Comparison of the effects of osmotic pump implantation with subcutaneous injection for administration of drugs after total body irradiation in mice.

The increasing potential for radiation exposure from nuclear accidents or terrorist activities has intensified the need to develop pharmacologic countermeasures against injury from total body irradiation (TBI). Many initial experiments to develop and test these countermeasures utilize murine irradiation models. Yet, the route of drug administration can alter the response to irradiation injury. Studies have demonstrated that cutaneous injuries can exacerbate damage from radiation, and thus surgical implantation of osmotic pumps for drug delivery could adversely affect the survival of mice following TBI. However, daily handling and injections to administer drugs could also have negative consequences. This study compared the effects of subcutaneous needlesticks with surgical implantation of osmotic pumps on morbidity and mortality in a murine model of hematopoietic acute radiation syndrome (H-ARS). C57BL/6 mice were sham irradiated or exposed to a single dose of 7.7 Gy 60Co TBI. Mice were implanted with osmotic pumps containing sterile saline seven days prior to irradiation or received needlesticks for 14 days following irradiation or received no treatment. All irradiated groups exhibited weight loss. Fewer mice with osmotic pumps survived to 30 days post irradiation (37.5%) than mice receiving needlesticks or no treatment (70% and 80%, respectively), although this difference was not statistically significant. However, mice implanted with the pump lost significantly more weight than mice that received needlesticks or no treatment. These data suggest that surgical implantation of a drug-delivery device can adversely affect the outcome in a murine model of H-ARS.

Manufacturing of Dexamethasone-Poly(d,l-Lactide-co-Glycolide) Implants Using Hot-Melt Extrusion: Within- and Between-Batch Product Performance Comparisons.

Purpose: Reliable drug therapy with injectable intravitreal implants requires implants of consistent quality. The purpose of this study was to prepare dexamethasone-poly(d,l-lactide-co-glycolide) (PLGA) biodegradable implants and assess implant quality within and between batches for different polymer compositions. Methods: Implants containing 20% w/w dexamethasone with 3 theoretical rates of release (fast, intermediate, and slow) were manufactured with decreasing proportion of acid-terminated PLGA (50:50) and increasing proportion of ester-terminated PLGA (50:50) in a batch process using hot-melt extrusion. The implants were manufactured without and with in-process modification of extrusion/conveyor speed in the late phase of each batch. Implant samples collected at early, middle, and late phases of each batch were analyzed for diameter, drug loading, mechanical properties (strength and toughness), and drug release. Results: With a fixed process, unlike a modified process with an increase in extrusion speed and reduction of conveyor speed in the late phase, all implant formulations tended to decrease in diameter and mechanical properties in the late phase. Drug release profiles for the intermediate and slow release compositions were similar with or without process modification, unlike the fast release composition. Addition of ester-terminated PLGA resulted in a slower drug release. When all formulations are grouped together, the implant diameter exhibited a moderate correlation with mechanical properties, but no correlation was observed with drug release. Conclusions: Within a hot-melt extrusion batch process, the dexamethasone-PLGA implant diameter and hence toughness and strength tend to decline in the latter phase. In-process adjustment of extrusion and conveyor speeds can improve batch consistency and, potentially, implant integrity or performance during or after injection. Process changes did not affect drug release for 2 of the 3 implant compositions.

Assessing Allied Health-Care Professional Time in Pediatric Type 1 Diabetes: Associations With Clinical Factors, Technology and Social Determinants.

OBJECTIVES: The factors associated with allied health-care professional (HCP) time spent face-to-face with patients in clinic have not been well described in type 1 diabetes (T1D) given the introduction of resource-intensive technologies and gaps in socioeconomic circumstances. The objective of this study was to evaluate clinical and social factors associated with nonphysician HCP time in a pediatric T1D practice. METHODS: Nonphysician HCP workload data, including time spent in direct clinical care over a 1-year period and nonclinic contacts, were linked to data from 723 pediatric subjects with T1D and evaluated in relation to key demographic, social and diabetes treatment factors. RESULTS: HCPs spent 145.7 min per patient on a median of 3 clinic visits, with certified diabetes educators (CDEs) being responsible for most clinic interactions compared with psychosocial staff. CDE time varied considerably according to T1D duration, with new-onset patients (≤1 year) taking a median of 392.0 min compared with 114.5 min for their established counterparts (p<0.0001). Among the established group (n=629), CDE time was strongly associated with continuous subcutaneous insulin infusion therapy initiation, psychosocial service use, glycated hemoglobin (A1C) and degree of marginalization (p<0.0001). Overall, CDE time increased by 8.6 min for each 1.0% increase in A1C (p=0.022) and by 16.3 min for each 1-U increase in marginalization (p=0.01). CONCLUSIONS: We observed HCP time was associated with multiple clinical factors in addition to overall marginalization. Although initial investments in education and continuous subcutaneous insulin infusion training were considerable, our results suggest that these lead to a decrease in time spent in clinic over time, and is largely driven by lower A1C.

Real-World Use of Do-It-Yourself Artificial Pancreas Systems in Children and Adolescents With Type 1 Diabetes: Online Survey and Analysis of Self-Reported Clinical Outcomes.

BACKGROUND: Patient-driven initiatives have made uptake of Do-it-Yourself Artificial Pancreas Systems (DIYAPS) increasingly popular among people with diabetes of all ages. Observational studies have shown improvements in glycemic control and quality of life among adults with diabetes. However, there is a lack of research examining outcomes of children and adolescents with DIYAPS in everyday life and their social context. OBJECTIVE: This survey assesses the self-reported clinical outcomes of a pediatric population using DIYAPS in the real world. METHODS: An online survey was distributed to caregivers to assess the hemoglobin A1c levels and time in range (TIR) before and after DIYAPS initiation and problems during DIYAPS use. RESULTS: A total of 209 caregivers of children from 21 countries responded to the survey. Of the children, 47.4% were female, with a median age of 10 years, and 99.4% had type 1 diabetes, with a median duration of 4.3 years (SD 3.9). The median duration of DIYAPS use was 7.5 (SD 10.0) months. Clinical outcomes improved significantly, including the hemoglobin A1c levels (from 6.91% [SD 0.88%] to 6.27% [SD 0.67]; P<.001) and TIR (from 64.2% [SD 15.94] to 80.68% [SD 9.26]; P<.001). CONCLUSIONS: Improved glycemic outcomes were found across all pediatric age groups, including adolescents and very young children. These findings are in line with clinical trial results from commercially developed closed-loop systems.

Disparities in Insulin Pump Therapy Persist in Youth With Type 1 Diabetes Despite Rising Overall Pump Use Rates.

PURPOSE: This study sought to determine if disparities in insulin pump therapy among youth with type 1 diabetes (T1DM) persist despite recent increases in overall pump use rates. DESIGN AND METHODS: All patients aged 6 months-17 years, diagnosed with T1DM, and completed 4+ outpatient diabetes visits at an academically-affiliated pediatric health care center from 2011 to 2016 were identified (n = 2131). Data were collected from existing electronic medical records and a multivariable logistic regression model was used to identify factors associated with insulin pump therapy. RESULTS: Findings revealed one novel factor (patients/families whose primary language is Spanish [OR 0.47, p = 0.038] or other non-English languages [OR 0.47, p = 0.028]) and confirmed several previously known factors associated with lower insulin pump use: patients who were older (10-14 years OR 0.38, p < 0.0001; 15+ years OR 0.15, p < 0.0001), male (OR 0.80, p = 0.021), non-Hispanic black (OR 0.59, p = 0.009), American Indian/Alaska Native (OR 0.19, p = 0.023), had either government (OR 0.42, p < 0.0001) or no insurance (OR 0.52, p = 0.004) and poor glycemic control (at least one HbA1c ≥ 8.5%; OR 0.54, p < 0.0001). CONCLUSION: Significant disparities in insulin pump use in youth with T1DM persist despite known benefits associated with pump therapy and underlying causes remain unclear. PRACTICE IMPLICATIONS: Health care providers should explore barriers to insulin pump therapy, including limited English language proficiency.

A Surgical Procedure for the Administration of Drugs to the Inner Ear in a Non-Human Primate Common Marmoset (Callithrix jacchus).

Hearing research has long been facilitated by rodent models, although in some diseases, human symptoms cannot be recapitulated. The common marmoset (Callithrix jacchus) is a small, easy-to-handle New World monkey which has a similar anatomy of the temporal bone, including the middle ear ossicular chains and inner ear to humans, than in comparison with that of rodents. Here, we report a reproducible, safe, and rational surgical approach to the cochlear round window niche for the drug delivery to the inner ear of the common marmoset. We adopted posterior tympanotomy, a procedure used clinically in human surgery, to avoid manipulation of the tympanic membrane that may cause conductive hearing loss. This surgical procedure did not lead to any significant hearing loss. This approach was possible due to the large bulla structure of the common marmoset, although the lateral semicircular canal and vertical portion of the facial nerve should be carefully considered. This surgical method allows us to perform the safe and accurate administration of drugs without hearing loss, which is of great importance in obtaining pre-clinical proof of concept for translational research.

Readmission and complications within 30 days after intrathecal baclofen pump placement.

AIM: To describe 30-day outcomes after intrathecal baclofen (ITB) pump placement in children and identify risk factors for readmission, reoperation, and perioperative complication using the National Surgical Quality Improvement Program-Pediatric (NSQIP-P) database. METHOD: Patients aged 0 to 18 years who underwent ITB pump placement (2012-2014) comprised the study cohort defined in the database. Multivariate regression analysis was performed using preoperative and perioperative data from the American College of Surgeons' NSQIP-P database. Outcomes of interest within 30 days of surgery were (1) unplanned reoperation; (2) unplanned readmission; and (3) composite postoperative event, including complication, reoperation, and/or readmission. RESULTS: We identified 423 surgeries; 246 (58.2%) patients were male, 177 (41.8%) patients were female. Median age was 12 years and 11 months. Median operative time was 70 minutes (interquartile range 56-97min). Mean length of stay was 3.8 days. The patient population had a high number of medical comorbidities. The overall readmission rate was 7.3%; mean postoperative admission date was 14.1 days after surgery. Of readmitted patients, 64.5% underwent reoperation. The most common indication for reoperation was surgical site infection. Female sex was associated with decreased risk of readmission (odds ratio [OR] 0.25, 95% confidence interval [CI] 0.09-0.65; p=0.01); American Society of Anesthesiologists Classification of greater than or equal to 3 was associated with decreased risk of unplanned return to surgery (OR 0.26, 95% CI 0.11-0.66; p=0.04); length of stay greater than or equal to 3 days at index surgery was associated with increased risk of composite 30-day perioperative event (OR 2.33, 95% CI 1.29-4.20; p=0.01). INTERPRETATION: Our data provide national perspectives on 30-day perioperative outcomes for ITB pump placement in children. Results illustrate NSQIP-P database collection methodology and highlight opportunities for quality improvement in clinical practice. WHAT THIS PAPER ADDS: Seven percent of patients who underwent intrathecal baclofen pump placement required readmission within 30 days. The most common indication for reoperation was surgical site infection.

Hidden Medical Devices in the School Setting: What the School Nurse Needs to Know About the Safe Use of Baclofen Pumps.

One of the "hidden" medical devices in the school setting is the baclofen pump, which is used for the treatment of spasticity. The goals of spasticity treatment are to decrease muscle tone, deformity, and pain in order to maximize function and ease of care for both child and caregiver. The use of an intrathecal baclofen pump, often for children with cerebral palsy, spinal cord injury, brain injury, or stroke, has been effective in spasticity treatment. It is important for school nurses to be aware of the safety implications associated with this type of device. The Specialized Health Needs Interagency Collaboration (SHNIC) program at the Kennedy Krieger Institute has complied education and materials that explain the use of baclofen pumps in children with spasticity and the role of the school nurse in providing staff training, developing emergency care plans, and creating a safe school environment for children with special health needs.

A Primer on Insulin Pump Therapy for Health Care Providers.

An estimated 1 million people use an insulin pump to manage their diabetes. Few medical professionals understand or feel comfortable caring for people who use an insulin pump. This article will help the medical professional understand the reasons why the insulin pump helps the user to achieve better glycemic control, have more flexibility, and enjoy a better quality of life. Additionally, this article discusses the advantages, disadvantages, candidate selection, contraindications, basic functions, and troubleshooting of the insulin pump.

Continuous Femoral Nerve Catheters Decrease Opioid-Related Side Effects and Increase Home Disposition Rates Among Geriatric Hip Fracture Patients.

OBJECTIVE: To evaluate the effect of continuous femoral nerve catheter (CFNC) for postoperative pain control in geriatric proximal femur fractures compared with standard analgesia (SA) treatment. DESIGN: Retrospective comparative study. SETTING: Academic Level 1 trauma center. PATIENTS/PARTICIPANTS: We retrospectively identified 265 consecutive geriatric hip fracture patients who underwent surgical treatment. INTERVENTION: One hundred forty-nine patients were treated with standard analgesia without nerve catheter whereas 116 patients received an indwelling CFNC. MAIN OUTCOME MEASUREMENT: Daily average preoperative and postoperative pain scores, daily morphine equivalent consumption, opioid-related side effects and discharge disposition. RESULTS: Patients with CFNC patients reported lower average pain scores preoperatively (1.9 ± 1.7 for CFNC vs. 4.7 ± 2 for SA; P < 0.0001), on postoperative day 1 (1.5 ± 1.6 for CFNC vs. 3 ± 1.7 for SA; P < 0.0001) and postoperative day 2 (1.2 ± 1.5 for CFNC vs. 2.6 ± 2.1 for SA; P < 0.0001). CFNC group consumed 39% less morphine equivalents on postoperative day 1 (4.4 ± 5.8 mg for CFNC vs. 7.2 ± 10.8 mg for SA; P = 0.005) and 50% less morphine equivalent on postoperative day 2 (3.4 ± 4.4 mg for CFNC vs. 6.8 ± 13 mg for SA; P = 0.105). Patients with CFNC had a lower rate of opioid-related side effects compared with patients with SA (27.5% for CFNC vs. 47% for SA; P = 0.001). More patients with CFNC were discharged to home with or without health services than patients with SA (15% for CFNC vs. 6% for SA; P = 0.023). CONCLUSION: Continuous femoral nerve catheter decreased daily average patient-reported pain scores, narcotic consumption while decreasing the rate of opioid-related side effects. Patients with CFNC were discharged to home more frequently. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Treprostinil Administered to Treat Pulmonary Arterial Hypertension Using a Fully Implantable Programmable Intravascular Delivery System: Results of the DelIVery for PAH Trial.

BACKGROUND: The use of systemic prostanoids in severe pulmonary arterial hypertension (PAH) is often limited by patient/physician dissatisfaction with the delivery methods. Complications associated with external pump-delivered continuous therapy include IV catheter-related bloodstream infections and subcutaneous infusion site pain. We therefore investigated a fully implantable intravascular delivery system for treprostinil infusion. METHODS: A multicenter, prospective, single-arm, clinical trial (DelIVery for Pulmonary Arterial Hypertension) was conducted by using an implantable intravascular delivery system. The implanted pumps were refilled percutaneously at least every 12 weeks. The primary end point was the rate of catheter-related complications using the new model 10642 catheter compared with a predefined objective performance criterion of 2.5 per 1,000 patient-days based on the literature. RESULTS: Patients (n = 60) with severe PAH (World Health Organization group 1) receiving a stable dose of IV treprostinil for at least 4 weeks received an implant device and were followed up for 12.1 ± 4.4 months. Six catheter-related complications occurred, corresponding to a complication rate of 0.27 per 1,000 patient-days. The 97.5% upper one-sided confidence bound of 0.59 was less than the predefined criterion of 2.5 per 1,000 patient-days (P < .0001). Plasma treprostinil levels at 1 week postimplantation were highly correlated with baseline levels (r = 0.91; P < .0001). The delivery system management time as reported by the patients was 2.5 ± 1.7 hours per week preimplantation, and this time decreased to 0.6 ± 0.8 hour per week at 6 months' postimplantation (P < .0001). All patients rated overall satisfaction with the implantable system as good, very good, or excellent at 6 weeks and 6 months. There were no catheter-related bloodstream infections or catheter occlusions. CONCLUSIONS: The implantable intravascular delivery system delivered treprostinil to patients with PAH with a low rate of catheter-related complications and a high rate of patient satisfaction. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01321073; URL: www.clinicaltrials.gov.

Injury and Liability Associated with Implantable Devices for Chronic Pain.

BACKGROUND: Due to an increase in implantable device-related anesthesia pain medicine claims, the authors investigated anesthesia liability associated with these devices. METHODS: After institutional review board approval, the authors identified 148 pain medicine device claims from 1990 or later in the Anesthesia Closed Claims Project Database. Device-related damaging events included medication administration events, infections, hematomas, retained catheter fragments, cerebrospinal fluid leaks, cord or cauda equina trauma, device placed at wrong level, stimulator incorrectly programmed, delay in recognition of granuloma formation, and other issues. RESULTS: The most common devices were implantable drug delivery systems (IDDS; 64%) and spinal cord stimulators (29%). Device-related care consisted of surgical device procedures (n = 107) and IDDS maintenance (n = 41). Severity of injury was greater in IDDS maintenance claims (56% death or severe permanent injury) than in surgical device procedures (26%, P < 0.001). Death and brain damage in IDDS maintenance claims resulted from medication administration errors (n = 13; 32%); spinal cord injury resulted from delayed recognition of granuloma formation (n = 9; 22%). The most common damaging events for surgical device procedures were infections, inadequate pain relief, cord trauma, retained catheter fragments, and subcutaneous hygroma. Care was more commonly assessed as less than appropriate (78%) and payments more common (63%) in IDDS maintenance than in surgical device procedure claims (P < 0.001). CONCLUSIONS: Half of IDDS maintenance claims were associated with death or permanent severe injury, most commonly from medication errors or failure to recognize progressive neurologic deterioration. Practitioners implanting or managing devices for chronic pain should exercise caution in these areas to minimize patient harm.

Impact of a theory-based video on initiation of long-acting reversible contraception after abortion.

OBJECTIVE: Adoption of long-acting reversible contraception (LARC) (ie, the intrauterine device or the contraceptive implant) immediately after abortion is associated with high contraceptive satisfaction and reduced rates of repeat abortion. Theory-based counseling interventions have been demonstrated to improve a variety of health behaviors; data on theory-based counseling interventions for postabortion contraception are lacking. STUDY DESIGN: Informed by the transtheoretical model of behavioral change, a video intervention was developed to increase awareness of, and dispel misconceptions about, LARC methods. The intervention was evaluated in a randomized controlled trial among women aged 18-29 years undergoing surgical abortion at a clinic in Chicago, IL. Participants were randomized 1:1 to watch the intervention video or to watch a stress management video (control), both 7 minutes in duration. Contraceptive methods were supplied to all participants free of charge. Rates of LARC initiation immediately after abortion were compared. RESULTS: Rates of LARC initiation immediately after abortion were not significantly different between the 2 study arms; 59.6% in the intervention and 51.6% in the control arm chose a LARC method (P = .27). CONCLUSION: This study resulted in an unexpectedly high rate of LARC initiation immediately after abortion. High rates of LARC initiation could not be attributed to a theory-based counseling intervention.

Contraceptive continuation in Hispanic women.

OBJECTIVE: The purpose of this study was to examine the effect of Hispanic ethnicity on the continuation and satisfaction of reversible contraceptive methods. STUDY DESIGN: We analyzed 12 months of data that were collected from 7913 participants in the Contraceptive CHOICE Project. Kaplan-Meier survival curves were used to estimate continuation, and Cox proportional hazard models were used to estimate the risk of discontinuation. RESULTS: Hispanic women were more likely to choose a long-acting reversible contraceptive (LARC) method compared with non-Hispanic black and non-Hispanic white women (80%, 73%, and 75%, respectively; P < .05). The 12-month continuation rates were higher for LARC methods than combined hormonal methods for all race/ethnicity (Hispanic women, 87% vs 40%; non-Hispanic black women, 85% vs 46%; non-Hispanic white women, 87% vs 56%). There was no statistical difference in discontinuation of LARC methods at 12 months. Eighty percent of LARC users reported high satisfaction levels at 12 months, regardless of race/ethnicity. CONCLUSION: Hispanic women in the Contraceptive CHOICE Project experienced high continuation and satisfaction for LARC methods, similar to women of other ethnicities.

The U.K. service level audit of insulin pump therapy in adults.

AIMS: The National Institute for Health and Clinical Excellence (NICE) published guidelines for the use of continuous subcutaneous insulin infusion in 2008 (technology appraisal 151). The first U.K.-wide insulin pump audit took place in 2012 with the aim of determining adherence to the guidance issued in NICE technology appraisal 151. The results of the adult service level audit are reported here. METHODS: All centres providing continuous subcutaneous insulin infusion services to adults with diabetes in the U.K. were invited to participate. Audit metrics were aligned to technology appraisal 151. Data entry took place online using a DiabetesE formatted data collection tool. RESULTS: One hundred and eighty-three centres were identified as delivering adult continuous subcutaneous insulin infusion services in the U.K., of which 178 (97.3%) participated in the audit. At the time of the audit, 13 428 adults were using insulin pump therapy, giving an estimated prevalence of use of 6%. Ninety-three per cent of centres did not report any barriers in obtaining funding for patients who fulfilled NICE criteria. The mean number of consultant programmed activities dedicated to continuous subcutaneous insulin infusion services was 0.96 (range 0-8), mean whole-time equivalent diabetes specialist nurses was 0.62 (range 0-3) and mean whole-time equivalent dietitian services was 0.3 (range 0-2), of which 39, 61 and 60%, respectively, were not formally funded. CONCLUSIONS: The prevalence of continuous subcutaneous insulin infusion use in the U.K. falls well below the expectation of NICE (15-20%) and that of other European countries (> 15%) and the U.S.A. (40%). This may be attributable, in part, to lack of healthcare professional time needed for identification and training of new pump therapy users.

The behavioural and neuropathological impact of intranigral AAV-α-synuclein is exacerbated by systemic infusion of the Parkinson's disease-associated pesticide, rotenone, in rats.

Despite the widely held belief that Parkinson's disease is caused by both underlying genetics and exposure to environmental risk factors, it is still widely modelled in preclinical models using a single genetic or neurotoxic insult. This single-insult approach has resulted in a variety of models that are limited with respect to their aetiological, construct, face and/or predictive validity. Thus, the aim of the current study was to investigate the interplay between genes and the environment as an alternative approach to modelling Parkinson's disease. To do so, rats underwent stereotaxic surgery for unilateral delivery of the Parkinson's disease-associated gene, α-synuclein, into the substantia nigra (using AAV vectors). This was followed 13 weeks later by subcutaneous implantation of an osmotic minipump delivering the Parkinson's disease-associated pesticide, rotenone (2.5mgkg(-1)day(-1) for 4 weeks). The effect of the genetic and environmental insults alone or in combination on lateralised motor performance (Corridor, Stepping and Whisker Tests), nigrostriatal integrity (tyrosine hydroxylase immunohistochemistry) and α-synucleinopathy (α-synuclein immunohistochemistry) was assessed. We found that exposing AAV-α-synuclein-treated rats to rotenone led to a model in which the classical Parkinson's disease triad of progressive motor dysfunction, nigrostriatal neurodegeneration and α-synucleinopathy was evident. However, delivering rotenone systemically was also associated with bilateral motor dysfunction and loss of body weight. Thus, although we have shown that Parkinson's disease can be modelled in experimental animals by combined exposure to both genetic and environmental risk factors, this approach is limited by systemic toxicity of the pesticide rotenone. Direct intracerebral delivery of rotenone may be more useful in longer-term studies as we have previously shown that it overcomes this limitation.

[Prevalence of autoimmune diseases and microangiopathy in children with diabetes type 1 over the years 2000-2010]. / Wystepowanie chorób autoimmunizacyjnych oraz mikroangiopatii u dzieci z cukrzyca typu 1 w latach 2000-2010.

INTRODUCTION: In the past decade the number of patients with type 1 diabetes treated with continuous subcutaneous insulin infusion (CSII) has increased rapidly. Treatment of the disease is focused on proper physical development and the prevention of complications. Aim of the study was to analyze changes in the treatment and clinical picture of type 1 diabetes in children over the years 2000 to 2010 with particular emphasis on the presence of autoimmune diseases and microangiopathy. MATERIAL AND METHODS: The study included 567 children diagnosed with type 1 diabetes under the care of outpatient diabetes clinic. We compared 251 children, diabetes outpatient clinic patients in 2000, with 316 children in 2010. Data were obtained from the outpatient and hospital records. We compared baseline demographic, anthropometric data, treatment regimen, type of insulin, metabolic control, prevalence of autoimmune diseases and microangipathy. RESULTS: In 2010 there was a reduction in the age of diagnosis of diabetes from 10 to 8 years (p=0.039). Significantly increased the proportion of children treated with CSII (up to 60.1%) and decreased the percentage of children using conventional insulin for the benefit of insulin analogs. The increase in HbA1c from 7.4 to 8.0% (p<0.001) has been shown and increase in proportion of patients with HbA1c >7.5% in 2010. The percentage of children with obesity increased from 5.2 to 13.7% (p=0.004) and there was a significant increase in SDS-BMI. The percentage of children with autoimmune diseases such as celiac (from 0,4 to 7,3%, p<0,001) and thyroid (from 6.9 to 21.3%, p<0.001) has increased. The incidence of retinopathy decreased from 6 to 1% (p=0.04), and albuminuria decreased insignificantly. CONCLUSIONS: Over the last decade, a significant change in the method of treatment in children diagnosed with type 1 diabetes has occurred. The deterioration of metabolic control, despite the frequent use in the treatment of CSII, may be due to increased frequency of obesity and additional autoimmune diseases in today´s patients. More similar to physiologic way of insulin infusion in nowadays treatment may influence the decrease in the prevalence of retinopathy.

Orthopedic surgery in children with intrathecal baclofen pumps.

AIMS: Children with cerebral palsy often have severe spasticity leading to deformity that requires multiple orthopedic surgeries. Intrathecal baclofen pump implantation effectively decreases severe spasticity. The objective of this study was to determine whether children who have a baclofen pump implanted at a young age have fewer orthopedic surgeries than those who have a baclofen pump implanted at later ages. METHODS: In this retrospective study of 310 children, we compared occurrence of surgery in relation to having or not having the baclofen pump, by using survival analysis with surgery as the outcome, presence of baclofen pump as the exposure of interest, modeled as a time-dependent variable, and age as the time scale. RESULTS: There was no significant effect of pump placement on overall surgery frequency. Analyses by type of surgery showed that those without a pump in place had a 64% lower hazard of scoliosis surgery. CONCLUSIONS: No evidence was found to indicate that children who have a baclofen pump implanted at a young age have fewer orthopedic surgeries than those who have a baclofen pump implanted at later ages.

Vascular response to zotarolimus-coated balloons in injured superficial femoral arteries of the familial hypercholesterolemic Swine.

BACKGROUND: Drug-coated balloons are rapidly emerging as a therapeutic alternative for the interventional treatment of peripheral vascular disease. The purpose of this study was to test the hypothesis that an angioplasty balloon coated with the mTOR inhibitor zotarolimus (ZCB) would inhibit neointimal hyperplasia in a novel injury-based superficial femoral artery model in the familial hypercholesterolemic swine. METHODS AND RESULTS: A total of 44 familial hypercholesterolemic swine were included (12 designated to study tissue pharmacokinetics and 32 to study safety and efficacy). Fogarty balloon denudation was performed in all superficial femoral artery segments, followed by balloon angioplasty. In the pharmacokinetic study, a total of 24 ZCBs (300 µg/cm(2)) were used. Zotarolimus was detected in arterial tissue at 5 minutes (162 ng/mg of tissue), 24 hours (5.9 ng/mg of tissue), and 28 days (0.007 ng/mg of tissue) after ZCB inflation. In the safety and efficacy study, superficial femoral artery segments were randomized to either high-dose (600 µg/cm(2), n=16), low-dose (300 µg/cm(2), n=16), or paired uncoated balloons (high-dose ZCB control, n=16; low-dose ZCB control, n=16). At 28 days, the percentage of angiographic stenosis was similar among all tested groups. Histological analysis demonstrated a reduction in neointimal formation in both ZCB groups compared with controls (high-dose ZCB 44% reduction, P=0.007; low-dose ZCB 22% reduction, P=0.08). There was no evidence of delayed arterial healing or vascular toxicity in any of the ZCB groups. CONCLUSIONS: The single delivery of zotarolimus via coated balloon is feasible, and therapeutic levels are maintained up to 28 days. The ZCB technology appears to be effective in the reduction of neointimal proliferation in the superficial femoral artery of the familial hypercholesterolemic swine.