The Role of Sodium-Glucose Cotransporter-2 Inhibitors in the Treatment of Polycystic Ovary Syndrome: A Review.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive-age women impacting their reproductive, mental, and metabolic health. Insulin resistance is a major driver of the pathophysiology of PCOS. There are several challenges with the management of this complex disorder including insufficient treatment options. Over the past 88 years, multiple hormonal and non-hormonal medications have been tried to treat the various components of this syndrome and there is no FDA (Food and Drug Administration)-approved medication specifically for PCOS yet. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors have a unique mechanism of inhibiting the coupled reabsorption of sodium and glucose in renal proximal convoluted tubules. This review aims to examine the efficacy and side-effect profile of SGLT-2 inhibitors in patients with PCOS. In a limited number of studies, SGLT-2 inhibitors appear to be effective in improving menstrual frequency, reducing body weight and total fat mass, lowering total testosterone and DHEAS levels, and improving some glycemic indices in women with PCOS. SGLT2 inhibitors are generally well tolerated. With future research, it is possible that SGLT-2 inhibitors could become a key therapeutic option for PCOS.

A multisite randomized controlled trial of an early palliative care intervention in children with advanced cancer: The PediQUEST Response Study Protocol.

BACKGROUND: The Pediatric Quality of Life and Evaluation of Symptoms Technology Response to Pediatric Oncology Symptom Experience (PQ-Response) intervention aims to integrate specialized pediatric palliative care into the routine care of children, adolescents, and young adults (AYAs) with advanced cancer. AIMS: To evaluate whether PQ-Response, compared to usual care, improves patient's health related quality of life (HRQoL) and symptom burden (aim 1), parent psychological distress and symptom-related stress (aim 2), and family and symptom treatment activation (aim 3). DESIGN: Multisite, randomized (1:1), controlled, un-blinded, effectiveness trial comparing PediQUEST Response (intervention) vs usual cancer care (control). SETTING: Five US large, tertiary level pediatric cancer centers. PARTICIPANTS: Children (≥2 years old)/AYAs who receive care at any of the participating sites because of advanced cancer or any progressive/recurrent solid or brain tumor and are palliative care "naïve." Target: 200 enrolled patient-parent dyads (minimum goal: 136 dyads randomized, N = 68/arm). INTERVENTIONS: PediQUEST Response: combines patient-mediated activation (weekly feedback of patient- and parent-reported symptoms and HRQoL to families and providers using the PediQUEST web system) with integration of the palliative care team. Usual Cancer Care: participants receive usual care, which can include palliative care consultation, and use PediQUEST web to answer surveys, with no feedback. METHODS: Following enrollment, patients (if ≥5 years) and one parent receive weekly PediQUEST-Surveys assessing HRQoL (Pediatric Quality of Life Inventory 4.0) and symptom burden (PediQUEST-Memorial Symptom Assessment Scale). After a 2-week run-in period, dyads who answer ≥2 PediQUEST surveys per participant (responders), are randomized (concealed allocation) and followed up for 16-weeks. Parents answer six additional surveys (parent outcomes). OUTCOMES: Primary: mean patient HRQoL score over 16-weeks as reported by a) the parent; and b) the patient if ≥5 years-old. Secondary: patient's symptom burden; parent's anxiety, depressive symptoms, symptom-related stress; family activation; and symptom treatment activation. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03408314) 1/24/18. https://clinicaltrials.gov/ct2/show/NCT03408314.

The moderating effect of age on the associations of cognitive and metacognitive beliefs with pediatric OCD symptoms.

Although considerable research has highlighted the importance of cognitive and metacognitive beliefs in adult obsessive-compulsive disorder (OCD), there has been limited investigation of these beliefs in pediatric OCD. The present study investigated the clinical correlates of cognitive and metacognitive beliefs in pediatric OCD. Previous studies found positive relations between OCD symptoms and these beliefs in pediatric patients, and we hypothesized these beliefs would also be positively related to pediatric OCD symptom severity. We additionally hypothesized age would moderate these relationships in consideration of previous studies highlighting age differences in symptom presentation and self-reported beliefs. We also explored age differences in belief endorsements. Youth aged 7-17 (n = 142) diagnosed with OCD completed self-report scales to measure cognitive and meta-cognitive beliefs. OCD severity was assessed using self-report and clinician-rated measures. Pearson correlations, moderation analyses, and independent-samples t-tests were used to test our hypotheses and aims. Significant positive relationships were observed between cognitive and metacognitive beliefs and self-reported OCD severity, although age did not moderate these relationships. Age differences were found in belief endorsements. In conclusion, cognitive and metacognitive beliefs appear clinically relevant to pediatric OCD cases, and we recommend clinicians assess these beliefs and incorporate cognitive components to corresponding evidence-based treatment.

Temporal precedence of the change in obsessive-compulsive symptoms and change in depressive symptoms during exposure and response prevention for pediatric obsessive-compulsive disorders.

The current study examined the temporal precedence of change in obsessive-compulsive symptoms and change in depressive symptoms during the course of an Exposure and Response Prevention (ERP) for pediatric OCD. Participants included 142 children and adolescents (7-17 years; mean age = 12.39, SD = 2.92; 51.40% female; 60.40% Non-Hispanic White) with a primary or co-primary diagnosis of OCD who received ERP in a two-site randomized controlled trial on d-cycloserine augmentation of CBT for pediatric OCD. Participants completed clinician-administered assessments of OC symptoms (Children's Yale-Brown Obsessive Compulsive Scale) and depressive symptoms (Children's Depression Rating Scale-Revised) from baseline to post-treatment follow-up. Lagged mediational analyses did not yield evidence in support of a mediating role for the change in OC symptoms in the effect of ERP on the change in depressive symptoms. In contrast, change in depressive symptoms mediated the effect of ERP treatment on the subsequent change in OC symptoms (95% confidence interval for indirect effect = -0.04 to -0.001), though the effect size was small. Controlling for the prior levels of the depressive symptoms this indirect effect became non-significant. Theoretical and clinical implications of the findings for the youth with OCD and comorbid depression are discussed.

Personality as a Predictor of Treatment Response to Escitalopram in Adults With Body Dysmorphic Disorder.

OBJECTIVE: Serotonin reuptake inhibitors (SRIs) are the first-line pharmacotherapy for body dysmorphic disorder (BDD), a common and severe disorder. However, predictors and correlates of treatment response are not well understood. A closer examination of baseline personality dimensions and disorders and of changes in personality during SRI treatment is needed to advance knowledge of this clinically important issue. METHOD: We conducted a secondary analysis of data from a pharmacotherapy relapse prevention trial of the SRI escitalopram in adults with BDD to examine personality dimensions and traits, as well as whether these variables predict and correlate with treatment response. A total of 65 participants with BDD completed the Revised NEO Personality Inventory (NEO PI-R) before starting open-label treatment with escitalopram and 42 participants completed the NEO PI-R after treatment. RESULTS: At baseline, participants with BDD displayed higher levels of neuroticism and lower levels of extraversion than a normed reference group. Higher baseline neuroticism was a significant predictor of nonresponse to escitalopram treatment, even when baseline depression severity was controlled for. Changes in neuroticism were not associated with treatment response. CONCLUSION: Our findings underscore the relationship between BDD and neuroticism, and they suggest a link between neuroticism and SRI treatment response.

Fear extinction learning as a predictor of response to cognitive behavioral therapy for pediatric obsessive compulsive disorder.

BACKGROUND: While cognitive behavior therapy (CBT) is an effective treatment for many children and adolescents with Obsessive Compulsive Disorder (OCD), therapeutic response is variable. Fear conditioning and extinction are central constructs underlying exposure-based CBT. Fear extinction learning assessed prior to CBT may be a useful predictor of CBT response for guiding treatment decisions. METHODS: Sixty-four youth who participated in a randomized placebo-controlled trial of CBT with and without d-cycloserine (DCS) completed a fear conditioning task. Skin conductance response (SCR) scores were used to measure fear acquisition and extinction to determine whether extinction learning could predict CBT response. RESULTS: CBT responders and non-responders appeared to acquire conditioned fear SCRs in a similar manner. However, differences between treatment responders and non-responders emerged during the extinction phase. A responder (responder, non-responder) by conditioned stimulus type (CS+, CS-) interaction showed that CBT responders differentiated the stimulus paired with (CS+) and without (CS-) the unconditioned stimulus correctly during early and late extinction, whereas the CBT non-responders did not (p = .004). CONCLUSIONS: While the small sample size makes conclusions tentative, this study supports an emerging literature that differential fear extinction may be an important factor underlying clinical correlates of pediatric OCD, including CBT response.

D-Cycloserine augmentation of cognitive behavior therapy for pediatric OCD: Predictors and moderators of outcome.

BACKGROUND: Over half of children receiving cognitive behavioral therapy (CBT) for obsessive compulsive disorder (OCD) do not fully remit. To improve response rates and enhance extinction learning, d-cycloserine (DCS) has been examined as an augmenting agent of CBT. To direct children with OCD towards treatments with the highest likelihood of success, the current study evaluated the conditions under which DCS augmentation works best (i.e., moderators) and the baseline characteristics associated with outcome, irrespective of treatment type (i.e., predictors). METHODS: Data came from a two-site randomized controlled trial (N = 142) in which children received either DCS + CBT (n = 70) or placebo + CBT. RESULTS: No baseline variables moderated the effects of DCS augmentation on CBT outcome. However, several predictor variables were associated with a decreased likelihood of achieving remission status, including higher family accommodation scores, higher impairment scores, higher depression scores, and higher externalizing scores. Furthermore, better insight at pre-treatment was associated with more improvement longitudinally on a clinician-rated summary measure of illness severity. LIMITATIONS: The current study did not examine all variables that had previously been shown to moderate or predict treatment outcome (e.g., family history of OCD or cognitive profile). CONCLUSIONS: The absence of significant moderators suggests that baseline factors cannot yet be used to determine who benefits most from DCS. To maximize treatment benefits for children presenting with identified predictors of worse treatment outcome, clinicians might need to adapt existing CBT protocols and administer additional interventions that address patients' specific problem areas.

Atypical symptom presentations in children and adolescents with obsessive compulsive disorder.

BACKGROUND: Common symptom presentations in youth with Obsessive Compulsive Disorder (OCD) are easily recognized and are included in the Children's Yale Brown Obsessive Compulsive Scale (CY-BOCS) symptom checklist. However, some youth may occasionally present with atypical or unusual symptoms that are less readily recognized as OCD and may be confused with other disorders that sometimes overlap, such as autism spectrum disorder or even psychosis. METHODS: Case synopses which are thematically linked and exemplify and illustrate two distinct types of unusual or atypical symptom presentations are described. These symptoms are embedded in the subjects' broader clinical picture, that more correctly identifies the atypical symptoms as a variant feature of OCD rather than some other diagnostic condition. RESULTS: We describe twenty-four children with OCD. Twelve children had obsessions related to adverse experiences of places, times or other people that were felt as horrific, abhorrent or disgusting. These obsessions led to contamination fears of any thoughts or actions associated with those places, events or people. In those whose OCD was a reaction to another person, the contamination obsession often took the form of fear of acquiring an unwanted trait or characteristic by association, which was then avoided. Twelve other youth had obsessions driven by a primary sensory experience that was intolerable, including tactile, olfactory, and auditory stimuli. These sensory experiences were sometimes linked to specific objects or people, driving time-consuming repetitive behaviors to avoid or alleviate the sensory discomfort. CONCLUSION: Recognition of atypical presentations of OCD, such as fear of contamination by association with adverse experiences and primary sensory intolerance leading to OCD will help clinicians to better identify and treat these unique symptoms.