Route Of Administration For Treatment Research Articles

Prevention and management of hypertensive crises in children with pheochromocytoma and paraganglioma.

Hypertensive crises in pediatric patients are rare conditions. However, determining their precise prevalence is more challenging than in adults due to the heterogeneity in the definition itself. These crises frequently occur without a prior diagnosis of hypertension and may indicate an underlying cause of secondary hypertension, including pheochromocytoma/paraganglioma (PPGL). The mechanisms of hypertensive crises in the pediatric population with PPGL are directly related to different types of catecholamine excess. Noradrenergic tumors typically present with sustained hypertension due to their predominant action on α1-adrenoceptors in the vasculature. Conversely, adrenergic tumors, through epinephrine binding to β2-adrenoceptors in addition to stimulation of α1- and α2-adrenoceptors, more frequently cause paroxysmal hypertension. Furthermore, the biochemical phenotype also reflects the tumor localization and the presence of a genetic mutation. Recent evidence suggests that more than 80% of PPGL in pediatric cases have a hereditary background. PPGL susceptibility mutations are categorized into three clusters; mutations in cluster 1 are more frequently associated with a noradrenergic phenotype, whereas those in cluster 2 are associated with an adrenergic phenotype. Consequently, the treatment of hypertensive crises in pediatric patients with PPGL, reflecting the underlying pathophysiology, requires first-line therapy with alpha-blockers, potentially in combination with beta-blockers only in the case of tachyarrhythmia after adequate alpha-blockade. The route of administration for treatment depends on the context, such as intraoperative or pre-surgical settings, and whether it presents as a hypertensive emergency (elevated blood pressure with acute target organ damage), where intravenous administration of antihypertensive drugs is mandatory. Conversely, in cases of hypertensive urgency, if children can tolerate oral therapy, intravenous administration may initially be avoided. However, managing these cases is complex and requires careful consideration of the selection and timing of therapy administration, particularly in pediatric patients. Therefore, facing these conditions in tertiary care centers through interdisciplinary collaboration is advisable to optimize therapeutic outcomes.

Porous silicon embedded in a thermoresponsive hydrogel for intranasal delivery of lipophilic drugs to treat rhinosinusitis

Intranasal delivery is the most preferred route of drug administration for treatment of a range of nasal conditions including chronic rhinosinusitis (CRS), caused by an infection and inflammation of the nasal mucosa. However, localised delivery of lipophilic drugs for persistent nasal inflammation is a challenge especially with traditional topical nasal sprays. In this study, a composite thermoresponsive hydrogel is developed and tuned to obtain desired rheological and physiochemical properties suitable for intranasal administration of lipophilic drugs. The composite is comprised of drug-loaded porous silicon (pSi) particles embedded in a poloxamer 407 (P407) hydrogel matrix. Mometasone Furoate (MF), a lipophilic corticosteroid (log P of 4.11), is used as the drug, which is loaded onto pSi particles at a loading capacity of 28 wt%. The MF-loaded pSi particles (MF@pSi) are incorporated into the P407-based thermoresponsive hydrogel (HG) matrix to form the composite hydrogel (MF@pSi-HG) with a final drug content ranging between 0.1 wt% to 0.5 wt%. Rheomechanical studies indicate that the MF@pSi component exerts a minimal impact on gelation temperature or strength of the hydrogel host. The in-vitro release of the MF payload from MF@pSi-HG shows a pronounced increase in the amount of drug released over 8 h (4.5 to 21-fold) in comparison to controls consisting of pure MF incorporated in hydrogel (MF@HG), indicating an improvement in kinetic solubility of MF upon loading into pSi. Ex-vivo toxicity studies conducted on human nasal mucosal tissue show no adverse effect from exposure to either pure HG or the MF@pSi-HG formulation, even at the highest drug content of 0.5 wt%. Experiments on human nasal mucosal tissue show the MF@pSi-HG formulation deposits a quantity of MF into the tissues within 8 h that is >19 times greater than the MF@HG control (194 ± 7 μg of MF/g of tissue vs. <10 μg of MF/g of tissue, respectively).

Comparison of efficacy between subcutaneous and intravenous application of moss-aGal in the mouse model of Fabry disease.

Fabry disease (FD, OMIM 301500) is a rare X-linked inherited lysosomal storage disorder associated with reduced activities of α-galactosidase A (aGal, EC 3.2.1.22). The current standard of care for FD is based on enzyme replacement therapy (ERT), in which a recombinantly produced version of αGal is intravenously (iv) applied to Fabry patients in biweekly intervals. Though the iv application is clinically efficacious, periodical infusions are inconvenient, time- and resource-consuming and they negatively impact the patients' quality of life. Subcutaneous (sc) injection, in contrast, is an established route of administration for treatment of chronic conditions. It opens the beneficial option of self-administration, thereby improving patients' quality of life and at the same time reducing treatment costs. We have previously shown that Moss-α-Galactosidase (moss-aGal), recombinantly produced in the moss Physcomitrium patens, is efficient in degrading accumulated Gb3 in target organs of murine model of FD and in the phase I clinical study, we obtained first efficacy evidence in human patients following single iv infusion. Here, we tested the efficacy of subcutaneous administration of moss-aGal and compared it with the results observed following iv infusion in Fabry mice. The obtained findings demonstrate that subcutaneously applied moss-aGal is correctly transported to target organs and efficacious in degrading Gb3 deposits there and thus suggest the possibility of using this route of administration for therapy of Fabry disease.

Protein Aggregates in Inhaled Biologics: Challenges and Considerations

Pulmonary delivery is the main route of administration for treatment of local lung diseases. Recently, the interest in delivery of proteins through the pulmonary route for treatment of lung diseases has significantly increased, especially after Covid-19 pandemic. The development of an inhalable protein combines the challenges of inhaled as well as biologic products since protein stability may be compromised during manufacture or delivery. For instance, spray drying is the most common technology for manufacture of inhalable biological particles, however, it imposes shear and thermal stresses which may cause protein unfolding and aggregation post drying. Therefore, protein aggregation should be evaluated for inhaled biologics as it could impact the safety and/or efficacy of the product. While there is extensive knowledge and regulatory guidance on acceptable limits of particles, which inherently include insoluble protein aggregates, in injectable proteins, there is no comparable knowledge for inhaled ones. Moreover, the poor correlation between in vitro setup for analytical testing and the in vivo lung environment limits the predictability of protein aggregation post inhalation. Thus, the purpose of this article is to highlight the major challenges facing the development of inhaled proteins compared to parenteral ones, and to share future thoughts to resolve them.

Clinical and financial implications of central venous catheters bloodstream infections in patients with multiple myeloma in the United States.

e20033 Background: Multiple Myeloma(MM) has an increased exposure to intravascular catheters due to the increased risk of severe infections and due to the route of treatment administration. Central Venous Catheter Bloodstream Infections(CVCBI) have significant mortality, imply a delay in treatment and increased cost as well. There is no prior report on the risk factors for poor outcome in MM patients that develop this complication. We aim to describe the predictors of mortality as well as the changes in cost that CVCBI implies. Methods: We retrieved adult patients with MM from the Nationwide Inpatient Sample database from 2016-2018. We used the ICD-10 codes to identify and compare patients who developed CVCBI with those that did not developed it. The main outcomes were hospital mortality and predictors of mortality. We computed the chi-squared test and the Mann-Whitney U-test. Mortality predictors are estimated using multivariate logistic regression and logistic fixed-effect methods to control for admission cohort and hospital time invariant characteristics. All analyses were performed using Stata Statistical Software version 14 (StataCorp, College Station, TX). Results: A total of 58,838 patients with MM were identified. The majority were white (63.5%), male (55.3%), with a median age of 70 (IQR 62-78). Most MM were not in remission (99.1%), followed by those in remission (1.3%) and relapse (0.3%). CVCBI was diagnosed in 264 (0.4%) of the MM patients. There was significantly higher mortality in the CVCBI group vs. the non-CVCBI group (8.7% vs. 5%; p &lt; 0.01), longer LOS (10 vs. 5 days; p &lt; 0.001), and higher median hospitalization cost (US$86,168 vs. US$43,511; p &lt; 0.001). In the multivariable analysis, CVCBI was associated with higher mortality (OR: 1.69; CI 95%: 1.14-2.52; p &lt; 0.001). Among patients with MM and CVCBI those that had achieved remission had a higher risk of death (OR: 2.87; CI 95%: 2.17-3.8; p &lt; 0.001). Other variables associated with mortality were age &gt; 65 (OR: 1.84; CI 95%: 1.59-2.15; p &lt; 0.001), concomitant chronic heart failure (CHF) (OR: 1.46; CI 95%: 1.29-1.65; p &lt; 0.001), chronic kidney disease (CKD) (OR: 1.43; CI 95%: 1.32-1.56; p &lt; 0.001), and weight loss (OR: 2.31; CI 95%: 1.91-2.8; p &lt; 0.001). When compared to medicare patients with higher mortality were more likely to be under medicaid(OR: 1.25; CI 95%: 1.02-1.55; p &lt; 0.05) and private insurances(OR: 1.31; CI 95%: 1.15-1.49; p &lt; 0.001). There was no significant association with sex, race/ethinicity or household income. Conclusions: In patients with Multiple Myeloma the development of Central Venous Catheter Bloodstream Infections was associated with a higher overall mortality, length of stay and cost of hospitalization. Age, CHF, CKD and weight loss were independent risk factors for poor outcome in this patient population. Further studies are required on developing strategies for the prevention of this complication.

Intranasal delivery of tetrabenazine nanoemulsion via olfactory region for better treatment of hyperkinetic movement associated with Huntington’s disease: Pharmacokinetic and brain delivery study

Tetrabenazine reduces chorea symptoms associated with Huntington’s disease by depleting monoamines in pre-synaptic vesicles. It exhibits low aqueous solubility and undergoes first pass metabolism due to which it has low oral bioavailability. The aim of present work was to formulate intranasal tetrabenazine loaded nanoemulsion for better management and treatment of hyperkinesia related with Huntington’s disease. A quality by design (QbD) technique was employed as statistical multivariate approach for formulation and optimization of nanoemulsion. Optimized formulation showed droplet size of 106.80 ± 1.96 nm with polydispersity index (PDI) value of 0.198 ± 0.005 and -9.63 ± 0.63 mV zeta potential. Ex-vivo drug permeation studies were carried out and found that the formulation has an augmented permeation by 1.68 times as compared to tetrabenazine suspension. MTT assay on neuro-2a cell lines showed that tetrabenazine loaded nanoemulsion displayed better cell viability than placebo and aqueous drug solution at ½ × Cmax, Cmax and 2 × Cmax. Pharmacokinetic parameters in brain after intranasal administration of tetrabenazine nanoemulsion were found to be Cmax = 3.497 ± 0.275 μg/mL, AUC0−12 = 29.196 ± 0.870 μg h/mL and elimination rate constant (ke) = 0.097 ± 0.012 h−1 where as in plasma the pharmacokinetic parameters were Cmax = 1.400 ± 0.084 μg/mL, AUC0−12 = 12.925 ± 0.340 μg h/mL and ke = 0.061 ± 0.010 h−1. Histopathological studies of porcine nasal mucosa showed that nasal mucosa remains intact when treated with tetrabenazine loaded nanoemulsion. Thus it can be concluded from study that optimized nanoemulsion formulation of a tetrabenazine was robust and its delivery through nasal route is a viable alternative to other routes of administration for treatment of hyperkinesia associated with Huntington’s disease.

PND9 NOVEL METHOD OF ADJUSTMENT FOR HETEROGENEOUS ROUTES OF ADMINISTRATION WITHIN A COST-EFFECTIVENESS ANALYSIS: A CASE STUDY IN MIGRAINE

Placebo can affect subjective outcomes like pain. Cost-effectiveness analyses (CEAs) that compare interventions versus no intervention (rather than “sham intervention/placebo”) should account for the placebo effect. We demonstrate a method to adjust network meta-analysis (NMA) for placebo effects (specifically, by route of treatment administration [ROA]). A Cochrane review of pain treatments estimated a standardized mean placebo effect, which was assumed to reflect the difference between no treatment and mean placebo effect. Bannuru 2015 estimated differences in placebo effect between three ROAs. It was assumed that three levels of placebo in Bannuru 2015 center around the mean placebo effect as estimated by Cochrane and that distribution of these ROAs correspond to the differences between subcutaneous (SC), intramuscular (IM), and intravenous (IV) ROAs. We applied these to an NMA of change in monthly migraine days (MMDs) informing a CEA of monoclonal antibody calcitonin gene-related peptide inhibitors (both IV and SC) or onabotulinumtoxinA (IM) over weeks 1-4 in patients with chronic migraine. We evaluated the impact of placebo adjustment on observed outcomes modeled as the additive effect of placebo and treatment. Compared to no adjustment, estimates for SC treatments with adjustment had decreased treatment effect (increase in MMDs) over weeks 1-4, ranging from 0.59 to 1.51 days depending on the specific treatment. Results over weeks 1-4 for IM treatment showed an improvement in treatment effect of -0.74 days, while IV treatment showed an improved treatment effect of -1.92 days. When added to the treatment effect, inclusion of the adjustment resulted in IV treatment having higher absolute improvements over all other treatments. Results were consistent with an analysis of weeks 9-12. This case study illustrates the importance of addressing varying placebo responses in indirect treatment comparisons informing CEAs.

Possible Influence of the Route of Treatment Administration on Treatment Adherence in Patients With Multiple Sclerosis

PurposeMultiple sclerosis is a chronic, demyelinating, and degenerative disease of the central nervous system with an immune-based pathologic origin. The present pilot study aimed to assess whether the change in the route of treatment administration is associated with a variation in adherence and whether there is a change in quality of life, treatment satisfaction, and fatigue. MethodsPatients with relapsing-remitting multiple sclerosis who were >18 years of age and who used to receive immunomodulatory parenteral treatment and were ready to change administration route were eligible for the study. Data were collected at baseline and 3 months later. Adherence, quality of life, treatment satisfaction, and fatigue were measured via the following questionnaires: Morisky-Green questionnaire on patient-reported medication adherence, Multiple Sclerosis Quality of Life Instrument, Treatment Satisfaction Questionnaire for Medication, and Modified Fatigue Impact Scale. FindingsThe study sample included 30 patients (mean age, 43.2 years; age range, 24–71 years; 60% female and 40% male). There was a significant improvement in adherence (p = 0.048). Mean (SD) physical and mental health quality-of-life summary scores varied from 52.50 (24.15) and 54.13 (21.24) to 67.55 (20.92) and 62.30 (21.75) (p < 0.001 and p = 0.001, d = −0.426 and d = −0.643, respectively). In the Treatment Satisfaction Questionnaire for Medication, an improvement of the score was observed in effectiveness of the medication (p = 0.0041, d = −0.563), adverse effects of the medication (p < 0.001, d = −0.976), convenience of the medication (p < 0.001, d = −1.235), and global satisfaction (p = 0.006, d = −0.725). Patients had a higher mean (SD) score (45.13 [26.7]) on the Modified Fatigue Impact Scale while receiving injectable treatment compared with that obtained with oral treatment (34.86 [23.16]; p = 0.009, d = 0.41). ImplicationsWhen the route of administration changed from injectable to oral, there was an increase in adherence, quality of life, and degree of patient satisfaction with their treatment and a decrease in the degree of fatigue.

Patient-Reported Factors in Treatment Satisfaction in Patients with Relapsed/Refractory Multiple Myeloma (RRMM).

Therapy choices in relapsed/refractory multiple myeloma (RRMM) should consider patient satisfaction with treatment, because it is associated with adherence to therapy, health outcomes, and medical safety. The primary objective of this pilot cross-sectional observational study was to ascertain factors associated with patient-reported treatment satisfaction in RRMM. Patients with a self-reported diagnosis of RRMM recruited from PatientsLikeMe, MyelomaCrowd, and Facebook were administered an electronic survey that included questions on demographics and clinical history, treatment experience, economic burden, and standardized patient-reported outcome measures, including the Treatment Satisfaction Questionnaire for Medication, Eastern Cooperative Oncology Group performance status (ECOG PS) measure, and Work Productivity and Activity Impairment Questionnaire: Specific Health Problem V2.0. Univariable and multivariable analyses were used to identify predictors of patient-perceived treatment satisfaction. One hundred sixty patients with RRMM participated in the study, with a median of two prior relapses and 66.3% reporting the most recent relapse within the last 12 months. ECOG PS ≥2 was associated with lower patient-reported global satisfaction and perceived effectiveness of current treatment. In addition to shorter time spent receiving therapy, orally administered treatment was the strongest predictor of higher satisfaction with treatment convenience. For patients receiving an injectable drug-containing regimen versus an all-oral regimen, respectively, time spent receiving multiple myeloma-directed therapy was higher (12.6 vs. 4.0 hours per month), and total monthly indirect costs were $1,033 and $241. Poor ECOG PS was linked to reduced treatment satisfaction and perceived effectiveness of current therapy, whereas an all-oral regimen was associated with increased treatment convenience satisfaction. This study suggests that attributes including better Eastern Cooperative Oncology Group performance status, less time spent receiving treatment, and oral route of treatment administration lead to higher patient-perceived satisfaction with relapsed/refractory multiple myeloma (RRMM) treatment. Oral route of administration was also associated with less time spent receiving treatment and reduced economic burden for patients. Increased attention to these factors in shared treatment decision making is warranted to help identify individual patient needs, preferences, and expectations for RRMM treatments, to resolve dissatisfaction issues, and to improve the experience of patients with RRMM.

Myxoma virus derived immune modulating proteins, M-T7 and Serp-1, reduce early inflammation after spinal cord injury in the rat model.

Spinal cord injury (SCI)-initiated inflammation was treated with anti-inflammatory reagents. We compared local spinal cord or intraperitoneal infusion of two Myxoma virus derived immune modulating proteins, Serp-1 and M-T7, with dexamethasone (DEX). Hemorrhage and necrosis after SCI initiate acomplex pathogenesis dominated by early, severe and highly destructive inflammatory macrophage infiltration. We examined sustained, 7-day, subdural infusion of either M-T7, achemokine modulator or Serp-1, aplasminogen activator and factor inhibitor. Mature male rats had epidural balloon crush SCI and sustained subdural infusion of Serp-1, M-T7, DEX or saline for 7 days via the osmotic pump. Aseparate group of rats with SCI had intra-peritoneal infusion. Clinical evaluation included endpoint monitoring with body weight, hemorrhagic cystitis and bilateral toe pinch response. Sections of the spinal cord were analyzed histologically and macrophage numbers counted by standardized protocol in the cavity of injury (COI). While the rats administered DEX demonstrated substantial body weight loss, dehydration and dermal atrophy consistent with steroid toxicity, rats infused with Serp-1 and M-T7 had no toxicity. Serp-1 improved withdrawal responses. Subdural infusion of Serp-1, M-T7 and DEX significantly reduced numbers of phagocytic, CD68-positive macrophages. With intraperitoneal infusion only M-T7 reduced macrophage counts, Serp-1 showed only atrend. Local infusion of highly active immune modulating proteins; Serp-1 and M-T7, targeting serine protease and chemokine pathways demonstrated excellent potential for neuroprotection after severe SCI in arat model, without adverse side effects. Sustained subdural infusion offers an alternative route of administration for treatment of SCI.

Formulation, Stability and Bioequivalency Study of Prepared Salbutamol Sulphate Nebules.

Salbutamol sulphate nebules is considered as the most rapid effective route ofadministration for treatment of acute attacks of asthma .This study was carried out to formulate a stable formula of salbutamol nebulescontaining 0.1% (2.5mg / 2.5ml) of the active ingredient in a buffered solution .Stability study in different buffers at pH 3 showed that the longest shelf life wasequal to 3.5 years for formula F .In addition the bioequivalency of this formulaincomparison to ventolin® nebules was measured and it was equal to (± 5.2) %.Also it was found that there was no significant difference between the formulaand ventolin® nebules regarding their pharmacokinetic parameters which includeelimination rate constant, elimination t 0.5 and amount of the unchanged drug excretedin urine, 30 min. after administration (p&lt;0.05) . This study may suggest that theprepared formula could be used successfully in the preparation of salbutamol sulphatenebules.

A Nationwide Survey on Patient's versus Physician´s Evaluation of Biological Therapy in Rheumatoid Arthritis in Relation to Disease Activity and Route of Administration: The Be-Raise Study.

ObjectivesBiological treatment of rheumatoid arthritis (RA) is one of the cornerstones of current treatment strategies for the disease. Surprisingly little information exists on whether the route of administration affects patients’ treatment satisfaction. It is equally unclear whether rheumatologists are able to accurately perceive their patients’ appreciation. Thus, the Belgian Be-raise survey aimed to examine whether RA patient’s experience of their current biological treatment coincided with the treating physician’s perception.MethodsA nationwide cross-sectional survey was conducted by 67 Belgian rheumatologists providing data obtained from 550 RA patients. Patients under stable dose of biologics for at least 6 months, were enrolled consecutively and all completed questionnaires. Separate questionnaires were completed by the treating rheumatologist which evaluated their patient’s perception of the route of treatment administration. This study therefore evaluates whether a treating physician perceives the satisfaction with the route of administration to the same degree as the patient.ResultsCompleted questionnaires were obtained from 293 and 257 patients who obtained treatment via the intravenous (IV) or subcutaneous (SC) route of administration, respectively. 58.4% of patients were in DAS28-CRP(3) remission. Patient satisfaction with disease control was higher (44% scored ≥ 9) than that of the treating physician (35%), regardless of the route of administration (p< 0.01). No differences were seen for the patients treated with an IV as opposed to a SC route of administration. The physician´s perception of patient’s satisfaction with disease control was markedly lower for IV treated patients as opposed to SC treated patients (p< 0.001).ConclusionsPatients’ satisfaction with biological treatment is high, but there is a considerable mismatch between patients´ and rheumatologists´ appreciation on the route of administration of biological therapy in RA. Physicians consistently consider IV biological therapy to be less satisfactory. Patient´s appreciation is largely dependent on disease control, irrespective of the route of administration. Therefore, and encouraging shared decision making, we suggest that physicians and patients discuss the route of administration of biologicals in an open way.

Recent Advances in Topical Ocular Drug Delivery.

Topical ocular drug delivery has been considered to be an ideal route of administration for treatment of ocular diseases related to the anterior segment of the eye. However, topical ocular delivery is a challenging task because of barriers such as nasolacrimal drainage, corneal epithelium, blood-ocular barriers, and metabolism in the eye. Approaches to improve ocular bioavailability include physical approaches such as formulations of drugs as solutions (Zymaxid(™)), suspensions (Zigran(®)), gels (Akten(®)) and chemical approaches such as prodrugs (Xalatan(™)), chemical delivery systems, and soft drugs. The purpose of this review article is to summarize recent advances in topical drug delivery to the anterior segment of the eye. Functional transporters in the corneal epithelium were also discussed as they provide prospects in topical ocular delivery. In addition to conventional delivery systems, novel delivery systems involving nanocarriers were also investigated for topical ocular delivery. Furthermore, due to increased interest, gene therapy applications of topical ocular delivery of genes to the anterior segment of the eye were also discussed. Research in topical ocular delivery is active for more than 50 years and proven to be advantageous for the treatment of many ocular diseases. However, there is scope for innovation in topical drug delivery to develop delivery systems with a high patient safety profile and compliance for effective clinical usefulness.

Methotrexate: A Gold Standard for Treatment of Rheumatoid Arthritis

ABSTRACTRheumatoid arthritis (RA) is a painful, debilitating disease characterized by inflammation of the joints, with the proliferation of the synovium and the progressive erosion of cartilage and bone. The treatment of RA is still unsatisfactory, but a number of powerful disease-modifying antirheumatic drugs have become available, such as methotrexate (MTX). Even in the current era of biological targeted therapies, MTX remains the initial preferred antirheumatic drug and is considered to be the gold standard for treatment of RA. The combination of its perceived efficacy, acceptable safety profile, and low cost, as well as decades of clinical experience, makes MTX the cornerstone of treatment for RA and the anchor drug in combination with various biological agents. In this review, the authors aim to summarize the research done in the field of drug delivery systems of MTX according to its routes of administration for treatment of RA. The last part of the review addresses combination therapy with MTX and future direction in the drug delivery of MTX. This review also provides the reader with a general overview of RA and its therapeutic strategies with respect of MTX, which may bring uniformity in medical practice for effective management of RA.

Insulin Pump Therapy Started at the Time of Diagnosis: Effects on Glycemic Control and Pancreatic β-Cell Function in Type 1 Diabetes

In the interest of preserving residual insulin secretory capacity present at the time of diagnosis with type 1 diabetes (T1D), we compared the efficacy of starting insulin pump therapy at diagnosis with standard multiple daily insulin injections (MDIs). We conducted a prospective, randomized, pilot trial comparing MDI therapy with continuous subcutaneous insulin therapy (pump therapy) in 24 patients, 8-18 years old, with newly diagnosed T1D. Subjects were evaluated at enrollment and 1, 3, 6, 9, and 12 months after initial diagnosis of T1D. Preservation of insulin secretion, measured by mixed-meal-stimulated C-peptide secretion, was compared after 6 and 12 months of treatment. Between-group differences in glycosylated hemoglobin (HbA1c), continuous glucose sensor data, insulin utilization, anthropometric measures, and patient satisfaction with therapy were also compared at multiple time points. Initiation of pump therapy within 1 month of diagnosis resulted in consistently higher mixed-meal tolerance test-stimulated C-peptide values at all time points, although these differences were not statistically significant. Nonetheless, improved glycemic control was observed in insulin pump-treated subjects (more time spent with normoglycemia, better mean HbA1c), and pump-treated subjects reported comparatively greater satisfaction with route of treatment administration. Initiation of insulin pump therapy at diagnosis improved glycemic control, was well tolerated, and contributed to improved patient satisfaction with treatment. This study also suggests that earlier use of pump therapy might help to preserve residual β-cell function, although a larger clinical trial would be required to confirm this.

A Comparison of Early Versus Late Conversion From Intravenous to Oral Therapy in the Treatment of Septic Arthritis

Clinical outcomes of children with bacterial septic arthritis, common in the pediatric age group, are often satisfactory with early recognition, prompt surgical drainage, and appropriate antibiotic therapy. However, the optimal duration and route of antibiotic administration for treatment of septic arthritis continues to be debated, as traditional treatment favored longer intravenous (IV) therapies yet oral regimens are increasingly available that are more cost effective, safe and produce satisfactory disease resolution. Records of 186 patients from two children's hospitals, one that was thought to convert from IV to oral antibiotic therapy considerably earlier than the other, treated between 1985 and 1995 for bacterial septic arthritis were reviewed. Patients with concurrent osteomyelitis were excluded. Patients at Hospital #1 were converted to oral antibiotics after 7.4+/-7.4 days of IV antibiotic therapy and at Hospital #2 after 18.6+/-13.6 (P<0.001) days of IV therapy. Both groups received an average of four weeks of total antibiotic treatment. There was similar time to defervescence (2.4+/-3.2 d vs. 2.4+/-3.8 d, P>0.05) and to normalization of erythrocyte sedimentation rate (35.7+/-19.7 d vs. 33.8+/-44.9 d, P>0.05) in the patients converted to oral therapy early compared to those converted late. One case of mild avascular necrosis with no clinical disability developed in a patient from Hospital #2. We conclude that the clinical outcome in patients with septic arthritis converted to oral antibiotic therapy early in their treatment based on defined criteria was similar to those converted late.

Antibiotic Therapy for Acute Pelvic Inflammatory Disease: The 2006 Centers for Disease Control and Prevention Sexually Transmitted Diseases Treatment Guidelines

Pelvic inflammatory disease (PID) is a substantial cause of reproductive morbidity in young women. A systematic review of the literature related to PID management was performed in preparation for the 2006 Centers for Disease Control and Prevention sexually transmitted diseases treatment guidelines. This search was conducted using PubMed and was limited to articles written in English and published between 1 January 2002 and 31 January 2005 that were related to PID treatment. Studies were evaluated for new data on PID with regard to site, route, and timing of antimicrobial administration; regimen adherence; experience in adolescents and women >35 years of age; coinfection with human immunodeficiency virus; and management of sex partners. Strong evidence suggests that neither site nor route of treatment administration affects the short- or long-term major outcome of women with mild or moderate clinical presentations. Data on these outcomes in women with more severe clinical presentations are inadequate to provide guidance as to the preferred agents or route of administration. Important contributions to the literature that impact the 2006 guidelines are described in this article.

ADHERENCE TO AMERICAN ACADEMY OF PEDIATRICS PRACTICE GUIDELINES FOR URINARY TRACT INFECTIONS AT OUR TEACHING INSTITUTION.

Introduction Urinary tract infection (UTI) is becoming a more common cause of bacterial infection for febrile illness in children. The American Academy of Pediatrics (AAP) developed “practice guidelines” for the management of UTI in children in 1999. The aim of this study was to evaluate the uniformity of adherence to AAP guidelines at our teaching institution. Methods The medical records of 405 patients (age 0-16 years) were retrospectively reviewed from the outpatient clinic, emergency room, and inpatient unit. Of these, 104 patients met the criteria. Data collected included age, gender, age of first UTI, presenting symptoms, method of urine collection, urinalysis, Gram stain, urine culture, repeat culture, imaging studies including renal ultrasonography (RUS), voiding cystourethrogram (VCUG), and treatment prescribed. UTI was defined as > 50,000 cfu/mL for catheterized specimens and > 105 cfu/mL for clean catch specimens. Results Overall, adherence to guidelines was as high as 97.1% in performance of urinalysis and 61% in imaging studies and 51% in urine Gram stains. The majority of patients who were tested for UTI presented with fever and 70% of urine specimens were collected by transurethral catheterization. The route of antibiotic administration for treatment of UTIs was exclusively parenteral in 12.5% of patients (mostly neonates Conclusion We conclude that there is great adherence to AAP guidelines for diagnosis of UTI, but there was less adherence to recommendations for renal imaging. Future studies to improve patient follow-up, financial coverage to improve access to care, and education of primary care providers to adherence of guidelines may increase the quality of care for children with UTI.

Intranasal Absorption of Flurazepam, Midazolam, and Triazolam in Dogs

Intranasal delivery of flurazepam, midazolam, and triazolam was studied in a dog model as a possible alternate route of drug administration for treatment of insomnia. Four beagles received each hypnotic by both intranasal and oral routes on two separate occasions. Plasma concentrations for each hypnotic after dosing were measured by electron-capture gas-liquid chromatography. The mean intranasal absorption rates (tmax) of flurazepam, midazolam, and triazolam were 1.7, 2.0, and 2.6 times faster, respectively, compared with oral dosing. The mean dose-normalized peak concentrations (Cmax) after intranasal delivery were 16.4, 2.9, and 3.4 times higher, respectively, versus oral administration. The mean dose-normalized AUCs estimated for these compounds after nasal administration were 2.4−, 2.5−, and at least 2-fold larger than after oral administration for midazolam, triazolam, and flurazepam, respectively. If these observations can be extrapolated to humans, the faster absorption achieved by the intranasal route would appear to benefit insomniacs characterized by difficulty in falling asleep because of an anticipated faster sedative effect onset. The higher peak concentrations and larger amounts absorbed in the case of intranasal midazolam and triazolam delivery may lead to dose reduction.

Pharmacokinetics of intraperitoneal teicoplanin in patients with chronic renal failure on continuous ambulatory peritoneal dialysis.

The pharmacokinetic profile of teicoplanin, a new glycopeptide antibiotic active against Gram-positive aerobic and anaerobic bacteria, is described in five patients with end-stage renal disease on continuous ambulatory peritoneal dialysis (CAPD). A single 3 mg kg-1 dose was given intraperitoneally in the dialysate during a 6 h dwell time. The drug appeared in the plasma within 15 min at 1.00-0.28 mg l-1 (mean +/- s.d. = 0.70 +/- 0.45) in all five subjects, and peak serum concentrations ranged from 5.53 to 2.80 mg l-1 (4.84 +/- 1.43) at 6 h. Approximately 70% (71 +/- 12) of teicoplanin was absorbed from the peritoneal dialysis fluid during a single 6 h dwell time. The rate constant for peritoneal transfer (lambda d) averaged 0.318 h-1 and the half-life (t1/2 lambda d) was 2.18 h. Further values were serum elimination half-life 114-173 h; total body clearance 263-532 ml h-1; steady-state volume of distribution 68-93 l. This drug profile closely agrees with data reported after intravenous injection in patients on CAPD and suggests that teicoplanin has bidirectional exchange characteristics through the peritoneal membrane, although transfer from the systemic circulation to peritoneal fluid is consistently low. Instillation of teicoplanin in CAPD fluid may be a useful route of administration for treatment of peritonitis and exit site infections in CAPD patients.