Risk factors for the recurrence of obstetrical anal sphincter injury and the role of a mediolateral episiotomy: an analysis of a national registry.

OBJECTIVE: The assessment of risk factors, including mediolateral episiotomy (MLE), for the recurrence of obstetric anal sphincter injury (rOASI). DESIGN: Population-based cohort study. SETTING: Data from the nationwide database of the Dutch Perinatal Registry (Perined). POPULATION: A cohort of 391 026 women at term, of whom 9943 had an OASI in their first delivery and had a second vaginal delivery of a liveborn infant in cephalic position. METHODS: Possible risk factors were tested for statistical significance using univariate and multivariate logistic regression analysis. MAIN OUTCOME MEASURES: Rate of rOASI. RESULTS: The rate of rOASI was 5.8%. Multivariate analysis identified a birthweight of ≥4000 g (adjusted OR, aOR, 2.1, 95% CI 1.6-2.6) and a duration of second stage of ≥30 minutes (aOR 1.8, 95% CI 1.4-2.3) as statistically significant risk factors for rOASI. Mediolateral episiotomy was associated with a statistically significant lower rate of rOASI in spontaneous vaginal delivery (SVD) (aOR 0.4, 95% CI 0.3-0.5) and in operative vaginal delivery (OVD) (aOR 0.2, 95% CI 0.1-0.5). CONCLUSIONS: Women with a history of OASI have a higher rate of OASI in their next delivery. Duration of the second stage of ≥30 minutes and a birthweight of ≥4000 g are significantly associated with an increased rate of rOASI. Mediolateral episiotomy is associated with a significantly lower rate of rOASI in both SVD and OVD. TWEETABLE ABSTRACT: Mediolateral episiotomy is associated with a significant lower recurrence rate of OASI in women with an OASI in their first delivery.

Word catheter and marsupialisation in women with a cyst or abscess of the Bartholin gland (WoMan-trial): a randomised clinical trial.

OBJECTIVE: To compare recurrence of a cyst or abscess of the Bartholin gland after surgical treatment using a Word catheter or marsupialisation. DESIGN: Multicentre, open-label, randomised controlled trial. SETTING: Eighteen hospitals in the Netherlands and one hospital in England. POPULATION: Women with a symptomatic cyst or abscess of the Bartholin gland. METHODS: Women were randomised to treatment with Word catheter or marsupialisation. MAIN OUTCOME MEASURES: The primary outcome was recurrence of the cyst or abscess within 1 year of treatment. The secondary outcomes included pain during and after treatment (measured on a 10-point scale), use of analgesics, and time from diagnosis to treatment. Analysis was by intention-to-treat. To assess whether marsupialisation would reduce the recurrence rate by 5% (from 20 to 15%) we needed to include 160 women (alpha error 0.05, beta error 0.2). RESULTS: One hundred and sixty-one women were randomly allocated to treatment by Word catheter (n = 82) or marsupialisation (n = 79) between August 2010 and May 2014. Baseline characteristics were comparable. Recurrence occurred in 10 women (12%) allocated to Word catheter versus eight women (10%) allocated to marsupialisation: relative risk (RR) 1.1, 95% confidence interval (CI) 0.64-1.91; P = 0.70. Pain scores after treatment were also comparable. In the first 24 hours after treatment, 33% used analgesics in the Word catheter group versus 74% in the marsupialisation group (P < 0.001). Time from diagnosis to treatment was 1 hour for placement of Word catheter versus 4 hours for marsupialisation (P = 0.001). CONCLUSIONS: In women with an abscess or cyst of the Bartholin gland, treatment with Word catheter and marsupialisation results in comparable recurrence rates. TWEETABLE ABSTRACT: Comparable recurrence rates for treatment of Bartholinic abscess/cyst with Word catheter and marsupialisation.

Risk indicators for obstetrical anal sphincter injury in vaginal birth after caesarean section compared to first vaginal delivery.

OBJECTIVES: Comparison of the rate of obstetric anal sphincter injury (OASI) between women having their first vaginal birth after caesarean section (CS) and true nulliparous women with a vaginal delivery. Assessment of risk indicators for OASI in women with vaginal birth after one CS (VBAC). STUDY DESIGN: 28 535 women with their first VBAC and a cohort of 275 439 nulliparous women with a vaginal delivery of a liveborn infant in a cephalic position from the Dutch perinatal registry were analyzed. We compared the OASI rate with univariate and multivariate analysis. In women with VBAC possible risk indicators for OASI were assessed using univariate and multivariate logistic regression analysis. RESULTS: The rate of OASI was 5.2% in women with vaginal birth after CS and 4.0% in women with a first vaginal delivery. The adjusted OR (aOR) for vaginal birth after an elective CS was higher (aOR 1.34, 95% CI 1.23-1.47) compared to vaginal birth after an emergency CS (aOR 1.16, 95% CI 1.08-1.25). In women with vaginal birth after emergency CS, the aOR for the indication non-progressive labor was 1.18 (95% CI 1.08-1.29), whereas CS for suspected fetal distress was not significantly associated with obstetric anal sphincter injury in VBAC. In the 28 535 women with a VBAC, mediolateral episiotomy (MLE), birth weight < 3000 g and maternal age < 25 years were associated with a significantly lower rate of OASI. A gestational age of 42 weeks, birth weight ≥ 3500 g, operative vaginal delivery and duration of the 2nd stage of labour of ≥ 60 min were associated with a significantly higher rate of OASI. CONCLUSIONS: Women with a VBAC have a higher rate of OASI in comparison with women with a first vaginal delivery, with the exception of women with a vaginal birth after an emergency CS for suspected fetal distress. Factors associated with a significantly lower rate for OASI were MLE, maternal age < 25 and birth weight < 3000 g. A gestational age of 42 weeks, birth weight between 3500 and 4000 g and ≥ 4000 g, operative vaginal delivery and duration of the 2nd stage of delivery longer dan 60 min were associated with a significantly higher rate of OASI.

PI3K/mTOR inhibitor omipalisib prolongs cardiac repolarization along with a mild proarrhythmic outcome in the AV block dog model.

Background: The phosphoinositide 3-kinase (PI3K) signaling pathway is an interesting target in cancer treatment. The awareness of the proarrhythmic risk of PI3K inhibitors was raised because PI3K is also involved in regulating signaling toward cardiac ion channels. Canine cardiomyocytes treated with PI3K inhibitors show an increased action potential duration and reduced cardiac repolarizing currents. Now, the potential proarrhythmic effect of chronic treatment of PI3K/mTOR inhibitor GSK2126458 (omipalisib) was investigated in the atrioventricular (AV) block dog model. Methods: Purpose-bred Mongrel dogs received complete AV block by ablation of the bundle of His and their hearts were paced in the right ventricular apex at VDD-mode (RVA-VDD). In this way, sinus rhythm was maintained for 15 ± 1 days and thereby bradycardia-induced cardiac remodeling was prevented. Dogs received 1 mg/kg omipalisib once (n = 3) or twice (n = 10) a day via oral administration for 7 days. Under standardized conditions (anesthesia, bradycardia at 60 beats/min, and a dofetilide challenge), potential proarrhythmic effects of omipalisib were investigated. Results: Twice daily dosing of omipalisib increased accumulative plasma levels compared to once daily dosing accompanied with adverse events. Omipalisib prolonged the QT interval at baseline and more strongly after the dofetilide challenge (490 ± 37 to 607 ± 48 ms). The arrhythmic outcome after omipalisib resulted in single ectopic beats in 30% of dogs perpetuating in multiple ectopic beats and TdP arrhythmia in 20% of dogs. Isolated ventricular cardiomyocytes from omipalisib-treated dogs showed a diminished IKs current density. Conclusion: Chronic treatment of PI3K/mTOR inhibitor omipalisib prolonged the QT interval in a preclinical model under standardized proarrhythmic conditions. Furthermore, this study showed that electrical remodeling induced by omipalisib had a mild proarrhythmic outcome.

Registered Replication Report: Rand, Greene, and Nowak (2012).

In an anonymous 4-person economic game, participants contributed more money to a common project (i.e., cooperated) when required to decide quickly than when forced to delay their decision (Rand, Greene & Nowak, 2012), a pattern consistent with the social heuristics hypothesis proposed by Rand and colleagues. The results of studies using time pressure have been mixed, with some replication attempts observing similar patterns (e.g., Rand et al., 2014) and others observing null effects (e.g., Tinghög et al., 2013; Verkoeijen & Bouwmeester, 2014). This Registered Replication Report (RRR) assessed the size and variability of the effect of time pressure on cooperative decisions by combining 21 separate, preregistered replications of the critical conditions from Study 7 of the original article (Rand et al., 2012). The primary planned analysis used data from all participants who were randomly assigned to conditions and who met the protocol inclusion criteria (an intent-to-treat approach that included the 65.9% of participants in the time-pressure condition and 7.5% in the forced-delay condition who did not adhere to the time constraints), and we observed a difference in contributions of -0.37 percentage points compared with an 8.6 percentage point difference calculated from the original data. Analyzing the data as the original article did, including data only for participants who complied with the time constraints, the RRR observed a 10.37 percentage point difference in contributions compared with a 15.31 percentage point difference in the original study. In combination, the results of the intent-to-treat analysis and the compliant-only analysis are consistent with the presence of selection biases and the absence of a causal effect of time pressure on cooperation.

Intranasal fluticasone propionate is more effective than terfenadine tablets for seasonal allergic rhinitis.

BACKGROUND: We compared the efficacy and tolerability of the intranasal corticosteroid fluticasone propionate with that of the antihistamine terfenadine in patients with seasonal allergic rhinitis. METHODS: Two hundred thirty-two adults and adolescents with seasonal allergic rhinitis received intranasal fluticasone propionate (200 micrograms once daily), terfenadine tablets (60 mg twice daily), or placebo for 2 weeks in a double-blind, randomized, parallel-group study. Main outcome measures were clinician- and patient-rated individual and total nasal symptom scores (based on ratings of nasal obstruction, sneezing, nasal itching, and rhinorrhea); clinician-rated overall response to therapy; changes in nasal inflammatory cell counts; adverse events; and morning plasma cortisol concentrations. RESULTS: Both clinician- and patient-rated total and individual nasal symptom scores were significantly lower in the fluticasone group than in either the terfenadine group or the placebo group at nearly every measured time point throughout the treatment period. After 2 weeks of therapy, clinician-rated total nasal symptom scores decreased by 49% in the fluticasone group compared with 27% in the terfenadine group and 19% in the placebo group. In general, therapy with terfenadine was not statistically distinguishable from that with placebo based on patient-rated total or individual nasal symptom scores. According to clinician ratings, 64% of fluticasone-treated patients compared with 49% and 44% of patients treated with terfenadine and placebo, respectively, experienced significant or moderate improvement. A greater percentage of fluticasone-treated patients compared with either terfenadine- or placebo-treated patients experienced reductions in intranasal eosinophil and basophil counts after 2 weeks of therapy. No unusual or serious drug-related adverse events were reported. Morning plasma cortisol concentrations after 2 weeks of therapy did not differ among groups. CONCLUSION: Fluticasone aqueous nasal spray, a well-tolerated corticosteroid preparation that can be administered once daily, is more effective than terfenadine tablets or placebo in controlling symptoms of seasonal allergic rhinitis.

The efficacy of fluticasone propionate aqueous nasal spray for allergic rhinitis and its relationship to topical effects.

Fluticasone propionate aqueous nasal spray is an intranasal corticosteroid for the treatment of patients with allergic rhinitis. This double-masked, double-dummy, parallel-group study was conducted to confirm that the efficacy of fluticasone propionate nasal spray is attributable to topical rather than systemic effects. A total of 304 patients with documented seasonal allergic rhinitis were randomly assigned to receive fluticasone propionate nasal spray 200 micrograms once daily (n = 77), oral fluticasone propionate 5 mg once daily (n = 73), oral fluticasone propionate 10 mg once daily (n = 77), or placebo (n = 77) for 14 days. Plasma fluticasone propionate concentrations were determined at baseline and after 14 days of treatment (day 15). Nasal symptoms were recorded daily by patients and assessed weekly by clinicians. On day 15, more patients in the oral fluticasone propionate 5-mg or 10-mg groups, compared with patients in the fluticasone propionate nasal spray group or the placebo group, had detectable plasma fluticasone propionate concentrations, and mean concentrations were higher in the oral fluticasone propionate groups. Both clinician- and patient-rated total and individual nasal symptom scores for obstruction, rhinorrhea, sneezing, and itching were significantly lower in the fluticasone propionate nasal spray group compared with either of the oral fluticasone propionate groups or the placebo group. With few exceptions, oral fluticasone propionate (5 mg or 10 mg) was not significantly different from placebo on any measures of efficacy. These findings indicate that the efficacy of fluticasone propionate nasal spray (200 micrograms once daily) in the treatment of allergic rhinitis results from direct topical effects rather than from indirect effects after systemic absorption.

Placebo-controlled, double-blind study of the efficacy and safety of triamcinolone acetonide aerosol nasal inhaler in pediatric patients with seasonal allergic rhinitis.

Triamcinolone acetonide (TAA) aerosol nasal inhaler has been shown to effectively relieve the symptoms of seasonal allergic rhinitis in adults and adolescents. We conducted a study to evaluate the efficacy and safety of once-daily administration of TAA aerosol nasal inhaler in pediatric patients aged 6 to 11 years with grass seasonal allergic rhinitis. This multicenter, randomized, double-blind, placebo-controlled, parallel-group study enrolled 116 children who were treated with either TAA aerosol nasal inhaler (220 micrograms/d) or placebo once daily for 2 weeks. Patients evaluated the severity of rhinitis symptoms (nasal stuffiness, discharge, sneezing, and itching) daily according to a four-point scale (0 = absent, 1 = mild, 2 = moderate, and 3 = severe). Patients' and physicians' global evaluations of overall treatment efficacy were assessed at the end of the 2-week treatment period. Patients treated with TAA aerosol nasal inhaler had significantly greater reductions in all nasal symptom scores overall and in virtually all symptoms at the end of week 1 and week 2 compared with those in the placebo group. Both patients' and physicians' global evaluations of efficacy favored TAA aerosol nasal inhaler over placebo. This study demonstrated that once-daily administration of 220 micrograms of TAA aerosol nasal inhaler was well tolerated and effectively reduced the symptoms of seasonal allergic rhinitis in pediatric patients.

A randomized, double-blind, placebo-controlled study comparing the efficacy and safety of ebastine (20 mg and 10 mg) to loratadine 10 mg once daily in the treatment of seasonal allergic rhinitis.

Few randomized studies have compared the H1-receptor antagonists loratadine and ebastine in seasonal allergic rhinitis (SAR) patients. The objective of this study was to compare the efficacy and safety of ebastine 20 mg (E20), ebastine 10 mg (E10), loratadine 10 mg (L10), and placebo (P), once daily, in controlling symptoms of SAR over a 4-week period. This was a double-blind, placebo-controlled, randomized, parallel-group study. Efficacy was assessed in 749 patients (12 to 70 years old) by SAR symptom scores (nasal discharge, congestion, itching, sneezing, and total eye symptoms) entered on diary cards every morning and every evening over the previous 12 hours (reflective score) and at the time of recording (snapshot score). The E20 group showed greater reductions from baseline compared with the L10 group in 2 daily reflective composite scores (nasal index [with or without congestion]) and in all 4 daily snapshot composite scores. E10 and L10 groups showed no significant differences in either the daily reflective or snapshot scores overall although E10 showed a greater improvement of nasal discharge snapshot score than L10. The efficacy of E20 at controlling the symptoms of SAR was well sustained during the fourth week of treatment, with significant differences over placebo in 22/36 total rhinitis symptom scores, followed by E10 (6/36), whereas L10 showed no differences (0/36). Patient and physician global evaluations at the final visit were not statistically significant for any treatment group compared with placebo. There was no significant difference among all groups in the number of patients who reported adverse events. In conclusion, ebastine 20 mg given once daily for 4 weeks in the treatment of SAR showed larger mean reductions from baseline in most rhinitis symptoms scores than loratadine 10 mg. Sustained efficacy was most frequently observed with ebastine 20 mg over placebo, whereas loratadine 10 mg did not provide a statistically significant improvement in any individual or composite symptom score at the end of the fourth week. Both ebastine 20 and 10 mg were well tolerated and proved safe in the treatment of SAR.

Tuberculosis screening among immigrants in The Netherlands: what is its contribution to public health?

Understanding the epidemiology of tuberculosis in migrant communities and designing adequate and comprehensive control strategies is a major challenge facing public health authorities in many low-prevalence countries. In The Netherlands, screening immigrants from tuberculosis high prevalence countries has been conducted since 1966. In this paper, we review risk factors for tuberculosis in migrant populations, the public health importance of tuberculosis and the current screening policy in The Netherlands. TB treatment outcome in migrant populations and operational considerations that ought to be taken into account to optimize current screening practices are also reviewed. The article recommends the setting-up of an information system to evaluate the effectiveness of screening immigrants in The Netherlands, and adjustment of screening policies where needed.

[Tuberculosis in asylum seekers in The Netherlands]. / Tuberculose bij asielzoekers in Nederland.

OBJECTIVE: To compare data of some features and treatment results of asylum seekers with TB in whom the diagnosis was made by a roentgenologic examination of the thorax a short time after arrival in the Netherlands with data of other TB-patients. DESIGN: Retrospective. SETTING: The Netherlands. METHOD: Data of patients with tuberculosis are collected in the National Tuberculosis Register. In 1993 this register included data of 1582 patients, among them III asylum seekers in whom TB was diagnosed after obligatory roentgenologic screening a short time after arrival in the Netherlands. The reason for examination, presence of complaints, forms of tuberculosis, presence of bacteriological confirmation, drug-resistance and results of treatment of them were compared with the data of other asylum seekers (n = 169) and other TB-patients (n = 1302). RESULTS: The diagnosis TB in asylum seekers who are screened obligatorily was bacteriologically confirmed in 34 of III (31%) of the cases, while in 72 of 169 (43%) other asylum seekers and in 729 of 1302 (56%) of the other TB-patients (p < 0.001 for the difference between obligatory screened asylum seekers and other TB-patients). Resistance against isoniazide and streptomycin was more frequent in asylum seekers (n = 106; 13% and 19% respectively) than in Dutch patients (n = 338; 2% and 3% respectively) (p < 0.001). Obligatory screened asylum seekers with bacteriologically confirmed TB were cured in 82% of the cases and this did not differ from the other groups. Asylum seekers and other immigrants showed a higher default-rate than Dutch patients did (p < 0.001). CONCLUSION: Among asylum seekers with tuberculosis discovered by the first obligatory screening was a lower percentage of bacteriological confirmation and a higher percentage of drug-resistance and defaulters. The results of treatment of asylum seekers with bacteriologically confirmed TB were good.

[Tuberculosis screening coverage of immigrants: marked attrition in follow-up screenings]. / Dekkingsgraad van tuberculosescreening bij immigranten: sterke afname bij vervolgscreening.

OBJECTIVE: To estimate the coverage of bi-annual follow-up screening for tuberculosis amongst immigrants, excluding asylum seekers. DESIGN: Retrospective cohort study. METHODS: Participation in bi-annual chest X-ray screening during the first 18 months was recorded for immigrants who underwent entry screening in 1996 in the following Dutch municipal health services (MHS's): Zuid-Kennemerland (Haarlem), Flevoland (Lelystad), Midden-Brabant (Tilburg) en West-Friesland (Hoorn). The number of immigrants that had left the country before the subsequent screening was taken into account in the Zuid-Kennemerland MHS data on screening coverage. RESULTS: Of the 2147 immigrants who underwent entry screening in 1996 (48% men and 52% women; 68% aged 15-34 years), 1075 (50%; range: 29-76) returned for the first follow-up screening and 620 (29%; 21-61) returned for the second. In MHS Zuid-Kennemerland, 113 of the 777 immigrants who had a chest X-ray at entry had left the country before the first follow-up screening, and another 89 had left before the second. Of the remaining persons, who were probably still in the Netherlands, 454 (68%; 454/777 = 58%) returned for the first follow-up screening, and 166 (29%; 166/777 = 21%) returned for the second. CONCLUSION: The coverage of screening for tuberculosis in immigrants decreased after the obligatory entry screening, even when corrected for those who left the country.

A comparison of the efficacy of fluticasone propionate aqueous nasal spray and loratadine, alone and in combination, for the treatment of seasonal allergic rhinitis.

BACKGROUND: Intranasal corticosteroids and oral antihistamines are both effective in the treatment of seasonal allergic rhinitis, although the therapeutic value of administering the two types of agents concurrently has rarely been evaluated. This study was designed to compared the efficacy, safety, and impact on quality of life of fluticasone propionate aqueous nasal spray (FP ANS), loratadine, FP ANS plus loratadine, and placebo (an aqueous nasal spray plus tablet) in the treatment of seasonal allergic rhinitis during the mountain cedar allergy season in south central Texas. METHODS: Six hundred patients with seasonal allergic rhinitis were treated for 2 weeks with either FP ANS 200 microgram once daily, loratadine 10 mg once daily, the FP ANS and loratadine regimens combined, or placebo in a multicenter, randomized, double-blind, double-dummy, parallel-group study. RESULTS: Clinician- and patient-rated total and individual nasal symptom scores after 7 and 14 days of therapy and overall evaluations were significantly lower (P < .001) in the FP ANS and FP ANS plus loratadine groups compared with the loratadine only and placebo groups. Loratadine was not statistically different from placebo in clinician and patient symptom score ratings nor in overall clinician and patient evaluations. FP ANS plus loratadine and FP ANS monotherapy were comparable in efficacy in almost all evaluations; for some patient-rated symptoms the combination was found superior. Mean score changes in the Rhinoconjunctivitis Quality of Life Questionnaire from baseline to day 14 showed significantly greater improvement (P < .001) in quality of life in the FP ANS group than in the group of patients receiving loratadine only or placebo and no significant benefit was demonstrated in the FP ANS plus loratadine group over the FP ANS monotherapy group. No serious or unusual drug-related adverse events were reported. Combining loratadine with FP ANS did not alter the adverse events profile or frequency.

Their pain gives us pleasure: How intergroup dynamics shape empathic failures and counter-empathic responses.

Despite its early origins and adaptive functions, empathy is not inevitable; people routinely fail to empathize with others, especially members of different social or cultural groups. In five experiments, we systematically explore how social identity, functional relations between groups, competitive threat, and perceived entitativity contribute to intergroup empathy bias: the tendency not only to empathize less with out-group relative to in-group members, but also feel pleasure in response to their pain (and pain in response to their pleasure). When teams are set in direct competition, affective responses to competition-irrelevant events are characterized not only by less empathy toward out-group relative to in-group members, but also by increased counter-empathic responses: Schadenfreude and Glückschmerz (Experiment 1). Comparing responses to in-group and out-group targets against responses to unaffiliated targets in this competitive context suggests that intergroup empathy bias may be better characterized by out-group antipathy rather than extraordinary in-group empathy (Experiment 2). We find also that intergroup empathy bias is robust to changes in relative group standing-feedback indicating that the out-group has fallen behind (Experiment 3a) or is no longer a competitive threat (Experiment 3b) does not reduce the bias. However, reducing perceived in-group and out-group entitativity can significantly attenuate intergroup empathy bias (Experiment 4). This research establishes the boundary conditions of intergroup empathy bias and provides initial support for a more integrative framework of group-based empathy.

The world population explosion: causes, backgrounds and -projections for the future.

UNLABELLED: At the beginning of the nineteenth century, the total world population crossed the threshold of 1 billion people for the first time in the history of the homo sapiens sapiens. Since then, growth rates have been increasing -exponentially, reaching staggeringly high peaks in the 20th century and slowing down a bit thereafter. Total world population reached 7 billion just after 2010 and is expected to count 9 billion by 2045. This paper first charts the differences in population growth between the world regions. Next, the mechanisms behind unprecedented population growth are explained and plausible scenarios for future developments are discussed. Crucial for the long term trend will be the rate of decline of the number of births per woman, called total fertility. Improvements in education, reproductive health and child survival will be needed to speed up the decline of total fertility, particularly in Africa. But in all scenarios, world population will continue to grow for some time due to population momentum. Finally, the paper outlines the debate about the consequences of the population explosion, involving poverty and food security, the impact on the natural environment, and migration flows. KEY WORDS: Fertility, family planning, world population, population growth, demographic transition, urbanization, population momentum, population projections.

Tuberculosis infection in children who are contacts of immigrant tuberculosis patients.

The present study aimed to determine what proportion of children who are in close contact with immigrant tuberculosis (TB) patients are infected with Mycobacterium tuberculosis. For 1.5 yrs, 14 municipal health services in The Netherlands collected data from all non-Dutch TB patients and their contacts. Close contacts aged < 16 yrs received a tuberculin skin test (TST). A positive TST was defined as an induration of > or = 10 mm among nonvaccinated children, and > or = 16 mm among bacille Calmette-Guérin-vaccinated children. In total, 244 patients had 359 close contacts aged < 16 yrs. Nine out of the 359 (2.5%) had TB. A TST test was given to 298 out of the 359 (83%). Of the 115 contacts of 44 extrapulmonary TB patients, three (3%) had a positive TST. Of the 186 contacts of 58 positive pulmonary TB patients, 30 (16%) had a positive TST. Contacts of sputum smear-positive patients significantly more often had a positive TST (25%), compared with the contacts of sputum smear-negative patients (7%). Children born abroad significantly more often had a positive TST (20%) than children born in The Netherlands (5%). In conclusion, the prevalence of active tuberculosis and latent tuberculosis infection among children who are close contacts of immigrant tuberculosis patients is high and warrants an expansion of contact investigation.

Efficacy and safety of ebastine 20 mg compared to loratadine 10 mg once daily in the treatment of seasonal allergic rhinitis: a randomized, double-blind, placebo-controlled study.

BACKGROUND: Few randomized studies have compared loratadine to ebastine in the symptomatic treatment of seasonal allergic rhinitis (SAR) patients. METHODS: This double-blind, placebo-controlled, randomized, parallel-group, comparative trial compared the efficacy and safety of ebastine 20 mg (E20), loratadine 10 mg (L10) and placebo (P), administered once daily, in the control of SAR symptoms over a 2-week period. An additional 2-week treatment period was included in order to check sustained efficacy and tolerability. RESULTS: A total of 703 patients were enrolled: 282 patients in the E20 group, 279 in the L10 group and 142 in the P group. E20 showed a greater decrease from baseline in the main efficacy variable (mean daily reflective total symptom score) than L10 (p = 0.0018) or P (p = 0.0024), whereas the difference between L10 and P was not significant. Moreover, reductions from baseline in all composite/individual daily reflective rhinitis symptom scores were significantly larger in patients receiving E20 than in patients receiving L10 or P. Most significant differences between E20 and L10 or P were maintained after 4 weeks of treatment. Overall, all treatments were safe and well tolerated. There was no significant difference in the percentage of patients who reported one or more adverse events (AEs) between the groups, and most AEs were mild to moderate (89.9%). CONCLUSIONS: E20 given once daily for 2 weeks was more effective in the treatment of SAR symptoms than L10 or P. E20 also showed a sustained efficacy after 4 weeks of treatment, and overall was well tolerated and proved safe.

New formulation of aqueous flunisolide nasal spray in the treatment of allergic rhinitis: comparative assessment of safety, tolerability, and efficacy.

This 6-week, multicenter, double-blind, randomized, placebo-controlled, parallel-group trial compared the safety, efficacy, and tolerability of a new formulation of flunisolide nasal spray with the original formulation in the treatment of allergic rhinitis due to mountain cedar pollenosis. It was conducted at three clinical centers in close geographic proximity. A total of 216 patients, ranging in age from 14 to 77 years (mean, 44 years), took at least one dose of study drug and therefore were evaluable for the safety analysis. A total of 185 patients (85%) completed the study, and 136 patients were evaluable for the efficacy analysis. Both formulations of flunisolide were comparable in terms of relief of rhinitis symptoms, and the new flunisolide formulation was better tolerated than the original formulation. Both active formulations were superior to their respective vehicles (P < 0.001) using multiple measures of allergic rhinitis symptoms relief. Use of escape medication (chlorpheniramine maleate) was significantly (P < or = 0.034) greater in the placebo group when compared with their respective active treatment groups. No therapeutic effect was observed with symptoms of allergic conjunctivitis. Significantly fewer patients who were treated with the new formulation flunisolide reported nasal burning and stinging when compared with the original formulation (P = 0.006). In conclusion, the new formulation showed similar efficacy and improved tolerability in the treatment of allergic rhinitis compared with the original formulation. This new formulation not only offers clinicians a useful therapeutic addition for the treatment of allergic rhinitis, but may also improve patient compliance.

A double-blind, controlled trial to assess the safety and efficacy of azelastine nasal spray in seasonal allergic rhinitis.

BACKGROUND: Azelastine solution is a topically (nasal) administered antiallergy drug with a preclinical profile suggestive of efficacy in patients with allergic rhinitis. OBJECTIVES: The study was designed to compare the effectiveness and safety of two dosages of azelastine nasal spray (2 sprays per nostril once daily and twice daily) with that of placebo in the treatment of patients with symptomatic seasonal allergic rhinitis. METHODS: Two hundred fifty-one patients (12 years of age or older) were randomized to treatment in this 2-week, double-blind, parallel-group study. Primary efficacy variables were Major Symptom Complex (nose blows, sneezes, runny nose, itchy nose, watery eyes) and Total Symptoms Complex (Major Symptom Complex plus itchy eyes/ears/throat/palate, cough, postnasal drip). RESULTS: Patients treated with azelastine had mean percent improvements in Total and Major Symptom Complex scores that were consistently superior to placebo at each evaluation point. Overall, improvements were statistically significant (p < or = 0.05) in the Total Symptoms Complex for both azelastine groups and in the Major Symptom Complex for the twice daily group with a trend toward statistical significance for the once daily group. Azelastine was superior to placebo in improving all individual rhinitis symptoms. Adverse experiences in the azelastine groups were minor and infrequent. CONCLUSION: The results support the efficacy and safety of azelastine nasal spray in the treatment of seasonal allergic rhinitis.