The role of genetic modifiers, inflammation and CFTR in the pathogenesis of Cystic fibrosis related diabetes.

Cystic fibrosis related diabetes (CFRD) generally reflects insufficient and/or delayed production of insulin, developing slowly over years to decades. Multiple mechanisms have been implicated in the pathogenesis of CFRD. CFTR function itself is a strong determinant of CFRD risk. Variants in CFTR that result in residual CFTR function and exocrine pancreatic sufficiency reduce the risk of CFRD by ten to twenty fold. Two groups of hypotheses have been proposed for the mechanism of CFTR impairing insulin secretion in CFRD: (1) ß-cell dysfunction results from ß cell intrinsic CFTR-dependent mechanisms of insulin secretion. (2) ß-cell dysfunction results from factors outside the ß cell. Genome-wide association studies have identified multiple susceptibility genes for type 2 diabetes, including TCF7L2, CDKN2A/B, CDKAL1, and IGF2BP2, as containing genetic modifiers of CFRD. These findings support the presence of intrinsic ß cell defects playing a role in CFRD pathogenesis. Oxidative stress and inflammation are ß cell-extrinsic mechanisms involved with CFRD. CFTR mutations render ß cells more susceptible to oxidative stress and also leads to defects in α-cell function, resulting in reduced suppression of glucagon secretion. Furthermore, CFRD is characterized by ß cell loss secondary to intra-islet inflammation. Recent studies have demonstrated the presence of multiple inflammatory mediators within the human CF islet. This review presents a concise overview of the current understanding of genetic modifiers of CFRD, oxidative stress, islet inflammation, and the controversies about the role of CFTR in the islet.

Cystic fibrosis-related diabetes: The patient perspective.

Cystic fibrosis-related diabetes (CFRD) affects nearly 20% of adolescents and 40-50% of adults. However, the impact on patients and their families is poorly understood. Here, we examine how patients perceive CFRD and identify gaps in our understanding of the patient experience. Despite its relatively high prevalence, data suggest that many individuals are not aware of the possibility of developing CFRD or compare it to other types of diabetes. Annual oral glucose tolerance testing (OGTT) may serve as an opportunity to provide education and prepare individuals for the possibility of developing abnormalities in glucose tolerance. Many cite lack of awareness of CFRD as the most difficult part of the diagnosis. While factors such as older age and a strong support system promote acceptance, most individuals view the diagnosis negatively and struggle to balance the demands of diabetes with other obligations, including airway clearance, nebulizer therapies, supplementation nutrition, and administration of vitamins and medications. Relatively few people with CFRD monitor their blood glucoses consistently, which is attributed to time constraints or an attempt to avoid pain. In addition, many feel that they are not prone to hypoglycemia and are not concerned with long-term complications, anticipating that they will succumb to their pulmonary disease before these become problematic. The adolescent period presents unique challenges for adherence as children work to develop autonomy. Factors that promote CFRD adherence include incorporating management into daily CF routines and the support of knowledgeable providers to help develop an individualized approach to management. Diabetes technology has the potential to reduce treatment burden and improve glycemic control, but data in CFRD are limited, and additional study is needed. Given that CFRD is associated with a decline in health-related quality of life, it is critical that providers understand patients' perspectives and address gaps in understanding and barriers to management.

A Clinician's guide to vitamin D supplementation for patients with cystic fibrosis.

Vitamin D deficiency is common in the general population, and even more so in patients with cystic fibrosis. Deficiency is exacerbated in cystic fibrosis patients because of a myriad of causes including malabsorption, decreased fat mass, reduced 25-hydroxylation of vitamin D, reduced exposure to sunlight, decreased vitamin D binding protein, and exposure to drugs that increase catabolism. In turn, vitamin D deficiency can contribute to poor bone health. Additionally, it may contribute to pulmonary decline in the form of worsening pulmonary function, increased colonization with pathogens, and increased pulmonary exacerbation. Because vitamin D deficiency is correlated with negative clinical effects in multiple organ systems of patients with cystic fibrosis, it is important to screen for and treat deficiency in these patients. The Cystic Fibrosis Foundation has issued guidelines for the treatment of vitamin D deficiency, targeting serum levels of 25-hydroxyvitamin D of at least 30 ng/ml. The guidelines offer age-specific escalating dose regimens depending on serum vitamin D levels, with monitoring at 12- week intervals after changing therapy. They address the literature on alternative vitamin D sources, such as UV lamps, ideal formulations (cholecalciferol in preference to ergocalciferol), and optimal vehicles of administration. Despite these detailed recommendations, most centers are still unable to achieve in-target serum vitamin D levels for many of their patients. Future research examining ideal treatment regimens to achieve serum targets and maximize clinical effects are needed. Moreover, it is unknown whether vitamin D sufficiency will be easier to achieve on new triple therapy cystic fibrosis drug combinations, and how these drugs will contribute to vitamin D-related clinical outcomes.

Comparing Opinions on Meaningful Recognition: Do Views of Trauma Nursing Leaders and Staff Align?

With increased demand for registered nurses (RN), due to increasing shortage and turnover rate, the role of meaningful recognition becomes of paramount importance. We hypothesized that RNs and leaders value forms of recognition differently, due to generational gap and changing health care environment. This study included 46 RN/support staff (RN/SS group) and 10 nurse leaders (leaders group) from a Level 1 trauma center. Mean values from 5-point Likert scale survey on 31 forms of recognition (grouped into 6 categories) and demographics (age, nursing experience, and gender) were compared. All participants were separated into groups: 35 years of age and younger (millennials; n = 29) and older than 35 years (Gen X/boomers; n = 27). Majority of RN/SS were 26-35 years of age (43.5%) and 50.0% had less than 3 years of nursing experience. Half of the leaders were 36-45 years of age (p = .01 vs. RN/SS), and 70.0% had 16 years of experience or greater (p = .001). There was 9:1 female-to-male ratio in both groups (p = .8). The RN/SS rated "salary increase" highest and leaders rated "celebration for years of service" highest (both means: 4.4). When categorized, "monetary rewards" ranked highest both by RN/SS and leaders (means: 4.4 and 4.1). Overall, there was no statistically significant difference between mean values. The Gen X/boomers rated statistically significantly higher 9 forms and 3 categories (written/public acknowledgment and private verbal feedback) than millennials. Mean values for forms/categories of recognition were lower for RN/SS than for leaders, but differences were not statistical. Age drove the most difference in most meaningful forms, as preference for monetary rewards stems from the younger generations' focus on work-life balance.

Adrenal Insufficiency in Pediatric Eosinophilic Esophagitis Patients Treated with Swallowed Topical Steroids.

Swallowed topical steroids (STS) are the only effective pharmacological therapy for eosinophilic esophagitis (EoE). Thus far, studies of small populations of EoE patients have reported conflicting results in relation to adrenal insufficiency (AI). We sought to measure AI in a clinical setting in children taking STS for EoE. We performed a quality improvement study of pediatric EoE patients seen in a multidisciplinary clinic, who were treated with STS for at least 3 months. Two hundred twenty-five patients completed questionnaires to assess for signs of AI. All patients were requested to have fasting morning cortisol levels completed and if abnormal (<5 µg/dL or 139 nmol/L) twice, endocrinology consultation, and low-dose adrenocorticotropic hormone stimulation test were performed. A peak stimulated cortisol level of <18 µg/dL or 500 nmol/L was diagnostic of AI. Five of 106 STS-treated EoE patients who had morning cortisol levels drawn had AI. All 5 of these patients had asthma and were on additional topical steroid treatments. The number of steroid modalities and dose of steroid were not significant risk factors. Despite this low percentage, the life-threatening potential of AI warrants patient screening, as patients with iatrogenic AI are typically asymptomatic until an emergency triggers adrenal crisis. Further multicenter studies are needed to better define the risk attributable to STS alone, particularly in patients receiving combined steroid modalities.

Reduction of Insulin Related Preventable Severe Hypoglycemic Events in Hospitalized Children.

OBJECTIVE: Insulin is a commonly used, high-risk medication in the inpatient setting. Incorrect insulin administration can lead to preventable hypoglycemic events, which are a significant morbidity in inpatient diabetes care. The goal of this intervention was to decrease preventable insulin-related hypoglycemic events in an inpatient setting in a tertiary care pediatric hospital. METHODS: Methods included the institution of several interventions such as nursing and physician education, electronic medical record order sets, electronic communication note templates, and the development of new care guidelines. RESULTS: After the institution of multiple interventions, the rate of preventable hypoglycemic events decreased from 1.4 preventable events per 100 insulin days to 0.4 preventable events per 100 insulin days. CONCLUSIONS: Through the use of a multi-interventional approach with oversight of a multidisciplinary insulin safety committee, a sustained decreased rate of severe preventable hypoglycemic events in hospitalized pediatric patients receiving insulin was achieved.

Use of Telemedicine to Improve Adherence to American Diabetes Association Standards in Pediatric Type 1 Diabetes.

BACKGROUND: The American Diabetes Association (ADA) recommends that children with type 1 diabetes (T1D) see a multidisciplinary team and have hemoglobin A1c (A1C) levels measured every 3 months. Patients in rural areas may not follow guidelines because of limited specialty care access. We hypothesized that videoconferencing would result in equivalent A1C compared with in-person visits and increased compliance with ADA recommendations. MATERIALS AND METHODS: The Barbara Davis Center (BDC) (Aurora, CO) telemedicine program provides diabetes care to pediatric patients in Casper and Cheyenne, WY, via remote consultation with annual in-person visits. Over 27 months, 70 patients were consented, and 54 patients completed 1 year in the study. RESULTS: Patients were 70% male, with a mean age of 12.1 ± 4.1 years and T1D duration of 5.4 ± 4.1 years. There was no significant change between baseline and 1-year A1C levels for patients with data at both time points. Patients saw diabetes specialists an average of 2.0 ± 1.3 times per year in the year prior to starting telemedicine and 2.9 ± 1.3 times (P < 0.0001) in the year after starting telemedicine. Patients and families missed significantly less school and work time to attend appointments. CONCLUSIONS: Our study suggests telemedicine is equivalent to in-person visits to maintain A1C, whereas families increase the number of visits in line with ADA recommendations. Patients and families miss less school and work. Decreased financial burden and increased access may improve overall diabetes care and compliance for rural patients. Further study is needed to detect long-term differences in complications screenings and the financial impact of telemedicine on pediatric diabetes care.

Early severe fetal Graves disease in a mother after thyroid ablation and thyroidectomy.

BACKGROUND: Fetal Graves disease rarely presents before 26 weeks of gestation. We report a case of severe fetal Graves disease at 18 weeks of gestation in a mother who had very elevated Graves disease antibodies despite being several years post-thyroid ablative therapy and thyroidectomy. CASE: A 36-year-old woman, gravida 1 para 0, with severe Graves disease post-radioiodine ablation followed by thyroidectomy on levothyroxine presented at 18 weeks of gestation for ultrasound examination. Her fetus was found to be severely tachycardic with a goiter. Propylthiouracil was initiated for fetal therapy. Delivery at 34 weeks of gestation was undertaken as a result of preterm premature rupture of membranes. The neonate experienced heart failure and pulmonary hypertension at birth but recovered with appropriate medical therapy. CONCLUSION: It is possible for fetal Graves disease to develop as early as 18 weeks of gestation, and women who have had thyroid ablation and postsurgical hypothyroidism remain at risk for this serious pregnancy complication.

Characterization of acute appendicitis in diabetic children.

PURPOSE: Children with diabetes mellitus (DM) who develop acute appendicitis can present a diagnostic and clinical challenge. No studies have examined this population since the advent of multiple dose insulin therapy, computed tomography, and laparoscopic surgery. We sought to characterize these children to identify their differences and how to best care for them. METHODS: We retrospectively examined the medical records of children with a preexisting diagnosis of DM treated for acute appendicitis. Values are presented as the mean±the standard error of the mean, and Student's t-test was used for statistical comparison. RESULTS: We identified 18 diabetic children treated for acute appendicitis, making this the largest series of its kind. These children had similar presentations compared to non-diabetics, with the exception of often presenting without fever (83.3% with an initial temperature <38 C). All children developed significant postoperative hyperglycemia (average high 382±18mg/dL), and most had glycemic control for ≤50% of the hospitalization (14/18, 77.8%), but they otherwise had typical postoperative courses. CONCLUSIONS: Diabetic children with appendicitis are often afebrile at presentation and have serum glucose levels that are difficult to control. Collaboration with pediatric endocrinologists is needed to appropriately manage these children during their hospitalization.

Quetiapine improves psychotic symptoms and cognition in Parkinson's disease.

Twenty-nine elderly patients who failed treatment with clozapine, risperidone, or olanzapine entered this 24-week, single-center, open-label trial to assess the efficacy of quetiapine (12.5-400 mg/day) for psychosis in patients with Parkinson's disease (PD). Psychiatric, motor, and cognitive assessments were administered at baseline and at periodic intervals for 24 weeks. These included the Brief Psychiatric Rating Scale (BPRS), Neuropsychiatric Inventory (NPI), Unified Parkinson's Disease Rating Scale (UPDRS) and tests of intellectual functioning, attention, and memory. Repeated measures statistical analysis was used to assess change from baseline. The results revealed significant improvements in the 24-week BPRS total score and NPI psychosis subscale scores, with no decline in UPDRS total or motor subscale scores. There was also significant improvement in recall scores on cognitive measures. These results indicate that quetiapine may treat psychotic symptoms and improve cognition without worsening motor function in patients with PD, suggesting that quetiapine is an effective and well-tolerated antipsychotic in this population.