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1.  Efficacy and safety of glucosamine, diacerein, and NSAIDs in osteoarthritis knee: a systematic review and network meta-analysis 
To conduct a systematic review and network meta-analysis of randomized controlled trials (RCTs) with the aims of comparing relevant clinical outcomes (that is, visual analog scores (VAS), total and sub-Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) scores, Lequesne algofunctional index, joint space width change, and adverse events) between diacerein, glucosamine, and placebo.
Medline and Scopus databases were searched from inception to 29 August 2014, using PubMed and Scopus search engines and included RCTs or quasi-experimental designs comparing clinical outcomes between treatments. Data were extracted from original studies. A network meta-analysis was performed by applying weight regression for continuous outcomes and a mixed-effect Poisson regression for dichotomous outcomes.
Thirty-one of 505 identified studies were eligible. Compared to placebo, glucosamine showed a significant improvement with unstandardized mean differences (UMD) in total WOMAC, pain WOMAC, function WOMAC, and Lequesne score of −2.49 (95% confidence interval (CI) −4.14, −0.83), −0.75 (95% CI: −1.18, −0.32), −4.78 (95% CI: −5.96, −3.59), and −1.03 (95% CI: −1.34, −0.72), respectively. Diacerein clinically improves visual analog scores, function WOMAC, and stiffness WOMAC with UMD values of −2.23 (95% CI: −2.82, −1.64), −6.64 (95% CI: −10.50, −2.78), and −0.68 (95% CI: −1.20, −0.16) when compared to placebo.
The network meta-analysis suggests that diacerein and glucosamine are equally efficacious for symptom relief in knee OA, but that the former has more side effects.
Electronic supplementary material
The online version of this article (doi:10.1186/s40001-015-0115-7) contains supplementary material, which is available to authorized users.
PMCID: PMC4359794  PMID: 25889669
Osteoarthritis; Gonarthrosis; Systematic review; Network meta-analysis; SYSADOA
2.  Health-related quality of life and happiness within an internal medicine residency training program: a longitudinal follow-up study 
While undergoing a hospital residency training program, residents often suffer anxiety and stress. This study aims to evaluate the change in health-related quality of life and happiness among internal medicine residents, and identify prognostic factors.
Thirty-eight residents in the Ramathibodi Hospital internal medicine training program completed the World Health Organization Quality of Life-BREF and happiness Measures questionnaires at three time points: commencement, day 100, and the end of the second year of training. Confidence, expectations, anxiety, and general health were rated. Analyses were performed with mixed linear regression.
Financial problems were reported for 16 residents (42.1%). At baseline, most residents had moderate-to-very high confidence, expectations, and general health but also moderate-to-very high anxiety. The health-related quality of life score was highest in the social domain followed by the environmental, psychological, and physical domains. Their psychological, physical, social, and environmental scores significantly decreased after enrollment. Their happiness and general health scores were significantly reduced after enrollment. The training program duration was negatively associated with all domains. Residents with greater confidence had higher health-related quality of life scores in the physical, psychological, and environmental domains. Moreover, their general health was positively associated with the social and environmental domains.
A reduction in health-related quality of life and happiness under the internal medicine residency program is reported. High confidence and good physical health may counterbalance the decline in health-related quality of life and happiness.
PMCID: PMC4439642  PMID: 25748482
Anxiety; Follow-up studies; Internship and residency; Linear models; Quality of life
3.  Severe vivax malaria: a systematic review and meta-analysis of clinical studies since 1900 
Malaria Journal  2014;13:481.
Malaria caused by Plasmodium vivax was long considered to have a low mortality, but recent reports from some geographical areas suggest that severe and complicated vivax malaria may be more common than previously thought.
The primary objective of this systematic review and meta-analysis was to describe the reported clinical characteristics and the geographical variation in prevalence of reported severe vivax malaria and its change over time derived from English-language articles published since 1900. Medline and Scopus databases were searched for original papers on severe vivax malaria, using as inclusion criteria modified 2010 WHO criteria for the diagnosis of severe falciparum malaria. Articles before 1949 were identified through reference lists in journals, textbooks, and personal collections of colleagues.
A total of 77 studies with reported severe vivax malaria and 63 studies with no reported severe vivax malaria (totaling 46,411 and 6,753 vivax malaria patients, respectively) were included. The 77 studies with reported severe vivax malaria were mainly from India (n = 33), USA (n = 8), Indonesia (n = 6), and Pakistan (n = 6). Vivax endemic countries not reporting severe vivax malaria beyond individual case reports included: the Greater Mekong Sub-region, China, North Korea, Bangladesh, Afghanistan, Middle East (except Qatar), the horn of Africa, and Madagascar. Only 17/77 reports were from before 2000. Vivax mono-infection was confirmed by PCR in 14 studies and co-morbidities were ruled out in 23 studies. Among the 77 studies reporting severe vivax malaria, severe thrombocytopenia (<50,000/mm3) was the most common “severe” manifestation (888/45,775 with pooled prevalence of 8.6%). The case fatality was 0.3% (353/46,411). Severity syndromes varied widely between different geographical areas, with severe anaemia being most prominent in areas of high transmission and chloroquine resistance.
Plasmodium vivax can cause severe and even fatal disease, but there is a recent increase in reports over the past 15 years with larger series restricted to a limited number of geographical areas. The biological basis of these variations is currently not known. More detailed epidemiological studies are needed which dissociate causation from association to refine the definition and estimate the prevalence of severe vivax malaria.
Electronic supplementary material
The online version of this article (doi:10.1186/1475-2875-13-481) contains supplementary material, which is available to authorized users.
PMCID: PMC4364574  PMID: 25486908
Plasmodiumvivax; Severe; Malaria; Complication; Prevalence; Systematic review; Meta-analysis
4.  A systematic review and meta-analysis of randomised controlled trials of delayed primary wound closure in contaminated abdominal wounds 
A systematic review and meta-analysis was conducted to compare surgical site infection (SSI) between delayed primary (DPC) and primary wound closure (PC) in complicated appendicitis and other contaminated abdominal wounds. Medline and Scopus were searched from their beginning to November 2013 to identify randomised controlled trials (RCTs) comparing SSI and length of stay between DPC and PC. Studies’ selection, data extraction, and risk of bias assessment were done by two independent authors. The risk ratio and unstandardised mean difference were pooled for SSI and length of stay, respectively. Among 8 eligible studies, 5 studies were done in complicated appendicitis, 2 with mixed complicated appendicitis and other types of abdominal operation and 1 with ileostomy closure. Most studies (75%) had high risk of bias in sequence generation and allocation concealment. Among 6 RCTs of complicated appendicitis underwent open appendectomy, the SSI between PC and DPC were not significantly different with a risk ratio of 0.89 (95% CI: 0.46, 1.73). DPC had a significantly 1.6 days (95% CI: 1.41, 1.79) longer length of stay than PC. Our evidence suggested there might be no advantage of DPC over PC in reducing SSI in complicated appendicitis. However, this was based on a small number of studies with low quality. A large scale RCT is further required.
PMCID: PMC4162947  PMID: 25221617
Delayed primary closure; Wound closure; Wound infection; Surgical site infection; Appendicitis; Meta-analysis
5.  Effects of prehospital adrenaline administration on out-of-hospital cardiac arrest outcomes: a systematic review and meta-analysis 
Critical Care  2014;18(4):463.
The aim of this study was to conduct a systematic review and meta-analysis for determining the effects of prehospital adrenaline administration on return of spontaneous circulation, hospital admission, survival to discharge and discharge with cerebral performance category 1 or 2 in out-of-hospital cardiac arrest patients.
MEDLINE and Scopus databases were searched to identify studies reported to March 2014. Study selection and data extraction were independently completed by two reviewers (PA and SR). The baseline characteristics of each study and number of events were extracted. Risk ratios (RR) and 95% confidence interval (CI) were estimated. Heterogeneity and publication bias were also explored.
In total 15 studies were eligible and included in the study. Of 13 adult observational studies, four to eight studies were pooled for each outcome. These yielded a total sample size that ranged from 2,381 to 421,459. A random effects model suggested that patients receiving prehospital adrenaline were 2.89 times (95% CI: 2.36, 3.54) more likely to achieve prehospital return of spontaneous circulation than those not administered adrenaline. However, there were no significant effects on overall return of spontaneous circulation (RR = 0.93, 95% CI: 0.5, 1.74), admission (RR = 1.05, 95% CI: 0.80, 1.38) and survival to discharge (RR = 0.69, 95% CI: 0.48, 1.00).
Prehospital adrenaline administration may increase prehospital return of spontaneous circulation, but it does not improve overall rates of return of spontaneous circulation, hospital admission and survival to discharge.
Electronic supplementary material
The online version of this article (doi:10.1186/s13054-014-0463-7) contains supplementary material, which is available to authorized users.
PMCID: PMC4145580  PMID: 25079607
6.  Risk prediction score for death of traumatised and injured children 
BMC Pediatrics  2014;14:60.
Injury prediction scores facilitate the development of clinical management protocols to decrease mortality. However, most of the previously developed scores are limited in scope and are non-specific for use in children. We aimed to develop and validate a risk prediction model of death for injured and Traumatised Thai children.
Our cross-sectional study included 43,516 injured children from 34 emergency services. A risk prediction model was derived using a logistic regression analysis that included 15 predictors. Model performance was assessed using the concordance statistic (C-statistic) and the observed per expected (O/E) ratio. Internal validation of the model was performed using a 200-repetition bootstrap analysis.
Death occurred in 1.7% of the injured children (95% confidence interval [95% CI]: 1.57–1.82). Ten predictors (i.e., age, airway intervention, physical injury mechanism, three injured body regions, the Glasgow Coma Scale, and three vital signs) were significantly associated with death. The C-statistic and the O/E ratio were 0.938 (95% CI: 0.929–0.947) and 0.86 (95% CI: 0.70–1.02), respectively. The scoring scheme classified three risk stratifications with respective likelihood ratios of 1.26 (95% CI: 1.25–1.27), 2.45 (95% CI: 2.42–2.52), and 4.72 (95% CI: 4.57–4.88) for low, intermediate, and high risks of death. Internal validation showed good model performance (C-statistic = 0.938, 95% CI: 0.926–0.952) and a small calibration bias of 0.002 (95% CI: 0.0005–0.003).
We developed a simplified Thai pediatric injury death prediction score with satisfactory calibrated and discriminative performance in emergency room settings.
PMCID: PMC3939810  PMID: 24575982
Logistic regression; Pediatric trauma and injury score; Prediction score; Injured child; Pediatric injury; Bootstrap
7.  Disparity in motorcycle helmet use in Thailand 
The dispersion of motorcycle related injuries and deaths might be a result of disparity in motorcycle helmet use. This study uses national roadside survey data, injury sentinel surveillance data and other national data sets in 2010 of Thailand, a country with high mortality related to motorcycle injuries, to explore the disparity in helmet use, explanatory factors of the disparity. It also assessed potential agreement and correlation between helmet use rate reported by the roadside survey and the injury sentinel surveillance. This report revealed helmet use rate of 43.7%(95% CI:43.6,43.9) nationwide with the highest rate (81.8%; 95% CI: 44.0,46.4) in Bangkok. Helmet use rate in drivers (53.3%; 95% CI: 53.2,53.8) was 2.5 times higher than that in passengers (19.3%; 95% CI:18.9,19.7). In relative terms (highest-to-lowest ratio,HLR), geographical disparity in helmet use was found to be higher in passengers (HLR=28.5). Law enforcement activities as indicated by the conviction rate of motorcyclists were significantly associated with the helmet use rate (spline regression coefficient = 3.90, 95% CI: 0.48,7.33). Together with the finding of HLR for conviction rate of 87.24, it is suggested that more equitable improvement in helmet use could be achieved by more equitable distribution of the police force. Finally, we found poor correlation (r=0.01; p value = 0.76) and no agreement (difference = 34.29%; 95% CI:13.48%, 55.09%) between roadside survey and injury sentinel surveillance in estimating helmet use rate. These findings should be considered a warning for employing injury surveillance to monitor policy implementation of helmet use.
PMCID: PMC3765770  PMID: 24119233
Inequity; Helmet use; Resource allocation; Law enforcement
8.  Meta-Analysis of Cytokine Gene Polymorphisms and Outcome of Heart Transplantation 
BioMed Research International  2013;2013:387184.
We performed a systematic review and meta-analysis with the aim of assessing the association between cytokine gene polymorphisms and graft rejection in heart transplantation. We identified relevant studies from Medline and Embase using PubMed and Ovid search engines, respectively. Allele frequencies and allele and genotypic effects were pooled. Heterogeneity and publication bias were explored. Four to 5 studies were included in pooling of 3 gene polymorphisms. The prevalences of the minor alleles for TNFα-308, TGFβ1-c10, and TGFβ1-c25 were 0.166 (95% CI: 0.129, 0.203), 0.413 (95% CI: 0.363, 0.462), and 0.082 (95% CI: 0.054, 0.111) in the control groups, respectively. Carrying the A allele for the TNFα-308 had 18% (95% CI of OR: 0.46, 3.01) increased risk, but this was not significant for developing graft rejection than the G allele. Conversely, carrying the minor alleles for both TGFβ1-c10 and c25 had nonsignificantly lower odds of graft rejection than major alleles, with the pooled ORs of 0.87 (95% CI: 0.65, 1.18) and 0.70 (95% CI: 0.40, 1.23), respectively. There was no evidence of publication bias for all poolings. An updated meta-analysis is required when more studies are published to increase the power of detection for the association between these polymorphisms and allograft rejection.
PMCID: PMC3762075  PMID: 24024189
9.  Hemoglobin Concentration and Pregnancy Outcomes: A Systematic Review and Meta-Analysis 
BioMed Research International  2013;2013:769057.
Objective. To conduct a systematic review and meta-analysis of hemoglobin effect on the pregnancy outcomes. Methods. We searched MEDLINE and SCOPUS from January 1, 1990 to April 10, 2011. Observational studies addressing association between hemoglobin and adverse pregnancy outcomes were selected. Two reviewers independently extracted data. A mixed logistic regression was applied to assess the effects of hemoglobin on preterm birth, low birth weight, and small for gestational age. Results. Seventeen studies were included in poolings. Hemoglobin below 11 g/dL was, respectively, 1.10 (95% CI: 1.02–1.19), 1.17 (95% CI: 1.03–1.32), and 1.14 (95% CI: 1.05–1.24) times higher risk of preterm birth, low birth weight, and small for gestational age than normal hemoglobin in the first trimester. In the third trimester, hemoglobin below 11 g/dL was 1.30 (95% CI: 1.08–1.58) times higher risk of low birth weight. Hemoglobin above 14 g/dL in third trimester decreased the risk of preterm term with ORs of 0.50 (95% CI: 0.26–0.97), but it might be affected by publication bias. Conclusions. Our review suggests that hemoglobin below 11 g/dl increases the risk of preterm birth, low birth weight, and small gestational age in the first trimester and the risk of low birth weight in the third trimester.
PMCID: PMC3741929  PMID: 23984406
10.  Efficacy of intravesical chondroitin sulphate in treatment of interstitial cystitis/bladder pain syndrome (IC/BPS): Individual patient data (IPD) meta-analytical approach 
Raw data from 3 similar clinical trials were analyzed in this individual participant data (IPD) meta-analysis to define any possible efficacy of intravesical 2% chondroitin sulphate in IC/BPS.
We pooled IPD from an open label and 2 small randomized placebo controlled trials assessing chondroitin sulphate in IC/BPS (similar inclusion/exclusion criteria, treatment, outcome assessment). Our primary objective was to compare rates of global response assessment (GRA) responsiveness between chondroitin sulphate and vehicle control. Secondary objectives compared the Interstitial Cystitis Symptom/Problem Index (ICSI/PI) total score and improvement rates, and average daily urine frequency. The treatment response was calculated for individual trials and pooled data using IPD meta-analysis for pooling proportions.
In total, 213 patients were included in the pooling analysis. At the end of the treatment period, the overall GRA response rates were 43.2 (95% CI: 35.0, 51.5) and 27.4 (95% CI: 17.6, 37.2) for the chondroitin sulphate and vehicle control groups, respectively. Pooled RR was 1.55 (p = 0.014, 95% CI: 1.09, 2.22). The chance of being an ICSI responder was similarly 54% higher in the chondroitin sulphate group. The small decrease in total ICSI score and urine frequency between the two groups was less impressive (−0.8 and −0.5 points respectively) and not statistically significant.
Benefits from intravesical chondroitin sulphate treatment in IC/BPS patients can be confirmed by increasing the power of the available data using an IPD meta-analytical approach. However, disconnect between response rates and severity scores underline the importance of choosing the right patient for this organ-specific treatment.
PMCID: PMC3699082  PMID: 23826048
11.  Prognostic factors of all-cause mortalities in continuous ambulatory peritoneal dialysis: a cohort study 
BMC Nephrology  2013;14:28.
The role of small solute clearance on mortalities in patients with CAPD has been controversial. We therefore conducted a study with 3 years' follow up in adult patients who participated in the CAPD-first policy.
There were 11,523 patients with end-stage renal disease who participated in the CAPD-first policy between 2008 and 2011. Among them, 1,177 patients were included in the retrospective cohort study. A receiver operating characteristic curve was applied to calibrate the cutoffs of tKt/V, rKt/V and tCrcl. Kaplan-Meier and Cox-regression models with time varying covariates were applied to estimate overall death rate, probability of death and prognosis, respectively.
The cutoffs of rKt/V and tKt/V were 0.25 and 1.75, respectively. The Cox regression suggested that the higher these clearance parameters, the lower the risks of death after adjusting for covariables. The risks of death for those above these cutoffs were 57% (HR = 0.43, 95% CI: 0.31, 0.60) and 29% (HR = 0.71, 95% CI: 0.52, 0.98) lower for rKt/V and tKt/V, respectively. Age, serum albumin, hemoglobin, systolic blood pressure, and ultra-filtration volume significantly affected the mortality outcome.
Our study suggested that the cutoffs of 0.25 and 1.75 for rKt/V and tKt/V might be associated with mortality in CAPD patients. A minimum tKt/V of 1.75 should be targeted, but increased dialysis dosage to achieve tKt/V > 2.19 adds no further benefit. Serum albumin, hemoglobin, SBP, and UF volume are also associated with mortality. However, our study may face with selection and other unobserved confounders, so further randomized controlled trials are required to confirm these cutoffs.
PMCID: PMC3575253  PMID: 23369065
Adequacy indices; CAPD; Continuous ambulatory peritoneal dialysis; Mortality; Peritoneal small solute clearance; Prognostic factors
12.  Evidence of association of APOE with age-related macular degeneration - a pooled analysis of 15 studies 
Human mutation  2011;32(12):1407-1416.
Age-related macular degeneration (AMD) is the most common cause of incurable visual impairment in high-income countries. Previous studies report inconsistent associations between AMD and apolipoprotein E (APOE), a lipid transport protein involved in low-density cholesterol modulation. Potential interaction between APOE and sex, and smoking status, has been reported. We present a pooled analysis (n=21,160) demonstrating associations between late AMD and APOε4 (OR=0.72 per haplotype; CI: 0.65–0.74; P=4.41×10−11) and APOε2 (OR=1.83 for homozygote carriers; CI: 1.04–3.23; P=0.04), following adjustment for age-group and sex within each study and smoking status. No evidence of interaction between APOE and sex or smoking was found. Ever smokers had significant increased risk relative to never smokers for both neovascular (OR=1.54; CI: 1.38–1.72; P=2.8×10−15) and atrophic (OR=1.38; CI: 1.18–1.61; P=3.37×10−5) AMD but not early AMD (OR=0.94; CI: 0.86–1.03; P=0.16), implicating smoking as a major contributing factor to disease progression from early signs to the visually disabling late forms. Extended haplotype analysis incorporating rs405509 did not identify additional risks beyondε2 and ε4 haplotypes. Our expanded analysis substantially improves our understanding of the association between the APOE locus and AMD. It further provides evidence supporting the role of cholesterol modulation, and low-density cholesterol specifically, in AMD disease etiology.
PMCID: PMC3217135  PMID: 21882290
age-related macular degeneration; AMD; apolipoprotein E; APOE; case-control association study
13.  Prevalence of Vitamin D insufficiency and low bone mineral density in elderly Thai nursing home residents 
BMC Geriatrics  2012;12:49.
Numerous emerging data from research on osteoporosis among Asians found differences from Caucasians. Therefore, the aim of this study was to determine the prevalence of vitamin D insufficiency and osteoporosis in elderly participants from two nursing homes in Thailand, a country located near the equator.
The subjects of this cross-sectional study comprised 93 elderly Thai women who were living in institutional long-term nursing homes for the aged. Demographic data, daily food and calcium intake, physical activity, and sunlight exposure were measured. Lumbar spine and femoral neck bone mineral density (BMD) and biochemical levels including serum 25 hydroxyvitamin D [25(OH)D] and bone turnover markers were assessed. Vitamin D insufficiency was defined as 25(OH)D level < 70 nmol/l.
The mean age of subjects was 75.2 ± 6.0 (SD) years. Dietary calcium intake was low (322 ± 158 mg/day) The mean 25(OH)D level was 64.3 ± 14.9 nmol/L and the prevalence of vitamin D insufficiency was 38.7% (95% CI: 28.8%, 49.4%). There was no correlation between serum 25(OH)D concentrations and age (r = −.11, p = 0.3). The mean BMD of lumbar spine and femoral neck were 0.92 ± 0.19 and 0.65 ± 0.10 g/cm2, respectively. Nearly a half of the subjects had osteopenia (44.1%, 95% CI: 33.8%, 54.8%) and osteoporosis (47.3%, 95% CI: 36.9%, 57.9%). Circulating C-terminal telopeptide of type I collagen (CTx) level correlated significantly with both lumbar spine (r = −0.26, p = 0.01) and femoral neck BMD (r = −0.25, p = 0.02).
More than one-third of Thai elderly women residing in nursing homes had vitamin D insufficiency. Almost all nursing home residents had osteoporosis and/or osteopenia.
PMCID: PMC3490934  PMID: 22938528
Vitamin D; Osteoporosis; Bone density; Aged; Nursing homes; Collagen type I trimeric cross-linked peptide
14.  A simplified clinical prediction score of chronic kidney disease: A cross-sectional-survey study 
BMC Nephrology  2011;12:45.
Knowing the risk factors of CKD should be able to identify at risk populations. We thus aimed to develop and validate a simplified clinical prediction score capable of indicating those at risk.
A community-based cross-sectional survey study was conducted. Ten provinces and 20 districts were stratified-cluster randomly selected across four regions in Thailand and Bangkok. The outcome of interest was chronic kidney disease stage I to V versus non-CKD. Logistic regression was applied to assess the risk factors. Scoring was created using odds ratios of significant variables. The ROC curve analysis was used to calibrate the cut-off of the scores. Bootstrap was applied to internally validate the performance of this prediction score.
Three-thousand, four-hundred and fifty-nine subjects were included to derive the prediction scores. Four (i.e., age, diabetes, hypertension, and history of kidney stones) were significantly associated with the CKD. Total scores ranged from 4 to 16 and the score discrimination was 77.0%. The scores of 4-5, 6-8, 9-11, and ≥ 12 correspond to low, intermediate-low, intermediate-high, and high probabilities of CKD with the likelihood ratio positive (LR+) of 1, 2.5 (95% CI: 2.2-2.7), 4.9 (95% CI: 3.9 - 6.3), and 7.5 (95% CI: 5.6 - 10.1), respectively. Internal validity was performed using 200 repetitions of a bootstrap technique. Calibration was assessed and the difference between observed and predicted values was 0.045. The concordance C statistic of the derivative and validated models were similar, i.e., 0.770 and 0.741.
A simplified clinical prediction score for estimating risk of having CKD was created. The prediction score may be useful in identifying and classifying at riskpatients. However, further external validation is needed to confirm this.
PMCID: PMC3199235  PMID: 21943205
15.  Corticosteroid and antiviral therapy for Bell's palsy: A network meta-analysis 
BMC Neurology  2011;11:1.
Previous meta-analyses of treatments for Bell's palsy are still inconclusive due to different comparators, insufficient data, and lack of power. We therefore conducted a network meta-analysis combining direct and indirect comparisons for assessing efficacy of steroids and antiviral treatment (AVT) at 3 and 6 months.
We searched Medline and EMBASE until September 2010 using PubMed and Elsviere search engines. A network meta-analysis was performed to assess disease recovery using a mixed effects hierarchical model. Goodness of fit of the model was assessed, and the pooled odds ratio (OR) and 95% confidence interval (CI) were estimated.
Six studies (total n = 1805)were eligible and contributed to the network meta-analysis. The pooled ORs for resolution at 3 months were 1.24 (95% CI: 0.79 - 1.94) for Acyclovir plus Prednisolone and 1.02 (95% CI: 0.73 - 1.42) for Valacyclovir plus Prednisolone, versus Prednisolone alone. Either Acyclovir or Valacyclovir singly had significantly lower efficacy than Prednisolone alone, i.e., ORs were 0·44 (95% CI: 0·28 - 0·68) and 0·60 (95% CI: 0·42 - 0·87), respectively. Neither of the antiviral agents was significantly different compared with placebo, with a pooled OR of 1·25 (95% CI: 0·78 - 1·98) for Acyclovir and 0·91 (95% CI: 0·63 - 1·31) for Valacyclovir. Overall, Prednisolone-based treatment increased the chance of recovery 2-fold (95% CI: 1·55 - 2·42) compared to non-Prednisolone-based treatment. To gain 1 extra recovery, 6 and 26 patients need to be treated with Acyclovir and prednisolone compared to placebo and prednisolone alone, respectively.
Our evidence suggests that the current practice of treating Bell's palsy with AVT plus corticosteroid may lead to slightly higher recovery rates compared to treating with prednisone alone but this does not quite reach statistical significance; prednisone remains the best evidence-based treatment.
PMCID: PMC3025847  PMID: 21208452
16.  The Quality of Meta-Analyses of Genetic Association Studies: A Review With Recommendations 
American Journal of Epidemiology  2009;170(11):1333-1343.
Although there has been a rapid rise in the publication of meta-analyses of genetic association studies, little is known about their methodological quality. The authors reviewed the quality of 120 randomly selected genetic meta-analyses published between 2005 and 2007. Data extracted included issues of general relevance and other issues specific to genetic epidemiology. Quality was markedly poorer in the 26% of the meta-analyses that accompanied a report on a primary study. Such meta-analyses were predominantly published in specialist journals, and their quality was positively associated with the impact factor of the journal. Among the meta-analyses that did not accompany a primary study, Human Genome Epidemiology reviews tended to score better than the others, although the comparison was limited by relatively small numbers. Comparison of the overall quality with that of genetic meta-analyses published before 2000 showed improvement in both conduct and reporting. However, the quality of the handling of specific genetic issues remains disappointingly low. For a few key general quality issues, the authors compared their findings with findings in other fields of medicine and found that general quality was similar. On the basis of this review, the authors provide practical recommendations for the conduct and reporting of genetic meta-analyses.
PMCID: PMC2778766  PMID: 19901000
epidemiologic methods; genetics; meta-analysis; principal component analysis
17.  A Clinical Decision Rule to Aid Ordering of Serum and Urine Protein Electrophoresis for Case-Finding of Paraproteins in Hospitalized Inpatients 
Journal of General Internal Medicine  2008;23(10):1688-1692.
To develop a simple clinical decision rule that could increase the yield of serum and urine protein electrophoresis (SPE/UPE) without loss of sensitivity.
A cross-sectional study of inpatients with a SPE/UPE performed over a 5-year period (2001–2006) with complete data on electrolytes, globulins, full blood count, creatinine, age, and gender.
A tertiary-care general teaching hospital serving the Hunter Valley in New South Wales, with a referral population of over 1 million.
A total of 14,374 adult patients admitted between January 2001–November 2006.
Main outcome measures
Paraprotein on serum and/or urine protein electrophoresis (SPE/UPE).
Five points were assigned for globulin >41 g/l, 3 points for age ≥60, 2 points for each of hemoglobin <121 and male gender, and 1 point for estimated glomerular filtration rate (eGFR) <60. Total scores of 0–5, 6–10, and ≥11 corresponded to positive likelihood ratios of an abnormal SPE/UPE of 1, 2.5, and 6.6, respectively. The predictive ability of this model was strong, with an area under the curve of ∼0.8. Results in the validation set were almost identical.
A clinical decision rule using simple clinical variables has the potential to improve the yield of SPE/UPE. This rule however needs to be verified prospectively.
PMCID: PMC2533374  PMID: 18665429
clinical decision rule; protein electrophoresis; predictive score; paraprotein
18.  Visceral fat and insulin resistance as predictors of non-alcoholic steatohepatitis 
AIM: To analyze the gene expression profiles of mice livers injured by Leigongteng and explore the relationship between the differentially expressed genes and liver damage.
METHODS: The experimental mice were randomly divided into a control group and a liver-injured group in which the mice were administrated 33 μγ of triptolide/kg per day for 30 d. Liver mRNAs were extracted from animals in both groups and were reverse-transcribed to cDNA with dUTP labeled by different fluorescence (Cy3, Cy5) as hybridization probes. The mixed probes were hybridized with oligonucleotide microarray chips. The fluorescent signal results were acquired by scanner and analyzed with software.
RESULTS: Among the 35 852 target genes, 29 genes were found to be significantly differentially expressed, with 20 genes up-regulated and 9 genes down-regulated. The reliability of the differentially expressed genes was validated by RT-PCR experiments of 5 randomly selected differentially expressed genes.
CONCLUSION: Based on the biological functions of the differentially expressed genes, it is obvious that the occurrence and development of liver damage induced by Leigongteng in mice are highly associated with immune response, metabolism, apoptosis and the cell skeleton of liver cells. This might be important for elucidating the regulatory network of gene expression associated with liver damage and it may also be important for discovering the pathogenic mechanisms of liver damage induced by Leigongteng.
PMCID: PMC4146802
Tripterygium Wilfordii Hook.f.; Gene expre-ssion profile; Oligonucleotide microarray; Mice
19.  Germline Missense Changes in the APC Gene and Their Relationship to Disease 
Familial adenomatous polyposis (FAP) is characterized by the presence of hundreds to thousands of adenomas that carpet the entire colon and rectum. Nonsense and frameshift mutations in the adenomatous polyposis coli (APC) gene account for the majority of mutations identified to date and predispose primarily to the typical disease phenotype. Some APC mutations are associated with a milder form of the disease known as attenuated FAP. Virtually all mutations that have been described in the APC gene result in the formation of a premature stop codon and very little is known about missense mutations apart from a common Ashkenazi Jewish mutation (1307 K) and a British E1317Q missense change. The incidence of missense mutations in the APC gene has been underreported since the APC gene lends itself to analysis using an artificial transcription and translation assay known as the Protein Truncation Test (PTT) or the In Vitro Synthetic Protein assay (IVSP).
In this report we have used denaturing high performance liquid chromatography to analyse the entire coding sequence of the APC gene to determine if a cohort of patients adhering to the diagnostic criteria of FAP to assess the frequency of missense mutations in the APC gene. Altogether 112 patients were studied and 22 missense mutations were identified. From the total of 22 missense changes, 13 were silent changes and the remaining 9 resulted in amino acid substitutions. One or more of these changes were identified multiple times in 62.5% of the population under study.
The results reveal that missense mutations in the APC gene appear not to radically alter protein function but may be associated with more subtle processing of RNA transcripts which in turn could result in the expression of differentially spliced forms of the APC gene which may interfere with the functional activity of the APC protein.
PMCID: PMC2839999  PMID: 20233475
APC; mutations; colorectal cancer; missense

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