Evaluation of intranasal nafamostat or camostat for SARS-CoV-2 chemoprophylaxis in Syrian golden hamsters.

Successful development of a chemoprophylaxis against SARS-CoV-2 could provide a tool for infection prevention implementable alongside vaccination programmes. Camostat and nafamostat are serine protease inhibitors that inhibit SARS-CoV-2 viral entry in vitro but have not been characterised for chemoprophylaxis in animal models. Clinically, nafamostat is limited to intravenous delivery and while camostat is orally available, both drugs have extremely short plasma half-lives. This study sought to determine whether intranasal dosing at 5 mg/kg twice daily was able to prevent airborne transmission of SARS-CoV-2 from infected to uninfected Syrian golden hamsters. SARS-CoV-2 viral RNA was above the limits of quantification in both saline- and camostat-treated hamsters 5 days after cohabitation with a SARS-CoV-2 inoculated hamster. However, intranasal nafamostat-treated hamsters remained RNA negative for the full 7 days of cohabitation. Changes in body weight over the course of the experiment were supportive of a lack of clinical symptomology in nafamostat-treated but not saline- or camostat-treated animals. These data are strongly supportive of the utility of intranasally delivered nafamostat for prevention of SARS-CoV-2 infection and further studies are underway to confirm absence of pulmonary infection and pathological changes.

Influenza vaccination status and outcomes among influenza-associated hospitalizations in Columbus, Ohio (2012-2015).

Prior studies suggest that the influenza vaccine is protective against some outcomes in hospitalized patients infected with influenza despite vaccination. We utilized surveillance data from Columbus, Ohio to investigate this association over multiple influenza seasons and age groups. Data on laboratory-confirmed influenza-associated hospitalizations were collected as a part of the Influenza Hospitalization Surveillance Project for the 2012-2013, 2013-2014, and 2014-2015 influenza seasons. The association between influenza vaccination status was examined in relation to the outcomes of severe influenza and diagnosis of pneumonia among patients receiving antiviral treatment. Data were analyzed using multivariable logistic regression. We observed no overall association between influenza vaccination status and severe influenza among hospitalized patients. During the 2013-2014 season, those who were vaccinated were 41% less likely to be diagnosed with pneumonia compared with those who were unvaccinated (OR = 0·59 95% CI 0·41-0·86). The influenza vaccine may provide a secondary preventive function against pneumonia among influenza cases requiring hospitalization. However, a protective effect was only observed in 2013-2014, an influenza H1N1 dominant year. Differences in circulating influenza virus strains and vaccine matching to the circulating strains during influenza seasons may impact this association.

Effect of body mass on the association between estrogen replacement therapy and mortality among elderly US women.

In observational studies, estrogen replacement therapy is associated with decreased cardiovascular disease rates and increased breast cancer rates. Recent evidence suggests that the impact of estrogen use on disease outcomes may vary by body mass. In a prospective study of 290,827 postmenopausal US women with no history of cancer or cardiovascular disease at enrollment in 1982, the authors examined the association between postmenopausal estrogen use and all-cause, coronary heart disease, stroke, all-cancer, and breast cancer death rates and whether these associations differed by body mass. After 12 years of follow-up, results from Cox proportional hazards models showed that all-cause death rates were lower among baseline estrogen users than never users (rate ratio (RR) = 0.82, 95% confidence interval (CI): 0.78, 0.87). The lowest relative risk was found for coronary heart disease (RR = 0.66, 95% CI: 0.58, 0.77). The inverse association between estrogen use and coronary heart disease mortality was strongest for thin women (body mass index <22 kg/m2) (RR = 0.49, p for interaction = 0.02). Breast cancer mortality did not increase with estrogen use overall, and no increased risk was observed for thin or heavy women. In this population, the reduction in coronary heart disease mortality among estrogen users was greatest for thinner women. Additional studies are needed to confirm or refute these results.

Family history of breast cancer as a predictor for fatal prostate cancer.

To examine the relation between family history of breast cancer in a mother or sister and a man's risk of fatal prostate cancer, we analyzed data from a prospective mortality study of adult men in the United States. During 12 years of follow-up, there were 3,141 deaths from prostate cancer in a cohort of 480,802 men who were cancer-free at study entry in 1982. Results from Cox proportional hazards models, adjusted for other risk factors, showed a modest increased risk of fatal prostate cancer associated with a family history of breast cancer (in the absence of a family history of prostate cancer) [rate ratio (RR) = 1.16; 95% confidence interval (CI) = 1.01-1.33]. The association was stronger among men younger than 65 years of age whose relatives were diagnosed with breast cancer before age 50 years (RR = 1.65; 95% CI = 0.88-3.10) and among Jewish men (RR = 1.73; 95% CI = 1.00-2.97). The increased risks observed in these subgroups may reflect genetic alterations underlying familial clustering of prostate and breast cancer.

Increased cancer mortality following a history of nonmelanoma skin cancer.

CONTEXT: Cancer registries have reported an increased incidence of melanoma and certain noncutaneous cancers following nonmelanoma skin cancer (NMSC). Whether these findings were attributable to intensified surveillance, shared risk factors, or increased cancer susceptibility remains unclear. OBJECTIVE: To determine whether a history of NMSC predicts cancer mortality. DESIGN: Prospective cohort with 12-year mortality follow-up adjusted for multiple risk factors. SETTING: Cancer Prevention Study II, United States and Puerto Rico. PARTICIPANTS: Nearly 1.1 million adult volunteers who completed a baseline questionnaire in 1982. MAIN OUTCOME MEASURE: Deaths due to all cancers and common cancers. RESULTS: After adjusting for age, race, education, smoking, obesity, alcohol use, and other conventional risk factors, a baseline history of NMSC was associated with increased total cancer mortality (men's relative risk [RR], 1.30; 95% confidence interval [CI], 1.23-1.36; women's RR, 1.26; 95% CI, 1.17-1.35). Exclusion of deaths due to melanoma reduced these RRs only slightly. Mortality was increased for the following cancers: melanoma (RR, 3.36 in men, 3.52 in women); pharynx (RR, 2.77 in men, 2.81 in women); lung (RR, 1.37 in men, 1.46 in women); non-Hodgkin lymphoma (RR, 1.32 in men, 1.50 in women); in men only, salivary glands (RR, 2.96), prostate (RR, 1.28), testis (RR, 12.7), urinary bladder (RR, 1.41), and leukemia (RR, 1.37); and in women only, breast (RR, 1.34). All-cause mortality was slightly increased (adjusted men's RR, 1.03 [95% CI, 1.00-1.06]; women's RR, 1.04 [95% CI, 1.00-1.09]). CONCLUSIONS: Persons with a history of NMSC are at increased risk of cancer mortality. Although the biological mechanisms are unknown, a history of NMSC should increase the clinician's alertness for certain noncutaneous cancers as well as melanoma.

Are geographic regions with high income inequality associated with risk of abdominal weight gain?

Geographic regions characterized by income inequality are associated with adverse mortality statistics, but the pathophysiologic mechanisms that mediate this ecologic relationship have not been elucidated. This study used a United States mail survey of 34158 male and 42741 female healthy-adult volunteers to test the association between residence in geographic regions with relative income inequality and the likelihood of weight gain at the waist. Respondents came from 21 states that were characterized by the household income inequality (HII) index, a measure reflecting the proportion of total income received by the more well off 50% of households in the state. The main outcome measure was self-reported weight gain mainly at the waist as opposed to weight gain at other anatomic sites. After controlling for age, other individual-level factors, and each state's median household income, men's likelihood of weight gain at the waist was positively associated (p = 0.0008) with the HII index. Men from states with a high HII (households above the median receive 81.6% to 82.6% of the income) described weight gain at the waist more often than men from states with a low HII (households above the median receive 77.0% to 78.5% of the income) (odds ratio = 1.12, 95% confidence interval 1.03 to 1.22). Women's results showed a non-significant trend in the same direction. An association between ecologically defined socio-environmental stress and abdominal obesity may help to clarify the pathophysiologic pathways leading to several major chronic diseases.

Risk factors for self-reported colon polyps.

OBJECTIVE: Investigate risk factors for colon polyp using multivariate analyses. DESIGN: In a group responding to a 1992 mail survey, we assessed the association between physician-diagnosed colon polyp and possible risk factors reported primarily 10 years earlier. SETTING: Survey respondents within the Cancer Prevention Study II. PARTICIPANTS: Respondents, 72,868 men and 81,356 women, who reported no polyp diagnosis when questioned in 1982 at ages 40 to 64 years. MEASUREMENTS AND MAIN RESULTS: The characteristics of 7,504 men (10.3%) and 5,111 women (6.3%) reporting a first colon polyp were compared with those of participants who did not report a polyp. After adjustments for age, family history of colorectal cancer, and other potential risk factors, polyp occurrence was associated with 1982 histories of smoking, former smoking, alcohol use of at least two drinks per day (odds ratios [ORs] from 1.5 to 1.1; all p < .005), and a body mass index > or = 28 kg/m2 (men's OR 1.06; 95% confidence interval [CI] 1.00, 1.13; women's OR 1.08; 95% CI 0.99, 1.17). Polyps were also associated with a diagnosis of gallbladder disease or gallstone at any time and with gallbladder surgery up to 1982 (OR from 2.7 to 1.3; all p < .001). Polyp occurrence was inversely associated with 1982 histories of high exercise level (men's OR 0.83; 95% CI 0.76, 0.91; women's OR 0.90; 95% CI 0.78, 1.03), frequent aspirin use in women (OR 0.85; 95% CI 0.77, 0.95), and high parity in women (OR 0.84; 95% CI 0.75, 0.94). Among participants lacking a clinically normal gallbladder, the polyp risks associated with smoking and high body mass index were reduced (p < .04 for interactions). CONCLUSIONS: Despite the limitations and potential biases in these self-reported data, the risk factors described here may be useful for identifying persons at modestly increased risk of having a colon polyp. The effect-modifying role of gallbladder status deserves further investigation.

Family history score as a predictor of breast cancer mortality: prospective data from the Cancer Prevention Study II, United States, 1982-1991.

A consistent predictor of a woman's risk for breast cancer is a family history of the disease. Most studies of family history and breast cancer have used the number of affected relatives in the family to calculate relative risk, but they have not considered the heterogeneity of the familial risk for breast cancer in a systematic way. With the use of data from a large prospective mortality study of US adults, the authors compared simple classification of family history of breast cancer (yes/no) to the method of using a quantitative family history score method, which takes into account the effects of family structure, age, and birth cohort as predictors of breast cancer mortality. After 9 years of follow-up, 1,428 cases of fatal breast cancer were observed among 453,073 women with complete information on number and age of siblings and family history. With the use of the family history score, about one-third of women with a positive family history of breast cancer were at no higher risk for breast cancer mortality than those without a family history of the disease. As a quantitative measure of relative risk for each family, family history score gave a better fit to the data, and it provided an incremental improvement of predictive accuracy of developing fatal breast cancer. Family history score can also be used as a categorical variable to stratify families. This allows researchers to focus on which risk groups would benefit from conducting further genetic analysis and to test the effects of genetic factors, environmental exposure, and gene-environment interactions on the etiology of the development of breast cancer.

Infertility and risk of fatal ovarian cancer in a prospective cohort of US women.

OBJECTIVES: It is difficult to separate the possible role of fertility drugs from underlying infertility as risk factors for ovarian cancer. The present study examined the relationship between self-reported infertility and death from ovarian cancer among married women unlikely to have been exposured to fertility drugs. METHODS: Women were selected for study from the 676,526 female participants in Cancer Prevention Study II (CPS-II). After twelve years of follow-up, 797 deaths from ovarian cancer were observed among women with no prior history of cancer or hysterectomy and 40 years of age or older in 1967 when ovulatory stimulants were approved in the United States. Cox proportional hazards modeling was used to compute rate ratios (RRs) and to adjust for other potential risk factors. RESULTS: Overall, self-reported infertility was not significantly associated with ovarian cancer mortality (adjusted rate ratio (RR) = 1.1, 95 percent confidence interval (CI) = 0.9-1.3). Ovarian cancer death rates among nulligravid women with self-reported infertility, however, were 40 percent higher than for nulligravid women who never tried to become pregnant (RR = 1.4, 95 percent CI = 0.9-2.4). Multigravid women who reported infertility problems were not at increased risk. CONCLUSIONS: These results suggest that infertility itself, without concomitant exposure to fertility drugs, may increase risk of fatal ovarian cancer among nulligravid women.

Contrasting factors associated with abdominal and peripheral weight gain among adult women.

OBJECTIVE: To identify contrasts between the risk factors associated with abdominal weight gain and those associated with peripheral weight gain. DESIGN: Prospective mail survey. SUBJECTS: 44080 white, non-Hispanic, healthy women who were questioned in 1982 (baseline age 40-54 y) and 1992 about weight, diet, alcohol use, smoking, 10 physical activities and other variables. MEASUREMENTS: Self reports in 1992 identified 4261 women who gained weight in the abdomen and 7440 women who gained in the periphery (sites other than the abdomen). Using identical logistic models adjusted for age, baseline body mass index (BMI) and numerous covariates, the abdominal-gain group and the peripheral-gain group were separately compared with 10,888 women who did not gain weight. RESULTS: The likelihood of abdominal gain exceeded that of peripheral gain (by comparison of estimated odds ratios, abdominal vs peripheral) for high meat eaters (1.50 vs 1.15), frequent users of liquor (1.09 vs 0.54), moderate cigarette smokers (0.86 vs 0.59), heavy cigarette smokers (0.96 vs 0.36), cigarette quitters (2.13 vs 1.63), women with high parity (1.52 vs 1.15) and those who reported major weight gain since age 18 y (1.22 vs 0.65). Abdominal gain was less likely than peripheral gain for high vegetable eaters (0.71 vs 0.91), women who exercised > or = 4 h/wk [(especially aerobics/ calisthenics (0.28 vs 0.91) or walking (0.84 vs 1.06)], women who completed menopause (0.74 vs 0.98) and consistent users of estrogen replacement therapy (0.93 vs 1.22). CONCLUSION: A behavior or characteristic may be associated differently with the risks of abdominal and peripheral weight gain. This insight could strengthen recommendations for preventing major chronic diseases.

Family history and risk of fatal prostate cancer.

To examine the relation between fatal prostate cancer and family history of prostate cancer in a first-degree relative, we analyzed data from a prospective mortality study of 481,011 men with no history of cancer at enrollment in 1982. During 9 years of follow-up, 1,922 deaths from prostate cancer occurred. Results from Cox proportional hazard models showed that family history of prostate cancer was related to fatal prostate cancer [rate ratio (RR) = 1.60; 95% confidence interval (CI) = 1.31-1.97]; men with two or more affected relatives had a greater than threefold increase in risk (RR = 3.19; 95% CI = 1.51-6.71). Men whose relatives were diagnosed with prostate cancer before age 65 years (RR = 2.03; 95% CI = 1.33-3.09) had a greater effect of family history than men whose relatives were diagnosed at older ages (RR = 1.50; 95% CI = 1.17-1.91). Rate ratios did not increase with decreasing age of the study participants. The 60% increase in risk for men with at least one affected relative is lower than that reported in previous studies.

Occupational risk factors for subgroups of non-Hodgkin's lymphoma.

The non-Hodgkin's lymphomas (NHL) are a diverse group of neoplasms of the lymphatic system whose incidence has been increasing in recent years. The Centers for Disease Control Selected Cancers Study, a population-based case-control study of several cancers, included a large number of cases of NHL and a pathology review, providing a rare opportunity to study risk factors for groups of NHL subtypes. We examined the relation between occupational exposures and three subgroups of NHL: small cell diffuse lymphomas (N = 185), follicular lymphomas (N = 268), and large cell diffuse lymphomas (N = 526). There were 1,659 controls available for comparison. After controlling for demographic variables and previously identified risk factors for NHL, we observed two interesting associations, one between solvent exposure and small cell diffuse lymphomas [odds ratio (OR) = 1.60; 95% confidence interval (CI) = 1.10-2.20], and the other between meat packaging/processing and follicular lymphomas (OR = 1.60; 95% CI = 0.99-2.60). The results of this exploratory analysis are primarily negative. Our lack of positive findings may indicate that the subgroups of NHL used may not be etiologically distinct and that further work needs to be done to develop an NHL classification system that is etiologically informative and useful for epidemiologic studies.

Stable behaviors associated with adults' 10-year change in body mass index and likelihood of gain at the waist.

OBJECTIVES: The purpose of this study was to identify behaviors associated with change in body mass index or with weight gain at the waist. METHODS: A cohort of 79236 White, non-Hispanic, healthy adults was questioned in 1982 and 1992 about diet and 10 physical activities. Estimates were made of the mean effects of stable behaviors on 10-year change in body mass index and on odds ratios for gain at the waist. RESULTS: Ten-year changes in body mass index was associated positively with meat consumption and smoking cessation and inversely with vegetable consumption, vitamin E supplementation, continued smoking, and some vigorous activities (e.g., jogging/running). Women's body mass index decreased with walking 4 or more hours per week and with regular alcohol intake, but these behaviors had a smaller effect on men's body mass index. weight gain was inversely associated with high vegetable consumption, walking 4 or more hours per week, and jogging/running 1 to 3 hours per week but not with less demanding physical activities. CONCLUSIONS: Simple derivation of behaviors associated with weight loss or reduced abdominal obesity may enhance programs designed to prevent obesity and chronic diseases.

Smoking and fatal prostate cancer in a large cohort of adult men.

The authors examined the relation between smoking and the risk of fatal prostate cancer in a large prospective mortality study of 450,279 men who were cancer free at enrollment in 1982. During 9 years of follow-up, 1,748 deaths occurred from prostate cancer. Cox proportional hazards modeling was used to adjust for other risk factors. Current cigarette smoking was associated with fatal prostate cancer (rate ratio = 1.34, 95% confidence interval (CI) 1.16-1.56). The rate ratio was greater at younger ages, decreasing from 1.83 (95% CI 1.04-3.24) among men below the age of 60 years to 1.11 (95% CI 0.79-1.58) among men aged 80 years and above (p for trend = 0.16). No trend in risk was observed with the number of cigarettes per day or with the duration of smoking among current smokers at baseline, and no increased risk was found among former smokers. Race did not significantly modify the association between cigarette smoking and fatal prostate cancer. These data, together with those of three other large prospective studies that find higher death rates from prostate cancer in current cigarette smokers, and inconsistent findings in incidence studies suggest that smoking may adversely affect survival in prostate cancer patients.