management and prevention. This consensus statement, an updated second edition, aims to continue raising awareness of these largely preventable injuries and, crucially, to stimulate action. DRPUs are relatively common and account for a growing proportion of HAPUs. Updated information on the incidence of DRPUs is described in chapter 1. Although it is recognised that DRPUs increase the financial burden of healthcare, there is little formal analysis of their economic impact. This needs to be addressed; robust evidence on the burden of DRPUs and the value that can be released by adopting prevention strategies is needed to help drive action. Our understanding of the pathophysiology of DRPUs has improved significantly over the past few years; this is described in chapter 2. One crucial difference between PUs and DRPUs is that body-weight forces are less significant in DRPUs, with the force being exerted from a device that is typically strapped or taped onto the body. Devices and their securement may generate high stress concentrations in tissues, leading to cell and tissue-damage pathways associated with sustained deformation. As more evidence is published on DRPUs, recurring themes are emerging, as outlined in chapter 3: The most vulnerable patients are bearing the brunt of DRPUs; paediatric and neonatal patients, and all those needing critical care are particularly susceptible. During the COVID-19 pandemic, a new high-risk population (people with severe COVID-19 infection) emerged. They are at increased risk of DRPUs because of their need for prolonged ventilatory support, especially when 'proning' Devices associated with DRPUs are often used to perform essential, life-saving functions. They include continuous positive airway pressure (CPAP) masks or endotracheal tubes. Minimising their use is clearly not an option, so practice innovation is needed Although the most common locations for DRPUs are the face, ears, lower legs and heels, any location where a device comes into close contact with the skin can be at risk. In the same vein, any device, whether needed for a medical purpose or not, has the capacity to cause injury if its use is not properly managed. Vigilance is needed for all patients. What can be done? The importance of routine risk assessment is covered in chapter 4. Although use of a validated risk assessment tool is the vital first step, this will not be enough on its own. Several steps can be taken to ensure the safe use of devices. These are described in chapter 5 and include device repositioning, cushioning with prophylactic dressings and moisture control (only where possible and clinically appropriate). Of key importance is the development of an institutional protocol and champions to ensure all necessary steps are adopted. For any of these changes to be put into practice, awareness of DRPUs needs to increase. A number of proposals are outlined in chapter 6. A change of focus among health professionals and policy makers, along with more investment in education and training, are needed. All patients being managed with a medical device must be considered as at high risk. The pandemic introduced the world to the problem of DRPUs in health professionals caused by the extended wear of personal protective equipment. Health professionals also have a right to expect institutional protocols and provision of devices that protect them from DRPUs. Cutting-edge ideas and technologies that may be available in the future are described in chapter 7. When designing new products, manufacturers of medical devices have a duty of care to investigate the risks of DRPUs associated with their products and mitigate them, wherever possible. Our developing understanding of how the design, structure and materials used in medical devices contribute to DRPUs will help us develop new solutions for tomorrow. The first step is for everyone involved to ask themselves, 'what can I do to help?' There is work to be done-your journey to reduce DRPUs starts here!.

It is unknown whether HTLV-1/2 prevalence has been stable or changing with time in Brazil. We present a 10-year (2007-2016) analysis of HTLV-1/2 infection in first-time blood donors from four blood banks in Brazil. The Brazilian blood centers participating in this multicenter Recipient Epidemiology and Donor Evaluation Study (REDS) are located in Recife in the Northeast and in São Paulo, Rio de Janeiro and Belo Horizonte located in the Southeast of the country. A previous REDS study using the same database from 2007 to 2009 showed that the prevalence per 100,000 donors was 222 in Recife, 83 in Belo Horizonte and 101 in São Paulo. From 2007 to 2016, HTLV-1/2 prevalence was calculated by year, blood center and birth cohort. Covariates included age, gender, schooling, self-reported skin color and type of donation. From 1,092,174 first-blood donations, in the general analysis, HTLV-1/2 infection predominated in females, donors over 50 years of age, black skin color and less educated. The average prevalence was 228 per 100,000 donors in Recife, 222 in Rio de Janeiro, 104 in Belo Horizonte and 103 in São Paulo. In the 10-year analysis, HTLV-1/2 prevalence was stable, but a trend was observed toward an increase in HTLV-1/2 infection among younger people (p < 0.001), males (p = 0.049), those with white skin color (p < 0.001), and higher education (p = 0.014). Therefore, this 10-year surveillance of the infection showed stable HTLV-1/2 prevalence overall but a trend toward increased prevalence among the younger and more educated donors despite Brazilian policies to control sexually transmitted infections being in place for more than 10 years.

The burden of cervical cancer is disproportionately distributed globally, with the vast majority of cases occurring in low- and middle-income countries. Women with human immunodeficiency virus (HIV) (WWH) are at increased risk of human papillomavirus (HPV) infection and cervical cancer as compared to HIV-negative individuals. HPV vaccination remains a priority in regions with a high burden of cervical cancer and high HIV prevalence. With HPV vaccines becoming more accessible, optimal use beyond the initial World Health Organization-recommended target population of 9 to 14-year-old girls is an important question. In March 2022, a group of experts in epidemiology, immunology, and vaccinology convened to discuss the state-of-the-science of HPV vaccination in WWH. This report summarizes the proceedings: review of HIV epidemiology and its intersection with cervical cancer burden, immunology, HPV vaccination including reduced-dose schedules and experience with other vaccines in people with HIV (PWH), HPV vaccination strategies and knowledge gaps, and outstanding research questions. Studies of HPV vaccine effectiveness among WWH, including duration of protection, are limited. Until data from ongoing research is available, the current recommendation for WWH remains for a multi-dose HPV vaccination regimen. A focus of the discussion included the potential impact of HIV acquisition following HPV vaccination. With no data currently existing for HPV vaccines and limited information from non-HPV vaccines, this question requires further research. Implementation research on optimal HPV vaccine delivery approaches for WWH and other priority populations is also urgently needed.

IntroductionThis study sought to determine whether a provider mobile phone application, used with or without a patient educational tool accessed on a computer tablet, would promote adherence to guidelines for cervical cancer screening and management of abnormal cytology in young women.MethodsThe study was conducted as a prospective cohort study in which 14 Family Planning, Access, Care, and Treatment provider clinics were randomized to 1 of 2 arms: (1) provider mobile phone application only or (2) provider mobile phone application plus patient educational tool. The provider mobile phone application gave information to providers regarding cervical cancer screening and management of abnormal cytology. The patient educational tool accessed on a computer tablet was a patient-centered educational tool. Each arm was compared with clinic control groups (no intervention) in a 2:1 ratio (control:intervention). Claims data were used to calculate and compare 18-month cytology (Pap) and colposcopy rates before the intervention and during the 18 months using the Poisson mixed-effect regression model. A sensitivity analysis examined the differences in the rate of change between each arm and controls. The study took place between July 2015 and December 2016, and analysis was performed in 2019.ResultsThe clinics randomized to the provider mobile phone application plus patient educational tool arm and their control group achieved similar 18-month Pap rates (0.52, 95% CI=0.37, 0.74 and 0.68, 95% CI=0.53, 0.86, respectively) as well as the provider mobile phone application arm and their control group (0.44, 95% CI=0.33, 0.58 and 0.41, 95% CI=0.34, 0.51; p-values >0.1). In the sensitivity analysis, the difference in the rate of change in Pap rates for the provider mobile phone application plus patient educational tool arm and their control group before and during the intervention was -0.22 and -0.09, respectively (p=0.02), but no differences were seen between the provider mobile phone application arm and their control group. No significant changes were observed for colposcopy rates.ConclusionsProviding clinicians and patients with information on guidelines had no demonstrable effect on 18-month Pap and colposcopy rates in the regression model; however, results from the sensitivity analysis for the patient educational tool were encouraging.Trial registrationThis study is registered at www.clinicaltrials.gov NCT02270021.

Background and objectivesWe recently reported the short-term results of this trial revealing that higher-calorie refeeding (HCR) restored medical stability earlier, with no increase in safety events and significant savings associated with shorter length of stay, in comparison with lower-calorie refeeding (LCR) in hospitalized adolescents with anorexia nervosa. Here, we report the 1-year outcomes, including rates of clinical remission and rehospitalizations.MethodsIn this multicenter, randomized controlled trial, eligible patients admitted for medical instability to 2 tertiary care eating disorder programs were randomly assigned to HCR (2000 kcals per day, increasing by 200 kcals per day) or LCR (1400 kcals per day, increasing by 200 kcals every other day) within 24 hours of admission and followed-up at 10 days and 1, 3, 6, and 12 months post discharge. Clinical remission at 12 months post discharge was defined as weight restoration (≥95% median BMI) plus psychological recovery. With generalized linear mixed effect models, we examined differences in clinical remission over time.ResultsOf 120 enrollees, 111 were included in modified intent-to-treat analyses, 60 received HCR, and 51 received LCR. Clinical remission rates changed over time in both groups, with no evidence of significant group differences (P = .42). Medical rehospitalization rates within 1-year post discharge (32.8% [19 of 58] vs 35.4% [17 of 48], P = .84), number of rehospitalizations (2.4 [SD: 2.2] vs 2.0 [SD: 1.6]; P = .52), and total number of days rehospitalized (6.0 [SD: 14.8] vs 5.1 [SD: 10.3] days; P = .81) did not differ by HCR versus LCR.ConclusionsThe finding that clinical remission and medical rehospitalization did not differ over 1-year, in conjunction with the end-of-treatment outcomes, support the superior efficacy of HCR as compared with LCR.

IntroductionSalivary metabolite profiles are altered in adults with HIV compared to their uninfected counterparts. Less is known about youth with HIV and how oral disorders that commonly accompany HIV infection impact salivary metabolite levels.ObjectiveAs part of the Adolescent Master Protocol multi-site cohort study of the Pediatric HIV/AIDS Cohort Study (PHACS) network we compared the salivary metabolome of youth with perinatally-acquired HIV (PHIV) and youth HIV-exposed, but uninfected (PHEU) and determined whether metabolites differ in PHIV versus PHEU.MethodsWe used three complementary targeted and discovery-based liquid chromatography-tandem mass spectrometry (LC-MS/MS) workflows to characterize salivary metabolite levels in 20 PHIV and 20 PHEU youth with and without moderate periodontitis. We examined main effects associated with PHIV and periodontal disease, and the interaction between them.ResultsWe did not identify differences in salivary metabolite profiles that remained significant under stringent control for both multiple between-group comparisons and multiple metabolites. Levels of cadaverine, a known periodontitis-associated metabolite, were more abundant in individuals with periodontal disease with the difference being more pronounced in PHEU than PHIV. In the discovery-based dataset, we identified a total of 564 endogenous peptides in the metabolite extracts, showing that proteolytic processing and amino acid metabolism are important to consider in the context of HIV infection.ConclusionThe salivary metabolite profiles of PHIV and PHEU youth were overall very similar. Individuals with periodontitis particularly among the PHEU youth had higher levels of cadaverine, suggesting that HIV infection, or its treatment, may influence the metabolism of oral bacteria.

Catherine Milne and colleagues present the findings of their review, ccna2@juno.com.

With the advent of combined antiretroviral therapies, the face of HIV infection has changed dramatically from a disease with almost certain mortality from serious comorbidities, to a manageable chronic condition with an extended lifespan. In this paper we present the more recent investigations into the epidemiology, microbiology, and pathogenesis of periodontal diseases in patients with HIV, and the effects of combined antiretroviral therapies on the incidence and progression of these diseases both in adults and perinatally infected children. In addition, comparisons and potential interactions between the HIV-associated microbiome, host responses, and pathogenesis in the oral cavity with the gastrointestinal tract and other areas of the body are presented. Also, the effects of HIV and combined antiretroviral therapies on comorbidities such as hyposalivation, dementia, and osteoporosis on periodontal disease progression are discussed.

BACKGROUND: Lower weight has historically been equated with more severe illness in anorexia nervosa (AN). Reliance on admission weight to guide clinical concern is challenged by the rise in patients with atypical anorexia nervosa (AAN) requiring hospitalization at normal weight. METHODS: We examined weight history and illness severity in 12- to 24-year-olds with AN (n = 66) and AAN (n = 50) in a randomized clinical trial, the Study of Refeeding to Optimize Inpatient Gains (www.clinicaltrials.gov; NCT02488109). Amount of weight loss was the difference between the highest historical percentage median BMI and admission; rate was the amount divided by duration (months). Unpaired t tests compared AAN and AN; multiple variable regressions examined associations between weight history variables and markers of illness severity at admission. Stepwise regression examined the explanatory value of weight and menstrual history on selected markers. RESULTS: Participants were 16.5 ± 2.6 years old, and 91% were of female sex. Groups did not differ by weight history or admission heart rate (HR). Eating Disorder Examination Questionnaire global scores were higher in AAN (mean 3.80 [SD 1.66] vs mean 3.00 [SD 1.66]; P = .02). Independent of admission weight, lower HR (β = -0.492 [confidence interval (CI) -0.883 to -0.100]; P = .01) was associated with faster loss; lower serum phosphorus was associated with a greater amount (β = -0.005 [CI -0.010 to 0.000]; P = .04) and longer duration (β = -0.011 [CI -0.017 to 0.005]; P = .001). Weight and menstrual history explained 28% of the variance in HR and 36% of the variance in serum phosphorus. CONCLUSIONS: Weight history was independently associated with markers of malnutrition in inpatients with restrictive eating disorders across a range of body weights and should be considered when assessing illness severity on hospital admission.

BACKGROUND:Lower weight has historically been equated with more severe illness in anorexia nervosa (AN). Reliance on admission weight to guide clinical concern is challenged by the rise in patients with atypical anorexia nervosa (AAN) requiring hospitalization at normal weight. METHODS:We examined weight history and illness severity in 12- to 24-year-olds with AN (n = 66) and AAN (n = 50) in a randomized clinical trial, the Study of Refeeding to Optimize Inpatient Gains (www.clinicaltrials.gov; NCT02488109). Amount of weight loss was the difference between the highest historical percentage median BMI and admission; rate was the amount divided by duration (months). Unpaired t tests compared AAN and AN; multiple variable regressions examined associations between weight history variables and markers of illness severity at admission. Stepwise regression examined the explanatory value of weight and menstrual history on selected markers. RESULTS:Participants were 16.5 ± 2.6 years old, and 91% were of female sex. Groups did not differ by weight history or admission heart rate (HR). Eating Disorder Examination Questionnaire global scores were higher in AAN (mean 3.80 [SD 1.66] vs mean 3.00 [SD 1.66]; P = .02). Independent of admission weight, lower HR (β = -0.492 [confidence interval (CI) -0.883 to -0.100]; P = .01) was associated with faster loss; lower serum phosphorus was associated with a greater amount (β = -0.005 [CI -0.010 to 0.000]; P = .04) and longer duration (β = -0.011 [CI -0.017 to 0.005]; P = .001). Weight and menstrual history explained 28% of the variance in HR and 36% of the variance in serum phosphorus. CONCLUSIONS:Weight history was independently associated with markers of malnutrition in inpatients with restrictive eating disorders across a range of body weights and should be considered when assessing illness severity on hospital admission.

AimTo examine oral biomarkers that have been associated with periodontal disease progression in HIV-infected adults in perinatally HIV-infected and HIV-exposed but uninfected youth.Material and methodsThis was a cross-sectional, multicentre substudy of youth participating in the Oral Health Pediatric HIV/AIDS Cohort study. Gingival crevicular fluid repository samples from participants with and without periodontal disease (using Gingival Index [GI] and Bleeding on Probing [BOP] parameters on dental examination) were tested for concentration levels of inflammatory biomarkers. Associations were assessed using Wilcoxon test and Spearman correlation.ResultsFor perinatal HIV youth (n = 129), the markers consistently elevated (p

Abstract Background Hormonal changes during the menstrual cycle play a key role in shaping immunity in the cervicovaginal tract. Cervicovaginal fluid contains cytokines, chemokines, immunoglobulins, and other immune mediators. Many studies have shown that the concentrations of these immune mediators change throughout the menstrual cycle, but the studies have often shown inconsistent results. Our understanding of immunological correlates of the menstrual cycle remains limited and could be improved by meta-analysis of the available evidence. Methods We performed a systematic review and meta-analysis of cervicovaginal immune mediator concentrations throughout the menstrual cycle using individual participant data. Study eligibility included strict definitions of the cycle phase (by progesterone or days since the last menstrual period) and no use of hormonal contraception or intrauterine devices. We performed random-effects meta-analyses using inverse-variance pooling to estimate concentration differences between the follicular and luteal phases. In addition, we performed a new laboratory study, measuring select immune mediators in cervicovaginal lavage samples. Results We screened 1570 abstracts and identified 71 eligible studies. We analyzed data from 31 studies, encompassing 39,589 concentration measurements of 77 immune mediators made on 2112 samples from 871 participants. Meta-analyses were performed on 53 immune mediators. Antibodies, CC-type chemokines, MMPs, IL-6, IL-16, IL-1RA, G-CSF, GNLY, and ICAM1 were lower in the luteal phase than the follicular phase. Only IL-1α, HBD-2, and HBD-3 were elevated in the luteal phase. There was minimal change between the phases for CXCL8, 9, and 10, interferons, TNF, SLPI, elafin, lysozyme, lactoferrin, and interleukins 1β, 2, 10, 12, 13, and 17A. The GRADE strength of evidence was moderate to high for all immune mediators listed here. Conclusions Despite the variability of cervicovaginal immune mediator measurements, our meta-analyses show clear and consistent changes during the menstrual cycle. Many immune mediators were lower in the luteal phase, including chemokines, antibodies, matrix metalloproteinases, and several interleukins. Only interleukin-1α and beta-defensins were higher in the luteal phase. These cyclical differences may have consequences for immunity, susceptibility to infection, and fertility. Our study emphasizes the need to control for the effect of the menstrual cycle on immune mediators in future studies.