Cardiovascular Outcomes of KCNJ5 Mutated Aldosterone-Producing Adenoma: A Systematic Review.

BACKGROUND: While clinical features of KCNJ5-mutated aldosterone-producing adenoma (APA) have been reported, evidence of its clinical outcomes is lacking. We aimed to synthesize available literature about the associations between KCNJ5 mutation with cardiovascular and metabolic outcomes among patients with APA. METHODS: In this systematic review of observational studies, MEDLINE and Embase were searched through August 2022. Two independent authors screened the search results and extracted data from eligible observational studies investigating cardiovascular or metabolic outcomes between KCNJ5-mutated APAs and KCNJ5-non-mutated APAs. Risk of Bias In Non-randomized Studies of Interventions was used to assess the quality of the included studies. RESULTS: A total of 573 titles/abstracts were screened and after the expert opinion of the literature, full text was read in 20 titles/abstracts, of which 12 studies were included. Across 3 studies comparing the baseline or change in the cardiac function between KCNJ5-mutated APAs and KCNJ5-non-mutated APAs, all studies reported the association between impaired cardiac functions and KCNJ5 mutation status. Among 6 studies evaluating the cure of hypertension after surgery, all studies showed that KCNJ5 mutation was significantly associated with the cure of hypertension. In quality assessment, 7 studies were at serious risk of bias, while the remaining studies were at moderate risk of bias. CONCLUSIONS: This systematic review provided evidence of the significant association between KCNJ5 mutation and unfavorable cardiovascular outcomes in patients with primary aldosteronism. Further research is needed to improve the quality of evidence on this topic and elucidate the underlying mechanisms of the potential burden of KCNJ5 mutation.

Depression Onset After a Spouse's Cardiovascular Event.

Importance: Although cardiovascular disease (CVD) is a known risk factor for depression, evidence is lacking regarding whether and to what extent a spouse's CVD is associated with the subsequent mental health of individuals. Objective: To examine the association between CVD onset in spouses and subsequent depression. Design, Setting, and Participants: This cohort study examined 277 142 matched married couples enrolled in the Japan Health Insurance Association health insurance program between April 2015 and March 2022, covering approximately 40% of the working-age population in Japan. Index individuals (primary insured) whose spouses (dependent) experienced incident CVD between April 2016 and March 2022 were 1:1 matched to controls whose spouses did not experience CVD. Matching was based on age, sex, income, or the onset date of the spouses' CVD. Data analysis was conducted from April 2016 to March 2022. Exposure: Spousal onset of CVD between fiscal years 2016 and 2021. The International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes were used to identify the composite CVD outcomes (stroke, heart failure, and myocardial infarction). Main Outcomes and Measures: Multivariate Cox proportional hazards models were used to investigate the association between spouses' new-onset CVD and individuals' depression, adjusting for sociodemographic characteristics and comorbidities of index individuals (diabetes, hypertension, and CVD) and spouses (diabetes, hypertension, and depression). Subgroup analyses were conducted according to sex, age, income levels, and history of CVD. Results: Among 277 142 matched pairs of married couples, 263 610 (95.1%) had a male index individual; the mean (SD) age of index individuals was 58.2 (10.2) years. A new onset of depression was observed in 4876 individuals (1.8%). In multivariable Cox models, there was an association between the spouse's CVD and the individuals' depression (hazard ratio, 1.13 [95% CI, 1.07-1.20]). The subgroup analysis found no evidence of heterogeneity in sex, age, income level, or CVD history. The results were consistent when additionally adjusted for health behaviors (smoking, alcohol consumption, physical activity, and use of antihypertensive drugs) and objectively measured physical health conditions (body mass index, blood pressure, cholesterol levels, glucose levels, and estimated glomerular filtration rate) (hazard ratio, 1.16 [95% CI, 1.06-1.28]). Conclusions and Relevance: In this nationwide cohort study of matched couples, a spouse's onset of CVD was associated with an increased risk of an individual's depression. These findings highlight the importance of preventive care for mental health disorders in individuals whose spouses experience incident CVD.

Identifying primary aldosteronism patients who require adrenal venous sampling: a multi-center study.

Adrenal venous sampling (AVS) is crucial for subtyping primary aldosteronism (PA) to explore the possibility of curing hypertension. Because AVS availability is limited, efforts have been made to develop strategies to bypass it. However, it has so far proven unsuccessful in applying clinical practice, partly due to heterogeneity and missing values of the cohorts. For this purpose, we retrospectively assessed 210 PA cases from three institutions where segment-selective AVS, which is more accurate and sensitive for detecting PA cases with surgical indications, was available. A machine learning-based classification model featuring a new cross-center domain adaptation capability was developed. The model identified 102 patients with PA who benefited from surgery in the present cohort. A new data imputation technique was used to address cross-center heterogeneity, making a common prediction model applicable across multiple cohorts. Logistic regression demonstrated higher accuracy than Random Forest and Deep Learning [(0.89, 0.86) vs. (0.84, 0.84), (0.82, 0.84) for surgical or medical indications in terms of f-score]. A derived integrated flowchart revealed that 35.2% of PA cases required AVS with 94.1% accuracy. The present model enabled us to reduce the burden of AVS on patients who would benefit the most.

The effect of poverty on the relationship between household education levels and obesity in U.S. children and adolescents: an observational study.

Background: Although ample evidence has shown the link between childhood obesity and socioeconomic status including family income and household education levels, the mediating role of poverty in the association between household education levels and childhood obesity is unclear. This study aimed to quantify the extent to which family poverty levels contribute to the association between household education levels and obesity among US children and adolescents. Methods: This cohort study used the nationally representative data of 21,754 US children and adolescents aged 6-17 years (National Health and Nutrition Examination Survey 1999-2018). We applied mediation analysis of the association between household education levels (less than high school, high school, and college or above) and obesity mediated through poverty (≤138% vs. >138% federal poverty level), adjusting for demographic characteristics of household head and their offspring. Obesity was defined as age- and sex-specific body mass index in the 95th percentile or greater using the 2000 Centers for Disease Control and Prevention growth charts. Findings: Among 21,754 children and adolescents (weighted N = 43,544,684; mean age, 11.6 years; female, 49%), 9720 (weighted percentage, 33.0%) were classified as living in poverty and 4671 (weighted percentage, 19.1%) met the criteria for obesity. Low household education level (less than high school) showed increased risks of poverty (adjusted relative risk [95% CI], 5.82 [4.90-6.91]) and obesity (adjusted relative risk [95% CI], 1.94 [1.68-2.25]) compared to high household education level (college or above). We also quantified that poverty mediated 18.9% of the association between household education levels and obesity among children and adolescents. The mediation effect was consistently observed across age, gender, and race/ethnicity. Interpretation: Poverty mediated the association between the low educational status of household heads and their offspring's obesity. Our findings highlight the importance of reducing obesity risk among the low-income population to minimize the burden of intergenerational health disparities due to socioeconomic status. Funding: Japan Society for the Promotion of Sciences (22K17392).

Neoadjuvant use of oncolytic herpes virus G47Δ prevents local recurrence after insufficient resection in tongue cancer models.

A complete resection of tongue cancer is often difficult. We investigate the usefulness of administering G47Δ (teserpaturev), a triple-mutated oncolytic herpes simplex virus type 1, prior to resection. G47Δ exhibits good cytopathic effects and replication capabilities in all head and neck cancer cell lines tested. In an orthotopic SCCVII tongue cancer model of C3H/He mice, an intratumoral inoculation with G47Δ significantly prolongs the survival. Further, mice with orthotopic tongue cancer received neoadjuvant G47Δ (or mock) therapy with or without "hemilateral" resection, the maximum extent avoiding surgical deaths. Neoadjuvant G47Δ and resection led to 10/10 survival (120 days), whereas the survivals for G47Δ alone and resection alone were 6/10 and 5/10, respectively: all control animals died by day 11. Furthermore, 100% survival was achieved with neoadjuvant G47Δ therapy even when the resection area was narrowed to "partial," providing insufficient resection margins, whereas hemilateral resection alone caused death by local recurrence in half of the animals. G47Δ therapy caused increased number of tumor-infiltrating CD8+ and CD4+ cells, increased F4/80+ cells within the residual tongues, and increased expression of immune-related genes in and around the tumor. These results imply that neoadjuvant use of G47Δ is useful for preventing local recurrence after tongue cancer surgery.

Association Between Educational Status and Mortality According to Diabetes Status Among US Adults.

Objective: To examine differences in the association between educational attainment and mortality by the presence of diabetes and diabetic retinopathy (DR)-a major complication of diabetes. Patients and Methods: We used a nationally representative sample of 54,924 US adults aged 20 years or older with diabetes from the National Health and Nutrition Examination Survey 1999-2018 and its mortality data through 2019. We applied the multivariable Cox proportional hazard models to investigate the associations between educational attainment (low, less than high school; middle, high school; and high, more than high school) and all-cause mortality according to diabetes status: nondiabetes, diabetes without DR, and diabetes with DR. Differences in the survival rate by educational attainment were evaluated using the slope inequality index (SII). Results: Among the 54,924 participants (mean age, 49.9 years), adults in the low educational group reported an increased risk of all-cause mortality compared with those of the high educational group in any diabetes status (nondiabetes-hazard ratio [HR], 1.69; 95% CI, 1.56-1.82; diabetes without DR-HR, 1.61; 95% CI, 1.37-1.90; diabetes with DR-HR, 1.43; 95% CI, 1.10-1.86). SIIs among the diabetes without DR group and diabetes with DR group were 22.17 and 20.87 per 1000 person-years, respectively, which were 2 times greater than those among the nondiabetes group (SII=9.94). Conclusion: The differences in the mortality risks owing to the educational attainment increased by the presence of diabetes regardless of the complication of DR. Our findings indicate that prevention of diabetes itself is critical to mitigate health disparities by socioeconomic status such as education status.

Retirement and cardiovascular disease: a longitudinal study in 35 countries.

BACKGROUND: Many countries have been increasing their state pension age (SPA); nonetheless, there is little consensus on whether retirement affects the risk of cardiovascular disease (CVD). This study examined the associations of retirement with CVD and risk factors. METHODS: We used harmonized longitudinal datasets from the Health and Retirement Study and its sister surveys in 35 countries. Data comprised 396 904 observations from 106 927 unique individuals aged 50-70 years, with a mean follow-up period of 6.7 years. Fixed-effects instrumental variable regressions were performed using the SPA as an instrument. RESULTS: We found a 2.2%-point decrease in the risk of heart disease [coefficient = -0.022 (95% confidence interval: -0.031 to -0.012)] and a 3.0%-point decrease in physical inactivity [-0.030 (-0.049 to -0.010)] among retirees, compared with workers. In both sexes, retirement was associated with a decreased heart disease risk, whereas decreased smoking was observed only among women. People with high educational levels showed associations between retirement and decreased risks of stroke, obesity and physical inactivity. People who retired from non-physical labour exhibited reduced risks of heart disease, obesity and physical inactivity, whereas those who retired from physical labour indicated an increased risk of obesity. CONCLUSIONS: Retirement was associated with a reduced risk of heart disease on average. Some associations of retirement with CVD and risk factors appeared heterogeneous by individual characteristics.

Association of Daily Step Patterns With Mortality in US Adults.

Importance: Previous studies have shown that individuals who regularly walk, particularly 8000 daily steps or more, experience lower mortality. However, little is known about the health benefits of walking intensively only a few days a week. Objective: To evaluate the dose-response association between the number of days an individual takes 8000 steps or more and mortality among US adults. Design, Setting, and Participants: This cohort study evaluated a representative sample of participants aged 20 years or older in the National Health and Nutrition Examination Surveys 2005-2006 who wore an accelerometer for 1 week and their mortality data through December 31, 2019. Data were analyzed from April 1, 2022, to January 31, 2023. Exposures: Participants were grouped by the number of days per week they took 8000 steps or more (0 days, 1-2 days, and 3-7 days). Main Outcomes and Measures: Multivariable ordinary least squares regression models were used to estimate adjusted risk differences (aRDs) for all-cause and cardiovascular mortality during the 10-year follow-up, adjusting for potential confounders (eg, age, sex, race and ethnicity, insurance status, marital status, smoking, comorbidities, and average daily step counts). Results: Among 3101 participants (mean [SD] age, 50.5 [18.4] years; 1583 [51.0%] women and 1518 [49.0%] men; 666 [21.5%] Black, 734 [23.7%] Hispanic, 1579 [50.9%] White, and 122 [3.9%] other race and ethnicity), 632 (20.4%) did not take 8000 steps or more any day of the week, 532 (17.2%) took 8000 steps or more 1 to 2 days per week, and 1937 (62.5%) took 8000 steps or more 3 to 7 days per week. Over the 10-year follow-up, all-cause and cardiovascular deaths occurred in 439 (14.2%) and 148 (5.3%) participants, respectively. Compared with participants who walked 8000 steps or more 0 days per week, all-cause mortality risk was lower among those who took 8000 steps or more 1 to 2 days per week (aRD, -14.9%; 95% CI -18.8% to -10.9%) and 3 to 7 days per week (aRD, -16.5%; 95% CI, -20.4% to -12.5%). The dose-response association for both all-cause and cardiovascular mortality risk was curvilinear; the protective association plateaued at 3 days per week. Different thresholds for the number of daily steps between 6000 and 10 000 yielded similar results. Conclusions and Relevance: In this cohort study of US adults, the number of days per week taking 8000 steps or more was associated with a lower risk of all-cause and cardiovascular mortality in a curvilinear fashion. These findings suggest that individuals may receive substantial health benefits by walking just a couple days a week.

Subtyping of Non-Small Cell Lung Carcinoma into Adenocarcinoma and Squamous Cell Carcinoma by Cytological Structural Features.

INTRODUCTION: This study aimed to clarify the diagnostic structural features in cytology specimens that are useful in subtyping non-small cell lung carcinoma (NSCLC) into adenocarcinoma (ADC) and squamous cell carcinoma (SQCC). METHODS: Cytology specimens (n = 233) of NSCLCs, which included ADCs (n = 149) and SQCCs (n = 84), were analyzed. The following cytological features were evaluated: isolated cell, flat sheet, three-dimensional cluster with irregular arrangement, papillary-like structure, micropapillary-like structure, acinar-like structure, palisading pattern, protrusion of nuclei at the periphery of the cluster, honeycomb pattern, streaming arrangement, three-dimensional sheets with regular arrangement, flattening at the periphery of the cluster, fuzzy pattern at the periphery of the cluster, and mutual inclusion. RESULTS: ADCs exhibited significantly higher frequencies of flat sheet (p < 0.001), papillary-like structure (p < 0.001), micropapillary-like structure (p = 0.028), acinar-like structure (p < 0.001), and protrusion of nuclei at the periphery of the cluster (p < 0.001) than SQCCs. The latter exhibited significantly higher frequencies of streaming arrangement (p < 0.001), three-dimensional sheets with regular arrangement (p < 0.001), flattening at the periphery of the cluster (p < 0.001), fuzzy pattern at the periphery of the cluster (p < 0.001), and mutual inclusion (p < 0.001) than ADCs. DISCUSSION: Cytological structural features, such as flat sheet, papillary-like structure, micropapillary-like structure, acinar-like structure, and protrusion of nuclei at the periphery of the cluster, indicated ADC, whereas streaming arrangement, three-dimensional sheets with regular arrangement, flattening at the periphery of the cluster, fuzzy pattern at the periphery of the cluster, and mutual inclusion indicated SQCC. Paying attention to these cytological structural features can enable the accurate subtyping of NSCLC into ADC and SQCC.

Association Between Aldosterone and Hypertension Among Patients With Overt and Subclinical Hypercortisolism.

Introduction: Hypertension is one of the most common clinical features of patients with overt and subclinical hypercortisolism. Although previous studies have shown the coexistence of autonomous cortisol and aldosterone secretion, it is unclear whether aldosterone plays a role in hypertension among patients with hypercortisolism. Therefore, we examined the associations of plasma aldosterone concentrations (PACs) with hypertension among patients with overt and subclinical hypercortisolism. Methods: This single-center retrospective cohort study included patients with adrenal tumor and serum cortisol levels after 1-mg dexamethasone suppression test >1.8 µg/dL (50 nmol/L). Using multivariable regression models adjusting for baseline characteristics, we investigated the association of PACs with systolic blood pressure and postoperative improvement of hypertension after the adrenalectomy. Results: Among 89 patients enrolled in this study (median age, 51 years), 21 showed clinical signs of Cushing syndrome (overt hypercortisolism) and 68 did not show clinical presentations (subclinical hypercortisolism). We found that higher PACs were significantly associated with elevated systolic blood pressure among patients with subclinical hypercortisolism (adjusted difference [95% CI] = +0.59 [0.19-0.99], P = 0.008) but not among those with overt hypercortisolism. Among 33 patients with subclinical hypercortisolism and hypertension who underwent adrenalectomy, the postoperative improvement of hypertension was significantly associated with higher PACs at baseline (adjusted risk difference [95% CI] = +1.45% [0.35-2.55], P = 0.01). Conclusion: These findings indicate that aldosterone may contribute to hypertension among patients with subclinical hypercortisolism. Further multi-institutional and population-based studies are required to validate our findings and examine the clinical effectiveness of the intervention targeting aldosterone for such patients.

The diagnostic ability to classify neoplasias occurring in inflammatory bowel disease by artificial intelligence and endoscopists: A pilot study.

BACKGROUND AND AIM: Although endoscopic resection with careful surveillance instead of total proctocolectomy become to be permitted for visible low-grade dysplasia, it is unclear how accurately endoscopists can differentiate these lesions, as classifying neoplasias occurring in inflammatory bowel disease (IBDN) is exceedingly challenging due to background chronic inflammation. We evaluated a pilot model of an artificial intelligence (AI) system for classifying IBDN and compared it with the endoscopist's ability. METHODS: This study used a deep convolutional neural network, the EfficientNet-B3. Among patients who underwent treatment for IBDN at two hospitals between 2003 and 2021, we selected 862 non-magnified endoscopic images from 99 IBDN lesions and utilized 6 375 352 images that were increased by data augmentation for the development of AI. We evaluated the diagnostic ability of AI using two classifications: the "adenocarcinoma/high-grade dysplasia" and "low-grade dysplasia/sporadic adenoma/normal mucosa" groups. We compared the diagnostic accuracy between AI and endoscopists (three non-experts and four experts) using 186 test set images. RESULTS: The diagnostic ability of the experts/non-experts/AI for the two classifications in the test set images had a sensitivity of 60.5% (95% confidence interval [CI]: 54.5-66.3)/70.5% (95% CI: 63.8-76.6)/72.5% (95% CI: 60.4-82.5), specificity of 88.0% (95% CI: 84.7-90.8)/78.8% (95% CI: 74.3-83.1)/82.9% (95% CI: 74.8-89.2), and accuracy of 77.8% (95% CI: 74.7-80.8)/75.8% (95% CI: 72-79.3)/79.0% (95% CI: 72.5-84.6), respectively. CONCLUSIONS: The diagnostic accuracy of the two classifications of IBDN was higher than that of the experts. Our AI system is valuable enough to contribute to the next generation of clinical practice.

Comparison of Echocardiographic Changes Between Surgery and Medication Treatment in Patients With Primary Aldosteronism.

Background Primary aldosteronism can cause cardiac dysfunction, including left ventricular hypertrophy, left ventricular diastolic dysfunction, and left atrial enlargement. A few studies have compared the cardioprotective effects between surgery and medication for primary aldosteronism, although most have not adjusted for baseline disease status. In this study, we investigated the difference in cardiovascular outcomes between surgery and medication treatment for primary aldosteronism after adjusting for baseline clinical characteristics, including aldosterone level and pretreatment echocardiographic information. Methods and Results We retrospectively analyzed 220 patients diagnosed with primary aldosteronism who underwent adrenalectomy (n=144) or medication treatment (n=76) between 2009 and 2019. Echocardiographic changes were evaluated pretreatment and 1 year posttreatment. The surgery group had lower potassium, lower plasma renin activity, and higher plasma aldosterone concentration than the medication group, indicating a severe primary aldosteronism phenotype in the former. The decrease in left ventricular mass index after treatment was significantly greater in the surgery group than in the medication group (P=0.047). However, this relationship was not noted after multivariable regression analysis (standard ß=-0.08, P=0.17). Additionally, decreased parameter values related to left ventricular diastolic dysfunction and left atrial enlargement were not different between the groups. Pretreatment echocardiographic values were most associated with changes in all echocardiographic parameters. The findings were consistent in the propensity score-matched analysis. Conclusions This study's findings suggest that there is no difference in cardioprotective efficacy between surgical and medication treatment under similar disease severity; however, it should be considered that several study participants with severe hyperaldosteronism were managed surgically.

Association between diabetes and adjuvant chemotherapy implementation in patients with stage III colorectal cancer.

AIMS/INTRODUCTION: Among colorectal cancer (CRC) patients, pre-existing diabetes is suggested to influence poor prognosis, but the impact on adjuvant chemotherapy implementation is largely unknown. We aimed to compare the implementation rate of adjuvant chemotherapy between CRC patients with and without pre-existing diabetes in a retrospective cohort study. MATERIALS AND METHODS: Colorectal cancer diagnosis information was obtained from the hospital-based cancer registry of patients with stage III CRC who underwent curative surgery in 2013 in Japan (n = 6,344). Health claims data were used to identify diabetes and chemotherapy. We examined the association between diabetes and the implementation rate of adjuvant chemotherapy using a generalized linear model adjusted for age, sex, updated Charlson Comorbidity Index, hospital type and prefecture. Furthermore, we applied a mediation analysis to examine the extent to which postoperative complications mediated the association. RESULTS: Of the 6,344 patients, 1,266 (20.0%) had diabetes. The mean ages were 68.2 and 71.3 years for patients without and with diabetes, respectively. Compared with those without diabetes, patients with diabetes were less likely to receive adjuvant chemotherapy (crude rate 58.9 and 49.8%; adjusted percentage point difference 4.6; 95% confidence interval 1.7-7.5). The difference was evident for patients aged <80 years, and larger for platinum-containing regimens than others. Mediation analysis showed that postoperative complications explained 9.1% of the inverse association between diabetes and adjuvant chemotherapy implementation. CONCLUSIONS: We observed that patients with stage III CRC and diabetes are less likely to receive adjuvant chemotherapy than those without diabetes, and postoperative complications might partially account for the association.

Characteristics of aldosterone-producing adenomas in patients without plasma renin activity suppression.

Primary aldosteronism (PA) usually accompanies suppressed plasma renin activity (PRA) through a negative feedback mechanism. While some cases of PA with unsuppressed PRA were reported, there have been no studies about the characteristics of PA with unsuppressed PRA; thus, these characteristics were examined herein. Nine patients with unsuppressed PRA and 86 patients with suppressed PRA were examined. All patients underwent segmental adrenal venous sampling (sAVS) and adrenalectomy, and were pathologically confirmed to have cytochrome P450 11B2 (CYP11B2)-positive aldosterone-producing adenoma according to international histopathology consensus criteria. Unsuppressed and suppressed PRA were defined as PRA levels of > 1.0 and ≤ 1.0 ng/mL/hr, respectively, in multiple blood samples obtained in the resting position. The unsuppressed PRA group had higher morning cortisol levels (12.6 [8.5, 13.5] vs. 8.5 [7.1, 11.0] µg/dL, P = 0.03) and higher cortisol levels after a 1 mg dexamethasone suppression test (DST) (2.2 [1.6, 2.5] vs. 1.3 [1.0, 1.9] µ g/dL, P = 0.004) than the suppressed PRA group. The unsuppressed PRA group also showed higher aldosterone levels on the non-surgical side during sAVS (P = 0.02 before adrenocorticotropic hormone (ACTH) stimulation, P = 0.002 after ACTH stimulation), a higher intensity of CYP17 expression in the resected adrenal gland (P = 0.02), and a lower clinical complete success rate 1 year after surgery (P = 0.04) compared with those in the suppressed PRA group. These findings suggest that PA should not be ruled out by unsuppressed PRA among patients with hypertension, particularly when their cortisol levels remain unsuppressed in the 1 mg DST. Meanwhile, it should be acknowledged that patients with unsuppressed PRA have higher aldosterone levels on the non-surgical side, and a lower likelihood of postoperative complete clinical success is to be expected.

Patient Adherence to Lung CT Screening Reporting & Data System-Recommended Screening Intervals in the United States: A Systematic Review and Meta-Analysis.

Lung cancer screening (LCS) is effective in reducing mortality, particularly when patients adhere to follow-up recommendations standardized by the Lung CT Screening Reporting & Data System (Lung-RADS). Nevertheless, patient adherence to recommended intervals varies, potentially diminishing benefit from screening. We conducted a systematic review and meta-analysis of patient adherence to Lung-RADS-recommended screening intervals. We systematically searched MEDLINE, EMBASE, Web of Science, the Cochrane Central Register of Controlled Trials, and major radiology and oncology conference archives between April 28, 2014, and December 17, 2020. Eligible studies mentioned patient adherence to the recommendations of Lung-RADS. The review protocol was registered with PROSPERO (CRD42020189326). We identified 24 eligible studies for qualitative summary, of which 21 were suitable for meta-analysis. The pooled adherence rate was 57% (95% confidence interval: 46%-69%) for defined adherence (e.g., an annual incidence screen was performed within 15 mo) among 6689 patients and 65% (95% confidence interval: 55%-75%) for anytime adherence among 5085 patients. Large heterogeneity in adherence rates between studies was observed (I2 = 99% for defined adherence, I2 = 98% for anytime adherence). Heterogeneous adherence rates were associated with Lung-RADS scores, with significantly higher adherence rates among Lung-RADS 3 to 4 than Lung-RADS 1 to 2 (p < 0.05). Patient adherence to Lung-RADS-recommended screening intervals is suboptimal across clinical LCS programs in the United States, especially among patients with results of Lung-RADS categories 1 to 2. To improve adherence rates, future research may focus on implementing tailored interventions after identifying barriers to LCS. We also propose a minimum standardized set of data elements for future pooled analyses of LCS adherence on the basis of our findings.

No Healthcare Utilization and Death.

BACKGROUND: An inappropriately low frequency of healthcare utilization has been reported to be associated with poor control of chronic diseases, accelerating healthcare disparities. However, the evidence is limited regarding the association between no healthcare utilization and mortality. OBJECTIVES: To examine whether individuals without healthcare utilization have the increased risks of mortality among the US general population. DESIGN: Prospective cohort study PARTICIPANTS: Adults aged ≥ 20 years (n = 39,067) in the National Health and Nutrition Examination Survey (NHANES)1999-2014 linked to national mortality data through December 2015. MAIN MEASURES: The exposure was the number of visits to healthcare providers during the past year (healthcare utilization): none, 1-3 times (referent), 4-9 times, or ≥ 10 times. Cox hazard regression models were employed to estimate the adjusted hazard ratios (aHR) of all-cause, cardiovascular, and cancer mortality adjusting for socio-demographic characteristics and comorbidities. KEY RESULTS: During a median follow-up of 7.4 years, participants without visit over the past year showed higher risks of all-cause mortality (aHR [95% CI] = 1.16 [1.04-1.30]) and cardiovascular mortality (aHR [95% CI] = 1.62 [1.28-2.05]) than those who visited the office 1-3 times. We found no evidence of the association between no visit and cancer mortality. The association between no providers' office visit and all-cause mortality was stronger among males (aHR [95% CI] = 1.22 [1.06-1.40]) than females (aHR [95% CI] = 0.97 [0.79-1.19]; p-for-interaction = 0.01) and among uninsured individuals (aHR [95% CI] = 1.22 [0.98-1.51]) than insured individuals (aHR [95% CI] = 1.09 [0.95-1.25]; p-for-interaction = 0.04). CONCLUSION: No providers' office visit over a year was associated with increased risks of all-cause and cardiovascular mortality. Further investigations are warranted to identify the underlying reasons for the elevated mortality risks due to no healthcare utilization.

Association of Serum Parathyroid Hormone Levels With All-Cause and Cause-Specific Mortality Among U.S. Adults.

OBJECTIVE: To examine whether parathyroid hormone (PTH) is associated with mortality among U.S. adults. METHODS: This study included 8286 U.S. adults aged ≥20 years with a measurement of serum intact PTH from the National Health and Nutrition Examination Survey 2003-2006 linked to national mortality data through 2015. Multivariable Cox proportional hazard regression models were employed to estimate the adjusted hazard ratio (aHR) of all-cause and cause-specific (cardiovascular and cancer) mortality according to intact PTH levels (low or low-normal, <38; middle-normal, 38-56; high-normal, 57-74; high, >74 pg/mL). We also stratified the analyses by serum albumin-adjusted calcium and 25-hydroxy vitamin D (25OHD) levels. RESULTS: During a median follow-up of 10.1 years, the mean age was 49 years, and 48% were men. After adjusting for potential confounders, both the high-normal and high PTH groups showed higher risks of all-cause mortality than the low or low-normal PTH group (high-normal PTH, aHR, 1.28; 95% confidence interval [CI], 1.10-1.48; high PTH, aHR, 1.42; 95% CI, 1.19-1.69]. When stratified by calcium and 25OHD levels, the association between high PTH and mortality was also found among participants with albumin-adjusted calcium levels of ≥9.6 mg/dL (aHR, 1.53; 95% CI, 1.17-2.01) and those with 25OHD levels of ≥20 ng/mL (aHR, 1.46, 95% CI, 1.17-1.82). We found no evidence of the increased cause-specific mortality risks in the high PTH group. CONCLUSION: Higher PTH levels were associated with an increased risk of all-cause mortality, particularly among participants with albumin-adjusted calcium levels of ≥9.6 mg/dL or 25OHD levels of ≥20 ng/mL.

Generalizability and Transportability of the National Lung Screening Trial Data: Extending Trial Results to Different Populations.

BACKGROUND: Randomized controlled trials (RCT) play a central role in evidence-based healthcare. However, the clinical and policy implications of implementing RCTs in clinical practice are difficult to predict as the studied population is often different from the target population where results are being applied. This study illustrates the concepts of generalizability and transportability, demonstrating their utility in interpreting results from the National Lung Screening Trial (NLST). METHODS: Using inverse-odds weighting, we demonstrate how generalizability and transportability techniques can be used to extrapolate treatment effect from (i) a subset of NLST to the entire NLST population and from (ii) the entire NLST to different target populations. RESULTS: Our generalizability analysis revealed that lung cancer mortality reduction by LDCT screening across the entire NLST [16% (95% confidence interval [CI]: 4-24)] could have been estimated using a smaller subset of NLST participants. Using transportability analysis, we showed that populations with a higher prevalence of females and current smokers had a greater reduction in lung cancer mortality with LDCT screening [e.g., 27% (95% CI, 11-37) for the population with 80% females and 80% current smokers] than those with lower prevalence of females and current smokers. CONCLUSIONS: This article illustrates how generalizability and transportability methods extend estimation of RCTs' utility beyond trial participants, to external populations of interest, including those that more closely mirror real-world populations. IMPACT: Generalizability and transportability approaches can be used to quantify treatment effects for populations of interest, which may be used to design future trials or adjust lung cancer screening eligibility criteria.