Pump It Up! A randomized clinical trial to optimize insulin pump self-management behaviors in adolescents with type 1 diabetes.

Individuals with type 1 diabetes (T1D) must engage in a variety of complex and burdensome self-management behaviors daily to maintain near normal blood glucose levels and prevent complications. There is a need for interventions to improve use of sophisticated diabetes technologies, such as insulin pumps, during adolescence - a very high-risk developmental period for individuals with T1D. All diabetes devices, including insulin pumps, store large amounts of behavioral data that can be downloaded and analyzed to evaluate adherence to recommended T1D self-management behaviors. The overall objective of the present study, Pump it Up!, was to use objectively downloaded insulin pump data to inform and test two interventions to optimize insulin pump use in adolescents with T1D and their caregivers. Multiphase Optimization Strategy (MOST) was used to achieve the overall goal of this study - to separately test the main effect of the Pump It Up! Personalized T1D Self-Management Behaviors Feedback Report and the main effect of Pump It Up! Problem-Solving Skills intervention to improve T1D self-management behaviors using a 2 × 2 factorial design. The purpose of this paper is to describe the Pump It Up! study design and rationale, and participant baseline characteristics. Longitudinal data analyses will be conducted, and moderating effects of psychosocial factors will be examined in relation to primary (insulin pump self-management behaviors) and secondary (A1C) outcomes.

Blood Glucose Monitoring Before and After Type 1 Diabetes Clinic Visits.

Objective: To determine patterns of blood glucose monitoring in children and adolescents with type 1 diabetes (T1D) before and after routine T1D clinic visits. Methods: Blood glucose monitoring data were downloaded at four consecutive routine clinic visits from children and adolescents aged 5-18 years. Linear mixed models were used to analyze patterns of blood glucose monitoring in patients who had at least 28 days of data stored in their blood glucose monitors. Results: In general, the frequency of blood glucose monitoring decreased across visits, and younger children engaged in more frequent blood glucose monitoring. Blood glucose monitoring increased before the T1D clinic visits in younger children, but not in adolescents. It declined after the visit regardless of age. Conclusions: Members of the T1D care team need to consider that a T1D clinic visit may prompt an increase in blood glucose monitoring when making treatment changes and recommendations. Tailored interventions are needed to maintain that higher level of adherence across time.

White Coat Adherence Occurs in Adolescents With Type 1 Diabetes Receiving Intervention to Improve Insulin Pump Adherence Behaviors.

BACKGROUND: To assess the occurrence of white coat adherence, defined as an increase in adherence to treatment regimens prior to a study appointment, in adolescents with type 1 diabetes (T1D) using insulin pumps and participating in a randomized adherence intervention trial. METHODS: Blood glucose monitoring (BGM) readings, carbohydrate inputs, and insulin boluses delivered were downloaded from the insulin pumps of adolescents, aged 10-18 years, at 3 consecutive T1D study visits. Linear mixed models were used to analyze patterns of BGM, carbohydrate inputs, and insulin boluses delivered in patients who had 40 consecutive days of data stored in their insulin pumps prior to the study visit. RESULTS: Stratified linear mixed models revealed that adolescents randomized to the Tailored Feedback Intervention group increased their blood glucose monitoring ( P < .01), carbohydrate inputs ( P < .0001), and insulin bolusing ( P < .0001) prior to study appointments. In contrast, white coat adherence did not occur in adolescents randomized to the Treatment as Usual group ( Ps > .42). CONCLUSIONS: White coat adherence may occur in adolescents participating in clinical trials. Meter and insulin pump data downloads representing the 1- to 2-week period prior to a study visit are likely to overestimate actual adherence during the time frame between study visits.

Efficacy and safety of triptorelin 6-month formulation in patients with central precocious puberty.

BACKGROUND: Triptorelin is an established treatment for central precocious puberty (CPP) as 1- and 3-month formulations. The current triptorelin 22.5 mg 6-month formulation is approved for prostate cancer therapy. This is the first study in patients with CPP. METHODS: The efficacy and safety of the triptorelin 6-month formulation in CPP were investigated. The primary objective was to evaluate the efficacy in achieving luteinizing hormone (LH) suppression to pre-pubertal levels at month 6. This was an international, non-comparative phase III study over 48 weeks. Eighteen medical centers in the US, Chile and Mexico participated. Forty-four treatment naïve patients (39 girls and five boys) aged at treatment start 2-8 years for girls and 2-9 years for boys with an advancement of bone age over chronological age ≥1 year were to be included. Triptorelin was administered im twice at an interval of 24 weeks. LH, follicle stimulating hormone (FSH) (basal and stimulated), estradiol (girls), testosterone (boys), auxological parameters, clinical signs of puberty and safety were assessed. RESULTS: Forty-one patients (93.2%) showed pre-pubertal LH levels (stimulated LH ≤5 IU/L) at month 6 and maintained LH suppression through month 12. The percentage of patients with LH suppression exceeded 93% at each time point and reached 97.7% at month 12. No unexpected drug-related adverse events were reported. CONCLUSIONS: The triptorelin 6-month formulation was safe and effective in suppressing the pituitary-gonadal axis in children with CPP. The extended injection interval may improve compliance and increase comfort in the management of CPP.

White Coat Adherence in Pediatric Patients With Type 1 Diabetes Who Use Insulin Pumps.

BACKGROUND: The purpose was to assess the occurrence of white coat adherence, defined as an increase in adherence to treatment regimens prior to a clinic appointment, in children and adolescents with type 1 diabetes (T1D) who use insulin pumps. METHODS: Blood glucose monitoring (BGM) data, carbohydrate inputs, and insulin boluses delivered were downloaded from the insulin pumps of children and adolescents, aged 7-19 years with T1D, at 2 consecutive routine diabetes clinic visits. Linear mixed models were used to analyze patterns of BGM, carbohydrate inputs, and insulin boluses delivered in patients who had ≥28 days of data stored in their insulin pumps. RESULTS: In general, younger children engaged in more frequent BGM, carbohydrate inputs, and insulin boluses delivered than older children and adolescents. White coat adherence occurred with frequency of BGM, carbohydrate inputs, and insulin boluses delivered, but only in younger children. CONCLUSIONS: Diabetes care providers need to be aware that white coat adherence may occur, particularly in young children. Providers routinely download meter and insulin pump data for the 1- to 2-week period before the clinic visit. For patients exhibiting white coat adherence, their data will overestimate the patient's actual adherence.

Importance of manually entering blood glucose readings when wireless-compatible meters are not being used with an insulin pump.

BACKGROUND: The objective was to determine if there were differences in blood glucose monitoring (BGM) data downloaded from insulin pumps of patients who use meters that wirelessly transmit data to their insulin pumps (i.e., wireless group) and those who do not (i.e., nonwireless group). METHODS: Blood glucose monitoring data were downloaded from the meters and insulin pumps of 47 children and adolescents with type 1 diabetes mellitus. Independent and paired t tests compared BGM data downloaded from meters and BGM data downloaded from insulin pumps. RESULTS: There were significant differences in BGM data downloaded from the insulin pumps of patients using wireless meters compared to those using nonwireless meters. Wireless patients appeared to engage in more BGM, had more low and in-range BG readings and fewer very high BG readingss than nonwireless patients. However, a comparison of BGM data downloaded from meters and insulin pumps of nonwireless patients indicated that their insulin pump data significantly underestimated the number of BGM readings conducted, as well as the number of low and in-range readings, while overestimating the number of very high BGM readings. CONCLUSIONS: Because patients who use nonwireless-compatible meters do not manually enter their low and in-range BGM readings into the insulin pump, BGM data downloaded only from pumps may provide an incomplete representation of BGM frequency or results. It is recommended that patients use meters that directly communicate with pumps or perform bolus calculations. Patients should be educated about the importance of manually entering all BGM readings if they do not use a wireless-compatible meter with their insulin pump.

Insulin bolusing software: the potential to optimize health outcomes in type 1 diabetes mellitus.

BACKGROUND: Insulin bolusing calculators alleviate the burden of having to calculate insulin bolus doses for patients with type 1 diabetes mellitus (T1DM). Three important pieces of information are needed: a blood glucose monitoring (BGM) result, carbohydrates to be consumed, and the amount of insulin bolus delivered. The purpose of this study was to describe insulin pump adherence behaviors associated with the use of bolus calculators in youth who use Medtronic insulin pumps. METHODS: Data were downloaded from the MiniMed Paradigm insulin pumps (Medtronic) of 31 youth with T1DM. Areas of adherence that were evaluated included fundamental insulin pump adherence behaviors (e.g., BGM, carbohydrate entry, and insulin bolusing), decisions about Wizard® recommendations, and three Wizard steps: BGM result-carbohydrate input-insulin bolus. RESULTS: On average, patients conducted BGM ≥4 times/day on 69% of days, inputted carbohydrates ≥3 times/day on 63% of days, and insulin bolused ≥3 times/day on 85% of days. Participants generally followed Wizard recommendations. Finally, participants completed all three Wizard steps (BGM, carbohydrate input, insulin bolus) within 30 min for an average of 29% of boluses. Almost 3% of boluses that were preceded by Wizard use were delivered without conducting BGM or inputting carbohydrates. CONCLUSION: There was substantial variability in insulin pump adherence behaviors (e.g., days when no BGM occurred, reliance on basal insulin). Interventions targeting insulin pump adherence behaviors have the potential to optimize diabetes health outcomes and glycemic control. Improving insulin pump software reports is one promising avenue for improving adherence.

WU and KI polyomaviruses in respiratory samples from allogeneic hematopoietic cell transplant recipients.

Data are limited regarding 2 new human polyomaviruses, KI polyomavirus (KIPyV) and WU polyomavirus (WUPyV), in immunocompromised patients. We used real-time PCR to test for these and 12 respiratory viruses in 2,732 nasal wash samples collected during the first year after allogeneic hematopoietic cell transplantation from 222 patients. Specimens were collected weekly until day 100; then at least every 3 months. One year after hematopoietic cell transplantation, the cumulative incidence estimate was 26% for KIPyV and 8% for WUPyV. Age <20 years predicted detection of KIPyV (hazard ratio [HR] 4.6) and WUPyV (HR 4.4), and detection of a respiratory virus in the previous 2 weeks predicted KIPyV detection (HR 3.4). Sputum production and wheezing were associated with detection of KIPyV in the past week and WUPyV in the past month. There were no associations with polyomavirus detection and acute graft versus host disease, cytomegalovirus reactivation, neutropenia, lymphopenia, hospitalization, or death.

Acute regulation of renal Na+/H+ exchanger NHE3 by dopamine: role of protein phosphatase 2A.

Nephrogenic dopamine is a potent natriuretic paracrine/autocrine hormone that is central for mammalian sodium homeostasis. In the renal proximal tubule, dopamine induces natriuresis partly via inhibition of the sodium/proton exchanger NHE3. The signal transduction pathways and mechanisms by which dopamine inhibits NHE3 are complex and incompletely understood. This manuscript describes the role of the serine/threonine protein phosphatase 2A (PP2A) in the regulation of NHE3 by dopamine. The PP2A regulatory subunit B56δ (coded by the Ppp2r5d gene) directly associates with more than one region of the carboxy-terminal hydrophilic putative cytoplasmic domain of NHE3 (NHE3-cyto), as demonstrated by yeast-two-hybrid, coimmunoprecipitation, blot overlay, and in vitro pull-down assays. Phosphorylated NHE3-cyto is a substrate for purified PP2A in an in vitro dephosphorylation reaction. In cultured renal cells, inhibition of PP2A by either okadaic acid or by overexpression of the simian virus 40 (SV40) small T antigen blocks the ability of dopamine to inhibit NHE3 activity and to reduce surface NHE3 protein. Dopamine-induced NHE3 redistribution is also blocked by okadaic acid ex vivo in rat kidney cortical slices. These studies demonstrate that PP2A is an integral and critical participant in the signal transduction pathway between dopamine receptor activation and NHE3 inhibition.

Clinical disease in children associated with newly described coronavirus subtypes.

OBJECTIVES: Coronaviruses cause upper respiratory illness and occasionally lower tract disease in susceptible populations. In this study we examined the prevalence of 4 human coronaviruses, including subtypes OC43, 229E, and the recently described NL63 and HKU1 in a pediatric population presenting to a children's hospital. PATIENTS AND METHODS: Specimens collected over a 1-year period from pediatric patients presenting with acute respiratory illness were analyzed for the presence of 4 coronavirus subtypes using consensus and subtype-specific real-time reverse-transcription polymerase chain reaction assays. The demographic and clinical characteristics associated with coronavirus infection were examined retrospectively. RESULTS: Coronaviruses were detected in 66 of 1043 children. Eight, 11, 19, and 28 specimens were positive for subtypes 229E, NL63, OC43, and HKU1, respectively. Coronaviruses were detected throughout the study period; all 4 of the subtypes were present simultaneously in December. The acute clinical features were similar across subtypes. Of 32 children infected with a coronavirus as the sole respiratory pathogen, 13 had lower respiratory tract disease. Children whose only detectable respiratory virus was a coronavirus were more likely to have underlying chronic disease than were children coinfected with another respiratory virus. CONCLUSIONS: Although 4 subtypes of coronavirus were detected, the recently discovered coronavirus subtypes NL63 and HKU1 accounted for the majority of coronaviruses detected in our cohort of mostly hospitalized children with respiratory symptoms. New subtypes likely represent a substantial portion of previously unexplained respiratory illnesses.

Comparison of real-time PCR assays with fluorescent-antibody assays for diagnosis of respiratory virus infections in children.

Conventional fluorescent-antibody (FA) methods were compared to real-time PCR assays for detection of respiratory syncytial virus (RSV), influenza virus type A (FluA), parainfluenza virus types 1, 2, and 3 (PIV1, PIV2, and PIV3), human metapneumovirus (MPV), and adenovirus (AdV) in 1,138 specimens from children with respiratory illnesses collected over a 1-year period. At least one virus was detected in 436 (38.3%) specimens by FA and in 608 (53.4%) specimens by PCR (P<0.001). Specimen quality was inadequate for FA in 52 (4.6%) specimens; 13 of these (25%) were positive by PCR. In contrast, 18 (1.6%) specimens could not be analyzed by PCR; 1 of these was positive by FA. The number of specimens positive only by PCR among specimens positive by PCR and/or FA was 18 (7.0%) of 257 for RSV, 18 (13.4%) of 134 for FluA, 25 (64.1%) of 39 for PIV1, 8 (88.9%) of 9 for PIV2, 17 (30.1%) of 55 for PIV3, and 101 (76.5%) of 132 for AdV. MPV was detected in 6.6% of all specimens and in 9.5% of the 702 specimens negative by FA. The mean number of virus copies per milliliter in specimens positive by both PCR and FA was significantly higher, at 6.7x10(7), than that in specimens positive only by PCR, at 4.1x10(4) (P<0.001). The PCR assays were significantly more sensitive than FA assays for detecting respiratory viruses, especially parainfluenza virus and adenovirus. Use of real-time PCR to identify viral respiratory pathogens in children will lead to improved diagnosis of respiratory illness.

Impact of a home-based activity and dietary intervention in people with slowly progressive neuromuscular diseases.

OBJECTIVE: To determine whether a home-based activity and dietary intervention can increase activity level, reduce caloric intake, and impact positively components of metabolic syndrome in a disabled population. DESIGN: Testing occurred at 3 points during the 6-month intervention period (baseline, 3mo, 6mo) and at 6 months postintervention. Each test point included laboratory testing of anthropometric and metabolic variables and 3 days of home-based activity and dietary monitoring. A personally tailored activity and dietary prescription based on baseline testing was implemented during the 6-month intervention period. SETTING: Human performance laboratory of a university and each subject's home. PARTICIPANTS: Twenty adult volunteer ambulatory subjects with several types of slowly progressive neuromuscular disease (NMD). INTERVENTION: Using a pedometer, subjects were instructed to increase number of steps by 25% over their baseline determined from home monitoring. An individualized dietary prescription was provided focusing on problematic issues identified from the baseline dietary profile. MAIN OUTCOME MEASURES: Body composition, physical activity, dietary intake, energy expenditure, gait efficiency, metabolic variables, and quality of life. RESULTS: At the end of the protocol, mean step count increased approximately 27% above baseline (P=.001) and caloric intake decreased over 300kcal/d (P=.002). Body fat percentage significantly decreased (from 33.3%+/-1.5% to 32.6%+/-1.6%, P=.032). Gait efficiency did not change, and metabolic variables did not show statistically significant improvement, although 2 of the 5 subjects originally meeting the criteria for metabolic syndrome at baseline no longer met the criteria at the end of the intervention period. Six months after completing the protocol, caloric intake remained significantly reduced (P=.02), but although mean step count remained elevated, it was not statistically significant. CONCLUSIONS: Using a home-based protocol, people with NMD can increase activity and reduce caloric intake. Although this 6-month program showed positive changes, it was insufficient to affect risk factors associated with metabolic syndrome. It remains to be seen if a program longer than 6 months or a more rigorous program could lead to a reduction in the risk factors associated with metabolic syndrome.

Detection and quantification of human metapneumovirus in pediatric specimens by real-time RT-PCR.

BACKGROUND: Human metapneumovirus (h MPV), a recently identified virus, causes respiratory illness in children. OBJECTIVES: A real-time reverse transcription-polymerase chain reaction (RT-PCR) assay was developed and used to detect and quantify h MPV in respiratory specimens. STUDY DESIGN: The quantitative RT-PCR assay amplified an approximately 70 base pair fragment from the h MPV fusion protein gene. The assay was validated and used to test respiratory specimens obtained from children seen at a hospital in Seattle, Washington, from December 2002 through May 2003. RESULTS: The assay detected 1000 h MPV copies/mL of specimen, did not detect 19 other respiratory viruses, and was able to detect and accurately quantify isolates from the four known h MPV genetic lineages in a proficiency panel of 20 previously tested samples. h MPV was detected in 52 (7.2%) of 719 pediatric respiratory specimens. The mean log10 copies/mL of h MPV in the 52 positive specimens was 7.67 (range=4.59-10.60). Children aged 7-12 months had a significantly higher h MPV prevalence (12.4%) than did children younger than 7 months (4.7%) (P<0.005). Children in this age group also had significantly higher levels of h MPV in their respiratory specimens (mean log 8.43 copies/mL) than did the younger children (mean log 6.93 copies/mL) (P=0.0025). CONCLUSIONS: The rapid real-time RT-PCR assay described here is a sensitive test for clarifying the epidemiology of and diseases associated with h MPV.

Metabolic syndrome in neuromuscular disease.

OBJECTIVES: To test the hypotheses that (1) people with neuromuscular disease (NMD) have multiple risk factors for cardiovascular disease and diabetes and (2) these risk factors worsen over time. DESIGN: Longitudinal testing with average 2.5-year follow-up. SETTING: Human performance laboratory of a university. PARTICIPANTS: Eleven ambulatory volunteers with slowly progressive NMD and 8 able-bodied controls, group-matched for age and body mass index (BMI) at baseline. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Percentage of body fat (%BF), physical activity, energy expenditure, blood lipids and glucose, and blood pressure. RESULTS: At baseline, NMD subjects were more obese (37%BF vs 34%BF, respectively) and more sedentary than the controls, spending less time in total activity (144 min/d vs 214 min/d) and in exercise (11 min/d vs 45 min/d). The NMD group also had numerous cardiovascular and metabolic risk factors, with low high-density lipoprotein cholesterol, high BMI, and high triglyceride being the most common. Additionally, 55% of the NMD group satisfied the criteria for metabolic syndrome, versus 0% in the control group. Most parameters did not significantly worsen during the average 2.5-year follow-up period in either group. CONCLUSIONS: People with NMD are at high risk for developing chronic diseases resulting from obesity and a sedentary lifestyle. Intervention studies aimed at reducing their risk for such chronic diseases are warranted.

Evaluation of quantitative and type-specific real-time RT-PCR assays for detection of respiratory syncytial virus in respiratory specimens from children.

BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract morbidity in young children and immunosuppressed patients. OBJECTIVES: To rapidly and accurately quantify and subtype RSV in respiratory samples, we developed and evaluated two real-time RT-PCR assays. STUDY DESIGN: A quantitative assay was designed using primers for a consensus region of the matrix protein gene and a subtype-specific assay for RSV-A and RSV-B detection was designed using primers for the polymerase gene. Quantitative RSV RT-PCR results of pediatric nasal wash samples submitted to the University of Washington Virology Laboratory from December 2002, through May 2003, were compared to those of an indirect fluorescent antibody RSV antigen detection assay (FA). RESULTS: Specificity of the RT-PCR assay was high, with no amplification of eleven common respiratory viruses and eight herpes viruses. Among 751 samples, RSV was detected in 267 (35.6%) by FA and in 286 (38.1%) by RT-PCR. Median RSV copy number in nasal wash samples that were positive by both FA and RT-PCR was 2.5 x 10(7) copies/mL versus a median of 3.0 x 10(4) copies/mL for samples positive by RT-PCR only (P < 0.001). The detection and quantity of RSV in respiratory specimens was associated with younger age, but not with gender or hospitalization. Among positive samples from this Seattle cohort, 52% were subtype A and 48% were subtype B. Both subtypes were detected with similar viral loads among all patient groups (stratified by age, gender, and hospitalization), and throughout the specimen collection period. CONCLUSIONS: These real-time RT-PCR assays provide a rapid, specific, and highly sensitive alternative for detecting, quantifying, and subtyping RSV in clinical specimens.

Concept of pre-death. Restlessness in dementia.

The circumstances surrounding the deaths of 23 patients on a behavior stabilization unit during a 1-year period were examined. The death rate was more than double that of previous years, and raised concern for the staff. The majority of deaths (n = 17) occurred within 2 months of admission to the unit, and 16 of the patients who died had a diagnosis of vascular or mixed dementia. The presenting behaviors for these patients may be similar to those of pre-death restlessness, a condition that may affect individuals in their last hours or days of life. No literature can be found linking pre-death restlessness with end-stage vascular dementia. The memory of how a person dies can linger for family and loved ones (Enck, 1992). Distress caused by behaviors with end-stage dementia may be alleviated if the symptoms of pre-death restlessness are recognized. It may be a relief for family and staff to know the patient is indeed dying, rather than exhibiting new and seemingly uncontrollable behaviors. In that situation, appropriate palliative care could be initiated for the patient's and family's comfort. Accurate nursing assessment, evaluation, communication, and documentation of both the behaviors and interventions is vital in supporting both patients and families.

Data collection strategies for accessing adolescent women's worlds.

A two-year study was initiated in 1999 to investigate adolescent women's health concerns pertaining to their relationships. Data were obtained from four groups of girls (ages 14-19; N = 31) that met for approximately 18 weeks each. To help equalize power in the groups and facilitate a respectful and caring environment, we encouraged each group to use a variety of strategies, including those based on feminist principles. Data collection procedures based on feminist values can enable researchers to gain rich descriptions on the lived experience of adolescent women. Such procedures can help create an environment in which individuals can articulate their concerns and collectively co-construct the meanings of life events in health-promoting and consciousness-raising ways.

Cigarette smoking and the disenfranchisement of adolescent girls: a discourse of resistance?

The consequences of smoking for women are of particular concern in light of recent observations that more adolescent females than males are taking up smoking. To date, few studies have explored gender differences in depth, but we do know that males and females smoke for different reasons and that current smoking prevention programs may be differentially effective depending on gender. Recent evidence suggests that the school environment may have an important influence on smoking. The purpose of this study, therefore, was to explore gender differences in the relationships between cigarette smoking and adolescents' experiences of school climate and their relationships with the school and significant adults in their lives. A secondary data analysis was done using a data set derived from a student survey conducted in 20 secondary schools in British Columbia (BC), Canada, which included 8,179 students in grades 8 to 12. Analyses were primarily descriptive. The results demonstrated that adolescent girls who smoke are more likely than either males or nonsmoking females to experience powerlessness in their school environment and to feel considerably less attachment to the school. Female smokers are more likely than males or female nonsmokers to be engaged in oppositional, distanced, and unsatisfactory relationships with important adults in their lives, particularly those who are in positions of relative power and authority. These findings are discussed in relation to critical and feminist perspectives that suggest smoking is part of a larger discourse of resistance within schools. The implications for health practitioners are discussed.