Association between lifetime smoking and cutaneous squamous cell carcinoma: A 2-sample Mendelian randomization study.

Background/Purpose: Cutaneous squamous cell carcinoma (cSCC) is one of the most common malignancies worldwide. While several environmental risk factors for cSCC are well established, there is conflicting evidence on cigarette smoking (and its potential causal effect) and cSCC risk. Furthermore, it is unclear if these potential associations represent causal, modifiable risk factors for cSCC development. This study aims to assess the nature of the associations between cigarette smoking traits (smoking initiation, amount smoked, and lifetime smoking exposure) and cSCC risk using two-sample Mendelian randomization analyses. Methods: Genetic instruments, based on common genetic variants associated with cigarette smoking traits (P < 5 × 10-8), were derived from published genome-wide association studies (GWASs). For cSCC, we used GWAS summary statistics from the Kaiser Permanente GERA cohort (7701 cSCC cases and 60,167 controls; all non-Hispanic Whites). Results: We found modest evidence that genetically determined lifetime smoking was associated with cSCC (inverse-variance weighted method: OR[95% CI] = 1.47[1.09-1.98]; P = .012), suggesting it may be a causal risk factor for cSCC. We did not detect any evidence of association between genetically determined smoking initiation or amount smoked and cSCC risk. Conclusion: Study findings highlight the importance of smoking prevention and may support risk-stratified cSCC screening strategies based on carcinogen exposure and other genetic and clinical information.

Global epidemiology of actinic keratosis in the general population: a systematic review and meta-analysis.

BACKGROUND: Actinic keratosis (AK) is a common dermatological condition, and among the most common dermatological diagnoses in older populations. Although the prevalence of AK depends on demographic and environmental factors, little is known about the global context of AK. OBJECTIVES: To provide a comprehensive and updated analysis of the global prevalence rate and incidence of AK in the general population through a systematic review and meta-analysis, and - through subgroup analyses - to identify high-risk phenotypes, demographic and lifestyle risk factors and regional variations in disease prevalence. METHODS: A systematic search of Embase, MEDLINE, Web of Science and Google Scholar was performed on 20 May 2022. Two reviewers independently screened and assessed the quality of each study using a validated critical appraisal checklist. Epidemiological measurements (e.g. prevalence) from individual studies performed in the general population were then pooled in a random-effects meta-analysis. Subgroup analyses (i.e. population age, geographical region, occupation, sex and study quality) were conducted. RESULTS: Of the 65 articles that made it through the full-text screening, 60 reported a point prevalence. A meta-analysis of these articles yielded an overall point prevalence of 14% [95% confidence interval (CI) 14-15]. In further analyses, the calculated prevalence rate varied depending on subgroup. The pooled incidence rate from the seven eligible studies analysed was 1928 per 100 000 person-years (PY; 95% CI -439 to 4294). CONCLUSIONS: This comprehensive meta-analysis provides an updated global prevalence rate of AK of 14%, indicating a significant worldwide disease burden. The incidence rate of AK was found to be 1928 per 100 000 PY, emphasizing a growing public health concern. However, high heterogeneity among studies suggests that various factors influence the AK prevalence rate, necessitating further research to understand the observed differences.

Longitudinal Assessment of the Prevalence of Actinic Keratosis and Extensive Risk Factor Evaluation: An Update from the Rotterdam Study.

Population-based studies available to analyze the prevalence, risk factors, and longitudinal outlook of actinic keratoses (AKs) are limited. These features mentioned earlier were assessed using Rotterdam study participants aged ≥40 years who underwent a full-body skin examination by a dermatology-trained physician. ORs with 95% confidence intervals were calculated for the associations between risk factors and the presence of AK. Among 8,239 eligible participants, the prevalence of one or more AKs was 21.1% (95% confidence interval = 20.2-22.0) and was higher in men. Male sex, age, lighter hair and eye color, baldness, genetic risk score, and digital photoaging measures (digitally assessed pigmented spots, telangiectasias, and global facial wrinkling) had a positive association with AK. Cigarette smokers had reduced odds of having AK, with current smokers having the lowest risk. Among patients with two AK assessments, there was no difference in the presence of AK during follow-up between treated and untreated participants. In conclusion, genetic risk score and digital photoaging measures showed associations with increased lesion count. At the individual level, patients were most likely to decrease in AK severity group over time, possibly regardless of whether or not participants were treated.

Nocturia and electrocardiographic abnormalities among patients at an inner-city cardiology clinic.

AIMS: Nocturia has been increasingly recognized as a potential manifestation of cardiovascular disease. However, the relationship between nocturia and electrocardiographic (ECG) abnormalities has not been studied. This study aims to characterize the diagnostic utility of nocturia in identifying left ventricular hypertrophy (LVH), left atrial enlargement (LAE), and prolonged QTc on ECG. METHODS: Retrospective analysis of nocturnal voiding frequency and contemporaneous ECG data from consecutive patients evaluated at a university-based outpatient cardiology clinic. Three sets of three incremental binary multiple logistic regression models controlling for (1) age, (2) sex and race, and (3) body mass index, hypertension, diabetes mellitus, and diuretic utilization were performed to determine whether nocturia was predictive of LVH, LAE, and prolonged QTc. RESULTS: Included patients (n = 143, 77.6% nocturia) were predominantly African-American (89.5%), female (74.1%), and obese (61.5%), of whom 44.1%, 41.3%, and 27.3% had LVH, LAE, and prolonged QTc, respectively. Older age, African-American race, obesity, hypertension, diuretic use, LVH, and LAE were significantly associated with nocturia on univariate analysis. No significant differences were observed in the strength of associations between nocturia and LVH, LAE, or QTc prolongation based on age. Nocturia independently predicted LVH in Models I-III (odds ratios [ORs], 2.99-3.20; relative risks [RRs], 1.18 for all, p ≤ .046) and LAE in Models I-III (ORs, 4.24-4.72; RRs, 1.21 for all, p ≤ .015). No significant associations were observed between nocturia and prolonged QTc. CONCLUSIONS: Nocturia may be a risk marker for underlying structural cardiac abnormalities.

Sodium restriction improves nocturia in patients at a cardiology clinic.

This study aims to determine whether dietary sodium restriction counseling decreases nocturnal voiding frequency in cardiology patients with concomitant nocturia. Patients who had established care at a cardiology clinic from 2015 to 2018 reporting ≥1 average nocturnal void(s) underwent a comprehensive sodium intake interview by their cardiologist, who provided them with individualized strategies for dietary sodium reduction and assessed adherence at follow-up. Average nocturnal voiding frequency and dietary adherence were documented in the medical record. A nocturia database was compiled for retrospective analysis. A total of 74 patients were included. Patients considered to be adherent with dietary sodium restriction at follow-up (n = 56) demonstrated a decrease in median nocturia frequency (2.5 [2.3-3.0] vs 1.0 [1.0-2.0] voids, P < .001). Among nonadherent patients (n = 18), median nocturia frequency did not significantly change from baseline to follow-up (2.0 [1.5-3.8] vs 2.0 [1.5-4.8] voids, P = .423). Median changes were significantly different between the adherent and nonadherent groups (P < .001). Examination of second follow-up available from 37 patients showed a continued effect. In conclusion, adherence with dietary sodium counseling appears to improve nocturia. Accordingly, dietary modification may represent an important adjunct therapy to lifestyle and pharmacologic interventions for decreasing nocturia frequency. Reduction in nocturnal voiding frequency may also reflect an additional benefit of dietary sodium restriction in accordance with best practice standards for cardiovascular disease.

Polyploid Superficial Cells that Maintain the Urothelial Barrier Are Produced via Incomplete Cytokinesis and Endoreplication.

The urothelium is an epithelia barrier lined by a luminal layer of binucleated, octoploid, superficial cells. Superficial cells are critical for production and transport of uroplakins, a family of proteins that assemble into a waterproof crystalline plaque that helps protect against infection and toxic substances. Adult urothelium is nearly quiescent, but rapidly regenerates in response to injury. Yet the mechanism by which binucleated, polyploid, superficial cells are produced remains unclear. Here, we show that superficial cells are likely to be derived from a population of binucleated intermediate cells, which are produced from mononucleated intermediate cells via incomplete cytokinesis. We show that binucleated intermediate and superficial cells increase DNA content via endoreplication, passing through S phase without entering mitosis. The urothelium can be permanently damaged by repetitive or chronic injury or disease. Identification of the mechanism by which superficial cells are produced may be important for developing strategies for urothelial repair.

Limited health care access impairs glycemic control in low income urban African Americans with type 2 diabetes.

Limited access to health care is associated with adverse outcomes, but few studies have examined its effect on glycemic control in minority populations. Our observational cross-sectional study examined whether differences in health care access affected hemoglobin A1c (HbA1c) levels in 605 patients with diabetes (56% women; 89% African American; average age, 50 years; 95% with type 2 diabetes) initially treated at a municipal diabetes clinic. Patients who had difficulty obtaining care had higher A1c levels (9.4% vs. 8.7%; p=0.001), as did patients who used acute care facilities (9.5%; p<0.001) or who had no usual source of care (10.3%; p<0.001) compared with those who sought care at doctors' offices or clinics (8.6%). In adjusted analyses, HbA1c was higher in persons who gave a history of trouble obtaining medical care (0.57%; p=0.04), among persons who primarily used an acute care facility to receive their health care (0.49%; p=0.047), and in patients who reported not having a usual source of care (1.08%; p=0.009). Policy decisions for improving diabetes outcomes should target barriers to health care access and focus on developing programs to help high-risk populations maintain a regular place of health care.

Barriers to diabetes education in urban patients: perceptions, patterns, and associated factors.

PURPOSE: This study explored patients' perceptions of barriers to diabetes education among a mostly African American population of adults with diabetes. METHODS: A survey was conducted among 605 new patients attending an urban outpatient diabetes clinic. The questionnaire gathered information on issues patients believed would adversely affect their ability to learn about diabetes. The type and frequency of education barriers were evaluated, and variables associated with reporting an obstacle were analyzed. RESULTS: Average patient age was 50 years, diabetes duration was 5.6 years, body mass index was 32 kg/m2, and hemoglobin A1C was 9.1%. The majority (56%) were women, 89% were African American, and 95% had type 2 diabetes. Most respondents (96%) had received some prior instruction in diabetes care; however, 53% anticipated future difficulties learning about diabetes. The most commonly cited concerns were poor vision (74%) and reading problems (29%). Patients with a perceived barrier to diabetes education were older (P < .001) than were persons without a barrier, and they differed in both employment and educational status (both P < .001). In adjusted analyses, older age, male gender, being disabled, and having an elementary education or less were associated with a significantly increased likelihood of having a barrier to diabetes education, whereas having a college education decreased the odds. Higher hemoglobin A1C levels also tended to be associated with a greater chance of reporting an education barrier (P = .05). CONCLUSIONS: A substantial number of persons anticipated a barrier to diabetes education. Interventions at multiple levels that address the demographic and socioeconomic obstacles to diabetes education are needed to ensure successful self-management training.

Evolving demographics and disparities in an urban diabetes clinic: implications for diabetes education and treatment.

OBJECTIVES: To compare demographics and disease characteristics in a multiethnic diabetes clinic population to identify changes over time. DESIGN: Analysis and comparison of demographics and disease characteristics of diabetes patients, recorded electronically at intake over 10 years. SETTING: An urban outpatient diabetes clinic. PATIENTS: A total of 8,551 African-American (88%), White (7%), or Hispanic (3%) patients (average age, 52 years; mean diabetes duration, 5.1 years; 59% women). MAIN OUTCOME MEASURES: Proportion of patients by ethnic group, age, diabetes duration, initial hemoglobin A1c, and body mass index. RESULTS: Between 1992 and 2001, the percentage of African-American patients was relatively unchanged (from 87.6% to 87.2%; P=.2), White patients decreased (from 9% to 5%; P=.0006), and Hispanic patients increased (from 1.3% to 5.5%; P<.0001). Among African-American patients, average age decreased from 52 to 50 years (P=.015), diabetes duration decreased from 5.6 years to 4.3 years (P=.0003), initial hemoglobin A1c decreased from 9.3% to 8.8% (P<.0001), and body mass index increased from 31 kg/m2 to 32.1 kg/m2 (P=.0001). Compared with African-American and White patients, Hispanic patients were younger (P<.0001) and had a lower body mass index (P<.0001) but had hemoglobin A1c comparable to that of African-American patients (9.3% vs 9.1%; P=.45) and higher than that of White patients (9.3% vs 8.7%; P=.0022). CONCLUSIONS: The demographic and disease profiles of patients in this urban diabetes clinic have shifted, and disparities in glycemic control and obesity exist. Modifications in treatment and education approaches may be necessary to compensate for a changing patient population.

Management of insulin therapy in urban diabetes patients is facilitated by use of an intelligent dosing system.

The Intelligent Dosing System (IDS, Dimensional Dosing Systems, Inc., Wexford, PA) is a software suite that incorporates patient-specific, dose-response data in a mathematical model, and then calculates the new dose of agent needed to achieve the next desired therapeutic goal. We evaluated use of the IDS for titrating insulin therapy. The IDS was placed on handheld platforms and provided to practitioners to use in adjusting total daily insulin dose. Fasting glucose, random glucose, and hemoglobin A1c were used as markers against which insulin could be adjusted. Values of markers expected at the next follow-up visit, as predicted by the model, were compared with levels actually observed. For 264 patients, 334 paired visits were analyzed. Average age was 54 years, diabetes' duration was 10 years, and body mass index was 33.2 kg/m(2); 57% were female, 88% were African American, and 92% had type 2 diabetes. The correlation between IDS suggested and actual prescribed total daily dose was high (r = 0.99), suggesting good acceptability of the IDS by practitioners. Significant decreases in fasting glucose, random glucose, and hemoglobin A1c levels were seen (all P < 0.0001). No significant difference between average expected and observed follow-up fasting glucose values was found (145 vs. 149 mg/dL, P = 0.42), and correlation was high (r = 0.79). Mean observed random glucose value at follow-up was comparable to the IDS predicted level (167 vs. 168 mg/dL, P = 0.97), and correlation was high (r = 0.73). Observed follow-up hemoglobin A1c was higher than the value expected (7.9% vs. 7.4%, P < 0.0055), but correlation was good (r = 0.70). These analyses suggest the IDS is a useful adjunct for decisions regarding insulin therapy even when using a variety of markers of glucose control, and can be used by practitioners to assist in attainment of glycemic goals.

Exercise preferences and barriers in urban African Americans with type 2 diabetes.

PURPOSE: The purpose of this study was to determine physical activity preferences and barriers to exercise in an urban diabetes clinic population. METHODS: A survey was conducted of all patients attending the clinic for the first time. Evaluation measures were type and frequency of favorite leisure-time physical activity, prevalence and types of reported barriers to exercise, and analysis of patient characteristics associated with reporting an obstacle to exercise. RESULTS: For 605 patients (44% male, 89% African American, mean age = 50 years, mean duration of diabetes = 5.6 years), the average frequency of leisure activity was 3.5 days per week (mean time = 45 minutes per session). Walking outdoors was preferred, but 52% reported an exercise barrier (predominantly pain). Patients who cited an impediment to physical activity exercised fewer days per week and less time each session compared with persons without a barrier. Increasing age, body mass index, college education, and being a smoker increased the odds of reporting a barrier; being male decreased the chances. Men reported more leisure-time physical activity than women. Exercise preferences and types of barriers changed with age. CONCLUSIONS: Recognition of patient exercise preferences and barriers should help in developing exercise strategies for improving glycemic control.