Risk prediction models for lung cancer in people who have never smoked: a protocol of a systematic review.

BACKGROUND: Lung cancer is one of the most commonly diagnosed cancers and the leading cause of cancer-related death worldwide. Although smoking is the primary cause of the cancer, lung cancer is also commonly diagnosed in people who have never smoked. Currently, the proportion of people who have never smoked diagnosed with lung cancer is increasing. Despite this alarming trend, this population is ineligible for lung screening. With the increasing proportion of people who have never smoked among lung cancer cases, there is a pressing need to develop prediction models to identify high-risk people who have never smoked and include them in lung cancer screening programs. Thus, our systematic review is intended to provide a comprehensive summary of the evidence on existing risk prediction models for lung cancer in people who have never smoked. METHODS: Electronic searches will be conducted in MEDLINE (Ovid), Embase (Ovid), Web of Science Core Collection (Clarivate Analytics), Scopus, and Europe PMC and Open-Access Theses and Dissertations databases. Two reviewers will independently perform title and abstract screening, full-text review, and data extraction using the Covidence review platform. Data extraction will be performed based on the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modeling Studies (CHARMS). The risk of bias will be evaluated independently by two reviewers using the Prediction model Risk-of-Bias Assessment Tool (PROBAST) tool. If a sufficient number of studies are identified to have externally validated the same prediction model, we will combine model performance measures to evaluate the model's average predictive accuracy (e.g., calibration, discrimination) across diverse settings and populations and explore sources of heterogeneity. DISCUSSION: The results of the review will identify risk prediction models for lung cancer in people who have never smoked. These will be useful for researchers planning to develop novel prediction models, and for clinical practitioners and policy makers seeking guidance for clinical decision-making and the formulation of future lung cancer screening strategies for people who have never smoked. SYSTEMATIC REVIEW REGISTRATION: This protocol has been registered in PROSPERO under the registration number CRD42023483824.

Arsenic in drinking water and lung cancer: A systematic review of 35 years of evidence.

The association between higher arsenic concentrations in drinking water and lung cancer is well-established. However, the risk associated with lower levels of arsenic exposure remains uncertain. This systematic review and meta-analysis summarizes the evidence on the relationship between exposure to arsenic in drinking water and lung cancer outcomes as measured over a broad range of exposures, including lower levels. A total of 51 studies were included in the review and 15 met criteria for inclusion in meta-analysis. Risk estimates for lung cancer incidence and mortality were pooled and analyzed separately using Bayesian hierarchical random-effects models with a Gaussian observation submodel for log(Risk), computed using the "brms" R package. For lung cancer incidence, the predicted posterior mean relative risks (RRs) at arsenic concentrations of 10, 50 and 150 µg/L were 1.11 (0.86-1.43), 1.67 (1.27-2.17) and 2.21 (1.61-3.02), respectively, with posterior probabilities of 79%, 100% and 100%, respectively, for the RRs to be >1. The posterior mean mortality ratios at 20, 50 and 150 µg/L were 1.22 (0.83-1.78), 2.10 (1.62-2.71) and 2.41 (1.88-3.08), respectively, with posterior probabilities being above 80%. In addition to observing the dose-response relationship, these findings demonstrate that individuals exposed to low to moderate levels of arsenic (<150 µg/L) were at an elevated risk of developing or dying from lung cancer. Given the widespread exposure to lower levels of arsenic, there is an urgent need for vigilance and potential revisions to regulatory guidelines to protect people from the cancer risks associated with arsenic exposure.

Prevalence of high-risk human papillomavirus infection and genotype distribution among Kazakhstani women with abnormal cervical cytology.

AIM: This study aimed to identify the prevalence and distribution of high-risk human papillomavirus (HR-HPV) types among Kazakhstani women with abnormal cervical cytology. METHODS: A cross-sectional study was performed from May 2019 to June 2020. Cervical samples were collected from women in the different regions of Kazakhstan. RESULTS: A total of 316 patients' samples were analysed for HR-HPV using real-time multiplex PCR. Cervical cytology abnormalities were reported according to the Bethesda classification. HPV detection by cytology showed a statistically significant association with HPV status and the number of HPV infection types (p < .05). Among women with abnormal cervical cytology, 62.4% were positive for HPV infection of those 79.4% had low-grade squamous intraepithelial lesions (LSIL), and 20.6% had high-grade squamous intraepithelial lesions (HSIL). Among patients with LSIL, 77.4% had HPV16 and 58.8% were infected with HPV18. Among patients with HSIL, 41.2% had HPV18 and 22.6% - HPV16. CONCLUSIONS: There is a high prevalence of HR-HPV types among Kazakhstani women with abnormal cervical cytology. The most identified types were HPV16, 18, 31, 33 and 52. There is an emergency need to implement an HPV vaccination program to prevent cervical lesion development.

Knowledge and attitudes of mothers toward HPV vaccination: A cross-sectional study in Kazakhstan.

BACKGROUND: Although recommended for all member states of World Health Organization, there is no national human papillomavirus vaccination program in Kazakhstan. Furthermore, there are no studies in Kazakhstan that evaluate the mothers' perception of human papillomavirus vaccines. OBJECTIVES: This study aims to assess the knowledge and attitudes toward human papillomavirus vaccination among mothers in Kazakhstan and the factors associated with their attitudes. DESIGN: A cross-sectional study was performed during the period of December 2021-February 2022. The STROBE guideline for cross-sectional studies was applied. METHODS: Paper-based structured questionnaires were filled out by 191 mothers, 141 of whom had daughters. The attitude score was assessed as per the Likert-type scale. The Chi-square and Fisher's exact tests, with a significance value of < 0.05 were used to analyze the relationships between the characteristics of mothers and their attitude scores. RESULTS: The following factors were significantly associated with mothers' attitudes toward human papillomavirus vaccination: a place of residence, family income, number of children, and refusal of vaccination for themselves (p < 0.005). Of all participants, only 45% of all mothers, 41% of mothers with a female, and 46% of mothers with male children had positive attitudes toward human papillomavirus vaccination. The child's gender was not a significant determinant. Overall, the level of knowledge about human papillomavirus vaccination was found to be low. The median total score is 0 out of 12 for women who have negative and neutral attitudes toward human papillomavirus vaccines. Among women who have positive attitudes toward HPV vaccines, the median score is around 3 points. CONCLUSION: Before the implementation of the human papillomavirus vaccination program into the Kazakhstani national vaccination calendar, comprehensive and adequate information and education campaigns are required on the national level for parents and the population in general.

Does Vaccination Protect against Human Papillomavirus-Related Cancers? Preliminary Findings from the United States National Health and Nutrition Examination Survey (2011-2018).

Most oropharyngeal and anogenital cancers are caused by human papillomavirus (HPV). Although HPV vaccines showed high efficacy against oropharyngeal and anogenital HPV infections, and cancer precursors in randomized clinical trials, there are limited data on the effectiveness of HPV vaccination against HPV-related cancers. We aimed to evaluate the association of HPV vaccination with HPV-related cancers among a nationally representative sample of United States adults, aged 20-59 years. In a cross-sectional study combining four cycles from the National Health and Nutrition Examination Survey, from 2011 through 2018, we used a survey-weighted logistic regression model, propensity score matching and multiple imputations by chained equations to explore the association of HPV vaccination with HPV-related cancers. Among 9891 participants, we did not find an association of HPV vaccination with HPV-related cancers (adjusted OR = 0.58, 95% CI 0.19; 1.75). Despite no statistically significant association between HPV vaccination and HPV-related cancers, our study findings suggest that HPV-vaccinated adults might have lower odds of developing HPV-related cancers than those who were not vaccinated. Given the importance of determining the impact of vaccination on HPV-related cancers, there is a need to conduct future research by linking cancer registry data with vaccination records, to obtain more robust results.

Epidemiology of type 1 and type 2 diabetes mellitus in Kazakhstan: data from unified National Electronic Health System 2014-2019.

BACKGROUND: We aimed to explore descriptive epidemiology of T1 and T2 Diabetes Mellitus (DM) and to investigate demographic factors and comorbidities associated with all-cause mortality by aggregating and utilizing large-scale administrative healthcare data from the Unified National Electronic Health System (UNEHS) of Kazakhstan for 2014-2019 years period. METHODS: A total of 475,539 individuals were included in the analyses. The median years of follow-up for Type 1 DM patients accounted for 4.7 years and 4.5 years in Type 2 DM patients. We used Kaplan-Meier and log-rank test to calculate failure function and differences in survival by age, sex, ethnicity, and comorbidities with all-cause mortality for Type 1 and Type 2 DM. Cox proportional hazards regression analysis was used to obtain crude and adjusted hazard ratios. RESULTS: Prevalence of Type 1 and Type 2 DM increased 1.7 times from 2014 to 2019. Mortality of Type 1 and Type 2 DM also increased 4 times and 6 times from 2014 to 2019, respectively. Male sex, older age and Kazakh ethnicity were associated with a higher risk of all-cause death compared to females, younger age and other nationalities than Kazakh in patients with Type 1 and Type 2 DM. Coronary artery disease, diabetic nephropathy, stroke, amputations and neoplasms were associated with a higher risk of all-cause death. CONCLUSION: The prevalence and mortality rate of Type 1 and Type 2 DM increased during the years 2014-2019 in Kazakhstan. Male sex, older age and Kazakh ethnicity were associated with a higher risk of all-cause death compared to females, younger age and other nationalities than Kazakh. Coronary artery disease, diabetic nephropathy, stroke, amputations and neoplasms were associated with a higher risk of all-cause death.

What Factors Are Associated with Attitudes towards HPV Vaccination among Kazakhstani Women? Exploratory Analysis of Cross-Sectional Survey Data.

Background. The high prevalence of HPV infection among Kazakhstani women and the absence of an HPV vaccination program are directly reflected in increasing rates of cervical cancer incidence and mortality. Kazakhstan made its first attempt at introducing the HPV vaccine in 2013, but was unsuccessful due to complications and low public acceptance. The attitudes of Kazakhstani women towards the vaccine were never measured. Therefore, this study aims to investigate the attitudes of women towards the HPV vaccine and determine factors associated with positive, negative, or neutral attitudes. Methods. A 29-item survey consisting of 21 demographic and contextual questions and 8 Likert-scale questions was distributed among women attending gynecological offices in four major cities of Kazakhstan from December 2021 until February 2022. Attitudes of women were measured based on their answers to the eight Likert-scale questions. Ordinal logistic regression was built to find associations between demographic characteristics and attitudes of women. Results. Two hundred thirty-three women were included in the final analysis. A total of 54% of women had positive attitudes towards the vaccine. The majority of women did not trust or had a neutral attitude towards the government, pharmaceutical industry, and traditional and alternative media. However, the trust of women was high in medical workers and scientific researchers. Women's age, education, number of children, effect of the 2013 HPV program, and trust in alternative medicine were included in the ordinal logistic model. Women with a low level of education, a high number of children, who believe in alternative medicine, and who were affected by the failed 2013 vaccination program were less likely to have a positive attitude towards the vaccine. Conclusions. Contrary attitudes towards HPV vaccination exist among Kazakhstani women, with approximately half having positive and almost half having negative or neutral attitudes towards the vaccine. An informational campaign that takes into consideration women's levels of trust in different agencies, as well as targets those who are the most uninformed, might help in a successful relaunch of the HPV vaccination program. However, more studies that cover a higher number of women are required.

The Prevalence, Incidence, Indications and Outcomes of Peripartum Hysterectomy in Kazakhstan: Data from Unified Nationwide Electronic Healthcare System 2014-2018.

PURPOSE: Peripartum hysterectomy is a surgical procedure performed as a life-saving surgery to manage severe postpartum hemorrhage. The prevalence of peripartum hysterectomy in high-resource settings is relatively low. However, maternal mortality due to postpartum hemorrhage and after peripartum hysterectomy remains high in developing countries. To date, there is a lack of information about the rates of peripartum hysterectomy and its common indications in Kazakhstan. Objectives were to study the prevalence, indications, and outcomes of peripartum hysterectomy using nationwide large-scale health-care data from the national registry. PATIENTS AND METHODS: We performed a descriptive, population-based study among women who underwent a peripartum hysterectomy in any health-care setting of the Republic of Kazakhstan during the period of 2014-2018. Data were collected from the Unified Nationwide Electronic Health System (UNEHS). RESULTS: Data included 3838 medical records of women who had a peripartum hysterectomy performed due to specific indications for the period of 5 years (2014-2018). The median age of the participants was 33 years old, with 60.7% of women aged between 18 and 34 years. The leading indications for peripartum hysterectomy were intrapartum hemorrhage (IPH) and postpartum hemorrhage (PPH) reported in 60% of the cases analyzed. The second most common indication was placental pathology - placental abruption and placenta previa in 9.6% and 7.9% of cases, respectively. In 1633 cases (42.4%), total abdominal hysterectomy was performed, while subtotal hysterectomy was done in 2195 cases (57.0%). Based on these data, the estimated prevalence of peripartum hysterectomies was calculated: overall weighted mean prevalence 1.93 per 1000 deliveries. CONCLUSION: IPH and PPH are the commonest indications for peripartum hysterectomy followed by placental pathology. Appropriate maternal care during labor and delivery should be reinforced to decrease the incidence of peripartum hysterectomy in Kazakhstan.

Knowledge and awareness of human papillomavirus infection and human papillomavirus vaccine among Kazakhstani women attending gynecological clinics.

Cervical cancer remains one of the top causes of cancer-related morbidity and mortality all over the world. Currently, however, there are no published studies to assess the knowledge of HPV and cervical cancer in Kazakhstan. This study aimed to assess the awareness of HPV, the knowledge of HPV as a cause of cervical cancer, and the awareness of HPV vaccination among Kazakhstani women visiting gynecological clinics across the country. In addition, the study aimed to identify the factors associated with the awareness of HPV and the HPV vaccine and knowledge of HPV as a major cause of cervical cancer. This was a cross-sectional survey-based study with 2,272 women aged between 18-70 years attending gynecological clinics, who were administered paper-based questionnaires. Data analysis included descriptive statistics consisting of mean values, standard deviations, and frequencies, where applicable. Differences in categorical variables between groups were analyzed using the Chi-square test with a significance value of <0.005. Crude odds ratio (OR) and adjusted odds ratio (AOR) with 95% corresponding confidence intervals were calculated in regression analysis using univariate and multivariable logistic regression models. The mean age of participants was 36.33±10.09 years. More than half (53%) of the participants had been screened for cervical cancer. Among those who were aware of HPV, 46% knew that HPV causes cervical cancer and 52% were aware of the HPV vaccine. The key factors related to outcome variables were age, ethnicity, education, family, number of deliveries, and menarche. From a subgroup analysis, results from the HPV test and Pap smear test were factors related to dependent variables such as awareness of HPV and awareness of HPV vaccination.

Seroprevalence and risk factors for hepatitis B and hepatitis C in three large regions of Kazakhstan.

BACKGROUND & AIMS: Kazakhstan has implemented comprehensive programs to reduce the incidence of Hepatitis B and Hepatitis C. This study aims to assess seroprevalence and risk factors for HBsAg and anti-HCV positivity in three large regions of Kazakhstan. METHODS: A cross-sectional study was conducted in three regions geographically remote from each other. Participants were randomly selected using a two-stage stratified cluster sampling and were surveyed by a questionnaire based on the WHO STEP survey instrument. Blood samples were collected for HBsAg and anti-HCV testing. RESULTS: A total of 4,620 participants were enrolled. The seroprevalence was 5.5% (95%CI: 3.6%-8.4%) for HBsAg and 5.1% (95%CI: 3.5%-7.5%) for anti-HCV antibodies. Both were more prevalent in the western and northern regions than in the southern. A history of blood transfusion was significantly associated with anti-HCV presence, with odds ratios (ORs) of 2.10 (95%CI: 1.37-3.21) and was borderline associated with HBsAg 1.39 (95%CI: 0.92-2.10), respectively. Having a family member with viral hepatitis was also borderline associated (2.09 (95%CI: 0.97-4.50)) with anti-HCV positivity. CONCLUSIONS: This study found a high-intermediate level of endemicity for HBsAg and a high level of endemicity for anti-HCV antibodies in three large regions of Kazakhstan. We found that history of surgery was not associated with HbsAg neither with anti-HCV seropositivity rates. Blood transfusion was associated with anti-HCV seropositivity, however, to investigate effectiveness of the introduced comprehensive preventive measures in health care settings, there is a need to conduct further epidemiological studies.

The Distribution and Prevalence of High-Risk HPV Genotypes Other than HPV-16 and HPV-18 among Women Attending Gynecologists' Offices in Kazakhstan.

Cervical cancer represents a great burden to public health of women. This study aimed to obtain a nationwide genotyping survey and analysis of high risk-HPV including those that are caused by HPV types other than HPV-16 and HPV-18, among women in Kazakhstan. This study was conducted based on the collection of survey and cervical swabs of 1645 women across the country. The samples were genotyped for high-risk HPV types based on real-time PCR methods. Collected data was analyzed with the focus on high-risk HPV types other than HPV-16 and -18. Infection was present in 22% of women who participated in the study. The most prevalent types were HPV-31 among single infections and HPV-68 among multiple infections. Conclusively, despite the lack of attention high-risk HPV types beyond HPV-16 and -18 get in attempts of cervical cancer prevention in Kazakhstan, their prevalence is high and plays a large role in cervical cancer epidemiological situation.

Prevalence of high-risk human papillomavirus infection among Kazakhstani women attending gynecological outpatient clinics.

OBJECTIVES: To conduct a nationwide high-risk human papillomavirus (HR-HPV) infection genotyping analysis of women attending gynecological clinics and identify factors associated with HR-HPV infection. METHODS: A cross-sectional survey-based study with 759 participants. Demographics, lifestyle, and medical history data were collected by questionnaire completed by gynecologists during patients' visits. Cervical swabs were used for HPV genotyping using AmpliSens kit. Data analysis included descriptive statistics consisting of mean values, standard deviations, and frequencies, where applicable. Ordinal logistic regression was performed to identify factors associated with HPV infection status. RESULTS: The mean age of participants was 36.51 ± 10.09 years. The majority of participants were aged 26-35 years. Less than half of the women (39%) were HPV positive; 26% had single HR-HPV, and 13% had multiple HR-HPV infection. The most prevalent HR-HPV genotypes were HPV-16 (54%), HPV-51 (7%), HPV-68 (7%), and HPV-18 (6%). Ordinal logistic regression demonstrated that older age, not being single, and having a history of sexually transmitted infections, decrease the odds of HPV infection. CONCLUSION: This study identified high prevalence of HR-HPV among Kazakhstani women. Our results showed that adding HPV testing to compulsory cervical cancer screening in Kazakhstan could improve the screening program and decrease cervical cancer rates.

Factors associated with cervical cancer screening behaviour of women attending gynaecological clinics in Kazakhstan: A cross-sectional study.

OBJECTIVE: Although cervical cancer could be prevented through medical screening, it remains one of the top causes of cancer-related morbidity and mortality all over the world. A number of factors may contribute to cervical cancer screening behaviour of women. The aim of this study was to investigate factors related to cervical cancer screening behaviour of women in Kazakhstan. METHODS: This was a cross-sectional survey-based study with a total of 1189 participants. Women attending gynaecological clinics aged between 18 and 70 years were administered paper-based questionnaires about their awareness of cervical cancer, the associated risk factors, and cervical cancer screening. Student t test or Wilcoxon rank-sum test and chi-square test or Fisher's exact test, where appropriate, were used to determine associations with categorical independent variables. RESULTS: The mean age of participants was 36.5 ± 10.1 years. Less than half (45.7%) of the participants had been screened for cervical cancer. The key factors related to the cervical cancer screening behaviour of women in this study included age, having a larger number of children, regular menstrual function, awareness of Pap smear test, and free screening programme for cervical cancer, and the causal association of human papillomavirus with cervical cancer. CONCLUSION: This study revealed several significant factors predicting screening behaviour in Kazakhstani women. To improve the rate of screening, there is a need to increase public knowledge and awareness of cervical cancer and opportunities for the free screening programme in the female population of Kazakhstan.

Association of rs12722 COL5A1 with pulmonary tuberculosis: a preliminary case-control study in a Kazakhstani population.

Lung cavitation is the classic hallmark of TB, which facilitates the disease development and transmission. It involves the degradation of lung parenchyma which is mainly made up of collagen fibers by metalloproteinases (MMPs) produced by activated monocyte-derived cells, neutrophils and stromal cells. The following population-based preliminary case-control study of adults with TB (50) and controls (112) without TB was used to investigate possible association between rs1800012 in COL1A1, rs12722 in COL5A1 genes and pulmonary TB in Kazakhstan. We examined 162 samples (50 cases and 112 controls) to study the associations between TB disease status and demographic variables along with single nucleotide polymorphisms related to COLA1 and COL5A1. The unadjusted χ2 and multivariable logistic regression was performed to find out relationships between SNP and other predictors. Preliminary findings suggest that there is a statistically significant association of age (AOR = 0.97, 95% CI:0.94-0.99, p value = 0.049), social status (AOR = 2.41, 95% CI:1.16-5.02, p value = 0.018), HIV status (AOR = 7.12, 95% CI:1.90-26.7, p value = 0.004) and heterozygous rs12722 SNP (AOR = 2.47, 95% CI:1.17-5.19, p value = 0.018) polymorphism of COL5A1 gene with TB susceptibility. The association of collagen genes with TB pathogenesis indicates that anti TB programs can include development of new drug regimens that include MMP inhibitors which has been found to be helpful in collagen remodeling and repair. Therapeutic targeting of MMPs will prevent extracellular matrix and collagen degradation and granuloma maturation.

Dose equivalency and efficacy of biosimilar erythropoietin stimulating agents: Data from real clinical practice.

Recently, biosimilar erythropoietin stimulating agents become available in Kazakhstan. Important properties of the biosimilar such as dose equivalency to the original medicine (originator) and the ability to maintain hemoglobin target levels remain insufficiently described in many clinical settings. Thus, the current study aims to determine dose equivalency and hemoglobin target levels in a cohort of dialysis patients who were switched from the originator to biosimilar. Retrospective data of 74 patients from different dialysis centers who received at least 6 months of originator and switched to biosimilar and had at least 6 months follow-up were analyzed. The clinical data of 32 male and 42 female patients were collected. The mean age was 52.5 ± 13.5 years. There is no significant difference in mean levels of hemoglobin during pre-switching from originator to biosimilar (6 months prior) and post switching period (9 months after). Additionally, a subgroup analysis of 59 patients who received originator (epoetin beta), 6 months before the switch, showed similar level of hemoglobin (110.7 ± 14 vs 113.2 ± 10 g/L, P = .05) 6 months after the switch to biosimilar (epoetin zeta) at the equivalent dose regimen (69.5 ± 29 vs 68.1 ± 30 IU/kg/wk, P = .55). However, after 9 months of switching, patients using lower doses of biosimilar (69.5 ± 29 vs 63.3 ± 30 IU/kg/wk, P < .01), showed significantly higher levels of hemoglobin (110.7 ± 14 vs 114.7 ± 8 g/L, P = .01) compared to preswitching period. In conclusion, long-term use of lower doses of biosimilar managed to maintain hemoglobin within the target levels.