Vascular Function and Uric Acid-Lowering in Stage 3 CKD.

Hyperuricemia may contribute to endothelial dysfunction in CKD. We evaluated whether lowering serum uric acid levels with allopurinol improves endothelial dysfunction in 80 participants ≥18 years of age with stage 3 CKD and asymptomatic hyperuricemia (≥7 mg/dl in men and ≥6 mg/dl in women) randomized in a double-blinded manner to receive placebo or allopurinol for 12 weeks. Randomization was stratified according to presence or absence of diabetes mellitus. We measured vascular endothelial function by brachial artery flow-mediated dilation. No significant differences existed between groups at baseline; 61% of the participants had diabetes mellitus in both groups. The placebo and the allopurinol groups had baseline serum uric acid levels (SDs) of 8.7 (1.6) mg/dl and 8.3 (1.4) mg/dl, respectively, and baseline flow-mediated dilation values (SDs) of 6.0% (5.0%) and 4.8% (5.0%), respectively. Compared with placebo, allopurinol lowered serum uric acid significantly but did not improve endothelial function. In participants without diabetes mellitus, allopurinol associated with a trend toward improved flow-mediated dilation (+1.4% [3.9%] versus -0.7% [4.1%] with placebo), but this was not statistically significant (P=0.26). Furthermore, we did not detect significant differences between groups in BP or serum levels of markers of inflammation and oxidative stress. In conclusion, allopurinol effectively and safely lowered serum uric acid levels in adults with stage 3 CKD and asymptomatic hyperuricemia but did not improve endothelial function in this sample of patients.

Gastric leiomyoma in a child with Gorlin-Goltz syndrome: First pediatric case.

Gorlin-Goltz syndrome (GGS), also known as nevoid basal cell carcinoma syndrome (MIM 109 400), is a rare genetic condition with a prevalence between 1/56 000 and 1/256 000. Clinical presentation is usually characterized by multiple basal cell carcinomas, odontogenic jaw keratocysts, palmar or plantar pitting and skeletal anomalies. It is furthermore associated with the development of various tumors beside basal cell carcinoma, among which medulloblastoma is the most frequent. Increased incidence of other mesenchymal neoplasms, however, is also well known: recently the first adult case of gastric leiomyoma in GGS was reported, and the inclusion of "fibromas and leiomyomas of other organs" in the minor criteria for the diagnosis was suggested. We report the first case of a pediatric patient with GGS who also developed a gastric leiomyoma: the present case illustrates the need for this change to the diagnostic criteria to encompass the highly variable presentations and phenotype in GGS.

Systematic Review and Meta-analysis to Compare the Short- and Long-term Outcomes of Non-operative Management With Early Operative Management of Simple Appendicitis in Children After the COVID-19 Pandemic.

BACKGROUND: Non-operative management (NOM) of simple appendicitis is becoming an increasingly researched treatment option. This systematic review aims to describe the short and long-term failure rates of NOM and the complication rate of appendicectomy in children with simple appendicitis. METHODS: The systematic review was registered a priori (CRD42022322149). Study inclusion criteria are: participants aged ≤ 18 years of age; groups undergoing both NOM and appendicectomy for simple appendicitis; outcomes including one or more of: NOM failure rate at 30 days or 1 year and beyond; study design: RCT or case control study. Four databases were searched and 3 reviewers determined study eligibility and data extraction. Risk of bias was assessed and meta-analysis was performed using Stata. RESULTS: The database search identified 2731 articles, 14 studies met the inclusion criteria; 4 RCTs and 10 case controlled studies. All studies had moderate-serious risk of bias. There were no deaths in either group in any study. Meta-analysis demonstrated a 30 day failure rate of 20 % (95 % CI 11-29 %) and 11 studies reported failure rate at 1 year or beyond at 32 % (95 % CI 25-38 %). Rates of significant complications of appendicectomy was 1 % (95 % CI 0-1 %). CONCLUSIONS: Non-operative management of simple appendicitis in children is safe, with moderate early success. The failure rate increases over time, resulting in eventual appendicectomy in a third of the children diagnosed with appendicitis. These data will enable clinicians to have an informed discussion with children and their parents about their treatment options for simple appendicitis. LEVEL OF EVIDENCE: II.

Testing the validity and reliability of the Person-Centered Contraceptive Counseling (PCCC) Performance Measure in a Real-World Contraceptive Access Program.

OBJECTIVES: To validate the Person-Centered Contraceptive Counseling (PCCC) patient-reported outcome performance measure and assess for differences by sociodemographic attributes using survey data from a multistate contraceptive access program. STUDY DESIGN: This analysis explored internal reliability and construct validity of the PCCC using survey data from 1413 patients who visited 15 health centers in Washington state and Massachusetts that had partnered with Upstream USA. RESULTS: Multiple psychometric indicators provided evidence of reliability and validity. Significant associations between the highest PCCC rating and conceptually-related survey questions (i.e., experience with bias/coercion and shared decision-making) provided further evidence of construct validity. CONCLUSIONS: Our findings demonstrate that the PCCC is valid and reliable. The results also highlight differences in experience of care by patient-reported race and ethnicity, income level, and language.

Quality Improvement to Eliminate Disparities in Developmental Screening for Patients Needing Interpreters.

Children from households with a preferred language other than English are less likely to receive timely identification and treatment for developmental delay than children of native English speakers. In dismantling this inequity, the role of primary care pediatrics is to establish equitable systems for screening and referral. This project, conducted in a network of twelve pediatric primary care centers, focused on eliminating a small but systematic disparity in developmental screening rates between families who did and did not require interpreters (86% versus 92%). The specific aim was to increase developmental screen completion among patients needing interpreters from 86% to 92% of age-appropriate well-child visits. Methods: Data were extracted from the electronic health record (EHR) to measure the proportion of 9-, 18-, 24-, and 30-month well-child visits at which developmental screens were completed, stratified by interpreter need (n = 31,461 visits; 7500 needing interpreters). One primary care center tested small changes to standardize processes, eliminate workarounds, and leverage EHR features using the Institute for Healthcare Improvement's Model for Improvement. The QI team plotted screen completion on control charts and spread successful changes to all 12 clinics. Statistical process control evaluated the significance of changes in screening rates. Results: For patients needing interpreters, screen completion rose across all clinics from 86% to 93% when the clinics implemented the new process. Screen completion for patients not needing interpreters remained at 92%. Conclusion: A standardized process supported by the EHR improved developmental screening among patients needing interpreters, eliminating disparities.

Systematic review and narrative synthesis of the impact of Appreciative Inquiry in healthcare.

BACKGROUND: Appreciative Inquiry is a motivational, organisational change intervention, which can be used to improve the quality and safety of healthcare. It encourages organisations to focus on the positive and investigate the best of 'what is' before thinking of 'what might be', deciding 'what should be' and experiencing 'what can be'. Its effects in healthcare are poorly understood. This review seeks to evaluate whether Appreciative Inquiry can improve healthcare. METHODS: Major electronic databases and grey literature were searched. Two authors identified reports of Appreciative Inquiry in clinical settings by screening study titles, abstracts and full texts. Data extraction, in duplicate, grouped outcomes into an adapted Kirkpatrick model: participant reaction, attitudes, knowledge/skills, behaviour change, organisational change and patient outcomes. RESULTS: We included 33 studies. One randomised controlled trial, 9 controlled observational studies, 4 qualitative studies and 19 non-controlled observational reports. Study quality was generally poor, with most having significant risk of bias. Studies report that Appreciative Inquiry impacts outcomes at all Kirkpatrick levels. Participant reaction was positive in the 16 studies reporting it. Attitudes changed in the seventeen studies that reported them. Knowledge/skills changed in the 14 studies that reported it, although in one it was not universal. Behaviour change occurred in 12 of the 13 studies reporting it. Organisational change occurred in all 23 studies that reported it. Patient outcomes were reported in eight studies, six of which reported positive changes and two of which showed no change. CONCLUSION: There is minimal empirical evidence to support the effectiveness of Appreciative Inquiry in improving healthcare. However, the qualitative and observational evidence suggests that Appreciative Inquiry may have a positive impact on clinical care, leading to improved patient and organisational outcomes. It is, therefore, worthy of consideration when trying to deliver improvements in care. However, high-quality studies are needed to prove its effects. PROSPERO REGISTRATION NUMBER: CRD42015014485.

A Rare Case of Complete Penile Agenesis.

Aphallia, or penile agenesis, is rare (1:30 million)1 and associated with other urogenital anomalies.2 Under 100 cases of aphallia have been reported worldwide.1 Pathogenesis is uncertain but thought to be failure of formation of the genital tubercle.2 We present a case of complete penile agenesis with anorectal and urological malformations.

Lessons Learned in Creating Interoperable Fast Healthcare Interoperability Resources Profiles for Large-Scale Public Health Programs.

OBJECTIVE: This article describes lessons learned from the collaborative creation of logical models and standard Health Level Seven (HL7) Fast Healthcare Interoperability Resources (FHIR) profiles for family planning and reproductive health. The National Health Service delivery program will use the FHIR profiles to improve federal reporting, program monitoring, and quality improvement efforts. MATERIALS AND METHODS: Organizational frameworks, work processes, and artifact testing to create FHIR profiles are described. RESULTS: Logical models and FHIR profiles for the Family Planning Annual Report 2.0 dataset have been created and validated. DISCUSSION: Using clinical element models and FHIR to meet the needs of a real-world use case has been accomplished but has also demonstrated the need for additional tooling, terminology services, and application sandbox development. CONCLUSION: FHIR profiles may reduce the administrative burden for the reporting of federally mandated program data.

Patterns and trends in contraceptive use among women attending Title X clinics and a national sample of low-income women.

OBJECTIVES: To describe the types of contraception used by women attending Title X-funded clinics and a comparable group of low-income reproductive-age women at risk of unintended pregnancy. STUDY DESIGN: We estimated the percentage of reproductive aged (15-44 years) women using contraception, by method type and level of effectiveness in preventing pregnancy (i.e., most, moderately, and less effective), using Title X Family Planning Annual Report (2006-2016) and National Survey of Family Growth (2006-2015) data. We divided most effective methods into permanent (female and male sterilization) and reversible (long-acting reversible contraceptives [LARCs]) methods. RESULTS: Among Title X clients during 2006-2016, use of LARCs increased (3-14%); use of moderately effective methods decreased (64-54%); and use of sterilization (~ 2%), less effective methods (21-20%), and no method (8-7%) was unchanged. These same trends in contraceptive use were observed in a comparable group of women nationally during 2006-2015, during which LARC use increased (5-19%, p < .001); moderately effective method use decreased (60-48%, p < .001); and use of sterilization (~5%), less effective methods (19%), and no method (11-10%) was unchanged. CONCLUSIONS: The contraceptive method mix among Title X clients differs from that of low-income women at risk of unintended pregnancy nationally, but general patterns and trends are similar in the two populations. Research is needed to understand whether method use patterns among low-income women reflect their preferences, access, or the conditions of the supply environment. IMPLICATIONS: This study contributes to our understanding of patterns and trends in contraceptive use among two groups of reproductive-age women - Title X clients and low-income women nationally who are at risk of unintended pregnancy. The findings highlight areas for further research.

An interlaboratory study of perfluorinated alkyl compound levels in human plasma.

We conducted an interlaboratory study which differed from the typical study of this type because of its emphasis on comparing intralaboratory variability in results. We sent specimens to six laboratories experienced in the analysis of perfluorinated alkyl compounds in blood matrices and that use stringent procedures to control and assure accuracy and precision. Each received an identical set of 60 plasma specimens that were analyzed in six completely independent batches. Split specimens were included so that within- and between-batch coefficients of variation could be calculated. All laboratories used liquid chromatography-tandem mass spectrometry (LC-MS/MS). The concentrations of perfluorooctanesulfonate (PFOS), perfluorooctanoate (PFOA), and perfluorohexanesulfonate (PFHxS) measured in the specimens in general showed a high level of agreement, although in some cases the agreement was only moderate. The average within- and between-batch coefficient of variation for PFOS was 9.1% and 9.3%; for PFOA was 14.5% and 14.5%; and for PFHxS was 14.5% and 17.0%. The recent availability of labeled internal standards, among other advances, has facilitated improvement in the accuracy and precision of the assays. Considering the degree of between-subject variation in levels among people in background-exposed populations, the results indicate that biomarker-based epidemiologic studies of associations with health could have reasonable precision.

Trends in Health Insurance Coverage of Title X Family Planning Program Clients, 2005-2015.

BACKGROUND: The federal Title X Family Planning Program supports the delivery of family planning services and related preventive care to 4 million individuals annually in the United States. The implementation of the 2010 Affordable Care Act's (ACA's) Medicaid expansion and provisions expanding access to health insurance, which took effect in January 2014, resulted in higher rates of health insurance coverage in the U.S. population; the ACA's impact on individuals served by the Title X program has not yet been evaluated. METHODS: Using administrative data we examined changes in health insurance coverage among Title X clinic patients during 2005-2015. RESULTS: We found that the percentage of clients without health insurance decreased from 60% in 2005 to 48% in 2015, with the greatest annual decrease occurring between 2013 and 2014 (63% to 54%). Meanwhile, between 2005 and 2015, the percentage of clients with Medicaid or other public health insurance increased from 20% to 35% and the percentage of clients with private health insurance increased from 8% to 15%. CONCLUSIONS: Although clients attending Title X clinics remained uninsured at substantially higher rates compared with the national average, the increase in clients with health insurance coverage aligns with the implementation of ACA-related provisions to expand access to affordable health insurance.

Unintended pregnancy and interpregnancy interval by maternal age, National Survey of Family Growth.

BACKGROUND: The relationship between unintended pregnancy and interpregnancy interval (IPI) across maternal age is not clear. METHODS: Using data from the National Survey of Family Growth, we estimated the percentages of pregnancies that were unintended among IPI groups (<6, 6-11, 12-17, 18-23, 24+ months) by maternal age at last live birth (15-19, 20-24, 25-29, 30-44 years). RESULTS: Approximately 40% of pregnancies were unintended and 36% followed an IPI<18 months. Within each maternal age group, the percentage of pregnancies that were unintended decreased as IPI increased. CONCLUSION: Unintended pregnancies are associated with shorter IPI across the reproductive age spectrum.

Youth-Friendly Family Planning Services for Young People: A Systematic Review Update.

CONTEXT: Youth-friendly family planning services may improve youth reproductive health outcomes. A systematic review conducted in 2011 was updated in 2016 to incorporate recent data examining the effects of youth-friendly family planning services on reproductive health outcomes and the facilitators and barriers facing young people in accessing family planning services. EVIDENCE ACQUISITION: PubMed, POPLINE, EMBASE, and other databases were used to identify relevant articles published from March 2011 through April 2016. EVIDENCE SYNTHESIS: Eighteen studies met inclusion criteria and were added to 19 studies from the review conducted in 2011. Of these, seven assessed the effect of youth-friendly services on outcomes: two showed a positive effect on reducing teen pregnancy, three on contraceptive use, and three on knowledge and patient satisfaction (not mutually exclusive). Facilitators or barriers were described in 32 studies. However, none were RCTs and most were at high risk for bias due to selection, self-report, and recall bias among others. CONCLUSIONS: The studies in this review suggest some positive effects of youth-friendly family planning services on reproductive health outcomes, but the need for more rigorous research persists. This review identified numerous factors relevant to young people's access to family planning services, reaffirming findings from the initial review: young people value confidentiality, supportive provider interaction, specialized provider training, and the removal of logistic barriers. Further, it illuminates the importance young people place on receiving comprehensive, client-centered family planning counseling. These findings should be considered when developing, implementing, and evaluating reproductive health services for young people. THEME INFORMATION: This article is part of a theme issue entitled Updating the Systematic Reviews Used to Develop the U.S. Recommendations for Providing Quality Family Planning Services, which is sponsored by the Office of Population Affairs, U.S. Department of Health and Human Services.

Long term follow-up and transition of care in anorectal malformations: An international survey.

BACKGROUND: The aim of the study was to assess current international practice in the long term follow-up, in managing active problems and transition of care for teenagers born with anorectal malformations (ARM). METHODS: An original survey was administered to delegates attending two large colorectal surgical meetings in 2015. The 21 questions covered long term follow-up, specific issues for teenagers and transition of care. RESULTS: 96/236 delegates completed the survey. Follow-up was routinely suspended before 10 year of age by 33% of respondents. 90% of them did not use a scoring system to assess or risks stratify patients, despite 81% stating that an objective score would be beneficial. 40% of respondents felt that >30% of their teenagers had ongoing active medical or psychosocial issues. 42% thought their patients were not ready to be transitioned. The process of transition should start around 13-16 years according to 54% of respondents. 72% had no protocol for transition and 82% did not hold multidisciplinary meetings with adult practitioners before transition. CONCLUSIONS: International consensus on the following aspects of the care in ARM is needed: structured long term follow-up, objective assessment and risk stratification scores, pathways of transition and methods to prepare patients, parents and adult practitioners.

Clinical Genetic Testing for the Cardiomyopathies and Arrhythmias: A Systematic Framework for Establishing Clinical Validity and Addressing Genotypic and Phenotypic Heterogeneity.

Advances in DNA sequencing have made large, diagnostic gene panels affordable and efficient. Broad adoption of such panels has begun to deliver on the promises of personalized medicine, but has also brought new challenges such as the presence of unexpected results, or results of uncertain clinical significance. Genetic analysis of inherited cardiac conditions is particularly challenging due to the extensive genetic heterogeneity underlying cardiac phenotypes, and the overlapping, variable, and incompletely penetrant nature of their clinical presentations. The design of effective diagnostic tests and the effective use of the results depend on a clear understanding of the relationship between each gene and each considered condition. To address these issues, we developed simple, systematic approaches to three fundamental challenges: (1) evaluating the strength of the evidence suggesting that a particular condition is caused by pathogenic variants in a particular gene, (2) evaluating whether unusual genotype/phenotype observations represent a plausible expansion of clinical phenotype associated with a gene, and (3) establishing a molecular diagnostic strategy to capture overlapping clinical presentations. These approaches focus on the systematic evaluation of the pathogenicity of variants identified in clinically affected individuals, and the natural history of disease in those individuals. Here, we applied these approaches to the evaluation of more than 100 genes reported to be associated with inherited cardiomyopathies and arrhythmias including hypertrophic cardiomyopathy, dilated cardiomyopathy, arrhythmogenic right ventricular dysplasia or cardiomyopathy, long QT syndrome, short QT syndrome, Brugada, and catecholaminergic polymorphic ventricular tachycardia, and to a set of related syndromes such as Noonan Syndrome and Fabry disease. These approaches provide a framework for delivering meaningful and accurate genetic test results to individuals with hereditary cardiac conditions.

Quantitative determination of perfluorooctanoic acid in serum and plasma by liquid chromatography tandem mass spectrometry.

A selective and sensitive method for analysis of perfluorooctanoic acid (PFOA) in human serum and plasma, utilizing liquid chromatography tandem mass spectrometry (LC-MS/MS), has been developed and thoroughly validated to satisfy strict FDA guidelines for bioanalytical methods. A simple, automated sample preparation procedure, involving extraction of the target analyte with acetonitrile on protein precipitation media in a 96-well plate format was developed, allowing efficient handling of large numbers of samples. The proposed method uses the calibration standards prepared in a surrogate matrix (rabbit serum or plasma) and (13)C-labeled PFOA as the internal standard to account for matrix effects, instrument drift, and extraction efficiency. Human serum and plasma could not be used for matrix matching of calibration standards as endogenous levels of PFOA observed in the control human serum and plasma significantly exceeded the targeted lower limit of quantitation (LLOQ) of the method. Precision and accuracy of the method were demonstrated by analysis of rabbit serum and plasma control samples fortified at 0.5, 5, and 40 ng/mL PFOA and human serum and plasma fortified at 1.0, 5.0, 40 ng/mL PFOA. The LLOQ of 0.5 ng/mL PFOA was experimentally demonstrated for rabbit and human serum and plasma. Within-day precision and accuracy, short-term stability, freeze-thaw stability, equivalence of response between PFOA and APFO (the ammonium salt of PFOA), and dilution of concentrated samples were also investigated. The results of the validation experiments comply with the precision and accuracy limits defined by the FDA guidance document: "Guidance for Industry, Bioanalytical Method Validation", May 2001.

Research in the CKD clinic: highs and lows.

Despite rates of CKD continuing to increase, the current evidence base used to guide CKD management is smaller than that for many other chronic diseases. Clinical investigators face multiple barriers to conducting research in patients with CKD. CKD patients have multiple comorbidities that make them a risky intervention target; thus, they are often excluded from trials. The lack of approved surrogate endpoints for kidney disease progression makes testing therapies to slow progression very challenging and expensive. Patients with CKD have higher rates of disability and lower educational status than the general population, which further complicates their participation in clinical trials. Despite these barriers, it is imperative that scientific progress be made in this patient population. Increasing education and information regarding CKD clinical trials through brochures and public awareness campaigns may increase trial participation. The U.S. Food and Drug Administration needs to approve the new definition of glomerular filtration rate decline because this will result in a decrease in the cost of clinical trials and make industry more likely to invest in trials in patients with CKD. Successful research in this patient population is possible, but it requires collaboration among investigators, health-care providers, patients, industry, and the National Institutes of Health.

Assessment of vascular function in patients with chronic kidney disease.

Patients with chronic kidney disease (CKD) have significantly increased risk of cardiovascular disease (CVD) compared to the general population, and this is only partially explained by traditional CVD risk factors. Vascular dysfunction is an important non-traditional risk factor, characterized by vascular endothelial dysfunction (most commonly assessed as impaired endothelium-dependent dilation [EDD]) and stiffening of the large elastic arteries. While various techniques exist to assess EDD and large elastic artery stiffness, the most commonly used are brachial artery flow-mediated dilation (FMDBA) and aortic pulse-wave velocity (aPWV), respectively. Both of these noninvasive measures of vascular dysfunction are independent predictors of future cardiovascular events in patients with and without kidney disease. Patients with CKD demonstrate both impaired FMDBA, and increased aPWV. While the exact mechanisms by which vascular dysfunction develops in CKD are incompletely understood, increased oxidative stress and a subsequent reduction in nitric oxide (NO) bioavailability are important contributors. Cellular changes in oxidative stress can be assessed by collecting vascular endothelial cells from the antecubital vein and measuring protein expression of markers of oxidative stress using immunofluorescence. We provide here a discussion of these methods to measure FMDBA, aPWV, and vascular endothelial cell protein expression.