Evaluating interactions of polygenic risk scores and NAT2 genotypes with tobacco smoking in bladder cancer risk.

Tobacco smoking is the most important risk factor for bladder cancer. Previous studies have identified the N-acetyltransferase (NAT2) gene in association with bladder cancer risk. The NAT2 gene encodes an enzyme that metabolizes aromatic amines, carcinogens commonly found in tobacco smoke. In our study, we evaluated potential interactions of tobacco smoking with NAT2 genotypes and polygenic risk score (PRS) for bladder cancer, using data from the UK Biobank, a large prospective cohort study. We used Cox proportional hazards models to measure the strength of the association. The PRS was derived using genetic risk variants identified by genome-wide association studies for bladder cancer. With an average of 10.1 years of follow-up of 390 678 eligible participants of European descent, 769 incident bladder cancer cases were identified. Current smokers with a PRS in the highest tertile had a higher risk of developing bladder cancer (HR: 6.45, 95% CI: 4.51-9.24) than current smokers with a PRS in the lowest tertile (HR: 2.41, 95% CI: 1.52-3.84; P for additive interaction = <.001). A similar interaction was found for genetically predicted metabolizing NAT2 phenotype and tobacco smoking where current smokers with the slow NAT2 phenotype had an increased risk of developing bladder cancer (HR: 5.70, 95% CI: 2.64-12.30) than current smokers with the fast NAT2 phenotype (HR: 3.61, 95% CI: 1.14-11.37; P for additive interaction = .100). Our study provides support for considering both genetic and lifestyle risk factors in developing prevention measures for bladder cancer.

Prospective Cohort Study of Ginseng Consumption in Association with Cancer Risk: Shanghai Women's Health Study.

BACKGROUND: Ginseng has been commonly used in Asian countries to promote longevity and health for >2000 years. Recent in vitro and in vivo studies, coupled with limited epidemiologic studies, have suggested that regular ginseng consumption may be related to lower cancer risk. OBJECTIVES: We evaluated the association of ginseng consumption with risk of total and 15 site-specific cancers in a large cohort study conducted among Chinese women. Given the previous literature on ginseng consumption and cancer risk, we hypothesized that ginseng consumption might be associated with varying risks of cancer. METHODS: This study included 65,732 female participants (mean age: 52.2 years) of the Shanghai Women's Health Study, an ongoing prospective cohort study. Baseline enrollment occurred between 1997 and 2000, and follow-up concluded on 31 December 2016. Ginseng use and covariates were assessed via an in-person interview conducted at the baseline recruitment. The cohort was followed for cancer incidence. Cox proportional hazard models were used to estimate HRs and 95% CIs for ginseng-cancer associations after adjusting for confounders. RESULTS: During a mean 14.7 years of follow-up, 5067 incident cancer cases were identified. Overall, regular ginseng use was mostly not associated with risk of any site-specific cancer, or all cancers combined. Short-term (<3 years) ginseng use was found to be significantly associated with increased risk of liver cancer (HR = 1.71; 95% CI: 1.04, 2.79; P = 0.035), whereas long-term (≥3 years) ginseng use was found to be associated with increased risk of thyroid cancer (HR = 1.40; 95% CI: 1.02, 1.91; P = 0.036). Long-term ginseng use was found to be significantly associated with decreased risk of lymphatic and hematopoietic tissue malignancy (HR = 0.67; 95% CI: 0.46, 0.98; P = 0.039) and non-Hodgkin's lymphoma (HR = 0.57; 95% CI: 0.34, 0.97; P = 0.039). CONCLUSIONS: This study provides suggestive evidence that ginseng consumption may be associated with risk of certain cancers.

Association of Ginseng Consumption With All-cause and Cause-specific Mortality: Shanghai Women's Health Study.

BACKGROUND: Ginseng, an herbal remedy, has been commonly used in Asian countries to promote longevity and health for over 2,000 years. However, the association of ginseng consumption with all-cause and cause-specific mortality is still unclear. We analyzed the association of total and major cause-specific mortality (cardiovascular disease [CVD], cancer, and other death) with consumption of ginseng (primarily American and white ginseng). METHODS: This study included 56,183 female participants with an average follow-up of 14.7 years in the Shanghai Women's Health Study, an ongoing prospective cohort study. Data were assessed via an in-person interview conducted at baseline recruitment. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for ginseng-mortality associations after adjusting for confounders. RESULTS: Compared with those who never used ginseng, regular ginseng use was associated with significantly reduced all-cause mortality (HR 0.92; 95% CI, 0.87-0.98). This inverse association was seen primarily among those who consumed ginseng for perceived general health benefit (HR 0.90; 95% CI, 0.85-0.96). A significant dose-response association was observed between duration of ginseng use and total mortality (HR 0.85, for using ≥6 years vs never use; P for trend <0.001), CVD mortality (HR 0.83; P for trend = 0.019), and other-cause mortality (HR 0.76; P for trend = 0.001). However, no dose-response association was observed between amount of ginseng consumption and mortality outcomes. CONCLUSION: Regular ginseng consumption, particularly over a long duration, was associated with decreased risk of all causes of death, death due to CVD, and death due to certain other diseases.

Association of cardiometabolic comorbidities with mortality among low-income Black and White Americans.

METHODS: Investigated the association of multiple cardiometabolic comorbidities with total/major cause-specific mortality and evaluate if this association might be modified by race among predominantly low-income Black and White participants. METHODS: The Southern Community Cohort Study, prospective cohort study. Participants (40-79 years) recruited predominantly from community health centers across 12 states in southeastern United States. Enrollment began in 2002 and concluded in 2009, follow-up until 2020. Cardiometabolic comorbidities (diabetes, hypertension, myocardial infarction, stroke) ascertained at the baseline survey. Cox proportional hazard models used. RESULTS: Study included 76,721 participants; 16,197, 41,944, 5,247, and 4,919 participants with prior diagnosis of diabetes, hypertension, myocardial infarction, and stroke, respectively at baseline. Compared to individuals with no comorbidity, individuals with any single comorbidity experienced a significantly 30 to 90% increased rate of death due to any causes. The increase in mortality was elevated with an increasing number of comorbidities, with HR of 3.81 (95% CI: 3.26-4.46) and a cumulative risk of 62.5% at age 75 years for total mortality for those with four comorbidities. The risk was high for death due to cardiovascular diseases (HR: 6.18, 95% CI: 5.12-7.47). These associations were stronger among Blacks than Whites. Individuals with four comorbidities at age 40 years were estimated to have a 16-year loss in life expectancy compared with those without any comorbidity. CONCLUSION: Cardiometabolic comorbidities were associated with increases in all-cause and major cause-specific mortality, particularly Black Americans. This study calls for effective measures to prevent cardiometabolic comorbidities to reduce premature deaths in underserved Americans.

Early physical medicine and rehabilitation for patients with acute respiratory failure: a quality improvement project.

OBJECTIVES: To (1) reduce deep sedation and delirium to permit mobilization, (2) increase the frequency of rehabilitation consultations and treatments to improve patients' functional mobility, and (3) evaluate effects on length of stay. DESIGN: Seven-month prospective before/after quality improvement project. SETTING: Sixteen-bed medical intensive care unit (MICU) in academic hospital. PARTICIPANTS: 57 patients mechanically ventilated 4 days or longer. INTERVENTION: A multidisciplinary team focused on reducing heavy sedation and increasing MICU staffing to include full-time physical and occupational therapists with new consultation guidelines. MAIN OUTCOME MEASURES: Sedation and delirium status, rehabilitation treatments, functional mobility. RESULTS: Compared with before the quality improvement project, benzodiazepine use decreased markedly (proportion of MICU days that patients received benzodiazepines [50% vs 25%, P=.002]), with lower median daily sedative doses (47 vs 15 mg midazolam equivalents [P=.09] and 71 vs 24 mg morphine equivalents [P=.01]). Patients had improved sedation and delirium status (MICU days alert [30% vs 67%, P<.001] and not delirious [21% vs 53%, P=.003]). There were a greater median number of rehabilitation treatments per patient (1 vs 7, P<.001) with a higher level of functional mobility (treatments involving sitting or greater mobility, 56% vs 78%, P=.03). Hospital administrative data demonstrated that across all MICU patients, there was a decrease in intensive care unit and hospital length of stay by 2.1 (95% confidence interval: 0.4-3.8) and 3.1 (0.3-5.9) days, respectively, and a 20% increase in MICU admissions compared with the same period in the prior year. CONCLUSIONS: Using a quality improvement process, intensive care unit delirium, physical rehabilitation, and functional mobility were markedly improved and associated with decreased length of stay.

Rehabilitation therapy and outcomes in acute respiratory failure: an observational pilot project.

PURPOSE: The aim of this study was to describe the frequency, physiologic effects, safety, and patient outcomes associated with traditional rehabilitation therapy in patients who require mechanical ventilation. MATERIALS AND METHODS: Prospective observational report of consecutive patients ventilated 4 or more days and eligible for rehabilitation in a single medical intensive care unit (ICU) during a 13-week period was conducted. RESULTS: Of the 32 patients who met the inclusion criteria, only 21 (66%) received physician orders for evaluation by rehabilitation services (physical and/or occupational therapy). Fifty rehabilitation treatments were provided to 19 patients on a median of 12% of medical ICU days per patient, with deep sedation and unavailability of rehabilitation staff representing major barriers to treatment. Physiologic changes during rehabilitation therapy were minimal. Joint contractures were frequent in the lower extremities and did not improve during hospitalization. In 53% and 79% of initial ICU assessments, muscle weakness was present in upper and lower extremities, respectively, with a decreased prevalence of 19% and 43% at hospital discharge, respectively. New impairments in physical function were common at hospital discharge. CONCLUSIONS: This pilot project illustrated important barriers to providing rehabilitation to mechanically ventilated patients in an ICU and impairments in strength, range of motion, and functional outcomes at hospital discharge.