Gene-environment Interaction on the Risk of Type 2 Diabetes Among Ethnic Minority Populations Living in Europe and North America: A Systematic Review.

BACKGROUND: The body of evidence on gene-environment interaction (GEI) related to type 2 diabetes (T2D) has grown in the recent years. However, most studies on GEI have sought to explain variation within individuals of European ancestry and results among ethnic minority groups are inconclusive. OBJECTIVE: To investigate any interaction between a gene and an environmental factor in relation to T2D among ethnic minority groups living in Europe and North America. METHODS: We systematically searched Medline and EMBASE databases for the published literature in English up to 25th March 2019. The screening, data extraction and quality assessment were performed by reviewers independently. RESULTS: 1068 studies identified through our search, of which nine cohorts of six studies evaluating several different GEIs were included. The mean follow-up time in the included studies ranged from 5 to 25.7 years. Most studies were relatively small scale and few provided replication data. All studies included in the review included ethnic minorities from North America (Native-Americans, African- Americans, and Aboriginal Canadian), none of the studies in Europe assessed GEI in relation to T2D incident in ethnic minorities. The only significant GEI among ethnic minorities was HNF1A rs137853240 and smoking on T2D incident among Native-Canadians (Pinteraction = 0.006). CONCLUSION: There is a need for more studies on GEI among ethnicities, broadening the spectrum of ethnic minority groups being investigated, performing more discovery using genome-wide approaches, larger sample sizes for these studies by collaborating efforts such as the InterConnect approach, and developing a more standardized method of reporting GEI studies are discussed.

Tubal flushing with oil- or water-based contrast medium: can we identify markers that indicate treatment benefit?

STUDY QUESTION: Can we identify patient characteristics that distinguish which ovulatory infertile women undergoing hysterosalpingography (HSG) benefit more or less from flushing with oil-based contrast medium compared to water-based contrast medium? SUMMARY ANSWER: In ovulatory infertile women, HSG with oil-based contrast medium resulted in higher 6-month ongoing pregnancy and live birth rates as compared to HSG with water-based contrast medium and this treatment effect was independent of characteristics of the couple. WHAT IS KNOWN ALREADY: We recently showed that in infertile women undergoing HSG, flushing with oil-based contrast medium resulted in more ongoing pregnancies than flushing with water-based contrast medium. STUDY DESIGN SIZE DURATION: We used data from our randomized clinical trial (RCT) in which 1,119 ovulatory infertile women undergoing HSG during fertility work-up were randomized for use of oil-based (N = 557) or water-based (N = 562) contrast medium. PARTICIPANTS/MATERIALS SETTING METHODS: We built logistic regression models to predict ongoing pregnancy and live birth (secondary outcome) as a function of the specific contrast, the specific marker, and marker-by-contrast-interaction. Markers considered were female age, maternal ethnicity, female smoking, body mass index (BMI), duration of infertility, infertility being primary or secondary, sperm quality, and previous appendectomy. MAIN RESULTS AND THE ROLE OF CHANCE: The 6-month ongoing pregnancy rates in the overall population were 39.7% after use of oil-based contrast versus 29.1% after use of water-based contrast medium [relative risk (RR), 1.37; 95% confidence interval (CI), 1.16-1.61; P < 0.001]. Among the studied baseline characteristics, BMI (P = 0.002) and semen volume (P = 0.02) were statistically significant prognosticators. The treatment effect of oil-based contrast was stronger in women with a BMI ≤30 kg/m2 [RR, 1.54; 95% CI, 1.23-1.92; P = 0.002], and in women whose partner had a semen volume >3 ml [RR, 1.77; 95% CI, 1.28-2.46; P = 0.02]. Also, in women who smoked, the treatment effect of flushing with oil was stronger, but this interaction did not reach statistical significance (P = 0.066). We found no positive effect of oil-based contrast in obese women. We found similar but weaker associations for live birth, which was probably due to lower number of events resulting in less power. LIMITATIONS REASONS FOR CAUTION: The RCT was restricted to infertile ovulatory women younger than 39 years of age without endocrinological disorders and at low risk for tubal pathology. Our results should not be generalized to infertile women who do not share these features. WIDER IMPLICATIONS OF THE FINDINGS: All infertile, ovulatory women younger than 39 years with a low risk for tubal pathology will benefit from an HSG with oil-based contrast; therefore, this should be offered to them after fertility work-up. STUDY FUNDING/COMPETING INTERESTS: The original H2Oil RCT was an investigator-initiated study that was funded by the two academic institutions (AMC and VUmc) of the Amsterdam UMC. The study displayed in this paper was funded by an unconditional research grant from Guerbet. B.W.M. is supported by an NHMRC Practitioner Fellowship (GNT1082548). K.D. reports consultancy for Guerbet, during the conduct of the study, and also reports research grants from Guerbet. C.B.L. reports grants from Guerbet, during the conduct of the study, and grants from Ferring, grants from Merck, and personal fees from Ferring, outside the submitted work. P.H. reports grants from Guerbet, during the conduct of the study, and grants from Ferring and Merck, outside the submitted work. V.M. reports receiving travel and speakers fee as well as research grants from Guerbet. B.W.M. reports consultancy for ObsEva, Merck, Merck KGaA, and Guerbet, and research grants from Guerbet and Merck. The other authors have no conflict of interest to declare. TRIAL REGISTRATION NUMBER: NTR 3270 www.trialregister.nl. TRIAL REGISTRATION DATE: 1 February 2012. DATE OF FIRST PATIENT'S ENROLMENT: 3 February 2012.

Development and evaluating multimarker models for guiding treatment decisions.

BACKGROUND: Despite the growing interest in developing markers for predicting treatment response and optimizing treatment decisions, an appropriate methodology to identify, combine and evaluate such markers has been slow to develop. We propose a step-by-step strategy for analysing data from existing randomised trials with the aim of identifying a multi-marker model for guiding decisions about treatment. METHODS: We start with formulating the treatment selection problem, continue with defining the treatment threshold, prepare a list of candidate markers, develop the model, apply the model to estimate individual treatment effects, and evaluate model performance in the study group of patients who meet the trial eligibility criteria. In this process, we rely on some well-known techniques for multivariable prediction modelling, but focus on predicting benefit from treatment, rather than outcome itself. We present our approach using data from a randomised trial in which 808 women with multiple pregnancy were assigned to cervical pessary or control, to prevent adverse perinatal outcomes. Overall, cervical pessary did not reduce the risk of adverse perinatal outcomes. RESULTS: The treatment threshold was zero. We had a preselected list of 5 potential markers and developed a logistic model including the markers, treatment and all marker-by-treatment interaction terms. The model was well calibrated and identified 35% (95% confidence interval (CI) 32 to 39%) of the trial participants as benefitting from pessary insertion. We estimated that the risk of adverse outcome could be reduced from 13.5 to 8.1% (5.4% risk reduction; 95% CI 2.1 to 8.6%) through model-based selective pessary insertion. The next step is external validation upon existence of independent trial data. CONCLUSIONS: We suggest revisiting existing trials data to explore whether differences in treatment benefit can be explained by differences in baseline characteristics of patients. This could lead to treatment selection tools which, after validation in comparable existing trials, can be introduced into clinical practice for guiding treatment decisions in future patients.

Evaluation of biomarkers for treatment selection using individual participant data from multiple clinical trials.

Biomarkers that predict treatment effects may be used to guide treatment decisions, thus improving patient outcomes. A meta-analysis of individual participant data (IPD) is potentially more powerful than a single-study data analysis in evaluating markers for treatment selection. Our study was motivated by the IPD that were collected from 2 randomized controlled trials of hypertension and preeclampsia among pregnant women to evaluate the effect of labor induction over expectant management of the pregnancy in preventing progression to severe maternal disease. The existing literature on statistical methods for biomarker evaluation in IPD meta-analysis have evaluated a marker's performance in terms of its ability to predict risk of disease outcome, which do not directly apply to the treatment selection problem. In this study, we propose a statistical framework for evaluating a marker for treatment selection given IPD from a small number of individual clinical trials. We derive marker-based treatment rules by minimizing the average expected outcome across studies. The application of the proposed methods to the IPD from 2 studies in women with hypertension in pregnancy is presented.

The FIGO Stage IVA Versus IVB of Ovarian Cancer: Prognostic Value and Predictive Value for Neoadjuvant Chemotherapy.

OBJECTIVE: The revised version of the International Federation of Gynaecology and Obstetrics (FIGO) staging system (2014) for epithelial ovarian cancer includes a number of changes. One of these is the division of stage IV into 2 subgroups. Data on the prognostic and predictive significance of this classification are scarce. The effect of neoadjuvant chemotherapy (NACT) versus primary debulking surgery (PDS) in relation to the subclassification of FIGO stage IV is also unknown. METHODS: We used data of the EORTC 55971 trial, in which 670 patients with previous stage IIIC or IV epithelial ovarian cancer were randomly assigned to PDS or NACT; 160 patients had previous stage IV. Information on previous FIGO staging and presence of pleural effusion with positive cytology were used to classify tumors as either stage IVA or IVB. We tested the association between stage IVA/IVB and survival to evaluate the prognostic value and interactions between stage, treatment, and survival to evaluate the predictive performance. RESULTS: Among the 160 participants with previous stage IV disease, 103 (64%) were categorized as stage IVA and 57 (36%) as stage IVB tumors. Median overall survival was 24 months in FIGO stage IVA and 31 months in stage IVB patients (P = 0.044). Stage IVB patients treated with NACT had 9 months longer median overall survival compared with IVB patients undergoing PDS (P = 0.025), whereas in IVA patients, no significant difference was observed (24 vs 26 months, P = 0.48). CONCLUSIONS: The reclassification of FIGO stage IV into stage IVA or IVB was not prognostic as expected. Compared with stage IVA patients, stage IVB patients have a better overall survival and may benefit more from NACT.

Can we identify subfertile couples that benefit from immediate in vitro fertilisation over intrauterine insemination?

OBJECTIVE: Available treatment options in couples with unexplained or mild male subfertility are intrauterine insemination with controlled ovarian hyperstimulation (IUI-COH) and in vitro fertilisation (IVF). IUI-COH is a less invasive treatment that is often used before proceeding with IVF. Yet as the IVF success rates might be higher and time to pregnancy shorter, expedited access to IVF might be the preferred option. To identify couples that could benefit from immediate IVF over IUI-COH, we assessed whether female age, duration of subfertility or prewash total motile count (TMC) can help to identify couples that would benefit from IVF over IUI-COH. STUDY DESIGN: We performed a secondary data-analysis of a multicentre open-label randomised controlled trial in three university and six teaching hospitals in the Netherlands. 116 couples with unexplained or mild male subfertility were randomised to one cycle of IVF with elective single embryo transfer with subsequent frozen-thawed embryo transfers or 3 cycles of IUI-COH. The primary outcome was an ongoing pregnancy within 4 months after randomisation. Our aim was to explore a possible differential effect of specific markers on the effectiveness of treatment. We chose to therefore assess female age, duration of subfertility and TMC as these have previously been identified as predictors. For each prognostic factor we developed a logistic regression model to predict ongoing pregnancy with that prognostic factor, treatment and a factor-by-treatment interaction term. RESULTS: Female age and duration of subfertility were not associated with better ongoing pregnancy chances after IVF compared to IUI-COH (p-value for interaction=0.65 and 0.26, respectively). Only when TMC was lower than 110 (×10(6)spermatozoa/mL), the probability of ongoing pregnancy was higher in women allocated to IVF (p-value for interaction=0.06). CONCLUSION: In couples with unexplained or mild male subfertility, a low TMC might lead to higher pregnancy rates after IVF than after IUI-COH. This finding needs to be validated in a larger trial before it can be applied in clinical practice.

Relevance of individual participant data meta-analysis for studies in obstetrics: delivery versus expectant monitoring for hypertensive disorders of pregnancy.

Like many other research subjects in obstetrics, research on immediate delivery versus expectant monitoring for women with hypertensive disorders of pregnancy faces certain challenges when it comes to interpretation and generalisation of the results; relatively rare outcomes are studied, in a clinically heterogeneous population, while the clinical practice in some countries has dictated that studies in term pregnancy were completed before earlier gestational ages could be studied. This has resulted in multiple smaller studies, some studying surrogate outcome measures, with different in- and exclusion criteria, and without enough power for reliable subgroup analyses. All this complicates the generation of definitive answers and implementation of the results into clinical practice. Performing multiple studies and subsequently pooling their results in a meta-analysis can be a way to overcome the difficulties of studying relatively rare outcomes and subgroups with enough power, as well as a solution to reach a final answer on questions involving an uncertain and possibly harmful intervention. However, in the case of the current studies on delivery versus expectant monitoring in women with hypertensive disorders of pregnancy, differences regarding eligibility criteria, outcome measures and subgroup definitions make it difficult to pool their results in an aggregate meta-analysis. Individual patient data meta-analysis (IPDMA) has the potential to overcome these challenges, because it allows for flexibility regarding the choice of endpoints and standardisation of inclusion and exclusion criteria across studies. In addition, it has more statistical power for informative subgroup analyses. We therefore propose an IPDMA on immediate delivery versus expectant monitoring for hypertensive disorders of pregnancy, and advocate the use of IPDMA for research questions in obstetrics that face similar challenges.

Echocardiographic estimation of left ventricular filling pressures in patients with mitral valve stenosis.

BACKGROUND: Estimation of left ventricular end-diastolic pressure (LVEDP) among patients with mitral valve disease may help to explain their symptoms. However, conventional Doppler measurements have limitations in predicting LVEDP in this group of patients. The aim of this study was to construct a Doppler-derived LVEDP prediction model based on the combined analysis of transmitral and pulmonary venous flow velocity curves. METHODS: Thirty-three patients with moderate to severe mitral stenosis (MS) who had indications for left heart catheterisation enrolled. Two-dimensional, M-mode, colour Doppler and tissue Doppler imaging indices, such as annular early diastolic velocity (Ea), isovolumic relaxation time (IVRT), pulmonary vein systolic and diastolic flow velocities, velocity propagation, left atrium area (LAA), interval between the onset of mitral E and annular Ea (TE-Ea), and Tei index were obtained. LVEDP was measured in all patients during left cardiac catheterisation. Linear correlation and multiple linear regressions were used for analysis. RESULTS: The mean of LVEDP was 9.9 ± 5.3 mmHg. In univariate analysis, the only significant relationship was noted with LAA (p = 0.05, R(2) = 0.11). However, in multivariate regression, LAA, Tei index and Ea remained in the model to predict LVEDP (p = 0.02, R(2) = 0.26). For prediction of LVEDP ≥ 15 mmHg, the best model consisted of LAA, IVRT and Ea, and had a sensitivity of 85% and specificity of 85%. CONCLUSIONS: Our results provided evidence that, in patients with moderate to severe MS, LVEDP can be estimated by combining Doppler echocardiographic variables of mitral flow. However, more studies are required to confirm these results.

Constructing pragmatic socioeconomic status assessment tools to address health equality challenges.

BACKGROUND: A key challenge for equality evaluation and monitoring, mainly in developing countries, is assessing socioeconomic status (SES) of individuals. This difficulty along with low technical competency, have resulted in many health information collected in these countries which are devoid of suitable SES indices. However, simplifying data collection requirements for estimating economic parameters seems to guarantee their wide adoption by survey and health information system (HIS) designers, resulting in immediate production of equity-oriented policy-relevant information. The goal of this study is obtaining adequate number of variables, which their combination can provide a valid assessment of SES in Iranian population. METHODS: The data source was Living Standards Measurement Study of Iran (2006). Data of 27,000 households on the ownership of 33 household assets was used for this analysis. Households of this study were divided into 5 groups in terms of SES status using principle component analysis. Then selection was made among the 33 variables so that a combination with minimum necessary number for obtaining SES status is reached. Agreement of the new combination (including minimum number of variables) with full variable combination (including all 33 variables) was assessed using weighted kappa. RESULTS: A minimum set of six variables including having kitchen, bathroom, vacuum cleaner, washing machine, freezer and personal computer could successfully discriminate SES of the population. Comparing this 6 item-index with the whole 33 item-index revealed that 65% of households were in the same quintiles, with a weighted kappa statistics of 0.76. For households in different quintiles, movement was generally limited to one quintile, with just 2% of households moving two or more quintiles. CONCLUSIONS: The proposed simple index is completely applicable in current Iran's society. It can be used in different survey and studies. The development is quite simple and can be done on a yearly basis using the updated National level data. Having such standardized simplified and up to date SES indices and incorporating them into all health data sources can potentially ease the measurement and monitoring of equity of health services and indices.

Which intrauterine growth restricted fetuses at term benefit from early labour induction? A secondary analysis of the DIGITAT randomised trial.

OBJECTIVE: The Disproportionate Intrauterine Growth Intervention Trial at Term (DIGITAT trial) showed that in women with suspected intrauterine growth restriction (IUGR) at term, there were no substantial outcome differences between induction of labour and expectant monitoring. The objective of the present analysis is to evaluate whether maternal or fetal markers could identify IUGR fetuses who would benefit from early labour induction. STUDY DESIGN: The DIGITAT trial was a multicenter, parallel and open-label randomised controlled trial in women who had a singleton pregnancy beyond 36+0 weeks' gestation with suspected IUGR (n=650). Women had been randomly allocated to either labour induction or expectant monitoring. The primary outcome was a composite measure of adverse neonatal outcome, defined as neonatal death before hospital discharge, Apgar score <7, umbilical artery pH <7.05, or admission to neonatal intensive care. Using logistic regression modelling, we investigated associations between outcome and 17 markers, maternal characteristics and fetal sonographic and Doppler velocimetry measurements, all collected at study entry. RESULTS: 17 (5.3%) infants in the induction group had an adverse neonatal outcome compared to 20 (6.1%) in the expectant monitoring group. The only potentially informative marker for inducing labour was maternal pre-pregnancy body mass index (BMI). Otherwise, we observed at best weak associations between a benefit from labour induction and maternal age, ethnicity, smoking, parity, pregnancy-induced hypertension or preeclampsia, Bishop score and gestational age, or fetal sonographic markers (gender, estimated fetal weight, body measurements, oligohydramnios, or umbilical artery pulsatility index and end diastolic flow). CONCLUSION: In late preterm and term pregnancies complicated by suspected intrauterine growth restriction, most of the known prognostic markers seem unlikely to be helpful in identifying women who could benefit from labour induction, except for maternal pre-pregnancy BMI.

Which patients benefit most from primary surgery or neoadjuvant chemotherapy in stage IIIC or IV ovarian cancer? An exploratory analysis of the European Organisation for Research and Treatment of Cancer 55971 randomised trial.

BACKGROUND: To investigate whether biomarkers consisting of baseline characteristics of advanced stage ovarian cancer patients can help in identifying subgroups of patients who would benefit more from primary surgery or neoadjuvant chemotherapy. METHODS: We used data of the European Organisation for Research and Treatment of Cancer (EORTC) 55971 trial in which 670 patients were randomly assigned to primary surgery or neoadjuvant chemotherapy. The primary outcome was overall survival. Ten baseline clinical and pathological characteristics were selected as potential biomarkers. Using Subpopulation Treatment Effect Pattern Plots (STEPP), biomarkers with a statistically significant qualitative additive interaction with treatment were considered as potentially informative for treatment selection. We also combined selected biomarkers to form a multimarker treatment selection rule. FINDINGS: The size of the largest metastatic tumour and clinical stage were significantly associated with the magnitude of the benefit from treatment, in terms of five-year survival (p for interaction: 0.008 and 0.016, respectively). Stage IIIC patients with metastatic tumours ⩽45 mm benefited more from primary surgery while stage IV patients with metastatic tumours >45 mm benefited more from neoadjuvant chemotherapy. In stage IIIC patients with larger metastatic tumours and in stage IV patients with less extensive metastatic tumours both treatments were equally effective. We estimated that by selecting treatments for patients based on largest metastatic tumour and clinical stage, the potential five-year survival rate in the population of treated patients would be 27.3% (95% confidence interval (CI) 21.9-33.0), 7.8% higher than if all were treated with primary surgery, and 5.6% higher if all were treated with neoadjuvant chemotherapy. INTERPRETATION: Although survival was comparable after primary surgery and neoadjuvant chemotherapy in the overall group of patients with ovarian cancer in the EORTC 55971 trial, we found in this exploratory analysis that patients with stage IIIC and less extensive metastatic tumours had higher survival with primary surgery, while patients with stage IV disease and large metastatic tumours had higher survival with neoadjuvant chemotherapy. For patients who did not meet these criteria, both treatment options led to comparable survival rates.

Trial designs for personalizing cancer care: a systematic review and classification.

There is an increasing interest in the evaluation of prognostic and predictive biomarkers for personalizing cancer care. The literature on the trial designs for evaluation of these markers is diverse and there is no consensus in the classification or nomenclature. We set this study to review the literature systematically, to identify the proposed trial designs, and to develop a classification scheme. We searched MEDLINE, EMBASE, Cochrane Methodology Register, and MathSciNet up to January 2013 for articles describing these trial designs. In each eligible article, we identified the trial designs presented and extracted the term used for labeling the design, components of patient flow (marker status of eligible participants, intervention, and comparator), study questions, and analysis plan. Our search strategy resulted in 88 eligible articles, wherein 315 labels had been used by authors in presenting trial designs; 134 of these were unique. By analyzing patient flow components, we could classify the 134 unique design labels into four basic patient flow categories, which we labeled with the most frequently used term: single-arm, enrichment, randomize-all, and biomarker-strategy designs. A fifth category consists of combinations of the other four patient flow categories. Our review showed that a considerable number of labels has been proposed for trial designs evaluating prognostic and predictive biomarkers which, based on patient flow elements, can be classified into five basic categories. The classification system proposed here could help clinicians and researchers in designing and interpreting trials evaluating predictive biomarkers, and could reduce confusion in labeling and reporting.

Inequality in maternal mortality in iran: an ecologic study.

BACKGROUND: Maternal mortality (MM) is an avoidable death and there is national, international and political commitment to reduce it. The objective of this study is to examine the relation of MM to socioeconomic factors and its inequality in Iran's provinces at an ecologic level. METHODS: The overall MM from each province was considered for 3 years from 2004 to 2006. The five independent variables whose relations were studied included the literacy rate among men and women in each province, mean annual household income per capita, Gini coefficients in each province, and Human Development Index (HDI). The correlation of Maternal Mortality Ratio (MMR) to the above five variables was evaluated through Pearson's correlation coefficient (simple and weighted for each province's population) and linear regression - by considering MMR as the dependent variable and the Gini coefficient, HDI, and difference in literacy rate among men and women as the independent variables. RESULTS: The mean MMR in the years 2004-2006 was 24.7 in 100,000 live births. The correlation coefficients between MMR and literacy rate among women, literacy rate among men, the mean annual household income per capita, Gini coefficient and HDI were 0.82, 0.90, -0.61, 0.52 and -0.77, respectively. Based on multivariate regression, MMR was significantly associated with HDI (standardized B=-0.93) and difference in literacy rate among men and women (standardized B=-0.47). However, MMR was not significantly associated with the Gini coefficient. CONCLUSION: This study shows the association between socioeconomic variables and their inequalities with MMR in Iran's provinces at an ecologic level. In addition to the other direct interventions performed to reduce MM, it seems essential to especially focus on more distal factors influencing MMR.

Asymmetrical distribution of atherosclerosis in the carotid artery: identical patterns across age, race, and gender.

BACKGROUND: Small autopsy studies and clinical practice indicated that carotid atherosclerosis develops in an asymmetrical helical pattern coinciding with regions of low shear stress. We investigated the distribution of carotid atherosclerosis as determined by maximum carotid intima-media thickness (CIMT), to assess if we could confirm this atherosclerotic configuration across various populations with different cardiovascular risk. METHODS AND RESULTS: We used the individual baseline CIMT data from 3364 subjects from four recent international multicentre randomized controlled trials in which the carotid artery was systematically examined using the same ultrasound protocol and method to quantify CIMT. For each subject, circumferential information on the maximum CIMT of the left and right carotid arteries was obtained for the common carotid, bifurcation, and internal carotid artery segments. In each segment (common, bifurcation, internal), mixed modelling was used to study the differences in CIMT between angles, sides, gender, age, race, and studies. Each segment showed a different circumferential CIMT pattern. In all segments there were statistically significant differences between maximum CIMT across circumferential angles (p < 0.001); on average CIMT was highest in the posteromedial wall of the bifurcation and internal carotid segments and in the anterolateral wall of the common carotid segment. This asymmetric circumferential pattern was found to be identical in men and women, in young and old age, in different race groups, and across the studies. CONCLUSIONS: We confirmed the asymmetrical helix-like distribution of atherosclerosis in the carotid arteries and expand the evidence by showing that the atherosclerotic configuration is similar across populations with different vascular risks and across gender, age, and race. This has implications for future design of carotid ultrasound studies, as the angle of insonation is an important predictor of maximum CIMT.

Antigliadin antibody in sporadic adult ataxia.

BACKGROUND: The most common neurologic manifestation of gluten sensitivity is ataxia, which accounts for up to 40% of idiopathic sporadic ataxia. Timing of diagnosis of gluten ataxia is vital as it is one of the very few treatable causes of sporadic ataxia and causes irreversible loss of Purkinje cells. Antigliadin antibody (AGA) of the IgG type is the best marker for neurological manifestations of gluten sensitivity. This study was conducted to measure the prevalence of gluten ataxia in a group of Iranian patients with idiopathic ataxia. METHODS: For 30 patients with idiopathic cerebellar ataxia, a questionnaire about clinical and demographic data was completed. Serum AGA (IgA and IgG) and antiendomysial antibody (AEA) were assessed. Gluten ataxic patients underwent duodenal biopsy. Magnetic resonance imaging was done for all patients to see if cerebellar atrophy is present. RESULTS: Only 2 patients had a positive IgG AGA (6.7%) who both had a positive AEA while none of them showed changes of celiac disease in their duodenal biopsies. Only presence of gastrointestinal symptoms and pursuit eye movement disorders were higher in patients with gluten ataxia. CONCLUSION: Prevalence of gluten ataxia in Iranian patients with idiopathic ataxia seems to be lower than most of other regions. This could be explained by small sample size, differences in genetics and nutritional habits and also effect of serologic tests in clinical versus research setting. Further researches with larger sample size are recommended.

Genomic markers to tailor treatments: waiting or initiating?

The decade since the publication of the Human Genome Project draft has ended with the discovery of hundreds of genomic markers related to diseases and phenotypes. However, the project has not yet delivered on its promise to tailor treatments for individuals. The number of genomic markers in clinical practice is very small. The number of markers to guide treatment decisions is even smaller. In order to speed up discovery and validation of genomic treatment selection markers, we call for considering the brilliant potential of randomized clinical trials. If biomedical research community can collaborate in organizing large-scale consortium of clinical trials associated with well-designed biobanks, these studies would soon act as huge laboratories for investigating genomic medicine; a big step forward towards personalizing medicine.