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Background & Aims: Vibration-controlled transient elastography (VCTE), which measures liver stiffness, has become an important tool for evaluating patients with nonalcoholic fatty liver disease (NAFLD). We aimed to determine the diagnostic accuracy of VCTE in detection of NAFLD in a multicenter cohort of patients., Methods: We performed a prospective study of 393 adults with NAFLD who underwent VCTE within 1 year of liver histology analysis (median time, 49 d; interquartile range, 25-78 d), from July 1, 2014, through July 31, 2017. Liver stiffness measurement (LSM) cut-off values for pairwise fibrosis stage and controlled attenuation parameter cut-off values for pairwise steatosis grade were determined using cross-validated area under the receiver operating characteristics curve (AUROC) analyses. Diagnostic statistics were computed at a sensitivity fixed at 90% and a specificity fixed at 90%., Results: LSM identified patients with advanced fibrosis with an AUROC of 0.83 (95% CI, 0.79- 0.87) and patients with cirrhosis with an AUROC of 0.93 (95% CI, 0.90-0.97). At a fixed sensitivity, a cut-off LSM of 6.5 kPa excluded advanced fibrosis with a negative predictive value of 0.91, and a cut-off LSM of 12.1 kPa excluded cirrhosis with a negative predictive value of 0.99. At a fixed specificity, LSM identified patients with advanced fibrosis with a positive predictive value of 0.71 and patients with cirrhosis with a positive predictive value of 0.41. Controlled attenuation parameter analysis detected steatosis with an AUROC of 0.76 (95% CI, 0.64-0.87). In contrast, the VCTE was less accurate in distinguishing lower fibrosis stages, higher steatosis grades, or the presence of NASH., Conclusions: In a prospective study of adults with NAFLD, we found VCTE to accurately distinguish advanced vs earlier stages of fibrosis, using liver histology as the reference standard., (Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Vibration-controlled transient elastography estimates liver stiffness measurement (LSM) and controlled attenuation parameter (CAP), which are noninvasive assessments of hepatic fibrosis and steatosis, respectively. However, prior vibration-controlled transient elastography studies reported high failure rates in patients with nonalcoholic fatty liver disease. We examined the performance characteristics of the FibroScan 502 Touch with two probes, medium (M+) and extra large (XL+), in patients with nonalcoholic fatty liver disease in a multicenter setting. A total of 1,696 exams were attempted in 992 patients (body mass index, 33.6 ± 6.5 kg/m 2 ) with histologically confirmed nonalcoholic fatty liver disease. Simultaneous assessment of LSM and CAP was performed using the FibroScan 502 Touch with an automatic probe selection tool. Testing was conducted twice in patients by either a single operator (87%) or two operators (13%). Failure was defined as the inability to obtain a valid examination. An examination was considered unreliable if LSM interquartile range/median was >30%. Significant disagreement between two readings was defined as >95% limits of agreement between two readings. A total of 1,641 examinations yielded valid results with a failure rate of 3.2% (55/1,696). The proportion of unreliable scans for LSM was 3.9%. The proportion of unreliable scans with operator experience in the top quartile (≥59 procedures) was significantly lower than that in the lower three quarters combined (1.6% versus 4.7%, P = 0.02 by Fisher's exact test). The significant disagreement between first and second readings for LSM and CAP when obtained back to back was 18% and 11%, respectively., Conclusion: Vibration-controlled transient elastography for estimation of LSM and CAP can be successfully deployed in a multicenter setting with low failure (3.2%) and high reliability (>95%) rates and high reproducibility. (Hepatology 2018;67:134-144)., (© 2017 by the American Association for the Study of Liver Diseases.)

The risks for four cancers, leukemia, lymphopoietic cancers (LHC), lung cancer and mesothelioma, were studied in workers from shipyards involved in nuclear powered ship overhauls. The population represented a sample of all workers based on radiation dose at study termination. The final sample included 28,000 workers with > or = 5.0 mSv, 10,462 workers with < 5.0 mSv and 33,353 non-nuclear workers. Nuclear workers had lower mortality rates for leukemia and LHC than US white males but higher rates of lung cancer and a significant five-fold excess of mesothelioma. Dose-dependent analyses of risks in the high exposure group indicated that for each cancer the risk increased at exposures above 10.0 mSv. An internal comparison of workers with 50.0 mSv exposures to workers with exposures of 5.0-9.9 mSv indicated relative risks for leukemia of 2.41 (95% CI: 0.5, 23.8), for LHC, 2.94 (95% CI: 1.0,12.0), for lung cancer, 1.26 (95% CI: 0.9, 1.9) and for mesothelioma, 1.61 (95% CI: 0.4, 9.7) for the higher exposure group. Except for LHC, these risks are not significant. However, the increasing risk with increasing exposure for these cancers, some of which are known to be related to radiation, suggests that low-level protracted exposures to gamma rays may be associated with these cancers. Other agents such as asbestos, which are common to shipyard work, may play a role especially in the risk of mesothelioma. Future follow up of the population would identify bounds on radiation risks for this population for comparison with similar risks estimated from other populations.

Objective: To characterize the effect of cytomegalovirus (CMV) retinitis and its treatment on visual acuity in patients with the acquired immunodeficiency syndrome., Methods: We evaluated 648 consecutive patients with the acquired immunodeficiency syndrome at 1 center for the prevalence of visual impairment at the time of CMV retinitis diagnosis and for the incidence of visual impairment across time., Results: Among affected eyes, the prevalence of a visual acuity measurement of 20/50 or worse or 20/200 or worse at the time of CMV retinitis diagnosis was 33% and 17%, respectively. White race and injection drug use were associated with a lower and a higher prevalence of visual impairment, respectively. At 1 year, the cumulative incidence of loss of 3, 6, and 10 lines of visual acuity was 42%, 30%, and 23%, respectively, and the incidence of visual impairment to the level of 20/50 or worse and 20/200 or worse was 34% and 24%, respectively. Patients who received highly active antiretroviral therapy had an approximately 75% lower risk of visual impairment, with the greatest benefit among those observed to have immune recovery. The incidence of loss of visual acuity did not significantly differ between eyes treated with systemic anti-CMV therapy only, initial ganciclovir implant therapy, or systemic followed by implant therapy., Conclusions: The prevalence of visual impairment at the time of CMV retinitis diagnosis is high and varies according to demographic characteristics. The incidence of visual impairment during follow-up is also high but is substantially lower among patients who receive highly active antiretroviral therapy, especially those observed to have immune recovery.

In order to investigate the nature of the association of involuntarily delayed first birth and risk of breast cancer, 1083 white women who had been evaluated and treated for infertility from 1945-1965 were followed prospectively through April 1978 to ascertain their breast cancer incidence. These women were categorized as to the cause of infertility into two groups, those with endogenous progesterone deficiency (PD) and those with nonhormonal causes (NH). Women in the PD group had 5.4 times the risk of premenopausal breast cancer compared to women in the NH group. This excess risk could not be explained by differences between the two groups in ages at menarche or menopause, history of oral contraceptive use, history of benign breast disease or age at first birth. Women in the PD group also experienced a 10-fold increase in deaths from all malignant neoplasms compared to the NH group. The incidence of postmenopausal breast cancer did not differ significantly between the two groups.

A community-wide study was conducted in metropolitan Baltimore in which the survival of 1,307 patients with acute myocardial infarction was examined according to use of anticoagulants. The adjusted in-hospital case-fatality rate was lower for patients receiving anticoagulants (18%) than for those not receiving this therapy (31%). This difference persisted in each period examined in the study (1966 and 1967 or 1971) and was found in 17 of 20 participating hospitals. For hospital survivors followed up for as long as ten years, a better survival was again found for those treated with anticoagulants in the acute phase compared with those not treated.

The ability of subjects to recall their year of hire, year of termination, and job title was studied by comparing reported information to that recorded in personnel records. Former shipyard workers were interviewed in 1982. A majority was first employed in one of two shipyards during the early 1940s and 1950s. kappa statistics and crude and adjusted measures of percent agreement were derived to determine whether reported work history agreed with what was recorded in the subjects' personnel record and to determine whether recall was associated with race, age of the respondent at the time of interview, years since leaving the yard, length of employment, and year of hire. After adjusting for other covariates, only the number of years since leaving the yard was associated with recall of year of hire and termination, but not job title. In addition, however, there were several other noteworthy findings. Individuals who were 65-69 years of age at the time of interview had the poorest recall. Recall of both the year of hire and the job title appears to improve with increasing length of employment.

A population-based study was conducted in metropolitan Baltimore, in which the prognosis of 504 patients hospitalized with acute myocardial infarction (MI) from July 1966 through June 1967 was compared with that of 803 patients hospitalized from January through December 1971. For patients admitted to coronary care units (CCUs), the in-hospital case-fatality rate (CFR) in 1971 (20%) was found to be significantly lower than that in 1966/67 (27.5%) (p less than .025), after simultaneous adjustment for 16 variables which may affect prognosis. No such significant difference was detected for patients not admitted to CCUs when the two time periods were compared. As a result of these time trends, CFRs were not significantly different between CCU and non-CCU patients in 1966/67, but in 1971 a significant advantage was shown for CCU patients (p less than .005). These results suggest that effectiveness of CCUs in prevention of in-hospital deaths increased between 1966/67 and 1971. For hospital survivors, regardless of admission to a CCU, no significant differences in long-term prognosis were found between patients discharged in 1971 and those discharged in 1966/67. This finding may reflect the lack of major therapeutic advances between the two study periods, aimed at reducing the progression of coronary atherosclerosis and/or the extent of the infarcted area.

A retrospective study of the relationship of oral contraception to thrombosis was made in 104 idiopathic cases, 357 other thrombotic cases (exclusive of cerebrovascular thrombosis), and 1302 matched controls. The relative risk for idiopathic case users was 7.2 times that for non-users; for the whole series it was 1.9. The apparent low risk for non-idiopathic cases is considered to be due to selective prescription of this method of contraception. The risk for women using formulations containing 100 mug or more of estrogen was higher than that for users of lower doses. Among the controls, the risk of gallbladder surgery was twice as high for users as non-users. Several theoretical sources of bias were searched for and shown not to be present. Histories of oral contraceptive use were found to be accurate. A definite risk of thrombosis exists even with the low-estrogen dosage currently employed in oral contraceptive steroids.

A matched-pair analysis of 228 cases of endometritis occurring over a two-year period in 4,823 elective abortion patients was carried out. Patients with postabortal endometritis were matched with control subjects for age, parity, race, pay status, time of abortion, and type of abortion procedure. The prevalence of endocervical gonorrhea was 2.7% in the entire group seeking abortion, with 14.7% of patients with gonorrhea subsequently developing endometritis. The matched-pair analysis detected a threefold increased risk for endometritis in patients with untreated gonoccocal endocervicitis when compared with control subjects (p less than 0.05). The significance of these findings to centers performing abortions is discussed.

A community-wide study was conducted to examine time trends in incidence rates of leukemia in children. Cases of acute leukemia, both lymphocytic (ALL) and nonlymphocytic (ANLL), newly diagnosed in children ages 0-19 years in the Baltimore area from 1960 to 1974 were ascertained. Over the 15 years, 286 children with acute leukemia were identified, of whom 77% had ALL. Incidence rates of ALL were two to three times as high in whites as in blacks, and remained virtually unchanged over time. However, the picture was quite different for ANLL. Initially, incidence rates were higher in whites than in blacks, but during the final five years the incidence increased dramatically in blacks so that it actually exceeded the rate among whites. The increase of ANLL in black children occurred primarily in blacks of high socioeconomic status. This suggests that the increase may have resulted from environmental influences associated with upward socioeconomic mobility in the black population in recent years.

Intra-amniotic hyperosmolar urea (59.7 per cent) augmented by intravenous oxytocin (332 millimicron per minute), prostaglandin F2alpha (20 mg.), prostaglandin F2alpha (10 mg.), or prostaglandin F2alpha (5 mg.) was utilized for 1,913 patients requesting elective midtrimester abortion. Injection-abortion intervals ranging from 13.70 to 21.49 hours were achieved with failure rates of 0.7 to 6.7 per cent. Despite frequent pre-existing medical conditions, the complication rate compared favorably with those of other methods for terminating midtrimester pregnancy such as saline amnioinfusion or dilatation and evacuation.

A population-based study was conducted in metropolitan Baltimore in which the short- and long-term prognosis of 283 patients with nontransmural myocardial infarction was compared with that of 953 patients with transmural infraction. After simultaneous adjustment for several variables, the in-hospital case fatality rate was greater for patients with transmural (30.1 percent) than with nontransmural (18.3 percent) infarction (P less than 0.01). However, for patients discharged alive from the hospital and followed up for as long as 10 years, no significant differences in survival were found between the groups with transmural and nontransmural infarction. A multiple adjustment procedure yield 3 year case fatality rates of 27.1 percent and 28.3 percent, respectively, for patients with transmural and nontransmural myocardial infarction surviving the acute phase. These results suggest that the long-term prognosis of patients with nontransmural infarction is as guarded as that of patients with transmural infarction and that attempts to prevent subsequent mortality should be diligently pursued in both groups of patients.

A study was carried out in metropolitan Baltimore in which the short- and long-term prognosis of 655 patients with anterior myocardial infarction (MI) was compared with that of 520 patients with inferior/posterior MI. The study was performed on a community-wide basis in two time periods before the clinical introduction and widespread use of beta-blockade therapy. After simultaneous adjustment for several socio-demographic and clinical variables, the in-hospital case fatality rate was greater for patients with anterior (27.5%) than for those with inferior/posterior MI (22.9%) (p less than 0.05). Similarly, for those discharged alive from the hospital and followed up for as long as 10 years, patients with infarction of the anterior wall had a significantly poorer long-term survival than that of patients with infarction of the inferior/posterior wall (p less than 0.05). These results suggest that closer surveillance should be directed at patients with anterior myocardial infarction, both during the acute phase and after hospital discharge.

A comparison between prescriber records and patient-reported oral contraceptive histories obtained during a case-control study of thromboembolism and oral contraceptive use served as the basis for evaluating the extent of agreement between these two sources of information. Agreement between oral contraceptive user and prescriber was highest on the name of the most recently-used product (89% agreement), and dropped to 62.5% on the name of the product taken before the more recent one. For total duration of oral contraceptive use (to within one month of hospital admission), agreement (defined as differences not exceeding one month) was 36%, while 39% showed the users reporting longer duration of use, and 25% showed users reporting shorter duration. Cases showed a higher rate of agreement with prescriber records than the controls on both the name of the product and the total duration of use. Disagreement from prescriber records in the direction of reporting longer duration of use was 45% for the controls compared to 27% for the cases. These results indicate that while user information in connection with the most recently used oral contraceptive can be acceptable in studies employing the case-control research strategy, user reports about previous oral contraceptive use may be less useful.

Analysis of data from the Ontario Perinatal Mortality Study has shown that perinatal mortality increases directly with the level of maternal smoking during pregnancy. Increases in smoking level are associated with increases in the frequency of early fetal deaths and of neonatal deaths due to premature delivery. These deaths in turn are associated with smoking-related increases in the incidence of bleeding during pregnancy, abruptio placentae, placenta previa, and premature and prolonged rupture of the membranes.

Our case-control study of the relation between estrogen use and endometrial cancer involved 451 cases and 888 controls. The overall risk of endometrial carcinoma was sixfold for estrogen users as compared with nonusers; long-term users (greater than five years) had a 15-fold risk. Excess risk was present for both diethylstilberstrol and conjugated estrogens. The risk associated with cyclic use was as great as that for continuous use. Increased risk was associated with estrogen use for all histologic grades of the tumor. The risk of advanced-stage carcinoma was fourfold for estrogen users, but rhe confidence interval was wide, and this question requires further study. Finally, this investigation contradicts the speculation that the association between this cancer and estrogen use can be explained by swifter diagnosis for estrogen users, misclassification of estrogen-related hyperplasia or treatment of early symptoms of the tumor with estrogen.

To identify components of smoking-related increased perinatal mortality, detailed analyses of data from the Ontario Perinatal Mortality Study (50,000 births, 1,300 deaths, 1960-1961) measured the relationship of maternal smoking to birth weight, gestation, placental complications, and perinatal mortality. Cross-tabulations with other factors and multiple adjustment showed increases with amount smoked of birth weights less than 2500 gm, gestations less than 38 weeks, placenta previa, abruptio placentae, and perinatal mortality. These significant, smoking-related increases were independent of mother's height, weight, hospital status, age-parity group, birthplace, previous pregnancy history, weight gain, time of registration, and sex of child. Maternal smoking had the strongest effect on birthweight in the 8 factor regression, and birth less than 2500 gm increased directly with smoking level from 20% to 340% in 37 data subgroups. Births less than 38 weeks increased 20% and 50% and perinatal mortality increased 20% and 35% for less than 1 pack and 1 + pack smokers, respectively, adjusted for 7 other factors. Placental complications increased consistently with smoking level in all of 37 subgroups except for primiparous less than 1 pack smokers. Adjusted rates increased 25% and 92% for placenta previa, 23% and 86% for abruptions among smokers of less than 1 pack and 1 + packs, respectively. These complications carry high perinatal mortality risk, and account for one-third to one-half of the perinatal deaths attributable to maternal smoking.

To see if the risk factors associated with fibroadenoma and cystic disease were similar to those reported for breast cancer, a retrospective study of benign breast tumor in a general population was conducted in Washington County, Maryland. The study population consisted of 320 white women 20 to 49 years of age who had had benign breast disease and 320 age-matched controls. More cystic disease cases than controls had the following characteristics, which had been reported to have been associated with breast cancer in other studies: higher socioeconomic status; fewer pregnancies; and a lack of association with lactation patterns. Nulliparity, late natural menopause and a maternal history of breast cancer were also more common among cystic cases than controls, although these differences could have occurred by chance. Cystic disease cases and controls did not differ with respect to other factors associated with breast cancer, such as early age at menarche, late age at first pregnancy, and negative history of artificial menopause. In contrast to cystic breast disease, fibroadenoma was not associated with most of the risk factors of breast cancer.

We studied 284 patients (20-74 years of age) with carcinoma of the breast and 367 controls; all were admitted to one hospital between 1969 and 1972. The disease was associated with nulliparity, first pregnancy over 20 years of age, premenopausal status, and a lower frequency of artificial menopause. After adjustment for these factors, no significant difference was found between the breast cancer patients and controls in their prior use of either estrogens or oral contraceptives, but the confidence limits on the relative risk, especially for oral contraceptives, were large.

Increased perinatal mortality among smokers' babies has been observed in many but not in all studies, with a statistically significant difference in some. This paper explores the hypothesis that maternal smoking may interact with other risk factors, so that a dose-related increase in perinatal mortality may be enhance or masked depending upon the presence or absence of these factors. Data are from the Ontario Perinatal Mortality Study of all single b irths in 10 teaching hospitals in Ontario in 1960-1961 a total of 51,490 births, including 701 fetal deaths and 655 early neonatal deaths. Perinatal mortality increased significantly with smoking, and was also affected by such factors as maternal age, parity, hospital status, previous pregnancy history, hemoglobin level, and others. Smoking frequencies also varied by many of these characteristics. Perinatal mortality was therefore analyzed by the amount smoked during pregnancy within subgroups of these antecedent risk factors. When smoking and other risk factors were cross-tabulated among 52 data subgroups, only the light smokers (less than 1 pack per day) under age 20 had lower perinatal mortality rates than their nonsmoking counterparts. In almost all subgroups the mortality increase with smoking was dose-related, but not in a simple, linear way. The increased risk of perinatal mortality associated with light smoking among young, low-parity, non-anemic mothers was less than 10 percent. At the other extreme, mothers of high parity, public hospital status, with previous low birthweight births, or with hemoglobin less than 11 gm had increased perinatal mortality risks of 70-100 percent when they were heavy smokers. The failure of some studies to find a significant increase in perinatal mortality with maternal smoking may be due to selection of study populations from the end of the spectrum where light smoking is associated with only a slight increase in perinatal risk. Other studies may select higher risk populations, where the influence of smoking on mortality is stronger. Depending on the magnitude of the difference, the amount smoked, and the size of the study, results might or might not be statistically significant.

Longitudinal data on caries experience were derived from the reexamination and interview of a cohort of 306 subjects with an average follow-up period of 33 years after the baseline examination. Analysis of the data was accomplished by the use of contingency tables utilizing enumeration statistics compared with a multiple regression analysis. The analyses indicated a strong association of caries experience at one point in time with the caries experience of that same person earlier in life. The regression model approach offers adjustment of any given independent variable for the effect of all other independent variables, providing a powerful means of bias reduction. The model is also useful in separating out the specific effect of an independent variable over and above the contribution of other variables. The model used explained 35% of the variability in the DMFS scores recorded. Similar models could be useful adjuncts in the analyses of dental epidemiologic data.

A community-wide study was conducted in metropolitan Baltimore in which the prognosis of 330 patients hospitalized with an acute myocardial infarction (MI) complicated by ventricular fibrillation or cardiac arrest (VFib/CA) was compared with that of 1,071 patients hospitalized with acute MI not complicated by VFib/CA. As expected, the in-hospital case-fatality rate among patients with MI complicated by VFib/CA was significantly higher than that in patients without VFib/CA. However, for patients discharged alive from the hospital, no significant differences in long-term survival were found between patients with MI with or without VFib/CA. These results suggest that attempts at preventing subsequent mortality should be diligently pursued in patients with MI who are discharged alive from the hospital regardless of the occurrence of VFib/CA in the acute phase.

Reproductive risk factors were estimated for 783 cases of cystic disease of the breast, 155 fibroadenoma, 94 miscellaneous breast conditions, and 284 breast cancers. Controls were matched for age, race, ever-married status, time of hospitalization and pay status. The most consistent attributes are a tendency to be still premenopausal, to have had her first pregnancy beyond the age of twenty-five years (or to have had none), and to have had fewer total pregnancies than the control. All are associated with a longer menstrual life prior to onset of the disease than the controls. Findings for cystic disease are compared with other studies. Patients with benign breast disease share some of the demonstrated risk factors for breast cancer.

Male employees of 2 East Coast telephone companies who participated in standardized respiratory surveys from 1961 to 1969 were followed to ascertain days of disability resulting from respiratory illnesses that lasted for more than a week. Subjects for this study were 1,386 white males between the ages of 40 and 65 yr who had had no disabling chest illnesses in the 3-yr period prior to examination. Several survey findings were predictive of subsequent days lost from work. Listed in order of importance, these were diminished forced expiratory volume, a history of ever having had asthma, marked shortness of breath, chronic cough and phlegm, and chronic wheeze. A history of ever having had hay fever was associated with a diminished risk of lost time because of respiratory illness.

Contrary to general belief, larvae of Ancylostoma duodenale do not always develop directly to adulthood upon invasion of man. In West Bengal, India, arrested development appears to be a seasonal phenomenon which results in (i) reduction of egg output wasted in seeding an inhospitable environment and (ii) a marked increase in eggs entering the environment just before the monsoon begins.