Estimation of the wastage rate of MMR and pentavalent vaccines in open and closed vials in three western provinces of Iran

Background: Vaccine wastage is one of quality indicators of immunization program and high vaccine wastage will increase overall costs and impede efforts towards a more efficient and sustainable program. We aimed at estimating of the wastage rates of Measles-Mumps-Rubella (MMR) and pentavalent (diphtheria-tetanus-pertussis-hepatitis B -Haemophilus influenza type b) vaccines in different vaccine vial sizes. Study design: Multicentre descriptive study using existing data. Methods: This study was in three provinces (Hamadan, Kermanshah and Kordestan) of Iran including 131,135 populations with 2,548 under-1years children. Twenty-seven health facilities were selected randomly from nine districts in three provinces of western part of Iran. Six-months data including vaccination and vaccine stock records collected from April to September 2017. Finally, number of opened vials and number of target population vaccinated were collected and data were analysed to estimate the wastage rates in both unopened and opened vials of both antigens. Results: The wastage rate for combined MMR 2-dose and 5-dose opened vials for three provinces was 29%(Hamadan 18%, Kermanshah 14% and Kordestan 52%). The wastage rate for combined pentavalent single-dose and 10-dose vials for three provinces was 17% (in Kordestan33%, 11% Kermanshah 11% and Hamedan 3%). The total average of pentavalent single-dose and 10-dose vials wastage rate was 5% and varied 13% for urban and 3% for rural areas. The average of discarded unopened vials wastage rate in all facilities for MMR was 3.9% (3.2% for MMR 2-dose vial and 10.2% for MMR 5-dose vial). This rate was 1.7% for pentavalent total (1.9% for single dose vial and 0.4% for 10 dose vial). Conclusion: The vaccine wastage rates in Iran are in line with other countries and lower than the suggested rate based on WHO policies for multi-dose vials. The wastage rates were different for in provinces, districts and health facilities. The MMR total wastage rate in rural is higher than those in urban areas. However, the pentavalent total wastage rate was higher in urban area

Bone mineral density status in patients with recent-onset rheumatoid arthritis

Background: Osteoporosis is a sizable comorbidity complication in Rheumatoid Arthritis (RA) sufferers. In the current study, the prevalence of osteopenia and osteoporosis in active RA sufferers and the association of disease-related factors of osteoporosis and reduced bone mineral density (BMD) have been examined. Methods: In this cross-sectional study, 300 new-onset symptoms (less than one year) RA patients without a history of glucocorticoids or DMARDs were selected. Biochemical blood measurements and BMD status were performed with dual-energy X-ray absorptiometry. According to the T-scores of the patients, they were divided into three groups: osteoporosis<-2.5, -2.5 < osteopenia <-1, and − 1 < normal. Also, the MDHAQ questionnaire, DAS-28, and FRAX criteria were calculated for all patients. Multivariate logistic regression was used to determine the associated factors of osteoporosis and osteopenia. Results: The Prevalence of osteoporosis and osteopenia was 27% (95%CI:22–32) and 45% (95%CI:39–51), respectively. The multivariate regression analysis showed that age could play a role as an associated factor for spine/hip Osteoporosis and Osteopenia. The female gender is also a predictor of Spine osteopenia Patients with Total hip Osteoporosis were more likely to have higher DAS-28 (OR 1.86, CI 1.16–3.14) and positive CRP (OR 11.42, CI 2.65–63.26). Conclusion: recent-onset RA patients are at risk for osteoporosis and its complications, regardless of using glucocorticoids or DMARDs. Demographic factors (e.g. age and female gender), patients’ MDHAQ scores, and disease-related factors(e.g., DAS-28, positive CRP were associated with reduced BMD levels. Therefore, it is recommended that clinicians investigate early BMD measurements to have a reasonable judgment for further interventions. © 2023, The Author(s), under exclusive licence to Tehran University of Medical Sciences

Pattern of contributing behaviors and their determinants among people living with HIV in Iran: A 30-year nationwide study

Introduction: A major shift in the routes of HIV transmission seams to be taking place in Iran. Our study aimed to investigate the 30-year trend of major HIV related behaviors in Iran. Methods: The national HIV/AIDS registry database (from September 1986 to July 2016 with data on 32,168 people newly diagnosed with HIV) was used to study the 30 years trend and demographic determinants of major HIV related behaviors. Results: The highest rate of drug injection (DI) among people living with HIV (PLHIV) was reported during 1996 to 1999 (p-for trend &lt; 0.001) while the highest rate of sexual activity by minorities or hard to reach groups was during 2004 to 2011 (p-for trend &lt; 0.001). Among males, drug injection was directly associated with being single (ORsingle/married = 1.34), being unemployed (ORunemployed/employed = 1.94) and having lower level of education (OR&lt;highschool/≥highschool = 2.21). Regarding females, drug injection was associated with being housewife (ORhousewife/employed = 1.35) and lower level of education (OR&lt;highschool/≥highschool = 1.85). In females, condomless sexual contact was more common among those younger (OR20−29/&lt;20 = 6.15), and married (ORmarried/single = 7.76). However, among males those being single (ORmarried/single = 0.82), being more educated (OR≥highschool/&lt;highschool = 1.24), and being unemployed (ORunemployed/employed = 1.53) reported more sexual activity by minoritised or hard to reach groups. Discussion: The pattern of major HIV related behaviors among Iranian males and females have been rapidly changing and people living with HIV (PLHIV) are being diagnosed at a younger age. Health education to younger individuals is an essential HIV controlling strategy among Iranian population. Implementation of surveys in hidden and hard-to-reach populations is also recommended. Copyright © 2023 Gheibi, Fararouei, Afrashteh, Akbari, Afsar Kazerooni and Shokoohi

Food insecurity status and its contributing factors in slums’ dwellers of southwest Iran, 2021: a cross-sectional study

Background: One major factor causing food insecurity is believed to be poverty. Approximately 20 million Iranians live in slums with a vulnerable socioeconomic context. The outbreak of COVID-19, on top of the economic sanctions against Iran, has increased this vulnerability and made its inhabitants prone to food insecurity. The current study investigates food insecurity and its associated socioeconomic factors among slum residents of Shiraz, southwest Iran. Methods: Random cluster sampling was used to select the participants in this cross-sectional study. The heads of the households completed the validated Household Food Insecurity Access Scale questionnaire to assess food insecurity. Univariate analysis was utilized to calculate the unadjusted associations between the study variables. Moreover, a multiple logistic regression model was employed to determine the adjusted association of each independent variable with the food insecurity risk. Results: Among the 1227 households, the prevalence of food insecurity was 87.20%, with 53.87% experiencing moderate and 33.33% experiencing severe food insecurity. A significant relationship was observed between socioeconomic status and food insecurity, indicating that people with low socioeconomic status are more prone to food insecurity (P < 0.001). Conclusions: The current study revealed that food insecurity is highly prevalent in slum areas of southwest Iran. The socioeconomic status of households was the most important determinant of food insecurity among them. Noticeably, the coincidence of the COVID-19 pandemic with the economic crisis in Iran has amplified the poverty and food insecurity cycle. Hence, the government should consider equity-based interventions to reduce poverty and its related outcomes on food security. Furthermore, NGOs, charities, and governmental organizations should focus on local community-oriented programs to make basic food baskets available for the most vulnerable households

Determinants of multimorbidity in older adults in Iran: a cross-sectional study using latent class analysis on the Bushehr Elderly Health (BEH) program

Background and objectives Multimorbidity, defined as the presence of two or more long-term health conditions in an individual, is one of the most significant challenges facing health systems worldwide. This study aimed to identify determinants of classes of multimorbidity among older adults in Iran. Research Design and methods In a cross-sectional sample of older adults (aged ≥ 60 years) from the second stage of the Bushehr Elderly Health (BEH) program in southern Iran, latent class analysis (LCA) was used to identify patterns of multimorbidity. Multinomial logistic regression was conducted to investigate factors associated with each multimorbidity class, including age, gender, education, household income, physical activity, smoking status, and polypharmacy. Results In 2,426 study participants (mean age 69 years, 52% female), the overall prevalence of multimorbidity was 80.2%. Among those with multimorbidity, 3 latent classes were identified. These comprised: class 1, individuals with a low burden of multisystem disease (56.9%); class 2, individuals with predominantly cardiovascular-metabolic disorders (25.8%) and class 3, individuals with predominantly cognitive and metabolic disorders (17.1%). Compared with men, women were more likely to belong to class 2 (odds ratio [OR] 1.96, 95% confidence interval [CI] 1.52–2.54) and class 3 (OR 4.52, 95% CI 3.22–6.35). Polypharmacy was associated with membership class 2 (OR 3.52, 95% CI: 2.65–4.68) and class 3 (OR 1.84, 95% CI 1.28–2.63). Smoking was associated with membership in class 3 (OR 1.44, 95% CI 1.01–2.08). Individuals with higher education levels (59%) and higher levels of physical activity (39%) were less likely to belong to class 3 (OR 0.41; 95% CI: 0.28–0.62) and to class 2 (OR 0.61; 95% CI: 0.38–0.97), respectively. Those at older age were less likely to belong to class 2 (OR 0.95). Discussion and implications A large proportion of older adults in Iran have multimorbidity. Female sex, polypharmacy, sedentary lifestyle, and poor education levels were associated with cardiovascular-metabolic multimorbidity and cognitive and metabolic multimorbidity. A greater understanding of the determinants of multimorbidity may lead to strategies to prevent its development

Burden of disease scenarios for 204 countries and territories, 2022–2050: a forecasting analysis for the Global Burden of Disease Study 2021

Background: Future trends in disease burden and drivers of health are of great interest to policy makers and the public at large. This information can be used for policy and long-term health investment, planning, and prioritisation. We have expanded and improved upon previous forecasts produced as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) and provide a reference forecast (the most likely future), and alternative scenarios assessing disease burden trajectories if selected sets of risk factors were eliminated from current levels by 2050. Methods: Using forecasts of major drivers of health such as the Socio-demographic Index (SDI; a composite measure of lag-distributed income per capita, mean years of education, and total fertility under 25 years of age) and the full set of risk factor exposures captured by GBD, we provide cause-specific forecasts of mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) by age and sex from 2022 to 2050 for 204 countries and territories, 21 GBD regions, seven super-regions, and the world. All analyses were done at the cause-specific level so that only risk factors deemed causal by the GBD comparative risk assessment influenced future trajectories of mortality for each disease. Cause-specific mortality was modelled using mixed-effects models with SDI and time as the main covariates, and the combined impact of causal risk factors as an offset in the model. At the all-cause mortality level, we captured unexplained variation by modelling residuals with an autoregressive integrated moving average model with drift attenuation. These all-cause forecasts constrained the cause-specific forecasts at successively deeper levels of the GBD cause hierarchy using cascading mortality models, thus ensuring a robust estimate of cause-specific mortality. For non-fatal measures (eg, low back pain), incidence and prevalence were forecasted from mixed-effects models with SDI as the main covariate, and YLDs were computed from the resulting prevalence forecasts and average disability weights from GBD. Alternative future scenarios were constructed by replacing appropriate reference trajectories for risk factors with hypothetical trajectories of gradual elimination of risk factor exposure from current levels to 2050. The scenarios were constructed from various sets of risk factors: environmental risks (Safer Environment scenario), risks associated with communicable, maternal, neonatal, and nutritional diseases (CMNNs; Improved Childhood Nutrition and Vaccination scenario), risks associated with major non-communicable diseases (NCDs; Improved Behavioural and Metabolic Risks scenario), and the combined effects of these three scenarios. Using the Shared Socioeconomic Pathways climate scenarios SSP2-4.5 as reference and SSP1-1.9 as an optimistic alternative in the Safer Environment scenario, we accounted for climate change impact on health by using the most recent Intergovernmental Panel on Climate Change temperature forecasts and published trajectories of ambient air pollution for the same two scenarios. Life expectancy and healthy life expectancy were computed using standard methods. The forecasting framework includes computing the age-sex-specific future population for each location and separately for each scenario. 95% uncertainty intervals (UIs) for each individual future estimate were derived from the 2·5th and 97·5th percentiles of distributions generated from propagating 500 draws through the multistage computational pipeline. Findings: In the reference scenario forecast, global and super-regional life expectancy increased from 2022 to 2050, but improvement was at a slower pace than in the three decades preceding the COVID-19 pandemic (beginning in 2020). Gains in future life expectancy were forecasted to be greatest in super-regions with comparatively low life expectancies (such as sub-Saharan Africa) compared with super-regions with higher life expectancies (such as the high-income super-region), leading to a trend towards convergence in life expectancy across locations between now and 2050. At the super-region level, forecasted healthy life expectancy patterns were similar to those of life expectancies. Forecasts for the reference scenario found that health will improve in the coming decades, with all-cause age-standardised DALY rates decreasing in every GBD super-region. The total DALY burden measured in counts, however, will increase in every super-region, largely a function of population ageing and growth. We also forecasted that both DALY counts and age-standardised DALY rates will continue to shift from CMNNs to NCDs, with the most pronounced shifts occurring in sub-Saharan Africa (60·1% [95% UI 56·8–63·1] of DALYs were from CMNNs in 2022 compared with 35·8% [31·0–45·0] in 2050) and south Asia (31·7% [29·2–34·1] to 15·5% [13·7–17·5]). This shift is reflected in the leading global causes of DALYs, with the top four causes in 2050 being ischaemic heart disease, stroke, diabetes, and chronic obstructive pulmonary disease, compared with 2022, with ischaemic heart disease, neonatal disorders, stroke, and lower respiratory infections at the top. The global proportion of DALYs due to YLDs likewise increased from 33·8% (27·4–40·3) to 41·1% (33·9–48·1) from 2022 to 2050, demonstrating an important shift in overall disease burden towards morbidity and away from premature death. The largest shift of this kind was forecasted for sub-Saharan Africa, from 20·1% (15·6–25·3) of DALYs due to YLDs in 2022 to 35·6% (26·5–43·0) in 2050. In the assessment of alternative future scenarios, the combined effects of the scenarios (Safer Environment, Improved Childhood Nutrition and Vaccination, and Improved Behavioural and Metabolic Risks scenarios) demonstrated an important decrease in the global burden of DALYs in 2050 of 15·4% (13·5–17·5) compared with the reference scenario, with decreases across super-regions ranging from 10·4% (9·7–11·3) in the high-income super-region to 23·9% (20·7–27·3) in north Africa and the Middle East. The Safer Environment scenario had its largest decrease in sub-Saharan Africa (5·2% [3·5–6·8]), the Improved Behavioural and Metabolic Risks scenario in north Africa and the Middle East (23·2% [20·2–26·5]), and the Improved Nutrition and Vaccination scenario in sub-Saharan Africa (2·0% [–0·6 to 3·6]). Interpretation: Globally, life expectancy and age-standardised disease burden were forecasted to improve between 2022 and 2050, with the majority of the burden continuing to shift from CMNNs to NCDs. That said, continued progress on reducing the CMNN disease burden will be dependent on maintaining investment in and policy emphasis on CMNN disease prevention and treatment. Mostly due to growth and ageing of populations, the number of deaths and DALYs due to all causes combined will generally increase. By constructing alternative future scenarios wherein certain risk exposures are eliminated by 2050, we have shown that opportunities exist to substantially improve health outcomes in the future through concerted efforts to prevent exposure to well established risk factors and to expand access to key health interventions. Funding: Bill & Melinda Gates Foundation

Burden of disease scenarios for 204 countries and territories, 2022–2050: a forecasting analysis for the Global Burden of Disease Study 2021

Background: Future trends in disease burden and drivers of health are of great interest to policy makers and the public at large. This information can be used for policy and long-term health investment, planning, and prioritisation. We have expanded and improved upon previous forecasts produced as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) and provide a reference forecast (the most likely future), and alternative scenarios assessing disease burden trajectories if selected sets of risk factors were eliminated from current levels by 2050. Methods: Using forecasts of major drivers of health such as the Socio-demographic Index (SDI; a composite measure of lag-distributed income per capita, mean years of education, and total fertility under 25 years of age) and the full set of risk factor exposures captured by GBD, we provide cause-specific forecasts of mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) by age and sex from 2022 to 2050 for 204 countries and territories, 21 GBD regions, seven super-regions, and the world. All analyses were done at the cause-specific level so that only risk factors deemed causal by the GBD comparative risk assessment influenced future trajectories of mortality for each disease. Cause-specific mortality was modelled using mixed-effects models with SDI and time as the main covariates, and the combined impact of causal risk factors as an offset in the model. At the all-cause mortality level, we captured unexplained variation by modelling residuals with an autoregressive integrated moving average model with drift attenuation. These all-cause forecasts constrained the cause-specific forecasts at successively deeper levels of the GBD cause hierarchy using cascading mortality models, thus ensuring a robust estimate of cause-specific mortality. For non-fatal measures (eg, low back pain), incidence and prevalence were forecasted from mixed-effects models with SDI as the main covariate, and YLDs were computed from the resulting prevalence forecasts and average disability weights from GBD. Alternative future scenarios were constructed by replacing appropriate reference trajectories for risk factors with hypothetical trajectories of gradual elimination of risk factor exposure from current levels to 2050. The scenarios were constructed from various sets of risk factors: environmental risks (Safer Environment scenario), risks associated with communicable, maternal, neonatal, and nutritional diseases (CMNNs; Improved Childhood Nutrition and Vaccination scenario), risks associated with major non-communicable diseases (NCDs; Improved Behavioural and Metabolic Risks scenario), and the combined effects of these three scenarios. Using the Shared Socioeconomic Pathways climate scenarios SSP2-4.5 as reference and SSP1-1.9 as an optimistic alternative in the Safer Environment scenario, we accounted for climate change impact on health by using the most recent Intergovernmental Panel on Climate Change temperature forecasts and published trajectories of ambient air pollution for the same two scenarios. Life expectancy and healthy life expectancy were computed using standard methods. The forecasting framework includes computing the age-sex-specific future population for each location and separately for each scenario. 95% uncertainty intervals (UIs) for each individual future estimate were derived from the 2·5th and 97·5th percentiles of distributions generated from propagating 500 draws through the multistage computational pipeline. Findings: In the reference scenario forecast, global and super-regional life expectancy increased from 2022 to 2050, but improvement was at a slower pace than in the three decades preceding the COVID-19 pandemic (beginning in 2020). Gains in future life expectancy were forecasted to be greatest in super-regions with comparatively low life expectancies (such as sub-Saharan Africa) compared with super-regions with higher life expectancies (such as the high-income super-region), leading to a trend towards convergence in life expectancy across locations between now and 2050. At the super-region level, forecasted healthy life expectancy patterns were similar to those of life expectancies. Forecasts for the reference scenario found that health will improve in the coming decades, with all-cause age-standardised DALY rates decreasing in every GBD super-region. The total DALY burden measured in counts, however, will increase in every super-region, largely a function of population ageing and growth. We also forecasted that both DALY counts and age-standardised DALY rates will continue to shift from CMNNs to NCDs, with the most pronounced shifts occurring in sub-Saharan Africa (60·1% [95% UI 56·8–63·1] of DALYs were from CMNNs in 2022 compared with 35·8% [31·0–45·0] in 2050) and south Asia (31·7% [29·2–34·1] to 15·5% [13·7–17·5]). This shift is reflected in the leading global causes of DALYs, with the top four causes in 2050 being ischaemic heart disease, stroke, diabetes, and chronic obstructive pulmonary disease, compared with 2022, with ischaemic heart disease, neonatal disorders, stroke, and lower respiratory infections at the top. The global proportion of DALYs due to YLDs likewise increased from 33·8% (27·4–40·3) to 41·1% (33·9–48·1) from 2022 to 2050, demonstrating an important shift in overall disease burden towards morbidity and away from premature death. The largest shift of this kind was forecasted for sub-Saharan Africa, from 20·1% (15·6–25·3) of DALYs due to YLDs in 2022 to 35·6% (26·5–43·0) in 2050. In the assessment of alternative future scenarios, the combined effects of the scenarios (Safer Environment, Improved Childhood Nutrition and Vaccination, and Improved Behavioural and Metabolic Risks scenarios) demonstrated an important decrease in the global burden of DALYs in 2050 of 15·4% (13·5–17·5) compared with the reference scenario, with decreases across super-regions ranging from 10·4% (9·7–11·3) in the high-income super-region to 23·9% (20·7–27·3) in north Africa and the Middle East. The Safer Environment scenario had its largest decrease in sub-Saharan Africa (5·2% [3·5–6·8]), the Improved Behavioural and Metabolic Risks scenario in north Africa and the Middle East (23·2% [20·2–26·5]), and the Improved Nutrition and Vaccination scenario in sub-Saharan Africa (2·0% [–0·6 to 3·6]). Interpretation: Globally, life expectancy and age-standardised disease burden were forecasted to improve between 2022 and 2050, with the majority of the burden continuing to shift from CMNNs to NCDs. That said, continued progress on reducing the CMNN disease burden will be dependent on maintaining investment in and policy emphasis on CMNN disease prevention and treatment. Mostly due to growth and ageing of populations, the number of deaths and DALYs due to all causes combined will generally increase. By constructing alternative future scenarios wherein certain risk exposures are eliminated by 2050, we have shown that opportunities exist to substantially improve health outcomes in the future through concerted efforts to prevent exposure to well established risk factors and to expand access to key health interventions

Evaluation of survival analysis models for predicting factors infuencing the time of brucellosis diagnosis

Background: Brucellosis or Malta fever is one of the most common zoonotic diseases in the world. In addition to causing human suffering and dire economic impact on animals, due to the high prevalence of Brucellosis in the western regions of Isfahan province, this study aimed to analyze effective factors in the time of Brucellosis diagnosis using parametric and semi-parametric models and to evaluate the goodness of fit of these models. Methods:This historical cohort study, 412 patients with Brucellosis in Fereydunshahr, Iran who had referred to hospital, rural & urban health centers and physicians' private clinics in Fereydunshahr between 2006 and 2016 were recruited through census sampling. The failure (or event) in this study, was diagnosis of Brucellosis based on positive immunologic tests (2-ME test ≥1:40 and Wright serology ≥1:80). In order to eliminate confounding variables, effective factors of the time of Brucellosis diagnosis were determined using univariate (P≤0.20) and multivariable (P<0.05) analysis according to Cox semi-parametric model and five parametric models (weibull, exponential, log-logic, log-normal and gompertz) and the best fitted model was identified. Data were analyzed using R software version 3.2.3. Results: According to the results of this study, occupation (farmer and livestock breeder), place of residence (urban), having a history of direct contact with livestock, simultaneous infection in other family members, and the newness of the disease (vs. recurrence) were identified as predictors of early detection of the disease. Conclusion: Despite the researchers' tendency to use Cox method in survival analysis, in this study, according to AIC, “Gopmpertz” parametric model was recognized as the best fitted regression model in the analysis of the effective factors in the definitive time of Brucellosis diagnosi

Determinants of delay in diagnosis and end stage at presentation among breast cancer patients in Iran: a multi-center study

One of the reasons for high mortality of breast cancer (BC) is long delay in seeking medical care and end stage at presentation. This study was designed to measure the association between a wide range of socio-demographic and clinical factors with diagnostic delay in BC and stage at presentation among Iranian patients. From June 2017 to December 2019, 725 patients with newly diagnosed BC in Shiraz and Kermanshah were selected and information on BC diagnosis delay was obtained from the patient's medical record. Data on socio-economic status was obtained via a structured interview. Our findings suggest that 45.8 of the patients were diagnosed at a late stage (stage 3 or higher). A total of 244 (34) patients had more than 3 months delay in diagnosis. We found a significant association between stage at diagnosis and place of residence (adjusted odds ratio (aOR rural vs. urban = 1.69, 95 CI 1.49-1.97), marital status (aOR 1.61, 95 CI 1.42-1.88), family history of BC (aOR 1.46, 95 CI 1.01-2.13), and history of benign breast disease (BBD) (aOR 1.94, 95 CI 1.39-2.72) or unaware of breast self-examination (BSE) (aOR 1.42, 95 CI 1.42-1.85), delay time (aOR 3.25, 95 CI 1.04-5.21), and left breast tumor (aOR right vs. left 2.64, 95 CI 1.88-3.71) and smoking (aOR no vs. yes 1.59, 95 CI 1.36-1.97). Also, delay in diagnosis was associated with age, family income, health insurance, place of residence, marital status, menopausal status, history of BBD, awareness of breast self-examination, type of first symptoms, tumor histology type, BMI and comorbidity (p < 0.05 for all). Factors including history of BBD, awareness of BSE, and suffering from chronic diseases were factors associated with both delay in diagnosis and end stage of disease. These mainly modifiable factors are associated with the progression of the disease