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Rationale: Epidemiologic studies on the consequences of sleep-disordered breathing invariably use the apnea-hypopnea index as the primary measure of disease severity. Although hypopneas constitute a majority of disordered breathing events, significant controversy remains about the best criteria used to define these events.Objectives: The current investigation sought to assess the most appropriate definition for hypopneas that would be best correlated with cardiovascular disease.Methods: A community sample of middle-aged and older adults was recruited as part of the Sleep Heart Health Study. Full-montage polysomnography was conducted and hypopneas were defined using different thresholds of oxyhemoglobin desaturation with and without arousals. Prevalent cardiovascular disease was assessed based on self-report. Logistic regression analysis was used to characterize the independent association between the hypopnea index and prevalent cardiovascular disease.Measurements and Main Results: Using a sample of 6,106 adults with complete data on cardiovascular disease status and polysomnography, the current study found that hypopneas associated with an oxyhemoglobin desaturation of 4% or more were associated with prevalent cardiovascular disease independent of confounding covariates. The adjusted prevalent odds ratios for quartiles of the hypopnea index using a 4% desaturation criterion were as follows: 1.00 (<1.10 events/h), 1.10 (1.01-3.20 events/h), 1.33 (3.21-7.69 events/h), and 1.41 (>7.69 events/h). Hypopnea measures based on less than 4% oxyhemoglobin desaturation or presence of arousals showed no association with cardiovascular disease.Conclusions: Hypopneas comprise a significant component of sleep-disordered breathing in the general community. By varying the criteria for defining hypopneas, this study demonstrates that hypopneas with a desaturation of at least 4% are independently associated with cardiovascular disease. In contrast, no association was observed between cardiovascular disease and hypopneas associated with milder desaturations or arousals. [ABSTRACT FROM AUTHOR]

Context: Sleep-disordered breathing (SDB) and sleep apnea have been linked to hypertension in previous studies, but most of these studies used surrogate information to define SDB (eg, snoring) and were based on small clinic populations, or both.Objective: To assess the association between SDB and hypertension in a large cohort of middle-aged and older persons.Design and Setting: Cross-sectional analyses of participants in the Sleep Heart Health Study, a community-based multicenter study conducted between November 1995 and January 1998.Participants: A total of 6132 subjects recruited from ongoing population-based studies (aged > or = 40 years; 52.8% female).Main Outcome Measures: Apnea-hypopnea index (AHI, the average number of apneas plus hypopneas per hour of sleep, with apnea defined as a cessation of airflow and hypopnea defined as a > or = 30% reduction in airflow or thoracoabdominal excursion both of which are accompanied by a > or = 4% drop in oxyhemoglobin saturation) [corrected], obtained by unattended home polysomnography. Other measures include arousal index; percentage of sleep time below 90% oxygen saturation; history of snoring; and presence of hypertension, defined as resting blood pressure of at least 140/90 mm Hg or use of antihypertensive medication.Results: Mean systolic and diastolic blood pressure and prevalence of hypertension increased significantly with increasing SDB measures, although some of this association was explained by body mass index (BMI). After adjusting for demographics and anthropometric variables (including BMI, neck circumference, and waist-to-hip ratio), as well as for alcohol intake and smoking, the odds ratio for hypertension, comparing the highest category of AHI (> or = 30 per hour) with the lowest category (< 1.5 per hour), was 1.37 (95% confidence interval [CI], 1.03-1.83; P for trend = .005). The corresponding estimate comparing the highest and lowest categories of percentage of sleep time below 90% oxygen saturation (> or = 12% vs < 0.05%) was 1.46 (95% CI, 1.12-1.88; P for trend <.001). In stratified analyses, associations of hypertension with either measure of SDB were seen in both sexes, older and younger ages, all ethnic groups, and among normal-weight and overweight individuals. Weaker and nonsignificant associations were observed for the arousal index or self-reported history of habitual snoring.Conclusion: Our findings from the largest cross-sectional study to date indicate that SDB is associated with systemic hypertension in middle-aged and older individuals of different sexes and ethnic backgrounds. [ABSTRACT FROM AUTHOR]

Background: Lynch syndrome is a hereditary cancer predisposition syndrome caused by germline mutations in DNA mismatch repair genes, which lead to high microsatellite instability and frameshift mutations at coding mononucleotide repeats in the genome. Recurrent frameshift mutations in these regions are thought to play a central role in the increased risk of various cancers, but no biomarkers are currently available for the surveillance of high microsatellite instability-associated cancers., Methods: A frameshift mutation-based biomarker panel was developed and validated by targeted next-generation sequencing of supernatant DNA from cultured high microsatellite instability colorectal cancer cells. This panel supported selection of 122 frameshift mutation targets as potential biomarkers. This biomarker panel was then tested using matched tumor, adjacent normal tissue, and buffy coat samples (53 samples) and blood-derived cell-free DNA (cfDNA) (38 samples) obtained from 45 high microsatellite instability and mismatch repair-deficient patients. We also sequenced cfDNA from 84 healthy participants to assess background noise., Results: Recurrent frameshift mutations at coding mononucleotide repeats were detectable not only in tumors but also in cfDNA from high microsatellite instability and mismatch repair-deficient patients, including a Lynch syndrome carrier, with a varying range of target detection (up to 85.2%), whereas they were virtually undetectable in healthy participants. Receiver operating characteristic curve analysis showed high sensitivity and specificity (area under the curve = 0.94) of the investigated panel., Conclusions: We demonstrated that frameshift mutations can be detected in cfDNA from high microsatellite instability and mismatch repair-deficient patients and asymptomatic carriers. The 122-target frameshift mutation panel described here has promise as a tool for improved surveillance of high microsatellite instability and mismatch repair-deficient patients, with the potential to reduce the frequency of invasive screening methods for this high-cancer-risk cohort., (Published by Oxford University Press 2024.)

Background: Genome integrity is essential for the survival of an organism. DNA mismatch repair (MMR) genes (e.g., MLH1, MSH2, MSH6 , and PMS2 ) play a critical role in the DNA damage response pathway for genome integrity maintenance. Germline mutations of MMR genes can lead to Lynch syndrome or constitutional mismatch repair deficiency syndrome, resulting in an increased lifetime risk of developing cancer characterized by high microsatellite instability (MSI-H) and high mutation burden. Although immunotherapy has been approved for MMR-deficient (MMRd) cancer patients, the overall response rate needs to be improved and other management options are needed., Methods: To better understand the biology of MMRd cancers, elucidate the resistance mechanisms to immune modulation, and develop vaccines and therapeutic testing platforms for this high-risk population, we generated organoids and an orthotopic mouse model from intestine tumors developed in a Msh2-deficient mouse model, and followed with a detailed characterization., Results: The organoids were shown to be of epithelial origin with stem cell features, to have a high frameshift mutation frequency with MSI-H and chromosome instability, and intra- and inter-tumor heterogeneity. An orthotopic model using intra-cecal implantation of tumor fragments derived from organoids showed progressive tumor growth, resulting in the development of adenocarcinomas mixed with mucinous features and distant metastasis in liver and lymph node., Conclusions: The established organoids with characteristics of MSI-H cancers can be used to study MMRd cancer biology. The orthotopic model, with its distant metastasis and expressing frameshift peptides, is suitable for evaluating the efficacy of neoantigen-based vaccines or anticancer drugs in combination with other therapies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer WL declared a shared affiliation with the authors SB, SS, and RS to the handling editor at the time of review., (Copyright © 2023 Song, Kerr, Sanders, Dai, Baxter, Somerville, Baugher, Mellott, Young, Lawhorn, Plona, Xu, Wei, Hu, Liu, Hutson, Karim, Burkett, Difilippantonio, Pinto, Gebert, Kloor, Lipkin, Sei and Shoemaker.)

Malignant mesothelioma (MMe) is a rare malignancy originating from the linings of the pleural, peritoneal and pericardial cavities. The best-defined risk factor is exposure to carcinogenic mineral fibers (e.g., asbestos). Genomic studies have revealed that the most frequent genetic lesions in human MMe are mutations in tumor suppressor genes. Several genetically engineered mouse models have been generated by introducing the same genetic lesions found in human MMe. However, most of these models require specialized breeding facilities and long-term exposure of mice to asbestos for MMe development. Thus, an alternative model with high tumor penetrance without asbestos is urgently needed. We characterized an orthotopic model using MMe cells derived from Cdkn2a +/- ;Nf2 +/- mice chronically injected with asbestos. These MMe cells were tumorigenic upon intraperitoneal injection. Moreover, MMe cells showed mixed chromosome and microsatellite instability, supporting the notion that genomic instability is relevant in MMe pathogenesis. In addition, microsatellite markers were detectable in the plasma of tumor-bearing mice, indicating a potential use for early cancer detection and monitoring the effects of interventions. This orthotopic model with rapid development of MMe without asbestos exposure represents genomic instability and specific molecular targets for therapeutic or preventive interventions to enable preclinical proof of concept for the intervention in an immunocompetent setting.

Study Objectives: To characterize the prospective associations of obstructive sleep apnea (OSA) with future echocardiographic measures of adverse cardiac remodeling., Methods: This was a prospective long-term observational study. Participants had overnight polysomnography followed by transthoracic echocardiography a mean (standard deviation) of 18.0 (3.7) y later. OSA was characterized by the apnea-hypopnea index (AHI, events/hour). Echocardiography was used to assess left ventricular (LV) systolic and diastolic function and mass, left atrial volume and pressure, cardiac output, systemic vascular resistance, and right ventricular (RV) systolic function, size, and hemodynamics. Multivariate regression models estimated associations between log10(AHI+1) and future echocardiographic findings. A secondary analysis looked at oxygen desaturation indices and future echocardiographic findings., Results: At entry, the 601 participants were mean (standard deviation) 47 (8) y old (47% female). After adjustment for age, sex, and body mass index, baseline log10(AHI+1) was associated significantly with future reduced LV ejection fraction and tricuspid annular plane systolic excursion (TAPSE) ≤ 15 mm. After further adjustment for cardiovascular risk factors, participants with higher baseline log10(AHI+1) had lower future LV ejection fraction (β = -1.35 [standard error = 0.6]/log10(AHI+1), P = 0.03) and higher odds of TAPSE ≤ 15 mm (odds ratio = 6.3/log10(AHI+1), 95% confidence interval = 1.3-30.5, P = 0.02). SaO2 desaturation indices were associated independently with LV mass, LV wall thickness, and RV area (all P < 0.03)., Conclusions: OSA is associated independently with decreasing LV systolic function and with reduced RV function. Echocardiographic measures of adverse cardiac remodeling are strongly associated with OSA but are confounded by obesity. Hypoxia may be a stimulus for hypertrophy in individuals with OSA., (© 2016 Associated Professional Sleep Societies, LLC.)

Importance: Obstructive sleep apnea (OSA) is more common among patients with asthma; whether asthma is associated with the development of OSA is unknown., Objective: To examine the prospective relationship of asthma with incident OSA., Design, Setting, and Participants: Population-based prospective epidemiologic study (the Wisconsin Sleep Cohort Study) beginning in 1988. Adult participants were recruited from a random sample of Wisconsin state employees to attend overnight polysomnography studies at 4-year intervals. Asthma and covariate information were assessed during polysomnography studies through March 2013. Eligible participants were identified as free of OSA (apnea-hypopnea index [AHI] of <5 events/h and not treated) by 2 baseline polysomnography studies. There were 1105 4-year follow-up intervals provided by 547 participants (52% women; mean [SD] baseline age, 50 [8] years)., Exposures: Questionnaire-assessed presence and duration of self-reported physician-diagnosed asthma., Main Outcomes and Measures: The associations of presence and duration of asthma with 4-year incidences of both OSA (AHI of ≥5 or positive airway pressure treatment) and OSA concomitant with habitual daytime sleepiness were estimated using repeated-measures Poisson regression, adjusting for confounders., Results: Twenty-two of 81 participants (27% [95% CI, 17%-37%]) with asthma experienced incident OSA over their first observed 4-year follow-up interval compared with 75 of 466 participants (16% [95% CI, 13%-19%]) without asthma. Using all 4-year intervals, participants with asthma experienced 45 cases of incident OSA during 167 4-year intervals (27% [95% CI, 20%-34%]) and participants without asthma experienced 160 cases of incident OSA during 938 4-year intervals (17% [95% CI, 15%-19%]); the corresponding adjusted relative risk (RR) was 1.39 (95% CI, 1.06-1.82), controlling for sex, age, baseline and change in body mass index, and other factors. Asthma was also associated with new-onset OSA with habitual sleepiness (RR, 2.72 [95% CI, 1.26-5.89], P = .045). Asthma duration was related to both incident OSA (RR, 1.07 per 5-year increment in asthma duration [95% CI, 1.02-1.13], P = .01) and incident OSA with habitual sleepiness (RR, 1.18 [95% CI, 1.07-1.31], P = .02)., Conclusions and Relevance: Asthma was associated with an increased risk of new-onset OSA. Studies investigating the mechanisms underlying this association and the value of periodic OSA evaluation in patients with asthma are warranted.

Study Objectives: To examine the combined impact of sleep disordered breathing (SDB) and metabolic syndrome (MetS) in endothelial dysfunction., Design: Cross-sectional assessment of endothelial function, MetS and SDB status in a population-based sample., Setting: Community-based cohort., Participants: Participants (n = 431) from the Wisconsin Sleep Cohort were studied between 2004 and 2007. MetS was defined following the National Cholesterol Education Program criteria. SDB severity was defined by the apnea-hypopnea index ([AHI] events/h of sleep) during overnight polysomnography. Fasting lipids, glucose, and insulin were measured and homeostasis model assessment was calculated to quantify insulin resistance (HOMA-IR). Multivariable linear regression was used to assess associations of brachial artery flow-mediated dilation (FMD) with SDB, MetS, and their interaction., Intervention: None., Measurements and Results: Participants averaged 60.2 years of age (SD 7.8 years), 44% were female, and 97% Caucasian. MetS was present in 35%; 22% had AHI ≥ 15 events/hour. Of the no-MetS group, 7% had AHI ≥ 15 events/hour. FMD (mean 5.5%; SD 3.5%) was inversely associated with age (r = -0.16, P = 0.001) and mean brachial artery diameter (r = -0.29, P < 0.001). Multivariate linear models adjusted for CVD risk factors showed that the negative association between SDB and FMD was present among subjects with MetS (β FMD(per unit log2(AHI+1)) = -0.55%, P = 0.014), but not among subjects with normal metabolic function (β = 0.13, not significant), P for interaction = 0.011., Conclusion: Sleep disordered breathing and concurrent metabolic syndrome are synergistically associated with worse endothelial function. Individuals with both of these conditions appear to be at a significantly higher risk for cardiovascular disease complications., (© 2014 Associated Professional Sleep Societies, LLC.)

Background: Sleep disordered breathing (SDB) has been associated with cardiovascular disease, hypertension, and insulin resistance. This article examines the association between SDB and the prevalence of metabolic syndrome (MS) in a community-based sample., Methods: A subset of participants in the Wisconsin Sleep Cohort Study (N=546) participated in an ancillary study to measure vascular and metabolic function. SDB was characterized using the apnea-hypopnea index (AHI) obtained in the polysomnography study closest to the collection of the metabolic measures. MS was defined using the National Cholesterol Education Program definition, and the homeostasis model assessment method (HOMA) was used to characterize insulin resistance., Results: SDB was significantly correlated with insulin resistance (Spearman r correlation between AHI and HOMA=0.30, P<0.0001). Compared with those without SDB (AHI <5), the age-sex-adjusted odds ratios of MS associated with mild (AHA 5-14.9) and moderate/severe SDB (AHI > or = 15 or CPAP) were 4.0 (95% CI 2.6, 6.3) and 5.3 (95% CI 3.2, 8.8), respectively. Additional adjustment for markers of sympathetic or neuroendocrine activation (urinary norepinephrine, cortisol, heart rate variability) did not materially alter these estimates. These associations were weaker but remained statistically significant after adjusting for body mass index., Conclusion: SDB might be considered an integral component of MS.

Daytime sleepiness, or difficulty in maintaining a desired level of wakefulness, is frequently viewed by the general population as a common experience and predictable consequence of insufficient sleep. However, daytime sleepiness can have a serious impact on an individual's health, safety, and quality of life. Despite the fact that population-based studies have found that 1 in 5 adults suffers from daytime sleepiness, there is a lack of consistency in how daytime sleepiness is defined, measured, and interpreted, which may affect the medical management of the disorder. For example, many measures of sleepiness based on sleep propensity and falling asleep tend to overlook patients with insomnia and sleepiness. Sleep scales that contain sensitive and specific questions are needed to measure fatigue and perceptions of sleepiness.

Study Objectives: To determine whether chronic sleep deprivation, sleep disruption, sleepiness, insomnia, and OSA are associated with increased healthcare use in a community-based population., Design: Cross-sectional study., Setting/participants: 6440 Sleep Heart Health Study (SHHS) participants recruited from ongoing cohort studies., Interventions: N/A., Measurements: Polysomnography results (Apnea Hypopnea Index (AHI), percent of sleep time with oxyhemoglobin saturation below 90% (CT90), arousal index) as well as data on sleep related symptoms, medication use, and chronic illness. The indirect measure of predicted healthcare utilization was the modified Chronic Disease Score (CDS) calculated from medication data., Results: After adjustment for age, gender, BMI and study site, subjects in the highest quartiles of AHI, CT90 and Epworth score had CDS that were 6%-9% higher than the lowest quartiles. The adjusted mean CDS for subjects with sleep apnea was similar to that for subjects with hypertension, chronic bronchitis or asthma and 18% greater than the mean CDS for subjects without sleep apnea. Among subjects who did not have significant sleep-disordered breathing, complaints of insomnia, sleepiness, fatigue, and not getting enough sleep were associated with increased CDS., Conclusions: This study demonstrated an association between subjective complaints of daytime sleepiness, inadequate sleep time, insomnia as well as objective measures of severity of SDB, and an indirect measure of healthcare utilization in a community-based sample. Though the percent increases in healthcare utilization observed were modest, the prevalence of these factors in the general population is high, and may therefore be associated with a substantial cost burden to the healthcare system.

K. A. Perkins (1996) recently proposed that nicotine reinforcement controls smoking to a greater degree among men than women and that consequently, nicotine replacement therapy (NRT) during smoking cessation should benefit men more than women. The authors tested this hypothesis. Polysomnographic measures of sleep and self-report indexes of tobacco withdrawal were collected pre- and postcessation from an active nicotine patch group and a placebo patch group in a randomized, double-blind clinical trial (N = 34). Objective sleep parameters supported Perkins's hypothesis and indicated that among women, NRT may be less effective at suppressing certain withdrawal responses compared with men and may produce some iatrogenic effects. Valid and reliable self-report measures of withdrawal did not reveal gender differences in response to NRT.

We studied the acute effects of apneas and hypopneas on blood pressure in a nonclinic population of middle-aged adults. Arterial pressure was measured noninvasively (photoelectric plethysmography) during an overnight, in-laboratory polysomnographic study in 72 men and 23 women enrolled in the Wisconsin Sleep Cohort Study, a population-based study of sleep-disordered breathing. Sleep-disordered breathing events (272 apneas and 1469 hypopneas) were observed in 92% of subjects. The across-subject mean decreases in arterial O2 saturation were 9+/-8% (SD) for apneas (17+/-8 seconds duration) and 4+/-3% for hypopneas (21+/-6 seconds duration; 41+/-17% of baseline ventilation). In both apneas and hypopneas, even those with only 1% to 3% O2 desaturations, blood pressure decreased during the event, followed by an abrupt increase in the postevent recovery period. Mean values for peak changes in blood pressure (difference between the maximum during the recovery period and the minimum during the event) were 23+/-10 mm Hg for systolic and 13+/-6 mm Hg for diastolic pressure. The strongest predictors of the pressor responses to apneas and hypopneas were (in order of importance): magnitude of the ventilatory overshoot, length of the event, magnitude of changes in heart rate and arterial O2 saturation, and presence or absence of electroencephalographic arousal. We speculate that these fluctuations may play a role in the pathogenesis of hypertension in individuals with subclinical sleep-disordered breathing.

Efficient automated detection of sleep-disordered breathing (SDB) from routine polysomnography (PSG) data is made difficult by the availability of only indirect measurements of breathing. The approach we used to overcome this limitation was to incorporate pulse oximetry into the definitions of apnea and hypopnea. In our algorithm, 1) we begin with the detection of desaturation as a fall in oxyhemoglobin saturation level of 2% or greater once a rate of descent greater than 0.1% per second (but less than 4% per second) has been achieved and then ask if an apnea or hypopnea was responsible; 2) an apnea is detected if there is a period of no breathing, as indicated by sum respiratory inductive plethysmography (RIP), lasting at least 10 seconds and coincident with the desaturation event; and 3) if there is breathing, a hypopnea is defined as a minimum of three breaths showing at least 20% reduction in sum RIP magnitude from the immediately preceding breath followed by a return to at least 90% of that "baseline" breath. Our evaluation of this algorithm using 10 PSG records containing 1,938 SDB events showed strong event-by-event agreement with manual scoring by an experienced polysomnographer. On the basis of manually verified computer desaturations, detection sensitivity and specificity percentages were, respectively, 73.6 and 90.8% for apneas and 84.1 and 86.1% for hypopneas. Overall, 93.1% of the manually detected events were detected by the algorithm. We have designed an efficient algorithm for detecting and classifying SDB events that emulates manual scoring with high accuracy.

Research has not adequately characterized the impact of tobacco withdrawal on objectively assessed sleep parameters despite the recent inclusion of insomnia as a nicotine withdrawal sign in the Diagnostic and Statistical Manual of Mental Disorders (4th ed.; American Psychiatric Association, 1994). Moreover, whether 24-hr nicotine replacement aids or interferes with sleep during withdrawal is unknown. In a double-masked, randomized clinical trial, 34 cigarette smokers who were motivated to quit received either active nicotine patches or placebo patches while quitting. Sleep was polysomnographically monitored for 2 precessation nights and 3 postcessation nights. The study demonstrates that among dependent smokers (a) tobacco withdrawal increases objectively assessed sleep disturbance (sleep fragmentation) and (b) nicotine replacement results in postcessation improvements in important polysomnographic measures of sleep quality (sleep fragmentation, Stage 3 and Stage 4 sleep).

To determine at what interval screening should be repeated to detect bladder cancer before it becomes muscle invasive 856 men who had 14 negative daily home tests for hematuria with a chemical reagent strip 9 months previously performed repeat tests. Of these men 50 (5.8%) had at least 1 positive test during the second 14-day screening period and 38 were evaluated, 15 of whom (39.5%) had significant urological pathological conditions, including 8 with malignancies. Bladder cancer was noted in 7 men, with no tumor invading the muscularis propria. The finding of 7 bladder cancers in 856 men (0.82%) who had a negative test 9 months previously indicates that bladder cancer has a brief preclinical duration and that testing must be repeated at least annually for screening to detect bladder cancer consistently before invasion occurs.

Objectives: Because repetitive hematuria home screening with a chemical reagent strip can detect early stage bladder cancer (BC) in asymptomatic middle-aged and elderly men, the ability of this screening to effect earlier detection and reduce BC mortality was investigated., Methods: Grades, stages, and outcomes of BCs detected by hematuria screening in 1575 men were compared with those of all newly diagnosed BCs in men age 50 years or older reported to the Wisconsin cancer registry in 1988. BC grades and stages were assigned by review of all pathology slides/blocks, and causes of deaths were determined from cancer registry records. As an additional control group, outcomes of BC cases diagnosed in men solicited to take part in screening, who declined, were also determined., Results: The proportions of low-grade (grades 1 and 2) superficial (Stages Ta and T1) versus high-grade (grade 3) or invasive (Stage T2 or higher) cancers in cases detected by hematuria screening (screened cases) and those reported to the tumor registry (unscreened cases) were not significantly different (52.4% versus 47.7% in 21 screened and 56.8% versus 43.3% in 511 unscreened cases) (P > 0.20). Of the high-grade or invasive cases, however, the proportion of late stage (T2 or higher) tumors was significantly lower in the screening-detected BCs compared to unscreened ones (P = 0.007). No screened case has died of BC (3- to 9-year follow-up), whereas 16.4% of unscreened cases have within 2 years of diagnosis (P = 0.025). Twenty-three of 1940 (1.2%) men who were solicited but chose not to participate in screening were diagnosed with BC within 18 months after what would have been their last home screening date, compared with 1.3% of participants having BC detected by screening. Thus, screening participants and those who were solicited and declined had similar likelihoods of developing BC., Conclusions: Hematuria home screening detects high-grade cancers before they become muscle invading and significantly reduces BC mortality.

Background: Recent evidence indicates that the prevalence of sleep-disordered breathing is remarkably high (24% for men and 9% for women) and that the public health burden attributable to sleep-disordered breathing is substantial. This investigation examines current and former cigarette smoking as potential risk factors for sleep-disordered breathing., Methods: Data were from 811 adults enrolled in the University of Wisconsin Sleep Cohort Study, Madison. The Sleep Cohort Study is a longitudinal, epidemiologic study that uses nocturnal polysomnography to investigate sleep-disordered breathing and other disorders of sleep. The presence and severity of sleep-disordered breathing was quantified by the frequency of apneas and hypopneas per hour of sleep., Results: Logistic regression analyses were used to control for potential confounding factors. Compared with never smokers, current smokers had a significantly greater risk of snoring (odds ratio, 2.29) and of moderate or worse sleep-disordered breathing (odds ratio, 4.44). Heavy smokers (> or = 40 cigarettes per day) had the greatest risk of mild sleep-disordered breathing (odds ratio, 6.74) and of moderate or worse sleep-disordered breathing (odds ratio, 40.47). Former smoking was unrelated to snoring and sleep-disordered breathing after adjustment for confounders., Conclusions: Current cigarette smokers are at greater risk for sleep-disordered breathing than are never smokers. Heavy smokers have the greatest risk while former smokers are not at increased risk for sleep-disordered breathing. Thus, smoking cessation should be considered in the treatment and prevention of sleep-disordered breathing.

Background: There is little epidemiological or clinical information on the relation between smoking and sleep disturbance, despite evidence suggestive of a relationship. The present study tested the hypothesis that cigarette smoking is associated with sleep disturbance., Methods: Survey data from 3,516 adults were collected as part of a longitudinal, epidemiologic study of sleep-disordered breathing. Symptoms of insomnia, hypersomnia, and parasomnia were assessed using diagnostic criteria from the Diagnostic and Statistical Manual of Mental Disorders (3rd ed., revised)., Results: Among both males and females, smoking was associated with difficulty initiating sleep, and difficulty waking up. Excessive daytime sleepiness was related to smoking only for females while nightmares and disturbing dreams were related to smoking only among males., Conclusions: Smoking was associated with difficulty initiating sleep and with a constellation of symptoms suggestive of sleep fragmentation. Sleep disturbance may be more prevalent among smokers due to the stimulant effects of nicotine, nightly withdrawal, an increased prevalence of sleep disordered breathing relative to nonsmokers, and/or an association with psychological disturbance. These results have important clinical and public health implications for reduction of the disease and disability associated with smoking and sleep disturbance.

Objective: To measure the independent association of sleep-disordered breathing (sleep apnea and habitual snoring) and hypertension in a healthy adult population., Design: A cross-sectional study of blood pressure during wakefulness and sleep among participants with and without sleep-disordered breathing., Setting: Community-based study., Participants: 147 men and women, aged 30 to 60 years, selected from Wisconsin State employees enrolled in the Wisconsin Sleep Cohort Study, an ongoing, prospective, epidemiologic study of sleep-disordered breathing., Measurements: Sleep and medical history interview, nocturnal polysomnography, and 24-hour ambulatory blood pressure monitoring in all participants., Results: Mean blood pressures were significantly higher among participants with sleep apnea (> or = 5 apneas or hypopneas per hour of sleep) compared with those without (131/80 +/- 1.7/1.1 mm Hg compared with 122/75 +/- 1.9/1.2 mm Hg during wakefulness and 113/66 +/- 1.8/1.1 mm Hg compared with 104/62 +/- 2/1.3 mm Hg during sleep, respectively; P < 0.05). The variability of the blood pressure during sleep was significantly greater in participants with sleep apnea or a history of snoring compared with those without (P < 0.05). After controlling for obesity, age, and sex, sleep apnea was significantly associated with hypertension in a dose-response fashion, with odds ratios ranging from 2.0 for 5 apneic or hypopneic episodes per hour of sleep to 5.0 for 25 apneic or hypopneic episodes., Conclusions: Our data indicate an association between hypertension and sleep apnea independent of obesity, age, and sex in a nonselected, community-based adult population.

A survey of health status, biodemographics, and use of health care services of all children under 2 years of age, consecutively admitted to the Baudeloque ward of the Central Hospital of Yaoundé, Cameroon, was conducted over a 12-month period (1984). During the admission procedure, each child's mother or surrogate mother was interviewed and the child was weighted according to study protocol; additional data were collected by review of hospital records. A total of 669 children were recruited into the study sample; there were no refusals. Nutritional status was estimated by categories based on weight for age. Overall, 43 per cent of the sample were of normal weight-for-age, and 6 per cent, 19 per cent, and 32 per cent were categorized as having severe, moderate, and mild malnutrition, respectively. Multinomial logit modelling was used to identify independent correlates of mild, moderate, and severe PEM simultaneously. The study findings underscore the broad health benefits of immunizations. Furthermore, any prior contact of mother or child with the health care system appears to be associated with better nutritional status on hospital admission. Children with mothers employed outside the home may benefit particularly from health services outreach programmes.

The majority of urinary tract tumors cause bleeding in the urine. A program designed to detect hematuria before it is grossly apparent may contribute to earlier detection and more successful treatment of these malignancies. To test this hypothesis a hematuria home screening study was conducted. A total of 1,340 healthy men 50 years old or older used chemical reagent strips for 14 consecutive days to test the urine. Of the men 283 (21.1%) had at least 1 episode of hematuria. Of the 192 hematuria positive men who received a complete urological evaluation 16 (8.3%) had urological cancers and 47 (24.5%) had other hematuria-causing diseases that required immediate treatment. The quantity and frequency of hematuria were not related to disease severity. A hematuria home screening regimen is feasible and economical, and may promote the early detection of urinary tract cancers and other diseases in men more than 50 years old.

The association between nitrate levels in public and private sources of drinking water and gastric cancer mortality in Wisconsin was investigated in a case-control study. All gastric cancer deaths of Wisconsin residents from 1982 through 1985 were compared with deaths from other causes (controls), and nitrate levels in the home drinking water of these residents were determined. Nitrate measures for public sources were obtained from historic nitrate data from municipal sources that existed in 1970. Nitrate measures for private water sources were obtained by testing the wells individually at the existing residences. Controls were matched individually to gastric cancer cases with respect to sex, year of birth, year of death, Wisconsin birth, and Wisconsin residency at the time of death. Matched-pair analyses were performed on the paired data, and the following levels of nitrate-nitrogen exposure were used as indicators of exposure: 0.5, 2.5, 5.0, and 10.0 mg/l. Matched-pair analysis was also performed for which private water supply constituted exposure. Odds ratios and 95% confidence intervals were, respectively, 0.92 (0.75, 1.12); 0.97 (0.74, 1.35); 0.86 (0.69, 1.08); 1.50 (0.12, 18.25); and 1.09 (0.82, 1.47) for exposure to private well-water sources. These results did not indicate an increased risk of gastric cancer at any level.

Tumor grade and stage are two of the strongest predictors for indolent versus aggressive clinical course in bladder cancer. To identify age-related trends in tumor aggressiveness the authors investigated the relationships of age with grade and stage. Pathologic specimens were obtained for 89% (527 of 590) of new bladder cancer cases among men older than 50 years of age reported to the state tumor registry in Wisconsin for 1988. Tumors were grouped as low grade (G1, G2) or high grade (G3), and as superficial (Ta) or invasive (greater than or equal to T1), according to the TNM system. This analysis included 485 transitional cell carcinomas (TCC) for which the authors determined stage-stratified and grade-stratified odds ratios for men 50 through 64 years of age and older than 65 years of age. Men older than 65 years of age with superficial TCC were more than three times as likely to have a high-grade malignancy than men 50 through 64 years of age (P = 0.01); the odds ratio was 3.44 (95% CI = 1.28, 9.26). A relationship was not apparent for invasive TCC. Age and stage were weakly associated for low-grade and high-grade TCC that may be due, in part, to the strong correlation of stage with grade as a prognostic indicator. These data suggest that men in older age groups are at increased risk for superficial bladder cancer of high grade, which portends an aggressive clinical course.

Historic and current biomedical data were used to quantify changes in obesity and non-insulin-dependent diabetes mellitus (NIDDM) over a 30 year period in a Navajo community. Medical charts from an earlier study (1955-1961) provided data on 827 adults. Field-based methods yielded data from 231 adults during a health survey in 1988. The adjusted prevalence of overweight (body mass index ≥27.8 males, ≥27.3 females) has increased from 18.9% to 43.7% (P = .0001) and the adjusted prevalence of NIDDM has increased from 1.2%-12.4% (P = .0001) in the community. Current members of the community have twice the risk of being diabetic or overweight than the U.S. general population. The recent and dramatic increases in these health conditions demonstrate the effect of an important environmental component which requires further investigation. © 1992 Wiley-Liss, Inc., (Copyright © 1992 Wiley-Liss, Inc., A Wiley Company.)

The relationship between non-insulin-dependent diabetes mellitus (NIDDM) and body fat distribution (BFD) as measured by waist/hip circumference (WHR) was investigated in a Navajo community. A sample of 136 females and 89 males, 20 years and older, was recruited using a cluster-sampling design. Fifty percent of the females and 30.3% of the males are overweight [body mass index (BMI) equivalent of >120% ideal body weight]. Prevalence of NIDDM is 14% in females and 10.1% in males. The sample is characterized by central BFD (mean WHR=0.897±0.075, females and mean WHR=0.963±0.071, males). WHR is significantly related to age and BMI in males (P < 0.05), but not in females. Adjusted odds ratios for risk of NIDDM prevalence with increasing WHR category were estimated from a multiple logistic regression model which controlled for age and BMI. The odds ratio and 95% confidence interval (95% CI) is 2.19 (1.14, 4.19) for risk of NIDDM prevalence for a female in the middle BFD category compared to a female in the low BFD category. Risk increases to 3.63 (95% CI=1.25, 10.52) for a female in the highest BFD category. Although there is an increased risk of NIDDM prevalence with central BFD for males, it is not statistically significant. Preferential energy storage in abdominal fat depots may be a phenotypic expression of the "Thrifty Genotype," which places American Indians at greater risk for metabolic disorders., (Copyright © 1991 Wiley-Liss, Inc., A Wiley Company.)

In an ongoing home screening study 231 men 50 or more years old without known causes of hematuria have tested their urine each week with a chemical reagent strip for the presence of blood. After 3 months of testing 23 patients have had hematuria at least once. Of these men 5 have had urinary cancers and 5 have had other serious underlying diseases requiring immediate treatment. In only 3 of these 10 men (only 1 with cancer) did hematuria occur in more than a third of the testings or on subsequent microscopic urinalysis. The degree of hematuria was unrelated to the seriousness of its cause. We conclude that in this population hematuria occurs so intermittently that when found on routine urinalysis, regardless of quantity, serious underlying pathological conditions must be ruled out aggressively. Furthermore, regular hematuria home testing appears to offer promise as an economical means to detect urinary cancers and other serious diseases in asymptomatic men 50 or more years old.

In a homescreening study 235 asymptomatic men, 50 years of age and older without known causes of hematuria, tested their urine each week with a chemical reagent strip for the presence of blood for 1 year. Forty-four men had hematuria at least once, and 31 had a full urologic evaluation. Of these, eight were found to have urinary cancers and seven had nonmalignant diseases warranting immediate treatment. In six of these 15 men (only two with cancer) hematuria occurred in over 1/3 of the testings, and in four hematuria was found on microscopic urinalysis at the time of urologic evaluation. The degree of hematuria was unrelated to the seriousness of its cause. We conclude that in this population hematuria occurs intermittently and when found, regardless of quantity or symptoms, serious underlying pathology must be ruled out. Furthermore, regular hematuria home testing offers a promising means of detecting urinary cancers and other diseases that warrant therapy in asymptomatic men 50 years of age and older.

The association between gastrointestinal, urinary tract, brain, lung, and breast cancer mortality and drinking water trihalomethane exposure, as estimated by average daily chlorine dosage of water source 20 years past, was investigated for Wisconsin white females by use of a death certificate-based case-control study design. A total of 8,029 cancer deaths and 8,029 controls (noncancer deaths) matched on county of residence, year of death, and age were taken from mortality records of 28 counties for the years 1972-77. Data on characteristics and treatment of municipal water supplied to the residences of cases and controls were obtained from questionnaires sent to the water superintendents of the 202 waterworks associated with the sample. By the use of logistic regression analysis, odds ratios for site-specific cancer death associated with high, medium, and low chlorine-dosed water as compared to unchlorinated water exposure were determined; the control variables were urbanicity, marital status, and occupation. With the exception of cancer of the colon, no anatomic cancer site was significantly associated with any chlorine dose exposure category. For colon cancer, odds ratios of 1.51 [95% confidence interval (Cl) = 1.06-2.14], 1.53 (95% Cl=1.08-2.00, and 1.53 (95% Cl-1.11-2.11) were obtained for high-, medium-, and low-dose chlorination, respectively (P less than or equal to 0.02). For colon cancer cases and controls exposed to water sources affected by rural runoff, odds ratios of 3.30 (95% Cl=1.45-7.47), 3.60 (95% Cl=1.57-8.26), and 2.74 (95% Cl=1.10-6.88) were observed for high, medium, and low chlorine dosages 20 years past (P less than or equal to 0.025).

This paper reports the case of a male adult, 47 years old, with a gunshot wound to the right thigh, with no previous history of abdominal or cardiovascular disease, and a consistently satisfactory circulatory state on admission and thereafter. He showed signs of perforation of the caecum on the 10th day following admission. The explanation for this has been hard to find, and a search of the literature revealed no previous similar reported occurrence.

The relationship between diet and subsite-specific colon cancer was investigated using dietary histories obtained from a statewide, population-based sample of 152 proximal colon cancer patients, 201 distal colon cancer patients and 618 general population controls. The results do not support hypotheses that (1) dietary fat and cholesterol are more strongly related to proximal colon cancer and (2) vegetables and other dietary sources of fiber are more strongly associated with distal colon cancer. Vegetable consumption over lifetime was consistently protective for both proximal and distal colon cancer. Odds ratios and 95% confidence intervals for the most significant dietary factors (based on high vs. low consumption) for proximal colon cancer were: salad, 0.29 (0.17, 0.48); miscellaneous vegetables, 0.58 (0.35, 0.97); cruciferous vegetables, 0.59 (0.35, 0.97); processed lunchmeat, 2.04 (1.31, 3.17); pan-fried foods, 1.79 (1.15, 2.80); eggs, 1.75 (1.02, 2.99) and for distal colon cancer they were: salad, 0.43 (0.28, 0.67); cruciferous vegetables, 0.44 (0.28, 0.71); cheese, 0.62 (0.40, 0.96); processed lunchmeat, 1.79 (1.17, 2.73); pan-fried foods, 1.55 (1.03, 1.27). The results support recommendations that the "prudent diet" (low-fat, high-vegetable) may reduce colon cancer risk.

A case-control study was conducted to test the hypothesis that chronic ingestion of trihalomethanes (THMs), occurring as chlorination byproducts in drinking water, carries a risk of colon cancer. Lifetime residential and water source histories and information on water-drinking habits, diet, sociodemographics, medical and occupation histories, lifestyle and other factors were obtained by questionnaire from a statewide sample of newly-diagnosed colon cancer cases (N = 347), controls with cancer of other sites (N = 639) and general population controls (N = 611). Since no data on past THM levels exists, it was necessary to devise a scheme to generate THM estimates for all Wisconsin water sources. For this, a statistical model based on quantitative THM measures and routinely-recorded data taken at 81 municipal water facilities was used in conjunction with individual residential histories to estimate lifetime and period-specific THM exposure for each case and control. Logistic regression was used to estimate odds ratios adjusted for age, sex and urban living, for colon cancer and THM exposure. The study results indicate that THM in Wisconsin drinking water does not pose a significant colon cancer risk. Odds ratios for exposure to the middle and highest category of lifetime cumulative THM were 1.05 (95% Cl = 0.66-1.68) and 0.93(95%Cl = 0.55-1.57) respectively, relative to the cancer control group, and 1.10 (95%Cl = 0.68-1.78) and 0.73 (95% Cl = 0.44-1.21) respectively, relative to the general population controls.(ABSTRACT TRUNCATED AT 250 WORDS)

A prospective study of 125 elderly patients (over 65 years) with proximal femoral fracture was carried out to compare pre-fracture sociomedical factors with the local and general complications following surgical treatment, in predicting mortality and length of stay. A poor pre-fracture mental state was more important than associated physical illness in predicting mortality. Pre-fracture mobility state was the most useful early prognostic predictor of length of hospitalization. Post-operative general complications were the most significant in predicting mortality and length of hospitalization, and more important than failure of operative technique.

Psychologically distressed patients and clients of health care and social service organizations are found to report somewhat more dissatisfaction with services than do the nondistressed. Four explanations for this relationship are examined: 1) the psychologically distressed are generally dissatisfied; 2) service providers react negatively to the psychologically distressed; 3) psychologically distressed patients are dissatisfied when service providers do not respond to their psychological needs; and 4) patients who deny their psychological distress tend to be dissatisfied. The results show that the psychologically distressed report more dissatisfaction because of the very high levels of dissatisfaction found among patients who deny having personal problems.