Dysregulated Amino Acid Sensing Drives Colorectal Cancer Growth and Metabolic Reprogramming Leading to Chemoresistance.

BACKGROUND & AIMS: Colorectal cancer (CRC) is a devastating disease that is highly modulated by dietary nutrients. Mechanistic target of rapamycin complex 1 (mTORC1) contributes to tumor growth and limits therapy responses. Growth factor signaling is a major mechanism of mTORC1 activation. However, compensatory pathways exist to sustain mTORC1 activity after therapies that target oncogenic growth factor signaling. Amino acids potently activate mTORC1 via amino acid-sensing GTPase activity towards Rags (GATOR). The role of amino acid-sensing pathways in CRC is unclear. METHODS: Human colon cancer cell lines, preclinical intestinal epithelial-specific GATOR1 and GATOR2 knockout mice subjected to colitis-induced or sporadic colon tumor models, small interfering RNA screening targeting regulators of mTORC1, and tissues of patients with CRC were used to assess the role of amino acid sensing in CRC. RESULTS: We identified loss-of-function mutations of the GATOR1 complex in CRC and showed that altered expression of amino acid-sensing pathways predicted poor patient outcomes. We showed that dysregulated amino acid-sensing induced mTORC1 activation drives colon tumorigenesis in multiple mouse models. We found amino acid-sensing pathways to be essential in the cellular reprogramming of chemoresistance, and chemotherapeutic-resistant patients with colon cancer exhibited de-regulated amino acid sensing. Limiting amino acids in in vitro and in vivo models (low-protein diet) reverted drug resistance, revealing a metabolic vulnerability. CONCLUSIONS: Our findings suggest a critical role for amino acid-sensing pathways in driving CRC and highlight the translational implications of dietary protein intervention in CRC.

Association of initial opioid prescription duration and an opioid refill by pain diagnosis: Evidence from outpatient settings in ten US health systems.

OBJECTIVE: The Centers for Disease Control and Prevention's 2022 Clinical Practice Guideline for Prescribing Opioids for Pain cautioned that inflexible opioid prescription duration limits may harm patients. Information about the relationship between initial opioid prescription duration and a subsequent refill could inform prescribing policies and practices to optimize patient outcomes. We assessed the association between initial opioid duration and an opioid refill prescription. METHODS: We conducted a retrospective cohort study of adults ≥19 years of age in 10 US health systems between 2013 and 2018 from outpatient care with a diagnosis for back pain without radiculopathy, back pain with radiculopathy, neck pain, joint pain, tendonitis/bursitis, mild musculoskeletal pain, severe musculoskeletal pain, urinary calculus, or headache. Generalized additive models were used to estimate the association between opioid days' supply and a refill prescription. RESULTS: Overall, 220,797 patients were prescribed opioid analgesics upon an outpatient visit for pain. Nearly a quarter (23.5%) of the cohort received an opioid refill prescription during follow-up. The likelihood of a refill generally increased with initial duration for most pain diagnoses. About 1 to 3 fewer patients would receive a refill within 3 months for every 100 patients initially prescribed 3 vs. 7 days of opioids for most pain diagnoses. The lowest likelihood of refill was for a 1-day supply for all pain diagnoses, except for severe musculoskeletal pain (9 days' supply) and headache (3-4 days' supply). CONCLUSIONS: Long-term prescription opioid use increased modestly with initial opioid prescription duration for most but not all pain diagnoses examined.

Disparities in State Medicaid Coverage of Tretinoin for Pigmentary Disorders Compared to Acne Vulgaris.

BACKGROUND: Melasma and post-inflammatory hyperpigmentation (PIH) are common cosmetic dermatologic conditions that predominantly affect patients with skin phototypes III-VI. Comparing treatment coverage for these pigmentary disorders to treatment coverage for acne vulgaris may demonstrate disparities in insurance coverage for diseases that primarily affect patients of color. OBJECTIVE: Describe differences in Medicaid coverage for topical tretinoin for melasma and PIH vs. acne vulgaris in all 50 states and the District of Columbia. METHODS: This is a cross-sectional study of Medicaid insurance plans in all 50 states and the District of Columbia conducted between February 1 and 28, 2023. Data was collected from online publicly available preferred drug lists, prior authorization criteria, and email/telephone inquiries. Information was collected regarding coverage restrictions, including age restrictions, diagnostic restrictions, preferred drug status, and prior authorization requirements. RESULTS: Complete coverage data for all three clinical indications was retrieved from 30 (58.8%) states; partial coverage data for acne vulgaris was retrieved from 16 (31.4%) states; no coverage data was retrieved from 5 (9.8%) states. Of states reporting coverage data, topical tretinoin is covered in 45 (97.8%) states for acne vulgaris and 10 (33.3%) states for melasma and post-inflammatory hyperpigmentation. There was decreased Medicaid coverage of topical tretinoin for acne vulgaris compared to melasma and PIH (P<0.05).  Conclusion: There is differential Medicaid coverage for acne vulgaris compared to pigmentary disorders which disproportionately affect patients of color. Greater advocacy is required to ensure equal treatment for conditions that affect racial minority patients. J Drugs Dermatol. 2024;23(6):e151-e153.     doi:10.36849/JDD.8069e  .

Prescription Opioid Dose Reductions and Potential Adverse Events: a Multi-site Observational Cohort Study in Diverse US Health Systems.

BACKGROUND: In response to the opioid crisis in the United States, population-level prescribing of opioids has been decreasing; there are concerns, however, that dose reductions are related to potential adverse events. OBJECTIVE: Examine associations between opioid dose reductions and risk of 1-month potential adverse events (emergency department (ED) visits, opioid overdose, benzodiazepine prescription fill, all-cause mortality). DESIGN: This observational cohort study used electronic health record and claims data from eight United States health systems in a prescription opioid registry (Clinical Trials Network-0084). All opioid fills (excluding buprenorphine) between 1/1/2012 and 12/31/2018 were used to identify baseline periods with mean morphine milligram equivalents daily dose of  ≥ 50 during six consecutive months. PATIENTS: We identified 60,040 non-cancer patients with  ≥ one 2-month dose reduction period (600,234 unique dose reduction periods). MAIN MEASURES: Analyses examined associations between dose reduction levels (1- < 15%, 15- < 30%, 30- < 100%, 100% over 2 months) and potential adverse events in the month following a dose reduction using logistic regression analysis, adjusting for patient characteristics. KEY RESULTS: Overall, dose reduction periods involved mean reductions of 18.7%. Compared to reductions of 1- < 15%, dose reductions of 30- < 100% were associated with higher odds of ED visits (OR 1.14, 95% CI 1.10, 1.17), opioid overdose (OR 1.41, 95% CI 1.09-1.81), and all-cause mortality (OR 1.39, 95% CI 1.16-1.67), but lower odds of a benzodiazepine fill (OR 0.83, 95% CI 0.81-0.85). Dose reductions of 15- < 30%, compared to 1- < 15%, were associated with higher odds of ED visits (OR 1.08, 95% CI 1.05-1.11) and lower odds of a benzodiazepine fill (OR 0.93, 95% CI 0.92-0.95), but were not associated with opioid overdose and all-cause mortality. CONCLUSIONS: Larger reductions for patients on opioid therapy may raise risk of potential adverse events in the month after reduction and should be carefully monitored.

Clinical Application of Artificial Intelligence for Non-melanoma Skin Cancer.

OPINION STATEMENT: The development and implementation of artificial intelligence is beginning to impact the care of dermatology patients. Although the clinical application of AI in dermatology to date has largely focused on melanoma, the prevalence of non-melanoma skin cancers, including basal cell and squamous cell cancers, is a critical application for this technology. The need for a timely diagnosis and treatment of skin cancers makes finding more time efficient diagnostic methods a top priority, and AI may help improve dermatologists' performance and facilitate care in the absence of dermatology expertise. Beyond diagnosis, for more severe cases, AI may help in predicting therapeutic response and replacing or reinforcing input from multidisciplinary teams. AI may also help in designing novel therapeutics. Despite this potential, enthusiasm in AI must be tempered by realistic expectations regarding performance. AI can only perform as well as the information that is used to train it, and development and implementation of new guidelines to improve transparency around training and performance of algorithms is key for promoting confidence in new systems. Special emphasis should be placed on the role of dermatologists in curating high-quality datasets that reflect a range of skin tones, diagnoses, and clinical scenarios. For ultimate success, dermatologists must not be wary of AI as a potential replacement for their expertise, but as a new tool to complement their diagnostic acumen and extend patient care.

Proliferative synovitis, an ultrasound pattern associated with ACPA-positive patients and erosive disease in rheumatoid arthritis.

OBJECTIVES: To analyse ultrasound (US) differences between rheumatoid arthritis (RA) patients according to autoantibody status and characterise the clinical and radiological features associated with the US pattern of seropositive patients. METHODS: We collected demographic and clinical data and bilateral hand US images of RA patients. We defined an extreme proliferative US pattern, encompassing synovial hypertrophy grade II-III with Power Doppler signal, which we called US proliferative synovitis (US PS). To better characterise US PS, MRI of the dominant hand and immunostaining of synovial biopsies were made in subgroups of 42 and 23 patients, respectively. RESULTS: We included 205 RA patients (84.8% seropositive). No significant differences in disease activity were found according to autoantibody status. US PS was found in 55.5% of seropositive and 16.1% of seronegative patients (p=0.0001). In the multivariate analysis, erosions [OR 4.90 95% CI (2.17-11.07), p=0.0001] and ACPA [OR 3.5 95% CI (1.39-10.7), p=0.009] but not RF status [OR 0.74 95% CI (0.31-1.71), p=0.483] were independently associated with US PS. After a mean follow-up of 46 months, US PS was independently associated with changes in therapy (OR 2.63, 95% CI 1.20-5.77, p=0.016). Ninety-four per cent of joints with US PS had RAMRIS synovitis sub-index grade 2-3. US PS was significantly associated with higher synovial vessel density (p=0.042). CONCLUSIONS: In RA patients, US PS was associated with ACPA status, erosive disease and an enhanced need to change disease-modifying anti-rheumatic drug therapy in the long-term. At synovial level, this US pattern was characterised by higher vessel density.

Attitudes and personal beliefs about the COVID-19 vaccine among people with COVID-19: a mixed-methods analysis.

BACKGROUND: Little research is available regarding vaccination attitudes among those recently diagnosed with COVID-19. This is important to investigate, particularly among those experiencing mild-to-moderate illness, given the ongoing need to improve uptake of both initial vaccine series and booster doses, and the divergent ways such an experience could impact attitudes. METHODS: From September 3 - November 12, 2021, all patients enrolled in Baylor Scott & White's "COVID-19 Digital Care Journey for Home Monitoring" were invited to participate in an online survey that included questions about vaccination status and attitudes/opinions regarding COVID-19 and the COVID-19 vaccines. Following an item asking about accordance of COVID-19 vaccination with religious/personal beliefs, participants were asked to describe those beliefs and how they relate to taking/not taking the vaccine. RESULTS: Of 8,075 patients age ≥ 18 years diagnosed with COVID-19 and invited to join the survey during the study period, 3242 (40.2%) were fully vaccinated. In contrast, among the 149 who completed the questionnaire, 95(63.8%) reported full vaccination. Responses differed significantly between vaccination groups. The vaccinated group strongly agreed that COVID-19 is a major public health problem, the vaccines are safe and effective, and their decision to vaccinate included considering community benefit. The unvaccinated group responded neutrally to most questions addressing safety and public health aspects of the vaccine, while strongly disagreeing with statements regarding vaccine effectiveness and other preventative public health measures. The vaccinated group strongly agreed that taking the vaccine accorded with their religious/personal beliefs, while the unvaccinated group was neutral. In qualitative analysis of the free text responses "risk perception/calculation" and "no impact" of religious/personal beliefs on vaccination decisions were frequent themes/subthemes in both groups, but beliefs related to the "greater good" were a strong driver among the vaccinated, while statements emphasizing "individual choice" were a third frequent theme for the unvaccinated. CONCLUSION: Our results show that two of the three factors that drive vaccine hesitancy (complacency, and lack of confidence in the vaccines) are present among unvaccinated adults recently diagnosed with COVID-19. They also show that beliefs emphasizing the importance of the greater good promote public health participation.

Multiplex immunofluorescence to measure dynamic changes in tumor-infiltrating lymphocytes and PD-L1 in early-stage breast cancer.

BACKGROUND: The H&E stromal tumor-infiltrating lymphocyte (sTIL) score and programmed death ligand 1 (PD-L1) SP142 immunohistochemistry assay are prognostic and predictive in early-stage breast cancer, but are operator-dependent and may have insufficient precision to characterize dynamic changes in sTILs/PD-L1 in the context of clinical research. We illustrate how multiplex immunofluorescence (mIF) combined with statistical modeling can be used to precisely estimate dynamic changes in sTIL score, PD-L1 expression, and other immune variables from a single paraffin-embedded slide, thus enabling comprehensive characterization of activity of novel immunotherapy agents. METHODS: Serial tissue was obtained from a recent clinical trial evaluating loco-regional cytokine delivery as a strategy to promote immune cell infiltration and activation in breast tumors. Pre-treatment biopsies and post-treatment tumor resections were analyzed by mIF (PerkinElmer Vectra) using an antibody panel that characterized tumor cells (cytokeratin-positive), immune cells (CD3, CD8, CD163, FoxP3), and PD-L1 expression. mIF estimates of sTIL score and PD-L1 expression were compared to the H&E/SP142 clinical assays. Hierarchical linear modeling was utilized to compare pre- and post-treatment immune cell expression, account for correlation of time-dependent measurement, variation across high-powered magnification views within each subject, and variation between subjects. Simulation methods (Monte Carlo, bootstrapping) were used to evaluate the impact of model and tissue sample size on statistical power. RESULTS: mIF estimates of sTIL and PD-L1 expression were strongly correlated with their respective clinical assays (p < .001). Hierarchical linear modeling resulted in more precise estimates of treatment-related increases in sTIL, PD-L1, and other metrics such as CD8+ tumor nest infiltration. Statistical precision was dependent on adequate tissue sampling, with at least 15 high-powered fields recommended per specimen. Compared to conventional t-testing of means, hierarchical linear modeling was associated with substantial reductions in enrollment size required (n = 25➔n = 13) to detect the observed increases in sTIL/PD-L1. CONCLUSION: mIF is useful for quantifying treatment-related dynamic changes in sTILs/PD-L1 and is concordant with clinical assays, but with greater precision. Hierarchical linear modeling can mitigate the effects of intratumoral heterogeneity on immune cell count estimations, allowing for more efficient detection of treatment-related pharmocodynamic effects in the context of clinical trials. TRIAL REGISTRATION: NCT02950259 .

Depression education fotonovela for engagement of Hispanic patients in treatment: a randomized clinical trial.

BACKGROUND: We report the primary outcomes from a randomized clinical trial testing a novel culturally-adapted patient education intervention to increase engagement of Hispanic patients in depression treatment. The Depression Education Fotonovela (DEF), Secret Feelings, incorporates popular images, cultural norms, and vivid pictures embedded within a soap opera narrative to increase depression knowledge and dispel myths about treatment. We then assessed engagement in a integrated care treatment model in response to the education intervention and subsequent changes in depression symptoms in a large community-based clinic whose patient population is majority Hispanic. METHOD: The sample included 150 adult Hispanic patients with a confirmed diagnosis of depression who were randomly assigned to either: [1] integrated care + fotonovela; or [2] integrated care + standard education. Differences between treatment groups were examined as were changes in depression, anxiety, depression knowledge, and stigma scores over time and engagement in treatment. RESULTS: Results indicated that while depression scores significantly decreased over time for participants (F [2.811, 416.054] = 197.69, p < .001, η2 = .572), no differences between the two education groups were found (F [1, 148] = 0.70, p = .403, η2 = .005). At 12-month follow-up, 101 patients (80.8%) reported a 50% of greater reduction in depression scores from baseline. CONCLUSIONS: We found little difference between the two education groups, suggesting that either may helpful for engaging Hispanic patients into care. Better tailoring of patient education, with the fotonovela or similarly adapted tools, will require more directly addressing the stigma associated with antidepressant medication. TRIAL REGISTRATION: The study was registered with www.clinicaltrials.gov : NCT02702596 , on 03/20/2016. Retrospectively registered.

Communication in children born very preterm: a prospective cohort study.

AIM: To compare language, speech, and voice of children born preterm and at term, and determine relevant predictors of outcome. METHOD: Three hundred infants (150 males, 150 females; 149 born at <30wks' gestation, 151 term-born) were prospectively recruited at birth from the Royal Women's Hospital. We administered the Preschool Language Scales, Fifth Edition, Diagnostic Evaluation of Articulation and Phonology, Grade Roughness Breathiness Asthenia Strain Scale, and Pediatric Voice Handicap Index at 3 years, and compared groups. We examined hypothesized predictors in children born preterm: gestational age at birth, birthweight, sex, chronic lung disease, high social risk, multilingualism, neurodevelopmental diagnosis, and oromotor feeding. RESULTS: Children born preterm had poorer language than children born at term (coefficient -5.43). Speech and voice were similar between groups (coefficients -0.70 to 1.63). Chronic lung disease predicted voice (coefficient 6.05); male sex (coefficients 4.54-6.18), high social risk (coefficient -6.02 to -9.30), and neurodevelopmental diagnosis (coefficients -16.42 to -20.61) predicted language. INTERPRETATION: Children born before 30 weeks' gestation had poorer language than children born at term. Children born preterm with neurodevelopmental disabilities or high social risk experience poorer language outcomes, and would benefit from enrichment of their language environment. WHAT THIS PAPER ADDS: Speech and voice outcomes were similar between children born preterm and at term. Male sex, high social risk, and neurodevelopmental diagnosis predicted language outcomes.

Construction of an ICF core set and ICF-based questionnaire assessing activities and participation in patients with systemic sclerosis.

OBJECTIVES: To develop an International Classification of Functioning, Disability and Health (ICF) core set for SSc and to conceive a patient-centred ICF-based questionnaire assessing activities and participation in patients with SSc. METHODS: The construction of the ICF core set followed two steps. In the first step, meaningful concepts related to SSc were collected using data source triangulation from patients (n = 18), experts (n = 10) and literature (n = 174 articles). In the second step, concepts were linked to the best-matching ICF categories by one reviewer according to prespecified linking rules. Finally, patient-reported activities and participation categories of the ICF core set were translated into understandable questions. RESULTS: After linking concepts to ICF categories, 150 ICF categories were collected from focus groups, 22 from experts and 82 from literature. After fusion of the sources and removal of duplicates, the ICF core set included 164 categories: one at the first level, 157 at the second level and six at the third level, with 50 categories on body functions, 15 on body structures, 52 on activities and participation, and 47 on environmental factors. Patient-reported ICF categories on activities and participation were translated into a patient-centred ICF-based 65-item questionnaire. CONCLUSION: The present study proposes an ICF core set that offers a conceptual framework for SSc patients' care and health policy. Using a patient-centred approach, a patient-centred ICF-based questionnaire, the Cochin Scleroderma ICF-65 questionnaire, assessing activities and participation in patients with SSc, was conceived. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov, NCT01848418.

Impact of an electronic medium delivery of warfarin education in a low income, minority outpatient population: a pilot intervention study.

BACKGROUND: Warfarin is classified as a high-alert medication for ambulatory healthcare and safe guards for high-alert medications are necessary, including the practice of mandatory patient education. The high cost of hospitalizations related to adverse events combined with the average bleeding event rate of 7-8% in spite of routine patient education, suggests the importance of new approaches to standardized health education on warfarin. We sought to evaluate the impact of a warfarin educational video using an electronic tablet on patient knowledge and to determine patients' satisfaction with the use of an electronic tablet for educational purposes in outpatient clinics serving a low income, minority population. METHODS: A warfarin educational video delivered on an electronic tablet (iPad) was delivered at two pharmacist-managed anticoagulation clinics to uninsured patients whose annual income is equal or less than two hundred percent below the poverty level were offered. Patients (n = 18) completed a pre-video and post-video knowledge test on warfarin before and after viewing the warfarin educational video on an electronic tablet and a follow-up test to measure the retention of knowledge and a patient satisfaction survey at 60 days. The primary outcome was change in knowledge test scores. Other outcome measures included adherence rates, adverse events, time in therapeutic INR range, and patient-reported satisfaction scores. RESULTS: The majority of patients were uninsured men taking warfarin for atrial fibrillation (n = 5). The median scores at post-video knowledge test and follow-up knowledge test were significantly higher than that for the pre-knowledge test (12 (11-12) vs. 10(8-11), p < 0.001). The study group had a 'time in therapeutic INR' range of 56.3%, a rate of adverse events of 24.5%, and a self-reported adherence rate to warfarin of 94.1%. The majority of patients also had positive responses to the patient satisfaction survey. CONCLUSIONS: Patient education delivered via iPad to facilitate knowledge of medication can serve as a useful tool for educating patients about warfarin and warfarin therapy. Use of an electronic medium may be a unique way to provide standard medication education to patients. TRIAL REGISTRATION: The study was retrospectively registered with: NCT03650777 ; 9/18/18.

Improving the identification and treatment of depression in low-income primary care clinics: a qualitative study of providers in the VitalSign6 program.

QUALITY PROBLEM: Despite its global burden and prevalence, Major Depressive Disorder often goes undetected and untreated, and is particularly pervasive in the primary care setting. INITIAL ASSESSMENT: One in four Texans lack health insurance, and people with behavioral health disorders are disproportionately affected. It is possible to provide high-quality depression treatment in primary care settings with outcomes equal to those provided by specialty care. The Center for Depression Research and Clinical Care offered an opportunity to transform service delivery practices in underserved primary care practices to improve quality, health status, patient experience and coordination. CHOICE OF SOLUTION: A point-of-care, web-based, self-report based software program, VitalSign6, was developed to provide universal depression screening in primary care practices and assist providers in monitoring and treating patients' symptoms using principles of Measurement-Based Care. IMPLEMENTATION: Implementation included a multi-faceted training program designed to build confidence and competence in participating clinics' medical providers and staff as well as ongoing performance improvement delivered by the VitalSign6 team. EVALUATION: Primary care providers (N = 11) were interviewed, using a semi-structured interview guide, with a focus on barriers and challenges to full integration, perceptions of the most/least valuable aspects of the program, and the program's impact on knowledge, attitudes and behaviors about depression screening and treatment. LESSONS LEARNED: More efficient technology is needed to reduce time wasted, as is training to reduce stigma and correct misconceptions about antidepressant medications. Provider buy-in is essential. CONCLUSIONS: Despite barriers, VitalSign6 increased knowledge, changed attitudes and enhanced providers' depression screening and treatment skills over time.

Culturally adapted depression education and engagement in treatment among Hispanics in primary care: outcomes from a pilot feasibility study.

BACKGROUND: Low use of anti-depressant medication, poor doctor-patient communication, and persistent stigma are key barriers to the treatment of depression in Hispanics. Common concerns include fears about the addictive and harmful properties of antidepressants, worries about taking too many pills, and the stigma attached to taking medications and seeking mental health treatments. In 2014, the Center for Medicare and Medicaid Services (CMS) funded the Depression Screening and Education: Options to Reduce Barriers to Treatment (DESEO) project to implement an education intervention designed to increase disease literacy and dispel myths about depression and its treatment among Hispanic patients thus reducing stigma and increasing treatment engagement. METHODS: The DESEO study utilized a one-group pretest-posttest design to assess the effects a culturally-adapted Depression Education Intervention's (DEI) on depression knowledge, stigma, and engagement in treatment in a sample of 350 Hispanic primary care patients with depression. The DEI utilized a fotonovela, a health education tool available in English and Spanish that uses posed photographs, captions, and soap opera narratives to raise awareness about depression and depression treatments. RESULTS: Participants reported significant decreases in depression symptoms and reported stigma about mental health care. Additionally, participants reported increased knowledge of depression yet greater negative perceptions about antidepressant medication. Finally, 89.5% of participants reported entering some form of treatment at follow-up. CONCLUSIONS: Culturally adapted depression education shows promise in increasing understanding of depression, decreasing stigma, and increasing treatment engagement among Hispanic patients in a community-based health center. Results have implications for practice in addressing common concerns about depression treatments which include fears about the addictive and harmful properties of antidepressants, worries about taking too many pills, and the stigma attached to taking psychotropic medications. TRIAL REGISTRATION: The study was retrospectively registered with www.clinicaltrials.gov : NCT02491034 July 2, 2015.

Exploring the speech and language of individuals with non-syndromic submucous cleft palate: a preliminary report.

BACKGROUND: Submucous cleft palate (SMCP) has a heterogeneous presentation and is often identified late or misdiagnosed. Diagnosis is prompted by speech, resonance or feeding symptoms associated with velopharyngeal insufficiency. However, the broader impacts of SMCP on communication have rarely been examined and therefore are poorly understood. AIM: To describe the communicative profile of individuals with non-syndromic SMCP by examining speech, language and pragmatics (social language). METHODS & PROCEDURES: Fifteen participants with SMCP aged 5;1-12;8, without a genetic diagnosis, participated in the study. Participants completed standardized assessments examining language, resonance, speech and non-verbal intellect. Parents also completed the Children's Communication Checklist (CCC-2), which provided a measure of overall communicative ability, including pragmatic skills. Formal language outcomes were compared with two cohorts: 36 individuals with overt non-syndromic clefts and 129 individuals with no history of clefting. OUTCOMES & RESULTS: Speech intelligibility was reduced secondary to hypernasality, disordered articulation and/or impaired phonology (n = 7) in children with SMCP. Poorer overall language outcomes were observed for children with SMCP compared with both those with overt clefts and no history of clefting (p < 0.001). Language scores for children with SMCP ranged from impaired (n = 6) to above the standardized mean (n = 4). Receptive and expressive language performance were independently correlated with non-verbal IQ (p < 0.01). Those with severe language impairment (n = 4) also had borderline or impaired non-verbal IQ. Parents reported that speech and semantics were the most affected sub-domains of communication, while scores were the highest for the initiation domain. Speech and language skills were correlated strongly with pragmatics (r = 0.877, p < 0.01). CONCLUSIONS & IMPLICATIONS: Overall, performance was variable within the SMCP group across speech, language and pragmatic assessments. In addition to well-documented speech difficulties, children with SMCP may have language or pragmatic impairments, suggesting that further neurodevelopmental influences may be at play. As such, for individuals with SMCP, additional clinical screening of language and pragmatic abilities may be required to ensure accurate diagnosis and guide both cleft and non-cleft related therapy programmes.

Speech Phenotyping in Unaffected Family Members of Individuals With Nonsyndromic Cleft Lip With or Without Palate.

OBJECTIVE: Subclinical phenotypes of nonsyndromic cleft lip with or without cleft palate (CL ± P) may be identified from clinically "unaffected" relatives and could be associated with specific cleft-related gene mutations. It has been hypothesized that velopharyngeal insufficiency (VPI) may be a subclinical phenotype of interest in this population, but this has not been explored quantitatively with appropriate control cohorts. The aim of this case-control study was to compare VPI in at-risk clinically unaffected relatives of individuals with nonsyndromic CL ± P with a low-risk matched normative Australian cohort. PARTICIPANTS: Clinically unaffected (ie, with no overt cleft) first-degree relatives of a proband with nonsyndromic CL ± P (n = 189) and noncleft controls (n = 207). MAIN OUTCOME MEASURE(S): Perceptual measures of VPI encompassing resonance, nasal emission, and articulation were evaluated using the Great Ormond Street Speech Assessment. Quantitative measures of VPI were obtained from the Nasometer II using standardized adult and pediatric speech stimuli. RESULTS: Both perceptual and instrumental measures showed no significant difference (P > .01) between the VPI in unaffected relatives and the noncleft comparison group. Mean nasalance scores for both groups were calculated and reported according to speech stimuli, age, and sex. CONCLUSIONS: Results suggest that VPI, measured through speech, is not a significant subclinical phenotype of nonsyndromic CL ± P. Therefore, further familial genetic investigations exploring VPI may not yield meaningful results. Exploration across multiple subclinical phenotypes in larger cohorts may enable researchers to better understand the multifaceted nature of this complex and heterogeneous anomaly.

Depression screening and education: an examination of mental health literacy and stigma in a sample of Hispanic women.

BACKGROUND: Mental health literacy consists of knowledge of a mental disorder and of the associated stigma. Barriers to depression treatment among Hispanic populations include persistent stigma which is primarily perpetuated by inadequate disease literacy and cultural factors. U.S.-born Hispanics are more likely to have depression compared to Hispanics born in Latin America and are less likely to follow a treatment plan compared to non-Hispanic whites. Hispanic women are more likely to access treatment through a primary care provider, making it an ideal setting for early mental health interventions. METHODS: Baseline data from 319 female Hispanic patients enrolled in Project DESEO: Depression Screening and Education: Options to Reduce Barriers to Treatment, were examined. The study implemented universal screening with a self-report depression screening tool (the 9-item Patient Health Questionnaire (PHQ-9) and took place at one federally qualified health center (FQHC) over a 24-month period. The current analysis examined the relationship between four culturally adapted stigma measures and depression knowledge, and tested whether mental health literacy was comparable across education levels in a sample of Hispanic women diagnosed with depression. RESULTS: Almost two-thirds of the sample had less than a high school education. Depression knowledge scores were significantly, weakly correlated with each the Stigma Concerns About Mental Health Care (ρ = - .165, p = .003), Latino Scale for Antidepressant Stigma (p = .124, p = .028), and Social Distance scores (p = .150, p = .007). Depression knowledge (F[2, 312] = 11.82, p < .001, partial η2 = .071), Social Distance scores (F[2, 312] = 3.34, p = .037, partial η2 = .021), and antidepressant medication stigma scores (F[2, 312] = 3.33, p = .037, partial η2 = .015) significantly varied by education category. Participants with at least some college education reported significantly greater depression knowledge and less stigma surrounding depression and medication than participants with lower education levels. CONCLUSIONS: Primary care settings are often the gateway to identifying undiagnosed mental health disorders, particularly for Hispanic women with comorbid physical health conditions. This study is unique in that it aims to examine the specific role of patient education level as a predictor of mental health literacy. For Hispanic women, understanding the mental health literacy of patients in a healthcare setting may improve quality of care through early detection of symptoms, culturally effective education and subsequent engagement in treatment. TRIAL REGISTRATION: The study was registered with https://clinicaltrials.gov/: NCT02491034 July 2, 2015.

Feeding behavior in three-year-old children born <30 weeks and term-born peers.

BACKGROUND: Feeding difficulties threaten growth, health and neurodevelopment, and are prevalent among infants born preterm. The literature differs on (i) whether these problems persist into early childhood, and (ii) risk factors in the preterm population. In this study we explore feeding difficulties and risk factors in preterm and term-born three-year-olds. OBJECTIVES: To determine whether three-year-olds born <30 weeks have poorer feeding outcomes than their term-born peers; and identify predictors of feeding outcomes in children born <30 weeks. METHODS: Feeding outcomes were examined in three-year-old children born <30 weeks, and a term-born comparison group, using parent report and the Behavioral Pediatric Feeding Assessment Scale (BPFAS). Factors hypothesized to be associated with feeding difficulties and preterm birth were examined in the preterm group, including: gestational age at birth, birth weight z-score, chronic lung disease (CLD), nasogastric tube (NGT) feeding at hospital discharge, age at breastfeeding cessation, oromotor feeding impairment at 12 months, weight at 12 months in kilograms and neurodevelopmental diagnoses. RESULTS: In 217 children (111 born <30 weeks, 106 term-born), parents of children born <30 weeks reported more feeding concerns on parent report questions than parents of term-born peers. CLD, NGT at discharge, neurodevelopmental diagnoses and weight at 12 months predicted these parent-reported outcomes. By contrast, there was no difference in BPFAS results between preterm and term groups, and BPFAS scores were predicted only by birth-weight z-score in the preterm group. CONCLUSIONS: Behavioral feeding outcomes for three-year-old children born <30 weeks were equivalent to term-born peers in this study, however parental concerns about feeding differed. Further investigation is required to identify the drivers of parent concerns about feeding. Children displaying core risk factors warrant specific follow-up of feeding outcomes.