Impact of rapid urbanization on the rates of infection by Vibrio cholerae O1 and enterotoxigenic Escherichia coli in Dhaka, Bangladesh

Background

In Bangladesh, increases in cholera epidemics are being documented with a greater incidence and severity. The aim of this prospective study was to identify the prevalence and importance of V. cholerae O1 and enterotoxigenic Escherichia coli (ETEC) as causal agents of severe diarrhea in a high diarrhea prone urban area in Dhaka city.

Methodology

Systematic surveillance was carried out on all diarrheal patients admitted from Mirpur between March 2008 to February 2010 at the ICDDR, B hospital. Stool or rectal swabs were collected from every third diarrheal patient for microbiological evaluation.

Principal Findings

Of diarrheal patients attending the hospital from Mirpur, 41% suffered from severe dehydration with 39% requiring intravenous rehydration therapy. More diarrheal patients were above five years of age (64%) than those below five years of age (36%). About 60% of the patients above five years of age had severe dehydration compared with only 9% of patients under five years of age. The most prevalent pathogen isolated was Vibrio cholerae O1 (23%) followed by ETEC (11%). About 8% of cholera infection was seen in infants with the youngest children being one month of age while in the case of ETEC the rate was 11%. Of the isolated ETEC strains, the enterotoxin type were almost equally distributed; ST accounted for 31% of strains; LT/ST for 38% and LT for 31%.

Conclusion

V. cholerae O1 is the major bacterial pathogen and a cause of severe cholera disease in 23% of patients from Mirpur. This represents a socioeconomic group that best reflects the major areas of high cholera burden in the country. Vaccines that can target such high risk groups in the country and the region will hopefully be able to reduce the disease morbidity and the transmission of pathogens that impact the life and health of people.     

Chronic maternal depression is associated with reduced weight gain in latino infants from birth to 2 years of age

Background

Latino children are at increased risk for mirconutrient deficiencies and problems of overweight and obesity. Exposures in pregnancy and early postpartum may impact future growth trajectories.

Objectives

To evaluate the relationship between prenatal and postnatal maternal depressive symptoms experienced in pregnancy and infant growth from birth to 2 years of age in a cohort of Latino infants.

Methods

We recruited pregnant Latina mothers at two San Francisco hospitals and followed their healthy infants to 24 months of age. At 6, 12 and 24 months of age, infants were weighed and measured. Maternal depressive symptoms were assessed prenatally and at 4-6 weeks postpartum. Women who had high depressive symptoms at both time periods were defined as having chronic depression. Logistic mixed models were applied to compare growth curves and risk for overweight and underweight based on exposure to maternal depression.

Results

We followed 181 infants to 24 months. At 12 and 24 months, respectively, 27.4% and 40.5% were overweight, and 5.6% and 2.2% were underweight. Exposure to chronic maternal depression was associated with underweight (OR = 12.12, 95%CI 1.86-78.78) and with reduced weight gain in the first 2 years of life (Coef = -0.48, 95% CI -0.94—0.01) compared with unexposed infants or infants exposed to episodic depression (depression at one time point). Exposure to chronic depression was also associated with reduced risk for overweight in the first 2 years of life (OR 0.28, 95%CI 0.03-0.92).

Conclusions

Exposure to chronic maternal depression in the pre- and postnatal period was associated with reduced weight gain in the first two years of life and greater risk for failure to thrive, in comparison with unexposed infants or those exposed episodically. The infants of mothers with chronic depression may need additional nutritional monitoring and intervention.     

Elbow Flexion Contractures in Childhood in Obstetric Brachial Plexus Lesions: A Longitudinal Study of 20 Neurosurgically Reconstructed Infants with 8-Year Follow-up

Objective

 Little knowledge exists on the development of elbow flexion contractures in children with obstetrical brachial plexus lesion (OBPL). This study aims to evaluate the prognostic significance of several neuromuscular parameters in infants with OBPL regarding the later development of elbow flexion contractures.

Methods

 Twenty infants with OBPL with insufficient signs of recovery in the first months of life who were neurosurgically reconstructed were included. At a mean age of 4.6 months, the following neuromuscular parameters were assessed: existence of flexion contractures, cross-sectional area (CSA) of upper arm muscles on MRI, Narakas classification, EMG results, and elbow muscle function using the Gilbert score. In childhood at follow-up at mean age of 7.7 years, we measured the amount of flexion contractures and the upper arm peak force (Newton). Statistical analysis is used to assess relations between these parameters.

Results

 Flexion contractures of greater than 10 degrees occurred in 55% of our patient group. The relation between the parameters in infancy and the flexion contractures in childhood is almost nonexistent. Only the Narakas classification was related to the development of flexion contractures in childhood (p = 0.006). Infant muscle CSA is related to childhood peak muscle force.

Conclusion

 The role of infancy upper arm muscle hypotrophy/hypertrophy, reinnervation, and early elbow muscle function in the development of childhood elbow contractures remains unclear. In this cohort prediction of childhood flexion, contractures were not possible using infancy neuromuscular parameters. We suggest that contractures might be an adaptive process to optimize residual muscle function.     

Frequent use of paracetamol and risk of allergic disease among women in an Ethiopian population

Introduction

The hypothesis that paracetamol might increase the risk of asthma and other allergic diseases have gained support from a range of independent studies. However, in studies based in developed countries, the possibility that paracetamol and asthma are associated through aspirin avoidance is difficult to exclude.

Objectives

To explore this hypothesis among women in a developing country, where we have previously reported aspirin avoidance to be rare.

Methods

In 2005/6 a population based cohort of 1065 pregnant women was established in Butajira, Ethiopia and baseline demographic data collected. At 3 years post birth, an interview-based questionnaire administered to 945 (94%) of these women collected data on asthma, eczema, and hay fever in the past 12 month, frequency of paracetamol use and potential confounders. Allergen skin tests to Dermatophagoides pteronyssinus and cockroach were also performed. The independent effects of paracetamol use on allergic outcomes were determined using multiple logistic regression analysis.

Findings

The prevalence of asthma, eczema and hay fever was 1.7%, 0.9% and 3.8% respectively; of any one of these conditions 5.5%, and of allergen sensitization 7.8%. Paracetamol use in the past month was reported by 29%, and associations of borderline significance were seen for eczema (adjusted OR (95% CI) = 8.51 (1.68 to 43.19) for 1–3 tablets and 2.19 (0.36 to 13.38) for ≥4 tablets, compared to no tablets in the past month; overall p = 0.055) and for ‘any allergic condition’ (adjusted OR (95% CI) = 2.73 (1.22 to 6.11) for 1–3 tablets and 1.35 (0.67 to 2.70) for ≥4 tablets compared to 0 in the past month; overall p = 0.071).

Conclusions

This study provides further cross-sectional evidence that paracetamol use increases the risk of allergic disease.     

Esophagitis in a high H. pylori prevalence area: severe disease is rare but concomitant peptic ulcer is frequent

Background

Few data are available on the prevalence of erosive and severe esophagitis in Western countries.

Objective

To retrospectively determine the prevalence and the factors predicting erosive esophagitis and severe esophagitis in a large series of endoscopies in Spain.

Design

Retrospective observational study. A multivariate analysis was performed to determine variables predicting severe esophagitis.

Setting

Databases of 29 Spanish endoscopy units.

Patients

Patients submitted to a diagnostic endoscopy during the year 2005.

Interventions

Retrospective review of the databases.

Main Outcome Measurements

Esophagitis severity (graded according to the Los Angeles classification) and associated endoscopic findings.

Results

Esophagitis was observed in 8.7% of the 93,699 endoscopies reviewed. Severe esophagitis (LA grade C or D) accounted for 22.5% of cases of the disease and was found in 1.9% of all endoscopies. Incidences of esophagitis and those of severe esophagitis were 86.2 and 18.7 cases per 100,000 inhabitants per year respectively. Male sex (OR 1.89) and advanced age (OR 4.2 for patients in the fourth age quartile) were the only variables associated with severe esophagitis. Associated peptic ulcer was present in 8.8% of cases.

Limitations

Retrospective study, no data on individual proton pump inhibitors use.

Conclusions

Severe esophagitis is an infrequent finding in Spain. It occurs predominantly in males and in older individuals. Peptic ulcer disease is frequently associated with erosive esophagitis.     

Serotype distribution and invasive potential of group B streptococcus isolates causing disease in infants and colonizing maternal-newborn dyads

Background

Serotype-specific polysaccharide based group B streptococcus (GBS) vaccines are being developed. An understanding of the serotype epidemiology associated with maternal colonization and invasive disease in infants is necessary to determine the potential coverage of serotype-specific GBS vaccines.

Methods

Colonizing GBS isolates were identified by vaginal swabbing of mothers during active labor and from skin of their newborns post-delivery. Invasive GBS isolates from infants were identified through laboratory-based surveillance. GBS serotyping was done by latex agglutination. Serologically non-typeable isolates were typed by a serotype-specific PCR method. The invasive potential of GBS serotypes associated with sepsis within seven days of birth was evaluated in association to maternal colonizing serotypes.

Results

GBS was identified in 289 (52.4%) newborns born to 551 women with GBS-vaginal colonization and from 113 (5.6%) newborns born to 2,010 mothers in whom GBS was not cultured from vaginal swabs. The serotype distribution among vaginal-colonizing isolates was as follows: III (37.3%), Ia (30.1%), and II (11.3%), V (10.2%), Ib (6.7%) and IV (3.7%). There were no significant differences in serotype distribution between vaginal and newborn colonizing isolates (P = 0.77). Serotype distribution of invasive GBS isolates were significantly different to that of colonizing isolates (P<0.0001). Serotype III was the most common invasive serotype in newborns less than 7 days (57.7%) and in infants 7 to 90 days of age (84.3%; P<0.001). Relative to serotype III, other serotypes showed reduced invasive potential: Ia (0.49; 95%CI 0.31–0.77), II (0.30; 95%CI 0.13–0.67) and V (0.38; 95%CI 0.17–0.83).

Conclusion

In South Africa, an anti-GBS vaccine including serotypes Ia, Ib and III has the potential of preventing 74.1%, 85.4% and 98.2% of GBS associated with maternal vaginal-colonization, invasive disease in neonates less than 7 days and invasive disease in infants between 7–90 days of age, respectively.     

Protective effect of hepatitis B vaccine combined with two-dose hepatitis B immunoglobulin on infants born to HBsAg-positive mothers

Background

Despite the use of hepatitis B (HB) vaccine and hepatitis B immunoglobulin (HBIG), a portion of infants are still non- or low-responders, or even immunoprophylaxis failure. We aimed to determine the immune response in the infants from the mothers being positive for hepatitis B surface antigen (HBsAg), by which the infants received three doses of HB vaccine in combination with two-dose 200 IU HBIG injections.

Methods

In this retrospective study, 621 infants from HBsAg-positive mothers in Beijing YouAn Hospital between January 2008 and December 2009 were included. All the infants were given three doses of 10 µg HB vaccine (at 0, 1 and 6 months of age) and two-dose of 200 IU HBIG (at birth and in 2 weeks of age). Serum HBsAg and antibody to HBsAg (anti-HBs) in all the infants were determined at 7 months of age.

Results

Of the 621 infants, 2.9% were immunoprophylaxis failure (positive for HBsAg), 1.4% were non-responders (anti-HBs undetectable), 95.7% were responders. The 594 responders could be categorized into three subsets, 22 were 10 to 99 IU/L for anti-HBs levels, 191 were 100 to 999 IU/L, and 381 were ≥1000 IU/L. The immunoprophylaxis failure rate was at 0% and 5.2% for the infants of HBeAg-negative and HBeAg-positive mothers(P<0.001). Infants from mothers with detectable HBV DNA had higher incidence of immunoprophylaxis failure than those of mothers without detectable HBV DNA (P = 0.002). The factors including gender, birth weight, gestation weeks, the rates of maternal HBeAg-positive, and detectable HBV DNA did not contribute to the no response to HB vaccination.

Conclusions

Through vaccination by three doses of HB and two-dose of HBIG, majority of the infants (95.7%) achieved a protective level of anti-HBs at 7 months of age. Maternal HBeAg-positive and HBV DNA detectable were associated with the immunoprophylaxis failure, but not contribute to the non- or low-response to HB vaccination.     

Household tobacco smoke and admission weight predict severe bronchiolitis in infants independent of deprivation: prospective cohort study

Objectives

To examine demographic, environmental and clinical factors associated with severe bronchiolitis in infants admitted to hospital and quantify the independent effects of these factors.

Design

Prospective cohort study.

Setting

Alder Hey Children''s Hospital, Liverpool, United Kingdom.

Participants

378 infants admitted to hospital with a diagnosis of bronchiolitis, of whom 299 (79%) were antigen positive to respiratory syncytial virus (RSV).

Outcome

Severity of disease during admission, defined as “no need for supplemental oxygen” (reference group), “any need for supplemental oxygen” and “any need for mechanical ventilation”.

Results

Univariate analysis found male sex (p = 0.035) and tobacco smoking by a household member (p<0.001) were associated with need for both supplemental oxygen and mechanical ventilation. Premature birth, low gestation, low birth weight, low admission weight and low corrected age on admission were also associated with need for mechanical ventilation (all p≤0.002). Deprivation scores (IMD 2004) were significantly higher in households where a member smoked compared to non-smoking households (p<0.001). The odds of smoking predicted by deprivation were 7 times higher (95%CI (3.59, 14.03)), when comparing the least and most deprived quintiles of the study population. Family history of atopic disease and deprivation score were not associated with severe disease. Multivariate multinomial logistic regression which initially included all covariates, found household tobacco smoking (adjusted OR = 2.45, 95%CI (1.60, 3.74) predicted need for oxygen supplementation. Household tobacco smoking (adjusted OR = 5.49, (2.78, 10.83)) and weight (kg) on admission (adjusted OR = 0.51, (0.40, 0.65)) were both significant predictors in the final model for mechanical ventilation. The same associations and similar size of effects were found when only children with proven RSV infection were included in analysis.

Conclusions

Low admission weight and householder tobacco smoking increased the risk of severe bronchiolitis in infants admitted to hospital. These effects were independent of a standard deprivation measure. NIHR Study Ref. DHCS/G121/10.     

Utility of quantitative sensory testing and screening tools in identifying HIV-associated peripheral neuropathy in Western Kenya: pilot testing

Background/Aim

Neuropathy is the most common neurologic complication of HIV but is widely under-diagnosed in resource-constrained settings. We aimed to identify tools that accurately distinguish individuals with moderate/severe peripheral neuropathy and can be administered by non-physician healthcare workers (HCW) in resource-constrained settings.

Methods

We enrolled a convenience sample of 30 HIV-infected outpatients from a Kenyan HIV-care clinic. A HCW administered the Neuropathy Severity Score (NSS), Single Question Neuropathy Screen (Single-QNS), Subjective Peripheral Neuropathy Screen (Subjective-PNS), and Brief Peripheral Neuropathy Screen (Brief-PNS). Monofilament, graduated tuning fork, and two-point discrimination examinations were performed. Tools were validated against a neurologist''s clinical assessment of moderate/severe neuropathy.

Results

The sample was 57% male, mean age 38.6 years, and mean CD4 count 324 cells/µL. Neurologist''s assessment identified 20% (6/30) with moderate/severe neuropathy. Diagnostic utilities for moderate/severe neuropathy were: Single-QNS - 83% sensitivity, 71% specificity; Subjective-PNS-total - 83% sensitivity, 83% specificity; Subjective-PNS-max and NSS - 67% sensitivity, 92% specificity; Brief-PNS - 0% sensitivity, 92% specificity; monofilament - 100% sensitivity, 88% specificity; graduated tuning fork - 83% sensitivity, 88% specificity; two-point discrimination - 75% sensitivity, 58% specificity.

Conclusions

Pilot testing suggests Single-QNS, Subjective-PNS, and monofilament examination accurately identify HIV-infected patients with moderate/severe neuropathy and may be useful diagnostic tools in resource-constrained settings.     

A phase II, randomized study on an investigational DTPw-HBV/Hib-MenAC conjugate vaccine administered to infants in Northern Ghana

Background

Combining meningococcal vaccination with routine immunization in infancy may reduce the burden of meningococcal meningitis, especially in the meningitis belt of Africa. We have evaluated the immunogenicity, persistence of immune response, immune memory and safety of an investigational DTPw-HBV/Hib-MenAC conjugate vaccine given to infants in Northern Ghana.

Methods and Findings

In this phase II, double blind, randomized, controlled study, 280 infants were primed with DTPw-HBV/Hib-MenAC or DTPw-HBV/Hib vaccines at 6, 10 and 14 weeks of age. At 12 months of age, children in each group received a challenge dose of serogroup A+C polysaccharides. Antibody responses were assessed pre, and one month-post dose 3 of the priming schedule and pre and 1 month after administration of the challenge dose. One month post-dose 3, 87.8% and 88.2% of subjects in the study group had bactericidal meningococcal serogroup A (SBA-MenA) and meningococcal serogroup C (SBA-MenC) antibody titres ≥1∶8 respectively. Seroprotection/seropositivity rates to the 5 antigens administered in the routine EPI schedule were non-inferior in children in the study group compared to those in the control group. The percentages of subjects in the study group with persisting SBA-MenA titres ≥ 1∶8 or SBA-MenC titres ≥1∶8 at the age of 12 months prior to challenge were significantly higher than in control group (47.7% vs 25.7% and 56.4% vs 5.1% respectively). The administration of 10 μg of serogroup A polysaccharide increased the SBA-MenA GMT by 14.0-fold in the DTPW-HBV/HibMenAC-group compared to a 3.8 fold increase in the control-group. Corresponding fold-increases in SBA-MenC titres following challenge with 10 μg of group C polysaccharide were 18.8 and 1.9 respectively. Reactogenicity following primary vaccination or the administration of the challenge dose was similar in both groups, except for swelling (Grade 3) after primary vaccination which was more frequent in children in the vaccine than in the control group (23.7%; 95%CI [19.6–28.1] of doses vs 14.1%; 95% CI [10.9–17.8] of doses). Fifty-nine SAEs (including 8 deaths), none of them related to vaccination, were reported during the entire study.

Conclusions

Three dose primary vaccination with DTPw-HBV/Hib-MenAC was non-inferior to DTPw-HBV/Hib for the 5 common antigens used in the routine EPI schedule and induced bactericidal antibodies against Neisseria meningitidis of serogroups A and C in the majority of infants. Serogroup A and C bactericidal antibody levels had fallen below titres associated with protection in nearly half of the infants by the age of 12 months confirming that a booster dose is required at about that age. An enhanced memory response was shown after polysaccharide challenge. This vaccine could provide protection against 7 important childhood diseases (including meningococcal A and C) and be of particular value in countries of the African meningitis belt.

Trial Registration

Controlled-Trials.com ISRCTN35754083     

Emergence of minor drug-resistant HIV-1 variants after triple antiretroviral prophylaxis for prevention of vertical HIV-1 transmission

Background

WHO-guidelines for prevention of mother-to-child transmission of HIV-1 in resource-limited settings recommend complex maternal antiretroviral prophylaxis comprising antenatal zidovudine (AZT), nevirapine single-dose (NVP-SD) at labor onset and AZT/lamivudine (3TC) during labor and one week postpartum. Data on resistance development selected by this regimen is not available. We therefore analyzed the emergence of minor drug-resistant HIV-1 variants in Tanzanian women following complex prophylaxis.

Method

1395 pregnant women were tested for HIV-1 at Kyela District Hospital, Tanzania. 87/202 HIV-positive women started complex prophylaxis. Blood samples were collected before start of prophylaxis, at birth and 1–2, 4–6 and 12–16 weeks postpartum. Allele-specific real-time PCR assays specific for HIV-1 subtypes A, C and D were developed and applied on samples of mothers and their vertically infected infants to quantify key resistance mutations of AZT (K70R/T215Y/T215F), NVP (K103N/Y181C) and 3TC (M184V) at detection limits of <1%.

Results

50/87 HIV-infected women having started complex prophylaxis were eligible for the study. All women took AZT with a median duration of 53 days (IQR 39–64); all women ingested NVP-SD, 86% took 3TC. HIV-1 resistance mutations were detected in 20/50 (40%) women, of which 70% displayed minority species. Variants with AZT-resistance mutations were found in 11/50 (22%), NVP-resistant variants in 9/50 (18%) and 3TC-resistant variants in 4/50 women (8%). Three women harbored resistant HIV-1 against more than one drug. 49/50 infants, including the seven vertically HIV-infected were breastfed, 3/7 infants exhibited drug-resistant virus.

Conclusion

Complex prophylaxis resulted in lower levels of NVP-selected resistance as compared to NVP-SD, but AZT-resistant HIV-1 emerged in a substantial proportion of women. Starting AZT in pregnancy week 14 instead of 28 as recommended by the current WHO-guidelines may further increase the frequency of AZT-resistance mutations. Given its impact on HIV-transmission rate and drug-resistance development, HAART for all HIV-positive pregnant women should be considered.     

Alcohol use disorders (AUD) among tuberculosis patients: a study from Chennai, South India

Background

Alcohol Use Disorders (AUDs) among tuberculosis (TB) patients are associated with nonadherence and poor treatment outcomes. Studies from Tuberculosis Research Centre (TRC), Chennai have reported that alcoholism has been one of the major reasons for default and mortality in under the DOTS programme in South India. Hence, it is planned to conduct a study to estimate prevalence of alcohol use and AUDs among TB patients attending the corporation health centres in Chennai, India.

Methodology

This is a cross-sectional cohort study covering 10 corporation zones at Chennai and it included situational assessment followed by screening of TB patients by a WHO developed Alcohol Use Disorders Identification Test AUDIT scale. Four zones were randomly selected and all TB patients treated during July to September 2009 were screened with AUDIT scale for alcohol consumption.

Results

Out of 490 patients, 66% were males, 66% were 35 years and above, 57% were married, 58% were from the low monthly income group of 8. Age (>35 years), education (less educated), income (ConclusionsAUD among TB patients needs to be addressed urgently and the findings suggest the importance of integrating alcohol treatment into TB care.     

Interferon-gamma release assays for the diagnosis of active tuberculosis in HIV-infected patients: a systematic review and meta-analysis

Background

Interferon-gamma release assays (IGRAs) have provided a new method for the diagnosis of Mycobacterium tuberculosis infection. However, the role of IGRAs for the diagnosis of active tuberculosis (TB), especially in HIV-infected patients remains unclear.

Methods

We searched PubMed, EMBASE and Cochrane databases to identify studies published in January 2001–July 2011 that evaluated the evidence of using QuantiFERON-TB Gold in-tube (QFT-GIT) and T-SPOT.TB (T-SPOT) on blood for the diagnosis of active TB in HIV-infected patients.

Results

The search identified 16 eligible studies that included 2801 HIV-infected individuals (637 culture confirmed TB cases). The pooled sensitivity for the diagnosis of active TB was 76.7% (95%CI, 71.6–80.5%) and 77.4% (95%CI, 71.4–82.6%) for QFT-GIT and T-SPOT, respectively, while the specificity was 76.1% (95%CI, 74.0–78.0%) and 63.1% (95%CI, 57.6–68.3%) after excluding the indeterminate results. Studies conducted in low/middle income countries showed slightly lower sensitivity and specificity when compared to that in high-income countries. The proportion of indeterminate results was as high as 10% (95%CI, 8.8–11.3%) and 13.2% (95%CI, 10.6–16.0%) for QFT-GIT and T-SPOT, respectively.

Conclusion

IGRAs in their current formulations have limited accuracy in diagnosing active TB in HIV-infected patients, and should not be used alone to rule out or rule in active TB cases in HIV-infected patients. Further modification is needed to improve their accuracy.     

The effectiveness of online cognitive behavioral treatment in routine clinical practice

Context

Randomized controlled trails have identified online cognitive behavioral therapy as an efficacious intervention in the management of common mental health disorders.

Objective

To assess the effectiveness of online CBT for different mental disorders in routine clinical practice.

Design

An uncontrolled before-after study, with measurements at baseline, posttest, 6-week follow-up, and 1-year follow-up.

Participants & Setting

1500 adult patients (female: 67%; mean age: 40 years) with a GP referral for psychotherapy were treated at a Dutch online mental health clinic for symptoms of depression (n = 413), panic disorder (n = 139), posttraumatic stress (n = 478), or burnout (n = 470).

Interventions

Manualized, web-based, therapist-assisted CBT, of which the efficacy was previously demonstrated in a series of controlled trials. Standardized duration of treatment varied from 5 weeks (online CBT for Posttraumatic stress) to 16 weeks (online CBT for Depression).

Main Outcome Measures

Validated self-report questionnaires of specific and general psychopathology, including the Beck Depression Inventory, the Impact of Event Scale, the Panic Disorder Severity Scale-Self Report, the Oldenburg Burnout Inventory, and the Depression Anxiety Stress Scales.

Results

Treatment adherence was 71% (n = 1071). Study attrition was 21% at posttest, 33% at 6-week FU and 65% at 1-year FU. Mixed-model repeated measures regression identified large short-term reductions in all measures of primary symptoms (d = 1.9±0.2 to d = 1.2±0.2; P<.001), which sustained up to one year after treatment. At posttest, rates of reliable improvement and recovery were 71% and 52% in the completer sample (full sample: 55%/40%). Patient satisfaction was high.

Conclusions

Results suggest that online therapist-assisted CBT may be as effective in routine practice as it is in clinical trials. Although pre-treatment withdrawal and long-term outcomes require further study, results warrant continued implementation of online CBT.     

Elimination of active trachoma after two topical mass treatments with azithromycin 1.5% eye drops

Background

Following an epidemiological study carried out in 2006 showing a high prevalence of blinding trachoma in the Far North Region of Cameroon, a trachoma elimination programme using the SAFE strategy was initiated: three yearly trachoma mass treatments were to be performed.

Methodology/Principal Findings

The entire district population (120,000 persons) was treated with azithromycin 1.5% eye drops in February 2008 and January 2009. To assess the effect of treatment on the prevalence of active trachoma, three epidemiological studies were conducted on a representative sample of children aged between 1 and 10 years. The first study was performed just prior to the first treatment, the second just prior to the 2nd treatment and the third one, one year later. The prevalence of active forms of trachoma (TF + TI) dropped from 31.5% (95%CI 26.4–37.5) before treatment to 6.3% (95%CI 4.1–9.6) one year after first treatment; a reduction of nearly 80%. One year after the second treatment, the prevalence decreased to 3.1% (95%CI 2.0–4.9), a total reduction of 90%. Furthermore, there were no more TI cases (only TF). There was no report of serious or systemic side effects. Tolerance was excellent.

Conclusions/Significance

Active trachoma mass treatment with azithromycin 1.5% eye drops is feasible, well tolerated, and effective.     

Respiratory paradoxical adverse drug reactions associated with acetylcysteine and carbocysteine systemic use in paediatric patients: a national survey

Objective

To report pediatric cases of paradoxical respiratory adverse drug reactions (ADRs) after exposure to oral mucolytic drugs (carbocysteine, acetylcysteine) that led to the withdrawal of licenses for these drugs for infants in France and then Italy.

Design

The study followed the recommendations of the European guidelines of pharmacovigilance for medicines used in the paediatric population.

Setting

Cases voluntarily reported by physicians from 1989 to 2008 were identified in the national French pharmacovigilance public database and in drug company databases.

Patients

The definition of paradoxical respiratory ADRs was based on the literature. Exposure to mucolytic drugs was arbitrarily defined as having received mucolytic drugs for at least 2 days (>200 mg) and at least until the day before the first signs of the suspected ADR.

Results

The non-exclusive paradoxical respiratory ADRs reported in 59 paediatric patients (median age 5 months, range 3 weeks to 34 months, 98% younger than 2 years old) were increased bronchorrhea or mucus vomiting (n = 27), worsening of respiratory distress during respiratory tract infection (n = 35), dyspnoea (n = 18), cough aggravation or prolongation (n = 11), and bronchospasm (n = 1). Fifty-one (86%) children required hospitalization or extended hospitalization because of the ADR; one patient died of pulmonary oedema after mucus vomiting.

Conclusion

Parents, physicians, pharmacists, and drug regulatory agencies should know that the benefit risk ratio of mucolytic drugs is at least null and most probably negative in infants according to available evidence.     

Hyperbilirubinemia and neurodevelopmental outcome of very low birthweight infants: results from the LIFT cohort

Background

Bilirubin-related neurotoxicity is an important clinical issue in very low birthweight (VLBW) infants, and the existing literature is inconsistent.

Objective

To analyze the relationship between maximal serum unconjugated bilirubin levels (SBL) and neurodevelopmental outcome at 2-year corrected age in VLBW infants.

Methods

Phototherapy was initiated in all infants born before 33 weeks of gestation, according to Maisels'' recommendations. Neurodevelopmental assessment at 2-year corrected age was performed in all infants that survived. SBLs collected during the first week of life were used to define three tertiles of max-SBL. The first tertile corresponded to infants with the lowest max-SBL.

Results and Conclusions

A total of 724 infants were included in the study, and among them, 631 (87%) were evaluated at two years old. The infants of the first tertile were younger and smaller than the infants of the other two tertiles, in accordance with Maisels'' recommendations for very small infants. No difference in the risk of impaired functional outcome among the three groups was observed. However, among infants weighing less than 1001 g, those in the third tertile had a poorer neurodevelopmental prognosis as compared to those in the second tertile (adjusted odds ratio = 6.8, 95% CI: 1.2–36.7, p = 0.03). Considering the results obtained, we propose 196 µmol/L (11.5 mg/dL) when birthweight varies between 1001 and 1500 g, and 170 µmol/L (9.9 mg/dL) when birthweight is less than 1001 g, as recommended max-SBLs (defined as maximal levels of 95^th percentile curves of SBLs in infants with an optimal outcome). When Maisels'' recommendations were applied, max SBLs were higher in 8% of infants weighing 1001–1500 g and in 15% of infants weighing less than 1001 g. Our data seems to validate Maisels'' recommendations in the overall population of infants born before 33 weeks of gestation, but not in infants weighing less than 1001 g.