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.

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.

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 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.

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.

Circadian variation of heart rate variability.

STUDY OBJECTIVE: The aim of the study was to examine the circadian variation in heart rate variability and to test the hypothesis that the variation is due to vagal influence. DESIGN: Human subjects, some with vagal neuropathy, underwent ambulatory 24 h electrocardiographic monitoring, the recordings being played back through an analyser which identified and timed successive pulse (R-R) intervals. Heart rate variability was measured for each 30 min period over 24 h as the standard deviation of the successive differences between R-R intervals, which filtered out low frequency components of heart rate variability that were not autonomic in origin. Modelled curves of heart rate variability were compared using analysis of variance. SUBJECTS: The subjects were aged between 33 and 65 years and were matched in three groups for age and sex. There were 11 healthy controls, 12 insulin dependent diabetics and seven alcoholics with vagal neuropathy. RESULTS: A significant circadian variation in heart rate variability was present, characterised by a rise during sleep. Mean heart rate variation was significantly reduced in groups with vagal neuropathy, although the amplitude of the cycle and time of peak variability was not significantly different. The circadian variation was sustained regardless of the degree of vagal neuropathy. CONCLUSIONS: The cycle of heart rate variability is not dependent on vagal interaction. It may be due to fluctuations in sympathetic activity affecting beat to beat variability.

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.

The effect of hypercapnia and hypoxemia on the cardiovascular responses to isoproterenol.

BACKGROUND: The reason for the increased risk of death with fenoterol and isoproterenol in asthma is unknown but may relate to their cardiovascular effects. Deaths from asthma usually occur outside hospital where hypoxemia, with or without hypercapnia, may exist. Both of these states can influence the cardiovascular system. We investigated whether different gas mixtures modified the cardiovascular effects of isoproterenol. METHOD: Nine healthy men were randomly assigned to receive each of three gas mixtures to achieve (1) normoxia-normocapnia, (2) hypercapnia (end-tidal PaCO2, 50 mm Hg), (3) hypoxemia-hypercapnia (arterial oxygen saturation, 90%; PaCO2, 50 mm Hg). Isoproterenol was administered with each of the gas mixtures. Cardiovascular measurements of heart rate, blood pressure, cardiac index, ejection fraction, fractional shortening, electromechanical systole, and the QTc interval were made before administration of the gases, as well as before and 5 minutes after isoproterenol administration. RESULTS: The changes after hypercapnia were not significantly different from those after normoxia-normocapnia. Hypoxemia-hypercapnia increased heart rate, systolic and diastolic blood pressure, QTc interval, cardiac index, ejection fraction, and fractional shortening. Isoproterenol increased heart rate, systolic blood pressure, QTc interval, cardiac index, ejection fraction, and fractional shortening while the subjects breathed the normoxia-normocapnia gas mixture. It caused similar changes with the other gas mixtures. The changes were additive. CONCLUSION: Isoproterenol and hypoxemia-hypercapnia will increase myocardial oxygen demand and could prove to be detrimental in severe asthma.

The pulmonary and extrapulmonary effects of inhaled beta-agonists in patients with asthma.

The cardiovascular, respiratory, and hypokalemic effects of repeated inhalation of fenoterol, albuterol, and isoproterenol were compared in 12 subjects with stable asthma according to a double-blind, crossover design. Ipratropium bromide served as a control providing bronchodilatation without extrapulmonary effects. Subjects inhaled the beta-agonists on an equal-weight basis (400 micrograms) at 0, 30, 40, and 45 minutes. Measurements of heart rate, blood pressure, total electromechanical systole (measure of inotropic activity), preejection period, QTc interval, plasma potassium levels, and forced expiratory volume in 1 second were made 5 minutes after each dose and again at 60 and 75 minutes. There were no differences in the bronchodilating effect between the beta-agonists. However, both fenoterol and isoproterenol resulted in greater positive inotropic stimulation than did albuterol, and fenoterol caused a greater fall in plasma potassium levels than did the other beta-agonists.

Lack of evidence for pituitary thyrotroph down-regulation after 1 week of oral thyrotrophin-releasing hormone and metoclopramide under conditions of constant peripheral thyroid hormone levels.

We investigated the pituitary thyrotrophin (TSH) response to repeated oral (non-pulsatile) thyrotrophin-releasing hormone (TRH) administration and potential modifying effects of dopamine antagonist treatment under conditions of constant peripheral thyroid hormone levels. In a randomized double-blind crossover trial, seven hypothyroid subjects, euthyroid on L-thyroxine, received 1 week each of oral TRH (40 mg, 12 hourly) plus metoclopramide (10 mg, 8 hourly) and TRH (40 mg, 12 hourly) plus placebo (one capsule, 8 hourly). At the beginning and end of each treatment period five samples of blood for estimation of serum TSH were taken over 1 h before ("baseline") and seven samples over 2 h after the treatment combination was given ("stimulated"). Serum free thyroxine, free triiodothyronine and prolactin levels also were measured. Mean log10 +/- SEM (log10 mIU/l) "baseline" serum levels TSH were -0.177 +/- 0.183 (median 0.345 mIU/l (untransformed); range (r) 0.03-10.11 mIU/l; first quartile (1q) 0.22 mIU/l; third quartile (3q) 2.48 mIU/l) before and 0.182 +/- 0.107 (median 1.385 mIU/l; r = 0.45-19.8 mIU/l; 1q = 0.9 mIU/l; 3q = 1.78 mIU/l) after 1 week of treatment (p < 0.02). There were no significant differences between oral TRH plus metoclopramide and oral TRH plus placebo. Peripheral thyroid hormone levels and the "stimulated" TSH response (expressed as area under curve after TRH and metoclopramide or placebo; min.log10 mIU/l) remained unchanged after 1 week. In the absence of changes in peripheral thyroid hormone levels, oral TRH over 1 week may not result in down-regulation of anterior pituitary thyrotrophs.2+ f2p4

The cardiovascular effects of inhaled fenoterol alone and during treatment with oral theophylline.

We have investigated whether oral theophylline potentiated the cardiovascular effects of fenoterol administered by metered-dose inhaler. Eight healthy subjects were investigated on four occasions. On successive days (1 and 2), the subjects were given doses of 400 micrograms, 600 micrograms, and 800 micrograms of fenoterol at 15-minute intervals (total dose, 1.8 mg) or matched placebo. Systolic time intervals, blood pressure, and the ECG were recorded at baseline and five minutes after each inhalation. Thereafter, the subjects were treated with slow-release theophylline for eight days. On days 9 and 10, the procedures on days 1 and 2 were repeated. The order of treatment was applied according to a crossover Latin-square design. The effects after theophylline alone were no different from placebo. Theophylline potentiated those hemodynamic effects of fenoterol due to enhanced cardiac sympathetic tone (mean +/- SE) as measured by a decrease in Q-S2I (-41.6 +/- 7.6 ms vs -27.3 +/- 5.9 ms; p = 0.0004), an increase in systolic BP (23.5 +/- 2.8 mm Hg vs 9.0 +/- 5.3 mm Hg; p = 0.00001), and an increase in heart rate (15.8 +/- 1.6 bpm vs 9.1 +/- 3.7 bpm; p = 0.0013). The responses mediated by beta 2-adrenergic receptor stimulation, namely, a decrease in PEP and diastolic BP, were not potentiated. Although fenoterol prolonged the Q-Tc interval and decreased T-wave amplitude, these effects were not potentiated by theophylline. Oral theophylline potentiates the positively inotropic and chronotropic effects of fenoterol.

Bronchial gland duct ectasia in fatal bronchial asthma: association with interstitial emphysema.

To determine the incidence of bronchial gland duct ectasia in fatal asthma and its association with interstitial emphysema, the histological features of 72 patients in whom death was considered to be due to asthma, and 72 matched control subjects in whom sudden death was not attributed to asthma, were reviewed. In all cases and controls, sections of two or more blocks of lung tissue stained with haematoxylin and eosin were obtained at necropsy. Bronchial gland duct ectasia was diagnosed if there was more than one abnormally dilated epithelial lined protrusion from a bronchus, extending through the smooth muscle layer. A histological diagnosis of asthma was made if four of the five following criteria were present: mucus plugging, basement membrane thickening, epithelial shedding, submucosal eosinophil leucocyte infiltration and smooth muscle hypertrophy. A histological diagnosis of asthma was made in 53 of 72 clinical cases of fatal asthma and in five of 72 control subjects. Interstitial emphysema was present in 10 clinical cases of fatal asthma, all of whom had bronchial gland duct ectasia and a histological diagnosis of asthma. Interstitial emphysema was not observed in control subjects. It is concluded that bronchial gland duct ectasia is a common histological feature of severe asthma, and that interstitial emphysema may be consequent on rupture of these dilated gland ducts.

Should treatment of mild to moderate hypertension be targeted? Results from a Markov cohort model incorporating multiple risk factors.

A series of guidelines for the treatment of mild to moderate hypertension have recommended that individuals with multiple cardiovascular risk factors should start treatment sooner, or at a lower level of diastolic pressure, compared with patients with an isolated elevation of blood pressure. A Markov cohort model was constructed to examine this claim. The cohorts consisted of mild to moderately hypertensive men with added cardiovascular risk factors: smoking, raised serum cholesterol, and presence of left ventricular hypertrophy on electrocardiogram. The results of the model confirm that the prognosis of hypertension is highly dependent on the presence of other risk factors. The average remaining life expectancy of two patients of identical age and level of diastolic pressure varied by as much as 10 to 24 years, depending on the presence of other risk factors. Depending on the patient, the gain in life expectancy due to treatment of hypertension ranged from 0.11 years to 1.03 years. However, the results also indicated that the additional benefit as a result of 'targeting' in people with multiple risk factors did not exceed 0.47 years for any of the patient categories analysed. The nature of these conclusions remained unaltered despite the use of quality-adjusted life years (QALYs), and varying assumptions about the benefit of treatment. In comparison the model indicated that the benefits of smoking cessation among hypertensive men were three to eight times greater than the expected benefits from antihypertensive therapy.

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.

A prospective randomized trial of external fixation and plaster cast immobilization in the treatment of distal radial fractures.

Distal radial fractures are common, and many methods of treatment have been reported but there are no studies that compare the different treatment methods. This randomized prospective study demonstrated no advantage in using an external fixator to immobilize reduced distal radial fractures over closed reduction and plaster cast immobilization in patients less than 60 years of age. The external fixator group had a significant complication rate.