Long term results of a phase II trial of hypofractionated adjuvant radiotherapy for early-stage breast cancer with volumetric modulated arc therapy and simultaneous integrated boost.

PURPOSE: to report toxicity and cosmetic outcome with a median follow-up of 6 years of a phase II trial of hypofractionated radiotherapy with volumetric modulated arc therapy (VMAT) and simultaneous integrated boost (SIB) for early-stage breast cancer after conservative surgery. MATERIALS AND METHODS: From August 2010 to September 2014, patients requiring adjuvant radiotherapy for early-stage breast cancer were treated according to a phase I-II protocol with SIB to 40.5 and 48 Gy to the breast and the boost region, respectively, with VMAT technique. The primary endpoint evaluated the treatment feasibility regarding adherence to required dose constraints for target, heart and lungs. Acute and late toxicity, local and distant control were secondary endpoints. RESULTS: 450 patients were included in the trial and analysed after a median follow-up of 6 years. Acute toxicity was already presented in a previous paper. Regarding late toxicity, 93% of patients had no skin alteration at five years, while 5.3% and 1.3% did record G1 and G2 residual toxicity, respectively. Cosmetic outcome was scored good or excellent in almost all cases (97.2%), fair only in 2.3% of patients. Residual tenderness in the irradiated breast was reported by 10% of patients. Cosmesis and breast pain improved during follow-up. Two cases of G2 pneumonitis and two cases of ischemic cardiopathy were registered during follow-up. Five cases presented local recurrence in the homolateral breast, four patients had a new primary cancer in the contralateral breast, while distant metastasis developed in 7 patients. CONCLUSION: After more than six years, hypofractionated VMAT with SIB for adjuvant radiotherapy in early-stage breast cancer patients remains a safe and effective approach. Mature data on skin toxicity and cosmetic outcome are encouraging. However, longer follow-up is required to evaluate local control, cardiac toxicity and secondary carcinogenesis.

Long-term outcomes after pancreatoduodenectomy for ampullary cancer: The influence of the histological subtypes and comparison with the other periampullary neoplasms.

BACKGROUND: Ampullary carcinoma (AC) is histologically classified as intestinal (In-AC), pancreaticobiliary (Pb-AC) or mixed-AC. The prognostic role of AC subtypes has been debated and remains unclear. The aims of this study were to evaluate outcomes after pancreatoduodenectomy (PD) for each subtype of AC and to compare these with pancreatic ductal adenocarcinoma [PDAC] and distal cholangiocarcinoma [DCC]. METHODS: PDs performed for AC between 2010 and 2018 were retrospectively evaluated. Histological subtype was obtained for all patients. One-year, 3-year and 5-year disease-free-survival (DFS) and overall survival (OS) rates were calculated. Kaplan-Meier survival analysis was performed to compare Pb-AC, In-AC and mixed-AC. Comparison with PDs performed for PDAC and DCC during the same period was also performed. RESULTS: A total of 97 patients undergoing PD for AC were evaluated: 34 (35.1%) In-AC, 54 (55.7%) Pb-AC and 9 mixed-AC (9.3%). DFS and OS rates for Pb-AC were significantly lower compared to In-AC (p < 0.05 and p < 0.01), but similar to mixed-AC (p = 0.3 and p = 0.4). Adjuvant therapy was not associated with increased survival, regardless of the histological subtype (p > 0.05). During the same period, 337 and 53 PDs for PDAC and DCC, respectively, were performed. In-AC was associated with significantly better outcomes compared to PDAC and DCC (p < 0.001); DFS and OS rates for Pb-AC and mixed AC were significantly higher compared to PDAC (p < 0.001), but similar to DCC (p > 0.05). CONCLUSIONS: Pb-AC has significantly worse survival compared to In-AC. Moreover, mixed-AC should be considered as Pb-AC. Pb-AC and mixed-AC seem to have better prognosis compared to PDAC, but similar to DCC.

How to manage thromboembolic risk in patient with SARS-CoV-2-related disease in the Emergency Department: A case report of cardiogenic shock due to massive pulmonary embolism.

BACKGROUND: Although the most known feature of SARS-CoV-2 associated infection is a mild to severe pneumonia, increasing evidence suggests the existence of an infection-associated risk of both arterial and venous thromboembolism (VTE), but the exact magnitude of this phenomenon is still unknown.Given that, it is important for the Emergency Physician to remember that a SARS-CoV-2 associated respiratory failure can be caused not only by the pulmonary parenchymal inflammation that characterizes the pneumonia, but also by an associated pulmonary thromboembolism. CASE REPORT: A healthy 73-years old woman admitted to the ED for dyspnea, fever and thoracic pain. Cardiac ultrasound, electrocardiogram and clinical findings suggested a diagnosis of cardiogenic obstructive shock due to acute pulmonary embolism, successfully treated with thrombolysis. A CT angiography confirmed the pulmonary embolism (EP) diagnosis and showed bilateral pneumonia, caused by SARS-CoV-2 infection. CONCLUSION: Considering the high prevalence of thromboembolic events in COVID-19 patients it is mandatory for the emergency physician to systematically evaluate signs of pulmonary thromboembolism, in order to perform the most patient-tailored therapy as soon as possible.

Effects of L-DOPA/benserazide co-treatment on colonic excitatory cholinergic motility and enteric inflammation following dopaminergic nigrostriatal neurodegeneration.

INTRODUCTION: The mainstay therapy for Parkinson's disease (PD) relies on L-3,4-dihydroxyphenylalanine (L-DOPA) plus a DOPA-decarboxylase inhibitor. However, their effects on colonic dysmotility and inflammation observed in PD are undetermined. This study examined the effects of L-DOPA plus benserazide (BE) on colonic motility and inflammation in rats with central nigrostriatal dopaminergic denervation. METHODS: Neurodegeneration was induced by 6-hydroxydopamine (6-OHDA) injection into the medial forebrain bundle (MFB). 6-OHDA animals were treated orally with L-DOPA/BE for 28 days, starting 28 days after 6-OHDA injection. At the end of treatment, in vivo colonic transit was evaluated by a radiologic assay. Electrically stimulated (ES) cholinergic contractions were recorded in vitro from colonic preparations, while acetylcholine release was measured in the incubation medium. Choline acetyltransferase (ChAT) and glial fibrillary acidic protein (GFAP) expression as well as eosinophil and mast cell density were examined in the colonic wall by immunohistochemistry. Colonic TNF and IL-1ß levels were also assayed. RESULTS: 6-OHDA animals displayed: 1) decrease in in vivo colonic transit; 2) impairment of ES-stimulated cholinergic contractions; 3) decreased acetylcholine release from myenteric nerves; 4) decrease in ChAT and increase in GFAP myenteric immunopositivity; 5) increase in eosinophil and mast cell density; 6) increase in TNF and IL-1ß levels. Treatment with L-DOPA/BE elicited an improvement of in vivo and in vitro colonic motor activity, a normalization of acetylcholine release, ChAT immunopositivity, as well as pro-inflammatory cytokine patterns, ganglionic GFAP levels, eosinophil and mast cell density. CONCLUSION: Under dopaminergic nigrostriatal denervation, treatment with L-DOPA/BE ameliorated colonic motility through a normalization of myenteric cholinergic neurotransmission, along with an improvement of colonic inflammation.

[Customer satisfaction in home care: methodological issues based on a survey carried out in Lazio]. / La qualità percepita in Assistenza domiciliare: considerazioni metodologiche alla luce di un'esperienza nel Lazio.

Home care customer satisfaction has been, until now, rarely evaluated. After illustrating the main italian regional surveys on this issue, the article presents a customer satisfaction survey carried out in the district of Civitavecchia (Local Health Unit 'Rome F'), Lazio, regarding 30 home care beneficiaries. Methodological aspects emerging from the survey are basically focused on: advantages and disadvantages of quantitative and qualitative approaches (possibly associated each other); main criteria of eligibility of people selected for interviewing, both patients or caregivers; conditions that maximize answers reliability, including training on interviewers. Authors highlight opportunity of using such kind of survey, integrated with other different tools, into a systemic vision, for promoting management changes coming from suggested problems, aimed at total quality management.

Utility of pedometer step recommendations for predicting overweight in children.

OBJECTIVE: The purpose of this study was to examine the utility of pedometer-based physical activity recommendations in predicting childhood adiposity. DESIGN: Subjects (n=608) (9.6 years) were from two Midwestern USA communities. Physical activity was assessed by a pedometer. The percentage of subjects meeting physical activity recommendations was determined using published recommendations. Overweight and obesity were determined based on reference values for the body mass index (BMI) developed by the International Obesity Task Force. An elevated waist circumference (WC) was determined based on age- and sex-specific reference values >75th percentile. RESULTS: Children who did not meet the pedometer recommendations were about two times more likely to be overweight/obese and have an elevated WC compared with those meeting recommendations. The BMI and WC were significantly different across pedometer step count groups in males and females. CONCLUSION: Subjects not meeting the recommendations for steps per day were more likely to be classified with the overweight phenotype than those meeting the recommendation. A dose-response relationship between pedometer steps per day and adiposity is also apparent.

Nickel ions release in patients with fixed orthodontic appliances.

AIM: The extent to which orthodontic appliances can cause contact allergies due to nickel release is a controversial matter. Since the data provided by literature are contrasting, the Authors think that it is important to analyse nickel ions released in organic tissues by means of a plasma spectrometer. METHODS: About 100 intact hairs were taken from 15 patients wearing fixed orthodontic appliances. The hairs had been washed 12 to 24 h before, in order to limit environmental contamination. The same procedure was carried out on a control group corresponding in sex, age and abode. The samples of hair were taken from at least 3 different scalp sites: frontal, vertex and occipital areas. RESULTS: According to the spectrophotometric analysis of the hair, there were no differences in nickel concentrations between the test group (0.50 mg/g on average) and control group (0.64 mg/g) (*P<0.005). The mean value was reduced even further if minimum and maximum values were excluded (test group 0.46 mg/g, control group 0.52 mg/g). Even though there was a slight difference (0.14 mg/g), it showed that more nickel concentration was found in the control sample (without orthodontic appliances) to a maximum of 2.20 mg/g. This suggests that environmental contamination, in particular diet, has an influence on ion concentration. Other studies also confirm that gut absorption of nickel released in the mouth by orthodontic appliances is much lower than the absorption of nickel release through diet. CONCLUSIONS: It can be assumed that orthodontic appliances do not release significant values of nickel to be a risk factor to the patient's health.

Violent video game effects on children and adolescents. A review of the literature.

Studies of violent video games on children and adolescents were reviewed to: 1) determine the multiple effects; 2) to offer critical observations about common strengths and weaknesses in the literature; 3) to provide a broader perspective to understand the research on the effects of video games. The review includes general theoretical and methodological considerations of media violence, and description of the general aggression model (GAM). The literature was evaluated in relation to the GAM. Published literature, including meta-analyses, are reviewed, as well as relevant unpublished material, such as conference papers and dissertations. Overall, the evidence supports hypotheses that violent video game play is related to aggressive affect, physiological arousal, aggressive cognitions, and aggressive behaviours. The effects of video game play on school performance are also evaluated, and the review concludes with a dimensional approach to video game effects. The dimensional approach evaluates video game effects in terms of amount, content, form, and mechanics, and appears to have many advantages for understanding and predicting the multiple types of effects demonstrated in the literature.

[The quality of medical records: a retrospective study in Lazio Region, Italy]. / La qualità della cartella clinica negli ospedali del Lazio.

INTRODUCTION: Medical records have an important role in the communication among different care providers and in forensic medicine. In Italy, information on completeness and correctness of medical records is scanty, whereas future hospital accreditation could take into account their quality as a proxy of good medical practice. PURPOSE: We performed a retrospective study in order to assess the quality of medical records in the Lazio region. METHODS: From all 37009 hospital discharges for five different diseases in 123 hospitals (acute myocardial infarction (AMI), coronary artery bypass surgery, pneumonia, cerebrovascular disorders, breast surgery), registered in the Regional Hospital Information System, we selected a random sample of 2022 (5.5% of the total). Ten physicians, previously trained, reviewed the relative medical charts and filled in "ad hoc" questionnaires. RESULTS: A total of 1960 (97% of the target) charts were reviewed. Organization and structure of data recording strongly varied. Important differences were found across the diseases for various items: presence of anamnesis 98.1% (range: from 95.6% for breast surgery to 100% for AMI); presence of physical examination 92.7% (range: from 88.1% for breast surgery to 98.5% for AMI), completeness of the daily medical records was good in 70.8% (range: from 34.2% for pneumonia to 93.9% for cerebrovascular disorders). Variability among different type of hospitals was also observed, being teaching hospitals and some private hospitals more accurate. CONCLUSIONS: Quality of medical records tended to vary across different type of hospitals and different diseases. Actions for improving the quality should be undertaken as a priority. Efforts have to be done in restructuring charts, creating guidelines and training caregivers. The development and application of computer based health information systems should help solving these problems.

Parents rate the ratings: a test of the validity of the American movie, television, and video game ratings.

BACKGROUND: Numerous studies have documented the potential effects on young audiences of violent content in media products, including movies, television programs, and computer and video games. Similar studies have evaluated the effects associated with sexual content and messages. Cumulatively, these effects represent a significant public health risk for increased aggressive and violent behavior, spread of sexually transmitted diseases, and pediatric pregnancy. In partial response to these risks and to public and legislative pressure, the movie, television, and gaming industries have implemented ratings systems intended to provide information about the content and appropriate audiences for different films, shows, and games. METHODS: We conducted a panel study to test the validity of the current movie, television, and video game rating systems. Participants used the KidScore media evaluation tool, which evaluates films, television shows, and video and computer games on 10 aspects, including the appropriateness of the media product for children on the basis of age. RESULTS: Results revealed that when an entertainment industry rates a product as inappropriate for children, parent raters agree that it is inappropriate for children. However, parent raters disagree with industry usage of many of the ratings designating material suitable for children of different ages. Products rated as appropriate for adolescents are of the greatest concern. The level of disagreement varies from industry to industry and even from rating to rating. CONCLUSIONS: Analysis indicates that the amount of violent content and portrayals of violence are the primary markers for disagreement between parent raters and industry ratings. Short-term and long-term recommendations are suggested.

Urinary histamine metabolite elevations during experimental influenza infection.

BACKGROUND: Although histamine is hypothesized to mediate symptoms induced by viral upper respiratory infections, elevations of this mediator have not been observed in nasal lavage fluids recovered from patients with viral upper respiratory infections. OBJECTIVE: The purpose of this study was to use a novel method to determine whether histamine is released during experimental influenza A infection. METHODS: Healthy adults (n = 15) were cloistered and inoculated intranasally with influenza A virus, and monitored for infection and illness. Daily morning void urines were collected and assayed for histamine and its metabolites by gas chromatography-mass spectrometry. Total histamine was calculated for each urine specimen by summing the assayed values of histamine and its metabolites. RESULTS: All subjects were infected and developed illness. ANOVA documented a significant effect of study day (viral infection) on urinary levels of total histamine (P < 0.02). Pairwise analysis showed a significant elevation 2 days after inoculation. CONCLUSIONS: These results provide the first direct evidence that histamine is released in vivo during infection with a virus that causes cold/flu symptoms.

A validity test of movie, television, and video-game ratings.

CONTEXT: Numerous studies have documented the potential effects on young audiences of violent content in media products, including movies, television programs, and computer and video games. Similar studies have evaluated the effects associated with sexual content and messages. Cumulatively, these effects represent a significant public health risk for increased aggressive and violent behavior, spread of sexually transmitted diseases, and pediatric pregnancy. In partial response to these risks and to public and legislative pressure, the movie, television, and gaming industries have implemented ratings systems intended to provide information about the content and appropriate audiences for different films, shows, and games. OBJECTIVE: To test the validity of the current movie-, television-, and video game-rating systems. DESIGN: Panel study. MEASURE: Participants used the KidScore media evaluation tool, which evaluates films, television shows, and video games on 10 aspects, including the appropriateness of the media product for children based on age. RESULTS: When an entertainment industry rates a product as inappropriate for children, parent raters agree that it is inappropriate for children. However, parent raters disagree with industry usage of many of the ratings designating material suitable for children of different ages. Products rated as appropriate for adolescents are of the greatest concern. The level of disagreement varies from industry to industry and even from rating to rating. Analysis indicates that the amount of violent content and portrayals of violence are the primary markers for disagreement between parent raters and industry ratings. CONCLUSIONS: As 1 part of a solution to the complex public health problems posed by violent and sexually explicit media products, ratings can have value if used with caution. Parents and caregivers relying on the ratings systems to guide their children's use of media products should continue to monitor content independently. Industry ratings systems should be revised with input from the medical and scientific communities to improve their reliability and validity. A single ratings system, applied universally across industries, would greatly simplify the efforts of parents and caregivers to use the system as well as the efforts of outside parties to monitor the use and validity of the system.

Urinary leukotriene E(4) excretion during the first month of life and subsequent bronchopulmonary dysplasia in premature infants.

BACKGROUND: Inflammation plays an important role in the pathogenesis of bronchopulmonary dysplasia (BPD), but the exact nature of this inflammatory process is incompletely understood. Older infants with established BPD have higher levels of urinary leukotriene E(4) (LTE(4)) compared to healthy infants of the same age. This suggests that cysteinyl leukotrienes may play a role in the abnormalities seen in BPD. OBJECTIVES: To measure urinary LTE(4) levels during the first month of life in premature infants, and to determine whether there are significant differences in premature infants who develop BPD, as compared to those who do not develop BPD. DESIGN: Prospective, blinded, controlled study. SETTING: Neonatal ICUs of a tertiary-care university hospital. METHODS: Thirty-seven premature infants (< 33 weeks of gestational age) were enrolled prospectively at birth. Urinary LTE(4) levels were measured blinded, using a standard radioimmunoassay technique at 2 days, 7 days, and 28 days of life. At 1 month of age, infants were classified as with or without BPD, based on need for supplemental oxygen, and characteristic chest radiographs. Clinical features and urinary LTE(4) were compared between the two groups. RESULTS: Mean +/- SD gestational age was 29 +/- 2.6 weeks. None of the infants had a family history of asthma. Thirteen of 37 infants were classified as having BPD at 28 days after birth. Mean gestational age in infants who developed BPD was 27 +/- 2.4 weeks, compared to 30 +/- 2 weeks in infants who did not develop BPD (p < 0.05). In infants with BPD, mean urinary LTE(4) levels of urinary creatinine were 1,762 +/- 2,003 pg/mg, 1,236 +/- 992 pg/mg, and 5,541 +/- 5,146 pg/mg at days 2, 7, and 28, respectively, compared to 1,304 +/- 1,195 pg/mg, 1,158 +/- 1,133 pg/mg, and 2,800 +/- 2,080 pg/mg in infants without BPD. LTE(4) levels at 2 days, 7 days, and 28 days did not correlate with the subsequent development of BPD. LTE(4) levels at day 28 were significantly higher than LTE(4) levels at day 2 and day 7 in both groups, even after correcting for gestational age or birth weight (p < 0.05). There was significant inverse correlation between LTE(4) levels at day 2 with gestational age and birth weight (p < 0.05). All 13 infants with BPD received steroid pulses, compared to 3 of 26 infants without BPD. Gestational age and use of postnatal steroid pulses, diuretics, and theophylline (for apnea of prematurity) were significantly associated with each other and with the subsequent development of BPD. CONCLUSION: Urinary LTE(4) levels measured on the second day of life in very-low-birth-weight infants inversely correlate with gestational age and birth weight. Urinary LTE(4) levels may reflect lung injury and/or inflammation in premature infants, not necessarily related to BPD as it is presently defined.

Effect of intranasal challenge with interleukin-6 on upper airway symptomatology and physiology in allergic and nonallergic patients.

BACKGROUND: Interleukin-6 (IL-6) is a potent regulator of airway inflammation and an important component of biologic homeostasis. Previously, a temporal relationship between the local elaboration of IL-6 and the development of upper airway symptoms and pathophysiologic findings was reported for patients experimentally infected with influenza A virus or rhinovirus. OBJECTIVE: The objective of this study was to determine the provocative effects of direct, intranasal administration of IL-6 on those symptoms, signs, and pathophysiologic findings that accompany viral upper respiratory infection. METHODS: In this double-blind, placebo-controlled, crossover trial, 10 symptomatic allergic, 10 asymptomatic allergic, and 10 nonallergic adult patients were pretreated with intranasal histamine and, after 15 minutes, were challenged with repeated doses of placebo (saline) or with increasing doses (0, 0.01, 0.1, and 1 microg/mL) of recombinant IL-6 at 20-minute intervals, during randomized paired sessions. Symptom scores, sneeze and cough counts, nasal secretion weights, nasal conductance (rhinomanometry), middle ear pressure (tympanometry), Eustachian tube function (sonotubometry), and pulmonary function (spirometry) were evaluated before and after the histamine challenge, after each dose of IL-6 or placebo, and then at 90 minutes and 2, 3, 4, 6, and 24 hours. RESULTS: At the doses used, intranasal challenge with IL-6 was well tolerated. At the 90-minute postchallenge endpoint, a significant effect of challenge substance and group assignment was documented for nasal secretion weight. Paired comparisons showed that the effect was greater for the allergic patients when compared with the nonallergic patients. There were no differences between placebo and IL-6 challenge for any of the other measured parameters. CONCLUSIONS: These results show that local IL-6 at relatively low doses can provoke increased nasal secretions in patients with allergic rhinitis.

Viral rhinitis.

Viral rhinitis is a common, morbid, and costly malady, often complicated by otitis media, sinusitis, and asthma. Current therapies are relatively ineffective and aimed at reducing symptoms rather than moderating underlying mechanisms. Nasal elevations of proinflammatory cytokines track symptom expression during viral rhinitis, and it is hypothesized that these chemicals orchestrate a common response to infection with many different viruses that cause rhinitis. Also, recent evidence supports a role for neurogenic inflammation in the development of complications. Future studies should dissect the role of proinflammatory cytokines and neuropeptides in the expression of symptoms, signs, pathophysiologies, and complications of viral rhinitis.

Effect of experimental influenza A infection on systemic immune and inflammatory parameters in allergic and nonallergic adult subjects.

BACKGROUND: The economic impact and medical complication rate of viral upper respiratory infections are well documented, but many of the physiologic, inflammatory, and immune responses to respiratory viruses have only recently been investigated. A previous study demonstrated differential systemic immune and inflammatory responses in allergic rhinitis (AR) and nonallergic rhinitis (NAR) subjects during experimental infection with rhinovirus-39. OBJECTIVE: The purpose of this study was to compare selected systemic immune and inflammatory responses to experimental influenza A virus (FLU) challenge in seronegative AR and NAR subjects. METHODS: Peripheral blood was obtained at baseline (study day 0) and 3, 6, 18, and 31 days after intranasal FLU challenge and assayed for leukocyte histamine release, serum immunoglobulins, and plasma histamine. RESULTS: All subjects were infected, as manifested by viral shedding in nasal secretions and/or seroconversion. FLU infection induced decreases in spontaneous leukocyte histamine release and increases in anti-immunoglobulin E-induced leukocyte histamine release, which were evident at least 1 month after infection, but caused no significant changes in serum immunoglobulins or plasma histamine. There were no differences between AR and NAR subjects for any of the study parameters. CONCLUSIONS: The results show that intranasal challenge with FLU induces changes in leukocyte histamine release, but not other systemic immune and inflammatory responses.

Intermittent doxercalciferol (1alpha-hydroxyvitamin D(2)) therapy for secondary hyperparathyroidism.

Hypercalcemia and hyperphosphatemia frequently necessitate vitamin D withdrawal in hemodialysis patients with secondary hyperparathyroidism. In short-term trials, doxercalciferol (1alpha-hydroxyvitamin D(2) [1alphaD(2)]) suppressed intact parathyroid hormone (iPTH) effectively with minimal increases in serum calcium and phosphorus (P) levels. This modified, double-blinded, controlled trial examined the efficacy and safety of 1alphaD(2) use in 138 hemodialysis patients with moderate to severe secondary hyperparathyroidism by using novel dose titration; 99 patients completed the study. Hemodialysis patients with secondary hyperparathyroidism were enrolled onto this study, consisting of washout (8 weeks), open-label 1alphaD(2) treatment (16 weeks), and randomized, double-blinded treatment with 1alphaD(2) or placebo (8 weeks). Oral 1alphaD(2) was administered at each hemodialysis session, with doses titrated to achieve target iPTH levels of 150 to 300 pg/mL. Baseline iPTH levels (897 +/- 52 [SE] pg/mL) decreased by 20% +/- 3.4% by week 1 (P: < 0.001) and by 55% +/- 2.9% at week 16; iPTH levels returned to baseline during placebo treatment but remained suppressed with 1alphaD(2) treatment. In 80% of the patients, iPTH level decreased by 70%, reaching the target level in 83% of the patients. Grouping patients by entry iPTH level (<600, 600 to 1,200, and >1,200 pg/mL) showed rapid iPTH suppression in the group with the lowest level; greater doses and longer treatment were required in the group with the highest level. During open-label treatment, serum calcium and P levels were 9.2 +/- 0.84 (SD) to 9.7 +/- 1.05 mg/dL and 5.4 +/- 1.10 to 5.9 +/- 1.55 mg/dL, respectively. During double-blinded treatment, serum calcium levels were slightly greater with 1alphaD(2) than placebo, but P levels did not differ. During double-blinded treatment, 3.26% and 0.46% of serum calcium measurements exceeded 11.2 mg/dL with 1alphaD(2) and placebo, respectively (P: < 0.01); median level was 11.6 mg/dL during hypercalcemia. Intermittent oral 1alphaD(2) therapy effectively suppresses iPTH in hemodialysis patients with secondary hyperparathyroidism, with acceptable mild hypercalcemia and hyperphosphatemia.

Clinical use of nebulized budesonide inhalation suspension in a child with asthma.

Childhood asthma contributes to significant morbidity among patients and significantly impacts the quality of life and daily routines of their caregivers. The parents or caregivers assume responsibility for tasks that children are too young to perform; this often includes daily administration of controller medications and nightly administration of reliever medications. Most young children do not have the coordination or understanding to effectively use pressurized metered-dose inhalers or inhalation-driven devices; thus nebulizer therapy often is preferred for children younger than 4 years of age. Budesonide inhalation suspension will be the first inhaled corticosteroid available for children younger than 4 years of age and the first inhaled corticosteroid for delivery by nebulization in the United States. This is a case report of a 3-year-old boy who received budesonide inhalation suspension as part of several double-blind and open-label studies evaluating the drug. Before study entry, the boy was experiencing more breakthrough wheezing episodes at night than the parents were used to, resulting in an increase in nighttime awakenings that required nebulizer therapy. These nighttime awakenings had a substantial impact on the quality of life of the entire family and interfered with the parents' ability to function at work. Even though they wanted to have more children, this situation discouraged them from doing so. Budesonide inhalation suspension improved overall asthma control and was well tolerated. The boy had a decrease in nighttime symptoms and an increase in both height and weight percentiles for his age. Importantly, use of budesonide inhalation suspension in this boy eased the management of severe asthma and improved the quality of life of the entire family. The parents subsequently decided to have a second child. Budesonide inhalation suspension represents a major breakthrough for infants and young children by providing a formulation that, on approval, can be delivered reliably by nebulizer for effective maintenance treatment of persistent asthma.