Podiatry intervention versus usual care to prevent falls in care homes: pilot randomised controlled trial (the PIRFECT study).

BACKGROUND: Common foot problems are independent risk factors for falls in older people. There is evidence that podiatry can prevent falls in community-dwelling populations. The feasibility of implementing a podiatry intervention and trial in the care home population is unknown. To inform a potential future definitive trial, we performed a pilot randomised controlled trial to assess: (i) the feasibility of a trial of a podiatry intervention to reduce care home falls, and (ii) the potential direction and magnitude of the effect of the intervention in terms of number of falls in care home residents. METHODS: Informed by Medical Research Council guidance on developing and evaluating complex interventions, we conducted a single blind, pilot randomised controlled trial in six care homes in the East of Scotland. Participants were randomised to either: (i) a three month podiatry intervention comprising core podiatry care, foot and ankle exercises, orthoses and footwear provision or (ii) usual care. Falls-related outcomes (number of falls, time to first fall) and feasibility-related outcomes (recruitment, retention, adherence, data collection rates) were collected. Secondary outcomes included: generic health status, balance, mobility, falls efficacy, and ankle joint strength. RESULTS: 474 care home residents were screened. 43 (9.1%) participants were recruited: 23 to the intervention, 20 to control. Nine (21%) participants were lost to follow-up due to declining health or death. It was feasible to deliver the trial elements in the care home setting. 35% of participants completed the exercise programme. 48% reported using the orthoses 'all or most of the time'. Completion rates of the outcome measures were between 93% and 100%. No adverse events were reported. At the nine month follow-up period, the intervention group per-person fall rate was 0.77 falls vs. 0.83 falls in the control group. CONCLUSIONS: A podiatry intervention to reduce falls can be delivered to care home residents within a pilot randomised controlled trial of the intervention. Although not powered to determine effectiveness, these preliminary data provide justification for a larger trial, incorporating a full process evaluation, to determine whether this intervention can significantly reduce falls in this high-risk population. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02178527 ; Date of registration: 17 June 2014.

Maternal and fetal factors which influence cord blood glucose levels in term infants delivered by cesarean section.

AIM: To assess factors contributing to cord venous glucose homeostasis in term infants delivered by elective cesarean section. METHODS: Observational study of women-infant pairs at delivery. Biochemical and clinical data were collected about factors which might affect the levels of glucose, lactate, norepinephrine, epinephrine, cortisol, human growth hormone, glucagon, and insulin. RESULTS: In the context of this data-set, three models explained a substantial amount regarding the variation: 79% of the variation in cord glucose levels is explained by levels of maternal glucose, cord venous pH, and cord lactate; 77% of the variation of cord lactate is explained by levels of cord venous pH, valine, maternal lactate and glucose, and cord norepinephrine; and 71% of the variation in cord norepinephrine is explained by levels of cord venous pO2, maternal lactate, cord insulin, cord GABA (gamma-aminobutyric acid), cord lactate, cord epinephrine, cord norepinephrine sulfate, and cord valine. CONCLUSIONS: Term infants delivered by cesarean section are relatively hyperinsulinemic (insulin:glucose ratio of 2.4) and glucose levels are strongly associated with maternal glucose levels, cord pO2, and lactate levels. There were no associations with levels of cord glucose and levels of cortisol, epinephrine and lactate, which have been shown to be important contributors to postnatal glucose homeostasis in some infant groups.

Tailored second-line therapy in asthmatic children with the Arg(16) genotype.

The Arg(16) ß(2) receptor genotype confers increased susceptibility to exacerbations in asthmatic children taking regular LABA (long-acting ß(2) agonists). We therefore evaluated using montelukast as an alternative to salmeterol as tailored second-line asthma controller therapy in children expressing this susceptible genotype. A total of 62 persistent asthmatic children with the homozygous Arg16 genotype were randomized to receive salmeterol (50 µg, b.i.d.) or montelukast (5 or 10 mg, once daily) as an add-on to inhaled fluticasone for 1 year. School absences (the primary outcome) were reduced with montelukast compared with salmeterol {difference in score=-0.40 [95% CI (confidence interval), -0.22 to -0.58]; P=0.005}. Salbutamol use was also reduced with montelukast compared with salmeterol [difference in score=-0.47 (95% CI, -0.16 to -0.79); P<0.0001]. Greater improvements occurred in both symptom and quality of life scores with montelukast against salmeterol, whereas there was no difference in FEV(1) (forced expiratory volume in 1 s). In conclusion, montelukast may be suitable as tailored second-line controller therapy instead of salmeterol in asthmatic children expressing the susceptible Arg(16) genotype, a move towards a personalized medicine approach to management.

Diagnostic accuracy of transrectal elastosonography (TRES) imaging for the diagnosis of prostate cancer: a systematic review and meta-analysis.

To assess the diagnostic performance of transrectal elastosonography (TRES) for the detection of prostate cancer. Two reviewers independently extracted the data from each study. Quality was assessed with a validated quality assessment tool for diagnostic accuracy studies. Diagnostic accuracy of TRES in relation to current standard references (transrectal ultrasonography [TRUS] biopsies and histopathology of radical prostatectomy [RP] specimens) was estimated. A bivariate random effects model was used to obtain sensitivity and specificity values. Hierarchical summary receiver operating characteristic (HSROC) were calculated. In all, 16 studies (2278 patients) were included in the review. Using histopathology of the RP specimen as reference standard, the pooled data of four studies showed that the sensitivity of TRES ranged between 0.71 to 0.82 and the specificity ranged between 0.60 to 0.95 (pooled diagnostic odds ratio [DOR] 19.6; 95% confidence interval [CI] 7.7-50.03). The sensitivity varied from 0.26 to 0.87 and specificity varied from 0.17 to 0.76 (pooled DOR 2.141; 95% CI 0.525 to -8.737) using TRUS biopsies (minimum of 10) as a reference standard. The quality of most studies was modest. SROC estimated 0.8653 area under the curve predicting high chances of detecting prostate cancer. There were no health economics or health-related quality of life of the participants reported in the studies and all the studies used compressional technique with no reported standardisation. The TRES technique appears to improve the detection of prostate cancer compared with systematic biopsy and shows a good accuracy in comparison with histopathology of the RP specimen. However, studies lacked standardisation of the technique, had poor quality of reporting and a large variation in the outcomes based on the reference standards and techniques used.

Preoperative serum C-reactive protein levels and post-operative lymph node ratio are important predictors of survival after pancreaticoduodenectomy for pancreatic ductal adenocarcinoma.

CONTEXT: There is paucity of data on the prognostic value of pre-operative inflammatory response and post-operative lymph node ratio on patient survival after pancreatic-head resection for pancreatic ductal adenocarcinoma. OBJECTIVES: To evaluate the role of the preoperative inflammatory response and postoperative pathology criteria to identify predictive and/or prognostic variables for pancreatic ductal adenocarcinoma. DESIGN: All patients who underwent pancreaticoduodenectomy for pancreatic ductal adenocarcinoma between 2002 and 2008 were reviewed retrospectively. The following impacts on patient survival were assessed: i) preoperative serum CRP levels, white cell count, neutrophil count, neutrophil/lymphocyte ratio, lymphocyte count, platelet/lymphocyte ratio; and ii) post-operative pathology criteria including lymph node status and lymph node ratio. RESULTS: Fifty-one patients underwent potentially curative resection for pancreatic ductal adenocarcinoma during the study period. An elevated preoperative CRP level (greater than 3 mg/L) was found to be a significant adverse prognostic factor (P=0.015) predicting a poor survival, whereas white cell count (P=0.278), neutrophil count (P=0.850), neutrophil/lymphocyte ratio (P=0.272), platelet/lymphocyte ratio (P=0.532) and lymphocyte count (P=0.721) were not significant prognosticators at univariate analysis. Presence of metastatic lymph nodes did not adversely affect survival (P=0.050), however a raised lymph node ratio predicted poor survival at univariate analysis (P<0.001). The preoperative serum CRP level retained significance at multivariate analysis (P=0.011), together with lymph node ratio (P<0.001) and tumour size (greater than 2 cm; P=0.008). CONCLUSION: A pre-operative elevated serum CRP level and raised post-operative lymph node ratio represent significant independent prognostic factors that predict poor prognosis in patients undergoing curative resection for pancreatic ductal adenocarcinoma. There is potential for future neo-adjuvant and adjuvant treatment strategies in pancreatic cancer to be tailored based on preoperative and postoperative factors that predict a poor survival.

Meta-analysis of Prolene Hernia System mesh versus Lichtenstein mesh in open inguinal hernia repair.

BACKGROUND: This study was designed to systematically analyse all published randomized clinical trials comparing the Prolene Hernia System (PHS) mesh and Lichtenstein mesh for open inguinal hernia repair. METHOD: A literature search was performed using the Cochrane Colorectal Cancer Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials in the Cochrane Library, MEDLINE, Embase and Science Citation Index Expanded. Randomized trials comparing the Lichtenstein Mesh repair (LMR) with the Prolene Hernia System were included. Statistical analysis was performed using Review Manager Version 5.1 software. The primary outcome measures were hernia recurrence and chronic pain after operation. Secondary outcome measures included surgical time, peri-operative complications, time to return to work, early and long-term postoperative complications. RESULTS: Six randomized clinical trials were identified as suitable, containing 1313 patients. There was no statistical difference between the two types of repair in operation time, time to return to work, incidence of chronic groin pain, hernia recurrence or long-term complications. The PHS group had a higher rate of peri-operative complications, compared to Lichtenstein mesh repair (risk ratio (RR) 0.71, 95% confidence interval 0.55-0.93, P=0.01). CONCLUSION: The use of PHS mesh was associated with an increased risk of peri-operative complications compared to LMR. Both mesh repair techniques have comparable short- and long-term outcomes.

Effect of high-dose allopurinol on exercise in patients with chronic stable angina: a randomised, placebo controlled crossover trial.

BACKGROUND: Experimental evidence suggests that xanthine oxidase inhibitors can reduce myocardial oxygen consumption for a particular stroke volume. If such an effect also occurs in man, this class of inhibitors could become a new treatment for ischaemia in patients with angina pectoris. We ascertained whether high-dose allopurinol prolongs exercise capability in patients with chronic stable angina. METHODS: 65 patients (aged 18-85 years) with angiographically documented coronary artery disease, a positive exercise tolerance test, and stable chronic angina pectoris (for at least 2 months) were recruited into a double-blind, randomised, placebo-controlled, crossover study in a hospital and two infirmaries in the UK. We used computer-generated randomisation to assign patients to allopurinol (600 mg per day) or placebo for 6 weeks before crossover. Our primary endpoint was the time to ST depression, and the secondary endpoints were total exercise time and time to chest pain. We did a completed case analysis. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN 82040078. FINDINGS: In the first treatment period, 31 patients were allocated to allopurinol and 28 were analysed, and 34 were allocated to placebo and 32 were analysed. In the second period, all 60 patients were analysed. Allopurinol increased the median time to ST depression to 298 s (IQR 211-408) from a baseline of 232 s (182-380), and placebo increased it to 249 s (200-375; p=0.0002). The point estimate (absolute difference between allopurinol and placebo) was 43 s (95% CI 31-58). Allopurinol increased median total exercise time to 393 s (IQR 280-519) from a baseline of 301 s (251-447), and placebo increased it to 307 s (232-430; p=0.0003); the point estimate was 58 s (95% CI 45-77). Allopurinol increased the time to chest pain from a baseline of 234 s (IQR 189-382) to 304 s (222-421), and placebo increased it to 272 s (200-380; p=0.001); the point estimate was 38 s (95% CI 17-55). No adverse effects of treatment were reported. INTERPRETATION: Allopurinol seems to be a useful, inexpensive, well tolerated, and safe anti-ischaemic drug for patients with angina. FUNDING: British Heart Foundation.

No differences in mortality between users of pancreatic-specific and non-pancreatic-specific sulphonylureas: a cohort analysis.

To assess whether users of pancreatic-specific sulphonylureas are at reduced risk of mortality and cardiovascular mortality compared with users of non-specific sulphonylureas, we conducted a cohort study in the population of Tayside, Scotland. We identified 3331 patients with type 2 diabetes who were newly treated with sulphonylureas between 1994 and 2001 and categorized them into those treated with only pancreatic-specific sulphonylureas and those treated with only non-specific sulphonylureas. The risks of mortality and cardiovascular mortality were compared in a survival analysis. There were 2914 patients treated with pancreatic-specific sulphonylureas only, of which 683 (23.4%) died. Of 186 patients treated with non-specific drugs only, 40 (21.5%) died. After adjusting for confounding factors, the adjusted risk ratios (with 95% CI) for mortality and cardiovascular mortality were 0.84 (0.61 to 1.17) and 0.81 (0.59 to 1.11) among the non-specific users compared with the pancreatic-specific users. This provides no evidence that there are differences between the two sulphonylureas types.

Estimation of typical food portion sizes for children of different ages in Great Britain.

It is often the case in dietary assessment that it is not practicable to weigh individual intakes of foods eaten. The aim of the work described was to estimate typical food portion weights for children of different ages. Using the data available from the British National Diet and Nutrition Surveys of children aged 1 1/2-4 1/2 years (1992-1993) and young people aged 4-18 years (1997), descriptive statistics were obtained, and predicted weights were calculated by linear, quadratic and exponential regression for each age group. Following comparison of energy and nutrient intakes calculated from actual (from an earlier weighed intake study) and estimated portion weights, the final list of typical portion sizes was based on median portion weights for the 1-3- and 4-6-year age groups, and age-adjusted means using linear regression for the 7-10-, 11-14- and 15-18-year age groups. The number of foods recorded by fifty or more children was 133 for each of the younger age groups (1-3 and 4-6 years) and seventy-five for each of the older age groups. The food portion weights covered all food groups. All portion sizes increased with age with the exception of milk in tea or coffee. The present study draws on a unique source of weighed data on food portions of a large sample of children that is unlikely to be repeated and therefore provides the best possible estimates of children's food portion sizes in the UK.

A comparison of bilateral and unilateral upper-limb task training in early poststroke rehabilitation: a randomized controlled trial.

OBJECTIVE: To compare the effects of bilateral task training with unilateral task training on upper-limb outcomes in early poststroke rehabilitation. DESIGN: A single-blinded randomized controlled trial, with outcome assessments at baseline, postintervention (6 wk), and follow-up (18 wk). SETTING: Inpatient acute and rehabilitation hospitals. PARTICIPANTS: Patients were randomized to receive bilateral training (n=56) or unilateral training (n=50) at 2 to 4 weeks poststroke onset. INTERVENTION: Supervised bilateral or unilateral training for 20 minutes on weekdays over 6 weeks using a standardized program. MAIN OUTCOME MEASURES: Upper-limb outcomes were assessed by Action Research Arm Test (ARAT), Rivermead Motor Assessment upper-limb scale, and Nine-Hole Peg Test (9HPT). Secondary measures included the Modified Barthel Index, Hospital Anxiety and Depression Scale, and Nottingham Health Profile. All assessment was conducted by a blinded assessor. RESULTS: No significant differences were found in short-term improvement (0-6 wk) on any measure (P>.05). For overall improvement (0-18 wk), the only significant between-group difference was a change in the 9HPT (95% confidence interval [CI], 0.0-0.1; P=.05) and ARAT pinch section (95% CI, 0.3-5.6; P=.03), which was lower for the bilateral training group. Baseline severity significantly influenced improvement in all upper-limb outcomes (P<.05), but this was irrespective of the treatment group. CONCLUSIONS: Bilateral training was no more effective than unilateral training, and in terms of overall improvement in dexterity, the bilateral training group improved significantly less. Intervention timing, task characteristics, dose, and intensity of training may have influenced the results and are therefore areas for future investigation.

Evaluation of a questionnaire to measure parent/carer and child/young person experience of NHS epilepsy services.

PURPOSE: To validate a patient-reported-experience-measure, PREM, of the NHS paediatric epilepsy service. METHODS: Section 1 of the PREM recorded demographic and clinical characteristics, and Section 2 collected information about the users' experience with the service. Section 2 included eighteen statements around three constructs: communication and provision of information to service users, interpersonal skills of staff, and clinic visits and accessibility to the services. Face validity, construct validity, internal reliability, and internal consistency were used to examine the robustness of these statements. The PREM was completed by parents/carers and also children/young people. RESULTS: PREMs were received from 145 of the 192 audit units; 2335 completed forms were returned; the attitude statements were completed by 750 children/young people and 1550 parents/carers. Face validity of the PREM was good. Construct validity was indecisive; confirmatory factor analysis of the hypothesised construct was weak. Exploratory factor analysis identified a four factor solution for the parent/carers dataset and a five factor solution for the children/young people's dataset. Internal reliability was good for the parent/carers dataset but less good for the children/young people. Internal consistency was moderately good for both datasets. CONCLUSIONS: These findings indicate that the PREM is likely to be a valid tool with the potential to elicit a wide variety of reliable views from parents/carers of children with epilepsy. The construct validity for the PREM should be reassessed with confirmatory factor analysis in a new dataset. More work needs to be undertaken with children/young people to design statements that capture their specific needs.

Global dengue death before and after the new World Health Organization 2009 case classification: A systematic review and meta-regression analysis.

BACKGROUND: Since the introduction of 2009 WHO dengue case classification, no literature was found regarding its effect on dengue death. This study was to evaluate the effect of 2009 WHO dengue case classification towards dengue case fatality rate. METHODS: Various databases were used to search relevant articles since 1995. Studies included were cohort and cross-sectional studies, all patients with dengue infection and must report the number of death or case fatality rate. The Joanna Briggs Institute appraisal checklist was used to evaluate the risk of bias of the full-texts. The studies were grouped according to the classification adopted: WHO 1997 and WHO 2009. Meta-regression was employed using a logistic transformation (log-odds) of the case fatality rate. The result of the meta-regression was the adjusted case fatality rate and odds ratio on the explanatory variables. RESULTS: A total of 77 studies were included in the meta-regression analysis. The case fatality rate for all studies combined was 1.14% with 95% confidence interval (CI) of 0.82-1.58%. The combined (unadjusted) case fatality rate for 69 studies which adopted WHO 1997 dengue case classification was 1.09% with 95% CI of 0.77-1.55%; and for eight studies with WHO 2009 was 1.62% with 95% CI of 0.64-4.02%. The unadjusted and adjusted odds ratio of case fatality using WHO 2009 dengue case classification was 1.49 (95% CI: 0.52, 4.24) and 0.83 (95% CI: 0.26, 2.63) respectively, compared to WHO 1997 dengue case classification. There was an apparent increase in trend of case fatality rate from the year 1992-2016. Neither was statistically significant. CONCLUSIONS: The WHO 2009 dengue case classification might have no effect towards the case fatality rate although the adjusted results indicated a lower case fatality rate. Future studies are required for an update in the meta-regression analysis to confirm the findings.

Population-level incidence and monitoring of adverse drug reactions with long-term amiodarone therapy.

INTRODUCTION: Amiodarone is associated with significant long-lasting adverse drug reactions (ADRs). Guidelines recommend laboratory monitoring during long-term use. However, data of compliance with laboratory monitoring are lacking. AIMS: The aim of this study was to assess laboratory monitoring of liver and thyroid function during amiodarone prescribing from 1989 to 2011 in the Tayside, UK, population (approximately 400 000) in relation to National Guidelines recommending laboratory monitoring every 6 months. We also report the population-level incidence of abnormal liver and thyroid function in relation to total exposure of amiodarone. METHODS: Utilizing well-established record-linkage database, a longitudinal retrospective analysis of 1413 patients on long-term amiodarone was carried out, analyzing prescribing, biochemical, and clinical data. RESULTS: Forty-six percent (46%), 28%, and 21% of patients underwent liver, thyroid, and combined testing, respectively, in accordance with guideline recommendations. Thirteen percent and 17% of patients did not have any ALT or TSH testing, respectively. During follow-up, 117 (9.5%) patients had an ALT 3×ULN and 16% patients had an abnormal TSH, (n=125, <0.4 mU/L and n=28, >10 mU/L). One hundred and forty patients (10%) required thyroxine replacement therapy, and 40 (3%) required on hyperthyroid medication. Total amiodarone exposure increased the likelihood of abnormal biochemical testing 2.5-fold after 4 years therapy for liver and thyroid function (P<.0005). CONCLUSION: In this population-based study, adherence to laboratory monitoring guidelines was suboptimal. There was a positive correlation with total amiodarone exposure and biochemical abnormalities and development of thyroid disease compared to the general population, highlighting the need for improvement and continued amiodarone monitoring.

Supplemental Iodide for Preterm Infants and Developmental Outcomes at 2 Years: An RCT.

BACKGROUND: The recommendation for enteral iodide intake for preterm infants is 30 to 40 µg/kg per day and 1 µg/kg per day for parenteral intake. Preterm infants are vulnerable to iodide insufficiency and thyroid dysfunction. The hypothesis tested whether, compared with placebo, iodide supplementation of preterm infants improves neurodevelopment. METHODS: A randomized controlled trial of iodide supplementation versus placebo in infants <31 weeks' gestation. Trial solutions (sodium iodide or sodium chloride; dose 30 µg/kg per day) were given within 42 hours of birth to the equivalent of 34 weeks' gestation. The only exclusion criterion was maternal iodide exposure during pregnancy or delivery. Whole blood levels of thyroxine, thyrotropin, and thyroid-binding globulin were measured on 4 specific postnatal days. The primary outcome was neurodevelopmental status at 2 years of age, measured by using the Bayley Scales of Infant Development-III. The primary analyses are by intention-to-treat, and data are presented also for survivors. RESULTS: One thousand two hundred seventy-three infants (637 intervention, 636 placebo) were recruited from 21 UK neonatal units. One hundred thirty-one infants died, and neurodevelopmental assessments were undertaken in 498 iodide and 499 placebo-supplemented infants. There were no significant differences between the intervention and placebo groups in the primary outcome: mean difference cognitive score, -0.34, 95% confidence interval (CI) -2.57 to 1.89; motor composite score, 0.21, 95% CI -2.23 to 2.65; and language composite score, -0.05, 95% CI -2.48 to 2.39. There was evidence of weak interaction between iodide supplementation and hypothyroxinemic status in the language composite score and 1 subtest score. CONCLUSIONS: Overall iodide supplementation provided no benefit to neurodevelopment measured at 2 years of age.

Vitamin A and lung function in CF.

Laboratory evidence suggests that vitamin A could have a protective effect on respiratory status in patients with cystic fibrosis (CF). This study shows a significant correlation between serum vitamin A concentrations and every aspect of lung function tested in 38 patients with stable CF. Serum vitamin D and vitamin E concentrations were also measured but did not show any significant correlations with lung function.

Assessing oral health-related quality of life in general dental practice in Scotland: validation of the OHIP-14.

OBJECTIVES: To validate the Oral Health Impact Profile (OHIP)-14 in a sample of patients attending general dental practice. METHODS: Patients with pathology-free impacted wisdom teeth were recruited from six general dental practices in Tayside, Scotland, and followed for a year to assess the development of problems related to impaction. The OHIP-14 was completed at baseline and at 1-year follow-up, and analysed using three different scoring methods: a summary score, a weighted and standardized score and the total number of problems reported. Instrument reliability was measured by assessing internal consistency and test-retest reliability. Construct validity was assessed using a number of variables. Linear regression was then used to model the relationship between OHIP-14 and all significantly correlated variables. Responsiveness was measured using the standardized response mean (SRM). Adjusted R(2)s and SRMs were calculated for each of the three scoring methods. Estimates for the differences between adjusted R(2)s and the differences between SRMs were obtained with 95% confidence intervals. RESULTS: A total of 278 and 169 patients completed the questionnaire at baseline and follow-up, respectively. Reliability - Cronbach's alpha coefficients ranged from 0.30 to 0.75. Alpha coefficients for all 14 items were 0.88 and 0.87 for baseline and follow-up, respectively. Test-retest coefficients ranged from 0.72 to 0.78. Validity - OHIP-14 scores were significantly correlated with number of teeth, education, main activity, the use of mouthwash, frequency of seeing a dentist, the reason for the last dental appointment, smoking, alcohol intake, pain and symptoms. Adjusted R(2)s ranged from 0.123 to 0.202 and there were no statistically significant differences between those for the three different scoring methods. Responsiveness - The SRMs ranged from 0.37 to 0.56 and there was a statistically significant difference between the summary scores method and the total number of problems method for symptomatic patients. CONCLUSIONS: The OHIP-14 is a valid and reliable measure of oral health-related quality of life in general dental practice and is responsive to third molar clinical change. The summary score method demonstrated performance as good as, or better than, the other methods studied.

Greater knowledge gain with structured than student-directed learning in Child Health: cluster randomized trial.

The aim of this study was to detect a difference in knowledge gain between students receiving structured versus student-directed learning for the two-week Child Health outpatient module. A total of 138 phase 3 (year 4) medical students in 10 two-week paediatric outpatient blocks at the Department of Child Health, University of Dundee, Scotland, were randomized to student-directed or structured learning between January and December 2002. Pre- and post-course tests were administered at the start and the end of the attachment; 129 students sat both tests. Results are presented as mean scores with standard deviations or 95% confidence intervals (CI) in parentheses. The primary outcome measure was gain in knowledge of the Child Health core curriculum that is covered in the outpatient setting. Although pre-course scores were similar (student-directed 25.3 (7.3); structured 24.8 (7.5)) the structured approach resulted in higher post-course scores in comparison with the student-directed approach (student-directed 41.8 (9.4); structured 53.8 (8.8); p < 0.01). Knowledge gain showed significant differences between the two learning approaches (student-directed 16.5 (3.7); structured 29.1 (3.8), difference = 12.6 (95% CI 11.3 to 13.9)). Low pre-course scores or gender did not affect knowledge gain. In the Child Health outpatient setting, the 'traditional' structured approach led to significantly greater knowledge gain in comparison with the 'novel' student-directed approach. The findings emphasize the importance of careful evaluation of novel medical education strategies before their implementation in medical schools, and the need for further research to define the effective methods for delivering medical education in Child Health.

Safety and Efficacy of Methotrexate in Psoriasis: A Meta-Analysis of Published Trials.

BACKGROUND: Methotrexate (MTX) has been used to treat psoriasis for over half a century. Even so, clinical data characterising its efficacy and safety are sparse. OBJECTIVE: In order to enhance the available evidence, we conducted two meta-analyses, one for efficacy and one for safety outcomes, respectively, according to PRISMA checklist. (Data sources, study criteria, and study synthesis methods are detailed in Methods). RESULTS: In terms of efficacy, only eleven studies met criteria for study design and passed a Cochrane risk of bias analysis. Based on this limited dataset, 45.2% [95% confidence interval 34.1-60.0] of patients achieve PASI75 at primary endpoint (12 or 16 weeks, respectively, n = 705 patients across all studies), compared to a calculated PASI75 of 4.4 [3.5-5.6] for placebo, yielding a relative risk of 10.2 [95% C.I. 7.1-14.7]. For safety outcomes, we extended the meta-analysis to include studies employing the same dose range of MTX for other chronic inflammatory conditions, e.g. rheumatoid arthritis, in order not to maximise capture of relevant safety data. Based on 2763 patient safety years, adverse events (AEs) were found treatment limiting in 6.9 ± 1.4% (mean ± s.e.) of patients treated for six months, with an adverse effect profile largely in line with that encountered in clinical practice. Finally, in order to facilitate prospective clinical audit and to help generate long-term treatment outcomes under real world conditions, we also developed an easy to use documentation form to be completed by patients without requirement for additional staff time. LIMITATIONS: Meta-analyses for efficacy and safety, respectively, employed non-identical selection criteria. CONCLUSIONS: These meta-analyses summarise currently available evidence on MTX in psoriasis and should be of use to gauge whether local results broadly fall within outcomes.

Serum thyroid hormones in preterm infants: associations with postnatal illnesses and drug usage.

CONTEXT: Transient hypothyroxinemia is common in infants less than 30 wk gestation and is associated with neurodevelopmental deficits. Reductions in T4 and T3 levels with TSH unchanged are the key features of severe illness using surrogate indices of overall severity of illness, but these do not inform the impact of individual disease conditions or drug use. OBJECTIVE: Our objective was to investigate the contribution of postnatal factors to the variations in serum levels of iodothyronines, thyroid-binding globulin, and TSH. DESIGN: We recruited a cohort of infants (23-34 wk gestation; n = 780) between January 1998 and September 2001. SETTING AND PATIENTS: The study involved 11 level III Scottish neonatal intensive care units and included cohorts of infants delivered at 23-34 wk gestation. MAIN OUTCOME: We assessed serum levels of iodothyronines, thyroid-binding globulin, and TSH at 7, 14, and 28 d adjusted for the potentially significant postnatal influences (n = 31). RESULTS: Serum levels of TSH, free T4, T3, and T4 are variably but significantly associated with bacteremia, endotracheal bacterial cultures, persistent ductus arteriosus, necrotizing enterocolitis, cerebral ultrasonography changes, oxygen dependence at 28 d, and the use of aminophylline, caffeine, dexamethasone, diamorphine, and dopamine. CONCLUSIONS: There are many more associations of postnatal factors with transient hypothyroxinemia than had previously been considered in preterm infants. Alternative strategies should be considered for correction of hypothyroxinemia rather than sole reliance on the direct therapy of hormone replacement. A more oblique preventative approach may be necessary through reduction in the incidence or severity of individual illness(es). Similarly, alternatives to those drugs that interfere with the hypothalamic-pituitary-thyroid axis should be evaluated (e.g. other inotropics instead of dopamine).

Transient hypothyroxinemia in preterm infants: the role of cord sera thyroid hormone levels adjusted for prenatal and intrapartum factors.

CONTEXT: Transient hypothyroxinemia is common in infants less than 30 wk gestation and is associated with neurodevelopmental deficits; it has no consensus definition. We previously suggested that appropriate ranges for postnatal serum T4 values are at least cord levels corrected to an equivalent gestational age if the fetuses had remained in utero. OBJECTIVE: The study objective is to investigate the contribution of prenatal and intrapartum factors (n = 27) to the variations in cord levels of iodothyronines, T4-binding globulin, and TSH, and to provide an appropriate definition of transient hypothyroxinemia. DESIGN: The study design is a cohort study (n = 620) in 11 Scottish neonatal intensive care units. PATIENTS: Infants were delivered at 23- to 42-wk gestation and recruited between January 1998 and September 2001. RESULTS: Using -2 SD of adjusted T4 cord levels applied to postnatal d-7 values of equivalent gestational age, 14% of the 23- to 27-wk group, 1% of the 28- to 30-wk group, and 3% of the 31- to 34-wk group are hypothyroxinemic; using -1 SD, the respective figures are 41, 23, and 12%. CONCLUSIONS: In the absence of neurodevelopmental follow-up studies to quantify transient hypothyroxinemia, a pragmatic criterion is necessary for selection of extreme preterm infants into clinical trials of T4 supplementation. We suggest the use of serum T4 levels on postnatal d 7 that are below -1 SD of adjusted cord T4 levels of equivalent gestational age. This criterion avoids over-recruitment of the more mature infants in whom universal T4 supplementation is detrimental to neurodevelopmental outcome, but still allows selection of the least mature entrants on whom universal T4 supplementation is beneficial.