Asthma is one of the most common chronic diseases of childhood. Allergen sensitization and high frequencies of comorbid allergic diseases are characteristic of severe asthma in children. Omalizumab, ...an anti-IgE mAb, is the first targeted biologic therapeutic approved for the treatment of moderate-to-severe persistent allergic asthma (AA) that remains uncontrolled despite high-dose inhaled corticosteroids plus other controller medications. Since its initial licensing for use in adults and adolescents 12 years of age and older, the clinical efficacy, safety, and tolerability of omalizumab have been demonstrated in several published clinical trials in children aged 6 to less than 12 years with moderate-to-severe AA. These studies supported the approval of the pediatric indication (use in children aged ≥6 years) by the European Medicines Agency in 2009 and the US Food and Drug Administration in 2016. After this most recent change in licensing, we review the outcomes from clinical trials in children with persistent AA receiving omalizumab therapy and observational studies from the past 7 years of clinical experience in Europe. Data sources were identified by using PubMed in 2016. Guidelines and management recommendations and materials from the recent US Food and Drug Administration's Pediatric Advisory Committee meeting are also reviewed.
Adults and adolescents were included in 3 phase 3 omalizumab trials in chronic idiopathic urticaria (CIU): ASTERIA I, ASTERIA II, and GLACIAL.
To describe the baseline clinical profile of adolescent ...patients with CIU enrolled in the omalizumab trials to add to the limited literature available on CIU in this population.
Data for patient demographics, baseline clinical disease characteristics, medical history, and previous CIU medication information (not efficacy assessments) from phase 3 omalizumab trials were pooled and descriptive statistical analyses performed for adolescent (12 to <18 years old) and adult (≥18 years old) subgroups. Inferential analysis was inappropriate, partly because of small sample size in the adolescent subgroup.
The pooled population of 975 patients with CIU included 39 adolescents (4.0%). Demographics of adolescents and adults with CIU were similar, but compared with adults, fewer adolescents had positive Chronic Urticaria Index test results. Baseline clinical disease characteristics were also similar between the subgroups, with the number of previous CIU medications slightly lower in adolescents compared with adults. Medical history and existing conditions in adolescents tended to be more allergy than cardiovascular related, and fewer experienced angioedema compared with adults.
Pooled data indicate differences in baseline demographic and clinical characteristics between adult and adolescent patient subgroups. This finding helps augment our understanding of the clinical profile of CIU in adolescents, but larger-scale studies in this population are warranted.
ClinicalTrials.gov Identifiers: NCT01287117 (ASTERIA I), NCT01292473 (ASTERIA II), and NCT01264939 (GLACIAL).
During the 24-week inhaled steroid dose-stable phase of a double-blind, randomized, controlled trial in children >=6 to <12 years old with inadequately controlled, moderate-to-severe, allergic ...asthma, clinically significant asthma exacerbation rates were reduced by 31% (p=0.007) with omalizumab (75-375 mg every 2 or 4 weeks) versus placebo.
Rationale Inflammatory biomarker profile, asthma severity, and concomitant asthma medication usage (e.g. LABAs) are likely associated with differing levels of response to asthma biologic medications. ......with the development of novel biologic agents, questions arise about the extent to which differing responses are due to the agents themselves or differences in the population examined.
Rationale The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR-I) examined patients with severe/difficult-to-treat asthma.
Methods This is a post-hoc descriptive analysis of pooled baseline data from three omalizumab trials in CIU/CSU patients who remained symptomatic despite H1-antihistamine treatment and ...H2-antihistamines and/or leukotriene receptor antagonists (LTRA) in one study.
Studies of patients' preferences for localized prostate cancer treatments have assessed radical prostatectomy and external radiation therapy, but none of them has evaluated brachytherapy. The aim of ...our study was to assess the preferences and willingness to pay of patients with localized prostate cancer who had been treated with radical prostatectomy, external radiation therapy, or brachytherapy, and their related urinary, sexual, and bowel side effects.
This was an observational, prospective cohort study with follow-up until 5 years after treatment. A total of 704 patients with low or intermediate risk localized prostate cancer were consecutively recruited from 2003 to 2005. The estimation of preferences was conducted using time trade-off, standard gamble, and willingness-to-pay methods. Side effects were measured with the Expanded Prostate Index Composite (EPIC), a prostate cancer-specific questionnaire. Tobit models were constructed to assess the impact of treatment and side effects on patients' preferences. Propensity score was applied to adjust for treatment selection bias.
Of the 580 patients reporting preferences, 165 were treated with radical prostatectomy, 152 with external radiation therapy, and 263 with brachytherapy. Both time trade-off and standard gamble results indicated that the preferences of patients treated with brachytherapy were 0.06 utilities higher than those treated with radical prostatectomy (P=.01). Similarly, willingness-to-pay responses showed a difference of €57/month (P=.004) between these 2 treatments. Severe urinary incontinence presented an independent impact on the preferences elicited (P<.05), whereas no significant differences were found by bowel and sexual side effects.
Our findings indicate that urinary incontinence is the side effect with the highest impact on preferences and that brachytherapy and external radiation therapy are more valued than radical prostatectomy. These time trade-off and standard gamble preference assessments as well as the willingness-to-pay estimation could be useful to perform respectively cost-utility or cost-benefit analyses, which can guide health policy decisions.
The quest for an appropriate system of management for tropical ecosystems necessitates that ecologists consider the accumulated experiences of indigenous peoples in their long-term management of ...local resources, a subject of current ethnoecology. This paper provides data and empirical evidence of an indigenous multiple-use strategy (MUS) of tropical forest management existing in Mexico, that can be considered a case of adaptive management. This conclusion is based on the observation that some indigenous communities avoid common modernization routes toward specialized, unsustainable, and ecologically disruptive systems of production, and yet probably achieve the most successful tropical forest utilization design, in terms of biodiversity conservation, resilience, and sustainability. This analysis relies on an exhaustive review of the literature and the authors' field research. Apparently, this MUS represents an endogenous reaction of indigenous communities to the intensification of natural resource use, responding to technological, demographic, cultural, and economic changes in the contemporary world. This transforms traditional shifting cultivators into multiple-use strategists. Based on a case study, three main features (biodiversity, resilience, and permanence) considered relevant to achieving adaptive and sustainable management of tropical ecosystems are discussed.
Background
In acute brain injury (ABI), the effects of hypoxemia as a potential cause of secondary brain damage and poor outcome are well documented, whereas the impact of hyperoxemia is unclear. The ...primary aim of this study was to assess the episodes of hypoxemia and hyperoxemia in patients with ABI during the intensive care unit (ICU) stay and to determine their association with in-hospital mortality. The secondary aim was to identify the optimal thresholds of arterial partial pressure of oxygen (PaO
2
) predicting in-hospital mortality.
Methods
We conducted a secondary analysis of a prospective multicenter observational cohort study. Adult patients with ABI (traumatic brain injury, subarachnoid aneurysmal hemorrhage, intracranial hemorrhage, ischemic stroke) with available data on PaO
2
during the ICU stay were included. Hypoxemia was defined as PaO
2
< 80 mm Hg, normoxemia was defined as PaO
2
between 80 and 120 mm Hg, mild/moderate hyperoxemia was defined as PaO
2
between 121 and 299 mm Hg, and severe hyperoxemia was defined as PaO
2
levels ≥ 300 mm Hg.
Results
A total of 1,407 patients were included in this study. The mean age was 52 (±18) years, and 929 (66%) were male. Over the ICU stay, the fractions of patients in the study cohort who had at least one episode of hypoxemia, mild/moderate hyperoxemia, and severe hyperoxemia were 31.3%, 53.0%, and 1.7%, respectively. PaO
2
values below 92 mm Hg and above 156 mm Hg were associated with an increased probability of in-hospital mortality. Differences were observed among subgroups of patients with ABI, with consistent effects only seen in patients without traumatic brain injury.
Conclusions
In patients with ABI, hypoxemia and mild/moderate hyperoxemia were relatively frequent. Hypoxemia and hyperoxemia during ICU stay may influence in-hospital mortality. However, the small number of oxygen values collected represents a major limitation of the study.
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