Ronald C. Samuels

Reduction in Sperm Levels after Testicular Irradiation of the Mouse: A Comparison with Man

The potential and limitations of applying extrapolation factors (EFs) to the results of animal studies to predict effects of toxic agents on human male fertility were evaluated using radiation data. The EF is the ratio of the dose to produce a given effect in the mouse to that necessary to produce the same effect in man. Sperm counts in mouse testes were compared to those in the ejaculates of human males (D. K. Clifton and W. J. Bremner, J. Androl. 4, 387-392 (1981)) at several different times after irradiation. EFs of between 2.6 and 7 were obtained at the time when minimum counts occur. However, it must be noted that the sperm being measured arose from different cell types: differentiating spermatogonia in the mouse vs stem spermatogonia in man. Sperm counts performed at times at which the sperm develop from irradiated stem cells in both species yielded EFs between 11 and 44. However, if sufficient time was allowed for maximum recovery in both species, the EF was less than 1.7. These results indicate that man appears to be much more sensitive than the mouse to the testicular effects of irradiation at 2 to 9 months postexposure, but both species are comparable in their sensitivity to irreversible damage. The use of EFs may be appropriate, but since the EF is very dependent on the time at which the comparison was made, different values must be used for prompt and permanent testicular injury.

Improving Accuracy in a Computerized Immunization Registry

BACKGROUND Bostons Department of Health and Hospitals established the Boston Immunization Information System (BIIS) as part of a city-wide effort to raise immunization rates. OBJECTIVES Our objectives were 1) to assess the validity of data entry in one computerized immunization database within this system; 2) to identify the types of errors made in data entry; and 3) to assess the effectiveness of an intervention to improve the accuracy of information in this database. METHODS Chart records were used as the gold standard in comparison with the computerized BIIS database. Children were considered up to date for immunizations if they had received 4 DTP, 3 polio, and 1 MMR by their second birthday. In March of 1995, billing records were used to identify all children born between March 1, 1992, and September 1, 1994, in one urban health center. These children were between 6 months and 36 months of age at the time. We compared the computer record with the chart, looking for and correcting errors such as incorrect dates and missing immunization data. An intervention was then begun, including a system for reviewing the accuracy of the computerized data at all well-child visits. In October of 1996, the chart review was repeated on children born between March 1, 1992, and September 1, 1995. This age range included all the children in the original review plus those born in the subsequent 12 months. Immunization rates before and after chart reviews were compared for children 24 to 36 months of age. RESULTS We initially reviewed 737 of 739 charts (99%). In the follow-up time period, we examined 881 of 943 charts (93%). During the first review, 333 of the 563 (59%) records contained at least one error in data entry, compared with 116 of 646 (18%) in the second review (P <.0001). During the second review, we also examined the type of errors. Thirty-eight percent of all errors represented vaccines that had not been entered into the computer. Before the study period, analysis of the computerized immunization record showed an immunization up-to-date rate of 24%. This increased to 41% after the initial chart review and to 75% after the intervention period (P <.0001). CONCLUSION Errors in data entry caused underestimates of immunization rates. Eliminating the errors increased immunization rates immediately through more accurate bookkeeping. Eighteen months later, immunization rates had continued to improve dramatically.

In vitro cytokine induction by TLR-activating vaccine adjuvants in human blood varies by age and adjuvant

Most infections occur in early life, prompting development of novel adjuvanted vaccines to protect newborns and infants. Several Toll-like receptor (TLR) agonists (TLRAs) are components of licensed vaccine formulations or are in development as candidate adjuvants. However, the type and magnitude of immune responses to TLRAs may vary with the TLR activated as well as age and geographic location. Most notably, in newborns, as compared to adults, the immune response to TLRAs is polarized with lower Th1 cytokine production and robust Th2 and anti-inflammatory cytokine production. The ontogeny of TLR-mediated cytokine responses in international cohorts has been reported, but no study has compared cytokine responses to TLRAs between U.S. neonates and infants at the age of 6months. Both are critical age groups for the currently pediatric vaccine schedule. In this study, we report quantitative differences in the production of a panel of 14 cytokines and chemokines after in vitro stimulation of newborn cord blood and infant and adult peripheral blood with agonists of TLR4, including monophosphoryl lipid A (MPLA) and glucopyranosyl lipid Adjuvant aqueous formulation (GLA-AF), as well as agonists of TLR7/8 (R848) and TLR9 (CpG). Both TLR4 agonists, MPLA and GLA-AF, induced greater concentrations of Th1 cytokines CXCL10, TNF and Interleukin (IL)-12p70 in infant and adult blood compared to newborn blood. All the tested TLRAs induced greater infant IFN-α2 production compared to newborn and adult blood. In contrast, CpG induced greater IFN-γ, IL-1β, IL-4, IL-12p40, IL-10 and CXCL8 in newborn than in infant and adult blood. Overall, to the extent that these in vitro studies mirror responses in vivo, our study demonstrates distinct age-specific effects of TLRAs that may inform their development as candidate adjuvants for early life vaccines.

Missed Appointments Factors Contributing to High No-Show Rates in an Urban Pediatrics Primary Care Clinic

Background. Missed appointments complicate primary care services. Objective. To determine factors associated with missed pediatric appointments. Design/Methods. A convenience sample of 1537 patients who missed appointments were called and 386 (25%) families completed the 26-item survey. Those with high no-show rates were compared with the rest using χ2 and Fisher’s exact tests. Initial covariates with P < .2 were included in a multivariate logistic regression model. Results. Common reasons for missing appointments were the following: forgot (27%), transportation problems (21%), and time off of work (14%). The high no-show group had more African Americans (P = .030) and older patients (P = .003). Higher no-show rates correlated with well child visits (P = .029) and perception of “excellent health” (P = .022). In the logistic regression model, well child appointments (odds ratio = 2.56) and increasing age in years (odds ratio = 1.11) were associated with higher no-show rates. Conclusions. Efforts to decrease no-show rates should target older patients and well child visits.

Lessons from pediatrics residency program directors' experiences with work hour limitations in New York State.

Purpose To evaluate the impact of residency work hour limitations on pediatrics residency programs in New York State, and to learn lessons that can be used nationally with the implementation of the Accreditation Council of Graduate Medical Educations similar rules. Method A three-page questionnaire was mailed to all pediatrics residency program directors in New York. The questionnaire assessed methods used to accommodate the work hour limitations and perceptions of the limitations’ effects. Results Twenty-one program directors responded (68%). Only large programs used night floats and night teams to meet work hour requirements. Programs of all sizes and in all settings used cross coverage and sent residents home immediately post call. About half of the programs hired additional nonresident staff, usually nurse practitioners, physician assistants, and/or attendings. The most frequently reported effects were decreases in the amount of time residents spent in inpatient settings, patient continuity in inpatient settings, flexibility of residents’ scheduling, and increased logistical work needed to maintain continuity clinic. A summary of advice to other program directors was “be creative” and “be flexible.” Conclusions New Yorks pediatrics residency programs used a variety of mechanisms to meet work hour restrictions. Smaller programs had fewer methods available to them to meet such restrictions. Although the logistical work needed to maintain continuity clinic increased greatly, continuity and outpatient settings themselves were not greatly affected by work hour limitations. Inpatient settings were more affected and experienced much more in the way of change.

Improving Immunization Rates in a Hospital-Based Primary Care Practice

OBJECTIVE: We implemented a quality improvement initiative aimed at reaching a 95% immunization rate for patients aged 24 months. The setting was a hospital-based pediatric primary care practice in Boston, Massachusetts. We defined immunization as full receipt of the vaccine series as recommended by the Centers for Disease Control and Prevention. METHODS: The initiative was team-based and structured around 3 core interventions: systematic identification and capture of target patients, use of a patient-tracking registry, and patient outreach and care coordination. We measured monthly overall and modified immunization rates for patients aged 24 months. The modified rate excluded vaccine refusals and practice transfers. We plotted monthly overall and modified immunization rates on statistical process control charts to monitor progress and evaluate impact. RESULTS: We measured immunization rates for 3298 patients aged 24 months between January 2009 and December 2012. Patients were 48% (n = 1576) female, 77.3% (n = 2548) were African American or Hispanic, and 70.2% (n = 2015) were publicly insured. Using control charts, we established mean overall and modified immunization rates of 90% and 93%, respectively. After implementation, we observed an increase in the mean modified immunization rate to 95%. CONCLUSIONS: A quality improvement initiative enabled our pediatric practice to increase its modified immunization rate to 95% for children aged 24 months. We attribute the improvement to the incorporation of medical home elements including a multidisciplinary team, patient registry, and care coordination.

Paediatric experiences with work-hour limitations.

OBJECTIVES To evaluate the perceived impact of work-hour limitations on paediatric residency training programmes and to determine the various strategies used to accommodate these restrictions. METHODS A three-page pre-tested survey was administered to programme directors at the 2004 Association of Paediatric Programme Directors meeting. The impact of work-hours was evaluated with Likert-type questions and the methods used to meet work-hour requirements were compared between large programmes (>or=30 residents) and small programmes. RESULTS Surveys were received from 53 programme directors. The majority responded that work-hour limitations negatively impacted inpatient continuity, time for education, schedule flexibility and attending staff satisfaction. Supervision by attending staff was the only aspect to significantly improve. Perceived resident satisfaction was neutral. To accommodate work-hour limitations, 64% of programmes increased clinical responsibility to existing non-resident staff, 36% hired more non-resident staff and 17% increased the number of residents. Only one programme hired additional non-clinical staff. Large programmes were more likely to use more total methods on the inpatient wards (P < 0.01) and in the intensive care units (P < 0.05) to accommodate work-hour limitations. CONCLUSIONS Programme directors perceived a negative impact of work-hours on most aspects of training without a perceived difference in resident satisfaction. While a variety of methods are used to accommodate work-hour limitations, programmes are not widely utilizing non-clinical staff to alleviate clerical burdens.

Home Safety Practices in an Urban Low-Income Population Level of Agreement Between Parental Self-Report and Observed Behaviors

Home-related injuries are overrepresented in children from low-income households. The objectives of this study were to determine frequencies of home safety behaviors and the level of agreement between parental self-report and observed safety practices in low-income homes. In a prospective, interventional home injury prevention study of 49 low-income families with children <5 years old, a trained home visitor administered baseline parental home safety behavior questionnaires and assessments. There was high agreement between caregiver self-report and home visitor observation for lack of cabinet latch (99%, 95% confidence interval [CI] = 88%-99%) and stair gate use (100%, 95% CI = 88-100%). There was lower agreement for the safe storage of cleaning supplies (62%, 95% CI = 46%-75%), sharps (74%, 95% CI = 59%-85%), and medicines/vitamins (83%, 95% CI = 69%-92%) because of the overreporting of safe practices. Self-reports of some home safety behaviors are relatively accurate, but certain practices may need to be verified by direct assessment.

Barriers to HPV immunization among blacks and latinos: a qualitative analysis of caregivers, adolescents, and providers.

BackgroundDespite recommendations that 11–12-year-olds receive the full three-shot Human papillomavirus (HPV) vaccine series, national HPV immunization coverage rates remain low. Disparities exist, with Blacks and Latinos being less likely than Whites to complete the series. We aimed to identify and compare barriers to HPV immunization perceived by healthcare providers, Black and Latino adolescents, and their caregivers to inform a clinic-based intervention to improve immunization rates.MethodsWe conducted semi-structured interviews between March and July 2014 with Black and Latino adolescents (n = 24), their caregivers (n = 24), and nurses (n = 18), and 2 focus groups with 18 physicians recruited from two pediatric primary care clinics. Qualitative protocol topics included: general perceptions and attitudes towards vaccines; HPV knowledge; and perceived individual and systems-level barriers affecting vaccine initiation and completion.ResultsThemes were identified and organized by individual and systems-level barriers to HPV immunization. Adolescents and their caregivers, particularly Blacks, expressed concerns about HPV being an untested, “newer” vaccine. All families felt they needed more information on HPV and found it difficult to return for multiple visits to complete the vaccine series. Providers focused on challenges related to administering multiple vaccines simultaneously, and perceptions of parental reluctance to discuss sexually transmitted infections.ConclusionsOptimizing HPV immunization rates may benefit from a multi-pronged approach to holistically address provider, structural, and individual barriers to care. Further research should examine strategies for providing multiple modalities of support for providers, including a routinized system of vaccine promotion and delivery, and for addressing families’ concerns about vaccine safety and efficacy.

Overweight Prevention in Pediatric Primary Care: A Needs Assessment of an Urban Racial/Ethnic Minority Population

The authors studied the prevalence of overweight-related behaviors in an urban clinic population, parents’ perceived willingness to change, and identified potential gaps in nutrition and physical activity promotion. A total of 324 parents of children aged 3 to 13 years were surveyed. Clinical heights and weights were used to calculate body mass index (BMI). Of the 324 children in the study, 55% were black and 28% were Hispanic. Approximately 151 (47%) children had a BMI ≥85th percentile, and overweight-related behaviors, such as TV viewing, were highly prevalent. Overall, parents reported a need for counseling to help their children eat healthier and be more active and seemed willing to make behavior changes in these areas. However, their willingness to change appeared lowest in areas that may improve their child’s weight status such as decreasing sedentary time and portion sizes. Overweight prevention efforts in primary care should include strategies to help clinicians negotiate behavior change with families.