Jia Wei Liu Jun Zi Tang: JWLJZT) on motor and non-motor symptoms, and on complications of conventional therapy in idiopathic Parkinson's disease (PD), using an add-on design. Fifty-five patients with PD were randomly allocated to receive either Chinese herbal medicine or placebo for 24 weeks. Primary outcome measure was the 39-item Parkinson's Disease Questionnaire (PDQ-39). Secondary outcome measures included the Unified Parkinson's Disease Rating Scale (UPDRS), Short-Form-36 Health Survey (SF-36), Geriatric Depression Scale (GDS), home diaries, and a range of category rating scales. JWLJZT resulted in a significant improvement in the UPDRS IVC when compared with placebo at 12 weeks (P = .039) and 24 weeks (P = .034). In addition, patients in the Chinese herbal medicine group also showed significant improvement in PDQ-39 communication scores at 12 weeks (P = .024) and 24 weeks (P = .047) when compared with the placebo group. There were no significant differences between treatment and control groups for SF-36 variables, GDS score or the mean daily “on-off” time. One case of mild diarrhea was noted in the treatment group. The findings suggest that JWLJZT can relieve some non-motor complications of conventional therapy and improve the communication ability in patients with PD. The results of this pilot study warrant larger multi-center clinical studies to assess long-term efficacy and tolerability of JWLJZT, and to elucidate the mechanisms by which it affects PD function.The objective of this clinical study is to examine the effects of a Chinese herbal medicine formula ( Epidemiological studies show that the prevalence of PD in industrialized countries is usually estimated at 0.3% of the whole population and at s of age .∼40 and 70% of patients after 5 years and 15 years of levodopa treatment, respectively, [Despite various advances in the understanding of PD, pharmacological treatment of PD by Western medicine is mainly for symptom management. Among different pharmacological treatments, levodopa remains the most efficacious and is still the mainstay of therapy . Howeverctively, . MoreoveIn view of the undesirable long-term side effects of Western medicine, many patients seek alternative treatment for PD. Traditional Chinese medicine (TCM) has been used for centuries to treat conditions such as trembling of hands and shaking of head that correspond to the modern term “PD”. Up to the present, Chinese herbal medicine remains very popular for management of PD in Asian countries such as China, Korea and Japan. In a study done by Rajendran et al., it was observed that 40% of patients with PD use at least one form of alternative therapy . Herbal Jia Wei Liu Jun Zi Tang” (JWLJZT) is an ancient formulation developed by a TCM doctor Zhang Lu in 1695 AD, with the specific function of tonifying the energy (Qi) of spleen and stomach; it has been used to treat symptoms that are now defined as PD [Unlike Western medicine, TCM diagnoses of PD fall into different categories according to the patient's fundamental constitution. According to TCM theory, PD is a condition that represents a depletion of energy, especially in the spleen and stomach. Herbal drugs have therefore been used in the treatment of PD under the general guideline of “strengthening the spleen and regulating the stomach”. “ed as PD . In thisAll idiopathic PD patients (aged 20–80 years) who presented to the Mr and Mrs Chan Hon Yin Modern Chinese Medicine Research and Service Centre of the Queen Elizabeth Hospital, Hong Kong, were screened for eligibility. Diagnosis of idiopathic PD was based on UK Brain Bank criteria . InclusiPatients with atypical or secondary Parkinsonism, pronounced clinically relevant cognitive impairment , severe concurrent illness or history of psychotic illness were excluded. Women who were pregnant, lactating or not maintaining proper contraception were not eligible. Concomitant use of Chinese medicines other than the study drug was not allowed. After assessment by a neurologist, eligible patients were assessed by a TCM practitioner to ensure their eligibility for the current TCM formulation according to TCM theories. Patients had to be diagnosed with the TCM syndrome of “asthenia of the spleen and stomach” before randomization . InformeThis was a prospective, randomized double-blinded placebo-controlled study. Patients were randomly allocated to receive either 24 weeks of active herbal formulation or placebo with each dose of their levodopa treatment. Stratified blocked randomization was carried out by dividing the sample at baseline into participants with H&Y stages I, II, III or IV, and then carrying out a blocked randomization within each of these four strata by a computer-generated list of random numbers. Randomization information was kept in a blinded format by an independent research assistant (S.C.M.) who had provided the active drugs and placebos. It was kept in a location far away from the clinic where patients were being assessed. Emergency envelopes with the randomization code were also kept with the TCM practitioner (Y.C.L.) at the School of Chinese Medicine in Hong Kong Baptist University. The assessor (W.F.K.) and patients were blinded to treatment allocation for the duration of the study. Treatment assignments were not revealed until the study was finished. The study started in February 2007 and finished in June 2008.Zhang Lu of the Qing Dynasty (1695). This formula is specific for the TCM syndrome that matches symptoms of PD, and it is the basis of many over-the-counter patent medicines that are widely available in Chinese herbal stores throughout the world. Based on the original recipe for JWLJZT, the herbal preparation used in this study contained 11 herbs as listed in Momordica charantia fruits. This was packed in the same manner as the active herbal medicine in opaque aluminum bags. All packages were distributed by an independent researcher in another room after the patients' visits. Patients were instructed to dissolve the granules in each package in hot water and drink once daily. For this study, we used herbal granules prepared according to the formula of TCM doctor Qi Scale (DSQS) [Baseline evaluation was performed before randomization and comprised: the 39-item Parkinson's Disease Questionnaire  ; Unifiede (DSQS) . Side efThe same TCM practitioner (W.F.K.) also assessed the patients during each visit based on standard TCM practice, including inspection, auscultation and olfaction, interrogation, pulse-taking and palpation. Alteration of the study herbal medications was not allowed during the study period.Follow-up evaluations were held for all patients at 12 weeks (on treatment) and 24 weeks (end of treatment). Assessment was carried out in the “on” state, that is, time of optimal medication effect as defined by the patient. Follow-up examinations were carried out at similar times of the day to attenuate effects of motor fluctuations.Based on previously published studies , 18, a st-test was applied to 12 weeks and 24 weeks—baseline differences, respectively, for the two groups of patients. Differences within groups before and after the 12 and 24 weeks treatment were determined using paired t-test. For non-normally distributed data, the Mann-Whitney U-test or Wilcoxon's rank sum test was used as appropriate. A P-value ≤.05 was considered to be statistically significant.All efficacy analyses were performed in the intent-to-treat (ITT) population, which comprised all randomized patients who had a baseline measurement and at least one measurement while on the study drug. Statistical analysis was performed using SPSS software version 12 . Normality of data was checked by K-S test. For normally distributed data, independent Student's A total of 106 patients with PD were screened, of which 55 met the inclusive criteria and were randomized. Twenty-eight patients were allocated to receive herbal medicine and 27 to receive placebo. The patient flow and reasons for exclusion are shown in P < .05). UPDRS Part IVC (other complications) scores in the TCM group were significantly improved from 1.09 to 0.64 points and 0.50 points at 12 and 24 weeks, respectively, (P < .05). Communications at 12 and 24 weeks significantly worsened in the placebo group from baseline 23.75 to 30.67 points and 29.67 points, respectively, . There was no difference between control group and TCM group in the items of the SF-36 Health Survey. There were also no significant changes in other parameters including GDS, DSQS, mean “off” time, and the structured interview items in the test and the control groups (Data not shown). The mean score of PDQ-39 single index, total UPDRS and other parameters with significant change are shown in P < .05). There was no group effect on the rest of the sections of PDQ-39. TCM reduced complications of therapy (UPDRS Part IV) more than placebo at 12 weeks (P = .03) but not at 24 weeks. However, there was a trend for TCM to improve the UPDRS Part IV score more than placebo at 24 weeks (P = .09). UPDRS Part IVC (other complications) score improved significantly more with TCM than with placebo at both time points (P < .05). There was no group effect on other parts of UPDRS (data not shown). For the measures in SF-36, GDS, DSQS, mean “off” time, and the structured interview items, there were no significant differences between the TCM group and the placebo group (data not shown). Comparisons between the TCM group and the control group in PDQ-39 single index, total UPDRS and other parameters with significant difference are summarized in Most patients tolerated the study drug well. One patient in the TCM group suffered from mild diarrhea. No other adverse effects were reported by patients.Despite widespread enthusiasm for TCM among the public, there is little controlled clinical data on its efficacy. In this research, we studied the efficacy of an ancient TCM formulation in treating idiopathic PD in Chinese patients. This study has various special features. First, while there are significant differences in the theory between TCM and conventional Western medicine, we were able to include patients with a diagnosis confirmed by both Western criteria of PD (UK Brain Bank) and TCM diagnostic criteria , 12. ThiJWLJZT, made from a Chinese herbal decoction, significantly reduced some non-motor complications in patients with PD under conventional medicine treatment. The major improvement was reflected by the reduction of score in UPDRS IVC which assessed gastrointestinal disorders, such as anorexia, nausea and vomiting, sleep disturbances, such as insomnia and hypersomnolence, and symptomatic orthostasis. In addition to the UPDRS IVC results, our results showed significant improvement in the whole UPDRS IV in JWLJZT groups after 12 and 24 weeks of treatment. However, these results are not conclusive because analysis of the UPDRS IV as three separate parts showed no significant changes in the dyskinesias section (UPDRS IVA) nor in the clinical fluctuations section (UPDRS IVB). Also, there was no significant change in the mean daily “off” time in both groups as measured by home diaries, despite a trend of reduction of mean daily “off” time in JWLJZT groups at 24 weeks . Our results are supported by the findings of a previous clinical trial which assessed the efficacy of another herbal medicine, “Zhenzhanning”(ZZN), in PD [The results of this study showed that ), in PD . It was ), in PD –23.Liu Jun Zi Tang (LJZT) in treating PD patients with clinical fluctuation. It focused on the influence of reduced gastric emptying in PD patients which may lead to fluctuations in the plasma levels of levodopa. As a result, they used LJZT and levodopa to treat seven PD patients with motor fluctuations. Assessment included observation of tremor, rigidity and bradykinesias, the patient's subjective scoring scale, absorption of Acetaminophen, and plasma level of levodopa. Two weeks later, the results showed that LJZT significantly improved patient's mobility and percentage of mean daily “on” time. Moreover, frequency of gastric discomfort, anorexia and nausea were lowered. In the meanwhile, improvement in gastric emptying and stability of plasma levodopa level was noted. This may explain why, in our study, JWLJZT could alleviate non-motor complications that are acute side effects of levodopa such as nausea, vomiting and orthostatic hypotension because these effects have been shown to be correlated with plasma levodopa concentrations [JWLJZT.A previous clinical study evaluated the effects of a prescription similar to ours  . Hiyama trations . FurtherJWLJZT significantly affects communications as assessed by the PDQ-39. Throughout the study, the control group's communication scores worsened, while in the treatment group, improvement was noted at 12 and 24 weeks. Differences between these two groups were significant. PDQ-39 measures communication in different contexts, including difficulty with speech, feeling unable to communicate properly and feeling ignored by people. In fact, changes in speech and voice in PD patients occur in up to 80–90% of cases and these changes can affect intelligibility, ability and desire to communicate [Naokangtai capsule” on 62 cases of PD patients [Another important observation of our RCT is that municate , 27. In municate . In consmunicate . Our finpatients . Their rpatients .JWLJZT had no effect on Parkinsonian motor abnormality. Distinct from conventional Western medicine, individualized treatment according to patient's current TCM symptom complex is regarded as a major feature of TCM. Nevertheless, because of difficulties in standardization and sufficient blinding for individualized treatment, we have not assessed the efficacy of individualized treatment in this trial. The potential drawback of standardized treatment is a possible loss in the efficacy of the Chinese herbal medicine treatments due to a lack of individualized therapy, as performed in the traditional way. A clinical trial with proper design is merited to evaluate the efficacy of individualized herbal treatment in patients with PD [In this study,  with PD .JWLJZT affects PD could point the way to further advances and even better clinical treatment of PD. Also, studies with larger sample sizes are required which would have increased statistical power and would be able to better determine if JWLJZT can offer long-term control of PD and retard the progression of this disease.In conclusion, the 11-herb TCM prescription resulted in significant improvement in some non-motor complications of conventional medicine treatment and communications abilities in patients with idiopathic PD. Studies of the biochemical mechanisms by which Grant EYS/07-08/01 from Eu Yan Sang (Hong Kong) Limited; faculty research grants FRG/08-09/I-01 from Hong Kong Baptist University.


Patients experiencing lower body pain resulting from bone metastases have greater levels of functional interference than those with upper body pain. The purpose of this study was to assess the levels of interference caused by pain after treatment with conventional radiotherapy using the Brief Pain Inventory (BPI) and to validate this tool for telephone use. After radiotherapy, a total of 159, 129, and 106 patients completed the BPI over the telephone at months 1, 2, and 3, respectively. Cronbach's alpha, confirmatory factor analysis, and discriminant validity tests were performed to assess the validity of the BPI. One-way ANOVA was used to compare BPI scores. There was no statistically significant difference in functional interference among patients after treatment. Internal consistency of the BPI was high. Functional interference may be inherently higher in patients with pain in the lower body. Telephone use of the BPI is reliable and recommended in this population. Bone metastases can occur in up to 70% of patients with advanced cancer , and theBone metastases have received much attention in the literature regarding effective treatments and management of pain resulting from the disease , 7–9. ThThe Brief Pain Inventory (BPI), developed by Cleeland and Ryan , has beeThe BPI is usually administered to patients prior to treatment in person. When following palliative patients, it is beneficial to reduce their number of visits to a health care centre. Studies in the past –15 have The Rapid Response Radiotherapy Program (RRRP) at the Odette Cancer Centre, Toronto, Canada provides rapid access to palliative radiotherapy. During the period lasting from May 2003 to June 2007, patients with bone metastases referred to the RRRP and subsequently treated with palliative radiotherapy were screened for eligibility for this prospective study assessing pain and functional interference using the Brief Pain Inventory (BPI). The institution's research ethics board had approved this study prior to commencement. Baseline data was collected, and patients were followed at four-week intervals following the end of radiotherapy for a total of 12 weeks . Patients were contacted by telephone for these followups by a trained research assistant. The BPI questions were read out loud, and the patient did not have a physical copy present when answering the items.The BPI is a validated multidimensional pain assessment tool developed by Cleeland and Ryan  which isThree questions regarding pain intensity and seven regarding pain interference are rated on an ordinal numerical scale with anchors of 0 (no pain/interference) to 10 (maximum pain/interference). Pain intensity is measured according to the worst pain experienced in the last three days, average pain in the last three days, and current pain. Pain interference assesses how that pain has affected general activity, mood, walking ability, normal work, relations with others, sleep, and enjoyment of life.Demographic results were expressed as means, standard deviations (SD), medians and interquartiles for continuous variables, and proportion for categorical values. Patients with complete data (no missing items on the BPI) were used for analysis. All analyses were repeated at all three follow-up intervals where data was collected. All analyses  were used to validate the psychometric properties of the BPI.Patients were separated into groups based on the location of pain: upper or lower skeletal metastases. Upper pain included patients receiving treatment to cervical or thoracic spine, shoulder girdle/upper extremity, ribs, and skull. Those receiving treatment to the lumbar spine, sacrum, or any of the pelvic girdle , femur , and tibia were classified as having “lower skeletal pain”. Those receiving treatment to the thoracolumbar spine were excluded from this portion of the analysis to prevent inaccurate reporting of pain location. One-way ANOVA was applied for comparing mean scores of BPI subscales in patients with lower or with upper skeletal bone metastases at different follow-ups and also at baseline.With two- and three-factor analysis, item-item correlations were examined to identify redundant questions. Standardized Cronbach's alpha was applied to estimate internal consistency within each subscale . ChangesCFA was used to examine the structure of the BPI as a single construct , two-factor (pain and interference), and three-factor model  for each follow-up period  . CovariaR-squared and t-statistic), and composite reliability were provided for the best two-factor and three-factor models. Composite reliability is a measure of the overall reliability of a collection of heterogeneous but similar items. The minimum acceptance level of composite reliability is 0.70, and the minimum critical t value is 3.29 for P = .001. Standardized factor loadings, associated statistics  were carried out to further evaluate highly correlated factors within the three-factor model. The variance extracted estimates the amount of variance that is explained by an underlying factor in relation to the amount of variance due to measurement error. Fornell and Larcker suggested that constructs should exhibit estimates of 0.50 or larger . It shouP  value of less than  .05 was considered as statistically significant.All analyses were performed using Statistical Analysis System (SAS version 9.2 for Windows) software. Confirmatory factor modeling was carried out using SAS covariance analysis of linear structural equations (PROC CALIS). A two-sided A total of 212, 159, and 133 patients at weeks 4, 8, and 12, respectively, had at least partial data. Of these patients, 159 (75%), 129 (81%), and 106 (80%) had complete data at weeks 4, 8, and 12, respectively, and this cohort formed the study population for analyses on pain and interference. Of the study population at week 4, median age was 65 (range: 30–89), 88 of patients (55%) were male, and 94 patients (60%) were classified as having lower body pain . At weekP  values not statistically significant). At week 8, mean values for pain, activity, and affect in patients with lower skeletal pain were 3.69, 4.63, and 3.39, respectively, in comparison to 3.42, 3.57, and 2.98 for those with upper skeletal pain . At 12 weeks posttreatment, pain was significantly worse for patients with upper skeletal pain than those with lower skeletal pain (P = .0278), but interference levels (both activity and affect) were similar.Analysis of baseline data showed that patients with lower skeletal pain had significantly greater activity interference than those with upper skeletal pain; this is similar to the result obtained by Wu et al.  in theirThere was internal consistency among all items except sleep at each follow-up period. Improvement in correlation was seen at each follow-up period and in both two- and three-factor subscales when the sleep item was improved. Alpha for two-factor analysis improved from 0.48 to 0.91 at 4 weeks, 0.54 to 0.91 at 8 weeks, and finally, 0.56 to 0.91 at 12 weeks. For the three-factor analysis, removal of sleep from the activity subscale improved alpha from 0.45 to 0.87 at 4 weeks, 0.48 to 0.90 at 8 weeks, and 0.53 to 0.90 at 12 weeks . In all In general, both the two-factor and the three-factor models demonstrated reasonably high levels of internal consistency, composite reliability, and convergent validity Tables  and 5. TFactor loading and associate statistics for the best two-factor and three-factor analyses were constructed at each follow-up period. The correlation between grouped items  was high for all three data sets  test indicated correlation of 0.88, 0.87, and 0.85 at weeks 4, 8, and 12, respectively, , the Chi-square difference test demonstrated significance between mixed and separated support at all followups. The variance-extracted test failed to confirm discriminant validity for all three sets of data. Despite these results, the combination of different analyses confirmed the validity of the construct since reasonably high levels of internal consistency, composite reliability, and convergent validity were present at weeks 4, 8, and 12. Although the two-factor model is adequate, the three-factor model is preferred since fewer covariance terms were needed to fit the model. Furthermore, this model satisfies an additional IMMPACT recommendation.Functional interference is a significant component of quality of life in advanced cancer patients which has seldom been addressed in the literature. It has been shown that improvement in metastatic bone pain will similarly improve functional interference as a result of this pain . The BPIThe fact that interference levels are worse in lower skeletal pain patients prior to radiotherapy suggests that in general people exhibiting lower body pain will have more functional interference than those with upper body pain, not only inclusive to patients with bone metastases pain. Studies, however, have suggested that there is an inherent difference among pain interference between cancer and noncancer patients  meaning The BPI has been used in numerous studies via telephone, to assess a patient's response to treatment. Although the questions remained the same whether asking a patient across the phone or in person, the differences in setting may affect responses and consequently the validity of the BPI. When comparing the statistical analyses to results of Wu et al., who validated the BPI in patients with bone metastases physically in clinic with the same methods , the simThe sleep item of BPI contributes little to both the activity or affect subscales of three-factor analysis and interference in general in the two-factor analysis. Previous papers have also noted this difference when conducting an analysis of the BPI , 22–24. A further point of research would be to test the correlation of the BPI with other musculoskeletal functional scales, such as the Western Ontario and McMaster University Osteoarthritis Index (WOMAC)  and the The BPI is a valid and reliable tool for use across the telephone and should be the preferred mode of contact when following up with advanced cancer patients. CFA of the BPI demonstrates validity with both the two- and three-factor models; however, the latter is preferred as fewer covariance terms are needed to fit the model and it satisfies an additional IMMPACT factor. Patients with lower skeletal pain resulting from bone metastases should receive prompt treatment to reduce their functional interference and improve their overall quality of life. The preferred modality for following palliative patients with quality-of-life assessments should be via the telephone as it reduces the travelling burden associated with multiple visits to a health care setting.The authors have no conflict of interests to disclose.


The aim of this study was to investigate and compare Ranson criteria (RC) and RC + serum CRP levels as a feasible, practical and precise method in acute pancreatitis (AP) cases admitted to the ICU in respect of length of stay (LOS) predicting severity of disease.This study was based on determination of RC scores in AP cases in a retrospective manner. On the other hand, this study included only the patients' zero-time RC scores, not the 48-hour scores, for the sake of more practical precision. Serum CRP levels were found to have prognostic importance in AP, significantly more than 150 mg/l in necrotizing AP, at 50 mg/l in this study. Therefore, patients' were evaluated for RC and RC + CRP scores for comparison. However, RC had been etiologically modified for presence of gall bladder stones (GBS); only the cases without GBS were included in order to prevent bias of results. In addition, necrotizing cases were assumed to increase CRP levels more than predicted and were also excluded. After the exclusion of cases, 89 patients' data were collected and compared for LOS in the ICU between 2005 and 2009.P < 0.05), RC + CRP together (P < 0.01) and CRP alone (P < 0.04). Severity of the disease and therefore LOS were increased for RC score >3 and CRP levels >50 mg/l. ROC analysis resulted in RC (AUC 0.895), RC + CRP (AUC 0.901) and CRP (AUC 0.823) for LOS.Statistical analysis of patients' data for significance and receiver operating curve (ROC) analysis to predict LOS, therefore pointing to disease severity, was executed. All of the statistical comparisons were found significant for predicting LOS; RC (AP cases usually require ICU care and treatment. There are some consented scoring systems such as RC, APACHE II and Glasgow in predicting disease severity and guiding the physician's approach. Although the most sensitive and specific method seemed to be APACHE II scoring, it is time consuming and complex. On the other hand, RC and Glasgow scorings need to be evaluated in 48 hours. In the end, in the hardworking hours on the ICU, we need a more practical method of provision. In this study, we have found no priority of RC, RC + CRP and CRP alone in predicting AP outcome, excluding GBS disease and necrotizing cases. We conclude that, practically, ICU physicians could substantially depend on CRP levels alone in the evaluation and approach in these specific cases of AP.


Overweight and obesity in pregnancy increase the risk of several adverse pregnancy outcomes. However, both mothers’ and fathers’ health play an important role for long-term health outcomes in offspring. While aspects of health and lifestyle of pregnant women have been reported, the health of expectant fathers and correlations of health variables within couples have received less attention. This study aimed to explore the prevalence and socio-demographic patterns of overweight and obesity in Swedish expectant parents, and to assess within-couple associations.This population-based, cross-sectional study investigated self-reported data from 4352 pregnant women and 3949 expectant fathers, comprising 3356 identified couples. Data were collected in antenatal care clinics between January 2008 and December 2011. Descriptive, correlation and logistic regression analyses were performed.The self-reported prevalence of overweight (BMI 25.0-29.99) and obesity (BMI ≥30.0) was 29% among women (pre-pregnancy) and 53% among expectant fathers. In a majority of couples (62%), at least one partner was overweight or obese. The odds of being overweight or obese increased relative to partner’s overweight or obesity, and women’s odds of being obese were more than six times higher if their partners were also obese in comparison with women whose partners were of normal weight . A socio-demographic gradient was found in both genders in relation to education, occupation and area of residence, with higher odds of being obese further down the social ladder. The cumulative influence of these factors showed a substantial increase in the odds of obesity for the least compared to the most privileged .The prevalence of overweight and obesity in expectant parents was high, with a clear social gradient, and a minority of couples reported both partners with a healthy weight at the onset of pregnancy. Partner influence on health and health behaviours, and the role both mothers and fathers play in health outcomes of their offspring, underpin the need for a more holistic and gender inclusive approach to the delivery of pregnancy care and postnatal and child health services, with active measures employed to involve fathers. It is well known that parent and child health are closely interlinked ,2, and tOverweight and obesity have become a major global health concern, and are now associated with more deaths worldwide than underweight . The preEven though current evidence suggests that both parents are important for offspring health ,30, the The research questions were: 1) What is the prevalence of overweight and obesity in expectant parents and couples, and what are the gender differences?, 2) Are there any within-couple associations of BMI?, and 3) What are the associations between socio-demographic characteristics, and overweight and obesity?Data for this population-based, cross-sectional study were obtained via the Salut Programme, an ongoing child health promotion programme in the county of Västerbotten , Sweden. The programme was initiated by the County Council in 2005, and aims to support health promotion activities in ANC, child health care (CHC), dental services, social services, pre-schools and schools, and also to develop an epidemiological surveillance system. The Salut Programme has been further described elsewhere -40. Data2) [BMI, defined as weight in kilograms divided by the square of height in metres (kg/m2) , was cal2) .Socio-demographic data were education, occupation, area of residence, country of birth, and the pregnant woman’s cohabitation status. We categorised educational levels into ≤9 years, 11–12 years (completed senior high school), >12 years, and a completed university degree; occupational status was categorised into 'employed’, 'studying’, 'parental leave/unpaid domestic work’, 'unemployed’, and 'sick leave/retirement’. We used the location of the ANC clinic as a proxy measure for area of residence. ANC clinics located in the two largest cities, Umeå and Skellefteå (including a radius of 15 kilometres), were defined as urban areas with a population density of 2300 and 1500 people per km2, respectively, [Country of birth was dichotomised into 'Sweden’ or 'other’, and women’s cohabitation into 'with expectant father’ or 'other/single’.ctively, , all othIn addition to descriptive data, the Chi-square test for independence was used to explore differences between categorised variables (with Yates Continuity Correction for 2 by 2 tables), and the independent samples t-test was used to compare differences in mean scores between groups. Within-couple associations of BMI were investigated using Spearman rank order correlation. Logistic regression analyses were used to estimate crude odds ratios (OR) and confidence intervals (95% CI) for within-couple associations of overweight and obesity. The relationship between categorised BMI and categorical independent variables were investigated using Chi Square tests. Logistic regression analyses were then undertaken to estimate crude odds ratios and 95% CI for the association between socio-demographic factors and overweight/obesity. The analyses were repeated in a multivariate logistic regression analysis where age and socio-demographic factors were used as adjustment variables. Finally, logistic regression analyses were performed to estimate age-adjusted odds ratios and 95% CI for the association between eight different combinations of socio-demographic factors and overweight/obesity. In these analyses, all variables were dichotomised. Data for pregnant women and expectant fathers were combined to increase robustness of the analyses, particularly as preliminary analyses revealed similar patterns for women and men. Because a correlation of BMI within couples was found, an exchangeable correlation structure was assumed and the parameters were estimated with generalised estimating equations. In all regression analyses, the reference population was participants with BMI <25.0, thus, obese participants were excluded in regressions for overweight, and overweight participants were excluded in regressions for obesity. Interaction analyses for independent variables in relation to BMI revealed no interactions. Sample sizes decreased in multivariate analyses, as complete data for each participant was required for inclusion. Statistical significance was defined as p<0.05 or a 95% CI excluding 1.0. SPSS Statistics software (version 19) was used in all analyses.Study participation was based on informed consent, and the study complied with the Helsinki Declaration. Ethics approval was obtained from the Ethics Review Board of Umeå University, Sweden (Ref. 2010-63-31M).Socio-demographic characteristics of study participants are given in Table As shown in Table As shown in Table We found a positive partner correlation for BMI . Furthermore, as shown in Table Significant associations were found between BMI and education, occupation, and area of residence, respectively, for both genders, but not between BMI and country of birth or pregnant women’s cohabitation status, respectively. We found a gradient in the odds of obesity for both women and expectant fathers in relation to educational level, occupational status and area of residence Table . The oddAs shown in Table Four main findings emerged from this study. First, overweight and obesity were prevalent in one third of women just prior to pregnancy and in more than half of expectant fathers. Second, in a majority of couples, at least one partner was overweight or obese. Third, BMI was correlated within couples, and the odds of being overweight or obese increased relative to partner’s overweight or obesity, with women having more than six times the odds of reporting obesity if their partners were obese, in comparison with women whose partners reported normal weight. Lastly, a clear stepwise socio-demographic pattern was found in relation to obesity, with higher odds of being obese further down the social ladder. This pattern was not as strong in relation to overweight.The combined prevalence of overweight and obesity in this study is similar to that previously reported from selected areas in Västerbotten , while tOur finding that at least one of the two partners reported overweight or obesity in a majority of couples has important long-term implications, as the prevalence of offspring overweight and obesity has been shown to be low in families with two normal-weight parents, while the risk gradually increases depending on whether one or both parents are overweight or obese as well as with increasing weight of the parents ,30,45,46The correlation of BMI within couples found in this study was similar to that reported in other populations ,50. The The clear socio-demographic gradients found in relation to obesity have also been reported in other studies ,59-61, wExpectant parents’ own awareness of maternal and offspring risks associated with parent overweight and obesity seems to be an understudied area . In a prThe strengths of this study are the large population-based sample, which enhances the external validity of the study findings, the inclusion of expectant fathers, and also that couples could be identified. The pregnant women had a similar mean age and mean BMI at enrolment as the general pregnancy population in Västerbotten and Sweden ,75. The An overestimation of height and an underestimation of weight has been common in self-report studies among both women and men ,79. ThisThe prevalence of overweight and obesity in expectant parents was high, with a clear social gradient, and a minority of couples reported both partners with a healthy weight at the onset of pregnancy. Partner influence on health and health behaviours, and the role both mothers and fathers play in health outcomes of their offspring, underpin the need for a more holistic and gender inclusive approach to the delivery of pregnancy care and postnatal and child health services, with active measures employed to involve fathers.The authors declare that they have no competing interests.KE, ML, EE, IM and AI designed the study. KE and ML conducted the analyses and KE drafted the manuscript. RS read and revised the manuscript with specific attention to language and clarity of presentation. All authors contributed in the writing process and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2458/13/923/prepubExcerpts from the pregnant woman’s questionnaire.Click here for fileExcerpts from the expectant father’s questionnaire.Click here for file


Blood glucose monitoring has been established as a valuable tool in the management of diabetes. Since maintaining normal blood glucose levels is recommended, a series of suitable glucose biosensors have been developed. During the last 50 years, glucose biosensor technology including point-of-care devices, continuous glucose monitoring systems and noninvasive glucose monitoring systems has been significantly improved. However, there continues to be several challenges related to the achievement of accurate and reliable glucose monitoring. Further technical improvements in glucose biosensors, standardization of the analytical goals for their performance, and continuously assessing and training lay users are required. This article reviews the brief history, basic principles, analytical performance, and the present status of glucose biosensors in the clinical practice. Worldwide, it is a leading cause of morbidity and mortality and a major health problem for most developed societies. The prevalence of diabetes continues to increase. The crude estimated prevalence of diabetes in adults in the United States (US) has been reported to be 9.6% 20.4 million) in 2003–2006 . Moreove million Multiple laboratory tests are used for the diagnosis and management of patients with diabetes. The blood glucose concentration is the major diagnostic criterion for diabetes with HbA1c level  and is aAccording to the recommendations of the ADA, SMBG should be used in patients on intensive insulin therapy (at least three times daily). And it may useful in patients using less frequent insulin injections, noninsulin therapies, or medical nutrition therapy alone .Due to such recommendations for maintaining normal blood glucose levels, a series of suitable glucose-measuring devices have been developed. Biosensor technology has developed rapidly and can play a key role providing a powerful analytical tool with major applications particularly in medicine. Today’s biosensor market is dominated by glucose biosensors. In 2004, glucose biosensors accounted for approximately 85% of the world market for biosensors, which had been estimated to be around $5 billion USD . The gluThis article reviews the brief history of biosensors, basic principles of operation, analytical performance requirements, and the present status of glucose biosensors. In addition, how to assess the reliability of testing in clinical practice will be discussed.2.A biosensor can be defined as a “compact analytical device or unit incorporating a biological or biologically derived sensitive recognition element integrated or associated with a physio-chemical transducer” . There aGenerally, glucose measurements are based on interactions with one of three enzymes: hexokinase, glucose oxidase (GOx) or glucose-1-dehydrogenase (GDH) ,31. The The basic concept of the glucose biosensor is based on the fact that the immobilized GOx catalyzes the oxidation of β-D-glucose by molecular oxygen producing gluconic acid and hydrogen peroxide . In ordeThe cofactor is regenerated by reacting with oxygen, leading to the formation of hydrogen peroxides.Hydrogen peroxide is oxidized at a catalytic, classically platinum (Pt) anode. The electrode easily recognizes the number of electron transfers, and this electron flow is proportional to the number of glucose molecules present in blood .H2O2→2HThree general strategies are used for the electrochemical sensing of glucose; by measuring oxygen consumption, by measuring the amount of hydrogen peroxide produced by the enzyme reaction or by using a diffusible or immobilized mediator to transfer the electrons from the GOx to the electrode. The number and types of GDH-based amperometric biosensors have been increasing recently. The GDH family includes GDH-pyrroquinolinequinone (PQQ) –39 and G+. GDH-PQQ is a particularly efficient enzyme system, with a rapid electron transfer rate, but it is relatively expensive [This mechanism requires neither oxygen nor NADxpensive .2O2. NAD is a major electron acceptor in the oxidation of glucose, during which the nicotinamide ring of NAD+ accepts a hydrogen ion and two electrons, equivalent to a hydride ion. The reduced form of this carrier generated in this reaction is called NADH, which can be electrochemically oxidized.GDH with NAD as a cofactor produces NADH rather than H3.Although a variety of glucose sensors are available, the glucose biosensor has changed little in principle over several years . However3.1.The concept of the biosensor for measuring glucose levels was first proposed in 1962 by Clark and Lyons from the Children’s Hospital of Cincinnati ,47. TheyThe first commercially successful glucose biosensor using Clark’s technology was the Yellow Springs Instrument Company analyzer  for the direct measurement of glucose in 1975, which was based on the amperometric detection of hydrogen peroxide. This analyzer was almost exclusively used in clinical laboratories because of its high cost due to the expensive platinum electrode.The first-generation glucose biosensors were based on the use of natural oxygen substrate and on the detection of the hydrogen peroxide produced. Measurements of peroxide formation have the advantage of being simpler, especially when miniature devices are being considered . HoweverConsiderable efforts during the late 1980s were devoted to minimize the interference of endogenous electroactive species, such as ascorbic acid, uric acid, and certain drugs. Another drawback was the restricted solubility of oxygen in biological fluids, which produced fluctuations in the oxygen tension, known as the “oxygen deficit” .3.2.i.e., second-generation glucose sensors. The improvements were achieved by replacing oxygen with non-physiological electron acceptors, called redox mediators that were able to carry electrons from the enzyme to the surface of the working electrode [The abovementioned limitations of the first-generation glucose biosensors were overcome by using mediated glucose biosensors, lectrode . A reduclectrode . A varielectrode –53. Ferrlectrode ,54–56. Tlectrode . Howeverlectrode .During the 1980s, mediator-based second-generation glucose biosensors, the introduction of commercial screen-printed strips for SMBG, and the use of modified electrodes and tailored membranes for enhancing the sensor performance were developed and implemented ,51,59–62Various strategies to facilitate electron transfer between the GOx redox center and the electrode surface have been employed, such as enzyme wiring of GOx by electron-conducting redox hydrogels, the chemical modification of GOx with electron-relay groups and the application of nanomaterial as electrical connectors ,63–65.3.3.in vivo monitoring of blood glucose. Conducting organic salts, such as tetrathiafulvalene-tetracyanoquinodimethane (TTF-TCNQ), are known to mediate the electrochemistry of pyrrole-quinolinequinone enzymes (GDH-PQQ) as well as of flavoproteins (GOx). And the absence of mediators provides the biosensors with superior selectivity. However, only a few enzymes including peroxidases have been proved to exhibit direct electron transfer at normal electrode surfaces [The third-generation glucose biosensors are reagentless and based on direct transfer between the enzyme and the electrode without mediators. Instead of mediators with high toxicity, the electrode can perform direct electron transfers using organic conducting materials based on charge-transfer complexes ,67. Thersurfaces ,68. Sevesurfaces ,67, the surfaces ,69,70, asurfaces .4.ex vivo monitoring of blood glucose was proposed in 1974 [in vivo glucose monitoring was demonstrated in 1982 [Continuous  in 1974 , while i in 1982 . CGMS woTwo types of continuous glucose monitoring systems are currently in use - a continuous subcutaneous glucose monitor and a continuous blood glucose monitor. However, due to surface contamination of the electrode by proteins and coagulation factors and the risk of thromboembolism, most of the CGMSs do not measure blood glucose directly. Therefore, subcutaneously implantable needle-type electrodes measuring glucose concentrations in interstitial fluid have been developed, which reflect the blood glucose level –77.et al. described the first needle-type enzyme electrode for subcutaneous implantation in 1982 [Shichiri  in 1982 . The fir in 1982 . The FDA in 1982 .Continuous subcutaneous glucose monitoring can also be achieved without direct contact between the interstitial fluid and transducer by using the microdialysis technique ,81. Glucin vivo CGMS include biocompatibility, calibration, long-term stability, specificity, linearity, and miniaturization. The accuracy of these innovative devices is lower than that of traditional glucose biosensors. Although CGM can be associated with improved glycemic control in adults and children with type 1 diabetes [However, numerous requirements of diabetes –86, the diabetes .5.Non-invasive glucose analysis is another goal of glucose sensor technology and significant efforts have been made to achieve this goal. Optical or transdermal approaches are the most common noninvasive glucose sensing methods ,89. The The GlucoWatch Biographer, manufactured by Cygnus, Inc. , was the first transdermal glucose sensor approved by the US FDA. This watch-like device was based on transdermal extraction of interstitial fluid by reverse iontophoresis. It never widely accepted in the market due to long warm up time, false alarm, inaccuracy, skin irritation and sweating. It was withdrawn in 2008. Considerable efforts have been made in the development of non-invasive glucose devices. However, reliable non-invasive glucose measuring method is still not available.6.Although laboratory analysis is the most accurate method for evaluating glucose levels, because of cost and time delays, POCT is widely used to determine glucose levels in the inpatient (ER/ICU/ward) and outpatient (office/home) setting. The majority of POC glucose biosensors rely on disposable, screen-printed enzyme electrode test strips . These pSince the launching of ExacTech in 1987, the portable glucose biosensors have achieved the most significant commercial success. Subsequently, many different devices have been introduced on the global market. The 2010 issue of the Diabetes Forecast Resource Guide, which has a clear focus on the US market, lists 56 different POC glucose sensors from 18 different companies. However, over 90% of the market consists of products manufactured by four major companies, including Abbott, Bayer, LifeScan, and Roche. A brief summary of the key features of commercially available glucose biosensors is provided in Currently, many POC devices can be directly connected to laboratory information systems via proprietary data management system. This significantly expands the data management and networking capabilities of bedside glucose biosensors, and allows for centralized quality control management.7.Glucose biosensors are easy to handle, require minimal amounts of blood, and can perform rapid measurements. Suboptimal measurement quality can lead to significant inaccuracies and increased patient morbidity and mortality. Therefore, a number of criteria for analytical performance have been recommended. In 1994, the ADA made available the first recommendations for the analytical performance of glucose biosensors, suggesting a <10% threshold of maximum allowable bias from reference methods for glucose concentrations between 1.6 and 22.2 mmol/L . This anin vitro glucose monitoring systems that measure glucose concentrations in capillary blood samples and procedures for the verification and validation of performance by the intended users.For most glucose monitoring devices, the analytical performance has been validated by healthcare professionals according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. However, the ISO Technical Committee ISO/TC 212 released a protocol to validate the accuracy and repeatability of glucose monitoring devices at three to five different glucose levels in the ISO 15197 guideline . These gThe U.S. FDA guidelines document also provides recommendations for POC glucose biosensors using capillary whole blood. It recommends the study designs, statistical evaluations, and presentations outlined in ISO 15197 for precision, accuracy, and user performance evaluations  and in t7.1.7.1.1.Repeatability is evaluated at five glucose concentrations spread across the measuring interval  and should be measured over a short span of time, not to exceed one day per meter, with the same user, meter, and reagent lot. At least 500 reagent system units and 10 meters are required, and the preferred sample for evaluation is venous blood. The samples are equilibrated to a temperature of 23 °C ± 5 °C and maintained within ±2 °C of the starting temperature during the experiments. A total of ten measurements per sample per meter are performed. The mean value, the standard deviation (SD) and the coefficient of variation (CV) for each meter from the ten measurements are calculated. The grand mean, the pooled variance, the pooled SD  and the pooled CV are calculated.7.1.2.Intermediate precision is defined as precision under “conditions where the test results are obtained with the same method on identical test items in the same location, but where other variables such as operators, equipment, calibration, environmental conditions, and/or time intervals differ.”Intermediate precision evaluation is performed with control materials at three glucose concentrations . The evaluation is conducted with multiple meters and different users over at least 10 days. At least 300 reagent system units and 10 meters are required. It requires one measurement per day of a sample from each glucose concentration for 10 days for each of 10 meters. The mean, SD and CV for each meter from the ten measurements are calculated. The grand mean, the pooled variance, the pooled SD  and the pooled CV are calculated. The SD and CV are measures of the intermediate precision of a single system over multiple days.7.2.System accuracy is evaluated with at least 100 different subjects and two different meters over at least 10 days with capillary blood samples. The glucose concentrations should be distributed as specified in 7.3.versus glucose concentration values.Glucose biosensors should be evaluated for linearity across the reportable range. Therefore, data collection requires two to four replicates from 5 to 11 samples with varying concentrations that are known relative to one another by the dilution ratio or by the formulation. The correlation coefficient and linear regression equations are calculated from the obtained results 7.4.If the glucose biosensors are evaluated by highly trained health care professionals only, they could miss the complications that are likely to occur by patients using the devices . The purAt least 50 subjects, with varying demographics , should be included for each lot. User studies are conducted using at least three different reagent lots at multiple sites. After reviewing the routinely provided training materials, the users perform their own finger sticks and test themselves using the devices. Immediately after the user’s self-test, the investigation site’s trained healthcare professional measures the user’s blood with the devices.The second blood sample should be collected within five minutes. The results are fitted to regression equations with confidence intervals and plots showing all data points. The results should include a comparison of the user results, professional results, and reference results.7.5.A number of variables can influence the reliability of the test results, including hematocrit, hypoxemia, hypotension, altitude, temperature, and humidity. Electrochemical interferents in the blood cause a false high glucose reading by donating non-glucose-derived electrons. An interfering molecule is a species that is electroactive at the operating potential of the amperometric sensor. Suggested standard interferents developed by the FDA include: acetaminophen, salicylic acid, tetracycline, dopamine, ephedrine, ibuprofen, L-DOPA, methy-DOPA, tolazamide, ascorbic acid, bilirubin, cholesterol, creatinine, triglycerides, and uric acid .Hematocrit values have a marked effect on the strip-based glucose assay ,104. OxyAscorbic acid is one of the most common interfering substances that affect the accuracy of glucose biosensors ,107. Foret al. [GDH-PQQ catalyzes not only the oxidation of glucose, but also of other sugars, such as maltose, maltriose, maltotetraose, and icodextrin  –110. MosVarious drugs have been shown to interfere with glucose . Acetami8.The measurement of blood glucose levels is carried out using various glucose biosensors for the screening, diagnosis, and long-term management of patients with diabetes. Since the prevalence of diabetes is increasing, novel glucose biosensor technologies, including POC devices, CGMS, and noninvasive glucose monitoring systems, have been developed during the last few decades. Recently, the value of glucose biosensors at the POCT by medical professionals and the SMBG by patients has been widely accepted. Rapid and effective corrections of blood glucose levels are based on regular glucose measurements using glucose biosensors.Glucose biosensors have evolved to be more reliable, rapid, and accurate and are also more compact and easy to use. Research for advanced technologies, including electrodes, membrane, immobilization strategies, and nanomaterials, continue to be performed. Despite the impressive advances in glucose biosensor technology, there are still several challenges related to the achievement of reliable glucose monitoring. The ADA recommends the accuracy of a blood glucose POC assay to be <5% of the measured value. However, many POC devices do not meet this criterion. Biosensor technology is less precise and less accurate than the methods used in central laboratories .A more systematic evaluation of the analytical performance of glucose biosensors is recommended to ensure reliable and accurate testing. Analytical requirements for suitable hospital or home POC devices include good linearity, precision, and correlation when compared to a clinical laboratory reference method as well as resistance to common interferences. The calibration of the devices and quality control should be performed on a regular basis according to the manufacturer’s instructions. User-dependent factors can also affect data quality, and by extension, treatment outcomes. The most commonly cited problems are incorrect use of the test strip, lack of quality control procedure, fingers that are not clean and dirty devices. Various studies have shown that education and continuous training can reduce errors caused by the aforementioned factors and improve measurement performance .Therefore, in addition to further technical improvements of the biosensors, standardization of the analytical goals for improved performance, and continuous assessment and training of lay users should be established.


The prevalence of type 2 diabetes has reached epidemic proportions worldwide, and the incidence of life-threatening complications of diabetes through continued exposure of tissues to high glucose levels is increasing. Advances in genotyping technology have increased the scale and accuracy of the genotype data so that an association genetic study has expanded enormously. Consequently, it is difficult to search the published association data efficiently, and several databases on the association results have been constructed, but these databases have their limitations to researchers: some providing only genome-wide association data, some not focused on the association but more on the integrative data, and some are not user-friendly. In this study, a user-friend database of type 2 diabetes genetic association of manually curated information was constructed.The list of publications used in this study was collected from the HuGE Navigator, which is an online database of published genome epidemiology literature. Because type 2 diabetes genetic association database (T2DGADB) aims to provide specialized information on the genetic risk factors involved in the development of type 2 diabetes, 701 of the 1,771 publications in the type 2 Diabetes case-control study for the development of the disease were extracted.In the database, the association results were grouped as either positive or negative. The gene and SNP names were replaced with gene symbols and rsSNP numbers, the association p-values were determined manually, and the results are displayed by graphs and tables. In addition, the study design in publications, such as the population type and size are described. This database can be used for research purposes, such as an association and functional study of type 2 diabetes related genes, and as a primary genetic resource to construct a diabetes risk test in the preparation of personalized medicine in the future. However, an increase in the incidence of diabetes has not been stopped over the last decade, highlighting the need for new approaches. According to the World Health Organization (WHO), the number of people with type 2 diabetes worldwide was approximately 170 million and 280 million in 2000 and 2010, respectively, which is expected to increase to 430 million by 2030 [The prevalence of type 2 diabetes has reached epidemic proportions worldwide with the largest increase in Asia, Africa and South America . The inchttp://www.ncbi.nlm.nih.gov/pubmed, which researchers normally access to obtain information. Moreover, a systematic comparison of published data is not possible without considerable effort. Since association studies may have false positives or true negatives, it is important to compare one study with another before drawing a conclusion as to whether the association is true or not. Furthermore, the genetic effect size expressed by the odds ratio in association analysis is not always easy to find from text files.Following the growth of genomics, the disease susceptibility of human genetic variations has been examined to provide a better understanding of the pathophysiology of diabetes. The advances in genotyping technologies have increased the scale and accuracy of genotype data, thereby expanding enormously the number of genetic studies demonstrating a relationship between diseases and genetic variations. Consequently, it is difficult to search the massive number of publications from the text files in PubMed http://geneticassociationdb.nih.gov, dbGAP http://www.ncbi.nlm.nih.gov/sites/entrez?db=gap[http://www.genome.gov/gwastudies[http://t2ddb.ibab.ac.in[http://www.t1dbase.org[With these problems in this field, considerable effort has been made to implement public genetic association databases. There are several genetic association databases, such as Genetic Association Database ez?db=gap from NCBwastudies from NHGbab.ac.in and T1Dbdbase.org. These dTo provide focused information on a T2D association study, this study designed the T2D Genetic Association Database (T2DGADB). T2DGADB using 701 publications of the T2D study provides genetic association data that was manually curated and searchable. The web-based application displays comprehensive summaries of the published T2D genetic association results for browsing, visualization and mining. In addition, the data was displayed graphically adding convenience to understanding them.http://hugenavigator.net) [The list of publications used in this study was collected from the HuGE Navigator  ,9, whichtor.net) , which wTo select the 701 T2D development papers, the abstracts of 1,771 articles were downloaded through PubMed to be classified into T2D case-control articles or others. This information along with the title, authors, abstract, journal, online or in print publication date and PubMed ID to hyperlink to PubMed Abstract plus were deposited in the T2D Genetic Association Database. In addition, the full text of the 701 articles were downloaded, if accessible, to obtain all available text, tables, figures and supplemental data from the original articles. 625 of the 701 articles could be accessed but 76 articles could not be downloaded or were not written in English.Since dbSNP builds and human genome builds were updated frequently from 2001 to 2009, it was important to change the Gene names, SNP positions and SNP rs number. Some articles reported only the SNP position and nucleotide change information  instead of SNP ID (rs number), and in a few cases, they used their own SNP ID . Old gene names and gene aliases were replaced with the Entrez gene official symbol .The author's own SNP ID or SNP position information was replaced with the rs number using the HuGE Navigator Variant Name Mapper, which is an online tool to map the common variation names and rs numbers of genetic variants. However, it was too limited to find all the SNPs missing their own rs number because only 1,159 genes and 5,646 variants were deposited in the database . An alternative method was to use other databases, NCBI dbSNP, USCS Genome Browser and UCSC In-Silico PCR tool, based on the information provided by the articles. Some papers reported amino acid change information instead of the SNP ID. In this case, they were changed into rs numbers using SNP GeneView of NCBI dbSNP . In some cases, a pair of PCR primer sequences was provided for the SNP. The UCSC In-Silico PCR tool can obtain a PCR product sequence with the primer sequences reported in the paper. The UCSC Genome Browser could confirm whether the locations of the PCR product sequences match the genes or chromosome locations described by the author, and the SNPs within the sequences were selected.T2DGADB contains information on the study design and SNP association result Figure . The stuSNP association information summarizes the results of an association study for each SNP or variant. It contains variation information, such as position information, common name of SNP as reported by the authors, dbSNP rs number, gene name, allele frequency of the reported allele, which is minor allele or risk allele, odds ratio and 95% confidence interval (CI) and p-value. Information on the covariants was added if the authors reported an adjusted p-value for the confounding factors. The association result was determined to be "associated" if the p-value was <0.05 or the odds ratio and 95% CI were in a suitable range. In some cases, the range of odds ratio and 95% CI was suitable but the association result was not associated because the adjusted p-value was not <0.05. In the case where both results were provided in the article, the adjusted p-value was used to determine the association.T2DGADB web interface was implemented in JSP, HTML and Javascript and run on CentOS (version 4.7) with the Apache-Tomcat (version 6.0.18) web server. MySQL (version 4.1.18) was used as the DBMS (Database Management System).Figure http://t2db.khu.ac.kr:8080  (Figure This study is a small step in the preparation of a personalized diagnosis system. Using this data, T2D candidate genes can be selected and their risk be estimated. Eventually, the diabetes genetic association database can be utilized to make a computer program that provides health care providers with the individual susceptibility to diabetes for personalized medicine, and can be expanded to the selection of high risk groups for preventive medicine.In this study, a user-friend database of T2D genetic association of manually curated information was constructed. This database can be used for research purposes, such as an association and functional study of T2D related genes, and as a primary genetic resource to construct a diabetes risk test in the preparation of personalized medicine in the future.http://t2db.khu.ac.kr:8080.T2DGADB is freely available for academic and commercial users at The authors declare that they have no competing interests.JEL, KWH, HKP and BO conceptualised and designed the project. JEL, KWH, HSJ and YSK designed database scheme, input data structure and data curation condition. JEL and BO drafted the manuscript. YSK, HKP and BO contributed to the intellectual content of the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-6947/10/76/prepub


Obesity impairs health related quality of life (HRQL) in adolescents, but most evidence in this area has mostly come from western societies. We wanted to test the hypothesis that obesity impairs HRQL in Kuwaiti adolescents, and to test for differences in HRQL assessed by self-report and parent-proxy report.TM with both adolescent self-reports (n = 500) and parent-proxy reports (n = 374).In 500 Kuwaiti 10–14 year olds HRQL was assessed using the Peds QLObesity was not significantly associated with HRQL in regression analysis. In a paired comparison of 98 pairs of obese adolescents vs. 98 healthy weight peers, impairment of HRQL reached significance only for physical score , not for psychosocial score or total score. In a paired comparison of parent-proxy vs. self-reports for the obese adolescents, total score , physical score , and psychosocial score  were all significantly lower in the parent reports.Obesity is not associated with marked impairment of HRQL in adolescents in Kuwait, in contrast to studies in western societies. This may reflect cultural differences in attitudes towards obesity. It is now well established, from systematic review and meta-analysis, that obesity impairs health-related quality of life (HRQL) of children and adolescents from western societies ,2. ThereIt has been suggested that the impact of child or adolescent obesity on HRQL is influenced by culture , but sinThe primary purpose of the present study was therefore to test the hypothesis that obesity is associated with impaired HRQL in Kuwaiti adolescents, as in western societies. A secondary aim was to test whether HRQL differed between self-reports and parent-proxy reports for the obese adolescents.The Pediatric Quality of Life Inventory  was used in the present study, with the Arabic Generic Version. The PedsQL™ is a generic HRQL questionnaire that has both self- and parent-proxy report forms . The forThe PedsQL™ measures a multidimensional construct that includes 23 items consisting of physical, emotional, social and school performance domains from which a total score, psychosocial score , and physical score are derived. Items are linearly transformed to a 0 to 100 scale, so that the higher the score, the better the HRQL.The sample was recruited from public (state) schools in Kuwait city, the capital of Kuwait. The original intention was to recruit adolescents from a random sample of public schools, but this proved not to be possible due to limited consent to participate from school head teachers. The Ministry of Education granted approval to the research team to invite all 80 intermediate schools in Kuwait City to participate in the study. Kuwait City has 41 male public intermediate schools and 39 female public intermediate schools. Only 10/80 intermediate school head teachers responded, from 3 girls schools and 7 boys schools, and of these 10, permission to conduct the study at school was granted by only three schools; two male and one female school. Participants and their families provided informed written consent. The PedsQL™4.0 Arabic version was completed independently by the adolescents at school and by their parents at home. The study was approved by the Medical Research Committee of the Ministry of Health and the Ethical Committee of the Ministry of Education in Kuwait.Study participants were included if within the eligible age range , and were either obese or healthy weight as defined below. Overweight pupils were excluded from the study sample in order to provide a marked contrast in weight status between the two groups of interest, and to minimize the impact of any mis-classification arising from use of the body mass index. Other exclusions were based on a brief medical history/checklist aimed at including only apparently healthy adolescents, and excluding participants with serious chronic or acute illness which might affect their HRQL.th centile, overweight as BMI of ≥ 85th centile and <95th centile, healthy weight was defined as BMI ≥ 3rd centile and < 85th centile. The US BMI reference data were used in the present study because the absolute BMI values at standard Kuwaiti centiles are extremely high [From the three schools which agreed to participate, screening of weight status to determine eligibility was carried out in a total of 1042 pupils . Pupils were categorised into healthy weight, overweight, and obese groups relative to reference data from the US CDC 2000 . Obesityely high . The totA pre-planned paired analysis of HRQL between obese and healthy weight participants, with pair matching for same sex, same school, same school year, and same ethnic group  yielded 98 pairs with 57 paired comparisons in boys and 41 paired comparisons in girls.All statistical analyses were performed using Minitab 16.0. Data were checked for normality by descriptive statistics and histograms with normal distribution curves. Both the descriptive data, and differences between groups (e.g. between self versus parent reports) were non-normally distributed and so non-parametric statistical tests were used. For the whole sample self-reports, the skewness and kurtosis values for the physical score were −1.10 and 1.70 , for the psychosocial score these were −1.42 and 2.48 and for the total score they were −1.14 and 1.07 , respectively. For the parent-proxy reports, skewness and kurtosis values for the total score were −0.49 and −0.66, for the psychosocial score −0.44 and −0.51, and for the physical score were −0.84 and −0.30, respectively.In order to test whether obesity was associated with impaired HRQL two statistical approaches were taken. First, multiple regression was used with HRQL  as the outcome and age, gender, and weight status as the explanatory variables. Second, paired comparisons were undertaken between obese versus healthy weight study participants. Wilcoxon signed-rank tests were used to determine the significance of differences in the paired scores between the obese and the healthy weight groups. We also used Wilcoxon signed-rank tests to determine the significance of any difference in scores between adolescent self-reports and parent-proxy reports in the obese group.The final study sample consisted of 500 adolescents, 224 obese and 276 healthy weight, 318 boys (63.6%) and 182 girls (36.4%), median age 12.3y. Of the 500 adolescent participants self- reports were available from all 500, but parent-proxy reports were available from 162 of the obese group and 212 from the healthy-weight group. Characteristics of study participants are summarized in Table Of the potential explanatory variables of age, gender, and weight status, only gender had a significant influence on adolescent self-reported HRQL . In parent-proxy reports, age  and gender (lower in girls than boys p < 0.01) had a significant impact on total score. There was no evidence that obesity was associated with impaired HRQL  in the regression analyses.Formal matched pairs were selected from the obese and healthy weight groups (n = 98 pairs). Median (IQR) ages of the healthy weight and obese groups were both 12.4 (2.1). Median (IQR) BMI Z scores were 0.1 (1.1) for the healthy weight group and 2.1 (0.4) for the obese group.Summary data are shown in Table As shown in Table There were 162 obese adolescents for the paired comparisons between self-reports and parent-proxy reports . Parent-proxy reports were significantly lower than self-reports for physical score , psychosocial score , and total score ., in contrast to findings from western samples [.The primary aim of the present study was to test whether the impairment of ‘total’ HRQL associated with obesity from western samples, as measured by the PedsQL™, ,2 was pr samples ,2 and so samples -7.The present study did find evidence of a deficit in the physical health domain of HRQL , but not for the psychosocial health domain .It is possible that the physical health effects of adolescent obesity might be more universal than psychosocial effects, Psychosocial effects of obesity might be more sensitive to cultural differences, e.g. in the perception of obesity. The apparent lack of impact of obesity on the psychosocial domain of HRQL in the present study might reflect cultural differences in the perception of obesity between Kuwait and western societies, but further research would be required to confirm this. The community-based nature of the sample might also have reduced any potential HRQL deficits associated with obesity. It is possible that HRQL is more greatly impaired in clinic based, treatment-seeking samples ,6,8,9.Recent systematic reviews have noted that almost all of the evidence reviewed has been from western countries ,2. Very We are aware of only one previous study of HRQL in adolescents and young adults in Kuwait: Al-Fayez and Ohaeri  used a dThe secondary aim of the present study was to test the hypothesis that parent-proxy and self- reports of HRQL might differ in obese adolescents. The present study showed that parent-reported HRQL was significantly lower than adolescent-reported HRQL, this emphasizes the potential value of obtaining both parent and self-reports of HRQL -25. MostThe novelty of the study setting (Arabian Gulf), relatively large sample, heterogeneity of the sample, and ability to compare HRQL between obese versus healthy weight adolescents, were the main study strengths.The present study also had a number of weaknesses. While the sample size was larger than in many previous studies included in recent systematic reviews ,2, the sIn conclusion, the present study suggests that adolescent obesity is not associated with marked impairment of HRQL in Kuwait, in contrast to what would have been expected from previous studies of largely western samples. This finding suggests that cultural differences might modify the impact of obesity on HRQL among adolescents.The authors have no conflicts of interest to declare.Both authors were involved in concept and study design; both drafted the manuscript and revised for critical intellectual content; both gave final approval for submission.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2431/13/105/prepub


Previous studies of risk factors for disability pension (DP) have mainly focused on psychosocial, or environmental, factors, while the relative importance of genetic effects has been less studied. Sex differences in biological mechanisms have not been investigated at all.The study sample included 46,454 Swedish twins, consisting of 23,227 complete twin pairs, born 1928–1958, who were followed during 1993–2008. Data on DP, including diagnoses, were obtained from the National Social Insurance Agency. Within-pair similarity in liability to DP was assessed by calculating intraclass correlations. Genetic and environmental influences on liability to DP were estimated by applying discrete-time frailty modeling.During follow-up, 7,669 individuals were granted DP (18.8% women and 14.1% men). Intraclass correlations were generally higher in MZ pairs than DZ pairs, while DZ same-sexed pairs were more similar than opposite-sexed pairs. The best-fitting model indicated that genetic factors contributed 49% (95% CI: 39–59) to the variance in DP due to mental diagnoses, 35% (95% CI: 29–41) due to musculoskeletal diagnoses, and 27% (95% CI: 20–33) due to all other diagnoses. In both sexes, genetic effects common to all ages explained one-third, whereas age-specific factors almost two-thirds, of the total variance in liability to DP irrespective of diagnosis. Sex differences in liability to DP were indicated, in that partly different sets of genes were found to operate in women and men, even though the magnitude of genetic variance explained was equal for both sexes.The findings of the study suggest that genetic effects are important for liability to DP due to different diagnoses. Moreover, genetic contributions to liability to DP tend to differ between women and men, even though the overall relative contribution of genetic influences does not differ by sex. Hence, the pathways leading to DP might differ between women and men. Disability pension (DP) is the ultimate consequence of permanent incapacity to work on medical grounds. It is not only a severe consequence for the individual in terms of, for example, income loss, but also for employers and society Musculoskeletal and psychiatric diagnoses jointly account for about 70% of all granted DPs Sex differences in DP have been widely investigated, and a higher incidence of DP has been reported among women compared with men To our knowledge, only one study has investigated the importance of genetic and environmental factors for DP, using a 30-year follow-up of Finnish twins The study was approved by the Stockholm Regional Ethical Review Board in Sweden, Dnr: 2007/524-31, 2007-05-08 and 2009-08-25.The data come from a large population-based prospective Swedish twin study, the Swedish Twin Study of Disability Pension and Sickness Absence (STODS), which includes all twins from the Swedish Twin Registry (STR) born in Sweden between 1925 and 1958  st 1993. Individuals who were no longer at risk of DP were older than 65, had emigrated, taken old-age retirement, or were on DP before or on January 1st 1993. Twin pairs with unknown zygosity or with information available for only one co-twin  were excluded from the data analyses. Thus, the final study sample included 46,454 twin individuals, whereof 2,547 male MZ, 4,164 male DZ, 3,001 female MZ and 4,380 female DZ twin pairs, and 9,135 OS twin pairs. The individuals were followed from January 1st 1993 to the date of DP, old-age retirement, emigration, age of 65, death, or to the last day of the follow-up, December 31st 2008. Thus, the individuals eligible for DP during follow-up were between 34 and 64 years-old.The study sample included all individuals that were alive, living in Sweden and at risk of DP on January 1th and 10th revisions of the International Classification of Diseases (ICD) In Sweden, any person younger than 65 years of age with a medically confirmed disease or injury that has led to permanent work incapacity can be granted DP. For all twins, data on date of and main diagnosis for DP were obtained from the National Social Insurance Agency for the years 1993–2008. DP diagnoses were based on the 9Data on old-age retirement and migration were acquired from Statistics Sweden, and on deaths during the follow-up from the National Board of Health and Welfare. All registry data were linked to the twins by using the unique ten-digit personal identification number assigned to all Swedish residents.Cumulative incidence rates of DP for each zygosity, sex, and diagnosis groups were calculated for all individuals. Incidence rates of DPs per 1000 person-years and numbers of concordant and discordant twin pairs were computed by age and sex. The first indication of whether genetic or environmental factors are important for liability to DP can be obtained by comparing how similar  MZ and DZ twin pairs are for DP. Within-pair similarity for liability to DP was assessed by calculating intraclass tetrachoric correlations for each zygosity, sex, and diagnosis group, and also within age groups. Descriptive statistics and intraclass correlations were computed using SAS statistical software Genetic and environmental influences on liability to DP were estimated by applying discrete-time frailty models of DP due to all diagnoses, and separately for DP due to mental diagnoses, musculoskeletal diagnoses, and other diagnoses. Discrete-time frailty modeling is an extension of discrete-time survival analysis using a general latent variable framework, which allows for description of the relationship between hazard and latent factors ti, where t = 1, 2, 3  and i = 1, 2 (each indicating a twin in a pair). The outcome variable Uti could obtain three values: value 0 ; value 1 ; and value 9  or due to an earlier DP event). Latent frailty (Fi) is common to all age intervals and is defined as a function of the event indicators (Uti) In discrete-time survival analysis, unlike continuous-time survival analysis, time-to-event is measured discretely The number of age intervals included in the model depended on the number of available concordant twin pairs for DP in each age interval and for each zygosity, sex, and DP diagnosis group. At least one concordant twin pair should be available in each category. For analyses of specific diagnoses, three age groups  could be created. However, there were too few concordant female and male twin pairs in each DP diagnosis group, and therefore the sex differences in liability to DP due to specific diagnoses could not be tested. Instead, we analyzed whether liability to DP differed between women and men when all DP diagnoses were pooled. For the computations, five age groups could be created: ≤45, 46–50, 51–55, 56–60, and 60–64 years.ti) is assumed to arise from individual differences in common liability to DP (Fi) caused by additive genetic effects (A), common environment (C), and unique environment (E). MZ twins are genetically identical at the sequence level, whereas DZ twins share on average half of all their segregating genes. Thus, the genetic correlation (rg) between MZ and DZ twins is set at 1.0 or 0.5. For OS twins, rg is first estimated freely, which gives an indication of whether the same genes are expressed in women and men, and tested for statistical significance by fixing it at 0.5, which is the expected genetic correlation when no sex-specific genetic effects are present.Following traditional twin methods, variation in the observed time-to-DP (Uc) is therefore set at 1.0 for both twin zygosities. Unique environment includes the individual influences that make twins dissimilar, and also measurement error. In this study, unique environment was modeled as one parameter unique to each twin for the whole follow-up period, and also as three or five parameters unique to each twin and each age interval (εt). The effects of all genetic and environmental factors were assumed to be constant at different age intervals  that members of a twin pair experience together or are jointly exposed to. The common environment correlation , where the lowest AIC value indicates the most parsimonious and best-explaining model.Model estimation was performed using the maximum-likelihood approach in the Mplus statistical software During follow-up, a total of 7,669 individuals were granted DP (18.8% of the women and 14.1% of the men). There were 1,197 (8.1%) women and 677 (5.0%) men who were granted DP due to musculoskeletal diagnoses, and 572 (3.9%) women and 312 (2.3%) men who were granted DP due to mental diagnoses. The distribution of DPs granted in different diagnostic categories is presented in The numbers of concordant  and discordant twin pairs for DP by diagnosis, sex, and zygosity group are shown in 2) explained 49% (95% CI: 39–59) of the variance in DP due to mental, 35% (95% CI: 29–41) due to musculoskeletal, and 27% (95% CI: 20–33) due to all other diagnoses. Unique environment (e2) played a minor role in liability to DP. Factors that were specific to each age (ε2) explained 45% (95% CI: 22–69), 62% (95% CI: 54–69), and 66% (95% CI: 55–77) of the variance in liability to DP due to mental, musculoskeletal, and all other diagnoses, respectively.The model-fitting analyses of pooled data for women and men based on the two zygosity groups showed that the genetic and unique environmental factors (AE) model best explained the variance in DP due to any diagnosis, and also in DP in each specific diagnostic group. The standardized parameter estimates of the AE model are presented in g free: Δχ2 = 0.48, Δdf = 2, p = 0.79) and a decrease in the AIC value. However, omitting component A resulted in a model with a much poorer fit , and also an increase in the AIC value. Further, quantitative sex differences were tested by fitting an AE model where genetic and environmental parameters were constrained to be equal for women and men. This resulted in a non-significant deterioration in model fit , and also a decreased AIC value. Finally, to examine whether genetic effects differed qualitatively between the sexes, the genetic correlation for OS twin pairs (rg) was set at 0.5. This did not produce a significantly poorer model fit to data , but there was an increased AIC value compared with Model IV. Hence, the AE model with equal parameters for women and men, but with freely estimated genetic correlation (Model IV), provided the best balance of parsimony and fit, as indicated by the lowest AIC value. Estimates of the variance components of the best-fitting model are presented in Model-comparison results for sex differences in liability to DP due to any diagnosis are presented in The present study aimed to investigate the effects of genetic and environmental factors on liability to DP in a population-based cohort of 46,454 twins initially eligible for DP and followed for 16 years. Also, sex differences in liability to DP were tested. Moderate to large genetic contributions were found for liability to DP, irrespective of the age at which DP was granted. At least equally important were the environmental factors influencing the trend in DP in each specific age group. No quantitative sex differences were found that is, the amount of variance explained by genetic and environmental factors for liability to DP was similar among both women and men. However, the results for DP, irrespective of underlying diagnosis, suggested that the genes operating in the pathways leading to DP may differ between women and men; that is, qualitative sex differences might be present.Results regarding genetic liability to DP due to different diagnoses are consistent with the findings of the previously mentioned study of the Finnish population Genetic influences on liability to DP can be explained in several ways. As reported in previous twin studies, musculoskeletal diseases and mental disorders were at least partly heritable The magnitudes of genetic and environmental influences on liability to DP were found to be similar among women and men. That is, there were no sex differences in the amount of variance explained by genetic and environmental factors for DP. However, the results suggest that the sets of genes contributing to the variation in liability to DP may not be identical for both sexes. That is, the heritable factors that affect the development of DP seem to be different in women and men. In addition to biologic dissimilarities between the sexes, these factors may also include, for example, different susceptibility to a disease, differential response to childhood adverse experiences, or variation in functional abilities . No previous studies have investigated this issue and, therefore, the current findings cannot be compared with those from other populations. However, genetic sex differences have been reported earlier in a few twin studies of psychopathology. For example, sex-specific genetic factors have been reported to be influential on depression Findings on sex-specific effects on liability to DP may also reflect sex differences with regard to each diagnosis. Because there were too few concordant twin pairs in each age group in our study, this hypothesis could not be tested. Thus, we cannot rule out the possibility that our findings of sex-specific genetic effects may depend, for example, on a different distribution of diseases between women and men. It is also possible that qualitative genetic differences between the sexes in liability to DP may be primarily due to the sex differences in, for example, psychiatric diagnoses, whereas similar sets of genes may operate in liability to DP due to musculoskeletal diagnoses. Worth noting is that specific diagnosis categories may have different development patterns in women and men. For example, schizophrenia and related psychotic disorders with a peak onset in young adulthood (<35 years) do not show major gender differences In line with the results of the Finnish study The incidence rate of DP was lower in the 60-years-and-older age group than in younger age groups. This may reflect the increasing number of old-age pensioners in this age group, and also the fact that most of the individuals with health problems have already been granted a DP. Alternatively, individuals with health problems that first arise at later ages may continue working and/or be on sick-leave until old-age retirement.The study has several strengths. The sample was large, population-based, and was followed for 16 years. Because all data were obtained by linking a number of national registers, there were no information or response biases. Information on all individuals was detailed and of high quality, with no loss to follow-up. Findings of potential sex differences for genetic liability to DP are, to our knowledge, reported here for the first time. The main limitation of the study relates to the relatively small number of DPs granted during the follow-up period. Since the earliest age of follow-up was around the mid-30 s, the processes leading to DP in young adults could not be investigated, and those with DP by the age of 35 were not included in the analyses. Despite the large sample and a reasonable follow-up time, the number of DPs granted was too small to investigate the genetic liability to DP of women and men in each DP diagnosis group. Therefore, further studies should be performed to examine this issue further by following individuals for a longer time, e.g. from young adulthood to retirement. Also, the liability to DP due to different diagnoses could be studied by pooling data on DP from several countries that have similar DP granting systems to Sweden.Another limitation concerns possible selection bias. For the data analyses, twins with unknown zygosity or with missing follow-up information on their co-twin were excluded from the cohort. The cumulative incidence of DP among excluded men was higher than among men in the total cohort (18.1% vs. 14.1%). For women, there was only a marginal difference between the incidence of DP in the excluded twins and that in the total cohort (18.8% vs. 18.0%). This suggests that more severe diseases or diseases of higher heritability may have been more prevalent among the excluded male twins. Thus, the genetic liability to DP reported in this study may be slightly underestimated. As suggested by the decreasing influence of genetic factors on liability to DP with increasing age, the genetic liability may be underestimated primarily at later ages. That is, individuals with higher genetic liability to DP may have a more severe disease and be granted DP earlier than others.The findings of this study are similar to those from the previous analyses of Finnish data, and suggest that genetic effects are important for liability to DP due to different diagnoses. Further, genetic effects contributing to liability to DP seem to be different among women and men. Hence, pathways leading to DP seem to differ for women and men, which should be borne in mind when interventions to prevent DP are planned. However, further large and prospective studies are needed to be able to identify specific factors that mediate genetic effects for each diagnosis and sex group, so as to increase our understanding of the obviously complex mechanisms involved in trends in DP.