ARFID at 10 years: A Review of Medical, Nutritional and Psychological Evaluation and Management.

PURPOSE OF REVIEW: Avoidant restrictive food intake disorder (ARFID) is a diagnostic term that was established 10 years ago to describe those patients with an eating disorder, mostly children and adolescents, who have poor nutrition that is not due to body image or weight concerns. This article reviews the diagnosis and subtypes of ARFID, as well as the medical, nutritional and psychological principles of evaluation and management of the disorder. RECENT FINDINGS: In the past 10 years, clinicians have refined their approaches to managing the two major subtypes of ARFID: (1) those patients with a longer-term restriction in the amount and/or variety of the foods they eat, and (2) those patients with a shorter-term decrease in eating because of fear of aversive consequences such as vomiting, choking, GI symptoms or an allergic reaction to food. In that same time, the field of psychology has been developing evidence-based approaches to management of ARFID in each of its manifestations. Each patient with ARFID presents with a unique set of medical, nutritional and psychological factors that requires an individualized and multi-disciplinary approach in the management of this difficult to treat disorder.

Interaction of human HelQ with DNA polymerase delta halts DNA synthesis and stimulates DNA single-strand annealing.

DNA strand breaks are repaired by DNA synthesis from an exposed DNA end paired with a homologous DNA template. DNA polymerase delta (Pol δ) catalyses DNA synthesis in multiple eukaryotic DNA break repair pathways but triggers genome instability unless its activity is restrained. We show that human HelQ halts DNA synthesis by isolated Pol δ and Pol δ-PCNA-RPA holoenzyme. Using novel HelQ mutant proteins we identify that inhibition of Pol δ is independent of DNA binding, and maps to a 70 amino acid intrinsically disordered region of HelQ. Pol δ and its POLD3 subunit robustly stimulated DNA single-strand annealing by HelQ, and POLD3 and HelQ interact physically via the intrinsically disordered HelQ region. This data, and inability of HelQ to inhibit DNA synthesis by the POLD1 catalytic subunit of Pol δ, reveal a mechanism for limiting DNA synthesis and promoting DNA strand annealing during human DNA break repair, which centres on POLD3.

Effect of a Multisectoral Agricultural Intervention on HIV Health Outcomes Among Adults in Kenya: A Cluster Randomized Clinical Trial.

Importance: Food insecurity and HIV health outcomes are linked through nutritional, mental health, and health behavior pathways. Objective: To examine the effects of a multisectoral agriculture and livelihood intervention on HIV viral suppression and nutritional, mental health, and behavioral outcomes among HIV-positive adults prescribed antiretroviral therapy (ART). Design, Setting, and Participants: This cluster randomized clinical trial was performed in 8 pairs of health facilities in Kenya. Participants were 18 years or older, living with HIV, and receiving ART for longer than 6 months; had moderate to severe food insecurity; and had access to arable land and surface water and/or shallow aquifers. Participants were followed up every 6 months for 24 months. Data were collected from June 23, 2016, to June 13, 2017, with follow-up completed by December 16, 2019. Data were analyzed from June 25 to August 31, 2020, using intention-to-treat and per-protocol methods. Interventions: A loan to purchase a human-powered irrigation pump, fertilizer, seeds, and pesticides combined with the provision of training in sustainable agriculture and financial literacy. Main Outcomes and Measures: The primary outcome was the relative change from baseline to the end of follow-up in viral load suppression (≤200 copies/mL) compared between study groups using difference-in-differences analyses. Secondary outcomes included clinic attendance, ART adherence, food insecurity, depression, self-confidence, and social support. Results: A total of 720 participants were enrolled (396 women [55.0%]; mean [SD] age, 40.38 [9.12] years), including 366 in the intervention group and 354 in the control group. Retention included 677 (94.0%) at the 24-month visit. HIV viral suppression improved in both groups from baseline to end of follow-up from 314 of 366 (85.8%) to 327 of 344 (95.1%) in the intervention group and from 291 of 353 (82.4%) to 314 of 333 (94.3%) in the control group (P = .86). Food insecurity decreased more in the intervention than the control group (difference in linear trend, -3.54 [95% CI, -4.16 to -2.92]). Proportions of those with depression during the 24-month follow-up period declined more in the intervention group (from 169 of 365 [46.3%] to 36 of 344 [10.5%]) than the control group (106 of 354 [29.9%] to 41 of 333 [12.3%]; difference in trend, -0.83 [95% CI, -1.45 to -0.20]). Self-confidence improved more in the intervention than control group (difference in trend, -0.37 [95% CI, -0.59 to -0.15]; P = .001), as did social support (difference in trend, -3.63 [95% CI, -4.30 to -2.95]; P < .001). Conclusions and Relevance: In this cluster randomized trial, the multisectoral agricultural intervention led to demonstrable health and other benefits; however, it was not possible to detect additional effects of the intervention on HIV clinical indicators. Agricultural interventions that improve productivity and livelihoods hold promise as a way of addressing food insecurity and the underpinnings of poor health among people living with HIV in resource-limited settings. Trial Registration: ClinicalTrials.gov Identifier: NCT02815579.

Association of the COVID-19 Pandemic With Adolescent and Young Adult Eating Disorder Care Volume.

Importance: The COVID-19 pandemic has affected youth mental health. Increases in site-specific eating disorder (ED) care have been documented; however, multisite studies demonstrating national trends are lacking. Objective: To compare the number of adolescent/young adult patients seeking inpatient and outpatient ED care before and after onset of the COVID-19 pandemic. Design, Setting, and Participants: Using an observational case series design, changes in volume in inpatient and outpatient ED-related care across 15 member sites (14 geographically diverse hospital-based adolescent medicine programs and 1 nonhospital-based ED program) of the US National Eating Disorder Quality Improvement Collaborative was examined. Sites reported monthly volumes of patients seeking inpatient and outpatient ED care between January 2018 and December 2021. Patient volumes pre- and postpandemic onset were compared separately for inpatient and outpatient settings. Demographic data such as race and ethnicity were not collected because this study used monthly summary data. Exposures: Onset of the COVID-19 pandemic. Main Outcomes and Measures: Monthly number of patients seeking inpatient/outpatient ED-related care. Results: Aggregate total inpatient ED admissions were 81 in January 2018 and 109 in February 2020. Aggregate total new outpatient assessments were 195 in January 2018 and 254 in February 2020. Before the COVID-19 pandemic, the relative number of pooled inpatient ED admissions were increasing over time by 0.7% per month (95% CI, 0.2%-1.3%). After onset of the pandemic, there was a significant increase in admissions over time of 7.2% per month (95% CI, 4.8%-9.7%) through April 2021, then a decrease of 3.6% per month (95% CI, -6.0% to -1.1%) through December 2021. Prepandemic, pooled data showed relative outpatient ED assessment volume was stable over time, with an immediate 39.7% decline (95% CI, -50.4% to -26.7%) in April 2020. Subsequently, new assessments increased by 8.1% (95% CI, 5.3%-11.1%) per month through April 2021, then decreased by 1.5% per month (95% CI, -3.6% to 0.7%) through December 2021. The nonhospital-based ED program did not demonstrate a significant increase in the absolute number of admissions after onset of the pandemic but did see a significant increase of 8.2 (95% CI, 6.2-10.2) additional inquiries for care per month in the first year after onset of the pandemic. Conclusions and Relevance: In this study, there was a significant COVID-19 pandemic-related increase in both inpatient and outpatient volume of patients with EDs across sites, particularly in the first year of the pandemic. Given inadequate ED care availability prior to the pandemic, the increased postpandemic demand will likely outstrip available resources. Results highlight the need to address ED workforce and program capacity issues as well as improve ED prevention strategies.

Relative energy deficiency in sport (RED - S).

Relative Energy Deficiency in Sport (RED-S) refers to a condition in which energy imbalance leads to impaired physiological function of multiple organ systems and expands on the diagnosis previously known as the Female Athlete Triad. Researchers attribute the medical complications of RED-S to low energy availability, in which energy availability is defined as dietary energy intake minus exercise energy expenditure divided by fat-free mass. This article reviews the history of this diagnosis, the changing terminology, and the reasons for the expansion. Accepted definitions of each part of the energy availability equation are considered and the difficulties that exist using these equations in practice or comparatively in the literature are assessed. The review analyzes the broad spectrum of health consequences of RED-S, especially as it relates to hypoestrogenemia and menstrual function, gives guidance to those caring for athletes on the identification and management of RED-S, and sheds lights on the important role of coaches, athletic trainers, and families in recognizing this diagnosis and in helping getting patients to care.

Menstrual disorders in adolescents and young adults with eating disorders.

Although amenorrhea is no longer a specific criterion required to make the diagnosis of anorexia nervosa (AN), the relationship between restrictive eating and menstrual status remains important in the diagnosis, treatment, and consequences for patients with eating disorders. Clinicians should understand the relationship between menstrual irregularities and malnutrition due to eating disorders, as it may be possible to intervene sooner if the diagnosis is made earlier. Treatment of AN (in those who are underweight) and atypical AN (in those who are not underweight) is aimed at cessation of restrictive thoughts and behaviors, restoration of appropriate nutrition and weight, and normal functioning of the body. While eating disorder thoughts and behaviors are helped by both therapy and nutrition, regular functioning of the body, including regular menstruation, is linked to both appropriate nutrition and weight. Patients who are not underweight based on their body mass index (BMI) may still have oligo/amenorrhea due to their caloric restriction; thus any patient who has irregular menses should have a detailed dietary evaluation as part of their workup. Timely diagnosis and treatment of patients with eating disorders and amenorrhea is important due to the impact on bone mass accrual for adolescents who have prolonged amenorrhea. Menstrual abnormalities may also be seen in patients with bulimia nervosa (BN).

Menstrual and reproductive health in female adolescents with developmental disabilities.

Youth with intellectual and developmental disabilities (I/DD) are impacted by pubertal changes and the onset of menses disproportionately. Despite the fact that for most youth with I/DD, the progression of puberty, menarche, and irregular cycles due to axis immaturity appear to be consistent with the general population, cyclic behavioral changes and premenstrual symptoms may be more common. Furthermore, for some disabled youth there are endocrine or medication effects that may impact menses disproportionately. Education and access to care is essential for this group to address many aspects of treatment, from prepubertal anticipatory guidance to menstrual management, with special attention required for addressing issues concerning hygiene, cyclic pain, behavior changes, sexuality, potential for abuse, and pregnancy prevention.1-4 This article will provide an overview of the policies and guidance available for management of the menstrual issues encountered in adolescents with intellectual and developmental disabilities and complex medical disorders. Included will be a review of studies that evaluate the different types of methods that are utilized for menstrual management and the different conditions that are encountered.

Dysmenorrhea in adolescents.

Studies show that between 41% and 91.5% of young women, school-aged and university-aged, are affected by dysmenorrhea. Primary dysmenorrhea, which is caused by the production of prostaglandins, is defined as cramping pain in the lower abdomen and/or pelvis occurring just before or during menstruation, in the absence of other diseases such as endometriosis, and typically lasting 1-3 days and with a negative physical examination. Secondary dysmenorrhea presents with similar signs and symptoms but is a result of underlying pelvic pathology, for example endometriosis or uterine fibroids. Dysmenorrhea most typically presents as abdominal cramping; however, it can also present with headaches, nausea, vomiting or other generalized symptoms. The diagnosis is mainly clinical, but other tests such as a pelvic examination, a pregnancy test and STI screening may be helpful in ruling out other sources of pain. Although the mainstay of treatment for dysmenorrhea is NSAIDs and hormonal therapy, lifestyle changes and complementary/alternative medicine can also be helpful approaches. Lifestyle changes include aerobic exercise and stretching, while complementary alternative medicine include peppermint, cinnamon, ginger and other herbs and supplements. Finally, endometriosis must be considered as a potential cause for secondary dysmenorrhea and would warrant a prompt referral to gynecology.

Abnormal uterine bleeding in adolescents.

Abnormal uterine bleeding (AUB) is a common diagnosis in the adolescent female population. In recent years, changes have been made to standardize nomenclature, evaluation and management of AUB in adolescents. The terms "abnormal uterine bleeding" and "heavy menstrual bleeding" have replaced terms including "dysfunctional uterine bleeding," "menorrhagia," "metrorrhagia", and "menometrorrhagia." Due to a high prevalence of these diagnoses in this population and resulting effects on quality of life, clinicians should understand and practice current evidence-based care, yet variability continues to exist. Evaluation should be focused on common etiologies of AUB in adolescents, namely non-structural causes, rather than those etiologies more common in adult females. The aim of this article is to review the existing definition, etiologies, pathophysiology, evaluation and management of AUB in adolescent females, with an emphasis on current universally accepted nomenclature and guidelines for use in clinical care.

Etiology and management of amenorrhea in adolescent and young adult women.

In this article, we will review the etiology and management of amenorrhea in adolescent and young adult women, beginning with the diagnostic work-up and followed by etiologies organized by system. Most cases of amenorrhea are caused by dysfunction of the hypothalamic-pituitary-ovarian (HPO) axis, which is the major regulator of the female reproductive hormones: estrogen and progesterone.  We begin by reviewing hypothalamic etiologies, including eating disorders and relative energy deficiency in sport. Then, pituitary causes of amenorrhea are reviewed, including hyperprolactinemia, empty sella syndrome, Sheehan's syndrome and Cushing's syndrome. Next, ovarian causes of amenorrhea are reviewed, including polycystic ovarian syndrome and primary ovarian insufficiency. Finally, other etiologies of amenorrhea are discussed, including thyroid disease, adrenal disease and reproductive tract anomalies. In conclusion, there is a wide and diverse range of causes of amenorrhea in adolescents that originate from any level of the HPO axis, as well as anatomic and chromosomal etiologies.   Treatment should be focused on the underlying cause. Preservation of bone density and risk of fractures should be discussed with amenorrheic patients since many causes of amenorrhea can result in decreased bone density and may be irreversible.

Broadly neutralizing antibody responses in the longitudinal primary HIV-1 infection Short Pulse Anti-Retroviral Therapy at Seroconversion cohort.

OBJECTIVE: Development of immunogens that elicit an anti-HIV-1 broadly neutralizing antibody (bnAb) response will be a key step in the development of an effective HIV-1 vaccine. Although HIV-1 bnAb epitopes have been identified and mechanisms of action studied, current HIV-1 envelope-based immunogens do not elicit HIV-1 bnAbs in humans or animal models. A better understanding of how HIV-1 bnAbs arise during infection and the clinical factors associated with bnAb development may be critical for HIV-1 immunogen design efforts. DESIGN AND METHODS: Longitudinal plasma samples from the treatment-naive control arm of the Short Pulse Anti-Retroviral Therapy at Seroconversion (SPARTAC) primary HIV-1 infection cohort were used in an HIV-1 pseudotype neutralization assay to measure the neutralization breadth, potency and specificity of bnAb responses over time. RESULTS: In the SPARTAC cohort, development of plasma neutralization breadth and potency correlates with duration of HIV infection and high viral loads, and typically takes 3-4 years to arise. bnAb activity was mostly directed to one or two bnAb epitopes per donor and more than 60% of donors with the highest plasma neutralization having bnAbs targeted towards glycan-dependent epitopes. CONCLUSION: This study highlights the SPARTAC cohort as an important resource for more in-depth analysis of bnAb developmental pathways.

Validation of a combined image derived input function and venous sampling approach for the quantification of [18F]GE-179 PET binding in the brain.

Blood-based kinetic analysis of PET data relies on an accurate estimate of the arterial plasma input function (PIF). An alternative to invasive measurements from arterial sampling is an image-derived input function (IDIF). However, an IDIF provides the whole blood radioactivity concentration, rather than the required free tracer radioactivity concentration in plasma. To estimate the tracer PIF, we corrected an IDIF from the carotid artery with estimates of plasma parent fraction (PF) and plasma-to-whole blood (PWB) ratio obtained from five venous samples. We compared the combined IDIF+venous approach to gold standard data from arterial sampling in 10 healthy volunteers undergoing [18F]GE-179 brain PET imaging of the NMDA receptor. Arterial and venous PF and PWB ratio estimates determined from 7 patients with traumatic brain injury (TBI) were also compared to assess the potential effect of medication. There was high agreement between areas under the curves of the estimates of PF (r = 0.99, p<0.001), PWB ratio (r = 0.93, p<0.001), and the PIF (r = 0.92, p<0.001) as well as total distribution volume (VT) in 11 regions across the brain (r = 0.95, p<0.001). IDIF+venous VT had a mean bias of -1.7% and a comparable regional coefficient of variation (arterial: 21.3 ± 2.5%, IDIF+venous: 21.5 ± 2.0%). Simplification of the IDIF+venous method to use only one venous sample provided less accurate VT estimates (mean bias 9.9%; r = 0.71, p<0.001). A version of the method that avoids the need for blood sampling by combining the IDIF with population-based PF and PWB ratio estimates systematically underestimated VT (mean bias -20.9%), and produced VT estimates with a poor correlation to those obtained using arterial data (r = 0.45, p<0.001). Arterial and venous blood data from 7 TBI patients showed high correlations for PF (r = 0.92, p = 0.003) and PWB ratio (r = 0.93, p = 0.003). In conclusion, the IDIF+venous method with five venous samples provides a viable alternative to arterial sampling for quantification of [18F]GE-179 VT.