Disease-related Risk Research Articles

Consequences of parental preconceptional irradiation: Endocrine-metabolic pathology in offspring

Epidemiological studies of late effects of preconceptional (prior to conception) radiation exposure are necessary in order to understand the risks of tumor and non-tumor pathology in next generations. Research of possible relation between parental preconceptional exposure and development of endocrine and metabolic disorders in the offspring is one of the topical issues of radiation hygiene. The objective of the study: comparative analysis of endocrine and metabolic pathology in children of the individuals exposed to long term preconceptional external gamma-radiation at the Mayak Production Association – at the first atomic industry facility on Russia. Materials and methods: A retrospective research was performed based on the Ozyorsk Children’s Health Registry. Ozyorsk – the city where Mayak Production Association is the enterprise forming the city. Analysis of endocrine and metabolic disorders was performed for 13880 children of 1949-1973 years of birth who were born and resided in Ozyorsk; parents of 9321 children of this number had accumulated doses of prolonged external gamma-radiation exposure at the production facility prior to conception. A comparative analysis of the structure and incidence of “Endocrine, nutritional and metabolic diseases” and nosological forms of this class of pathology was performed. Characteristic features of parental preconceptional exposure were analyzed in relation to thyroid pathology in children. Relative risk of endocrine and metabolic disorders among the children of exposed and unexposed parents was calculated for the whole disease class and for certain nosologies. Results: A significant predominance of thyroid diseases, particularly, iodine deficiencies, was detected at an earlier age among the offspring of Mayak Production Association workers compared to the control group; these cases were mostly related to low dose parental preconceptional exposure. Thyroid cancer was further detected in 0.16% (15/9321) of the studied cohort of the offspring of exposed parents with average manifestation age of 42.6. Relative risk of thyroid diseases was significantly higher among the exposed parents’ offspring compared to the controls: 2.0 among boys (95% confidence interval 1.38-2.9), 1.59 among girls (1.25-2.02) and in the group as a whole – 1.64 (1.34- 2.01). Relative risk of thyroid diseases related to iodine deficiency among the offspring of Mayak Production Association personnel was almost twice higher than the in the control group: 1.92 (1.3-2.84) among boys, 1.68 (1.29-2.2) among girls, 1.7 (1.36-2.12) in the whole group. Discussion and conclusion: A statistically significant overweight of non-tumor thyroid pathology in the offspring of Mayak Production Association personnel cannot be explained through external reasons taking into account similar climate and geographic conditions, possible technogenic exposure and the same unified medical survey of the followed children. We cannot exclude increased sensibility if thyroid tissue to iodine deficiency and its predisposition to hypertrophy and hyperplasia among the offspring of individuals exposed to long term occupational contact with ionizing radiation sources; that should be taken into account in the course of medical monitoring of these patients. Further research of transgenerational effects in the offspring of personnel of radiation hazardous production facilities are needed for complete understanding of the role of parental occupational exposure in health risks for further generations.

Associations between mortality and exposure to psychotropic medication: A population-based cohort study for depressive disorders.

Use of antidepressants and antipsychotics to treat depressive disorders is becoming increasingly prevalent. This study investigated how the use and cumulative dosage of these medications affect the mortality risk in a Taiwan's national cohort of individuals ages 15 years and older who were diagnosed with depressive disorders in 2010 and followed up for 5 years. An age- and gender-matched control group was identified. The mean defined daily doses of antidepressants and antipsychotics were calculated, and survival analyses were conducted to examine the effects of exposure dosage on overall mortality and mortality due to cardiovascular diseases, in comparison with the control sample. A total of 400,042 individuals (255,288 women; 63.8%) with depressive disorders were identified. A low-to-moderate dosage of antidepressants was associated with a decrease in cardiovascular disease-related mortality risks compared to no exposure for those with depressive disorders. By contrast, a dose-related increase was found when using antipsychotics, with a 1.6-, 2.4- and 2.9-fold risk in the low, moderate and high exposure groups, respectively, for overall mortality, and a 1.2-, 2.4- and 3.5-fold risk in the low, moderate and high exposure groups, respectively, for cardiovascular disease-related mortality, relative to the control sample. For individuals with depression, use of low-to-moderate dosage antidepressants was associated with decreased mortality. However, use of antipsychotics was found to be associated with a dose-related increase in overall and cardiovascular disease-related mortality risks. Adverse health outcomes should be also considered when prescribing psychotropic medications to patients with depressive disorders.

Incidental Findings and Low-Value Care.

Incidental imaging findings are common and analogous to the results of screening tests when screening is performed of unselected, low-risk patients. Approximately 15-30% of all diagnostic imaging and 20-40% of CT examinations contain at least one incidental finding. Patients with incidental findings but low risk for disease are likely to experience length bias, lead-time bias, overdiagnosis, and overtreatment that create an illusion of benefit while conferring harm. This includes incidental detection of many types of cancers that, although malignant, would have been unlikely to affect a patient's health had the cancer not been detected. Detection of some incidental findings can improve health, but most do not. Greater patient- and disease-related risk increase the likelihood an incidental finding is important. Clinical guidelines for incidental findings should more deeply integrate patient risk factors and disease aggressiveness to inform management. Lack of outcome and cost-effectiveness data have led to reflexive management strategies for incidental findings that promote low-value and sometimes harmful care.

Gutted: constipation in children with chronic kidney disease and on dialysis

Functional constipation is a common problem in otherwise healthy children. Children with chronic kidney disease (CKD) and on dialysis have additional disease-related risk factors including the uremic milieu, fluid and dietary restrictions, and decreased physical activity, as well as treatment-related risk factors such as dialysis therapy and polypharmacy that contribute to and compound the problem. Constipation causes significant distress for children and their caregivers. In children on peritoneal dialysis, severe constipation can impede catheter function and ultrafiltration. Accumulating evidence points to a possible bidirectional relationship between constipation and CKD, potentially mediated by gut dysbiosis with consequent increased generation of gut-derived uremic toxins and disruption of intestinal epithelium integrity leading to translocation of noxious luminal contents into the circulation inducing systemic inflammation. Effective management of constipation is required but there is little published data on the safety and effectiveness of treatments in adults or children with CKD. In this review, we discuss the diagnosis and epidemiology of functional constipation, provide an overview of its pathophysiology, summarize the therapeutic management, and reflect on the challenges in children with CKD.

Ecological Study on Global Health Effects due to Source-Specific Ambient Fine Particulate Matter Exposure.

Ambient air pollution of fine particulate matter with diameters less than 2.5 μm (PM2.5) is associated with millions of premature deaths per year, recognized as a leading global health concern. The dose-response relation between ambient PM2.5 exposure and mortality risk is the most fundamental information for assessments of the health effects of PM2.5. The existing dose-response relations were generally developed based on the assumption of equal contribution to toxicity from various sources. However, the sources of PM2.5 may significantly influence health effects. In this study, we conducted an ecological study to investigate the global long-term correlation between source-specific PM2.5 exposure and cause-specific mortality risk (SPECM) based on the regional aggregate data of the publically available official health databases from 528 regions worldwide with a total registered population of 3.2 billion. The results provided preliminary epidemiological evidence for differing chronic health effects across various sources. The relative mortality risks of lung cancer and circulatory diseases were closely correlated with the primary emissions from industrial and residential combustion sources. Chronic lower respiratory diseases were mostly associated with the mass concentration of particulate matter.

Post-migration food habits of New Zealand South Asian migrants: Implications for health promotion practice

IntroductionSouth Asian migrants in western countries have a high risk for diet related diseases post-migration. Hence knowledge on food habits that change post-migration, which are detrimental to health, are critical for health promotion initiatives to reduce this disease burden. Objectiveto describe food consumption changes post-migration according to sex and duration of residence in New Zealand among South Asian migrants. MethodsA cross-sectional mail survey of 150 self-selected people of South Asian ethnicity aged 25–59 years in New Zealand. ResultsThe study achieved responses from 112 participants (75%) with a mean age of 36 (7.5) years. Consumption of green leafy vegetables reduced post-migration for females and in new migrants (P < 0.05). Fruit consumption increased in both genders and across duration of residence (P < 0.05). Only 15% of males and 36% of females met the 3 + a day recommendation for vegetable consumption. Consumption of traditional breads, breakfast items and rice (males) decreased whilst that of breakfast cereals increased (P < 0.05). Consumption of low-fat milk, cheese, ice-cream, butter (females) and margarine increased, whilst ghee decreased (P < 0.05). Consumption of fish, lentils, traditional sweets and savouries decreased, whilst meat, processed meat, chicken, potato chips, cakes and pastries (females) and alcohol (males) increased (P < 0.05), post-migration. Thirty-three percent of males and 24% of females consumed takeaways “weekly or more often”, with the majority (male: 51%; female: 36%) consuming European foods such as pizzas and pastas. Thirteen percent of males and 26% of females consumed festival foods “weekly or more often.” More than half the participants were obese with BMI increasing with duration of residence (P = 0.025). ConclusionsA food-based health promotion initiative focused on inadequate consumption of fruits and vegetables, increased consumption of dairy foods such as cheese and ice cream, and high fat European takeaway foods would be warranted particularly in new South Asian migrants.

Sex and gender-specific aspects in prediabetes and diabetes mellitus-clinical recommendations (Update 2023)

Metabolic diseases dramatically affect the life of men and women from infancy up to old age in different and manifold ways and are amajor challenge for the healthcare system. The treating physicians are confronted with the different needs of women and men in the clinical routine. Gender-specific differences affect pathophysiology, screening, diagnostic and treatment strategies of diseases as well as the development of complications and mortality rates. Impairments in glucose and lipid metabolism, regulation of energy balance and body fat distribution and therefore the associated cardiovascular diseases, are greatly influenced by steroidal and sex hormones. Furthermore, education, income and psychosocial factors play an important role in the development of obesity and diabetes differently in men and women. Males appear to be at greater risk of diabetes at ayounger age and at alower body mass index (BMI) compared to women but women feature adramatic increase in the risk of diabetes-associated cardiovascular diseases after the menopause. The estimated future years of life lost owing to diabetes is somewhat higher in women than men, with ahigher increase in vascular complications in women but ahigher increase of cancer deaths in men. In women prediabetes or diabetes are more distinctly associated with ahigher number of vascular risk factors, such as inflammatory parameters, unfavourable changes in coagulation and higher blood pressure. Women with prediabetes and diabetes have amuch higher relative risk for vascular diseases. Women are more often morbidly obese and less physically active but may have an even greater benefit in health and life expectation from increased physical activity than men. In weight loss studies men often showed ahigher weight loss than women; however, diabetes prevention is similarly effective in men and women with prediabetes with arisk reduction of nearly 40%. Nevertheless, along-term reduction in all cause and cardiovascular mortality was so far only observed in women. Men predominantly feature increased fasting blood glucose levels, women often show impaired glucose tolerance. Ahistory of gestational diabetes or polycystic ovary syndrome (PCOS) as well as increased androgen levels and decreased estrogen levels in women and the presence of erectile dysfunction or decreased testosterone levels in men are important sex-specific risk factors for the development of diabetes. Many studies showed that women with diabetes reach their target values for HbA1c, blood pressure and low-density lipoprotein (LDL)-cholesterol less often than their male counterparts, although the reasons are unclear. Furthermore, sex differences in the effects, pharmacokinetics and side effects of pharmacological treatment should be taken more into consideration.

Defining Biventricular Abnormalities by Cardiac Magnetic Resonance in Pre-Dialysis Patients with Chronic Kidney Disease.

The aim of the study was to investigate biventricular structural and functional abnormalities in pre-dialysis patients across stages of chronic kidney disease (CKD) by cardiac magnetic resonance (CMR). Fifty-one CKD patients with CMR exams were retrospectively analyzed. Patients were divided into three groups according to estimated glomerular filtration rate (eGFR): CKD 1 group (patients with normal eGFR≥90 mL/min/1.73 m2, n = 20), CKD 2-3 group (patients with eGFR< 90 to ≥30 mL/min/1.73 m2, n = 14), and CKD 4-5 group (patients with eGFR<30 mL/min/1.73 m2, n = 17). Twenty-one age- and sex-matched healthy controls (HC) were recruited. CMR-derived left ventricular (LV) and right ventricular (RV) structural and functional measures were compared. Association between CMR parameters and clinical measures was assessed. There was an increasing trend in RV mass index (RVMi) and LV mass index (LVMi) with the occurrence and development of CKD from HC group to CKD 4-5 group although no significant difference was observed between CKD 1 group and HC group. LV global radial strain and LV global circumferential strain dropped and native T1 value elevated significantly in CKD 4-5 group compared with the other three groups (all p < 0.05), while RV strain measures, RV ejection fraction, and LV ejection fraction showed no significant difference among 4 groups (all p > 0.05). Elevated LV end-diastolic volume index (β = 0.356, p = 0.016) and RV end-systolic volume index (β = 0.488, p = 0.001) were independently associated with RVMi. Increased systolic blood pressure (β = 0.309, p = 0.004), LV end-systolic volume index (β = 0.633, p < 0.001), and uric acid (β = 0.261, p = 0.013) were independently associated with LVMi. Meanwhile, serum phosphorus (β = 0.519, p = 0.001) was independently associated with native T1 value. In pre-dialysis CKD patients, left and right ventricular remolding has occurred. RVMi and LVMi were the first changed CMR indexes in the development of CKD when eGFR began to drop. Because fluid volume overload was the independent risk factor for RVMi and LVMi increase, reasonable controlling fluid volume overload may slow down the progression of biventricular remolding and may reduce related cardiovascular disease risk.

How Could Different Obesity Scenarios Alter the Burden of Type 2 Diabetes and Liver Disease in Saudi Arabia?

Introduction: Obesity is a major risk factor for type 2 diabetes (T2DM) and liver disease, and obesity-attributable liver disease is a common indication for liver transplant. Obesity prevalence in Saudi Arabia (SA) has increased in recent decades. SA has committed to the WHO “halt obesity” target to shift prevalence to 2010 levels by 2025. We estimated the future benefits of reducing obesity in SA on incidence and costs of T2DM and liver disease under two policy scenarios: (1) SA meets the “halt obesity” target; (2) population body mass index (BMI) is reduced by 1% annually from 2020 to 2040. Methods: We developed a dynamic microsimulation of working-age people (20–59 years) in SA between 2010 and 2040. Model inputs included population demographic, disease and healthcare cost data, and relative risks of diseases associated with obesity. In our two policy scenarios, we manipulated population BMI and compared predicted disease incidence and associated healthcare costs to a baseline “no change” scenario. Results: Adults <35 years are expected to meet the “halt obesity” target, but those ≥35 years are not. Obesity is set to decline for females, but to increase amongst males 35–59 years. If SA’s working-age population achieved either scenario, >1.15 million combined cases of T2DM, liver disease, and liver cancer could be avoided by 2040. Healthcare cost savings for the “halt obesity” and 1% reduction scenarios are 46.7 and 32.8 billion USD, respectively. Conclusion: SA’s younger working-age population is set to meet the “halt obesity” target, but those aged 35–59 are off track. Even a modest annual 1% BMI reduction could result in substantial future health and economic benefits. Our findings strongly support universal initiatives to reduce population-level obesity, with targeted initiatives for working-age people ≥35 years of age.

A METHOD FOR ASSESSING THE RISK OF DEVELOPMENT OF DISEASE COMPLICATIONS WITH METABOLIC SYNDROME BASED ON THE CUMULATIVE DISTRIBUTION FUNCTION

It is relevant to assess the risks of related diseases based on the electronic data of patients in order to prevent the progress of further complications of metabolic syndrome (MS). This article describes the Archimedean copula-based method of assessing the risks of developing related diseases based on diagnosis and risk factors associated with complications and readmissions.

Machine learning-based ovarian cancer prediction with XGboost and stochastic gradient boosting models

Ovarian cancer is one of the most common types of gynecological malignancies with its high mortality rate, silent and occult tumor growth, late onset of symptoms and diagnosis in advanced stages. Therefore, the need to develop new diagnostic techniques to predict the course of the disease and the prognosis of this malignancy has increased. In this study, ovarian cancer and benign ovarian tumor samples will be classified to create an accurate diagnostic predictive model using the machine learning method XGBoost and Stochastic Gradient Boosting and disease-related risk factors will be determined. This current study considered the open-access ovarian cancer and benign ovarian tumor samples data set. For this purpose, data from 349 patients were included. The data set was divided as 80:20 as a training and test dataset. XGBoost and Stochastic Gradient Boosting were constructed for the classification via five-fold cross-validation. Accuracy, balanced accuracy, sensitivity, specificity, positive predictive value, and negative predictive value performance metrics were evaluated for model performance. Among the performance criteria in the test stage obtained from the XGBoost model that has the best classification result; accuracy, balanced accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and F1 score were obtained as 89.5%, 88.7%, 85.7%, 91.7%, 85.7%, 91.7%, and 85.7%, respectively. According to the variable importance obtained as a result of the model, the variables most associated with the diagnosis were CA72-4, HE4, LYM%, ALB, EO%, BUN, RBC, NEU, and MCV, respectively. The applied machine learning model successfully classified ovarian cancer and created a highly accurate diagnostic prediction model. The results from the study revealed effective parameters that can diagnose ovarian cancer with high accuracy. With the parameters determined as a result of the modeling, the clinician will be able to simplify and facilitate the decision-making process for the diagnosis of ovarian cancer.

Assessment of indicators of reproductive health of the population of the Trans-Ural Republic of Bashkortostan in 2000–2020

BACKGROUND: The reproductive health of a population depends on many factors one of which is chemical pollution of the environment caused by both natural conditions and man-made impacts. The population living in geochemical provinces is often subject to pathological conditions caused by a lack, excess or imbalance of macro- and microelements. This study was carried out in the Republic of Bashkortostan in areas of natural and man-made anomalies with excessive content of heavy metals in the environment.&#x0D; AIM: To analyze the demographic profile and assess the reproductive health of the population of the Trans-Ural zone of the Republic of Bashkortostan.&#x0D; MATERIALS AND METHODS: A descriptive ecological study of the trend of reproductive health of the population of the Trans-Ural zone of the Republic of Bashkortostan was carried out using average population indicators. Statistical data presented in the open press by the Ministry of Health of the Republic of Bashkortostan for the 20002020 period were used. These data included demographic indicators, infant mortality, frequency of congenital malformations, and morbidity of children within the first year of life.&#x0D; RESULTS: In all the areas studied, there was a tendency for a decrease in the birth rate and an increase in the mortality rate. The highest average birth rate of 19.8 was recorded in the Burzyansky District and the lowest of 13.1 in the Zilairsky District, which was higher than the republican average of 12.4. During the study period, there was a significant decrease in infant mortality both in the republic and in the Trans-Urals regions. Average infant mortality rates relative to congenital malformations among newborns in the Sibay, Baymaksky, and Zianchurinsky Districts as well as the relative risk of blood diseases in children of the first year of life in most of the studied areas was higher than the average republican level.&#x0D; CONCLUSION: Reproductive health of the population of Sibay for the period 20002020 is exposed to a higher risk of congenital malformations and infant mortality than the average republican level. In the Baymaksky, Zianchurinsky, Uchalinsky and Khaibullinsky Districts, the risk of developing blood diseases in children within the first year of life was higher than the average republican level. The results further indicate the need to take measures to reduce risks and improve the safety of reproductive health of the population of the mining region.

Accurate genome-wide genotyping from archival tissue to explore the contribution of common genetic variants to pre-cancer outcomes

PurposeThe contribution of common genetic variants to pre-cancer progression is understudied due to long follow-up time, rarity of poor outcomes and lack of available germline DNA collection. Alternatively, DNA from diagnostic archival tissue is available, but its somatic nature, limited quantity and suboptimal quality would require an accurate cost-effective genome-wide germline genotyping methodology.Experimental designBlood and tissue DNA from 10 individuals were used to benchmark the accuracy of Single Nucleotide Polymorphisms (SNP) genotypes, Polygenic Risk Scores (PRS) or HLA haplotypes using low-coverage whole-genome sequencing (lc-WGS) and genotype imputation. Tissue-derived PRS were further evaluated for 36 breast cancer patients (11.7 years median follow-up time) diagnosed with DCIS and used to model the risk of Breast Cancer Subsequent Events (BCSE).ResultsTissue-derived germline DNA profiling resulted in accurate genotypes at common SNPs (blood correlation r2 > 0.94) and across 22 disease-related polygenic risk scores (PRS, mean correlation r = 0.93). Imputed Class I and II HLA haplotypes were 96.7% and 82.5% concordant with clinical-grade blood HLA haplotypes, respectively. In DCIS patients, tissue-derived PRS was significantly associated with BCSE (HR = 2, 95% CI 1.2–3.8). The top and bottom decile patients had an estimated 28% and 5% chance of BCSE at 10 years, respectively.ConclusionsArchival tissue DNA germline profiling using lc-WGS and imputation, represents a cost and resource-effective alternative in the retrospective design of long-term disease genetic studies. Initial results in breast cancer suggest that common risk variants contribute to pre-cancer progression.

Sodium-glucose co-transporter 2 inhibitors and erythrocytosis: a review

Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are a class of anti-hyperglycaemic agents widely used in the treatment of type 2 diabetes mellitus (T2DM). They function by reducing renal glucose reabsorption and thereby promote urinary glucose excretion, resulting in improvement in glycaemic control. In large-scale clinical trials, SGLT2i have been shown to reduce cardiovascular mortality, non-fatal myocardial infarction and stroke significantly. In addition, clinical evidence suggests that they are renal protective as their use reduces the relative risk of end-stage renal disease and death from renal causes. These positive results have led to a rapid uptake of SGLT2i in clinical practice. Recently, clinical studies and case reports have suggested a link between SGLT2i therapy and erythrocytosis. The authors discuss possible mechanisms at cellular level that may cause erythrocytosis and explore its clinical relevance in people living with T2DM who are taking SGLT2i therapy.

Modification of the all-cause and cardiovascular disease related mortality risk with changes in the metabolic syndrome status: a population-based prospective cohort study in Taiwan

AimTo examine whether changes in metabolic syndrome (MetS) status over time are associated with risk of all-cause and cardiovascular disease related (CVD) mortality. MethodsThis prospective cohort study consisted of 544,749 individuals who participated in a self-funded comprehensive health surveillance program offered by Taiwan MJ Health Management Institution between 1998 and 2016. We included 236,216 adults who had at least two repeated MetS measures 5.9 (4.6) years apart and were followed up for mortality over 18.8 (5.2) years. Participants were classified according to the change in their MetS status as follows: MetS-free at both time points (n = 173,116), MetS-developed (n = 22,607), MetS-recovered (n = 13,616), and MetS-persistent (n = 26,877). Multivariable Cox proportional hazards model was used to determine the association between change in MetS status and risk of all-cause and CVD mortality. ResultsOver the 4,436,842 person-years follow-up period, 14,226 participants died, including 2671 (19%) of CVD-related causes. The crude CVD mortality rate per 1000 person-years in the study groups were MetS-free, 0.32; MetS-developed, 0.75; MetS-recovered, 1.22; and MetS-persistent, 2.00 (P < 0.001). Compared to the persistent MetS group, participants in the MetS-recovered group had a lower risk of all-cause (adjusted hazard ratio [aHR], 0.87; 95%CI, 0.82–0.92) and CVD mortality (aHR, 0.81; 95% confidence interval [CI], 0.71–0.93). Development of MetS increased the risk for all-cause (aHR, 1.11; 95%CI, 1.05–1.17) and CVD mortality (aHR, 1.22; 95%CI, 1.07–1.39), compared to the MetS-free group. ConclusionRecovery from MetS was significantly associated with a lower risk of all-cause and CVD mortality, whereas development of MetS was associated with increased risk.

Impact of Severe Acute Respiratory Syndrome Coronavirus 2 Variants on Inpatient Clinical Outcome.

Prior observation has shown differences in COVID-19 hospitalization risk between SARS-CoV-2 variants, but limited information describes hospitalization outcomes. Inpatients with COVID-19 at 5 hospitals in the eastern United States were included if they had hypoxia, tachypnea, tachycardia, or fever, and SARS-CoV-2 variant data, determined from whole-genome sequencing or local surveillance inference. Analyses were stratified by history of SARS-CoV-2 vaccination or infection. The average effect of SARS-CoV-2 variant on 28-day risk of severe disease, defined by advanced respiratory support needs, or death was evaluated using models weighted on propensity scores derived from baseline clinical features. Severe disease or death within 28 days occurred for 977 (29%) of 3369 unvaccinated patients and 269 (22%) of 1230 patients with history of vaccination or prior SARS-CoV-2 infection. Among unvaccinated patients, the relative risk of severe disease or death for Delta variant compared with ancestral lineages was 1.30 (95% confidence interval [CI]: 1.11-1.49). Compared with Delta, the risk for Omicron patients was .72 (95% CI: .59-.88) and compared with ancestral lineages was .94 (.78-1.1). Among Omicron and Delta infections, patients with history of vaccination or prior SARS-CoV-2 infection had half the risk of severe disease or death (adjusted hazard ratio: .40; 95% CI: .30-.54), but no significant outcome difference by variant. Although risk of severe disease or death for unvaccinated inpatients with Omicron was lower than with Delta, it was similar to ancestral lineages. Severe outcomes were less common in vaccinated inpatients, with no difference between Delta and Omicron infections.

1946. Efficacy of Approved versus Unapproved Vaccines for SARS-CoV-2 Infection in Randomised Blinded Clinical Trials

Abstract Background Five SARS-CoV-2 vaccines are approved in North America and/or Europe: Pfizer/BioNTech, Moderna, Janssen, Oxford-AstraZeneca and Novavax. Other vaccines have been developed, including Sinopharm, SinoVac, QazVac, Covaxin, Soberana, Corbevac, Medicago, Clover and Cansino, but are not approved in high income countries. This meta-analysis compared the efficacy of approved and unapproved vaccines in randomised clinical trials (RCTs). Methods A systematic review of clinical trial registries, PUBMED and EMBASE identified placebo-controlled RCTs of SARS-CoV-2 vaccines prospectively evaluating risks of symptomatic or severe infection with clearly defined endpoints. For each trial, risk of bias was assessed using Cochrane tool 2.0 and the CONSORT checklist. In the pre-defined meta-analysis, relative risks of symptomatic infection and severe disease were compared for each vaccine versus placebo, using Cochrane-Mantel Haenszel Tests (random effects method). Results There were 21 RCTs assessing efficacy of the COVID-19 vaccines identified. One RCT was excluded for high risk of bias. Ten RCTs in 206,667 participants evaluated 5 approved vaccines; 10 RCTs in 158,599 participants evaluated 8 unapproved vaccines. In the meta-analysis, prevention of symptomatic infection was 84% (95% C.I. 68-92%) for approved vaccines versus 72% (95% C.I. 65-77%) for unapproved vaccines, with no significant difference between vaccine types (p=0.13). Prevention of severe SARS-CoV-2 infection was 95% (95% C.I. 78-99%) for approved vaccines versus 84% (95% C.I. 72-91%) for unapproved vaccines (p=0.12). In addition, the risk of serious adverse events was similar between vaccine types (p=0.49). Efficacy of approved and unapproved SARS-CoV-2 vaccines Percentage efficacy of approved and unapproved SARS-CoV-2 vaccines against symptomatic infection (Panel A) and severe disease (Panel B). Vaccines are arranged by approval-status (approved vaccines to the left and unapproved vaccines to the right of discontinuous line) and colour-coded by vaccine type. Error bars represent 95% confidence intervals. RIBSP, Research Institute for Biological Safety Problems; IFV, Instituto Finlay de Vacunas. Conclusion This meta-analysis of 20 RCTs in 365,266 participants, showed no significant difference in efficacy between the approved and unapproved SARS-CoV-2 vaccines for endpoints of either symptomatic or severe infection. Differences in study design, end-point definitions, variants and prevalence of infection may have influenced the results. Head-to-head RCTs will be required to make definitive conclusions. If efficacy is proved definitively, new patent-free vaccines could lower costs of worldwide SARS-CoV-2 vaccination campaigns significantly. Disclosures All Authors: No reported disclosures.

Effects of air pollution and weather on the initial COVID-19 outbreaks in United States, Italy, Spain, and China: A comparative study.

Contrasting effects have been identified in association of weather (temperature and humidity) and pollutant gases with COVID-19 infection, which could be derived from the influence of lockdowns and season change. The influence of pollutant gases and climate during the initial phases of the pandemic, before the closures and the change of season in the northern hemisphere, is unknown. Here, we used a spatial-temporal Bayesian zero-inflated-Poisson model to test for short-term associations of weather and pollutant gases with the relative risk of COVID-19 disease in China (first outbreak) and the countries with more cases during the initial pandemic (the United States, Spain and Italy), considering also the effects of season and lockdown. We found contrasting association between pollutant gases and COVID-19 risk in the United States, Italy, and Spain, while in China it was negatively associated (except for SO2 ). COVID-19 risk was positively associated with specific humidity in all countries, while temperature presented a negative effect. Our findings showed that short-term associations of air pollutants with COVID-19 infection vary strongly between countries, while generalized effects of temperature (negative) and humidity (positive) with COVID-19 was found. Our results show novel information about the influence of pollution and weather on the initial outbreaks, which contribute to unravel the mechanisms during the beginning of the pandemic.

HPB P50 Prediction and Management of Choledocholithiasis in Gallstone Related Disease

Abstract Background Acute cholecystitis, pancreatitis and cholangitis are common presentations to the general surgery on-call shift, the management of which can be complicated by evidence of choledocholithiasis. Risk scoring systems exist to help guide the requirement for further imaging or endoscopy for these patients. Our audit reviewed the American Society for Gastrointestinal Endoscopy (ASGE) scoring system for choledocholithiasis prediction and associated management guidelines against current practices at a tertiary hospital to assess how well common practice matches guideline recommendations based on choledocholithiasis risk. Our aim was to assess how current practice for investigation of possible choledocholithiasis interlinks with CBD stone risk scoring systems, whether risk scoring is useful in management of a gallstone related disease risk and if a choledocholithiasis risk prediction tool could optimize resource usage. Methods We retrospectively identified a cohort of patients presenting acutely to the surgical unit over a three-month period with symptoms suggestive of cholecystitis, cholangitis or pancreatitis. Patients were identified from prospectively maintained, electronic records of surgical in-patients and on-call surgical patient lists. Patients meeting local guideline criteria for diagnosis of pancreatitis (serum lipase greater than 3 times the upper limit of normal or CT confirmed pancreatic inflammation) or Tokyo Guidelines 2018 for diagnosis of cholecystitis and cholangitis were included. Those with non-gallstone pathology, previous cholecystectomies and incomplete data were excluded. Patients were categorized into respective risk strata according to the ASGE scoring system and their ongoing management was compared against those guidelines. Subgroup analyses on outcomes and complications for those in each risk strata and in those with age over 55 years of elevated bilirubin as risk factors were also performed. Results 78 patients were identified with 13 categorized as high-risk, 46 intermediate risk and 19 low-risk. 12 of 13 patients (92%) at high risk had evidence of choledocholithiasis on MRCP, CT or USS. 10 of 12 patients (83%) subsequently had a definitive ERCP or preceding cholecystectomy. No low-risk patient had evidence of choledocholithiasis on imaging. 90% of this group have had or are awaiting cholecystectomy. 1 patient, who declined cholecystectomy, re-presented 8 months later with choledocholithiasis. Within the intermediate risk category, there was greater discrepancy in the predictive value of choledocholithiasis. 17 of 46 (37%) patients had an MRCP or EUS with 4 having choledocholithiasis and all going on to have duct clearance. 29 patients (63%) did not have MRCP or EUS, instead receiving either USS, CT or both. 2 patients in this group were unfit for further procedure and received no further imaging, 2 patients had evidence of choledocholithiasis and 25 had no evidence of choledocholithiasis. To date 12 patients have had or are awaiting a cholecystectomy and a further 12 have declined or were not fit for cholecystectomy. 8 patients were stratified as intermediate risk on age &amp;gt;55 alone with no patients having evidence of choledocholithiasis. Conclusions Although based on a small retrospective study, risk prediction using the ASGE scoring tool works effectively in high and low risk patient cohorts, but appears to over predict choledocholithiasis in the intermediate risk group, particularly when based on age alone. Patients with high risk of choledocholithiasis should proceed to duct clearance without further imaging, whilst low risk patients can proceed directly to cholecystectomy. Over investigation dictated by the guidelines for the intermediate risk group is likely to lead to poor compliance as shown in our dataset and may lead to increased burden on imaging services, particularly in hospitals serving more elderly populations.

High-risk meat and fish cooking methods of polycyclic aromatic hydrocarbons formation and its avoidance strategies

According to recent research, human exposures to polycyclic aromatic hydrocarbons (PAHs) are mainly through the food route. Food such as meat and fish are two primary sources of dietary protein. However, a certain level of unawareness and poor cooking education leads to the formation of PAHs in cooked meat and fish meals. PAHs are classified as human carcinogens that poses a risk of cancer and related diseases. This review studied high-quality published articles on cooked meat and fish, emphasizing the level of PAHs contaminations, cooking methods, and related parameters. Additionally, verities of easy-feasible PAHs avoidance strategies for meat and fish cooking are summarized. Meat and fish cooking methods such as smoking, grilling, barbecuing, roasting, and traditional frying amalgamated with the risk of PAHs contamination. In accordance with expectations, there are some strategies to avoid PAHs contamination in cooked meat and fish up to 100%, including low-fat content, fuel/wood types, smoking filters, and different types of marination. This study comprehensively identified the manner in which PAHs avoidance strategies aligned with present safety guidelines.