Moving the Needle Toward Equity: What NIH Is Doing to Promote Diversity, Inclusion, and Accessibility in Research on Intellectual and Developmental Disabilities.

As a major funder of research on intellectual and developmental disabilities (IDD), NIH has a broad view of the profound impact of cultural and structural barriers on the characteristics of IDD study populations and the composition of the IDD research workforce. While long overdue, multiple efforts are currently underway across NIH aimed at addressing these barriers and increasing meaningful representation in biomedical and behavioral research.

Why Definitional Clarity Matters: Implications for the Operationalization of Emotional Well-Being.

The National Institutes of Health (NIH) is increasingly prioritizing research on health-promoting processes. Park et al. (this issue) respond to a call made by NIH to advance the study of emotional well-being (EWB) and to increase understanding of the fundamental constituents of EWB across the lifespan and among diverse subgroups. They propose a definition of EWB that provides an organizing framework for research on 'psychological aspects of well-being' and health. We commend this important first step and urge consideration of three important issues related to operationalization - the process by which an abstract concept is transformed into variables that can be measured - in future research on EWB. We expect that an iterative process of construct refinement and empirical validation will advance the study of EWB, producing scientific discoveries that can be leveraged to enhance health across the lifespan.

Communication between neonatologists and parents when prognosis is uncertain.

OBJECTIVE: When an infant's prognosis is uncertain, communication between neonatologists and parents surrounding goals of care and decision-making can be challenging. This qualitative study explored communication between neonatologists and parents to discover qualities which may enhance or impede parent-clinician partnership under such difficult circumstances. STUDY DESIGN: Guided by the National Cancer Institute (NCI) Patient Centered Communication framework, semi-structured individual interviews were conducted and analyzed regarding neonatologist and parent perceptions of their communication. Subjects consisted of nine dyads of neonatologists and English-speaking parents whose infant had an uncertain prognosis. RESULTS: Parents were overall satisfied with neonatologists' communications concerning their infant's uncertain trajectory. Nonetheless, both experienced challenges and distress during communication, impeding collaboration and engagement. CONCLUSIONS: Families and neonatologists value principles of patient centered communication but report challenges implementing this practice. Incorporating a multidisciplinary approach in settings of prognostic uncertainty to foster patient centered communication, may enhance communication surrounding NICU care.

Cosmetic outcomes following appendectomy in children: a comparison of surgical techniques.

BACKGROUND: Although cosmetic superiority is widely stated as an advantage of single-incision laparoscopy, there are limited studies looking at cosmetic outcome. We sought to determine patients' cosmetic satisfaction after undergoing appendectomy by the single-incision laparoscopic appendectomy (SILA), multiport laparoscopic appendectomy (LA), or open appendectomy (OA) procedure. PATIENTS AND METHODS: Five hundred eighty pediatric patients who underwent appendectomy at a single institution between February 2010 and July 2011 were identified and asked to complete the Patient Scar Assessment Scale (PSAS), a validated evaluation tool for linear scars. In addition, patients were asked the "Ultimate Question" (UQ), which correlates with a patient's overall satisfaction. Linear regression models were used to examine differences between surgical approaches with statistical significance set at P<.05. Covariates for all models included patient demographics, length of stay, and surgeon. RESULTS: In total, 212 surveys were returned (SILA, 122; LA, 41; OA, 49) for a response rate of 37%. Regression models demonstrated significantly higher mean total PSAS scores for patients who underwent SILA and laparoscopic appendectomy (LA) appendectomy procedures compared with the open procedure (SILA, 8.70; LA, 8.86; OA, 8.01; ß=-0.21, P<.05). Patients who experienced the SILA and LA procedures reported significantly higher mean UQ scores compared with OA (SILA, 9.79; LA, 9.75; OA, 9.39; ß=-0.22, P<.05). SILA patients reported a 10 on the UQ significantly more often (91.1%) compared with either LA (81%) or OA (75.5%) (P<.05). CONCLUSIONS: SILA or LA appendectomy was associated with significantly increased cosmetic satisfaction by patients and their families when compared with OA. This is the first study to show that pediatric patients value attempts to minimize scarring with laparoscopic surgery. Further studies are needed to determine if specific patient factors influence satisfaction with scars.

Interventions to modify health care provider adherence to asthma guidelines: a systematic review.

BACKGROUND AND OBJECTIVE: Health care provider adherence to asthma guidelines is poor. The objective of this study was to assess the effect of interventions to improve health care providers' adherence to asthma guidelines on health care process and clinical outcomes. METHODS: Data sources included Medline, Embase, Cochrane CENTRAL Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, Educational Resources Information Center, PsycINFO, and Research and Development Resource Base in Continuing Medical Education up to July 2012. Paired investigators independently assessed study eligibility. Investigators abstracted data sequentially and independently graded the evidence. RESULTS: Sixty-eight eligible studies were classified by intervention: decision support, organizational change, feedback and audit, clinical pharmacy support, education only, quality improvement/pay-for-performance, multicomponent, and information only. Half were randomized trials (n = 35). There was moderate evidence for increased prescriptions of controller medications for decision support, feedback and audit, and clinical pharmacy support and low-grade evidence for organizational change and multicomponent interventions. Moderate evidence supports the use of decision support and clinical pharmacy interventions to increase provision of patient self-education/asthma action plans. Moderate evidence supports use of decision support tools to reduce emergency department visits, and low-grade evidence suggests there is no benefit for this outcome with organizational change, education only, and quality improvement/pay-for-performance. CONCLUSIONS: Decision support tools, feedback and audit, and clinical pharmacy support were most likely to improve provider adherence to asthma guidelines, as measured through health care process outcomes. There is a need to evaluate health care provider-targeted interventions with standardized outcomes.

Improving immunization delivery using an electronic health record: the ImmProve project.

OBJECTIVE: Though an essential pediatric preventive service, immunizations are challenging to deliver reliably. Our objective was to measure the impact on pediatric immunization rates of providing clinicians with electronic health record-derived immunization prompting. METHODS: Operating in a large, urban, hospital-based pediatric primary care clinic, we evaluated 2 interventions to improve immunization delivery to children ages 2, 6, and 13 years: point-of-care, patient-specific electronic clinical decision support (CDS) when children overdue for immunizations presented for care, and provider-specific bulletins listing children overdue for immunizations. RESULTS: Overall, the proportion of children up to date for a composite of recommended immunizations at ages 2, 6, and 13 years was not different in the intervention (CDS active) and historical control (CDS not active) periods; historical immunization rates were high. The proportion of children receiving 2 doses of hepatitis A immunization before their second birthday was significantly improved during the intervention period. Human papillomavirus (HPV) immunization delivery was low during both control and intervention periods and was unchanged for 13-year-olds. For 14-year-olds, however, 4 of the 5 highest quarterly rates of complete HPV immunization occurred in the final year of the intervention. Provider-specific bulletins listing children overdue for immunizations increased the likelihood of identified children receiving catch-up hepatitis A immunizations (hazard ratio 1.32; 95% confidence interval 1.12-1.56); results for HPV and the composite of recommended immunizations were of a similar magnitude but not statistically significant. CONCLUSIONS: In our patient population, with high baseline uptake of recommended immunizations, electronic health record-derived immunization prompting had a limited effect on immunization delivery. Benefit was more clearly demonstrated for newer immunizations with lower baseline uptake.

Implementing developmental screening and referrals: lessons learned from a national project.

OBJECTIVES: To assess the degree to which a national sample of pediatric practices could implement American Academy of Pediatrics (AAP) recommendations for developmental screening and referrals, and to identify factors that contributed to the successes and shortcomings of these efforts. BACKGROUND: In 2006, the AAP released a policy statement on developmental surveillance and screening that included an algorithm to aid practices in implementation. Simultaneously, the AAP launched a 9-month pilot project in which 17 diverse practices sought to implement the policy statement's recommendations. METHODS: Quantitative data from chart reviews were used to calculate rates of screening and referral. Qualitative data on practices' implementation efforts were collected through semistructured telephone interviews and inductively analyzed to generate key themes. RESULTS: Nearly all practices selected parent-completed screening instruments. Instrument selection was frequently driven by concerns regarding clinic flow. At the project's conclusion, practices reported screening more than 85% of patients presenting at recommended screening ages. They achieved this by dividing responsibilities among staff and actively monitoring implementation. Despite these efforts, many practices struggled during busy periods and times of staff turnover. Most practices were unable or unwilling to adhere to 3 specific AAP recommendations: to implement a 30-month visit; to administer a screen after surveillance suggested concern; and to submit simultaneous referrals both to medical subspecialists and local early-intervention programs. Overall, practices reported referring only 61% of children with failed screens. Many practices also struggled to track their referrals. Those that did found that many families did not follow through with recommended referrals. CONCLUSIONS: A diverse sample of practices successfully implemented developmental screening as recommended by the AAP. Practices were less successful in placing referrals and tracking those referrals. More attention needs to be paid to the referral process, and many practices may require separate implementation systems for screening and referrals.

The role of clinic culture in implementation of primary care interventions: the case of Reach Out and Read.

OBJECTIVE: Reach Out and Read (ROR) is a primary care-based intervention supported by considerable evidence regarding its efficacy. Implementation of ROR, however, varies across participating sites. The objective of this study was to identify practice attributes associated with variability in ROR implementation. METHODS: Twenty primary care providers and 70 support staff from 7 clinics in Baltimore, Maryland, participated in semistructured interviews. Sites were purposefully selected on the basis of the perceived success of their ROR program implementation. All interviews were transcribed and inductively analyzed to identify themes. Themes were compared to predictors postulated by a conceptual model for team effectiveness across a variety of workplace settings. RESULTS: Only one theme (integration of ROR procedures) addressed the design of ROR implementation within clinics. Nearly all other themes identified group processes and group psychosocial traits broadly reflective of clinic culture. At struggling sites, staff found their jobs burdensome and communication lacking. They demonstrated disrespect for patients and families. In this context, they experienced difficulty integrating ROR into their daily routines. Staff at successful sites worked as a team and expressed strong commitments to their communities. Integration of ROR at these sites tended to occur smoothly. Providers from all sites reported strong pressures to increase productivity, and thought that these pressures impaired their ability to deliver high-quality primary care. CONCLUSIONS: Clinic culture influences the implementation of an efficacious primary care intervention. Characteristics of clinic culture therefore need to be identified and taken into account in future efforts to improve its implementation.

Clinical and genetic determinants of intracellular tenofovir diphosphate concentrations in HIV-infected patients.

BACKGROUND: Nucleos(t)ide reverse transcriptase inhibitors (NRTIs), such as tenofovir, require intracellular phosphorylation for pharmacologic activity. Drug transporters may contribute to the intracellular disposition of NRTIs. OBJECTIVE: We characterized intracellular tenofovir diphosphate (TFV-DP) concentrations in HIV-infected patients (n = 30), and investigated associations between TFV-DP concentrations and polymorphisms in the drug transporter genes SLC22A6, ABCC2, and ABCC4. METHODS: Subjects were genotyped for 6 single-nucleotide polymorphisms: 2 in SLC22A6 (encodes influx transporter, human organic anion transporter 1), 728G>A and 453G>A; 2 in ABCC2 (encodes efflux transporter, multidrug resistance protein [MRP] 2), -24C>T and 1249G>A; and 2 in ABCC4 (encodes efflux transporter, MRP4), 3463A>G and 4131T>G. RESULTS: The mean TFV-DP was 76.1 fmol/10(6) cells (range: 16.3 to 212 fmol/10(6) cells). Tenofovir apparent oral and renal clearances were significantly predictive of intracellular TFV-DP concentrations. For every 1-L/h decrease in tenofovir renal clearance, there was, on average, an 8% increase in TFV-DP (P = 0.002). We identified a novel relation between ABCC4 3463A>G genotype and TFV-DP. ABCC4 3463G variants had TFV-DP concentrations 35% higher (29 fmol/10(6) cells) than wild type (P = 0.04). CONCLUSION: This study provides direction for future investigations to elucidate the contribution of clinical characteristics and drug transporter genotype to TFV-DP safety and efficacy.

Prevalence and early identification of language delays among at-risk three year olds.

The aims of this study were fourfold: to document the prevalence of language delays in a sample of at-risk 3 year olds; to assess the effectiveness of a home visiting program in preventing early language delays; to determine how often parents, pediatric providers, and home visitors identified early language delays; and to assess the effectiveness of a home visiting program in improving early identification of language delays. The Preschool Language Scale, Third Edition (PLS-3) was administered to 513 at-risk 3 year olds participating in a randomized trial of home visiting services. Families randomized to home visiting were expected to receive weekly to quarterly visits throughout the 3 years of this study. The content of home visits included teaching parents about child development, role-modeling parenting skills, and linking families to a medical home. Identification of delays was measured using structured parent interviews and review of primary care and home visiting records. At age 3 years, 10% of children had severe language delays, defined as scoring >or=2 SD below the national mean on the PLS-3, whereas 49% scored >or=1 SD below the national mean. No differences in prevalence were seen between children who did and did not receive home visiting. Among children with severe delays, 42% were identified by parents, 33% by pediatric providers, and 24% by home visitors. Among children with any delays, 24% were identified by parents, 25% by pediatric providers, and 17% by home visitors. No differences in rates of identification were seen between children who did and did not receive home visiting. Thus, while language delays were highly prevalent among these at-risk children, rates of identification were low, even among children with severe delays. Home visiting was not effective in either preventing language delays or improving early identification. This suggests that pediatric providers and home visiting programs need to reexamine their approaches to recognizing and intervening with early language delays.

The Gln4863Ala mutation within a putative, pore-lining trans-membrane helix of the cardiac ryanodine receptor channel alters both the kinetics of ryanoid interaction and the subsequent fractional conductance.

The specific, high-affinity interaction of the plant toxin ryanodine with its molecular target the ryanodine receptor channel (RyR) has been instrumental in RyR research. Alanine scanning of putative pore regions of mouse RyR2 has highlighted the amino acid Gln4863, predicted to lie within trans-membrane helix TM10, as an important determinant of ryanodine binding. We have investigated the effects of several ryanodine derivatives, guanidinopropionylryanodine, 21-p-nitrobenzoylamino-9alpha-hydroxyryanodine, 8beta-amino-9alpha-hydroxyryanodine, and 21-amino-9alpha-hydroxyryanodine, with the mouse Q4863A RyR2 mutant at the single-channel level. Our results demonstrate that the rate of dissociation of all ryanoids investigated is increased by the mutation. The modification of channel function after ryanoid binding is qualitatively similar for wild-type and mutant, but in several cases, single-channel conductances were increased with Q4863A. These novel findings have been interpreted within the framework of existing comparative molecular field analysis studies on ryanoids. We suggest that replacement of a glutamine by an alanine residue at position 4863 causes RyR2 to simultaneously alter interactions with both ends of the ryanoid molecule.

Developmental surveillance of infants and young children in pediatric primary care.

PURPOSE OF REVIEW: This article reviews the importance of appropriate developmental surveillance in early childhood, what is known about its effectiveness in current pediatric practice, and ways in which its delivery can be improved to optimize child outcomes. RECENT FINDINGS: Many infants and young children with developmental delays or risk factors for poor developmental outcomes are not identified by pediatric practitioners in a timely manner. When they are identified, they are often not referred to appropriate early intervention services or early childhood development programs. They are therefore denied the opportunity to benefit from programs documented to have long-lasting benefits for children. Structuring developmental screening around the use of validated parent questionnaires improves the rates at which children with developmental needs are appropriately identified. At the same time, lowering thresholds for referral improves the rates at which children with identified needs receive appropriate services. SUMMARY: Pediatric practitioners are uniquely positioned to improve children's developmental outcomes through early identification and referral of children with developmental delays or risk factors for poor developmental outcomes. Unfortunately, inappropriate screening practices, high thresholds for referral, misplaced concerns about causing parental anxiety, and unfamiliarity with local resources all diminish the effectiveness with which many practitioners conduct developmental surveillance. Recent studies show that small changes in screening and referral practices have the potential to greatly improve the effectiveness of developmental surveillance. This, in turn, has the potential to improve lifelong outcomes for children.