Established Risk Factors Research Articles

The association of low serum magnesium levels with frailty among hemodialysis patients

Frailty is common among hemodialysis patients and is associated with mortality and fractures. Hypomagnesemia is also known to be a risk factor for mortality and fractures and has been shown to be significantly associated with muscle performance indexes. However, little is known about the association between hypomagnesemia and frailty. We enrolled 339 outpatients who underwent hemodialysis and assessed frailty using the Clinical Frailty Scale (CFS), a 7-point subjective assessment tool based upon clinical judgment. We examined the association between serum magnesium levels and frailty evaluated using the CFS. The median CFS score was 3 points, and 49 (14.5%) patients had frailty (CFS score ≥ 5). In multiple regression analysis, serum magnesium levels were independently associated with increased CFS scores (β = − 0.126, P = 0.005) adjusted for age, body mass index, diabetes, cardiovascular diseases, prevalent fractures, serum albumin and C-reactive protein. The adjusted odds ratio for frailty was 2.85 [95% confidence interval (CI) 1.23–6.97, P = 0.014] in the lower serum magnesium group categorized based on the median value. Furthermore, with regard to model discrimination, adding serum magnesium levels to the established risk factors significantly improved net reclassification (0.520, P < 0.001) and integrated discrimination (0.023, P = 0.031). Lower serum magnesium levels may be associated with the severity and definition of frailty independent of well-known risk factors.

Modifiable risk factors for multiple sclerosis have consistent directions of effect across diverse ethnic backgrounds: a nested case–control study in an English population-based cohort

BackgroundMultiple sclerosis is a leading cause of non-traumatic neurological disability among young adults worldwide. Prior studies have identified modifiable risk factors for multiple sclerosis in cohorts of White ethnicity, such as infectious mononucleosis, smoking, and obesity during adolescence/early adulthood. It is unknown whether modifiable exposures for multiple sclerosis have a consistent impact on risk across ethnic groups.AimTo determine whether modifiable risk factors for multiple sclerosis have similar effects across diverse ethnic backgrounds.MethodsWe conducted a nested case–control study using data from the UK Clinical Practice Research Datalink. Multiple sclerosis cases diagnosed from 2001 until 2022 were identified from electronic healthcare records and matched to unaffected controls based on year of birth. We used stratified logistic regression models and formal statistical interaction tests to determine whether the effect of modifiable risk factors for multiple sclerosis differed by ethnicity.ResultsWe included 9662 multiple sclerosis cases and 118,914 age-matched controls. The cohort was ethnically diverse (MS: 277 South Asian [2.9%], 251 Black [2.6%]; Controls: 5043 South Asian [5.7%], 4019 Black [4.5%]). The age at MS diagnosis was earlier in the Black (40.5 [SD 10.9]) and Asian (37.2 [SD 10.0]) groups compared with White cohort (46.1 [SD 12.2]). There was a female predominance in all ethnic groups; however, the relative proportion of males was higher in the South Asian population (proportion of women 60.3% vs 71% [White] and 75.7% [Black]). Established modifiable risk factors for multiple sclerosis—smoking, obesity, infectious mononucleosis, low vitamin D, and head injury—were consistently associated with multiple sclerosis in the Black and South Asian cohorts. The magnitude and direction of these effects were broadly similar across all ethnic groups examined. There was no evidence of statistical interaction between ethnicity and any tested exposure, and no evidence to suggest that differences in area-level deprivation modifies these risk factor-disease associations. These findings were robust to a range of sensitivity analyses.Conclusions and relevanceEstablished modifiable risk factors for multiple sclerosis are applicable across diverse ethnic backgrounds. Efforts to reduce the population incidence of multiple sclerosis by tackling these risk factors need to be inclusive of people from diverse ethnicities.

How much disease risk is due to old age and established risk factors?

Improved healthcare is leading to older populations and increasing numbers of individuals experiencing multiple diseases, possibly concurrently (multimorbidity). This article asks whether the observed number of new diseases is more than expected based on age and established risk factors alone, assuming that disease risk is unchanged by prior or pre-existing disease. This is accomplished by designing a new epidemiological approach, where the expected number of disease types are estimated for individuals without prior disease, by combining individual risk predictions with a "Poisson-Binomial" model to estimate the expected number of new diseases and its confidence interval. For 123 diseases in men and 99 diseases in women, the expected number of new diseases based on age and established risk factors was approximately of that observed, with the observed number of new diseases approximately times that predicted. The differences could not be explained by natural statistical variation, and provide a rigorous statistical demonstration of lower disease risk for individuals without any previous disease. The multiple of was sufficiently consistent across different diseases to prevent its use for classification of disease types, but there were differences for subgroups such as smokers with high body mass index, and for some classes of disease (as defined by the International Classification of Diseases, version 10). The results suggest that empirical modeling might allow reliable predictions of future hospital admissions, and confirm the value of conventional epidemiological approaches that study disease risk in healthy individuals. The implications and future possibilities of this new approach are discussed.

Kidney Function and Risk of Renal Cell Carcinoma.

We evaluated the temporal association between kidney function, assessed by estimated glomerular filtration rate (eGFR), and the risk of incident renal cell carcinoma (RCC). We also evaluated whether eGFR could improve RCC risk discrimination beyond established risk factors. We analyzed the UK Biobank cohort, including 463,178 participants of whom 1,447 were diagnosed with RCC during 5,696,963 person-years of follow-up. We evaluated the temporal association between eGFR and RCC risk using flexible parametric survival models, adjusted for C-reactive protein and RCC risk factors. eGFR was calculated from creatinine and cystatin C levels. Lower eGFR, an indication of poor kidney function, was associated with higher RCC risk when measured up to 5 years prior to diagnosis. The RCC HR per SD decrease in eGFR when measured 1 year before diagnosis was 1.26 [95% confidence interval (95% CI), 1.16-1.37], and 1.11 (95% CI, 1.05-1.17) when measured 5 years before diagnosis. Adding eGFR to the RCC risk model provided a small improvement in risk discrimination 1 year before diagnosis with an AUC of 0.73 (95% CI, 0.67-0.84) compared with the published model (0.69; 95% CI, 0.63-0.79). This study demonstrated that kidney function markers are associated with RCC risk, but the nature of these associations are consistent with reversed causality. Markers of kidney function provided limited improvements in RCC risk discrimination beyond established risk factors. eGFR may be of potential use to identify individuals in the extremes of the risk distribution.

Indexed oxygen delivery during pediatric cardiopulmonary bypass is a modifiable risk factor for postoperative acute kidney injury.

Acute kidney injury after pediatric cardiac surgery is a common complication with few established modifiable risk factors. We sought to characterize whether indexed oxygen delivery during cardiopulmonary bypass was associated with postoperative acute kidney injury in a large pediatric cohort. This was a retrospective analysis of patients under 1year old undergoing cardiac surgery with cardiopulmonary bypass between January 1, 2013, and January 1, 2020. Receiver operating characteristic curves across values ranging from 260 to 400 mL/min/m2 were used to identify the indexed oxygen delivery most significantly associated with acute kidney injury risk. We included 980 patients with acute kidney injury occurring in 212 (21.2%). After adjusting for covariates associated with acute kidney injury, an indexed oxygen delivery threshold of 340 mL/min/m2 predicted acute kidney injury in STAT 4 and 5 neonates (area under the curve=0.66, 95% CI=0.60 - 0.72, sensitivity=56.1%, specificity=69.4%). An indexed oxygen delivery threshold of 400 mL/min/m2 predicted acute kidney injury in STAT 1-3 infants (area under the curve=0.65, 95% CI=0.58 - 0.72, sensitivity=52.6%, specificity=74.6%). Indexed oxygen delivery during cardiopulmonary bypass is a modifiable variable independently associated with postoperative acute kidney injury in specific pediatric populations. Strategies aimed at maintaining oxygen delivery greater than 340 mL/min/m2 in complex neonates and greater than 400 mL/min/m2 in infants may reduce the occurrence of postoperative acute kidney injury in the pediatric population.

Abstract P148: Association Of Hypertension With Cardiovascular Disease In The United States

Background: Hypertension is strongly associated with cardiovascular disease (CVD). Nevertheless, its relative importance compared with other established CVD risk factors among U.S. adults is unclear. Objective: To determine the prevalence of CVD risk factors and compare their association with CVD in a large U.S. population. Methods: The 2017 and 2019 Behavioral Risk Factor Surveillance System queried a representative sample of U.S. adults about hypertension (HTN), diabetes, and high cholesterol based on health professional diagnosis, obesity (BMI ≥30 from self-reported weight and height), smoking, and physical inactivity. We used logistic regression to examine the association between risk factors and CVD (nonfatal stroke and/or nonfatal myocardial infarction). Coefficients were compared using Wald tests. Models were also examined across sex (male vs. female), race (Black vs. White), and age (≥ 65 and &lt;65), using interaction terms. Results: The weighted sample was 21.0% age ≥65 years, 51.3% female, 70.0% Non-Hispanic White, and 11.6% Non-Hispanic Black. While all risk factors were associated with CVD, HTN was most strongly associated with CVD in the fully adjusted model (OR = 2.26; P -values comparing to other coefficients were all &lt;0.001). There was no evidence of effect modification across sex and race (all P -interaction values &gt;0.05), the association between hypertension and CVD was stronger for age &lt;65 years ( P &lt;0.001). Nevertheless, hypertension was still the strongest risk factor among both age groups. Conclusion: In this large U.S. sample, hypertension was the most prevalent and strongest CVD risk factor and should be a primary focus of policy focused on CVD prevention.

Impact of the COVID-19 pandemic in mortality due to respiratory diseases: A comparative analysis of 2021 and 2020 vs 2019 in Spain

IntroductionWe previously reported an increase in respiratory mortality in 2020 in Spain after COVID-19. It is unclear if this rise is sustained in the longer-term. We aimed to determine whether respiratory mortality in 2021 in Spain returned to pre-pandemic levels. Material and methodsIn an observational, large study using official National Institute of Statistics data, we explored deaths due to respiratory diseases, that is, all causes of death by the standard WHO list of diseases of the respiratory system plus COVID-19, tuberculosis and lung cancer. Using the latest available official data of Spain, we analyzed changes in the mortality pattern in Spain from January 2019 to December 2021. We endorsed STROBE guidance for observational research. ResultsThere were 98,714 deaths due to respiratory diseases in 2021 in Spain, corresponding to 21.9% of all deaths, becoming second in the ranking of causes of death. Respiratory diseases mortality in Spain has not returned to pre-pandemic levels in 2021, still with an increase of 30.3% (95% CI 30.2–30.4) compared to rates in 2019. All respiratory-specific causes of death decreased in 2021, except for lung cancer, that increased in women and decreased in men compared to 2019 (both p<0.05). In a multivariate analysis some established risk factors for respiratory diseases mortality were confirmed, such as male gender and older age; further, an association with reduced mortality in rural Spain was observed, still with a large geographical variability. ConclusionsThe COVID-19 pandemic has had a lasting impact on deaths due to respiratory diseases and certain specific causes of death in 2021, and it has disproportionately affected certain regions.

Estuarine Hypoxia—Identifying High Risk Catchments Now and Under Future Climate Scenarios

AbstractHypoxic blackwater events occur worldwide, affecting inland and coastal waters. These events have been exacerbated by man‐made floodplain drainage, leading to large‐scale fish kills and ecological degradation. This paper presents a new method to identify estuarine catchment areas that are most likely to generate hypoxic conditions. The method uses established risk factors, including vegetation type, inundation extent and duration, ground‐truthed in eastern Australia. A catchment is at higher risk of hypoxic blackwater generation if (a) it is located where floodwaters are high and/or drainage is impeded, (b) the site topography includes an extensive, low‐lying floodplain; and/or (c) the land‐use and environmental characteristics have a high deoxygenation potential. Consequent impacts to an estuary are determined by the floodplain connectivity with the estuary, and the discharge characteristics of the catchment drainage system. Where multiple, proximate catchments have similar drainage conditions, compounding plumes of hypoxic blackwater can overwhelm the assimilation capacity of the estuary. Climate change may significantly increase the volume and frequency of blackwater events in estuarine environments as a result of reduced drainage due to sea level rise, higher temperatures, and more intense and sporadic rainfall events. It is recommended that management measures be introduced to mitigate the effects of climate change and avoid further widespread hypoxic blackwater events.

Non-Genetic Risk Factors for Dementia and Alzheimer’s Disease

Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder linked to multiple genetic and environmental factors. Despite its complex pathology and still undetermined etiology, a number of factors have been found to be closely associated with the incidence of AD. Although the molecular mechanisms linking many of these factors with AD are unclear and not necessarily causative, their identification and control might be key preventative measures. Cardiovascular diseases, diabetes, obesity and other life-style habits are recognized as established risk factors for AD. Other emerging factors investigated as potential contributors to the overall risk of dementia include anemia, obstructive respiratory diseases, vitamin D deficiency, thyroid imbalance, inflammation and depression. This review summarizes established risk factors; it also provides an insight into emerging factors as modifiable elements, the control of which may reduce the risk of AD and dementia.

Clostridioides difficile Infection in Pediatric Inflammatory Bowel Disease.

Children with inflammatory bowel disease (IBD) are at increased risk of C. difficile infection (CDI) and experience worse outcomes associated with an infection. In this article, we review recent research on the incidence, diagnosis, complications, and treatment options for CDI in children with IBD. Children with IBD have an elevated incidence of CDI, but their CDI risk does not associate with established risk factors in adults with IBD. Existing testing methodologies are inadequate at differentiating CDI from C. difficile colonization in children with IBD. Fecal microbiota transplantation offers a durable cure for recurrent CDI. CDI remains a frequent occurrence in children with IBD. Careful clinical monitoring should be used to diagnose CDI and patients with co-occurring IBD and CDI require careful surveillance for worse outcomes. Future research should explore the optimal diagnosis and treatment modalities in this unique patient population.

An analysis of iris pattern as a risk factor for skin cancer development in immunosuppressed renal transplant recipients.

Renal transplant recipients are at increased risk of keratinocyte skin cancers with a tendency to have multiple, aggressive and difficult to treat tumours. The eye and the skin share the same embryological ectoderm. Iris pattern has recently been reported as a predictive risk factor for skin cancer in non-immunosuppressed Southern European (Grigore et al., J Eur Acad Dermatol Venereol, 2018, 1662) and Irish populations (Ridge et al., J Eur Acad Dermatol Venereol, 2022, e542). To analyse if an individual's iris pattern is an independent risk factor for the development of keratinocyte skin cancers in renal transplant recipients. Iris patterns of 110 renal transplant recipients were evaluated using the Simionescu visual three-step technique (iris periphery, colarette and iris freckling [Simionescu et al., Ann Res Rev Biol, 2014, 2525]). Established risk factors for skin cancer in transplant patients were recorded as confounding factors. Observational cross-sectional study including 110 renal transplant population. Thirty-one participants had skin cancer. In the skin cancer group, iris periphery was blue/grey in 74.3% (p = 0.053, OR 2.5), the colarette was light brown in 57.1% (p < 0.0043) and iris freckles were present in 55%(p = 0.044). Dark brown and blue colarettes were observed in controls. Binary Logistic Regression analysis showed light brown colarette is a significant independent risk factor for skin cancer (OR 4.54, p < 0.02, CI 1.56-10.57). Within this renal transplant population a blue iris periphery, light brown colarette and presence of freckling confers an independent risk for keratinocyte skin cancer. Iris pattern is a useful tool for identification of transplant patients at risk of keratinocyte skin cancer and an easy-to-use technique for risk evaluation in this cohort. This is the first study looking at iris pattern and keratinocyte skin cancer risk in renal transplant population.

Epidemiology and Risk Factors for Stroke in Chronic Kidney Disease: A Narrative Review.

Patients with chronic kidney disease (CKD) have a higher risk ofboth ischemic and hemorrhagic stroke. This association appears to be partly independent from the higher prevalence of established risk factors for stroke in patients with CKD, including hypertension and atrial fibrillation. In the present review we aim to discuss the impact of CKD on the risk of stroke and stroke-related consequences, and explore the pathophysiology underpinning the increased risk of stroke in patients with CKD. We cover the clinical association between renal dysfunction and cerebrovascular disease including stroke, silent brain infarct, cerebral small vessel disease, microbleeds, and white matter hyperintensity, and discuss the underlying mechanisms.

Dipeptidyl peptidase 3 plasma levels predict cardiogenic shock and mortality in acute coronary syndromes.

Dipeptidyl peptidase 3 (DPP3) is a protease involved in the degradation of angiotensin II which disturbs peripheral blood pressure regulation and compromises left ventricular function. This study examined the relationship of circulating DPP3 (cDPP3) with cardiogenic shock (CS) and mortality in patients presenting with acute coronary syndromes (ACS). Plasma cDPP3 levels were assessed at baseline and 12-24 hours after presentation in patients with ACS prospectively enrolled into the multicentre SPUM-ACS study (n = 4787). Circulating DPP3 levels were associated with in-hospital CS when accounting for established risk factors including the ORBI risk score (per log-2 increase, hazard ratio [HR] 1.38, 95% confidence interval [CI] 1.05-1.82, P = 0.021). High cDPP3 was as an independent predictor of mortality at 30 days (HR 1.87, 95% CI 1.36-2.58, P < 0.001) and at 1 year (HR 1.61, 95% CI 1.28-2.02, P < 0.001) after adjustment for established risk factors and the GRACE 2.0 score. Compared to values within the normal range, persistently elevated cDPP3 levels at 12-24 hours were associated with 13.4-fold increased 30-day mortality risk (HR 13.42, 95% CI 4.86-37.09, P < 0.001) and 5.8-fold increased 1-year mortality risk (HR 5.79, 95% CI 2.70-12.42, P < 0.001). Results were consistent across various patient subgroups. This study identifies cDPP3 as a novel marker of CS and increased mortality in patients with ACS. Circulating DPP3 offers prognostic information beyond established risk factors and improves early risk assessment.

ChatGPT and most frequent urological diseases: analysing the quality of information and potential risks for patients.

Artificial intelligence (AI) is a set of systems or combinations of algorithms, which mimic human intelligence. ChatGPT is software with artificial intelligence which was recently developed by OpenAI. One of its potential uses could be to consult the information about pathologies and treatments. Our objective was to assess the quality of the information provided by AI like ChatGPT and establish if it is a secure source of information for patients. Questions about bladder cancer, prostate cancer, renal cancer, benign prostatic hypertrophy (BPH), and urinary stones were queried through ChatGPT 4.0. Two urologists analysed the responses provided by ChatGPT using DISCERN questionary and a brief instrument for evaluating the quality of informed consent documents. The overall information provided in all pathologies was well-balanced. In each pathology was explained its anatomical location, affected population and a description of the symptoms. It concluded with the established risk factors and possible treatment. All treatment answers had a moderate quality score with DISCERN (3 of 5 points). The answers about surgical options contain the recovery time, type of anaesthesia, and potential complications. After analysing all the responses related to each disease, all pathologies except BPH achieved a DISCERN score of 4. ChatGPT information should be used with caution since the chatbot does not disclose the sources of information and may contain bias even with simple questions related to the basics of urologic diseases.

Trio-based GWAS identifies novel associations and subtype-specific risk factors for cleft palate

Cleft palate (CP) is one of the most common craniofacial birth defects; however, there are relatively few established genetic risk factors associated with its occurrence despite high heritability. Historically, CP has been studied as a single phenotype, although it manifests across a spectrum of defects involving the hard and/or soft palate. We performed a genome-wide association study using transmission disequilibrium tests of 435 case-parent trios to evaluate broad risks for any cleft palate (ACP) (n= 435), and subtype-specific risks for any cleft soft palate (CSP), (n= 259) and any cleft hard palate (CHP) (n= 125). We identified a single genome-wide significant locus at 9q33.3 (lead SNP rs7035976, p= 4.24×10-8) associated with CHP. One gene at this locus, angiopoietin-like 2 (ANGPTL2), plays a role in osteoblast differentiation. It is expressed both in craniofacial tissue of human embryos and developing mouse palatal shelves. We found 19 additional loci reaching suggestive significance (p<5×10-6), of which only one overlapped between groups (chromosome 17q24.2, ACP and CSP). Odds ratios for the 20 loci were most similar across all 3 groups for SNPs associated with the ACP group, but more distinct when comparing SNPs associated with either subtype. We also found nominal evidence of replication (p<0.05) for 22 SNPs previously associated with orofacial clefts. Our study to evaluate CP risks in the context of its subtypes and we provide newly reported associations affecting the broad risk for CP as well as evidence of subtype-specific risks.

Association of mitochondrial DNA copy number with chronic kidney disease in older adults

BackgroundMitochondrial dysfunction in kidney cells has been implicated in the pathogenesis of chronic kidney disease (CKD). Estimation of mitochondrial DNA copy number (mtDNA-CN) is considered a convenient method for representing mitochondrial function in large samples. However, no study has investigated the association between mtDNA-CN and CKD in older adults with the highest prevalence. The objective is to examine cross-sectional and prospective associations between mtDNA-CN values and CKD risk in older adults to determine whether mtDNA-CN represents a novel potential biomarker for the recognition of CKD risk.Patients and methodsIn a Chinese community-based cohort of over 65-year-olds, we included 14,467 participants (52.6% females). CKD was defined by eGFR < 60 mL/min/1.73 m2 or ICD-10 codes (patients = 3831 (26.5%)). Participants had peripheral blood levels of mtDNA-CN calculated from probe intensities of the Axiom CAS Array.ResultsThe risk of CKD prevalence decreased with mtDNA-CN per 1-SD increment, independent of established risk factors for older CKD (odds ratio [OR] per SD 0.90, 95% confidence interval [CI] 0.86, 0.93, P < 0.001), and has comparable strength of association with these established risk factors. Furthermore, the progression of kidney function was stratified according to the worsening of eGFR categories. The risk of kidney function progression to a more severe stage gradually decreased as the mtDNA-CN increased (P trend < 0.001). Non-CKD participants in the highest quartile of mtDNA-CN had a lower risk of developing CKD compared to the lowest quartile within 2 years of follow-up, reducing the risk of CKD by 36% (95% CI 0.42, 0.97; P = 0.037).ConclusionsBased on the analysis of the largest sample to date investigating the association between mtDNA-CN and CKD in older adults, higher levels of mtDNA-CN were found to be associated with a lower risk of CKD, suggesting that a reduced level of mtDNA-CN is a potential risk factor for CKD.

The association between triglyceride glucose index and arthritis: a population-based study

ObjectivesInsulin resistance is a well-established contributor to inflammation; however, the specific association between the triglyceride glucose (TyG) index, a biomarker reflecting insulin resistance, and arthritis remains unexplored. As a result, the main aim of this study was to examine the correlation between the TyG index and arthritis.MethodsThis observational study used data from the National Health and Nutrition Examination Survey (NHANES), which was conducted between 2007 and 2018. To investigate the relationship between the TyG index and arthritis, various statistical analyses were employed, including weighted multivariable logistic regression analysis, subgroup analysis, curve fit analysis, and threshold effect analysis.ResultsIn total, 14,817 patients were enrolled in the trial, with 4,191 individuals (28.29%) diagnosed with arthritis. An increased risk of arthritis was found to be significantly correlated with higher TyG index values (odds ratio OR = 1.15, 95% confidence interval CI: 1.07–1.23), according to the results of multivariable logistic regression analysis after full adjustment. Subgroup analysis and interaction tests further indicated that the TyG index exhibited an additive effect when combined with other established risk factors, including age (OR = 1.29; 95% CI: 1.17–1.41), body mass index (BMI) (OR = 1.43; 95% CI: 1.24–1.69), and diabetes (OR = 1.20; 95% CI: 1.11–1.31). Additionally, curve fit analysis and threshold effect analysis demonstrated a nonlinear relationship with a breakpoint identified at 8.08 µmol/L.ConclusionThe TyG index was positively correlated with arthritis in adults under 60 years of age in the United States who had normal weight and no diabetes. Further large-scale prospective studies are warranted for a comprehensive analysis of the role of the TyG index in arthritis.

Diabetes in childhood cancer survivors: emerging concepts in pathophysiology and future directions.

With advancements in cancer treatment and supportive care, there is a growing population of childhood cancer survivors who experience a substantial burden of comorbidities related to having received cancer treatment at a young age. Despite an overall reduction in the incidence of most chronic health conditions in childhood cancer survivors over the past several decades, the cumulative incidence of certain late effects, in particular diabetes mellitus (DM), has increased. The implications are significant, because DM is a key risk factor for cardiovascular disease, a leading cause of premature death in childhood cancer survivors. The underlying pathophysiology of DM in cancer survivors is multifactorial. DM develops at younger ages in survivors compared to controls, which may reflect an "accelerated aging" phenotype in these individuals. The treatment-related exposures (i.e., chemotherapy, radiation) that increase risk for DM in childhood cancer survivors may be more than additive with established DM risk factors (e.g., older age, obesity, race, and ethnicity). Emerging research also points to parallels in cellular processes implicated in aging- and cancer treatment-related DM. Still, there remains marked inter-individual variability regarding risk of DM that is not explained by demographic and therapeutic risk factors alone. Recent studies have highlighted the role of germline genetic risk factors and epigenetic modifications that are associated with risk of DM in both the general and oncology populations. This review summarizes our current understanding of recognized risk factors for DM in childhood cancer survivors to help inform targeted approaches for disease screening, prevention, and treatment. Furthermore, it highlights the existing scientific gaps in understanding the relative contributions of individual therapeutic exposures and the mechanisms by which they exert their effects that uniquely predispose this population to DM following cancer treatment.

Impact of Indoor Air Quality and Breathing on Back and Neck Pain: A Systematic Review.

Back pain and neck pain are important public health concerns and are among the most common and disabling conditions globally. However, the relationships among indoor air quality (IAQ), breathing parameters (pulmonary function, respiratory disorders), and back pain and neck pain have not been adequately assessed. The purpose of this study was to systematically review the literature about the impact of IAQ and breathing parameters on back pain and neck pain (PROSPERO ID: CRD42022380515). CINAHL, EMBASE, PEDRo, and PubMed databases were searched through January 19, 2023. Inclusion criteria for study eligibility were observational studies (except case reports) or randomized controlled trials (RCTs), published in peer-reviewed journals in the English language, human research, original research, examined the relationships between IAQ, or breathing parameters with back pain or neck pain. Review procedures were conducted and reported according to PRISMA recommendations. Empirical evidence statements were developed for observational studies, and grades of evidence statements were developed for RCTs. Sixty-seven eligible studies were found (54 observational studies and 13 RCTs) that enrolled 345,832 participants. None of the studies assessed the combined impact of IAQ and breathing parameters on back pain or neck pain. No level 1 studies were found, which precludes making strong statements about causality and strong recommendations about the efficacy of IAQ and breathing exercise interventions for reducing pain and disability related to back pain and neck pain. Evidence indicates that poor IAQ and respiratory disorders are related to an increased risk of back pain and neck pain. Conflicting evidence exists about the association between pulmonary function with back pain and neck pain. Evidence for breathing exercise interventions was mixed with numerous limitations. This review provides preliminary evidence on the relationships of IAQ and breathing parameters with back pain and neck pain, which can be used to guide future research and clinical implementation efforts. Assuming positive findings in subsequent research, a wide range of stakeholders involved with this complex human-building-environment interface can be equipped to address IAQ and breathingparameters, along with other established risk factors to help those suffering from back pain and neck pain.

Epidemiology of Motoric Cognitive Risk Syndrome in the Kerala Einstein Study: Protocol for a Prospective Cohort Study.

The southern India state of Kerala has among the highest proportion of older adults in its population in the country. An increase in chronic age-related diseases such as dementia is expected in the older Kerala population. Identifying older individuals early in the course of cognitive decline offers the best hope of introducing preventive measures early and planning management. However, the epidemiology and pathogenesis of predementia syndromes at the early stages of cognitive decline in older adults are not well established in India. The Kerala Einstein Study (KES) is a community-based cohort study that was established in 2008 and is based in the Kozhikode district in Kerala state. KES aims to establish risk factors and brain substrates of motoric cognitive risk syndrome (MCR), a predementia syndrome characterized by the presence of slow gait and subjective cognitive concerns in individuals without dementia or disability. This protocol describes the study design and procedures for this KES project. KES is proposing to enroll a sample of 1000 adults ≥60 years old from urban and rural areas in the Kozhikode district of Kerala state: 200 recruited in the previous phase of KES and 800 new participants to be recruited in this project. MCR is the cognitive phenotype of primary interest. The associations between previously established risk factors for dementia as well as novel risk factors (apathy and traumatic brain injury) and MCR will be examined in KES. Risk factor profiles for MCR will be compared between urban and rural residents as well as with individuals who meet the criteria for mild cognitive impairment (MCI). Cognitive and physical function, medical history and medications, sociodemographic characteristics, lifestyle patterns, and activities of daily living will be evaluated. Participants will also undergo magnetic resonance imaging and electrocardiogram investigations. Longitudinal follow-up is planned in a subset of participants as a prelude to future longitudinal studies. KES (2R01AG039330-07) was funded by the US National Institutes of Health in September 2019 and received approval from the Indian Medical Council of Research to start the study in June 2021. We had recruited 433 new participants from urban and rural sites in Kozhikode as of May 2023: 41.1% (178/433) women, 67.7% (293/433) rural residents, and 13.4% (58/433) MCR cases. Enrollment is actively ongoing at all the KES recruitment sites. KES will provide new insights into risk factors and brain substrates associated with MCR in India and will help guide future development of regionally specific preventive interventions for dementia. DERR1-10.2196/49933.