Weight Loss and Weight Regain in Usual Clinical Practice: Results From the TARGET-NASH Observational Cohort.

First-line treatment for nonalcoholic fatty liver disease (NAFLD) focuses on weight loss through lifestyle modifications.1,2 Weight loss ≥5% results in reduction of steatosis and weight loss ≥10% has been associated with improvement in hepatic inflammation and fibrosis.3 The incidence and sustainability of weight loss among patients with NAFLD were estimated and associating factors identified.

Opioid Use Is More Common in Nonalcoholic Fatty Liver Disease Patients with Cirrhosis, Higher BMI, and Psychiatric Disease.

BACKGROUND: Opioid use is a topic of growing concern among patients with nonalcoholic fatty liver disease (NAFLD). Given safety concerns of opioids, proactively identifying subgroups of patients with an increased probability of opioid use may encourage practitioners to recommend alternative therapies for pain, thus reducing the likelihood of opioid misuse. This work assessed the prevalence and patient characteristics associated with opioid use in a real-world cohort of patients with NAFLD. METHODS: TARGET-NASH, an observational study of participants at 55 academic and community sites in the United States, includes patients with NAFLD defined by pragmatic case definitions. Opioid use was defined as any documented opioid prescriptions in the year prior to enrollment. The association between patient characteristics and the odds of opioid use were modeled with stepwise multivariable logistic regression and tree ensemble methods (Classification and regression tree/Boosted Tree). RESULTS: The cohort included 3,474 adult patients with NAFLD including 18.0% with documented opioid use. Variables associated with opioid use included presence of cirrhosis (OR 1.51, 95% CI 1.16-1.98), BMI ≥32 kg/m2 (OR 1.29, 95% CI 1.05-1.59), depression (OR 1.87, 95% CI 1.50-2.33), and anxiety (OR 1.59, 95% CI 1.27-1.98). In the boosted tree analysis, history of back pain, depression, and fibromyalgia had the greatest relative importance in predicting opioid use. CONCLUSION: Prescription opioids were used in nearly 1 of 5 patients with NAFLD. Given the safety concerns of opioids in patients with NAFLD, alternative therapies including low-dose acetaminophen and nonpharmacologic treatments should be considered for these patients.

Patient Characteristics and Outcomes of 11 721 Patients With Coronavirus Disease 2019 (COVID-19) Hospitalized Across the United States.

BACKGROUND: As coronavirus disease 2019 (COVID-19) disseminates throughout the United States, a better understanding of the patient characteristics associated with hospitalization, morbidity, and mortality in diverse geographic regions is essential. METHODS: Hospital chargemaster data on adult patients with COVID-19 admitted to 245 hospitals across 38 states between 15 February and 20 April 2020 were assessed. The clinical course from admission, through hospitalization, and to discharge or death was analyzed. RESULTS: A total of 11 721 patients were included (majority were >60 years of age [59.9%] and male [53.4%]). Comorbidities included hypertension (46.7%), diabetes (27.8%), cardiovascular disease (18.6%), obesity (16.1%), and chronic kidney disease (12.2%). Mechanical ventilation was required by 1967 patients (16.8%). Mortality among hospitalized patients was 21.4% and increased to 70.5% among those on mechanical ventilation. Male sex, older age, obesity, geographic region, and the presence of chronic kidney disease or a preexisting cardiovascular disease were associated with increased odds of mechanical ventilation. All aforementioned risk factors, with the exception of obesity, were associated with increased odds of death (all P values < .001). Many patients received investigational medications for treatment of COVID-19, including 48 patients on remdesivir and 4232 on hydroxychloroquine. CONCLUSIONS: This large observational cohort describes the clinical course and identifies factors associated with the outcomes of hospitalized patients with COVID-19 across the United States. These data can inform strategies to prioritize prevention and treatment for this disease.

International observational atopic dermatitis cohort to follow natural history and treatment course: TARGET-DERM AD study design and rationale.

INTRODUCTION: As new topical and systemic treatments become available for atopic dermatitis (AD), there is a need to understand how treatments are being used in routine clinical practice, their comparative effectiveness and their long-term safety in diverse clinical settings. METHODS AND ANALYSIS: The TARGET-DERM AD cohort is a longitudinal, observational study of patients with AD of all ages, designed to provide practical information on long-term effectiveness and safety unobtainable in traditional registration trials. Patients with physician-diagnosed AD receiving prescription treatment (topical or systemic) will be enrolled at academic and community clinical centres. Up to 3 years of retrospective medical records, 5 years of prospective medical records, and optional biological samples and patient-reported outcomes will be collected. The primary aims include characterisation of AD treatment regimens, evaluation of response to therapy, and description of adverse events. ETHICS AND DISSEMINATION: TARGET-DERM has been approved by a central IRB (Copernicus Group IRB, 5000 Centregreen Way Suite 200, Cary, North Carolina 27513) as well as local and institutional IRBs. No additional Ethics Committee reviews. Results will be reviewed by a publications committee and submitted to peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03661866, pre-results.

Special education use in elementary school by children with nonsyndromic orofacial clefts.

BACKGROUND: Children with nonsyndromic orofacial clefts (NS OFCs) may require exceptional children's (EC) services for academic delays. We examined EC service use of children with and without NS OFCs in NC in elementary school. METHODS: We included 559 children with NS OFCs and 6,822 children without birth defects who had NC educational records. We estimated prevalence ratios, trends in enrollment, and characteristics of eligibility classification using descriptive statistics and logistic regression by cleft subtype and race/ethnicity. We estimated the odds of third grade retention by EC enrollment using logistic regression with inverse probability of treatment weights. RESULTS: Children with NS OFCs were 3.02 (95% CI: 2.50, 3.64) times as likely to receive third grade special education (SE) services compared to unaffected peers. The prevalence odds was highest among children with CL+P (OR: 4.61, 95% CI: 3.49, 6.09) declining by 54% by fifth grade. The prevalence odds of SE for white children was approximately 1.50 times that for African American children in fourth and fifth grades. Approximately 33% of children with NS OFCs within each racial/ethnic group received SE in third grade. African American children were twice as likely to receive services under specific learning disability. Children with NS OFCs receiving EC services were 44% (OR: 0.56; 95% CI: 0.13, 2.38) less likely to be retained in third grade compared to children with NS OFCs who were not receiving services. CONCLUSIONS: Children with NS OFCs are more likely to receive SE services in elementary school compared to their unaffected peers. The eligibility category differed by racial/ethnic group.

Academic Achievement Among Children With Nonsyndromic Orofacial Clefts : A Population-Based Study.

OBJECTIVE: Children with orofacial clefts (OFCs) may experience poor reading proficiency, learning disabilities, and academic underachievement. We examined the association between nonsyndromic (NS) OFCs and end-of-grade (EOG) performance in reading and math from third through eighth grade in a sample subgroup. PARTICIPANTS: We identified a cohort of 559 children with NS-OFCs and 6822 children without birth defects, classifying cleft type by cleft lip alone, with or without cleft alveolar ridge (CL); cleft lip with cleft palate (CL+P); and cleft palate only (CP). MAIN OUTCOME MEASURES: Using logistic regression, we estimated the odds of not meeting grade-level standards among children with NS-OFCs compared to unaffected peers. Using longitudinal analyses, we estimated the odds of not meeting grade-level standards and average change in test scores through eighth grade. RESULTS: Children with NS-OFCs were 1.22 (95% CI: 0.96, 1.83) times as likely not to meet grade-level standards in reading compared to unaffected peers. The effect was similar for math (OR: 1.17; 95% CI: 0.92, 1.48). Children with CL+P were 1.33 (95% CI: 0.86, 1.83) and 1.74 (95% CI: 1.19, 2.56) times as likely not to meet grade-level standard in reading and in both subjects, respectively, compared to unaffected peers. The average rate of change in both scores was similar for children with and without OFCs. CONCLUSIONS: Poor academic performance appears greatest for children with CL+P, a finding compatible with previous observations and hypothesized mechanisms associating orofacial clefts with subtle abnormalities in brain development. Academic performance monitoring and referral for academic assistance is warranted.

Nasal Airway Dysfunction in Children with Cleft Lip and Cleft Palate: Results of a Cross-Sectional Population-Based Study, with Anatomical and Surgical Considerations.

BACKGROUND: The aesthetic aspects of the cleft lip nasal deformity have been appreciated for over a century, but the functional implications have remained largely underappreciated or misunderstood. This study describes the frequency and severity of nasal obstructive symptoms among children with cleft lip and/or cleft palate, addressing the hypotheses that age, cleft type, and severity are associated with the development of nasal obstructive symptoms. METHODS: Children with nonsyndromic cleft lip and/or cleft palate and a comparison group of unaffected children born from 1997 to 2003 were identified through the North Carolina Birth Defects Monitoring Program and birth certificates. Nasal airway obstruction was measured using the validated Nasal Obstruction Symptom Evaluation scale. RESULTS: The survey was completed by parental proxy for 176 children with cleft lip and/or cleft palate and 333 unaffected children. Nasal obstructive symptoms were more frequently reported in cleft lip with cleft palate compared with unaffected children (p < 0.0001); children who had isolated cleft lip with or without alveolus and isolated cleft palate were not statistically different from unaffected children. Patients with unilateral cleft lip with cleft palate were found to be more severely affected than bilateral cases. Nasal obstruction was observed in early childhood, although severity worsened in adolescence. CONCLUSIONS: This population-based study reports a high prevalence of nasal obstructive symptoms in children with cleft lip and/or cleft palate based on type and severity of the cleft. The authors encourage cleft teams to consider using this or similar screening methods to identify which children may benefit from functional rhinoplasty. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, I.

Issues involved in the phenotypic classification of orofacial clefts ascertained through a state birth defects registry for the North Carolina Cleft Outcomes Study.

BACKGROUND: Epidemiologic studies involving birth defects are extremely sensitive to phenotype accuracy and precision. We devised a case review and classification protocol for a project to study school achievement in children with idiopathic, nonsyndromic orofacial clefts to improve the reliability of phenotypic classification from the statewide birth defects registry. METHODS: Surveillance-program abstraction data and medical records at the birth or treating hospitals were used when available. Exclusion criteria included: median cleft lip; Tessier cleft; premaxillary agenesis; presence of a recognizable syndrome, phenotype, association, or sequence (other than Robin sequence); clefts with other malformations not considered to be normal or common variants in the newborn; and cases with documented or suspected genetic or teratogenic causes. RESULTS: Of 712 children identified with orofacial clefts, 153 were excluded, leaving 559 nonsyndromic orofacial cleft cases of unknown cause in the final study. These cases were grouped into the following clinically meaningful types: cleft lip with or without cleft alveolus; cleft lip and cleft palate; and cleft palate only. This review and classification process resulted in the elimination of 21.5% of the original cohort of identified cases, with most exclusions being due to suspected syndromic associations. CONCLUSION: Verbatim descriptions of the clinical findings are critical for accurate classification of diagnoses. This review process improved the precision of orofacial cleft phenotype classification for our study. Precision would have been further improved if all of the cases had verbatim descriptions of diagnoses and all medical records could have been reviewed by the classification team.

Classification, epidemiology, and genetics of orofacial clefts.

Orofacial clefts (OFCs) include a broad range of facial conditions that differ in cause and disease burden. In the published literature, there is substantial ambiguity in both terminology and classification of OFCs. This article discusses the terminology and classification of OFCs and the epidemiology of OFCs. Demographic, environmental, and genetic risk factors for OFCs are described, including suggestions for family counseling. This article enables clinicians to counsel families regarding the occurrence and recurrence of OFCs. Although much of the information is detailed, it is intended to be accessible to all health professionals for use in their clinical practices.

Long-term use of fluticasone propionate/salmeterol fixed-dose combination and incidence of cataracts and glaucoma among chronic obstructive pulmonary disease patients in the UK General Practice Research Database.

OBJECTIVES: Some large population-based studies have reported a dose-related increased risk of cataracts and glaucoma associated with use of inhaled corticosteroids (ICS) in patients with asthma or chronic obstructive pulmonary disease (COPD). We evaluated the association between use of ICS-containing products, specifically fluticasone propionate/salmeterol fixed-dose combination (FSC), and incidence of cataracts and glaucoma among patients with COPD in a large electronic medical record database in the United Kingdom. METHODS: We identified a cohort of patients aged 45 years and over with COPD in the General Practice Research Database (GPRD) between 2003 and 2006. Cases of incident cataracts or glaucoma were defined based on diagnosis and procedure codes and matched to controls from the risk set to estimate odds ratios (OR) and 95% confidence intervals (CI). The association with FSC or ICS exposure was modeled using conditional logistic regression. Medication exposure was assessed with respect to recency, duration, and number of prescriptions prior to the index date. Average daily dose was defined as none, low (1-250 mcg), medium (251-500 mcg), high (501-1000 mcg), or very high (1001+ mcg) using fluticasone propionate (FP) equivalents. RESULTS: We identified 2941 incident cataract cases and 327 incident glaucoma cases in the COPD cohort (n = 53,191). FSC or ICS prescriptions were not associated with risk of incident cataracts or glaucoma for any exposure category, after adjusting for confounders. We observed a lack of a dose response in all analyses, where low dose was the reference group. The odds of cataracts associated with FSC dose were medium OR: 1.1 (95% CI: 0.9-1.4); high OR: 1.2 (95% CI: 0.9-1.5); and very high OR: 1.2 (95% CI: 0.9-1.7). The odds of glaucoma associated with FSC dose: medium OR: 1.0 (95% CI: 0.5-2.1); high OR: 1.0 (95% CI: 0.5-2.0); and very high OR: 1.0 (95% CI: 0.4-2.8). CONCLUSIONS: FSC or other ICS exposure was not associated with an increased odds of cataracts or glaucoma, nor was a dose-response relationship observed in this population-based nested case-control study of COPD patients in the United Kingdom.

Long-term use of fluticasone propionate/salmeterol fixed-dose combination and incidence of nonvertebral fractures among patients with COPD in the UK General Practice Research Database.

INTRODUCTION: There has been inconsistent evidence on the association between use of inhaled corticosteroids (ICS) and increased risk of nonvertebral fractures in patients with asthma or chronic obstructive pulmonary disease (COPD). In a large population-based study in the United Kingdom, we estimated the association between fluticasone propionate/salmeterol fixed-dose combination (FSC) and other ICS use and nonvertebral fracture incidence among patients with COPD. METHODS: We identified a cohort of patients aged ≥ 45 years with COPD in the General Practice Research Database (GPRD) between 2003 and 2006. We used a nested case-control design to estimate the odds of incident nonvertebral fractures associated with prior prescriptions of FSC and other ICS, applying conditional logistic regression and controlling for potential confounders. Exposure to FSC and other ICS was assessed by recency, duration, and number of prescriptions. Average daily dose was defined as low, medium, high, or very high using fluticasone propionate equivalents. RESULTS: We identified 1523 nonvertebral fracture cases among 53 191 patients with COPD at risk in the cohort. Use of FSC in the year prior to the index date was associated with a statistically significant increase in the odds of nonvertebral fractures (odds ratio [OR], 1.25; 95% confidence interval [CI], 1.07-1.47); however, there was no increase in the odds of nonvertebral fractures for other ICS use (OR, 1.12; 95% CI, 0.97-1.30). When examining results by the recent use of prescriptions, an exposure that occurred farther from the index date was associated with a significant increase in nonvertebral fracture (26-52 days prior OR, 1.36; 95% CI, 1.04-1.77; 53-365 days prior OR, 1.39; 95% CI, 1.07-1.78), whereas categories of more recent use (0-12 days prior or 13-25 days prior) were not associated with nonvertebral fractures relative to no FSC use. No pattern of association between increasing levels of FSC or other ICS average daily dose and increased odds of nonvertebral fracture was observed. CONCLUSION: We did not observe a consistent association between prescriptions of FSC or other ICS in terms of recent use or average daily dose in the prior year and increases in the odds of nonvertebral fractures in patients with COPD, although ever use of FSC was associated with a slight elevation in the odds.