Fran Dong

Barriers to the Use of Herpes Zoster Vaccine

BACKGROUND The herpes zoster vaccine is the most expensive vaccine recommended for older adults and the first vaccine to be reimbursed through Medicare Part D. Early uptake has been 2% to 7% nationally. OBJECTIVE To assess current vaccination practices, knowledge and practice regarding reimbursement, and barriers to vaccination among general internists and family medicine physicians. DESIGN Mail and Internet-based survey, designed through an iterative process and conceptually based on the Health Belief Model. SETTING National survey conducted from July to September 2008. PARTICIPANTS General internists and family medicine physicians. MEASUREMENTS Survey responses on current vaccination practices, knowledge and practice regarding reimbursement, and barriers to vaccination. RESULTS Response rates were 72% in both specialties (301 general internists and 297 family medicine physicians). Physicians in both specialties reported similar methods for delivering vaccine, which included stocking and administering the vaccine in their offices (49%), referring patients to a pharmacy to purchase the vaccine and bring it back to the office for administration (36%), and referring patients to a pharmacy for vaccine administration (33%). Eighty-eight percent of providers recommend herpes zoster vaccine and 41% strongly recommend it, compared with more than 90% who strongly recommend influenza and pneumococcal vaccines. For physicians in both specialties, the most frequently reported barriers to vaccination were financial. Only 45% of respondents knew that herpes zoster vaccine is reimbursed through Medicare Part D. Of respondents who began administering herpes zoster vaccine in their office, 12% stopped because of cost and reimbursement issues. LIMITATIONS Survey results represent reported but not observed practice. Surveyed providers may not be representative of all providers. CONCLUSION Physicians are making efforts to provide herpes zoster vaccine but are hampered by barriers, particularly financial ones. Efforts to facilitate the financing of herpes zoster vaccine could help increase its use. PRIMARY FUNDING SOURCE Centers for Disease Control and Prevention.

Effectiveness and Net Cost of Reminder/Recall for Adolescent Immunizations

OBJECTIVE: To assess the effectiveness of reminder/recall (R/R) for immunizing adolescents in private pediatric practices and to describe the associated costs and revenues. METHODS: We conducted a randomized controlled trial in 4 private pediatric practices in metropolitan Denver. In each practice, 400 adolescents aged 11 to 18 years who had not received 1 or more targeted vaccinations (tetanus-diphtheria-acellular pertussis, meningococcal conjugate, or first dose of human papillomavirus vaccine for female patients) were randomly selected and randomized to intervention (2 letters and 2 telephone calls) or control (usual care) groups. Primary outcomes were receipt of >1 targeted vaccines and receipt of all targeted vaccines 6 months postintervention. We calculated net additional revenue for each additional adolescent who received at least 1 targeted vaccine and for those who received all targeted vaccines. RESULTS: Eight hundred adolescents were randomized to the intervention and 800 to the control group. Baseline rates of having already received tetanus-diphtheria-acellular pertussis, meningococcal conjugate, and first dose of human papillomavirus vaccine before R/R ranged from 33% to 54%. Postintervention, the intervention group had significantly higher proportions of receipt of at least 1 targeted vaccine (47.1% vs 34.6%, P < .0001) and receipt of all targeted vaccines (36.2% vs 25.2%, P < .0001) compared with the control group. Three practices had positive net revenues from R/R; 1 showed net losses. CONCLUSIONS: R/R was successful at increasing immunization rates in adolescents and effect sizes were comparable to those in younger children. Practices conducting R/R may benefit financially if they can generate additional well-child care visits and keep supply costs low.

GAD65 Autoantibodies Detected by Electrochemiluminescence Assay Identify High Risk for Type 1 Diabetes

The identification of diabetes-relevant islet autoantibodies is essential for predicting and preventing type 1 diabetes (T1D). The aim of the current study was to evaluate a newly developed electrochemiluminescence (ECL)-GAD antibody (GADA) assay and compare its sensitivity and disease relevance with standard radioassay. The assay was validated with serum samples from 227 newly diagnosed diabetic children; 68 prediabetic children who were prospectively followed to T1D; 130 nondiabetic children with confirmed islet autoantibodies to insulin, GAD65, IA-2, and/or ZnT8 longitudinally followed for 12 ± 3.7 years; and 181 age-matched, healthy, antibody-negative children. The ECL-GADA assay had a sensitivity similar to that of the standard GADA radioassay in children newly diagnosed with T1D, prediabetic children, and high-risk children with multiple positive islet autoantibodies. On the other hand, only 9 of 39 nondiabetic children with only a single islet autoantibody (GADA only) by radioassay were positive for ECL-GADA. GADA not detectable by ECL assay is shown to be of low affinity and likely not predictive of future diabetes. In conclusion, the new ECL assay identifies disease-relevant GADA by radioassay. It may help to improve the prediction and correct diagnosis of T1D among subjects positive only for GADA and no other islet autoantibodies.

Proinsulin/Insulin Autoantibodies Measured With Electrochemiluminescent Assay Are the Earliest Indicator of Prediabetic Islet Autoimmunity

OBJECTIVE We evaluated a novel electrochemiluminescent assay for insulin/proinsulin autoantibodies (ECL-IAA) as a new marker of the onset of islet autoimmunity and as a predictor of type 1 diabetes. RESEARCH DESIGN AND METHODS The Diabetes Autoimmunity Study in the Young (DAISY) prospectively follows children at increased genetic risk for development of islet autoimmunity (defined as presence of autoantibodies to insulin, GAD65, IA-2, or zinc transporter 8 [ZnT8]) and type 1 diabetes (general population of children and first-degree relatives). Serial serum samples from subjects who progressed to type 1 diabetes and who had their first islet autoantibodies measured by age 18 months (N = 47) were tested using ECL-IAA. RESULTS Almost all prediabetic children tested positive for ECL-IAA (46 of 47, 98%) during follow-up. ECL-IAA was almost always the first autoantibody to appear (94% total; 21% very first [by itself]; 23% with only mIAA; 19% with another islet autoantibody [GAD or ZnT8]; and 30% with ≥2 other antibodies [mIAA, GAD, IA-2, or ZnT8]). Among the 46 subjects who were ECL-IAA positive, ECL-IAA antedated the onset of other islet autoantibodies by a mean of 2.3 years (range, 0.3–7.2 years). Both the age of appearance of autoantibody and IAA levels (but not GAD65, IA2, or ZnT8 levels) are major determinants of the age of diabetes onset. CONCLUSIONS This new ECL-IAA assay defines more precisely the onset of prediabetic autoimmunity and may help identify events triggering islet autoimmunity, as well as allow earlier intervention for type 1 diabetes. Nearly all young children progressing to diabetes are insulin autoantibody positive.

Dysregulated Toll-Like Receptor–Induced Interleukin-1β and Interleukin-6 Responses in Subjects at Risk for the Development of Type 1 Diabetes

We tested the hypothesis that altered Toll-like receptor (TLR) signaling may be involved in early stages of type 1 diabetes (T1D). To do so, we analyzed TLR-induced interleukin (IL)-1β and IL-6 responses in freshly isolated peripheral blood mononuclear cells (PBMNCs) from seropositive compared with seronegative subjects. Similar frequencies of myeloid dendritic cells (mDCs), plasmacytoid DCs (pDCs), and monocytes were observed in seropositive and seronegative subjects. Subjects with autoantibodies had increased proportions of monocytes expressing IL-1β ex vivo. Activating PBMNCs with TLR3, TLR4, or TLR7/8 agonists in vitro led to increased percentages of IL-1β–expressing monocytes and mDCs from seropositive versus seronegative subjects. TLR ligation also resulted in a diminished IL-6 response in seropositive individuals as lower frequencies of IL-6–expressing monocytes and mDCs were induced. The dysregulated TLR-induced IL-1β and IL-6 pathways were more readily detectable in children aged <11 years and from 11 to <21 years, respectively, and did not involve altered HbA1c or the presence of one or more autoantibodies. Finally, subjects with autoantibodies had lower amounts of serum chemokine (C-X-C motif) ligand 10 compared with autoantibody-negative subjects. Our data may imply that alterations in innate immune pathways are detectable in genetically susceptible individuals and could be linked with the early course of T1D.

The Association Between Rural Residence and the Use, Type, and Quality of Depression Care

OBJECTIVE To assess the association between rurality and depression care. METHODS Data were extracted for 10,319 individuals with self-reported depression in the Medical Expenditure Panel Survey. Pharmacotherapy was defined as an antidepressant prescription fill, and minimally adequate pharmacotherapy was defined as receipt of at least 4 antidepressant fills. Psychotherapy was defined as an outpatient counseling visit, and minimally adequate psychotherapy was defined as > or = 8 visits. Rurality was defined using Metropolitan Statistical Areas (MSAs) and Rural Urban Continuum Codes (RUCCs). RESULTS Over the year, 65.1% received depression treatment, including 58.8% with at least 1 antidepressant prescription fill and 24.5% with at least 1 psychotherapy visit. Among those in treatment, 56.2% had minimally adequate pharmacotherapy treatment and 36.3% had minimally adequate psychotherapy treatment. Overall, there were no significant rural-urban differences in receipt of any type of formal depression treatment. However, rural residence was associated with significantly higher odds of receiving pharmacotherapy (MSA: OR 1.16 [95% CI, 1.01-1.34; P= .04] and RUCC: OR 1.04 [95% CI, 1.00-1.08; P= .05]), and significantly lower odds of receiving psychotherapy (MSA: OR 0.62 [95% CI, 0.53-0.74; P < .01] and RUCC: OR 0.91 [95% CI, 0.88-0.94; P < .001]). Rural residence was not significantly associated with the adequacy of pharmacotherapy, but it was significantly associated with the adequacy of psychotherapy (MSA: OR 0.53 [95% CI, 0.41-0.69; P < .01] and RUCC: OR 0.92 [95% CI, 0.86-0.99; P= .02]). Psychiatrists per capita were a mediator in the psychotherapy analyses. CONCLUSIONS Rural individuals are more reliant on pharmacotherapy than psychotherapy. This may be a concern if individuals in rural areas turn to pharmacotherapy because psychotherapists are unavailable rather than because they have a preference for pharmacotherapy.

Improving prediction of type 1 diabetes by testing non-HLA genetic variants in addition to HLA markers.

The purpose of this study was to explore whether non‐human leukocyte antigen (non‐HLA) genetic markers can improve type 1 diabetes (T1D) prediction in a prospective cohort with high‐risk HLA‐DR,DQ genotypes.

Pediatricians’ Attitudes About Collaborations With Other Community Vaccinators in the Delivery of Seasonal Influenza Vaccine

OBJECTIVE Achieving universal influenza vaccination among children may necessitate collaborative delivery involving both practices and community vaccinators. We assessed among pediatricians nationally their preferences regarding location of influenza vaccination for patient subgroups and their attitudes about collaborative delivery methods. METHODS The design/setting was a national survey conducted from July 2009 to October 2009. Participants included a representative sample of pediatricians from the American Academy of Pediatrics. RESULTS The response rate was 79% (330 of 416). Physicians felt strongly that vaccination should occur in their practice for children with chronic conditions (52%) and healthy 6-24-month-old infants (48%), but few felt strongly about healthy 5-18-year-olds (17%). Most (78%) thought having multiple delivery sites increased vaccination rates, and 86% thought that influenza vaccine should be available at school. Physicians reported being very/somewhat willing to hold joint community clinics with public health entities (76%) and to suggest to patient subgroups that they receive vaccine at community sites, including public clinics or pharmacies (76%). The most frequently reported barriers to collaborative delivery with community sites or school-located delivery included concerns about the following: estimating the amount of vaccine to order if children are vaccinated elsewhere (community 56%; school 80%); transfer of vaccine records (community 57%; school 78%); and reluctance of families to go outside of the office (community 45%; school 74%). CONCLUSIONS Most physicians are in favor of school-located or collaborative influenza vaccine delivery with community vaccinators, especially for healthy school-aged children. Collaborative approaches will require planning to ensure transfer of records, effective targeting of subgroups, and provisions to protect providers from being left with extra influenza supply.

Early Childhood Infections and the Risk of Islet Autoimmunity: The Diabetes Autoimmunity Study in the Young (DAISY)

OBJECTIVE Type 1 diabetes is a common chronic childhood disease, and the incidence is increasing globally. Childhood infections are considered a potential environmental trigger of type 1 diabetes. Alternatively, improved hygiene and reduced childhood infections could explain the increase in type 1 diabetes in developed countries. The association of reported illnesses during infancy and later development of islet autoimmunity (IA) were examined in the Diabetes Autoimmunity Study in the Young. RESEARCH DESIGN AND METHODS Complete illness interviews through 9 months of age were collected for 1,729 children—1,174 without a family history of type 1 diabetes and 555 with a first-degree relative with type 1 diabetes. Persistent IA was defined as positive antibodies to insulin, glutamic acid decarboxylase, or tyrosine phosphatase on at least two consecutive study visits. RESULTS There were 109 children with persistent IA among the 1,729 children with illness records. A greater number of gastrointestinal illnesses were associated with an increased risk of IA, but only among children who were exposed to gluten-containing grains (wheat or barley) either <4 months of age (hazard ratio 1.37 [95% CI 1.22–1.55]; P < 0.0001) or ≥7 months of age (1.12 [1.05–1.19]; P = 0.0005) compared with 4–6 months of age (P for interaction = 0.02). There were no associations of upper respiratory symptoms, respiratory illnesses, or fevers with IA. CONCLUSIONS Specific pathogens such as enteroviruses or rotavirus may increase the risk of IA in the presence of existing inflammation induced by diet.

Incidence of diabetic ketoacidosis at diagnosis of type 1 diabetes in Colorado youth, 1998-2012.

Incidence of Diabetic Ketoacidosis at Diagnosis of Type 1 Diabetes in Colorado Youth, 1998-2012 Diabetic ketoacidosis (DKA) at time of type 1 diabetes (T1D) diagnosis is life threatening and has detrimental long-term effects. It may reflect delayed access to health care, lower quality of care, or income inequality.1 In Scandinavian countries, incidence of DKA at diagnosis has decreased below 20%.2 Little is known about long-term trends in the United States. We examined the temporal trends in DKA at T1D diagnosis between 1998 and 2012 in Colorado and factors associated with DKA.