Clinical, Immunological, and Genetic Features in Patients with NFKB1 and NFKB2 Mutations: a Systematic Review.

BACKGROUND: Inborn errors of immunity (IEIs) encompass various diseases with diverse clinical and immunological symptoms. Determining the genotype-phenotype of different variants in IEI entity precisely is challenging, as manifestations can be heterogeneous even in patients with the same mutated gene. OBJECTIVE: In the present study, we conducted a systematic review of patients recorded with NFKB1 and NFKB2 mutations, two of the most frequent monogenic IEIs. METHODS: The search for relevant literature was conducted in databases including Web of Science, PubMed, and Scopus. Information encompassing demographic, clinical, immunological, and genetic data was extracted from cases reported with mutations in NFKB1 and NFKB2. The comprehensive features of manifestations in patients were described, and a comparative analysis of primary characteristics was conducted between individuals with NFKB1 loss of function (LOF) and NFKB2 (p52-LOF/IκBδ-gain of function (GOF)) variants. RESULTS: A total of 397 patients were included in this study, 257 had NFKB1 mutations and 140 had NFKB2 mutations. There were 175 LOF cases in NFKB1 and 122 p52LOF/IκBδGOF cases in NFKB2 pivotal groups with confirmed functional implications. NFKB1LOF and p52LOF/IκBδGOF predominant cases (81.8% and 62.5% respectively) initially presented with a CVID-like phenotype. Patients with NFKB1LOF variants often experienced hematologic autoimmune disorders, whereas p52LOF/IκBδGOF patients were more susceptible to other autoimmune diseases. Viral infections were markedly higher in p52LOF/IκBδGOF cases compared to NFKB1LOF (P-value < 0.001). NFKB2 (p52LOF/IκBδGOF) patients exhibited a greater prevalence of ectodermal dysplasia and pituitary gland involvement than NFKB1LOF patients. Most NFKB1LOF and p52LOF/IκBδGOF cases showed low CD19 + B cells, with p52LOF/IκBδGOF having more cases of this type. Low memory B cells were more common in p52LOF/IκBδGOF patients. CONCLUSIONS: Patients with NFKB2 mutations, particularly p52LOF/IκBδGOF, are at higher risk of viral infections, pituitary gland involvement, and ectodermal dysplasia compared to patients with NFKB1LOF mutations. Genetic testing is essential to resolve the initial complexity and confusion surrounding clinical and immunological features. Emphasizing the significance of functional assays in determining the probability of correlations between mutations and immunological and clinical characteristics of patients is crucial.

A systematic review and meta-analysis on mortality rate following total pelvic exenteration in cancer patients.

BACKGROUND: Total pelvic exenteration (TPE), an en bloc resection is an ultraradical operation for malignancies, and refers to the removal of organs inside the pelvis, including female reproductive organs, lower urological organs and involved parts of the digestive system. The aim of this meta-analysis is to estimate the intra-operative mortality, in-hospital mortality, 30- and 90-day mortality rate and overall mortality rate (MR) following TPE in colorectal, gynecological, urological, and miscellaneous cancers. METHODS: This is a systematic review and meta-analysis in which three international databases including Medline through PubMed, Scopus and Web of Science on November 2023 were searched. To screen and select relevant studies, retrieved articles were entered into Endnote software. The required information was extracted from the full text of the retrieved articles by the authors. Effect measures in this study was the intra-operative, in-hospital, and 90-day and overall MR following TPE. All analyzes are performed using Stata software version 16 (Stata Corp, College Station, TX). RESULTS: In this systematic review, 1751 primary studies retrieved, of which 98 articles (5343 cases) entered into this systematic review. The overall mortality rate was 30.57% in colorectal cancers, 25.5% in gynecological cancers and 12.42% in Miscellaneous. The highest rate of mortality is related to the overall mortality rate of colorectal cancers. The MR in open surgeries was higher than in minimally invasive surgeries, and also in primary advanced cancers, it was higher than in recurrent cancers. CONCLUSION: In conclusion, it can be said that performing TPE in a specialized surgical center with careful patient eligibility evaluation is a viable option for advanced malignancies of the pelvic organs.

The role of fetal heart rate in first trimester sonograms in prediction of fetal sex: a systematic review and meta-analysis.

BACKGROUND: Early fetal sex determination is worthy of providing alertness about possible x-linked disorders, as well as predicting sex-related pregnancy complications and outcomes. Satisfying the curiosity of parents is another advantage. In this way, several studies have been performed which have shown conflicting results. AIM: We planned a systematic review for identifying any plausible role of Fetal Heart Rate (FHR) for early predicting fetal sex during the first trimester of non-complicated pregnancies. METHODS: This is a meta-analysis in which PubMed and Scopus databases were searched using different related keywords to find similar articles up to December 2022. Then the articles were screened to find eligible articles and finally, the articles entered in the meta-analysis were analyzed using Stata software (Stata Corp, College Station, TX). Standardized mean difference (SMD) and their 95% confidence interval (CI) were estimated. RESULTS: A total of 223 articles were evaluated and five articles were included in the meta-analysis. The results showed that there is a significant heterogeneity between the articles (p = 0.012, I-squared = 69.0%). The results of meta-analysis with a random model showed that there is no significant difference between male and female genders in terms of mean FHR (SMD = 0.04, 95%CI = -0.09-0.16, Z = 0.59, p = 0.553). CONCLUSION: This systematic review and meta-analysis showed that even though male fetuses show faster FHR but such sex-related difference is minimal. Therefore, first-trimester FHR is not a reliable predictive test for fetal sex determination. Further studies are recommended to achieve a more precise conclusion. TRIAL REGISTRATION: PROSPERO: CRD42023418291.

Effect of an educational intervention based on the theory of planned behavior on improving medication adherence in patients with multiple sclerosis treated with injectable disease-modifying drugs: randomized controlled trial.

BACKGROUND: Adherence to prescribed treatment in chronic diseases, as occurs in multiple sclerosis (MS), is a critical factor for a successful therapeutic response. This study aimed to investigate the effect of educational program based on Theory of Planned Behavior (TPB) on treatment adherence in patients with multiple sclerosis (MS) receiving injectable immunomodulatory drugs. METHODS: The present study is an educational randomized controlled trial research that was conducted on 100 patients with MS who had gone to MS clinic in Tehran city (Iran). The samples were randomly assigned to the intervention (N = 50) and control groups (N = 50). Data collection instrument was a researcher-made questionnaire based on TPB. Then, educational program was performed for the intervention group through four educational sessions. After three months, data collection was repeated for the two groups and data were analyzed. RESULTS: The knowledge and performance of the intervention group on treatment adherence drugs increased from 56.25 ± 20.3 to 78.31 ± 15.57 and 56.22 ± 5.76 to 71.62 ± 12.01 after the education respectively (p < 0.001). The mean of construct of TPB in the intervention group also increased after the intervention (p < 0.05). CONCLUSION: Applying the TPB model proved is very effective in developing an educational program for patients with MS, to enhance treatment adherence drugs. Besides such programs, follow-up education for controlling and monitoring are highly recommended. TRIAL REGISTRATION: This trial has been registered at Iranian Registry of Clinical Trials, IRCT20210808052109N1. Prospectively registered at 12-Aug-2021, (12/8/2021) available at: URL: https://en.irct.ir/trial/57994.

Periostin level in gingival crevicular fluid in periodontal disease: a systematic review and meta-analysis.

BACKGROUND: Periostin, a secreted adhesion molecule, is a matricellular protein secreted most in periodontal ligament and periosteum. Periostin is also needed for integrity and maturation of periodontal tissue. This meta-analysis was conducted to compare the gingival crevicular fluid (GCF) periostin levels in subjects having periodontal disease and healthy periodontium. METHODS: In this meta-analysis, three international database including PubMed, Scopus and Web of Science were searched and 207 studies retrieved. Also, the Google Scholar was searched to find more related studies (two studies were found). To assess the risk of bias of included studies, the Newcastle-Ottawa assessment scale adapted for case-control was used. Finally, required data was extracted and included into analysis. All statistical analysis were done using Stata software. RESULTS: Eight studies were included in this meta-analysis. Results showed that GCF periostin level is significant lower in chronic periodontitis group compare to healthy people (the standardized mean difference (SMD) = -3.15, 95% CI = -4.45, -1.85, p < 0.001). The syntheses of studies shown a significant decrease in the periostin level of chronic periodontitis patients compared to the gingivitis patients (SMD = -1.50, 95%CI = -2.52, -0.49, P = 0.003), while the mean level of periostin between the gingivitis patients and healthy group has no significant difference (SMD = -0.88, 95%CI = -2.14, 0.38, P = 0.173). CONCLUSION: The mean concentration of GCF periostin in people with chronic periodontitis significantly decreased compared to people with gingivitis and also compared to healthy people, while no significant difference was observed between the two groups with gingivitis and healthy people. Therefore, this marker may be used as a diagnostic criterion for the disease, which requires further studies.

Bacterial biofilm prevalence in dental unit waterlines: a systematic review and meta-analysis.

BACKGROUNDS: Numerous studies have shown that dental unit water lines (DUWLs) are often contaminated by a wide range of micro-organisms (bacteria, fungi, protozoa) and various prevalence have been reported for it in previous studies. Therefore, this review study aims to describe the prevalence of bacterial biofilm contamination of DUWLs. METHODS: This is a systematic review and meta-analysis in which the related keywords in different international databases, including Medline (via PubMed) and Scopus were searched. The retrieved studies were screened and the required data were extracted from the included studies. Three standard methods including American Dental Association (ADA), The Center for Disease Control and Prevention (CDC) and contaminated > 100 CFU/ml(C-100) standards were used to assess the bacterial biofilm contamination of DUWLs. All studies that calculated the prevalence of bacterial biofilm contamination of DUWLs, and English full-text studies were included in the meta-analysis. Studies that did not have relevant data or used unusual laboratory methods were excluded. Methodological risk of bias was assessed by a related checklist and finally, the data were pooled by fixed or random-effect models. RESULTS: Seven hundred and thirty-six studies were identified and screened and 26 related studies were included in the meta-analysis. The oldest included study was published in 1976 and the most recent study was published in 2020. According to the ADA, CDC and C-100 standards, the prevalence of bacterial contamination was estimated to be 85.0% (95% confidence interval (CI): 66.0-94.0%), 77.0% (95%CI: 66.0-85.0%) and 69.0% (95%CI: 67.0-71.0%), respectively. The prevalence of Legionella Pneumophila and Pseudomonas Aeruginosa in DUWLs was estimated to be 12.0% (95%CI: 10.0-14.0%) and 8.0% (95%CI: 2.0-24.0%), respectively. CONCLUSION: The results of this review study suggested a high prevalence of bacterial biofilm in DUWLs; therefore, the use of appropriate disinfecting protocol is recommended to reduce the prevalence of contamination and reduce the probable cross-infection.

Global, regional, and national cancer deaths and disability-adjusted life-years (DALYs) attributable to alcohol consumption in 204 countries and territories, 1990-2019.

BACKGROUND: Alcohol consumption is a risk factor for a number of communicable and non-communicable diseases, including several types of cancer. This article reports the burden of cancers attributable to alcohol consumption by age, sex, location, sociodemographic index (SDI), and cancer type from 1990 to 2019. METHODS: The Comparative Risk Assessment approach was used in the 2019 Global Burden of Disease study to report the burden of cancers attributable to alcohol consumption between 1990 and 2019. RESULTS: In 2019, there were globally an estimated 494.7 thousand cancer deaths (95% uncertainty interval [UI], 439.7 to 554.1) and 13.0 million cancer disability-adjusted life-years (DALYs; 95% UI, 11.6 to 14.5) that were attributable to alcohol consumption. The alcohol-attributable DALYs were much higher in men (10.5 million; 95% UI, 9.2 to 11.8) than women (2.5 million; 95% UI, 2.2 to 2.9). The global age-standardized death and DALY rates of cancers attributable to alcohol decreased by 14.7% (95% UI, 6.4% to 23%) and 18.1% (95% UI, 9.2% to 26.5%), respectively, over the study period. Central Europe had the highest age-standardized death rates that were attributable to alcohol consumption(10.3; 95% UI, 8.7 to12.0). Moreover, there was an overall positive association between SDI and the regional age-standardized DALY rate for alcohol-attributable cancers. CONCLUSIONS: Despite decreases in age-standardized deaths and DALYs, substantial numbers of cancer deaths and DALYs are still attributable to alcohol consumption. Because there is a higher burden in males, the elderly, and developed regions (based on SDI), these groups and regions should be prioritized in any prevention programs.

Mapping age- and sex-specific HIV prevalence in adults in sub-Saharan Africa, 2000-2018.

BACKGROUND: Human immunodeficiency virus and acquired immune deficiency syndrome (HIV/AIDS) is still among the leading causes of disease burden and mortality in sub-Saharan Africa (SSA), and the world is not on track to meet targets set for ending the epidemic by the Joint United Nations Programme on HIV/AIDS (UNAIDS) and the United Nations Sustainable Development Goals (SDGs). Precise HIV burden information is critical for effective geographic and epidemiological targeting of prevention and treatment interventions. Age- and sex-specific HIV prevalence estimates are widely available at the national level, and region-wide local estimates were recently published for adults overall. We add further dimensionality to previous analyses by estimating HIV prevalence at local scales, stratified into sex-specific 5-year age groups for adults ages 15-59 years across SSA. METHODS: We analyzed data from 91 seroprevalence surveys and sentinel surveillance among antenatal care clinic (ANC) attendees using model-based geostatistical methods to produce estimates of HIV prevalence across 43 countries in SSA, from years 2000 to 2018, at a 5 × 5-km resolution and presented among second administrative level (typically districts or counties) units. RESULTS: We found substantial variation in HIV prevalence across localities, ages, and sexes that have been masked in earlier analyses. Within-country variation in prevalence in 2018 was a median 3.5 times greater across ages and sexes, compared to for all adults combined. We note large within-district prevalence differences between age groups: for men, 50% of districts displayed at least a 14-fold difference between age groups with the highest and lowest prevalence, and at least a 9-fold difference for women. Prevalence trends also varied over time; between 2000 and 2018, 70% of all districts saw a reduction in prevalence greater than five percentage points in at least one sex and age group. Meanwhile, over 30% of all districts saw at least a five percentage point prevalence increase in one or more sex and age group. CONCLUSIONS: As the HIV epidemic persists and evolves in SSA, geographic and demographic shifts in prevention and treatment efforts are necessary. These estimates offer epidemiologically informative detail to better guide more targeted interventions, vital for combating HIV in SSA.

Epidemiology of familial multiple sclerosis in Iran: a national registry-based study.

BACKGROUND: Admittedly, little is known about the epidemiological signatures of familial multiple sclerosis (FMS) in different geographical regions of Iran. OBJECTIVE: To determine the epidemiology and the risk of FMS incidence in several provinces of Iran with a different ethnic population including, Fars, Tehran, Isfahan (Persians), and Mazandaran (Mazanis), Kermanshah (Kurds), and Chaharmahal and Bakhtiari (Lors). METHODS: This cross-sectional registry-based study was performed on nationwide MS registry of Iran (NMSRI) data collected from 2018 to 2021. This system, registers baseline characteristics, clinical presentations and symptoms, diagnostic and treatments at regional and national levels. RESULTS: A total of 9200 patients including, 7003 (76.1%) female and 2197 (23.9%) male, were participated. About 19% of patients reported a family history of MS; the order from highest to lowest FMS prevalence was as follows: Fars (26.5%), Chaharmahal and Bakhtiari (21.1%), Tehran (20.5%), Isfahan (20.3%), Mazandaran (18.0%), and Kermanshah (12.5%). Of all FMS cases, 74.7% (1308 cases) were female and 25.3% (442 cases) were male. FMS occurrence was much more common in females than males (P-value = 0.001). Further, the mean age at onset was 30 years among FMS cases. A substantially higher probability of relapsing-remitting MS and secondary-progressive MS was found among FMS cases than sporadic MS (SMS) (P_value = 0.001). There was no significant difference in Expanded Disability Status Scale (EDSS) scores between FMS and SMS. The majority of FMS cases were observed among first-degree relatives, with the highest rate in siblings. There was a significant association between MS risk and positive familial history in both maternal and paternal aunt/uncle (P_value = 0.043 and P_value = 0.019, respectively). Multiple sclerosis occurrence among offspring of females was higher than males (P_value = 0.027). CONCLUSIONS: In summary, our findings imply a noteworthy upward trend of FMS in Iran, even more than the global prevalence, which suggests a unique Atlas of FMS prevalence in this multi-ethnic population. Despite the highest rate of FMS within Persian and Lor ethnicities, no statistically significant difference was observed among the provinces.

The association between dietary inflammatory index, dietary antioxidant index, and mental health in adolescent girls: an analytical study.

BACKGROUND: Diet is considered as one of the modifiable factors that appears to exert a vital role in psychological status. In this way, we designed this study to examine the association between dietary inflammatory index (DII), dietary antioxidant index (DAI), and mental health in female adolescents. METHODS: This cross-sectional study included 364 female adolescents selected from high schools in the five regions of Tabriz, Iran. A 3-day food record was used to extract the dietary data and calculate DII/DAI scores. DII and DAI were estimated to assess the odds of depression, anxiety, and stress based on the Depression Anxiety Stress Scales-21. Adjusted relationships of the DII and DAI with depression, anxiety, and stress were determined using multiple regression after adjusting for age, energy intake, BMI, family income and mother and father education. Overweight was defined as body mass index (BMI)-for-age > + 1 z-score relative to world health organization standards. RESULTS: Depression, anxiety, and stress were observed in 21.4%, 26.6%, and 25.7% of subjects, respectively. The percentage of overweight among adolescents was 19.4%. The association between DII and score of mental health profile was positive among subjects in the third tertile of DII compared to subjects in the first tertile. However, this association was not statistically significant after adjusting for confounding variables. Moreover, there was a significant inverse association between DAI and depression and anxiety; and a statistically insignificant association between DAI and stress after adjusting for confounders. CONCLUSIONS: Our results highlighted the importance of a healthy and anti-inflammatory diet on mental health in female adolescents. Therefore, modifying unhealthy dietary habits are likely to be effective in the management of psychosocial disorders.

Estimating the Marginal Causal Effect and Potential Impact of Waterpipe Smoking on Risk of Multiple Sclerosis Using the Targeted Maximum Likelihood Estimation Method: A Large, Population-Based Incident Case-Control Study.

There are few if any reports regarding the role of lifetime waterpipe smoking in the etiology of multiple sclerosis (MS). In a population-based incident case-control study conducted in Tehran, Iran, we investigated the association between waterpipe smoking and MS, adjusted for confounders. Cases (n = 547) were patients aged 15-50 years identified from the Iranian Multiple Sclerosis Society between 2013 and 2015. Population-based controls (n = 1,057) were persons aged 15-50 years recruited through random digit telephone dialing. A doubly robust estimation method, the targeted maximum likelihood estimator (TMLE), was used to estimate the marginal risk ratio and odds ratio for the association between waterpipe smoking and MS. The estimated risk ratio and odds ratio were both 1.70 (95% confidence interval: 1.34, 2.17). The population attributable fraction was 21.4% (95% confidence interval: 4.0, 38.8). Subject to the limitations of case-control studies in interpreting associations causally, these results suggest that waterpipe use, or strongly related but undetermined factors, increases the risk of MS. Further epidemiologic studies, including nested case-control studies, are needed to confirm these findings.

Global, regional, and national burden of other musculoskeletal disorders 1990-2017: results from the Global Burden of Disease Study 2017.

OBJECTIVES: To describe the level and trends of point prevalence, deaths and disability-adjusted life years (DALYs) for other musculoskeletal (MSK) disorders, i.e. those not covered by specific estimates generated for RA, OA, low back pain, neck pain and gout, from 1990 to 2017 by age, sex and sociodemographic index. METHODS: Publicly available modelled estimates from the Global Burden of Disease (GBD) 2017 study were extracted and reported as counts and age-standardized rates per 100 000 population for 195 countries and territories between 1990 and 2017. RESULTS: Globally, the age-standardized point prevalence estimates and deaths rates of other MSK disorders in 2017 were 4151.1 and 1.0 per 100 000. This was an increase of 3.4% and 7.2%, respectively. The age-standardized DALY rate in 2017 was 380.2, an increase of 3.4%. The point prevalence estimate was higher among females and increased with age. This peaked in the 65-69 year age group for both females and males in 2017, followed by a decreasing trend for both sexes. At the national level, the highest age-standardized point prevalence estimates in 2017 were seen in Bangladesh, India and Nepal. The largest increases in age-standardized point prevalence estimates were observed in Romania, Croatia and Armenia. CONCLUSION: The burden of other MSK disorders is proven to be substantial and increasing worldwide, with a notable intercountry variation. Data pertaining to specific diseases within this overarching category are required for future GBD MSK estimates. This would enable policymakers to better allocate resources and provide interventions appropriately.

Clinical, immunological and genetic findings in patients with UNC13D deficiency (FHL3): A systematic review.

BACKGROUND: Familial hemophagocytic lymphohistiocytosis (FHL) is a rare autosomal recessive immune disorder that is caused by mutations in 6 different genes related to the formation and function of secretory lysosomes within cytotoxic T lymphocytes and natural killer (NK) cells. Thus, defect in these genes is associated with the accumulation of antigens due to defective cytotoxic function. FHL type 3 (FHL3) accounts for nearly 30-40% of FHL, and its underlying reason is mutation in UNC13D gene which encodes Munc13-4 protein. METHODS: For the first time, we aimed to systematically review clinical features, immunologic data, and genetic findings of patients with FHL3. We conducted electronic searches for English-language articles in PubMed, Web of Science, EMBASE, and Scopus databases to collect comprehensive records related to patients with UNC13D mutations. RESULTS: A total of 279 abstracts were initially reviewed for inclusion. Among them, 57 articles corresponding to 322 individual FHL3 patients fulfilled our selection criteria. Finally, 73 and 249 patients were considered as severe and mild feature groups, respectively. Our results confirmed that fever, hepatosplenomegaly, and hemophagocytosis are common clinical features in the disease. Moreover, reduced fibrinogen and NK cell activity, as well as increased ferritin and triglycerides, are important markers for early diagnosis of the FHL3 disease. Investigation of genotype showed that the most prevalent type and zygosity of UNC13D are splice-site errors and compound heterozygous, respectively. CONCLUSION: FHL3 patients have a wide range of clinical manifestations, which makes it difficult to diagnose. Therefore, it seems that the sequencing of the entire UNC13D gene (coding and non-coding regions) is the most appropriate way to accurate diagnosis of FHL3 patients.

Multiple sclerosis projection in Tehran, Iran using Bayesian structural time series.

BACKGROUND: The prevalence of Multiple Sclerosis (MS) has been increasing worldwide and the highest prevalence ratio among Asian countries was reported in Iran. This study aims to estimate the increase in MS occurrence during more than three decades in Tehran and forecast the future condition of the disease using time series approaches for the next ten years. METHODS: The cross-sectional study was conducted from 1999 to 2019 based on records of MS cases from Iranian MS Society (IMSS) registry system. The prevalence was estimated using population data presented by the Statistical Centre of Iran. Through Bayesian Structural Time Series (BSTS) model, we want to predict the prevalence of familial and sporadic MS in the next ten years. . RESULTS: Among 22,421 cases with MS, 16,831 (75.1 %) were female and 5589 (24.9 %) were male. Female to male ratio was 3.0:1 and the number of familial MS cases were 2982 (13.3 %) of subjects. Female gender was less responsible for higher rate of MS in familial definition (beta = 0.020) in comparison to sporadic cases (beta = 0.034). Forecasting by BSTS revealed an increase in MS prevalence for the next ten years so that the prevalence rate for total, familial and sporadic MS respectively begins with 189.50 (183.94-195.14), 25.69 (24.97-26.45) and 163.74(159.06-168.57) in 2020 and ends with 220.84 (171.48-266.92), 30.79 (24.16-37.15), and 189.33(146.97-230.19) in 2029. CONCLUSIONS: According to the findings, MS prevalence increased during three decades and it will increase over the next ten years. Tehran province is one of the regions with highest MS prevalence in Asia. The results of present study indicated that females are at higher risk for MS than males in both sporadic and familial MS.

The causal effect and impact of reproductive factors on breast cancer using super learner and targeted maximum likelihood estimation: a case-control study in Fars Province, Iran.

OBJECTIVES: The relationship between reproductive factors and breast cancer (BC) risk has been investigated in previous studies. Considering the discrepancies in the results, the aim of this study was to estimate the causal effect of reproductive factors on BC risk in a case-control study using the double robust approach of targeted maximum likelihood estimation. METHODS: This is a causal reanalysis of a case-control study done between 2005 and 2008 in Shiraz, Iran, in which 787 confirmed BC cases and 928 controls were enrolled. Targeted maximum likelihood estimation along with super Learner were used to analyze the data, and risk ratio (RR), risk difference (RD), andpopulation attributable fraction (PAF) were reported. RESULTS: Our findings did not support parity and age at the first pregnancy as risk factors for BC. The risk of BC was higher among postmenopausal women (RR = 3.3, 95% confidence interval (CI) = (2.3, 4.6)), women with the age at first marriage ≥20 years (RR = 1.6, 95% CI = (1.3, 2.1)), and the history of oral contraceptive (OC) use (RR = 1.6, 95% CI = (1.3, 2.1)) or breastfeeding duration ≤60 months (RR = 1.8, 95% CI = (1.3, 2.5)). The PAF for menopause status, breastfeeding duration, and OC use were 40.3% (95% CI = 39.5, 40.6), 27.3% (95% CI = 23.1, 30.8) and 24.4% (95% CI = 10.5, 35.5), respectively. CONCLUSIONS: Postmenopausal women, and women with a higher age at first marriage, shorter duration of breastfeeding, and history of OC use are at the higher risk of BC.

The effect of body mass index on sperm DNA fragmentation: a systematic review and meta-analysis.

BACKGROUND: Current evidence supports the association between the high sperm DNA fragmentation (SDF) and the poor fertilization rate following either natural conception or assisted reproductive techniques (ART). On the other hand, there are conflicting results regarding the decreased sperm DNA integrity in men with high body mass index (BMI). OBJECTIVE: We aimed at the present systematic review and meta-analysis at evaluating the association between BMI and SDF. METHODS: We searched databases of Medline, Embase, Scopus, and Web of Science up to May 2019, to identify observational studies that assessed the associations between BMI and SDF. BMI was classified, according to the standard BMI classifications, into six categories including underweight (<18.5), normal weight (18.5-24.99), overweight (25-29.99), class I obesity (30-34.99), class II obesity (35-39.99), and class III obesity (≥40). Standardized mean differences (SMDs) and 95% confidence intervals (CIs) of SDF were calculated by using a random-effects model for BMI categories. RESULTS: The initial extensive literature search yielded 33,739 potentially relevant articles (3,917 from Medline, 781 from Embase, 12,685 from Scopus, and 9,348 from Web of Science). Fourteen studies (nine cross-sectional, four cohort, and one case-control studies), with a total number of 8,255 participants, were included in the meta-analysis. Finally, three studies reported higher SDF levels in obese men (BMI = 30-34.99) compared with normal-weight men (BMI < 25) (SMD: 0.23, 95% CI: 0.01, 0.46, P = 0.05, I2 = 0%), but there was no difference between other categories. CONCLUSIONS: There is insufficient data to demonstrate a positive association between BMI and SDF. Our findings provide a rationale for conducting further cohort studies for evaluation of the association between BMI and SDF, considering potential confounders.

Global, regional and national burden of osteoarthritis 1990-2017: a systematic analysis of the Global Burden of Disease Study 2017.

OBJECTIVES: To report the level and trends of prevalence, incidence and years lived with disability (YLDs) for osteoarthritis (OA) in 195 countries and territories from 1990 to 2017 by age, sex and Socio-demographic index (SDI; a composite of sociodemographic factors). METHODS: Publicly available modelled data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 were used. The burden of OA was estimated for 195 countries and territories from 1990 to 2017, through a systematic analysis of prevalence and incidence modelled data using the methods reported in the GBD 2017 Study. All estimates were presented as counts and age-standardised rates per 100 000 population, with uncertainty intervals (UIs). RESULTS: Globally, the age-standardised point prevalence and annual incidence rate of OA in 2017 were 3754.2 (95% UI 3389.4 to 4187.6) and 181.2 (95% UI 162.6 to 202.4) per 100 000, an increase of 9.3% (95% UI 8% to 10.7%) and 8.2% (95% UI 7.1% to 9.4%) from 1990, respectively. In addition, global age-standardised YLD rate in 2017 was 118.8 (95% UI 59.5 to 236.2), an increase of 9.6% (95% UI 8.3% to 11.1%) from 1990. The global prevalence was higher in women and increased with age, peaking at the >95 age group among women and men in 2017. Generally, a positive association was found between the age-standardised YLD rate and SDI at the regional and national levels. Age-standardised prevalence of OA in 2017 ranged from 2090.3 to 6128.1 cases per 100 000 population. United States (6128.1 (95% UI 5729.3 to 6582.9)), American Samoa (5281 (95% UI 4688 to 5965.9)) and Kuwait (5234.6 (95% UI 4643.2 to 5953.6)) had the three highest levels of age-standardised prevalence. Oman (29.6% (95% UI 24.8% to 34.9%)), Equatorial Guinea (28.6% (95% UI 24.4% to 33.7%)) and the United States 23.2% (95% UI 16.4% to 30.5%)) showed the highest increase in the age-standardised prevalence during 1990-2017. CONCLUSIONS: OA is a major public health challenge. While there is remarkable international variation in the prevalence, incidence and YLDs due to OA, the burden is increasing in most countries. It is expected to continue with increased life expectancy and ageing of the global population. Improving population and policy maker awareness of risk factors, including overweight and injury, and the importance and benefits of management of OA, together with providing health services for an increasing number of people living with OA, are recommended for management of the future burden of this condition.

Evidence of an increased prevalence of multiple sclerosis: a population-based study of Tehran registry during 1999-2018.

BACKGROUND: The epidemiological characteristics of multiple sclerosis (MS) have been investigated in various studies, which have revealed that the prevalence of MS varies across countries. The present study was conducted to investigate the longitudinal prevalence of MS in Tehran, Iran. METHODS: The present population-based study was conducted in Tehran, the capital of Iran from 1999 to 2018 based on the annual report data provided by the Iranian MS Society (IMSS) registry system. The age-standardized and crude prevalence were estimated using population data presented by the Statistical Centre of Iran. RESULTS: A total of 21,580 MS cases were registered and included in the analysis. Among the participant patients, 24.99% (5393) and 75.01% (16,187) of cases were male and female, respectively. The mean age of MS onset was 28.8 years (S.D: 8.7). The age-standardized prevalence (ASP) of MS increased from 73.7 (95%CI: 72.1-75.2) per 100,000 people in 2006 to 137.6 (95% CI: 135.7-139.5) per 100,000 people in 2018. The ASP of MS in 2018 was estimated to be 67.9 (95%CI: 66.0-69.8) and 207.3 (95%CI: 204.0-210.7) per 100,000 people among males and females, respectively. The age-standardized female-to-male ratio of MS ranged from 3.7 (in 2010) to 2.06 (in 2017). CONCLUSION: The findings of this study suggested that the prevalence of MS in Tehran province is relatively high, and the occurrence of the disease is more common in the age groups under 40 years as compared with older-aged groups. In line with reports provided for various regions of the world, the prevalence of MS was higher among women. Similarly, the findings of this study revealed that the female-to-male ratio was 2.14 in 2018.

Comparison of child abuse history in patients with and without functional abdominal pain: a case-control study.

BACKGROUND: Gastrointestinal (GI) disorders are ranked first amongst medical diseases as a trigger of requests for mental health counselling. Child abuse has been regarded as one of the main causes of the development of functional abdominal pain (FAP) in children. This study aimed, therefore, to compare the prevalence of child abuse experience among two groups of patients with and without FAP. METHODS: A case-control study of children in Arak, Iran, in which experience of child abuse was compared in children with (n = 100) and without functional abdominal pain (n = 100). Three categories of child abuse - emotional abuse, physical abuse, and neglect - were assessed using the Child Abuse Questionnaire. The data were analyzed using Stata software. RESULTS: After adjusting for potential confounders, there were group differences in emotional abuse (96% vs. 81%, aOR = 5.13, 95% CI: 1.3-20.3, p = 0.017), neglect (28% vs. 8%, aOR = 4.27, 95% CI: 1.8-11.8, p = 0.001) and total child abuse score (98% vs. 84%, aOR = 8.2, 95% CI: 1.5-43.8, p = 0.014) but not in physical abuse (57% vs. 46%, aOR = 1.47, 95% CI: 0.81-2.60, p = 0.728). CONCLUSIONS: As the prevalence of child abuse is higher in patients with FAP, child abuse appears to be related to the occurrence of FAP in children. However, the results of this study cannot be generalized to Iranian society generally and further longitudinal studies are recommended.

Estimating global injuries morbidity and mortality: methods and data used in the Global Burden of Disease 2017 study.

BACKGROUND: While there is a long history of measuring death and disability from injuries, modern research methods must account for the wide spectrum of disability that can occur in an injury, and must provide estimates with sufficient demographic, geographical and temporal detail to be useful for policy makers. The Global Burden of Disease (GBD) 2017 study used methods to provide highly detailed estimates of global injury burden that meet these criteria. METHODS: In this study, we report and discuss the methods used in GBD 2017 for injury morbidity and mortality burden estimation. In summary, these methods included estimating cause-specific mortality for every cause of injury, and then estimating incidence for every cause of injury. Non-fatal disability for each cause is then calculated based on the probabilities of suffering from different types of bodily injury experienced. RESULTS: GBD 2017 produced morbidity and mortality estimates for 38 causes of injury. Estimates were produced in terms of incidence, prevalence, years lived with disability, cause-specific mortality, years of life lost and disability-adjusted life-years for a 28-year period for 22 age groups, 195 countries and both sexes. CONCLUSIONS: GBD 2017 demonstrated a complex and sophisticated series of analytical steps using the largest known database of morbidity and mortality data on injuries. GBD 2017 results should be used to help inform injury prevention policy making and resource allocation. We also identify important avenues for improving injury burden estimation in the future.