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Summary Background Data from 12-week placebo-controlled trials have led to mounting concerns about increased mortality in patients with Alzheimer's disease (AD) who are prescribed antipsychotics; however, there are no mortality data from long-term placebo-controlled trials. We aimed to assess whether continued treatment with antipsychotics in people with AD is associated with an increased risk of mortality. Methods Between October, 2001, and December, 2004, patients with AD who resided in care facilities in the UK were enrolled into a randomised, placebo-controlled, parallel, two-group treatment discontinuation trial. Participants were randomly assigned to continue with their antipsychotic treatment (thioridazine, chlorpromazine, haloperidol, trifluoperazine, or risperidone) for 12 months or to switch their medication to an oral placebo. The primary outcome was mortality at 12 months. An additional follow-up telephone assessment was done to establish whether each participant was still alive 24 months after the enrolment of the last participant (range 24–54 months). Causes of death were obtained from death certificates. Analysis was by intention to treat (ITT) and modified intention to treat (mITT). This trial is registered with the Cochrane Central Registry of Controlled Trials/National Research Register, number ISRCTN33368770. Findings 165 patients were randomised (83 to continue antipsychotic treatment and 82 to placebo), of whom 128 (78%) started treatment (64 continued with their treatment and 64 received placebo). There was a reduction in survival in the patients who continued to receive antipsychotics compared with those who received placebo. Cumulative probability of survival during the 12 months was 70% (95% CI 58–80%) in the continue treatment group versus 77% (64–85%) in the placebo group for the mITT population. Kaplan–Meier estimates of mortality for the whole study period showed a significantly increased risk of mortality for patients who were allocated to continue antipsychotic treatment compared with those allocated to placebo (mITT log rank p=0·03; ITT p=0·02). The hazard ratio for the mITT group was 0·58 (95% CI 0·35 to 0·95) and 0·58 (0·36 to 0·92) for the ITT population. The more pronounced differences between groups during periods of follow up longer than 12 months were evident at specific timepoints (24-month survival 46% vs 71%; 36-month survival 30% vs 59%). Interpretation There is an increased long-term risk of mortality in patients with AD who are prescribed antipsychotic medication; these results further highlight the need to seek less harmful alternatives for the long-term treatment of neuropsychiatric symptoms in these patients. Funding UK Alzheimer's Research Trust.

Background: Large clinical outcome studies (AIM-HIGH and HPS-2THRIVE) are underway testing the strategy of adding high dose nicotinic acid (NA) to statin treatment. However, the effect of this on atherosclerosis progression is unknown. Hypothesis: Nicotinic acid 2g daily would reduce change in carotid wall area, assessed by MRI, compared to placebo. Methods: We performed a double-blind randomized placebo-controlled study of 2g once daily modified release NA added to background statin therapy in 71 patients with low HDL-C known coronary heart disease with type 2 diabetes mellitus or carotid / peripheral atherosclerosis The pre-specified primary end point was the change in carotid artery wall area, assessed by MRI, after 1 year. We compared the treatment effect using a mixed effect model adjusting for baseline covariates. Results: 22/35 NA and 29/36 placebo patients completed MRI at all time points. Baseline characteristics were similar. In the NA treated group, HDL-C increased 23% (39±6 to 48±7 mg/dL), and LDL-C decreased 19% (85±23 to 69±21 mg/dL). At 12 months, the NA group had a significantly higher reduction in carotid wall area compared to placebo (adjusted treatment difference [95% CI] = −1.64 mm 2 [−3.12, −0.16]; P=0.03). Median (IQR) change in carotid wall area was −1.42 mm 2 (−2.65, 0.79) for NA and 0.47 mm 2 (−0.97, 2.59) for placebo. At 12 months the change in carotid plaque index (calculated by the recognised method of normalising wall area to total vessel area) was also reduced compared to placebo (treatment difference −0.016 [−0.03, −0.0022]; P = 0.02). Even as early as six months, although there was no treatment difference for change in absolute carotid wall area (−0.98 mm 2 [−2.45, 0.49]; P = 0.2), change in carotid plaque index was already significantly lower in the NA treated group (−0.016 [−0.03, 0.0019]; P = 0.03). Conclusions: This is the first demonstration that addition of high dose modified-release nicotinic acid, to statin-treated patients with low HDL-C, reduces carotid atherosclerosis at 12 months compared to placebo.

Beating heart coronary artery bypass grafting (CABG) improves early post-operative cardiac function in patients with at least moderate ventricular function but its effects in patients with significantly impaired ventricular function is uncertain. We compared a novel hybrid technique of on-pump beating heart (ONBEAT) to conventional cardioplegic arrest (ONSTOP) in CABG patients with impaired ventricular function using cardiac magnetic resonance (CMR) and biochemical markers. In a single centre randomized trial, 50 patients with impaired ventricular function undergoing CABG were randomly assigned to ONBEAT or ONSTOP. Patients underwent CMR assessment for function and delayed hyperenhancement (HE) for irreversible injury pre-operatively and early post operatively; in addition serum was taken for cTn I and CKMB (0,1,6,24,48 and 120 hours) after surgery. Forty-five patients completed surgery with follow up imaging. Pre-operative characteristics were well matched except for a higher incidence of renal impairment in ONBEAT patients (glomerular filtration rate 58 versus 68 ml.min−1, p=0.02). Mean ± SD cardiac index (CI): ONBEAT 2.85±0.53 and ONSTOP 2.62±0.59L.min−1.m−2. After surgery both groups sustained minor changes to CI (4% reduction ONBEAT, p = 0.43 versus 1% increase ONSTOP, p = 0.97) without significant inter-group difference. The incidence of new HE was significantly higher in the ONBEAT group (p = 0.04) with 6/17 patients (35%) sustaining 8.2 ± 5.2 g of new HE each compared with 2/23 patients (9%) in the ONSTOP group each with 9.8 ± 9.0 g of new HE, p = 0.86. Furthermore serum markers of myocardial injury were higher in ONBEAT patients; median AUC for Troponin I 461[226 – 1141]μg/L versus 160[98 – 357]μg/L, p=0.002 and CKMB 862[499 – 1768]ng/mL versus 549[447–704]ng/mL p=0.004. The incidence of new irreversible myocardial injury was significantly higher in ONBEAT patients, although there was no effect on global cardiac function. Inadequate coronary perfusion in patients with severe proximal coronary disease and low cardiac output may render distal coronary territories ischemic in the absence of formal myocardial protection.

Context Immunization with a meningococcal tetravalent (serogroup ACWY) glycoconjugate vaccine is recommended for all US adolescents. However, the currently licensed vaccine is poorly immunogenic in infancy, when the highest rates of disease are observed. Objective To determine the immunogenicity of a novel tetravalent CRM197-conjugated meningococcal vaccine (MenACWY) in infants. Design, Setting, and ParticipantsRandomized, open-label, controlled study of 225 UK and 196 Canadian 2-month-olds from August 2004 to September 2006.Intervention UK infants received a primary course of MenACWY (at 2, 3, and 4 months or 2 and 4 months) or Neisseria meningitidis serogroup C monovalent meningococcal glycoconjugate vaccine (MenC) (at 2 and 4 months). All received MenACWY at 12 months. Canadian infants received MenACWY at 2, 4, and 6 months or 2 and 4 months; at 12 months they received MenACWY, a plain tetravalent polysaccharide vaccine, or no vaccine. Main Outcome MeasurePercentage of infants with a human complement serum bactericidal activity (hSBA) titer ≥1:4 after a primary course of MenACWY and after a 12-month booster. Safety and reactogenicity of MenACWY were also assessed.Results According to the prespecified per-protocol analysis, the percentages (95% CIs) of MenACWY 2-, 3-, and 4-month recipients with hSBA titers ≥1:4 after primary immunization were serogroup A, 93% (84%-98%); C, 96% (89%-99%); W-135, 97% (90%-100%); and Y, 94% (86%-98%). With a post hoc intention-to-treat analysis with imputed values for missing data, these values were unchanged for serogroups C and Y; for serogroup A, values were 92% (84%-97%), and for W-135, 97% (91%-99%). For the per-protocol analysis of MenACWY 2-, 4-, and 6-month recipients, the percentages (95% CIs) of responders were A, 81% (71%-89%); C, 98% (92%-100%); W-135, 99% (93%-100%); and Y, 98% (92%-100%). With the imputed value analysis, these values were A, 83% (74%-89%); C, 98% (93%-99%); W-135, 99% (94%-100%); and Y, 98% (92%-99%). At least 84% of MenACWY 2- and 4-month recipients achieved hSBA titers ≥1:4 for serogroups C, W-135, and Y after primary immunization, as did at least 60% for serogroup A (per-protocol and imputation analysis). At least 95% of primary and booster MenACWY recipients achieved hSBA titers ≥1:4 for serogroups C, W-135, and Y at 13 months, as did at least 84% for serogroup A (per-protocol and imputation analysis). During the primary immunization course, postimmunization pain on leg movement was observed in 2% of UK MenACWY 2- and 4-month recipients and 4% of MenC 2- and 4-month recipients; a temperature of 38°C or greater was observed in 4% and 2% in these groups, respectively. ConclusionMenACWY is well tolerated and immunogenic in infancy.Trial Registration clinicaltrials.gov Identifier: NCT00262002

We conducted a phase 3 randomized controlled trial looking at the immunogenicity and safety of a novel combined Haemophilus influenzae type b and Neisseria meningitidis serogroup C tetanus toxoid conjugate vaccine, Hib-MenC-TT in a 2-, 3-, and 4-month primary infant immunization schedule. SBA MenC titers > or =1:8 and anti-PRP concentrations > or =0.15 microg/mL were measured in 99.2% and 100%, respectively, of the infants receiving Hib-MenC-TT.

Background: Our objective was to systematically assess the differences in features, results, and usability of currently available meta-analysis programs. Methods: Systematic review of software. We did an extensive search on the internet (Google, Yahoo, Altavista, and MSN) for specialized meta-analysis software. We included six programs in our review: Comprehensive Meta-analysis (CMA), MetAnalysis, MetaWin, MIX, RevMan, and WEasyMA. Two investigators compared the features of the software and their results. Thirty independent researchers evaluated the programs on their usability while analyzing one data set. Results: The programs differed substantially in features, ease-of-use, and price. Although most results from the programs were identical, we did find some minor numerical inconsistencies. CMA and MIX scored highest on usability and these programs also have the most complete set of analytical features. Conclusion: In consideration of differences in numerical results, we believe the user community would benefit from openly available and systematically updated information about the procedures and results of each program's validation. The most suitable program for a meta-analysis will depend on the user's needs and preferences and this report provides an overview that should be helpful in making a substantiated choice.

Children who have siblings and/or who attend day care have higher rates of nasopharyngeal colonization with pneumococci than lone children do. Pneumococcal colonization is usually asymptomatic but is a prerequisite for invasive disease. We studied the effect of social mixing with other children on immunity to a pneumococcal vaccine. One hundred sixty children aged 1 year were immunized with a 7-valent conjugate pneumococcal vaccine. A blood sample was obtained before and 9 to 11 days after the vaccine. The concentration and avidity of antibody against vaccine pneumococcal serotypes (4, 6B, 9V, 14, 18C, 19F, and 23F) were studied in relation to pneumococcal carriage rate and measures of social mixing. Children with increased social mixing had higher antibody concentrations against serotypes 4, 9V, 14, and 23F than lone children did. The least-carried serotype, serotype 4, was the one of the most immunogenic. This contrasts with serotype 6B, the most common nasopharyngeal isolate but the least immunogenic. Social mixing in infancy enhances the immune response to a Streptococcus pneumoniae polysaccharide-protein conjugate vaccine at 1 year of age. Exposure to pneumococci in the first year of life may induce immunological priming. An alternative explanation is that differences in immunological experience, such as increased exposure to respiratory viral infections in early childhood, alters the response to vaccines perhaps by affecting the balance between Th1 and Th2 cytokines. The low immunogenicity of serotype 6B polysaccharide might make conditions more favorable for carriage of the 6B organism and explain why 6B pneumococci were more frequently isolated than other serotypes.

A preliminary cross-sectional study of 72 Hong Kong Chinese infants suggested that these infants learn to roll from supine-to-prone before rolling from prone-to-supine i.e. the opposite to teaching in most western texts. Three-hundred and sixty mothers were recruited postpartum and asked to record, on a chart, information related to the developmental milestone of rolling over for their infants (49% male) during the next 9 months. Telephone reminders were given at 4 and 8 months and, by the end of the study, information had been obtained from 240 mothers (67% of original sample, 51% male infants). Mean ages of rolling over were 5.1 months (SD1.5) for supine-to-prone and 5.7 months (SD1.3) for prone-to-supine. Age of rolling over from supine-to-prone was not influenced by usual sleep position, infant's sex, mother's intention to breastfeed infant, number of siblings, marital status, main daytime caregiver, or feeding method over 9 months. Hong Kong Chinese infants roll from supine-to-prone before they roll from prone-to-supine.

Meta-analysis has become a well-known method for synthesis of quantitative data from previously conducted research in applied health sciences. So far, meta-analysis has been particularly useful in evaluating and comparing therapies and in assessing causes of disease. Consequently, the number of software packages that can perform meta-analysis has increased over the years. Unfortunately, it can take a substantial amount of time to get acquainted with some of these programs and most contain little or no interactive educational material. We set out to create and validate an easy-to-use and comprehensive meta-analysis package that would be simple enough programming-wise to remain available as a free download. We specifically aimed at students and researchers who are new to meta-analysis, with important parts of the development oriented towards creating internal interactive tutoring tools and designing features that would facilitate usage of the software as a companion to existing books on meta-analysis. We took an unconventional approach and created a program that uses Excel as a calculation and programming platform. The main programming language was Visual Basic, as implemented in Visual Basic 6 and Visual Basic for Applications in Excel 2000 and higher. The development took approximately two years and resulted in the 'MIX' program, which can be downloaded from the program's website free of charge. Next, we set out to validate the MIX output with two major software packages as reference standards, namely STATA (metan, metabias, and metatrim) and Comprehensive Meta-Analysis Version 2. Eight meta-analyses that had been published in major journals were used as data sources. All numerical and graphical results from analyses with MIX were identical to their counterparts in STATA and CMA. The MIX program distinguishes itself from most other programs by the extensive graphical output, the click-and-go (Excel) interface, and the educational features. The MIX program is a valid tool for performing meta-analysis and may be particularly useful in educational environments. It can be downloaded free of charge via http://www.mix-for-meta-analysis.info or http://sourceforge.net/projects/meta-analysis .

To document causes of all unexpected child deaths under 2 years of age during a 4-year period (1999-2003), and to identify factors associated with sudden infant death syndrome (SIDS) in Hong Kong.The case-control component of the study compared information from SIDS deaths (n=16) with healthy controls (n=223) identified randomly from all births in Hong Kong. Coroner records of all deaths under 2 years of age were later reviewed.SIDS risk factors included prone sleep position, smoking by mother, bedsharing with someone other than the parents, and baby found with head covered. Eighteen deaths were officially classified as SIDS but, on review of the coroner records, there were 33 potential SIDS deaths (many labelled as unascertained/unknown).Hong Kong SIDS incidence has fallen from 0.3/1000 (95% CI: 0.18-0.46 in 1987) to 0.16/1000 (95% CI: 0.11-0.22 in 1999-2002). Despite the small number of cases, key SIDS risk factors are shown to be important in this population. Hong Kong needs to take steps to standardise the investigation and management of these deaths and to establish a child mortality review mechanism to provide feedback to the public, to the health authorities, and to health professionals.

Objectives To assess the clinical effectiveness of surgical stabilisation (spinal fusion) compared with intensive rehabilitation for patients with chronic low back pain. Design Multicentre randomised controlled trial. Setting 15 secondary care orthopaedic and rehabilitation centres across the United Kingdom. Participants 349 participants aged 18-55 with chronic low back pain of at least one year's duration who were considered candidates for spinal fusion. Intervention Lumbar spine fusion or an intensive rehabilitation programme based on principles of cognitive behaviour therapy. Main outcome measure The primary outcomes were the Oswestry disability index and the shuttle walking test measured at baseline and two years after randomisation. The SF-36 instrument was used as a secondary outcome measure. Results 176 participants were assigned to surgery and 173 to rehabilitation. 284 (81%) provided follow-up data at 24 months. The mean Oswestry disability index changed favourably from 46.5 (SD 14.6) to 34.0 (SD 21.1) in the surgery group and from 44.8 (SD14.8) to 36.1 (SD 20.6) in the rehabilitation group. The estimated mean difference between the groups was –4.1 (95% confidence interval –8.1 to –0.1, P = 0.045) in favour of surgery. No significant differences between the treatment groups were observed in the shuttle walking test or any of the other outcome measures. Conclusions Both groups reported reductions in disability during two years of follow-up, possibly unrelated to the interventions. The statistical difference between treatment groups in one of the two primary outcome measures was marginal and only just reached the predefined minimal clinical difference, and the potential risk and additional cost of surgery also need to be considered. No clear evidence emerged that primary spinal fusion surgery was any more beneficial than intensive rehabilitation.

Background: Continued or recurrent bleeding after endoscopic treatment for bleeding ulcer is a major adverse prognostic factor. Identification of such ulcers may allow for alternate treatments. Aim: To determine factors predicting treatment failure with combined adrenaline injection and heater probe thermocoagulation. Methods: Consecutive patients with bleeding peptic ulcers who received endoscopic therapy between January 1995 and March 1998 were studied. Data on clinical presentation, endoscopic findings, and treatment outcomes were collected prospectively. Multiple logistic regression analysis was used to identify independent risk factors for treatment failure. Results: During the study period, 3386 patients were admitted with bleeding peptic ulcers: 1144 (796 men, 348 women) with a mean age of 62.5 (SD 17.6) years required endoscopic treatment. There were 666 duodenal ulcers (58.2%), 425 gastric ulcers (37.2%), and 53 anastomotic ulcers (4.6%). Initial haemostasis was successful in 1128 patients (98.6%). Among them, 94 (8.2%) rebled in a median time of 48 hours (range 3–480). Overall failure rate was 9.6%. Mortality rate was 5% (57/1144). Multiple logistic regression analysis revealed that hypotension (odds ratio (OR) 2.21, 95% confidence interval (CI) 1.40–3.48), haemoglobin level less that 10 g/dl (OR 1.87, 95% CI 1.18–2.96), fresh blood in the stomach (OR 2.15, 95% CI 1.40–3.31), ulcer with active bleeding (OR 1.65, 95% CI 1.07–2.56), and large ulcers (OR 1.80, 95% CI 1.15–2.83) were independent factors predicting rebleeding. Conclusions: Larger ulcers with severe bleeding at presentation predict failure of endoscopic therapy.

A range of options are available for the conservative treatment of carpal tunnel syndrome (CTS).1-4 Non-operative methods include immobilisation of the affected hand with wrist splint; local injection of steroids and drugs such as diuretics and non-steroidal anti-inflammatory drugs.6-11 These oral drugs are thought to decrease the volume of swollen tissue within the CTS and are widely used, but there is limited clinical evidence for their role. This prospective randomised, double blind, placebo controlled study aimed at evaluating the effect of oral steroids in the symptomatic treatment of CTS. We recruited patients with newly diagnosed CTS of more than three months' duration with confirmatory electrophysiological results (prolonged median nerve distal motor latencies >4 ms or median ulnar palmar sensory latency difference >0.5 ms) including electromyographic recordings of the abductor …

IMPLICATIONS: There is always a danger of arterial puncture during central venous access. One can usually identify an inadvertent arterial puncture when the aspirated blood is bright red. This sign is removed if one were to put saline in the aspirating syringe, as dusky venous blood turns bright red on dilution.

OBJECTIVE: To examine the association of some common medical conditions with functional limitation in elderly Chinese aged 70 years and over, to estimate the percentage of disability attributable to individual diseases, and to attempt to identify predisposing factors by documenting the development of functional limitation over an 18-month period in those subjects with a particular disease who were independent initially. SUBJECTS AND METHODS: The cross-sectional data set consisted of 2,032 (999 M, 1,033 F) subjects aged 70 years and over recruited by random sampling (stratified by age and sex) of all recipients of old-age and disability allowance, which covers over 90% of the elderly population. Information regarding medical condition and functional assessment of ten basic activities of daily living using the Barthel Index were obtained by personal interviews and physical assessment of the respondents at their places of residence. The longitudinal data set consisted of 1,334 subjects with no functional limitation at baseline who were alive after 18 months. Functional status was reassessed. RESULTS: After adjusting for age and sex, diseases associated with severe functional limitation (Barthel Index < 15) were dementia, stroke, Parkinson's disease, and fractures. Those associated with mild to moderate functional limitation (Barthel Index 15-19) were the same, with the addition of asthma and diabetes mellitus. The attributable fraction for severe limitation was highest for stroke, dementia, and fractures. Stroke and arthritis were identified as diseases predisposing to mild to moderate functional limitation over an 18-month period among those subjects who were independent initially. CONCLUSION: Stroke, dementia, and fractures were the main chronic diseases associated with severe functional limitation in elderly Hong Kong Chinese. Attempts to reduce the disability burden in this population should target these diseases.

Objective: To determine the influence of some cardiovascular risk factors (hypertension, diabetes mellitus, smoking habit, physical activity, obesity, adverse lipid profile) in elderly Chinese aged 70 years and over, on overall mortality and morbidity from stroke and ischaemic heart disease. Design: Longitudinal study relating 18-month outcome to baseline values. Subjects: 2,032 subjects (999 men, 1,033 women), mean age 80 years, recruited by random sampling of the Old Age and Disability Allowance Schemes, which covers 90% of the Hong Kong elderly subjects, stratified by sex and 5-year age groups from 70 years onwards. Methods: At baseline, subjects were visited by interviewers to collect information regarding medical conditions, smoking habit, physical activity, and to measure their height, weight, skinfold thickness, and waist/hip ratio. A follow-up survey was carried out 18 months later to establish the development of any new stroke or ischaemic heart disease, and to note any deaths and the cause of such deaths from death certification. Results: In multivariate analysis overall mortality was negatively associated with body mass index and participation in physical activity, after adjusting for age and sex. Death from stroke was associated with a higher systolic blood pressure at baseline. Among survivors, the only significant associations observed were a negative association between body mass index and the development of heart disease, and a positive association between systolic blood pressure and development of stroke. Conclusions: Few associations between cardiovascular risk factors and morbidity and mortality were demonstrated in elderly Chinese with a mean age of 80 years. The only modifiable risk factor appears to be systolic blood pressure.

Body composition measurement by dual energy absorptiometry was carried out in 160 men (age 45-87 years) and 407 women (age 20-88 years) consisting of volunteers and 25 men and 14 women with chronic obstructive airways disease (COAD) not receiving steroids from a hospital respiratory clinic. The objectives of this study were to provide normal reference values for adult Chinese including the elderly; to examine the effect of age and COAD on body composition; and to compare the use of body mass index (BMI) as a measure of obesity or malnutrition compared with body composition measurements. Values for body composition were different when compared with studies in the Caucasian population. In both sexes, height and lean mass decreased in a linear fashion with aging. In men, total body water increased till the 55-65 age group and then decreased. In women, total body water and bone mineral content also decreased with aging in a linear fashion. Changes in weight, BMI, fat mass and percentage fat with aging were also present in women and followed a quadratic trend. BMI was not a sensitive index of obesity or undernutrition, having approximately only 50-60% sensitivity in detecting high percentage fat or low standardised lean mass values. COAD was associated with low BMI only. Body composition measurements changes with aging, and should be used instead of BMI as a better indication of obesity or undernutrition. Reference values derived from the appropriate ethnic group should be used.

Epidemiological and clinical studies have indicated that the thalassaemias may confer protection against malaria. The study reported here investigated this protective effect in vitro, using a new approach which controls for the potential effect of red cell size and age on the virulence of the parasite. A Percoll density gradient method was used to separate alpha- and beta-thalassaemic trait, haemoglobin H and normal red blood cells (RBC) into fractions of different density. Correlations between RBC density, age and size in fractions of all genotypes were established using red cell creatine as an index of cell age. The development of Plasmodium falciparum over 3 erythrocytic cycles (144 h) in whole blood as well as fractionated samples was monitored by slide microscopy and flow cytometry. A significantly reduced rate of parasite invasion and growth was demonstrated in RBC from all thalassaemic genotypes tested. Poor reinvasion rates were noted in the second and third cycles. Increased duration of culture and red cell age also had a greater negative impact on parasite growth in thalassaemic RBC. This poor growth rate was also associated with the arrest of parasite growth at the schizont stage (schizont maturation arrest) and the accumulation of abnormal, trophozoite/schizont stage parasites in the older thalassaemic RBC fractions. These findings suggest a defect in the number and viability of merozoites generated by parasites growing in thalassaemic RBC. Age related factors such as oxidant stress may play a key role in mediating this kind of protective mechanism and deserve further investigation.

ODASS is now at its lowest level in real terms for 25 years. When governments flaunt such commitments it is easy to be pessimistic. Yet the commitments and programme of action of WSSD provide an idealised blueprint from which steps can be taken to advocate for change. Dissemination of information clearly identifying what governments have, and have not, achieved will be a further part of this process. To this end we analysed British ODASS in greater detail. Although British ODASS has been criticised for being inappropriate, it is also thought by some to be one of the more effective and poverty-focused aid programmes. The results outlined below are thus not intended to represent a bestcase or worst-case scenario, but to draw attention to the issues and make constructive recommendations to improve the effectiveness and appropriateness of ODASS. The average annual British ODASS for the 5 years 1989–93 was 0·3% of gross national product (GNP), equivalent to an average of US$2982 million (£1=US$1.75) per annum. 56% of this aid was bilateral (arrangement between UK and individual recipient country) and 41% was multilateral (ODASS given to international organisations such as the European Union [47%], World Bank [29%], United Nations’ organisations [17%], other [7%]). The remaining 3% of British ODASS went on administration. The median percentage of bilateral British ODASS allocated to the social development sectors of education and health was 8% and 5%, respectively. 60% of bilateral education aid was other or unspecified, and only 6% was specifically allocated to primary education. 38% of bilateral ODASS was directed to the world’s least developed countries. Theoretically, these countries should be the recipients of the bulk of ODASS. Bilateral British ODASS spending on health and education in the least developed countries was 2·2% and 2·7%, respectively. Only 0·6% of bilateral British ODASS was spent specifically on primary (0·1%) and secondary (0·5%) education in such countries. During the 5 years 1989–93, of 128 countries receiving bilateral British ODASS, only 19 received assistance for primary education, 36 for secondary, and 75 for tertiary education. Primary and secondary education—arguably the key to social and economic development—receive only a fraction of ODASS worldwide. The World Bank and other international aid agencies are giving increasing lipservice to the importance of primary education. Yet our analysis estimates that only 0·0002% of British GNP is spent on primary education in the world’s least developed countries (bilateral aid). This staggeringly low percentage is of especial concern in view of the generally good reputation of British ODASS. An important step to help achieve the goals of the WSSD would be to “We are witnessing in countries throughout the world the expansion of prosperity for some, unfortunately accompanied by an expansion of unspeakable poverty for others. This glaring contradiction is unacceptable and needs to be corrected through urgent actions.”

Agents which decrease gastric mucosal blood flow (GMBF) are postulated to have beneficial effects in arresting gastrointestinal bleeding in cirrhotic patients with portal hypertension. Our objective was to test the hypothesis that in a dose that significantly lowers wedged hepatic venous pressure (WHVP), a bolus injection of somatostatin will significantly decrease GMBF in patients with portal hypertensive gastropathy (PHG). In this placebo-controlled, double-blind, crossover study, 20 cirrhotic patients with PHG were randomly assigned to receive either somatostatin followed by placebo (Group A) or placebo followed by somatostatin (Group B). Wedged hepatic venous pressure was monitored. GMBF in the antrum and corpus was assessed by reflectance spectrophotometry. Indices of hemoglobin concentration (IHb) and indices of oxygen content (ISO2) were recorded. Nine patients were assigned to Group A, and 11 to Group B. Mild PHG was seen in 16 patients, and severe PHG in 4 patients. Baseline WHVP, IHb, and ISO2 were similar in both treatment groups. Wedged hepatic venous pressure (WHVP) was significantly lowered [median, 17.6%; interquartile range (-27.0,-12.6%); P = 0.0008] after a 250-microg bolus injection of somatostatin. This dose of somatostatin significantly reduced IHb both in the antrum [-10.2% (-23.4, 0.4%)] and in the corpus [-5.8% (-16.6, 5.6%)] compared to placebo (P = 0.02 and 0.04, respectively). Intravenous bolus injection of 250 microg somatostatin significantly reduces WHVP and GMBF in patients with PHG. Whether this ability to decrease the GMBF in PHG makes somatostatin an effective treatment in acute gastrointestinal bleeding in PHG deserves to be studied.

Aims Combining the licensed Haemophilus influenzae type b (Hib) and serogroup C meningococcal (MenC) conjugate vaccine (Hib-MenC-TT) and DTaP-IPV vaccine could reduce the number of injections needed to administer the United Kingdom routine infant immunisation schedule. We aimed to demonstrate immunologic non-inferiority for Hib and MenC using a 6-in-1 combination vaccine (DTPa-IPV/Hib-MenC-TT) compared to a schedule using DTPa-IPV-Hib-TT and MenC-CRM197 conjugate vaccines. Secondary objectives included demonstration of non-inferiority of diphtheria, tetanus and polio immunogenicity; persistence of immune response to all antigens at 12 months of age and the response to a 12 month Hib-MenC-TT booster. Methods Open-label, randomised, multi-centre, UK study. Combination group received DTPa-IPV/Hib-MenC-TT at 2, 3, 4 months. Control group received DTPa-IPV-Hib-TT at 2, 3, 4 months and MenC-CRM197 at 3, 4 months. Both groups received Hib-MenC-TT booster at 12 months. Concomitant vaccines: pneumococcal conjugate vaccine at 2, 4, 13 months; MMR at 13 months. Blood tests were performed at 4, 5, 12 and 13 months. Results 142 children were randomised in each group. 100 children were included in the according-to-protocol cohort for analysis of immunogenicity following the booster vaccine in the combination group; and 112 children in the control group. One month post-primary immunisations 100% of the combination group and 93.3 % of control children had anti-PRP IgG concentration ≥0.15 μg/mL. 96.2% and 100% respectively had rSBA-MenC titres ≥1:8. One month post-booster all children met these thresholds. At 13 months of age, anti-PRP geometric mean concentrations (with 95% confidence intervals) were 66.7 (53.3-83.5) in the combination group and 26.9 (20.9-34.6) in the control group (4.35 [3.51-5.39] and 3.04 [2.21-4.19] respectively at 5 months). rSBA-MenC geometric mean titres (GMTs) were 3062.9 (2421.2-3874.6) and 954.0 (761.3-1195.5) respectively (393.2 [292.5-528.7] and 3110.5 [2612-3704.2] respectively at 5 months). Conclusion Non-inferiority of DTPa-IPV/Hib-MenC-TT compared to DTPa-IPV-Hib-TT plus MenC-CRM197 was demonstrated. The lower rSBA-MenC GMTs after primary immunisations and greater booster responses in the combination group suggest that immune priming might be inversely related to post-primary antibody responses. Furthermore, greater immunogenicity of TT conjugates used in primary and booster MenC vaccines in this group may be important.

Background Reporting of the flow of participants through each stage of a randomized trial is essential to assess the generalisability and validity of its results. We assessed the type and completeness of information reported in CONSORT (Consolidated Standards of Reporting Trials) flow diagrams published in current reports of randomized trials. Methods A cross sectional review of all primary reports of randomized trials which included a CONSORT flow diagram indexed in PubMed core clinical journals (2009). We assessed the proportion of parallel group trial publications reporting specific items recommended by CONSORT for inclusion in a flow diagram. Results Of 469 primary reports of randomized trials, 263 (56%) included a CONSORT flow diagram of which 89% (237/263) were published in a CONSORT endorsing journal. Reports published in CONSORT endorsing journals were more likely to include a flow diagram (62%; 237/380 versus 29%; 26/89). Ninety percent (236/263) of reports which included a flow diagram had a parallel group design, of which 49% (116/236) evaluated drug interventions, 58% (137/236) were multicentre, and 79% (187/236) compared two study groups, with a median sample size of 213 participants. Eighty-one percent (191/236) reported the overall number of participants assessed for eligibility, 71% (168/236) the number excluded prior to randomization and 98% (231/236) the overall number randomized. Reasons for exclusion prior to randomization were more poorly reported. Ninety-four percent (223/236) reported the number of participants allocated to each arm of the trial. However, only 40% (95/236) reported the number who actually received the allocated intervention, 67% (158/236) the number lost to follow up in each arm of the trial, 61% (145/236) whether participants discontinued the intervention during the trial and 54% (128/236) the number included in the main analysis. Conclusions Over half of published reports of randomized trials included a diagram showing the flow of participants through the trial. However, information was often missing from published flow diagrams, even in articles published in CONSORT endorsing journals. If important information is not reported it can be difficult and sometimes impossible to know if the conclusions of that trial are justified by the data presented.

Resume Randomised controlled trial to compare surgical stabilisation of the lumbar spine with an intensive rehabilitation programme for patients with chronic low back pain: The MRC spine stabilisation trial. BJM 2005 ; 330:1233-9. Prepare par Karen Grimmer, membre du comite de redaction, Australian Journal of Physiotherapy . Questions L’arthrodese est-elle plus efficace qu’un programme de reeducation intensive en terme d’amelioration de la capacite fonctionnelle, la marche, la qualite de vie et la souffrance psychologique des patients atteints de lombalgies chronique ? Quelle est la frequence des complications avec les deux types de traitements ? Protocole d’etude Essai controle randomise multicentrique en simple insu avec analyse en intention a traiter et la participation de 15 centres britanniques de chirurgie orthopedique et de reeducation fonctionnelle. Patients 349 patients âges de 18 a 55 ans presentant une lombalgie chronique depuis au moins un an consideres comme candidats a une arthrodese etaient randomises dans deux groupes de traitement, le premier par arthrodese (176 patients dont 139 ont effectivement eu une arthrodese) et le second par un programme de reeducation intensive basee sur les principes de la therapie cognitive comportementale (173 patients dont 151 ont effectivement participe au programme de reeducation). Interventions La technique de fusion etait laissee a la discretion du chirurgien. Le programme de reeducation intensive comportait des exercices quotidiens cinq jours par semaine pendant trois semaines. Mesures Ont ete mesures a 0, 6, 12 et 24 mois, l’indice d’Oswestry (echelle de 0-100), le perimetre de marche, la qualite de vie (SF-36) et l’impact psychologique (DRAM). Les criteres d’evaluation principaux etaient l’incapacite fonctionnelle et le perimetre de marche a deux ans. Resultats Le suivi etait de deux ans chez 81 % des patients. A deux ans, l’amelioration de l’incapacite fonctionnelle etait legerement plus grande dans le groupe arthrodese : moyenne et 95 % IC (4,1 [0,4-8,1]). Tous les autres parametres montraient une amelioration clinique sans differences significatives entre les deux groupes. Dix-neuf complications peroperatoires etaient notees dans le groupe arthrodese et aucune complication dans le groupe de reeducation intensive. Conclusions L’arthrodese permet une amelioration legerement plus importante qu’un programme de reeducation intensive en terme de capacite fonctionnelle chez les sujets souffrant de lombalgie chronique, candidats eventuels a une arthrodese. Les complications sont observees chez 14 % des patients traites chirurgicalement tandis que le taux de complications dans le groupe de reeducation est de 0 %.

To the Editor: We read with great interest the preliminary study by Niskakangas et al,1 “Association of Apolipoprotein E Polymorphism With Outcome After Aneurysmal Subarachnoid Hemorrhage.” Although in this paper the authors concluded that there is a significant association between apolipoprotein E e4 (apoE e4) and the outcome of subarachnoid hemorrhage (SAH) patients, we have some reservations about the methodology and its data analysis. The classification of CT findings used in this study was different from the original study of Fisher et al2: there are only 4 grades in Fisher’s grading scale, instead of the 5 grades shown in the article by Niskakangas et al. Each grade was clearly defined in the Fisher study, whereas the scale used in the Niskakangas study falls short of a clear definition. In their statistical analysis section, the authors then mention that the CT findings were allocated to 1 of the 4 categories. It would be helpful if the authors could clarify how they grouped the 5 grades into 4 categories during the statistical analysis. We noticed there was a fundamental problem with the data collection and presentation on the neurological outcome of patients. Patients from groups both with and without apoE e4 had a 0- to 57-month follow-up. This may contribute to inaccuracy and bias in the assessment of the patients neurological outcome after a SAH. The convention in neurological outcome assessment prescribes a duration of at least 6 months from the time of hemorrhage to the time of assessment, in order to ensure that the patient’s clinical condition and recovery are stable before assessment. …