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.

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.

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.

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.

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.

Does oral sodium bicarbonate therapy improve function and quality of life in older patients with chronic kidney disease and low-grade acidosis (the BiCARB trial)? Study protocol for a randomized controlled trial.

BACKGROUND: Metabolic acidosis is more common with advancing chronic kidney disease, and has been associated with impaired physical function, impaired bone health, accelerated decline in kidney function and increased vascular risk. Although oral sodium bicarbonate is widely used to correct metabolic acidosis, there exist potential risks of therapy including worsening hypertension and fluid overload. Little trial evidence exists to decide whether oral bicarbonate therapy is of net benefit in advanced chronic kidney disease, particularly in older people who are most commonly affected, and in whom physical function, quality of life and vascular health are at least as important outcomes as decline in renal function. METHODS/DESIGN: BiCARB is a multi-centre, double-blind, placebo controlled, randomised trial evaluating the clinical and cost-effectiveness of oral sodium bicarbonate in the management of older people with chronic kidney disease and severely reduced glomerular filtration rate (GFR) who have a mild degree of metabolic acidosis. The trial will recruit 380 patients from renal, Medicine for the Elderly, and primary care services across centres in the United Kingdom. Male and female patients aged 60 years and older with an estimated glomerular filtration rate of <30 mL/min/1.73 m(2), not on dialysis, and with serum bicarbonate concentrations <22 mmol/L will be eligible for participation. The primary clinical outcome for the trial is the between-group difference in the Short Physical Performance Battery score at 12 months. Secondary outcomes include muscle strength, quality of life measured using the EQ-5D score and KDQoL tools, cost effectiveness, renal function, presence of albuminuria and blood pressure. Markers of bone turnover (25-hydroxyvitamin D, 1,25-hydroxyvitamin D, tartrate-resistant acid phosphatase-5b and bone-specific alkaline phosphatase) and vascular health (B-type natriuretic peptide) will be measured. Participants will receive a total of 24 months of either bicarbonate or placebo. The results will provide the first robust test of the overall clinical and cost-effectiveness of this commonly used therapy in older patients with severely reduced kidney function. TRIAL REGISTRATION: www.isrctn.com; ISRCTN09486651, registered 17 February 2012.

Recent trends in glaucoma surgery in Scotland, England and Wales.

OBJECTIVE: To evaluate national trends of trabeculectomy, aqueous shunts and cycloablation performed in Scotland, England and Wales from 1993 to 2012. METHODS: The annual numbers of trabeculectomies and aqueous shunts carried out between 1993 and 2012 were obtained from national Scottish, English and Welsh National Health Service databases. The annual rates of trabeculectomy, aqueous shunts and cycloablation were calculated per 100,000 of the population and analysed in the following age groups: 0-14 years, 15-59 years, over 60 years. RESULTS: The highest annual rate of trabecuelctomy was in 1995, this was followed by a sharp decline and subsequent stable rates since 2000. The total annual rates of aqueous shunts have increased more than sixfold from 2003 to 2012. In the 0-14 years age group from 2003 to 2012 the ratio of trabeculectomy to aqueous shunts has reversed; trabeculectomy rates have decreased while rates of aqueous shunts have increased. From 2003 to 2012, rates of cyclocryotherapy have reduced while rates of photocoagulation to the ciliary body have doubled. CONCLUSIONS: Trabeculectomy is the most commonly performed glaucoma operation. Aqueous shunts are rapidly increasing in the surgical management of glaucoma. During the study period, the ratio of trabeculectomy to aqueous shunts has reversed in the younger age group (0-14 years). Rates of cyclocyrotherapy to the ciliary body have dramatically declined while laser photocoagulation to the ciliary body is gaining wider acceptability.

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.

A summary of the iodine supplementation study protocol (I2S2): a UK multicentre randomised controlled trial in preterm infants.

This paper summarises the study protocol for the randomised controlled trial of iodine supplementation in preterm infants. Iodine is essential for the synthesis of thyroxine, and thyroxine is essential for normal brain development in utero and for the first 2-3 years of life. The recommended iodine intake in parenteral nutrition regimens is 1 µg/kg/day and commercially available parenteral solutions for infants reflect these recommendations. In the absence of other iodine sources, infants are vulnerable to negative iodine balance and insufficiency. As many preterm infants are fed parenterally for prolonged periods with solutions which have been shown to be iodine-deficient, the I2S2 Trial was designed to establish whether iodine supplementation of preterm infants benefits neurodevelopment.

High-potency statin and ezetimibe use and mortality in survivors of an acute myocardial infarction: a population-based study.

OBJECTIVE: To determine all-cause mortality in patients with a first myocardial infarct who were treated with simvastatin compared with high-potency statin and simvastatin/ezetimibe combination. BACKGROUND: Despite statin use, residual cardiovascular risk remains. Therapeutic options include more potent statins or addition of ezetimibe. There is no clinical outcome data on the use of ezetimibe in such patients. METHODS: Retrospective longitudinal study using the United Kingdom General Practice Research Database. Patients who had survived 30 days after their first acute myocardial infarct (AMI), had not received prior statin or ezetimibe therapy and were started on a statin within 30 days of AMI were included. Three groups were identified according to their follow-up: (i) simvastatin monotherapy; (ii) high-potency statin group (patients who started on simvastatin and switched to atorvastatin or rosuvastatin); and (iii) ezetimibe/statin combination group (patients who received ezetimibe in addition to statin). RESULTS: 9597 patients (57% male, mean age of 65 ± 13 years) matched study criteria: simvastatin (n=6990 (72.8%)); high-potency statin (n=1883, (19.6%)); and ezetimibe/statin combination (n=724 (7.5%)). During a mean follow-up of 3.2 years, there were 1134 (12%) deaths. In the multivariate proportional hazards model, the adjusted HR for high-potency statin and ezetimibe group were 0.72 (95% CI 0.59 to 0.88, p<0.001) and 0.96 (95% CI 0.64 to 1.43, p=0.85), respectively. A similar result was also obtained in the propensity score analysis that took into account covariates that predicted drug treatment groups. CONCLUSIONS: Patients switched to a high-potency statin had a significantly reduced mortality compared with simvastatin monotherapy. There was no observed mortality benefit in the ezetimibe group.

Maternal and umbilical cord levels of T4, FT4, TSH, TPOAb, and TgAb in term infants and neurodevelopmental outcome at 5.5 years.

CONTEXT: Relatively little is known in euthyroid populations about the changes in maternal thyroid hormones during pregnancy, the nature of the relationship to cord thyroid hormone levels, and subsequent infant neurodevelopment. OBJECTIVES: The aim of the study was to describe the relationship between maternal and cord thyroid hormone parameters and to describe their associations with neurodevelopment at 5.5 years. DESIGN: We conducted a follow-up of women and their children born at or over 37 weeks' gestation. MAIN OUTCOMES: We measured maternal levels of TSH, thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb), T(4), and free T(4) (FT(4)) at 10 and 34 weeks and at delivery, and cord levels of T(4), FT(4), TPOAb, and TgAb. The association of cord thyroid hormone parameters with McCarthy scale scores adjusted for the major confounders of neurodevelopment. RESULTS: Fifteen percent of the women were TPOAb-positive, and 12% were TgAb-positive; the proportion of women with mildly elevated TSH levels increased during pregnancy with the maximum (14%) at delivery. Lower perceptual performance and motor scores were found with TgAb-positive women and lower perceptual performance scores with TgAb-positive cord levels; otherwise, unadjusted maternal levels of TPOAb, TgAb, and TSH and unadjusted cord levels of FT(4), TPOAb, and TgAb were not associated with neurodevelopment at 5.5 years. Low cord T(4) levels were associated with significant increments in four McCarthy scales: General Cognitive Index, Verbal, Quantitative, and Memory scales-increments that persisted after adjustment at 11.4, 7.8, 7.6, and 7.8 points, respectively. CONCLUSIONS: Lower levels of cord T(4) were associated with increments in the McCarthy scales in the domains that tested cognitive and verbal abilities at 5.5 years.

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.

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.

The effect of metformin on insulin resistance and exercise parameters in patients with heart failure.

AIMS: Chronic heart failure (CHF) is an insulin-resistant state. The degree of insulin resistance (IR) correlates with disease severity and is associated with reduced exercise capacity. In this proof of concept study, we have examined the effect of metformin on IR and exercise capacity in non-diabetic CHF patients identified to have IR. METHODS AND RESULTS: In a double-blind, placebo-controlled study, 62 non-diabetic IR CHF patients (mean age, 65.2 ± 8.0 years; male, 90%; left ventricular ejection fraction, 32.6 ± 8.3%; New York Heart Association class I/II/III/IV, 11/45/6/0) were randomized to receive either 4 months of metformin (n = 39, 2 g/day) or matching placebo (n = 23). IR was defined by a fasting insulin resistance index (FIRI) ≥2.7. Cardiopulmonary exercise testing and FIRI were assessed at baseline and after 4 months of intervention. Compared with placebo, metformin decreased FIRI (from 5.8 ± 3.8 to 4.0 ± 2.5, P < 0.001) and resulted in a weight loss of 1.9 kg (P < 0.001). The primary endpoint of the study, peak oxygen uptake (VO(2)), did not differ between treatment groups. However, metformin improved the secondary endpoint of the slope of the ratio of minute ventilation to carbon dioxide production (VE/VCO(2) slope), from 32.9 ± 15.9 to 28.1 ± 8.8 (P = 0.034). In the metformin-treated group, FIRI was significantly related to the reduction of the VE/VCO(2) slope (R = 0.41, P = 0.036). CONCLUSION: Metformin treatment significantly improved IR but had no effect on peak VO(2), the primary endpoint of our study. However, metformin treatment did result in a significant improvement in VE/VCO(2) slope. TRIAL REGISTRATION: NCT00473876.

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.

Mild maternal thyroid dysfunction at delivery of infants born ≤34 weeks and neurodevelopmental outcome at 5.5 years.

CONTEXT: Mild maternal thyroid dysfunction during early pregnancy is associated with poor neurodevelopment in affected offspring. Most studies are population based or are smaller populations of term/late preterm infants. No studies were found that focused on more preterm infants. OBJECTIVE: Our objective was to describe the relationship between mild maternal thyroid dysfunction at delivery of infants born ≤34 wk and neurodevelopment at 5.5 yr. DESIGN: The study design was follow-up of women and children recruited in Scotland between 1998 and 2001. MAIN OUTCOME: We evaluated delivery levels of maternal TSH, free T(4) (FT(4)), and T(4) and the association with McCarthy Scale scores adjusted for 26 confounders of neurodevelopment. RESULTS: Maternal serum levels and McCarthy scores were available for 143 women and 166 children. After adjustment for confounders, there were significant 3.2, 2.1, and 1.8 point decrements, respectively, in general cognitive index, verbal subscale, and the perceptual performance subscale for each milliunit per liter increment in maternal TSH. Maternal FT(4) levels were variably associated with neurodevelopment. After adjustment, significant associations were found for the general cognitive index, motor scale, and quantitative subscale; each picomole per liter decrease in FT(4) was associated with an increase of 1.5, 1.7, and 0.9 points, respectively. Maternal T(4) levels showed little relationship with neurodevelopment. None of the women in this analysis had overt hypothyroidism, but mild hypothyroidism was evident in 27%; thyroglobulin antibody (TgAb) was ≥ 40 U/ml in 28% of the women. CONCLUSIONS: Higher maternal levels of TSH at delivery of infants born preterm were associated with significantly lower scores on the general cognitive index at 5.5 yr.

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.

Effect of Metformin on mortality in patients with heart failure and type 2 diabetes mellitus.

Type 2 diabetes mellitus (DM) plus chronic heart failure (CHF) is a common but lethal combination and therapeutic options are limited. Metformin is perceived as being relatively contraindicated in this context, although mounting evidence indicates that it may be beneficial. This study was carried out to investigate the use of metformin therapy for treating patients with DM and CHF in a large population-based cohort study. The Health Informatics Centre-dispensed prescribing database for the population of Tayside, Scotland (population ∼400,000) was linked to the Diabetes Audit and Research in Tayside Scotland (DARTS) information system. Patients with DM and incident CHF from 1994 to 2003 receiving oral hypoglycemic agents but not insulin were identified. Cox regression was used to assess differences in all-cause mortality rates between patients prescribed metformin and patients prescribed sulfonylureas with adjustment for co-morbidities and other therapies. Four hundred twenty-two study subjects (mean ± SD 75.4 ± 0.5 years of age, 46.2% women) were identified: metformin monotherapy (n = 68, mean age 75.5 ± 1.1 years, 48.5% women), sulfonylurea monotherapy (n = 217, mean age 76.7 ± 0.7 years, 45.2% women), and combination (n = 137, mean age, 73.4 ± 0.7 years, 46.7% women). Fewer deaths occurred in metformin users, alone or in combination with sulfonylureas, compared to the sulfonylurea monotherapy cohort at 1 year (0.59, 95% confidence interval 0.36 to 0.96) and over long-term follow up (0.67, 95% confidence interval 0.51 to 0.88). In conclusion, this large observational data suggest that metformin may be beneficial in patients with CHF and DM. These findings need to be verified by a prospective clinical trial.