Are There Differences Among Evidence-Based Psychotherapies for Treating Different DSM-5 PTSD Symptom Clusters? A Systematic Review and Meta-analysis of Controlled Clinical Trials.

ABSTRACT: Posttraumatic stress disorder (PTSD) is a heterogeneous disease defined by four Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) symptom clusters: reexperiencing, avoidance, negative alterations in cognitions and mood, and hyperarousal. There are effective evidence-based psychotherapies (EBPs) for PTSD. However, given the variety of PTSD clinical presentations, we conducted the first meta-analysis investigating whether DSM-5 PTSD symptom clusters show different responses to EBPs. We systematically reviewed the literature for controlled clinical trials in five databases, performed a meta-analysis, and evaluated the methodological quality of the studies. We screened 633 studies and included seven. Three showed high risk, two showed some concerns, and one showed a low risk of bias. The symptom clusters do not seem to respond differently to EBPs (SMD cluster B: -0.40; 95% confidence interval [CI], -0.87 to 0.08; cluster C: -0.49; 95% CI, -0.90 to -0.08; cluster D: -0.44; 95% CI, -0.94 to 0.05; cluster E: -0.54; 95% CI, -1.07 to -0.0), even when analyzed by the therapeutic focuses. The findings dovetail nicely with the network theory of PTSD symptom, as although it is a heterogeneous disorder, the EBPs seem to promote a kind of cascade of symptom improvement.

The efficacy of internet-delivered cognitive-behavioral therapy for posttraumatic stress disorder according to the mean age of patients: a systematic review and meta-analysis.

Internet-delivered cognitive-behavioral therapy (I-CBT) is effective in treating post-traumatic stress disorder (PTSD) symptoms, offering enhanced accessibility and cost-effectiveness. However, it's important to note that these technologies may not be suitable for all age groups. Therefore, we conducted a systematic review and meta-analysis to determine if the effectiveness of I-CBT in treating PTSD varies based on the patients' mean age. We conducted a systematic review of the literature, focusing on randomized controlled trials (RCTs) in the ISI Web of Science, PubMed/MEDLINE, and PsycINFO databases. Following this, we performed a meta-analysis and evaluated the risk of bias using the Cochrane risk of bias quality assessment tool. In this study, we examined patient-related factors (civil or military status, age, and gender), clinical characteristics (baseline PTSD severity and type of trauma), and treatment characteristics (type of intervention, synchronous or asynchronous delivery, and the number of sessions) as independent variables. The dependent variable was the reduction in mean PTSD symptoms. Five RCTs out of 1,552 screened studies were included in this review, all of which showed some level of concern regarding potential bias. Our meta-analysis indicates that I-CBT is equally effective regardless of patients' mean age. Since all RCTs included only provide the mean age of the patients, further randomized controlled trials should address the effectiveness of I-CBT among different age groups.

Post-traumatic stress disorder as a predictor for incident hypertension: a 3-year retrospective cohort study.

BACKGROUND: The goal of the present study was to investigate the association between PTSD and the onset of hypertension in previously normotensive individuals in a population living in the stressful environment of the urban slums while controlling for risk factors for cardiovascular disease (CVD). METHODS: Participants were 320 normotensive individuals who lived in slums and were attending a family doctor program. Measurements included a questionnaire covering sociodemographic characteristics, clinical status and life habits, the Posttraumatic Stress Disorder Checklist - Civilian Version, and the Beck Depression Inventory. Incident hypertension was defined as the first occurrence at the follow-up review of the medical records of (1) systolic blood pressure of 140 mm Hg or higher or diastolic blood pressure of 90 mm Hg or higher, (2) the participant started taking antihypertensive medication, or (3) a new diagnosis of hypertension made by a physician. Differences in sociodemographic, clinical, and lifestyle characteristics between hypertensive and non-hypertensive individuals were compared using the χ2 and t tests. Multivariate Cox proportional hazards models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: Six variables - age, educational level, body mass, smoking, diabetes, and PTSD diagnosis - showed a statistically significant (p ≤ 0.20) association with the hypertensive status. In the Cox regression, only PTSD diagnosis was significantly associated with incident hypertension (multivariate HR = 1.94; 95% CI 1.11-3.40). CONCLUSIONS: The present findings highlight the importance of considering a diagnostic hypothesis of PTSD in the prevention and treatment of cardiovascular diseases.

Machine learning applied to fMRI patterns of brain activation in response to mutilation pictures predicts PTSD symptoms.

BACKGROUND: The present study aimed to apply multivariate pattern recognition methods to predict posttraumatic stress symptoms from whole-brain activation patterns during two contexts where the aversiveness of unpleasant pictures was manipulated by the presence or absence of safety cues. METHODS: Trauma-exposed participants were presented with neutral and mutilation pictures during functional magnetic resonance imaging (fMRI) collection. Before the presentation of pictures, a text informed the subjects that the pictures were fictitious ("safe context") or real-life scenes ("real context"). We trained machine learning regression models (Gaussian process regression (GPR)) to predict PTSD symptoms in real and safe contexts. RESULTS: The GPR model could predict PTSD symptoms from brain responses to mutilation pictures in the real context but not in the safe context. The brain regions with the highest contribution to the model were the occipito-parietal regions, including the superior parietal gyrus, inferior parietal gyrus, and supramarginal gyrus. Additional analysis showed that GPR regression models accurately predicted clusters of PTSD symptoms, nominal intrusion, avoidance, and alterations in cognition. As expected, we obtained very similar results as those obtained in a model predicting PTSD total symptoms. CONCLUSION: This study is the first to show that machine learning applied to fMRI data collected in an aversive context can predict not only PTSD total symptoms but also clusters of PTSD symptoms in a more aversive context. Furthermore, this approach was able to identify potential biomarkers for PTSD, especially in occipitoparietal regions.

Remibrutinib, a novel BTK inhibitor, demonstrates promising efficacy and safety in chronic spontaneous urticaria.

BACKGROUND: Chronic spontaneous urticaria (CSU) is inadequately controlled in many patients and greatly affects quality of life. Remibrutinib, a highly selective, oral, novel covalent Bruton tyrosine kinase inhibitor, might be effective in CSU. OBJECTIVE: This first-in-patient trial aimed to evaluate the efficacy and safety of remibrutinib in CSU treatment and characterize the dose-response. METHODS: This randomized, double-blind, placebo-controlled, phase 2b dose-finding trial evaluated remibrutinib (12 weeks) in patients inadequately controlled with second-generation H1-antihistamines, with at least moderately active CSU, with or without prior anti-IgE treatment (NCT03926611). Patients received remibrutinib 10 mg once daily, 35 mg once daily, 100 mg once daily, 10 mg twice daily, 25 mg twice daily, 100 mg twice daily, or placebo (1:1:1:1:1:1:1 ratio). The main end points were weekly Urticaria Activity Score change from baseline at week 4 and safety. RESULTS: Overall, 311 patients were randomized. Reduced symptom score was observed for all remibrutinib doses from week 1 until week 12, with weekly Urticaria Activity Score change from baseline at week 4: -19.1 (10 mg once daily), -19.1 (35 mg once daily), -14.7 (100 mg once daily), -16.0 (10 mg twice daily), -20.0 (25 mg twice daily), -18.1 (100 mg twice daily), and -5.4 for placebo (nominal P < .0001 for all doses vs placebo). Most adverse events were mild or moderate, with no dose-dependent pattern. CONCLUSION: Remibrutinib was highly effective in the treatment of CSU over the entire dose range, with a rapid onset of action and a favorable safety profile.

The top-100 cited articles on post-traumatic stress disorder: a historical bibliometric analysis.

This is a bibliometric analysis of the most-cited articles on post-traumatic stress disorder (PTSD) with the objective of identifying citation patterns for researchers, journals, centers, periods, topics, and nations. A search was conducted in Thomson Reuters' WoS Core Collection employing the expression TI = (posttraumatic stress disorder OR post-traumatic stress disorder OR PTSD). The 100 most-cited articles were downloaded, and the relevant data were extracted and analyzed. These studies had a total of 69,649 citations, ranging from a minimum of 360 to a maximum of 6029 citations, with an average of 696.49, a standard deviation of 720.92, mode of 369, and a median of 512. Eighty-eight percent of the most-cited articles on PTSD originated from the USA, with just six cities accounting for 52% of the publications and the Boston area alone responsible for almost one-fifth of the total output. The universities of Yale and Harvard headed the ranking of institutions with larger numbers of highly-cited articles. Female researchers represented 42.3% of all authors, 51% of the first authors, and 48% of the corresponding authors. The proportion of M.D. authors decreased significantly between the 1980-1999 (42%) and the 2000-2019 (27.2%) periods while that of Ph.D. authors increased from 44% to 57.4%. The most studied population was military veterans (28%). Female victims of sexual or physical violence, traumatized children, and adult survivors of childhood abuse were assessed in only 6-7% of the most-cited publications. Ten clinical trials evaluated psychological interventions but only three investigated pharmacotherapy. We concluded that influential research on PTSD remains centralized in the USA. A balanced gender representation in publications was found. There was a heavy reliance on combat veterans as the study population. Few highly-cited studies on the pharmacotherapy for PTSD were identified. Focused efforts are needed to address these challenges.

Stuck in a Moment: Tonic Immobility Predicts Poor Quality of Life in Treated PTSD Patients.

BACKGROUND: Posttraumatic stress disorder (PTSD) is a prevalent and disabling multisystem disorder, with significant physical and psychiatric morbidity and poor quality of life (QOL). Although peritraumatic reactions - tonic immobility and dissociation - are established predictors of PTSD severity and development, there is a dearth of investigation assessing the impact of peritraumatic reactions on QOL of PTSD patients. Quality of life has become increasingly important in health care and research as a reliable outcome measure. It comprises psychological, physical, social and environmental domains, providing important information about the impact of diseases on patient's life. This study aims to investigate the impact of peritraumatic tonic immobility and peritraumatic dissociation on QOL of PTSD civilian outpatients. SUBJECTS AND METHODS: It is a cross-sectional study of 50 victims of urban violence with current PTSD, recruited in a specialized outpatient clinic. Instruments used were: Structured Clinical Interview IV, Peritraumatic Dissociative Experiences Questionnaire, Tonic Immobility Scale and WHOQOL-BREF (psychological, physical, social and environmental domains). Linear regression models were fitted to evaluate the impact of peritraumatic reactions - tonic immobility and dissociation - on WHOQOL-BREF scores. We controlled for sex as potential confounding. RESULTS: The severity of peritraumatic tonic immobility negatively impacted on psychological and environment domains of quality of life. For each additional point on the Tonic Immobility Scale, there was a decreased of 0.8 points on the scores of these domains of WHOQOL-BREF. Neither the peritraumatic reactions showed effects on physical nor social domains. Possible limitations of this study include cross-sectional design, relatively small sample size of tertiary center outpatients and recall bias. CONCLUSIONS: Peritraumatic tonic immobility is related to poor quality of life, adding new insights about the relationship between this immobility reaction and PTSD.

MP-AzeFlu in Moderate-to-Severe Allergic Rhinitis: A Literature Review.

Allergic rhinitis (AR) is prevalent, and many patients present with moderate-to-severe symptomatic disease. The majority of patients are not satisfied with their AR treatment, despite the use of concurrent medications. These gaps underscore the need for treatment with more effective options for moderate-to-severe AR. The authors' objective was to review systematically the efficacy and safety of MP-AzeFlu for the treatment of AR. The primary outcomes studied were nasal, ocular, and total symptoms. Other outcomes included time to onset and of AR control, quality of life, and safety. Searches of PubMed and Cochrane databases were conducted on May 14, 2020, with no date restrictions, to identify publications reporting data on MP-AzeFlu. Clinical studies of any phase were included. Studies were excluded if they were not in English, were review articles, did not discuss the safety and efficacy of MP-AzeFlu for AR symptoms. Treatment of AR with MP-AzeFlu results in effective, sustained relief of nasal and ocular symptoms, and faster onset and time to control compared with intranasal azelastine or fluticasone propionate. Long-term use of MP-AzeFlu was safe, with benefits in children, adults, and adults aged ≥65 years. Other treatment options, including fluticasone propionate and azelastine alone or the combination of intranasal corticosteroids and oral antihistamine, do not provide the same level of efficacy as MP-AzeFlu in terms of rapid and sustained relief of the entire AR symptom complex. Furthermore, MP-AzeFlu significantly improves patient quality of life. MP-AzeFlu is a currently available combination that may satisfy all these patient needs and expectations.

Quantifying Mechanical Abrasion of MWCNT Nanocomposites Used in 3D Printing: Influence of CNT Content on Abrasion Products and Rate of Microplastic Production.

Manufactured nanomaterials (MNMs) are incorporated as "nanofillers" into consumer products to enhance properties of interest. Multiwalled carbon nanotubes (MWCNTs) are known for their unique properties and have many applications in polymers. However, the release of MWCNTs during the nanoenabled product life cycle is concerning. During the use phase, mechanical stresses can produce fragmented materials containing MNMs. The degree of MNM release, the resulting exposure to these materials, and the potential impacts of their release are active research topics. In this study, we describe methodological improvements to study the abrasion of plastics containing MNMs (nanocomposites) and report on characteristics of abrasion products produced and rates of microplastic production. The abrasion device developed for this work allows for the measurement of power inputs to determine scaled release rates. Abrasion rates for plastics used in 3D printing were found to be 0.27 g/m2/s for the PETG polymer and 0.3 g/m2/s for the 2% MWCNT-PETG nanocomposite. Embedded and protuberant MWCNTs appeared to impact the particle size, shape, hydrophobicity, and surface charge of the microplastics, while the inclusion of MWCNTs had a small effect on microplastic production. Measurements of power input to the abrasion process provided a basis for estimating microplastic production rates for these nanocomposites.

Review of efficacy of ciclesonide for the treatment of asthma in children.

Background: Ciclesonide (CIC) is an inhaled corticosteroid (ICS) approved for the maintenance treatment of asthma in patients ages ≥ 12 years. The prodrug aspect of CIC is associated with a safety profile that may make it ideal for children. Objective: The objective was to summarize efficacy results from the eight phase III, randomized, double-blind, controlled trials in children with asthma conducted during CIC clinical development. Methods: Four trials compared CIC 40, 80, or 160 µg/day with placebo. Two trials compared CIC 160 µg/day with fluticasone propionate 200 µg/day, one trial compared CIC 80 or 160 µg/day with fluticasone 200 µg/day, and one trial compared CIC 160 µg/day with budesonide 400 µg/day. Results: The primary end point was met by at least two CIC doses versus placebo in the trials in which the primary end point was the change from baseline in lung function outcome (forced expiratory volume in 1 second [FEV1] % predicted or morning peak expiratory flow [PEF]). A trial that compared CIC with placebo did not meet the primary end point of superiority in time-to-first severe wheeze exacerbation or lack of improvement. The primary end point of noninferiority to the active control (fluticasone or budesonide) in the change from baseline in a lung function outcome (FEV1, morning PEF, evening PEF) was met with the CIC 160-µg dose in all active control trials. CIC generally demonstrated statistically significant improvements in forced expiratory flow at 25%-75% of forced vital capacity, asthma symptoms, rescue medication use, and asthma control when compared with placebo and noninferiority for these outcomes compared with fluticasone or budesonide. Conclusion: In children with asthma, once-daily CIC significantly improved large and small airway function, asthma symptoms, and asthma control, and reduced rescue medication use compared with placebo. CIC was comparable with other ICS used to treat asthma in children, which demonstrated its worth for the pediatric population.

Safety of ciclesonide in children with asthma: A review of randomized controlled trials.

Background: Parental concerns about the adverse effects of asthma medications can lead to nonadherence and uncontrolled asthma in children. Ciclesonide (CIC) is a prodrug, with low oropharyngeal deposition and bioavailability that may minimize the risk of local and systemic adverse effects. CIC is U.S. Food and Drug Administration approved for asthma in children ages ≥ 12 years. Objective: To summarize safety results from the 13 phase II or III randomized controlled trials conducted in children with asthma during CIC clinical development. Methods: Four 12- to 24-week trials compared the safety of once-daily CIC 40, 80, or 160 µg/day with placebo; four 12-week trials compared the safety of CIC 80 or 160 µg/day with either fluticasone or budesonide; one 12-month trial compared the long-term safety of CIC 40, 80, or 160 µg/day with fluticasone; one 12-month trial compared growth velocity of CIC 40 or 160 µg/day with placebo; and three cross-over trials compared short-term growth velocity and hypothalamic-pituitary-adrenal (HPA) axis effects of CIC 40, 80, or 160 µg/day with placebo or fluticasone. Results: In all, 4399 children were treated with CIC. The incidence of treatment-emergent adverse events (AE) was similar among the CIC doses and between CIC and placebo in short-term studies and between CIC and fluticasone in the long-term safety study. No CIC-related serious AEs were reported in any study. The incidence of treatment-related oral candidiasis was low and similar between CIC (≤0.5%) and placebo (≤0.7%) or active controls (≤0.5%) in the short-term studies. There was no clinically relevant HPA axis suppression or reduction in growth velocity associated with CIC. Conclusion: Data from 13 studies demonstrate that CIC is associated with low rates of oropharyngeal AEs, with no indication of clinically relevant systemic effects in children with asthma. The favorable safety profile and demonstrated improvements in asthma control make CIC an ideal inhaled corticosteroid for the treatment of asthma in children.

Absence of definitive scientific evidence that benzodiazepines could hinder the efficacy of exposure-based interventions in adults with anxiety or posttraumatic stress disorders: A systematic review of randomized clinical trials.

BACKGROUND AND OBJECTIVES: Exposure-based interventions (EBIs) are the first-line treatment for anxiety disorders and posttraumatic stress disorder. Although common, the association between EBIs and benzodiazepines is controversial. Therefore, we systematically reviewed the literature to evaluate if benzodiazepines could undermine the efficacy of EBIs in treating these disorders. METHODS: We conducted a systematic review aiming for randomized clinical trials (RCTs) in ISI Web of Science, Scopus, PubMed/MEDLINE, and PsycINFO databases. We scrutinized the reference list of selected papers and other systematic reviews. Finally, we evaluated the methodological quality and the scientific evidence of the studies. RESULTS: We screened 1,529 studies and included 12 RCTs in this review (all showing some concerns or high risk of bias). Benzodiazepines did not impact the efficacy of EBIs in nine studies at posttreatment, improved efficacy in two, and reduced it in one. In the follow-up, benzodiazepines (after its discontinuation) did not impact the efficacy in six studies and reduced it in five. The scientific level of evidence achieved was B for both phases. CONCLUSIONS: Until now there is no definitive evidence that benzodiazepines could hinder the EBIs' efficacy for treating posttraumatic stress disorder and anxiety disorders.

Intravenous Cetirizine Versus Intravenous Diphenhydramine for the Treatment of Acute Urticaria: A Phase III Randomized Controlled Noninferiority Trial.

STUDY OBJECTIVE: Acute urticaria is a frequent presentation in emergency departments (EDs), urgent care centers, and other clinical arenas. Treatment options are limited if diphenhydramine is the only intravenous antihistamine offered because of its short duration of action and well-known adverse effects. We evaluate cetirizine injection, the first second-generation injectable antihistamine, for acute urticaria in this multicenter, randomized, noninferiority, phase 3 clinical trial. METHODS: Adult patients presenting to EDs and urgent care centers with acute urticaria requiring an intravenous antihistamine were randomized to either intravenous cetirizine 10 mg or intravenous diphenhydramine 50 mg. The primary endpoint was the 2-hour pruritus score change from baseline, with time spent in treatment center and rate of return to treatment centers as key secondary endpoints. Frequency of sedation and anticholinergic adverse effects were also recorded. RESULTS: Among 262 enrolled patients, the 2-hour pruritus score change from baseline for intravenous cetirizine was statistically noninferior to that for intravenous diphenhydramine (-1.6 versus -1.5; 95% confidence interval -0.1 to 0.3), and in favor of cetirizine. Treatment differences also favored cetirizine for mean time spent in treatment center (1.7 versus 2.1 hours; P=.005), return to treatment center (5.5% versus 14.1%; P=.02), lower change from baseline sedation score at 2 hours (0.1 versus 0.5; P=.03), and adverse event rate (3.9% versus 13.3%). CONCLUSION: Intravenous cetirizine is an effective alternative to intravenous diphenhydramine for treating acute urticaria, with benefits of less sedation, fewer adverse events, shorter time spent in treatment center, and lower rates of revisit to treatment center.

Treatment with azelastine hydrochloride and fluticasone propionate in a single delivery device of young children and adolescents with allergic rhinitis.

Background: Allergic rhinitis (AR) is the most common chronic noncommunicable disease worldwide that affects any age during the human life span but raises particular concerns among the parents and caregivers of the children who are affected. H1-receptor antagonists and corticosteroids provide the most effective way of bringing the condition under control. Intranasal application of these medications has the advantage of a faster onset of action and avoids systemic unwanted adverse effects. The only combination treatment, which comprises azelastine hydrochloride and fluticasone propionate, so far in a single advanced delivery system has proven its efficacy and safety in clinical trials of adult patients with AR. Objective: To critically review and identify gaps in the existing data for children in all different strata of pediatric ages. Methods: We searched the specialized medical literature for publications on the efficacy and safety of the combined formulation of azelastine and fluticasone in a single delivery device in adolescents (ages < 18 years) and children (ages < 12 years). Results: Altogether, 12 peer-reviewed articles have been published about trials that also involved subjects in different strata of the pediatric ages, seven of the articles pooled adolescents and adults. Three articles presented the results of studies in children ages 4 to 11 years specifically designed to overcome the difficulties that children experience in expressing themselves verbally. Conclusion: All the trials with the novel combination product that involved young children and adolescents documented its efficacy, effectiveness, and safety. However, the numbers of the youngest children (ages 4 and 5 years) were low, which suggested that further data about safety and efficacy in this age group are needed.

Pre-traumatic vs post-traumatic OCD in PTSD patients: Are differences in comorbidity rates and functional health status related to childhood abuse?

OBJECTIVE: The goal of this study was to compare the clinical and functional status and the trauma-related characteristics of PTSD patients with comorbid OCD whose onset predated the index traumatic event (pre-traumatic OCD) with those of PTSD patient whose comorbid OCD only emerged after the exposure to the traumatic event (post-traumatic OCD). METHODS: Sixty-three individuals with PTSD and comorbid OCD were evaluated with the Structured Clinical Interview for DSM-IV AXIS I Disorders and completed the Posttraumatic Stress Disorder Checklist - Civilian Version, the Beck Depression Inventory, the Beck Anxiety Inventory, the Trauma History Questionnaire and the 36-Item Short-Form Health Survey. RESULTS: A history of childhood abuse was significantly more frequent among PTSD patients with pre-traumatic OCD (45.2%) than among their counterparts with post-traumatic OCD (16%). PTSD patients with pre-traumatic OCD had higher rates of psychiatric comorbidity in general and showed a lower functional health status in a physical domain (SF-36 Role Limitation due to Physical Health). In contrast, PTSD patients with post-traumatic OCD had a decreased functional health status in a psychological domain (SF-36 Emotional Well Being). The effect sizes were in the medium to large range. CONCLUSIONS: A history of child abuse may be an important, but often neglected, factor accounting for clinical, functional, and trauma-related differences between pre-traumatic and posttraumatic OCD in PTSD patients.

A review of the efficacy and safety of once-daily tiotropium Respimat 2.5 micrograms in adults and adolescents with asthma.

BACKGROUND: Despite current guidelines, many patients with asthma remain symptomatic, particularly those intolerant of, unresponsive to, or uncontrolled by long-acting beta 2-agonists (LABAs). Tiotropium bromide, delivered through the Respimat soft-mist inhaler in 2 puffs of 1.25 micrograms each, is approved for the long-term, maintenance treatment of asthma in patients aged ≥6 years. OBJECTIVE: An overview of the use of once-daily tiotropium Respimat 2.5 micrograms in adults and adolescents with varying degrees of asthma severity. The role of the parasympathetic nervous system in the pathophysiology of asthma, the development of tiotropium for respiratory disease, and the value of the Respimat inhaler are also discussed. METHODS: A literature search of all phase II and phase III trials of once-daily tiotropium Respimat 2.5 micrograms. RESULTS: Once-daily tiotropium Respimat 2.5 micrograms was studied in five phase III studies: three studies in adults and two in adolescents aged 12-17 years. Tiotropium Respimat 2.5 micrograms demonstrated efficacy in adults and adolescents with mild, moderate, or severe asthma, showing significant improvements in lung function and asthma control in patients with uncontrolled asthma despite inhaled corticosteroids (ICS) or ICS plus LABA use. The adverse event profile of tiotropium was very acceptable, with safety similar to placebo. CONCLUSION: Once-daily tiotropium Respimat 2.5 micrograms has positive attributes that include efficacy, a safety profile similar to placebo, once-daily dosing, administration by inhalation, and delivery in the easy-to-use and consistent-dosing Respimat device. However, more data are needed on the effects of tiotropium on clinical outcomes, patients' day-to-day lives, and real-world effectiveness.

Safety of a novel intranasal formulation of azelastine hydrochloride and fluticasone propionate in children: A randomized clinical trial.

BACKGROUND: The safety of a novel intranasal formulation of azelastine hydrochloride (AZE) and fluticasone propionate (FP) has been established in adults and adolescents with allergic rhinitis but not in children <12 years old. OBJECTIVE: To evaluate the safety and tolerability of an intranasal formulation of AZE and FP in children ages 4-11 years with allergic rhinitis. METHODS: The study was a randomized, 3-month, parallel-group, open-label design. Qualified patients were randomized in a 3:1 ratio to AZE/FP (n = 304) or fluticasone propionate (FP) (n = 101), one spray per nostril twice daily, and to one of three age groups: ≥4 to <6 years, ≥6 to <9 years, and ≥9 to <12 years. Safety was assessed by child- or caregiver-reported adverse events, nasal examinations, vital signs, and laboratory assessments. RESULTS: The incidence of treatment-related adverse events (TRAEs) was low in both the AZE/FP (16%) and FP-only (12%) groups after 90 days' continuous use. Epistaxis was the most frequently reported TRAE in both groups (AZE/FP, 9%; FP, 9%), followed by headache (AZE/FP, 3%; FP, 1%). All other TRAEs in the AZE/FP group were reported by ≤1% of the children. The majority of TRAEs were of mild intensity and resolved spontaneously. Results of nasal examinations showed an improvement over time in both groups, with no cases of mucosal ulceration or nasal septal perforation. There were no unusual or unexpected changes in laboratory parameters or vital signs. CONCLUSION: The intranasal formulation of AZE and FP was safe and well tolerated after 3 months' continuous use in children with allergic rhinitis.The study was registered on ClinicalTrials.gov (NCT01794741).

The worldwide incidence of neonaticide: a systematic review.

Neonaticide is the killing of a neonate on the day of its birth by his/her own mother. Neonaticidal women were reported to be predominantly young, unmarried, and primiparous. The motive for murdering the newborn relates to the shame, the fear of rejection, and abandonment by significant others, and the social stigmas associated with an illegitimate birth. The goal of the present study was to conduct a systematic review of the scientific literature and identify population-based studies reporting the incidence of neonaticide in different countries. A total of 485 abstracts were screened. After applying the inclusion/exclusion criteria, 10 studies were selected. Additional searches identified two more articles. Most of these studies were from Europe, where incidence varied from 0.07 (Finland, 1980-2000 period) to 8.5 neonaticides per 100000 births (Austria, 1975-2001 period). More recent studies have indicated that a growing proportion of neonaticidal women are married, multiparous, and suffers from mental disorders. Preventive measures, such as anonymous free delivery, were shown to reduce the incidence of neonaticide, although this effect may be short-lived. Despite social and institutional changes, neonaticide persists even in the most socially advanced, liberal, and prosperous societies in the world.

Diagnosis and management of allergic conjunctivitis in pediatric patients.

BACKGROUND: Allergic conjunctivitis (AC), although one of the most common ocular disorders in pediatric patients, is frequently overlooked, misdiagnosed, and undertreated in children. OBJECTIVE: To guide pediatric health care professionals in the optimal diagnosis and management of AC in pediatric patients. METHODS: To identify any existing best practice guidelines for the diagnosis and treatment of AC in pediatric patients, a review of the literature published between 2004 and January 2015 was conducted. Diagnosis and treatment algorithms and guidelines for pediatric patient referrals were then developed. RESULTS: A literature search to identify best practice guidelines for the treatment of AC in pediatric patients failed to return any relevant articles, which highlighted the need for best practice recommendations. Based on publications on adult AC and clinical experience, this review provides step-by-step guidance for pediatric health care professionals, including recognizing clinical features of AC, establishing a comprehensive medical history, and performing a thorough physical examination to ensure a correct diagnosis and the optimal treatment or referral to an eye care specialist or allergist when required. In addition to established drug treatments, the role of subcutaneous and sublingual immunotherapy is discussed to inform pediatric health care professionals about alternative treatment options for patients who do not tolerate pharmacotherapy or who do not respond sufficiently. CONCLUSION: The diagnostic and treatment algorithms and guidelines provided in this review help address the current literature and educational gap and may lead to improvements in diagnosis and management of pediatric AC.