Time interval between the onset of symptoms and diagnosis of multiple sclerosis and the influential factors: A national registry-based study.

OBJECTIVE: The time to diagnosis of multiple sclerosis (MS) is of great importance for early treatment, thereby reducing the disability and burden of the disease. The purpose of this study was to determine the time from the onset of clinical symptoms to the diagnosis of MS and to evaluate the factors associated with a late diagnosis in Iranian MS patients. METHODS: The present cross-sectional study was conducted on patients with MS who were registered in the National MS Registry System of Iran (NMSRI). RESULTS: Overall, 23291 MS patients registered in 18 provinces of Iran were included in this study. The mean (standard deviation) interval between the onset of the disease and diagnosis of MS was 13.42 (32.40) months, and the median was one month. The diagnostic interval of 41.6% of patients was less than one month, and 14.8% of them had a one-month time to diagnosis. Patients with an age of onset below 18 years and those diagnosed after the age of 50 years had a longer time to diagnosis (P<0.001). Patients with primary progressive MS (PPMS) had the longest time to diagnose and those with relapsing-remitting MS (RRMS) had the shortest time (P<0.001). The results of negative binominal regression showed that the average rate of delay in diagnosis in women was 12% less than that in men. The average delay in diagnosis in patients with a positive family history of MS was 23% more than that in others. The rate of delay in the diagnosis of patients with PPMS and secondary progressive MS was 2.22 and 1.66 times higher, respectively, compared with RRMS. CONCLUSION: The findings of the present study revealed that more than half of the MS patients were diagnosed within a one-month interval from the symptom onset, which is an acceptable period. More attention should be paid to patients' access to medical facilities and MS specialists.

The relationship between pesticide exposures and primary headaches in adults: A cross-sectional study based on Rafsanjan cohort study.

Objectives: Toxic substances can trigger headaches. The prevalence of pesticide use and headaches was high among the population of Rafsanjan. Methods: A cross-sectional study was used to collect data from 9991 adults who participated via sampling people aged 35-70 years old of both genders from the Rafsanjan Cohort Study (RCS) in Iran. Demographic characteristics, habits, chronic primary headache (CPH), and episodic primary headache (EPH) were measured. Results: The prevalence of CPH and EPH were 7.4 % and 29.9 % respectively. The multivariable model showed the odds of EPH increased significantly by the pesticide exposure on farm OR: 1.16 (1.02-1.34), in yard OR: 1.18 (1.01-1.39), duration of pesticide exposure in yard > median OR: 1.35 (1.06-1.73), at home OR: 1.31 (1.17-1.46), duration of pesticide exposure at home ≤ median OR: 1.24 (1.10-1.40) and > median OR: 1.38 (1.22-1.57). Also, pesticide preparation OR: 1.20 (1.03-1.39), duration of exposure in pesticide preparation ≤ median OR: 1.31 (1.09-1.57), and duration of exposure in managed spraying pesticide > median OR: 1.28 (1.04-1.57) increased odds of EPH. These results showed that the odds of CPH increased in participants using pesticides at home OR: 1.22 (1.02-1.48), duration of pesticide exposure at home > median OR: 1.37 (1.11-1.70), and duration of pesticide exposure in pesticide preparation > median OR: 0.47 (0.27-0.82). The odds of EPH increased with more pesticide exposures (18 %) and duration of pesticide exposure (25 %). Conclusions: As evidenced by the obtained results, there is a relationship between pesticide exposure and headaches.

Association between metabolic syndrome and stroke: a population based cohort study.

Both metabolic syndrome (MetS) and stroke are associated with increased risk of mortality. Here, we aimed to assess the prevalence of MetS among adults using three definitions (Adult Treatment Panel III (ATP-III), International Diabetes Federation (IDF) and IDF ethnic specific cut-off for Iranian criteria) and its association with stroke. We performed a cross-sectional study of a total of 9991 adult participants of Rafsanjan Cohort Study (RCS), as part of the Prospective epidemiological research studies in Iran (PERSIAN cohort study). The MetS prevalence was evaluated in participants according to the different criteria. Multivariate logistic regression analyses were conducted to assess the association between three definitions of MetS with stroke. We found that MetS was significantly associated with higher odds of stroke according to NCEP-ATP III (odds ratio (OR): 1.89, 95% confidence interval (CI) 1.30-2.74), international IDF (OR:1.66, 95% CI: 1.15-2.40) and Iranian IDF (OR:1.48, 95% CI: 1.04-2.09) after adjusted for variables confounders. Furthermore, after adjustment, in receiver operating characteristic (ROC) curve, the AUROC was 0.79 (95% CI = 0.75-0.82), 0.78(95% CI = 0.74-0.82) and 0.78(95% CI = 0.74-0.81) for presence of MetS according to NCEP-ATP III, international IDF and Iranian IDF, respectively. ROC analyses revealed that all of these three criteria for MetS are "moderately accurate" for the identification of increased stroke risk.In conclusion, our results showed that MetS was associated with increased odds of stroke. Our findings implicate the importance of early identification, treatment, and ultimately prevention of the metabolic syndrome.

Dietary antioxidants and liver enzymes in Rafsanjan, a Region in Southeast Iran.

Oxidative stress has been considered the main contributor to liver injury. Dietary antioxidants would be expected to improve liver function. The hepatoprotective effects of antioxidants are controversial. In the present study, the associations of some dietary antioxidants and the levels of serum liver enzymes were examined. This cross-sectional study was conducted using the Rafsanjan Cohort Study (RCS) data as a population-based prospective cohort which is a part of the Prospective Epidemiological Research Studies in IrAN (PERSIAN). A total of 9942 participants aged 35-70 years old were included in this study. Among this population, 4631 (46.59%) were male, and 5311 (53.42%) were female. Dietary intakes were collected by a validated food frequency questionnaire (FFQ) with 128 items. Aspartate transaminase (AST), Alanine transaminase (ALT), γ-glutamyl transferase (GGT), and Alkaline phosphatase (ALP) were measured by a biotecnica analyzer. Dichotomous logistics regression models were used to investigate the association between the elevated liver enzymes and intake of dietary antioxidants using crude and adjusted models. In the adjusted model, in subjects with higher consumption of Se, Vit A, Vit E, ß-carotene, α-carotene, and ß-cryptoxanthin, the odds ratios of elevated ALP were decreased compared to the reference group (ORs 0.79 (0.64-0.96), 0.80 (0.66-0.98), 0.73 (0.60-0.89), 0.79 (0.64-0.96), 0.78 (0.64-0.95), 0.80 (0.66-0.98), and 0.79 (0.64-0.98), respectively). Subjects with higher consumption of Se, Vit A, Vit E, and provitamin A carotenoids (ß-carotene, α-carotene, ß-cryptoxanthin) showed decreased odds of elevated ALP. These findings support the hypothesis that Se, Vit A, Vit E, and provitamin A carotenoids may be associated with improvements in ALP and act as suppressors against the development of liver injury.

Sleep duration, hypnotic drug use, and risk factors: cross- sectional study.

Both short sleep duration (SSD) and long sleep duration (LSD) are associated with an increased risk of morbidity and mortality. Here, we aimed to assess the prevalence of sleep duration disturbances among adults in association with demographic, medication use, personal habits, and chronic diseases, while also considering the impact of hypnotic drug use. We performed a cross-sectional study of 9991 adult participants of the Rafsanjan Cohort Study (RCS), as part of the Prospective epidemiological research studies in Iran (PERSIAN). Multivariate logistic regression analyses were conducted to assess the association between short (< 6 h) and long (> 9 h) sleep duration with demographic and lifestyle parameters and common non-communicable diseases. Additionally, we performed stratified analysis to investigate the association of sleep duration with the abovementioned factors and diseases, in groups with and without hypnotic drug use. We found higher odds of SSD significantly associated with age (P < 0.001), BMI (P < 0.001), physical activity (P < 0.001), and depression (P = 0.023). LSD displayed a positive association with the female sex (P < 0.001), opium consumption (P < 0.001), and history of MI (P = 0.045), and a reverse connection with education (P = 0.007), physical activity (P < 0.001) and alcohol consumption (P = 0.027). Stratifying for the hypnotic drug use, our sensitivity analyses indicated that in hypnotic drug users, education (P = 0.034) and physical activity (P < 0.001) were associated with LSD, in this group, significantly increased odds ratio of LSD were associated with opium consumption (P = 0.046) and thyroid dysfunction (P = 0.037). Our findings demonstrated the demographic and lifestyle factors and diseases associated with long and short sleep duration in the population of the RCS. Additionally, after stratifying for hypnotic drug use, our results indicated that some diseases are only associated with abnormal sleep duration upon using hypnotic drugs.

Cross-sectional analysis of potential risk factors of the pineal gland calcification.

The Pineal gland (PG) is the site of production of melatonin as an important central hormone in the body. It is not known yet whether PG calcification (PGC) is an age-associated physiological process or a pathologic condition caused by lifestyle-factors and metabolic-dysregulations.Here, we performed a cross-sectional analysis on 586 patients referred to have Computed Tomographic (CT) scans (above 15 years old), in the Ali Ebne Abi Taleb hospital radiology center in 2017-2018. Based on the CT-scans of the brain, the presence of PGC was recorded and a score of scale 0 to 6 (PGC_score) was calculated for its intensity based on the volume and the Hounsfield units of the calcified pineal. Logistic and ordered logistic regression tests were employed to determine potential risk factor of PGC and higher PGC_score, respectively, testing the factors age, sex, history of cardiovascular and metabolic diseases, smoking and opioid use. We found male sex (OR: 2.30 (95% CI:1.39-3.82) and smoking cigarettes (OR: 4.47 (95% CI:1.01-19.78)) as the main potential risk factors for the pineal gland calcification. For PGC_score, we found age to be dose-dependently associated with PGC_score only in patients aged below 63 (p-trend < 0.001). Stratifying for age, in patients < 63 years old, we found age, male sex (positive association) and dyslipidemia (negative association) as the main significantly associated factors of PGC_score. On the contrary, in patients aged > = 63, cigarette smoking was the only significantly associated factor of higher PGC_score.In conclusion, our results indicate that at ages below 63, age, male sex and blood lipid are the main associated factors of higher PGC, but at ages above that, the lifestyle factor smoking is significantly associated with higher pineal gland calcification.

Late-onset multiple sclerosis in Iran: A report on demographic and disease characteristics.

BACKGROUND: Today, it is estimated that around 5% of multiple sclerosis (MS) patients are in the late-onset category (age at disease onset ≥ 50). Diagnosis and treatment in this group could be challenging. Here, we report the latest update on the characteristics of Iranian patients with late-onset MS (LOMS). METHODS: This cross-sectional study used the information provided by the nationwide MS registry of Iran (NMSRI). The registrars from 14 provinces entered data of patients with a confirmed diagnosis of MS by neurologists. Patients with disease onset at or later than 50 years of age were considered LOMS. RESULTS: Of 20,036 records, the late-onset category included 321 patients (1.6%). The age-standardized LOMS prevalence was around 75 per 100,000 people. 215 patients (67%) were female. Median Expanded Disability Status Scale (EDSS) was 3 (interquartile range: 1.5-5). The majority of the cases (56%) suffered from relapsing-remitting (RR) course while 20% were diagnosed with primary progressive (PP) MS. Significantly higher proportion of male sex, PPMS, and higher EDSS were seen in the late-onset group compared with early-onset and adult-onset cases (p-value < 0.05). Seventy-five (23%) patients did not receive any disease-modifying treatment. DISCUSSION: The more prominent degenerative pathology of LOMS may be the underlying mechanism of the observed differences in comparison to non-LOMS. CONCLUSION: There are substantial differences and knowledge gaps regarding LOMS which could be the subject of further research.

Outcome predictors in anterior and posterior ischemic strokes: a study based on the Iranian SITS registry.

Ischemic stroke is the major form of stroke with two separate vascular territories. Many risk factors are related to stroke outcomes in both territories. The present descriptive research was carried out on the basis of data obtained from the Safe Implementation of Treatments in Stroke (SITS) registry on Iranian intravenous thrombolysis ischemic stroke cases. Vascular territory involved in each case and three-month excellent outcome, functional independence, mortality rate, and brain hemorrhage occurrence were determined. Univariable and multivariable logistics regression analyses were utilized in order to investigate association of ischemic stroke outcomes with the vascular territory involved and other related factors. Among 1566 patients 95.4% was anterior circulation stroke patients and 4.6% was posterior circulation stroke cases. There is no significant association between vascular territory with mortality (OR of PCS vs ACS: 0.74, 95% CI 0.37-1.46), excellent functional outcome (OR 0.72, 95% CI 0.44-1.19), functional outcome (OR 0.86, 95% CI 0.52-1.42) and local hemorrhage (OR 0.98, 95% CI 0.30-3.21). Among major risk factors, age, diabetes, NIHSS score and admission duration, increased significantly odds of three-month mortality, excellent outcome, and functional independence in the multivariate analysis. The highest of odds was in NIHSS score with a dose-response association. The vascular territory was not an outcome predictor in ischemic strokes. The most important predictor was baseline NIHSS.

Economic and Social Standing of Individuals in Iran Diagnosed with Multiple Sclerosis.

BACKGROUND: Multiple sclerosis (MS) may be affected by socioeconomic status (SES). This study aims to explore the determinants of SES among Iranian patients with MS and examine how these factors relate to disability and disease progression. METHODS: All patients with MS listed in the nationwide MS registry of Iran (NMSRI) until January 8, 2022, were included in this population-based study. RESULTS: Among the 5153 patients, most were female (74.5%), married (70.8%), and did not hold an academic degree (53.8%). Unemployment (OR: 3.75) and being unmarried (OR: 2.60) were significantly associated with Expanded Disability Status Scale (EDSS)≥6, and the time to progression was shorter in the unemployed group (P value: 0.03). There was also a significant negative correlation between the time to progression and the age at disease onset. CONCLUSION: The study suggests that providing financial and social support to MS patients and their families through investment could reduce both individual and societal burdens.

Cross-sectional study of passive opiate smoking in relation to stroke and some of stroke attributable risk factors in women.

Opiate use is related to neuropathological disorders, stroke and stroke attributable risk factors. However, secondary exposure to opiate in relation to the above-mentioned complications is studied only in animal models and remains to be evaluated in human populations. We tested whether passive exposure to opiate is associated with stroke and the known stroke predictive factors. We carried out a cross-sectional study of 1541 never smoker women who participated in the Rafsanjan Cohort Study (RCS) with their husbands (2015-2017 recruitment phase). RCS is one of the 19 geographic districts of the Prospective Epidemiological Research Studies in Iran (PERSIAN cohort study). Unadjusted and adjusted multiple logistic regression analyses were performed to evaluate the relationship between second-hand opiate exposure (husband opiate smoking after marriage) and the odds ratio of stroke and the following stroke risk factors and predictive parameters: overweight/obesity (BMI > 25), cholesterol (chol) > 200 mg/dl, fasting blood sugar (FBS) > 125 mg/dl, low density lipoprotein (LDL) > 100 mg/dl, triglyceride (TG) > = 150 mg/dl, hypertension, diabetes, and chronic headache. We observed a significant increased adjusted odds ratio (OR) of stroke (OR = 3.43, 95% CI:1.33-8.82) and its risk factors LDL > 100 mg/dl (OR = 1.37, 95% CI:1.01-1.87) and FBS > 125 mg/dl (OR = 1.58, 95% CI:1.08-2.30) in women associated with husbands' opiate smoking. This relationship was observed after adjusting for the confounding parameters including age, education years, and first-degree family history of the relevant diseases. The increased odds ratio for stroke and high LDL displayed a dose-sensitive trend with years of husband's opiate smoking after marriage (respective p-trends: 0.02 & 0.01). We did not observe a significant association between passive opiate smoking and high TG, high Chol or the diseases diabetes, hypertension and chronic headache. However, 89% increased odds ratio of chronic headache was observed to be associated with passive opiate smoking for more than 10 years (OR = 1.89, 95% CI:1.02-3.50). We found an increased risk of stroke and high LDL and FBS in women associated with passive opiate smoking. Furthermore, a dose-sensitive connection was found between the risks of stroke, high LDL and chronic headache with the years of passive opiate exposure. Our results point to the necessity of the future analyses, which further assess whether passive opiate exposure could be considered as an independent risk factor for stroke and metabolic diseases.

Evaluation of the relationship between opioid addiction and metabolic syndrome and its components in the adult population from Rafsanjan city; a cohort study.

BACKGROUND: We aimed to assess the association between opioid addiction and metabolic syndrome (MetS) risk and its components. METHODS: We used data obtained from the Rafsanjan Cohort Study (RCS), as a part of the prospective epidemiological research studies in IrAN (PERSIAN). The diagnosis of MetS was accomplished using three criteria of the International Diabetes Federation (IDF), Iranian IDF, and National Cholesterol Education Panel-Adult Treatment Panel III (NCEP-ATP III). Using a questionnaire, data for the demographic, anthropometric, and laboratory indices was collected. RESULTS: The prevalence of MetS was 38.30, 31.58, and 34.42% based on the IDF international, IDF Iranian, and NCEP-ATP III criteria. According to the IDF international criteria, 666 (17.45%) cases were using opioids and there was a statistically significant difference between opioid use and prevalence of MetS (p < 0.001). Based on the NCEP-ATP III criteria, there was a significant difference in the prevalence of MetS based on opioid use (p < 0.001). Use of opioids was associated significantly with a decreased odds of MetS in the multivariate model based on the IDF international (Adjusted OR = 0.85, 95% CI 0.74-0.98) and IDF Iranian criteria (Adjusted OR = 0.83, 95% CI 0.72-0.95). CONCLUSIONS: Prevalence of MetS was lower in subjects using opioids. Opioid use was associated with a decreased risk of MetS development.

Cohort-based analysis of maternal age at menarche in relation to young adult offspring anthropometric and metabolic parameters.

OBJECTIVES: Age of menarche is a determinant factor of cardiometabolic risk, adiposity and stature at adulthood. However, little is known about the transgenerational effects of age of menarche, especially beyond childhood of any offspring, and the studies remain limited to anthropometric outcomes in children at birth or before adolescence. In the present study, we aim to investigate the relationship of maternal age at menarche (MAM) with anthropometric and metabolic parameters in the young adult offspring (aged 15-35 years) in a Persian population. DESIGN, PATIENTS AND MEASUREMENTS: In this cohort-based cross-sectional study, we recruited 1139 mother-young adult dyads enroled in Rafsanjan Cohort Study (RCS) at adult RCS (aged 35-70 years) and youth RCS (aged 15-35 years) as part of the comprehensive PERSIAN (Prospective Epidemiological Research Studies in IrAN). In this study, MAM was categorized to early (MAM < 12 years), normal (12 ≤ MAM ≤ 14) and late menarche (MAM > 14 years). For these analyses, bivariate and multiple logistic regression models were used to investigate the relationships between late or early MAM and offspring anthropometric and metabolic parameters. RESULTS: Early MAM displayed a significant association with an increased odds ratio (OR) of tall stature adjusting for sex, age, socioeconomic status index, maternal age at birth and maternal height (as genetically determined factor). Sensitivity analysis by sex indicated this relationship to be specific to male offspring only (adjusted OR: 1.84 95% CI: 1.13-3.00, p value: .014). In addition, late MAM displayed a significant association with reduced OR of overweight/obesity and abdominal obesity in daughters only (obesity adjusted OR: 0.49, 95% CI: 0.27-0.88, p value: .018, abdominal obesity adjusted OR: 0.44, 95% CI: 0.23-0.82, p value: .010). dose-response analysis by categorization of MAM, further supported our results. On the contrary, our analyses do not support a significant relationship between MAM and youth metabolic indices, that is, metabolic syndrome, fasting blood sugar (FBS), high-density lipoprotein (HDL) and triglyceride (TG). CONCLUSIONS: The results of the present study indicate an association of maternal age of menarche with anthropometric measures of offspring in young adulthood in a sex differential manner. The data does not support a significant relationship between the metabolic indices FBS, TG and HDL in offspring with MAM. Overall, this study provides evidence for the intergenerational effects of age at menarche in the development of anthropometric measures in offspring in young adulthood (15-35), which is the first study of this kind in this age range.

Vitamin B12 Administration Facilitates The Antipsychotic And Pain-Relieving Effects Of Quetiapine, In The Alzheimer Patients With Psychotic Symptoms.

BACKGROUND: Psychotic symptoms in Alzheimer's disease (AD) patients are a problem in medicine. The efficacy of the vitamin B12 on the treatment of the psychotic symptoms of the AD patients in the association with antipsychotic drugs Quetiapine and Risperidone, was evaluated in this Study. METHODS: The effects of vitamin B12 along with two other drugs were studied on the Mini-Mental State Examination (MMSE), Clinical Global Impression (CGI), Brief Psychiatric Rating Scale (BPRS) and pain Visual Analogue Scale (VAS) in 47 AD patients with psychotic symptoms, including 4 groups, psychotic AD patients treated with Risperidone, Risperidone plus vitamin B12, Quetiapine and Quetiapine plus vitamin B12 . RESULTS: The results showed that Quetiapine improved all of the psychotic criteria, while Quetiapine plus vitamin B12 had better results on BPRS after 2 weeks, VAS score and MMSE. Risperidone also improves all of the criteria except MMSE and drug efficacy index, while, vitamin B12 neutralize the effects of the Risperidone on the BPRS, VAS, and severity of illness. CONCLUSION: Due to these results, Quetiapine is the preferred antipsychotics drug and Vitamin B12 plays an effective role in treatment as an adjunct therapy.

Vitamin B12 in Association with Antipsychotic Drugs Can Modulate the Expression of Pro-/Anti-Inflammatory Cytokines in Alzheimer Disease Patients.

INTRODUCTION: Patients with Alzheimer disease (AD) suffer from psychotic symptoms including pain. The current antipsychotic drugs confer limited effectiveness, and hence new strategies are being designed to decrease pain in order to increase antipsychological effectiveness. Vitamin B12 is a safe supplementary drug to decrease pain. Additionally, cytokines participate in the pathogenesis of immune-related diseases such as AD. Thus, the main aim of this clinical trial study was to determine the effects of treatment with risperidone and quetiapine, as antipsychotic drugs, with and without vitamin B12 on the psychotic symptoms of AD patients and the expression of IL-6, IL-8, tumor growth factor (TGF)-ß, tumor necrosis factor (TNF)-α, and endothelin (ET)-1). MATERIAL AND METHODS: Serum levels of IL-6, IL-8, TGF-ß, TNF-α, and ET-1 were evaluated in the following groups: healthy controls, nonpsychotic AD patients, psychotic AD patients, psychotic AD patients under treatment with risperidone, psychotic AD patients under treatment with risperidone plus vitamin B12, psychotic AD patients under treatment with quetiapine, and psychotic AD patients under treatment with quetiapine plus vitamin B12. RESULTS: Treatment with antipsychotic drugs plus vitamin B12 led to a decreased expression of IL-8 and TNF-α and an increased expression of TGF-ß. Vitamin B12 in association with quetiapine reduced the pain in psychotic AD patients. DISCUSSION: Proinflammatory cytokines play important roles in the pathogenesis of psychosis in AD patients. Antipsychotic drugs plus vitamin B12 can reduce and induce the expression of proinflammatory and anti-inflammatory cytokines to improve psychotic symptoms in AD patients.

Unusual recovery of aphasia in a polyglot Iranian patient after ischemic stroke.

INTRODUCTION: Aphasia is a language disorder resulting from a lesion in the cerebral cortex. In this case report, we present a polyglot patient who recovered from aphasia by speaking his newly active learned language. CASE REPORT: A 69 years old male referred with acute onset right hemiparesis and global aphasia. After imaging, he treated with 75 mg r-TPA (0.9 mg/kg). After the fourth day of hospitalization, he could name some objects and some short phrases but interestingly only in French language (although his mother language was Persian). DISCUSSION: In our patient, recovery was first in the last learned language and his learning memory was recovered earlier than his native languages. As in our case, we can expect to have different recovery theory that means active learning language could be the first part of recovery in aphasia.