Incidence of multiple sclerosis in Iran: a nationwide, population-based study.

OBJECTIVES: The incidence of multiple sclerosis (MS) is not well known in Iran. This study was conducted to estimate the trends in annual MS incidence in Iran from March 21, 2010, to March 20, 2016. STUDY DESIGN: Longitudinal study. METHODS: In this longitudinal study, data for all MS patients fulfilling McDonald criteria were obtained from a national registry, coordinated by the Ministry of Health (MOH). In Iran, all MS patients are eligible to receive public care and treatment services based on their records in this registry, and thus nearly all MS patients are registered in this database. The annual incidence rates were calculated based on year of diagnosis and were standardized using the World Health Organization (2000-2025) population as a standard. RESULTS: In this registry, 36,287 (8202 [22.6%] males and 28,085 [77.4%] females) confirmed MS cases were registered by the MOH between 2010 and 2016. The female-to-male ratio was 3.11. The mean age of patients was 31.6 ± 0.9 years at the time of diagnosis. It was 31.3 ± 0.8 and 32.3 ± 0.9 for females and males, respectively. Overall incidence rate was 6.7/100,000 population (95% confidence interval [CI]: 6.2-7.2); 10.5 and 3.0 in females and males, respectively. The age-adjusted incidence rates increased significantly from 4.4 (95% CI: 4.3-4.6) in 2010 to 5.8 (95% CI: 5.7-6.0) in 2016, with its peak at 6.5 (95% CI: 6.3-6.6) in 2014. CONCLUSIONS: This study revealed that Iran is a high-risk area for MS disease and that MS incidence and female-to-male ratio are more or less comparable with the dominant patterns in developed countries. Also, this study showed that the incidence trend of MS in Iran is similar to regional and global observed patterns.

Clinical and laboratory evaluation of cured and non-cured patients with cutaneous leishmaniasis treated by Glucantime.

BACKGROUND & OBJECTIVES: Insufficient treatment of cutaneous leishmaniasis (CL) by conventional drugs is a major barrier in control strategies. This study was aimed to evaluate Glucantime efficacy and the susceptibility of Glucantime unresponsive and responsive CL isolates in the field and laboratory. METHODS: Chi-square test (x[2]) was used to determine the significance of difference between proportions in Glucantime-treated patients. The inhibitory activity of various concentrations of Glucantime against Leishmenia tropica stages was evaluated by a colorimetric cell viability MTT and macrophage assays. Mixed model, t-test and ANOVA were performed to determine the significance of difference between various concentrations of Glucantime unresponsive or responsive isolates and untreated control group and p <0.05 was defined as significant level. Altogether, 89.8% of the patients were cured by Glucantime, whilst 10.2% remained non-cured. RESULTS: The overall Glucantime efficacy in different age groups and genders was similar. The IC50 values of promastigotes and amastigotes for Glucanime unresponsive isolates were 2.1 and 2.6 times higher than the equivalent rates obtained for responsive cases, respectively. The overall mean number of amastigotes within macrophages in unresponsive isolates was significantly higher (32.68 ± 1.24) than that in responsive ones (18.68 ± 1.52, p <0.001). Glucantime unresponsive and responsive field isolates of anthroponotic CL (ACL) caused by L. tropica strongly correlated to in vitro assays. INTERPRETATION & CONCLUSION: Monitoring of Glucantime unresponsiveness by the health surveillance system is extremely important, where anthroponotic transmission occurs in humans. Hence, physicians should be aware of such clinical unresponsive presentations with ACL for antimonial therapeutic failure to improve management of disease in endemic regions.

Seroprevalence and risk factors of Toxoplasma gondii infection among healthy blood donors in south-east of Iran.

This prospective cross-sectional study was aimed to evaluate the prevalence of IgM and IgG anti-T. gondii antibodies and the associated risk factors among healthy blood donors in Kerman province, south-eastern Iran. Structured questionnaires (before the donors gave blood) were used to obtain information on risk factors for infection. Totally, 500 serum samples from healthy blood donors of Kerman Blood Transfusion Organization (KBTO) at Kerman, Iran, were screened for IgG and IgM anti-T. gondii antibodies by enzyme-linked immunosorbent assay (ELISA) and Roche Elecsys Toxo IgM assay. Real-time PCR was used to detect DNA of T. gondii in the IgM-positive samples. Seroprevalence of IgG and IgM anti-T. gondii antibodies was 28.8% and 3.2%, respectively. In the multiple logistic regression, it could be observed that living in rural regions, having B blood type, being in contact with cats, consuming raw vegetables and raw milk/egg and doing agricultural activities were independent risk factors for Toxoplasma seropositivity. T. gondii DNA was also found in one (9.0%) of IgM-positive samples. In this study, it was found that T. gondii infection was present among healthy blood donors in south-east of Iran. Therefore, it is suggested to design screening programmes for preventing transfusion-transmitted toxoplasmosis.

Molecular and morphological characterization of the tapeworm Taenia hydatigena (Pallas, 1766) in sheep from Iran.

Although Taenia hydatigena is one of the most prevalent taeniid species of livestock, very little molecular genetic information exists for this parasite. Up to 100 sheep isolates of T. hydatigena were collected from 19 abattoirs located in the provinces of Tehran, Alborz and Kerman. A calibrated microscope was used to measure the larval rostellar hook lengths. Following DNA extraction, fragments of cytochrome c oxidase 1 (CO1) and 12S rRNA genes were amplified by the polymerase chain reaction method and the amplicons were subjected to sequencing. The mean total length of large and small hooks was 203.4 µm and 135.9 µm, respectively. Forty CO1 and 39 12S rRNA sequence haplotypes were obtained in the study. The levels of pairwise nucleotide variation between individual haplotypes of CO1 and 12S rRNA genes were determined to be between 0.3-3.4% and 0.2-2.1%, respectively. The overall nucleotide variation among all the CO1 haplotypes was 9.7%, and for all the 12S rRNA haplotypes it was 10.1%. A significant difference was observed between rostellar hook morphometry and both CO1 and 12S rRNA sequence variability. A significantly high level of genetic variation was observed in the present study. The results showed that the 12S rRNA gene is more variable than CO1.

Effect of folic acid and zinc sulphate on endocrine parameters and seminal antioxidant level after varicocelectomy.

Varicocele is among the most common problems which may lead to male infertility. Spermatogenesis is impaired as a consequence of this vascular defect, through mechanisms that are not well described. This study aimed to evaluate serum hormonal level (inhibin B, FSH and testosterone) and seminal plasma antioxidant defence levels after folic acid and zinc sulphate administration in varicocelectomised patients. Participants were randomly allocated to four experimental groups. Our randomisation schedule was as follows: zinc sulphate/folic acid, folic acid, zinc sulphate and placebo. The patients underwent varicocelectomy, before which a blood and semen sample were obtained and also three and six months after varicocelectomy for evaluation of blood hormonal level (FSH, testosterone, inhibin B) and seminal oxidative stress status (nitric oxide, superoxide dismutase, total antioxidant capacity). Patients in different groups took orally one capsule per day after dinner following varicocelectomy for 6 months. A significant rise in peripheral blood inhibin B and seminal plasma activity was detected in the zinc sulphate/folic acid group after 6 months. The present clinical trial indicates a change in the hormonal status of varicocelectomised patients following long-term administration of zinc sulphate and folic acid.

Does the missing data imputation method affect the composition and performance of prognostic models?

BACKGROUND: We already showed the superiority of imputation of missing data (via Multivariable Imputation via Chained Equations (MICE) method) over exclusion of them; however, the methodology of MICE is complicated. Furthermore, easier imputation methods are available. The aim of this study was to compare them in terms of model composition and performance. METHODS: Three hundreds and ten breast cancer patients were recruited. Four approaches were applied to impute missing data. First we adopted an ad hoc method in which missing data for each variable was replaced by the median of observed values. Then 3 likelihood-based approaches were used. In the regression imputation, a regression model compared the variable with missing data to the rest of the variables. The regression equation was used to fill the missing data. The Expectation Maximum (E-M) algorithm was implemented in which missing data and regression parameters were estimated iteratively until convergence of regression parameters. Finally, the MICE method was applied. Models developed were compared in terms of variables significantly contributed to the multifactorial analysis, sensitivity and specificity. RESULTS: All candidate variables significantly contributed to the MICE model. However, grade of disease lost its effect in other three models. The MICE model showed the best performance followed by E-M model. CONCLUSION: Among imputation methods, final models were not the same, in terms of composition and perform-ance. Therefore, modern imputation methods are recommended to recover the information.

Multiple imputation in survival models: applied on breast cancer data.

BACKGROUND: Missing data is a common problem in cancer research. While simple methods such as completecase (C-C) analysis are commonly employed for handling this problem, several studies have shown that these methods led to biased estimates. We aim to address the methodological issues in development of a prognostic model with missing data. METHODS: Three hundred and ten breast cancer patients were enrolled. At first, patients with missing data on any of four candidate variables were omitted. Secondly, missing data were imputed 10 times. Cox regression model was fitted to the C-C and imputed data. Results were compared in terms of variables retained in the model, discrimination ability, and goodness of fit. RESULTS: Some variables lost their effect in complete-case analysis, due to loss in power, but reached significance level after imputation of missing data. Discrimination ability and goodness of fit of imputed data sets model was higher than that of complete-case model (C-index 76% versus 72%; Likelihood Ratio Test 51.19 versus 32.44). CONCLUSION: Our findings showed inappropriateness of ad hoc complete-case analysis. This approach led to loss in power and imprecise estimates. Application of multiple imputation techniques to avid such problems is recommended.

Tamoxifen resistance in early breast cancer: statistical modelling of tissue markers to improve risk prediction.

BACKGROUND: For over two decades, the Nottingham Prognostic Index (NPI) has been used in the United Kingdom to calculate risk scores and inform management about breast cancer patients. It is derived using just three clinical variables - nodal involvement, tumour size and grade. New scientific methods now make cost-effective measurement of many biological characteristics of tumour tissue from breast cancer biopsy samples possible. However, the number of potential explanatory variables to be considered presents a statistical challenge. The aim of this study was to investigate whether in ER+ tamoxifen-treated breast cancer patients, biological variables can add value to NPI predictors, to provide improved prognostic stratification in terms of overall recurrence-free survival (RFS) and also in terms of remaining recurrence free while on tamoxifen treatment (RFoT). A particular goal was to enable the discrimination of patients with a very low risk of recurrence. METHODS: Tissue samples of 401 cases were analysed by microarray technology, providing biomarker data for 72 variables in total, from AKT, BAD, HER, MTOR, PgR, MAPK and RAS families. Only biomarkers screened as potentially informative (i.e., exhibiting univariate association with recurrence) were offered to the multivariate model. The multiple imputation method was used to deal with missing values, and bootstrap sampling was used to assess internal validity and refine the model. RESULTS: Neither the RFS nor RFoT models derived included Grade, but both had better predictive and discrimination ability than NPI. A slight difference was observed between models in terms of biomarkers included, and, in particular, the RFoT model alone included HER2. The estimated 7-year RFS rates in the lowest-risk groups by RFS and RFoT models were 95 and 97%, respectively, whereas the corresponding rate for the lowest-risk group of NPI was 89%. CONCLUSION: The findings demonstrate considerable potential for improved prognostic modelling by incorporation of biological variables into risk prediction. In particular, the ability to identify a low-risk group with minimal risk of recurrence is likely to have clinical appeal. With larger data sets and longer follow-up, this modelling approach has the potential to enhance an understanding of the interplay of biological characteristics, treatment and cancer recurrence.