Eczema-protective probiotic alters infant gut microbiome functional capacity but not composition: sub-sample analysis from a RCT.

Probiotic Lactobacillus rhamnosus HN001 given in early life has been shown to reduce infant eczema risk, but its effect on gut microbiota development has not been quantitatively and functionally examined. The aim of this study was to investigate the impact of early life probiotic exposure on the composition and functional capacity of infant gut microbiota from birth to 2 years considering the effects of age, delivery mode, antibiotics, pets and eczema. We performed shotgun metagenomic sequencing analysis of 650 infant faecal samples, collected at birth, 3, 12, and 24 months, as part of a randomised, controlled, 3-arm trial assessing the effect of L. rhamnosus HN001, Bifidobacterium animalis subsp. lactis HN019 supplementation on eczema development in 474 infants. There was a 50% reduced eczema risk in the HN001 probiotic group compared to placebo. Both mothers (from 35 weeks gestation until 6 months post-partum if breastfeeding) and infants (from birth to 2 years) received either a placebo or one of two probiotics, L. rhamnosus HN001 (6×109 cfu), or B. animalis subsp. lactis HN019 (9×109 cfu). L. rhamnosus HN001 probiotic supplementation was associated with increased overall glycerol-3 phosphate transport capacity and enrichment of L. rhamnosus. There were no other significant changes in infant gut microbiota composition or diversity. Increased capacity to transport glycerol-3-phosphate was positively correlated with relative abundance of L. rhamnosus. Children who developed eczema had gut microbiota with increased capacity for glycosaminoglycan degradation and flagellum assembly but had no significant differences in microbiota composition or diversity. Early life HN001 probiotic use is associated with both increased L. rhamnosus and increased infant gut microbiota functional capacity to transport glycerol-3 phosphate. The mechanistic relationship of such functional alteration in gut microbiota with reduced eczema risk and long-term health merits further investigation.

Effect of early probiotic supplementation on childhood cognition, behaviour and mood a randomised, placebo-controlled trial.

AIM: To determine whether probiotic supplementation in early life improves neurocognitive outcomes assessed at 11 years of age. METHODS: A total of 474 children who were born March 2004-Aug 2005 participated in a two-centre randomised placebo-controlled trial of infants at risk of developing allergic disease. Pregnant women were randomised to take Lactobacillus rhamnosus strain HN001, Bifidobacterium animalis subsp. lactis strain HN019 or placebo daily from 35 weeks gestation until six months if breastfeeding, and their infants the same treatment from birth to two years. Intelligence, executive function, attention, depression and anxiety were assessed when the children were 11 years of age. RESULTS: A total of 342 (72.2%) children were assessed (HN001 n = 109, HN019 n = 118 and placebo n = 115). Overall, there were no significant differences in the neurocognitive outcomes between the treatment groups. CONCLUSION: HN001 and HN019 given in early life were not associated with neurocognitive outcomes at 11 years of age in this study. However, we cannot exclude that other probiotics may have a beneficial effect. Further clinical trials are indicated.

Effect of Lactobacillus rhamnosus HN001 in Pregnancy on Postpartum Symptoms of Depression and Anxiety: A Randomised Double-blind Placebo-controlled Trial.

BACKGROUND: Probiotics may help to prevent symptoms of anxiety and depression through several putative mechanisms. OBJECTIVE: The aim of this study was to evaluate the effect of Lactobacillus rhamnosus HN001 (HN001) given in pregnancy and postpartum on symptoms of maternal depression and anxiety in the postpartum period. This was a secondary outcome, the primary outcome being eczema in the offspring at 12months of age. DESIGN, SETTING, PARTICIPANTS: A randomised, double-blind, placebo-controlled trial of the effect of HN001 on postnatal mood was conducted in 423 women in Auckland and Wellington, New Zealand. Women were recruited at 14-16weeks gestation. INTERVENTION: Women were randomised to receive either placebo or HN001 daily from enrolment until 6months postpartum if breastfeeding. OUTCOME MEASURES: Modified versions of the Edinburgh Postnatal Depression Scale and State Trait Anxiety Inventory were used to assess symptoms of depression and anxiety postpartum. TRIAL REGISTRATION: Australia NZ Clinical Trials Registry: ACTRN12612000196842. FINDINGS: 423 women were recruited between December 2012 and November 2014. 212 women were randomised to HN001 and 211 to placebo. 380 women (89.8%) completed the questionnaire on psychological outcomes, 193 (91.0%) in the treatment group and 187 (88.6%) in the placebo group. Mothers in the probiotic treatment group reported significantly lower depression scores (HN001 mean=7·7 (SD=5·4), placebo 9·0 (6·0); effect size -1·2, (95% CI -2·3, -0·1), p=0·037) and anxiety scores (HN001 12·0 (4·0), placebo 13·0 (4·0); effect size -1·0 (-1·9, -0·2), p=0·014) than those in the placebo group. Rates of clinically relevant anxiety on screening (score>15) were significantly lower in the HN001 treated mothers (OR=0·44 (0·26, 0·73), p=0·002). INTERPRETATION: Women who received HN001 had significantly lower depression and anxiety scores in the postpartum period. This probiotic may be useful for the prevention or treatment of symptoms of depression and anxiety postpartum. FUNDING SOURCE: Health Research Council of New Zealand (11/318) and Fonterra Co-operative Group Ltd.

Certainty and safe consequence responses provide additional information from multiple choice question assessments.

BACKGROUND: Clinicians making decisions require the ability to self-monitor and evaluate their certainty of being correct while being mindful of the potential consequences of alternative actions. For clinical students, this ability could be inferred from their responses to multiple-choice questions (MCQ) by recording their certainty in correctness and avoidance of options that are potentially unsafe. METHODS: Response certainty was assessed for fifth year medical students (n = 330) during a summative MCQ examination by having students indicate their certainty in each response they gave on the exam. Incorrect responses were classified as to their inherent level of safeness by an expert panel (response consequence). Analyses compared response certainty, response consequence across student performance groupings. RESULTS: As students' certainty in responses increased, the odds they answered correctly increased and the odds of giving unsafe answers decreased. However, from some ability groups the odds of an incorrect response being unsafe increased with high certainty. CONCLUSIONS: Certainty in, and safeness of, MCQ responses can provide additional information to the traditional measure of a number correct. In this sample, even students below standard demonstrated appropriate certainty. However, apart from those scoring lowest, student's incorrect responses were more likely to be unsafe when they expressed high certainty. These findings suggest that measures of certainty and consequence are somewhat independent of the number of correct responses to MCQs and could provide useful extra information particularly for those close to the pass-fail threshold.

Trends in the incidence of intensive care unit invasive mechanical ventilation and subsequent 2-year survival in very elderly New Zealanders.

BACKGROUND: The number of elderly in the general population is growing. There are therefore implications for the provision of intensive care unit (ICU) care to elderly patients. AIM: Our aim was to determine the incidence of ICU invasive mechanical ventilation (IMV), long-term outcomes of patients treated with IMV, and trends in these variables over a 10-year period in New Zealand, with a focus on very elderly patients (aged 80 years and over). METHODS: Analysis of New Zealand public hospital discharge data from July 1999 to June 2010, with linked long-term mortality data. Transfers or readmissions to different hospitals were linked using a national unique patient identifier. RESULTS: There were 58 003 patients treated with IMV in a New Zealand ICU. Of these patients, 6.6% were very elderly. Population rates of ICU IMV declined or were static over all age groups. The 2-year mortality rate ranged from 15% in patients aged 16-39 years to 52% in the very elderly. The 2-year mortality rates for the very elderly were highest for acute medical patients (78%), followed by acute surgical admissions (46%) and elective admissions (35%). The 2-year mortality rate for all patients declined over the study period, and declined or was static for all age groups and admission types. In the very elderly, the standardised mortality ratio of patients surviving at 1 year who survived their second year after admission, compared with the age-matched general population, was lower than all other age groups. CONCLUSION: For very elderly patients over the period 1999-2009, the population rate of IMV was static and 2-year mortality declined.

Early supplementation with Lactobacillus rhamnosus HN001 reduces eczema prevalence to 6 years: does it also reduce atopic sensitization?

BACKGROUND: The role of probiotics in prevention of allergic disease is still not clear; efficacy may depend on the timing, dose, duration, and specific probiotic used. Using a double-blind randomized placebo-controlled trial (Australian New Zealand Clinical Trials Registry: ACTRN12607000518460), we have shown that in a high-risk birth cohort, maternal supplementation from 35 weeks gestation until 6 months if breastfeeding and infant supplementation from birth until 2 years with Lactobacillus rhamnosus HN001 (HN001) (6 × 10(9) cfu/day) halved the cumulative prevalence of eczema at 2 and 4 years. Bifidobacterium animalis subsp lactis HN019 (HN019) (9 × 10(9) cfu/day) had no significant effect. OBJECTIVE: To determine whether differences in effects of HN001 and HN019 on eczema persist to age 6 years, and to investigate effects on sensitization. METHODS: Standard procedures were used to assess eczema (The UK Working Party's Criteria), eczema severity (SCORAD), atopic sensitization [skin prick tests (SPT), total and specific IgE] and standard questions used for asthma, wheeze, and rhinoconjunctivitis. RESULTS: HN001 was associated with significantly lower cumulative prevalence of eczema (HR = 0.56, 95% CI 0.39-0.80), SCORAD ≥ 10 (HR = 0.69, 0.49-0.98) and SPT sensitization (HR = 0.69, 95% CI 0.48-0.99). The point prevalence of eczema (RR = 0.66, 95% CI 0.44-1.00), SCORAD ≥ 10 (RR = 0.62, 95% CI 0.38-1.01) and SPT sensitization (RR = 0.72, 95% CI 0.53-1.00) were also reduced among children taking HN001. HN019 had no significant effect on any outcome. CONCLUSION AND CLINICAL RELEVANCE: This study provides evidence for the efficacy of the probiotic L. rhamnosus HN001 in preventing the development of eczema and possibly also atopic sensitization in high risk infants to age 6 years. The absence of a similar effect for HN019 indicates that benefits may be species specific.

A protective effect of Lactobacillus rhamnosus HN001 against eczema in the first 2 years of life persists to age 4 years.

BACKGROUND: Using a double blind randomized placebo-controlled trial (Australian New Zealand Clinical Trials Registry: ACTRN12607000518460), we have shown that in a high risk birth cohort, maternal supplementation from 35 weeks gestation until 6 months if breastfeeding and infant supplementation until 2 years with Lactobacillus rhamnosus HN001 (HN001) (6 × 10(9) cfu/day) halved the cumulative prevalence of eczema by age 2 years. Bifidobacterium animalis subsp lactis HN019 (HN019) (9 × 10(9) cfu/day) had no effect. OBJECTIVE: The aim of this study was to investigate the associations of HN001 and HN019 with allergic disease and atopic sensitization among these children at age 4 years, 2 years after stopping probiotic supplementation. METHODS: The presence (UK Working Party's Diagnostic Criteria) and severity SCORing Atopic Dermatitis (SCORAD) of eczema and atopy (skin prick tests) and parent-reported symptoms of asthma and rhinoconjunctivitis were assessed using standard protocols and questions. RESULTS: Four-hundred and seventy-four infants were eligible at birth of whom 425 (90%) participated in this follow-up. The cumulative prevalence of eczema by 4 years (Hazard ratio (HR) 0.57 (95% CI 0.39-0.83)) and prevalence of rhinoconjunctivitis at 4 years (Relative risk 0.38 (95% CI 0.18-0.83)) were significantly reduced in the children taking HN001; there were also nonsignificant reductions in the cumulative prevalence of SCORAD ≥ 10 (HR 0.74 (95% CI 0.52-1.05), wheeze (HR 0.79 (95% CI 0.59-1.07)) and atopic sensitization (HR = 0.72 (95% CI 0.48-1.06)). HN019 did not affect the prevalence of any outcome. CONCLUSIONS AND CLINICAL RELEVANCE: This study showed that the protective effect of HN001 against eczema, when given for the first 2 years of life only, extended to at least 4 years of age. This, together with our findings for a protective effect against rhinoconjunctivitis, suggests that this probiotic might be an appropriate preventative intervention for high risk infants.

Killing the canary: the international epidemiology of the homicide of media workers.

OBJECTIVES: To describe the international epidemiology of the homicide of media workers, and investigate country-level risk factors. METHODS: Data on the homicides occurring from 2002 to 2006 were collected and collated from five international databases. Analyses included consideration of seven existing international indices relating to human development, and to the social and political functioning of states. RESULTS: During the 5-year period, 370 deaths in 54 countries met our definitions of homicides and media workers. Almost all (89%) were nationals of the country in which they died. The annual number of such homicides globally has more than doubled, from 41 in 2002 to 104 in 2006 (including 49 in Iraq in 2006). Less than 25% of the homicides of media workers over the last 5 years have resulted in an arrest or prosecution. Statistically significant associations (p<0.001; Political Terror Scores, OR 1.15; Corruption Perceptions Index, OR 0.53; Overall Failed State Index, OR 1.05; Failed State Index 7, OR 1.52; Failed State Index 9, OR 1.55; Failed State Index 10, OR 1.61) were found on logistic regression between the occurrence of the homicide of media workers in countries and scoring on six of the seven indices associated with country-level sociopolitical development. These indices reflected high levels of political terror and corruption, low government legitimisation, poor human rights, and uncontrolled armed groups. However, in terms of the homicide rate for countries, these associations were significant for only four of the seven indices (the general functionality of government, ability of governments to control armed groups, the level of political terror, and the level of violation of rights). CONCLUSIONS: The homicide of media workers increased substantially in this 5-year period and was found to be particularly concentrated in selected countries such as Iraq. The authors were able to identify specific sociopolitical risk factors for homicide occurrence, and for homicide rates at the country level.

Comparison of two clinical Bleb grading systems.

PURPOSE: To evaluate 2 recently described grading systems for clinical grading of filtering surgery blebs: the Moorfields Bleb Grading System (MBGS) and the Indiana Bleb Appearance Grading Scale (IBAGS). DESIGN: Observational comparative study. PARTICIPANTS: Twenty-four glaucoma filtering blebs in 24 eyes of 17 patients. METHODS: Three observers in a prospective agreement study compared MBGS with IBAGS during slit-lamp examination. MAIN OUTCOME MEASURES: Comparison analyses were performed, including agreement, repeatability, and intraclass correlation coefficient (ICC). RESULTS: A wide range of bleb characteristics was represented in the cohort. Acceptable levels of intrasystem agreement were found in both systems: for IBAGS, overall agreement at the 0.5- and 1.0-unit levels were 80.6% and 97.6%, respectively, and for MBGS, these were 78.4% and 97.4% for morphologic and vascularity indices. Repeatability coefficients ranged from 0.5 to 1.4 for MBGS and 0.8 to 1.2 for IBAGS. The ICC values in the MBGS ranged from 0.18 to 0.72 for single measures and 0.39 to 0.88 for average measures. For IBAGS, the single-measure ICC values were between 0.06 and 0.53, and the average-measure ICC values were between 0.16 and 0.77. The MBGS ICC values for bleb size were higher than for IBAGS. CONCLUSIONS: Both methods are reproducible clinically and had generally high levels of interobserver agreement. Both have minor deficiencies that should be amenable to improvement. The MBGS performed similarly to the IBAGS for reproducibility, had higher ICC values for morphologic features, and captured extra vascularity data with probable clinical implications.

Fast foods - are they a risk factor for asthma?

BACKGROUND: Lifestyle changes over the last 30 years are the most likely explanation for the increase in allergic disease over this period. AIM: This study tests the hypothesis that the consumption of fast food is related to the prevalence of asthma and allergy. METHODS: As part of the International Study of Asthma and Allergies in Childhood (ISAAC) a cross-sectional prevalence study of 1321 children (mean age = 11.4 years, range: 10.1-12.5) was conducted in Hastings, New Zealand. Using standard questions we collected data on the prevalence of asthma and asthma symptoms, as well as food frequency data. Skin prick tests were performed to common environmental allergens and exercise-induced bronchial hyperresponsiveness (BHR) was assessed according to a standard protocol. Body mass index (BMI) was calculated as weight/height2 (kg/m2) and classified into overweight and obese according to a standard international definition. RESULTS: After adjusting for lifestyle factors, including other diet and BMI variables, compared with children who never ate hamburgers, we found an independent risk of hamburger consumption on having a history of wheeze [consumption less than once a week (OR = 1.44, 95% CI: 1.06-1.96) and 1+ times a week (OR = 1.65, 95% CI: 1.07-2.52)] and on current wheeze [consumption less than once a week (OR = 1.17, 95% CI: 0.80-1.70) and 1+ times a week (OR = 1.81, 95% CI: 1.10-2.98)]. Takeaway consumption 1+ times a week was marginally significantly related to BHR (OR = 2.41, 95% CI: 0.99-5.91). There was no effect on atopy. CONCLUSIONS: Frequent consumption of hamburgers showed a dose-dependent association with asthma symptoms, and frequent takeaway consumption showed a similar association with BHR.

Obesity and asthma in 11-12 year old New Zealand children in 1989 and 2000.

BACKGROUND: There has been a concurrent increase in the prevalence of obesity and asthma in recent years in New Zealand and other countries. METHODS: Two cross sectional surveys performed in 1989 and 2000 were used to test this association in children of mean age 11.7 years. Body mass index (BMI) was calculated as weight/height2 (kg/m2) and obesity and overweight defined according to an international standard. Standard questions were used to measure the prevalence of asthma symptoms. RESULTS: Significant increases in the prevalence of reported symptoms and disease between 1989 and 2000 were not explained by a concurrent increase in the prevalence of obesity. In 2000, multivariate analysis showed that increasing BMI standard deviation score was significantly associated with current wheeze (p=0.002), inhaled steroid use (p=0.004), and the use of any medication (p=0.001). None of the associations was significantly different for boys or girls. CONCLUSION: There is some evidence for an association of obesity with asthma symptoms and treatment but this does not explain the increasing prevalence of this disease.

Hip fracture incidence in New Zealand, revisited.

AIM: Earlier predictions of the incidence of hip fractures in the older adult population suggested that by 2011 the rate would rise to epidemic proportions. The purpose of this study was to compare the number hip fractures occuring in New Zealand from 1988 to 1999 with the hip fracture rate predicted in 1990 by Rockwood, Horne and Cryer. METHODS: Data on the number of patients admitted to New Zealand hospitals with a diagnosis of fractured neck of femur were obtained, and compared with weighted regression and baseline predictions of Rockwood et al. RESULTS: The numbers of hip fractures for females, from 1988 to 1993, were similar to the number predicted, yet have been significantly lower than stated predictions since 1995. For males, hip fracture numbers since 1995 were less than the weighted regressions predicted (NS). CONCLUSIONS: Numbers of hip fractures since 1995 have been fewer than predicted. Possible reasons for maintaining the rates of hospitalisation due to fractured neck of femur at pre-1995 levels, are discussed.

Reducing post-tonsillectomy pain with cryoanalgesia: a randomized controlled trial.

OBJECTIVE/HYPOTHESIS: To evaluate the use of cryoanalgesia in reducing post-tonsillectomy pain. STUDY DESIGN: A prospective, randomized double-blind study of 59 consecutive patients (age range, 8-40 y) undergoing tonsillectomy for recurrent tonsillitis. METHODS: All patients underwent bipolar tonsillectomy. At the completion of the tonsillectomy patients were randomly assigned to a control or a cryotherapy group. The cryotherapy patients had both their tonsillar fossa "supercooled" to between -20 degrees C and -32 degrees C for 1 minute. Patients recorded their pain using a visual analogue scale over the next 10 days. Patients were also monitored for postoperative complications, time until resumption of a normal diet, time back to work or school, and analgesic consumption. RESULTS: The two groups were similar for age and sex. There was a 28.3% reduction in mean pain scores over the 10 days in the cryotherapy compared to the control group. This difference did not significantly depend on the day after operation or time of the day. Cryotherapy patients also returned to work or school, on average, 4 days earlier than controls. There was no significant difference in postoperative complications between the two groups. CONCLUSION: Cryotherapy is a new technique that significantly reduces post-tonsillectomy pain without evidence of causing additional complications.

The sexual activity of 654 fourth form Hawkes Bay students.

AIMS: To describe the self reported patterns of sexual behaviour of 4th form High School Students from the Hawkes Bay region of New Zealand, in 1998. METHODS: Subjects completed a self administered written anonymous questionnaire in a supervised classroom situation. RESULTS: 654 4th form students, median age fourteen years, completed the questionnaire--45% male, 54% female. 39.4% of the sample reported having had sex/intercourse. Maori students were nearly three times (74.9%) as likely as European students (26.7%) to be sexually active (p < 0.0001). 20.1% of these sexually active 4th formers report more than five partners. 11.9% of the total group and 30.2% of those who are sexually active, reported having first sex at age 12 or younger. CONCLUSIONS: The sexual activity of this sample of 4th form students is higher than reported previously in New Zealand, particularly so for Maori. Further research is needed to examine sexual behaviours and attitudes of young New Zealanders in the different communities to enhance the development and provision of geographically and culturally appropriate early sexuality education programmes and services. These should be designed to have particular relevance to the needs of young Maori.

An investigation into the incidence of toxoplasmosis in pregnancy in New Zealand.

AIM: To estimate the incidence of toxoplasmosis in pregnancy in New Zealand and consider whether there is a case for screening women in pregnancy. METHODS: The risk of maternal and fetal infection with toxoplasmosis was derived by first determining the rate of maternal seroconversion based on seroprevalence studies. The age-specific number of seroconversions in pregnancy was then estimated from the birth rate. Using reported fetal infection rates after primary maternal infection, the expected number of congenitally infected infants in one year was estimated. These incidences were compared with the number of recognised cases of toxoplasmosis infection in pregnancy and the actual number of positive IgM results at the Wellington Hospital laboratory. Using national births data, this incidence was extrapolated to estimate the number of expected cases in New Zealand. RESULTS: The annual seroconversion rate was 0.62% (95% confidence interval 0.39-0.86). On this basis, 164 primary maternal infections are expected annually with 66 fetuses being infected. Ten patients tested positive for IgM in Wellington, which averaged only one case per year being identified over the time examined in this study. CONCLUSIONS: Very few of the expected cases in pregnancy are diagnosed. Reporting rates were low when toxoplasmosis was a notifiable disease. Other means of improving detection, reporting and the avoidance of infection are discussed. More information is required before screening can be recommended in New Zealand.

Acute cervical cord injury complicating Klippel-Feil deformity and mimicking 'man in the barrel' syndrome.

This case illustrates the need to recognize a high cervical cord injury as a cause for bi-brachial weakness with intact bi-crural power, a pattern termed aptly by Sage as 'man in the barrel' syndrome. The patient who had an undiagnosed Klippel-Feil deformity had incurred his cervical injury after a collapse.

Treatment of hypothyroidism with once weekly thyroxine.

We compared daily T4 therapy with 7 times the normal daily dose administered once weekly in 12 hypothyroid subjects in a randomized cross-over trial. At the end of each treatment we measured serum free T4 (FT4), free T3 (FT3), rT3, and TSH levels and multiple markers of thyroid hormone effects at the tissue level repeatedly for 24 h. Compared with daily administration, the mean serum TSH before the administration of weekly T4 was higher (weekly, 6.61; daily, 3.92 microIU/mL; P < 0.0001), and the mean FT4 (weekly, 0.98; daily, 1.35 ng/dL; P < 0.01) and FT3 (weekly, 208, daily, 242 pg/dL; P < 0.01) were lower. A minimally elevated serum total cholesterol during weekly administration (weekly, 246.8; daily, 232.6 mg/dL; P < 0.03) was the only evidence of hypothyroidism at the tissue level. Compared with daily administration, the mean peak FT4 following weekly administration of T4 was significantly higher (weekly, 2.71; daily, 1.59 ng/dL; P < 0.0001), as was the mean peak FT3 level (weekly, 285; daily, 246 pg/dL; P < 0.01). None of the tissue markers of thyroid hormone effect changed compared to daily T4, and there was no evidence of treatment toxicity, including cardiac toxicity. During weekly T4 administration, autoregulatory mechanisms maintain near-euthyroidism. For complete biochemical euthyroidism a slightly larger dose than 7 times the normal daily dose may be required.