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Background: Low-radiation-dose spiral CT (LDCT) scanning is capable of detecting lung neoplasms in asymptomatic individuals. To determine whether such detection can reduce lung cancer mortality, a randomized controlled trial (RCT) of LDCT scanning is necessary. Methods: The feasibility of conducting an RCT in asymptomatic individuals who are at high risk for lung cancer was explored in the Lung Screening Study (LSS), a 12-month special project of the ongoing Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial. During the fall of 2000, six PLCO screening centers recruited a total of 3,318 heavy or long-term smokers who were not participants in the PLCO trial and randomized them to receive either a screening LDCT scan (1,660 participants) or screening posteroanterior view chest radiograph (CXR) [1,658 participants]. Results: The screens were completed on 96% of subjects in the LDCT scan arm and 93% of subjects in the CXR arm. A total of 20.5% of screened subjects in the LDCT scan arm and 9.8% of those in the CXR arm had findings that were suspicious for lung cancer. Thirty lung cancers in subjects in the LDCT arm and 7 lung cancers in patients in the CXR arm were diagnosed following a positive screening result. Additional data from the LSS indicated that, among persons who were at elevated risk for lung cancer, CT scan use was not pervasive, interest in participating in an RCT of LDCT scanning was strong, and few subjects randomized to CXR either refused their examination or sought a CT scan after their study CXR. Interpretation: The results of the LSS demonstrated convincingly the feasibility of an RCT of LDCT scanning in the United States. [ABSTRACT FROM AUTHOR]

Studies the effect of cataract surgery on elderly persons' self-images. Elderly persons' self-images before the cataract; Improvement in their self-images and outlook after surgery.

Background: To provide an understanding of important aspects of the participant recruitment and data collection, become aware of any potential problems, and obtain necessary information in order to design a large-scale randomized controlled trial (RCT) for lung cancer and colorectal cancer (CRC) screening in China., Methods: This feasibility study was a multicentered, open-label, pilot randomized trial. A total of 2696 participants who were at high risk of lung cancer were recruited from three screening centers and randomly allocated to arm 1 ( n  = 894), annual low-dose computed tomography (LDCT) plus a baseline colonoscopy; arm 2 ( n  = 902), biennial LDCT plus annual fecal immunochemical test (FIT) with OC-Sensor (OC-FIT); and arm 3 ( n  = 900), annual Insure-FIT plus Septin 9 blood test. Information on randomization, compliance, positivity rate, cancer case detection, and contamination with screening for lung cancer and CRC were collected., Results: Participant characteristics were similar across study arms. The compliance rate of annual LDCT screening in arm 1 was 86.4% (95% CI: 83.9%, 88.5%) at baseline (T0), and 69.0% (95% CI: 65.8%, 72.0%) and 70.7% (95% CI: 67.6%, 73.7%) at the following two rounds (T1 and T2). The compliance rates of biennial LDCT screening in arm 2 were similar to those in arm 1 in the corresponding rounds. The compliance rate was 55.5% (95% CI: 52.2%, 58.8%) for colonoscopy in arm 1, while the compliance rates of OC-FIT, Insure-FIT, and the Septin 9 test in arms 2 and 3 were all approximately 90% at T0, decreasing to 65%-80% at T1 and T2. The positivity rate, cancer case detection rate, and contamination rate of screening for lung cancer and CRC were also reported., Conclusion: In this pilot study, the feasibility of an RCT in China of lung cancer and CRC screening was demonstrated., Competing Interests: The authors declare that they have no conflict of interests., (© 2021 Chinese National Cancer Center. Published by Elsevier B.V.)

Cardiovascular (CV) toxicity from cancer therapy is a significant and growing concern. Conventional oncology clinical trial designs focused singularly on cancer treatment efficacy have not provided sufficient information on both CV risk factors and outcomes. Similarly, traditional CV trials evaluating standard interventions typically exclude cancer patients, particularly those actively receiving cancer therapy. Neither trial type simultaneously evaluates the balance between CV toxicity and cancer outcomes. However, there is increasing collaboration among oncologists and cardiologists to design new cardio-oncology trials that address this important need. In this review, we detail five ongoing, oncology-based trials with integrated CV endpoints. Key design features include: 1) a careful assessment of baseline risk factors for CV disease; 2) an introduction of cardioprotective interventions at various timepoints in cancer therapy; 3) a balance of the risk of subclinical CV injury with the need for ongoing cancer treatment; and 4) an understanding of the time profile for development of clinically apparent CV toxicity. Additional critical priorities in cardio-oncology clinical research include harmonization of data collection and definitions for all physician- and patient-reported exposures and outcomes., Competing Interests: Disclosures: No conflicts of interest exist.

Background: The objective of this investigation was to evaluate the association between toenail selenium concentration and lung cancer risk in male smokers., Methods: We conducted a nested case-control study within the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study cohort. This substudy included 250 randomly selected incident lung cancer cases and 250 controls matched on age (up to +/- 5 years), intervention group assignment, and date of randomization (+/- 15 days). Odds ratios (ORs) and 95% confidence intervals (CIs) were determined using conditional logistic regression methods. Finland began fortification of agricultural fertilizers in the fall of 1984, increasing the dietary intake, plasma, and toenail selenium concentrations for the population. The present analyses were based on the calculated residual of toenail selenium after regressing it on date of randomization. The selenium residual and the interaction of the residual with date of randomization were included in models with smoking status and body mass index as covariates., Results: We observed a suggestion of a protective association for higher selenium status among men who entered the trial early (when the range of selenium values included very low levels). The OR for men with adjusted toenail selenium concentrations at the 75th percentile compared to those with the lowest selenium concentrations ranged between 0.20 (0.09-0.44) for men randomized earliest in the trial and 0.61 (0.27-1.41) for men randomized in the fifth year., Conclusions: These results suggest that low selenium status may be associated with increased risk for lung cancer.

Background: The Mayo Lung Project (MLP) was a randomized, controlled clinical trial of lung cancer screening that was conducted in 9211 male smokers between 1971 and 1983. The intervention arm was offered chest x-ray and sputum cytology every 4 months for 6 years; the usual-care arm was advised at trial entry to receive the same tests annually. No lung cancer mortality benefit was evident at the end of the study. We have extended follow-up through 1996., Methods: A National Death Index-PLUS search was used to assign vital status and date and cause of death for 6523 participants with unknown information. The median survival for lung cancer patients diagnosed before July 1, 1983, was calculated by use of Kaplan-Meier estimates. Survival curves were compared with the log-rank test., Results: The median follow-up time was 20.5 years. Lung cancer mortality was 4.4 (95% confidence interval [CI] = 3.9-4.9) deaths per 1000 person-years in the intervention arm and 3.9 (95% CI = 3.5-4.4) in the usual-care arm (two-sided P: for difference =.09). For participants diagnosed with lung cancer before July 1, 1983, survival was better in the intervention arm (two-sided P: =.0039). The median survival for patients with resected early-stage disease was 16.0 years in the intervention arm versus 5.0 years in the usual-care arm., Conclusions: Extended follow-up of MLP participants did not reveal a lung cancer mortality reduction for the intervention arm. Similar mortality but better survival for individuals in the intervention arm indicates that some lesions with limited clinical relevance may have been identified in the intervention arm.

Plasma lipid and serum apoprotein concentrations were determined in twenty-nine individuals with Gaucher type I disease. Plasma total cholesterol, low density lipoprotein (LDL) cholesterol and high density lipoprotein (HDL) cholesterol were all significantly reduced in the patients with Gaucher disease compared to a group of matched control subjects. Total, LDL and HDL cholesterol were lower in males than in females with Gaucher disease. These sex differences appeared to be inversely correlated with the severity of disease manifestations which were greater in the males. Serum levels of apoprotein-B and apoprotein-AI, the major structural apoproteins of LDL and HDL, respectively, were decreased in the subjects with Gaucher disease. Thus, the reductions in LDL and HDL cholesterol were associated with reduced numbers of lipoprotein particles in plasma. In contrast, apoprotein-E, a protein which is secreted by several tissues, including activated macrophages and which may mediate hepatic catabolism of lipoproteins, was elevated in the patients. Since macrophages may also catabolize lipoproteins, Gaucher disease may serve as a model for the effect of activated macrophages upon human lipoprotein metabolism.

Characterization of the hypocholesterolemia observed in polycythemia vera and agnogenic myeloid metaplasia revealed significant reductions in plasma total cholesterol, low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol in an age- and sex-matched comparison with the Framingham population. Men with myeloproliferative disease also had significantly lower total and LDL cholesterol levels than did those with relative or secondary polycythemia. LDL and HDL cholesterol were significantly correlated, suggesting a generalized disturbance of cholesterol metabolism, unexplained by nutritional status. Evaluation of the relationship among hematic cell proliferation, degree of myeloid metaplasia and hypocholesterolemia by multiple regression analysis revealed that spleen size was the variable of most significance in explaining the variation in plasma total, LDL and HDL cholesterol levels. Uncontrolled disease activity was accompanied by a decline in LDL cholesterol levels. Splenectomy or control of proliferation with chemotherapy or splenic irradiation reversed this abnormality. Levels of plasma total and lipoprotein cholesterol provide information that may be of value in diagnosis and assessment of myeloproliferative disease activity.

Factors influencing onset of remission in myasthenia gravis were evaluated in 2062 patients, of whom 962 had had thymectomy. Multivariate analysis showed that appearance of early remissions among all patients was significantly and independently influenced by thymectomy, by milder disease, and by absence of coexisting thymomas. Patients with mild generalized symptoms treated with thymectomy reached remission more frequently, even when compared with those with ocular myasthenia treated without surgery. Short duration of disease before thymectomy in mild cases was another factor associated with earlier remissions. Mortality for all patients was significantly and independently influenced by severity of symptoms, age, associated thymomas, and failure to remove the thymus. Patients without thymectomy and with thymomas had, in addition, earlier onset of extrathymic neoplasms. Morbidity after the transcervical approach was minimal. This study demonstrates that early thymectomy by the transcervical approach, when technically feasible, has significant clinical advantages over the transthoracic approach and should be advocated for all patients with myasthenia gravis, including those with ocular disease.

Fetal thoracic circumference and thoracic length measurements were obtained by ultrasonographic examination on 576 women between 16 and 40 weeks gestation. Nomograms for thoracic circumference and thoracic length with respect to gestational age were developed. Growth of both thoracic parameters was observed to be linear throughout gestation. In normal pregnancy the ratios of thoracic circumference to abdominal circumference and thoracic length to humerus length remained virtually constant at 0.89 and 0.93, respectively.

Caffeine, which has been linked to benign breast disease, has an antineoplastic effect in experimental animals, whereas in tissue cultures it inhibits mitoses and induces cell differentiation. We examined caffeine and coffee intake in 101 women with breast cancer to determine whether either or both influence cell differentiation in tumors as well. Nutrient analysis was performed by the Nutrition Coding Center of the University of Minnesota with the Nutrition Data system from the National Heart, Lung, and Blood Institute. Stepwise logistic regression, with tumor differentiation (well and moderate versus poor) as the dependent variable, was used. The analysis indicates that caffeine and/or coffee intake has a significant association with tumor differentiation as women with moderately to well-differentiated tumors had higher caffeine and coffee intake. This raises the question whether caffeine or coffee consumption may help induce cell differentiation and slow tumor growth.

Eighty-one therapeutic trials of alcohol withdrawal were found that have been published in English since 1954; controls were randomized in 29 (RCTs). Two thousand three hundred thirteen patients were randomized. Variable pretreatment description prevented estimates of delirium tremens and convulsion prevalence, but only four deaths were reported. Endpoints were thus entirely subjective in these moderately ill patients. Protocol quality of the RCTs was graded by a previously developed system for evaluating adequacy of descriptions, blinding, and essential measurements. Mean score obtained was .49 +/- .03 (1 SE). (A perfect paper would score 1.00.) Data presentations and statistical analyses scored .18 +/- .03. There was little evidence of improvement of scores over time. Papers lacked confidence intervals, proper handling of dropouts, and adequate details of side effects. In five RCTs, six comparisons showed that benzodiazepines are clearly superior to placebo (p less than .001), but conclusions about comparisons with other drugs were not possible. In none of eight "negative" comparisons was the probability of a type II error (beta) considered. Discovery of more effective symptomatic agents or methods of reducing the death rate will require more rigid protocols and analyses as well as larger studies to allow the use of more critical endpoints such as occurrence of delirium tremens, convulsions, or death.

The hemodynamic effects of a nifedipine infusion were investigated in eight dogs given fentanyl/pancuronium/nitrous oxide/oxygen anesthesia. Nifedipine (20 micrograms/kg) was given intravenously over two minutes immediately prior to each 30-minute infusion at 2 micrograms/kg/min, 4 micrograms/kg/min, and 6 micrograms/kg/min. The range of plasma nifedipine levels obtained was 52.1 to 113.7 ng/mL. The predominant hemodynamic effects were significant reductions in systemic vascular resistance (SVR) and mean aortic pressure (MAP), accompanied by a rise in cardiac index and heart rate (HR). Administration of calcium chloride (20 mg/kg) after the nifedipine infusion had no effect on SVR or MAP, but HR was significantly reduced. Serum epinephrine and norepinephrine levels increased after the infusion of nifedipine and suggested that fentanyl did not completely overcome the sympathetic response to the profound vasodilatation. The resulting tachycardia in combination with diastolic hypotension from nifedipine could have a detrimental effect on the myocardial oxygen balance.

To define the association of age-related changes in bone mineral content to gonadal function in normal men, we measured radial (largely cortical) and vertebral (largely trabecular) bone mineral content (BMC), testosterone (total and free), estrone and estradiol-17B levels in 62 healthy subjects, ages 30 to 92. Radial BMC fell 2 to 3.4% per decade but vertebral trabecular BMC declined more rapidly at 12% per decade. Of the sex steroids measured the only statistically significant change occurred in free testosterone levels which decreased with age (r = -.57, P less than .0001). Free testosterone levels correlated significantly with trabecular vertebral BMC (r = .458, P less than .0002) but not with bone mineral measures at the predominantly cortical radial sites. However, by multiple regression analysis free testosterone did not add to the effect of age on vertebral BMC. There were no associations of total testosterone, estrone, or estradiol levels to bone mineral content at any of the three sites measured in these healthy men. Age-related declines in male gonadal function do not appear to be of primary importance in male age-related bone loss.

Residual flow to the infarct zone was assessed by coronary angiography during the acute phase of myocardial infarction in 130 patients. In 36 patients, the infarct-related coronary artery was not completely obstructed, thereby providing residual anterograde flow to the infarct area (Group I). Complete obstruction of the infarct vessel with residual flow to the infarct zone by means of collateral circulation was observed in 56 patients (Group II). Complete obstruction of the infarct vessel without residual flow was seen in 38 patients (Group III). Ejection fraction during the acute phase of infarction was found to be significantly higher in Group I (55 +/- 13%) than in either Group II (48 +/- 13%) or Group III (50 +/- 10%) (p less than 0.05). Group II patients had a longer history of angina pectoris (14.2 +/- 21.4 months) than did Group III patients (0.7 +/- 3.1 months) (p less than 0.01). Patients in Group I and Group II were more likely to be taking antianginal medication (56 and 54%, respectively) than were the patients in Group III (16%) (p less than 0.01). Thirty-seven patients in whom reperfusion techniques were not employed had repeat angiography in the chronic phase of infarction, enabling assessment of spontaneous changes in left ventricular function and coronary morphology.(ABSTRACT TRUNCATED AT 250 WORDS)

A prospective study was undertaken in 42 normal twin pregnancies to determine the value of routine ultrasound evaluation in the prenatal diagnosis of intrauterine growth retardation (IUGR) and intra-pair growth discordancy in twin gestations. Use of multiple sonographic parameters significantly improved diagnostic accuracy when compared with the use of single parameters, such as biparietal diameter (BPD) alone in the prepartum diagnosis of these two entities.

This study of biventricular segmental timing sequences compared patterns of the first-harmonic phase with those of multiharmonic Fourier-analysis-derived parameters to determine their suitability for the classification of patients using an automatic pattern recognition scheme. The study involved nine patients with normal ECGs, six with left bundle branch block, 4 with right bundle branch block, and 6 with right-ventricular pacemakers; all patients had normal left-ventricular function. The segmental sequence described by the time of end systole was similar to that described by the first-harmonic phase, with a lower correlation using the time of maximum filling rate, and a rather poor correlation of the time of maximum ejection rate with the other parameters. Thus, despite theoretical difficulties, timing patterns described by phase best agreed with those of the time of end systole. Intersegmental timing differences were used as criteria for discriminating between groups by means of a sequential logic tree. Using either phase, time of end systole or time of maximum ejection rate, all patients were correctly classified into the four ECG categories. More intersegmental timing differences were useful as criteria for phase (57) than for the time of end systole (45) or the time of maximum ejection rate (30). The first-harmonic phase was more efficient than the time of end systole for separating patient groups. Sequential biventricular timing disorders can be objectively classified using either first-harmonic or multiharmonic Fourier analysis, and their patterns can be automatically recognized and used for classification.

The efficacy of adjunctive imipramine hydrochloride treatment for syndromally defined postpsychotic depression was assessed in a six-week, double-blind, placebo-controlled study. All patients had been diagnosed as having schizophrenia or schizoaffective disorder, all were receiving stable doses of fluphenazine decanoate, and all had received benztropine mesylate in an attempt to rule out neuroleptic-induced akinesia. Patients randomized to imipramine therapy fared significantly better in terms of their global improvement and in terms of individual symptoms that are components of the depression syndrome. There were no significant differences in outcome psychosis ratings or side effects. This study indicates the existence of an identifiable syndrome of secondary depression in this patient group that is likely to respond favorably to treatment with adjunctive imipramine.

Axillary node involvement, hormone receptors, tumor differentiation, and obesity have been linked to breast cancer prognosis. We have evaluated which of these factors have an independent association with disease-free survival using the Cox Proportional Hazards model. The study was carried out in 377 patients with breast cancer who underwent mastectomy and axillary node dissection between 1977 and 1984. In the univariate analysis all of the above factors were associated with differences in disease-free survival, and all entered the stepwise model. Among women with negative nodes and those with one to three positive nodes, tumor differentiation was a significant indicator of prognosis, while hormone receptors did not have prognostic significance. The opposite was noted in women with four or more involved nodes, among whom negative hormone receptors was the only significant marker of poor prognosis together with presence of obesity. Among young women node involvement and hormone receptors were significant prognostic indicators, while among older women all four variables were independent prognostic markers. These results indicate a marked heterogeneity among subgroups of women with breast cancer in relation to prognostic markers.

A retrospective study of 40 female-to-male transsexuals was performed to investigate the frequency of endocrine dysfunction prior to hormonal treatment with testosterone. Two patients had laparoscopic evidence of polycystic ovarian disease (PCOD) prior to androgen treatment. Nine additional subjects had clinical evidence of PCOD, including ultrasonographic evidence of multicystic and enlarged ovaries in three patients and/or evidence of hirsutism and oligomenorrhea associated with increased androgen levels and/or an increased plasma luteinizing hormone (LH)/follicle-stimulating hormone (FSH) ratio. Two subjects had evidence of gonadal dysgenesis. Plasma levels of testosterone, prolactin, LH/FSH ratio, and dehydroepiandrosterone sulfate were significantly increased in 30 female transsexuals prior to testosterone treatment when compared to normal adult female controls studied in the early follicular phase of the menstrual cycle. These data indicate that female transsexuals have an increased incidence of endocrine dysfunction (32.5%) which should be investigated prior to hormonal treatment.

To evaluate the use of antibiotics given prophylactically of colon surgery, we examined 26 trials published from 1965 to 1980 in which patients given various antibiotic regiments were compared with controls given no antibiotic treatment. In 22 (85 per cent of these trials) antibiotics reduced postoperative wound infection (p less than 0.05 in 14). Combining the results of the trials published from 1965 to 1975 reveals a 95 per cent confidence interval from the true difference in infection rates of 14 +/- 6 per cent (36 per cent for control group vs. 22 per cent for treatment group) and the true difference in death rates of 6.7 +/- 4.4 per cent (11.2 per cent for control group vs 4.5 per cent for treatment group). Yet trials employing control groups given no treatment continue to be reported. Since the use of such controls is justified only when no effective alternative therapy exists, we believe that any further trials of antibiotic prophylaxis in colon surgery should employ a previously proved standard. However, steadily increasing efficacy of treatment means that comparisons of new therapies with standard therapies will become prohibitively expensive because of the large number of patients required.

Purpose: Sarcoidosis is a disease in which the proliferation of monocyte-macrophage-derived cells is observed. In other diseases characterized by expansion of the monocyte-macrophage system, such as Gaucher's disease and myeloid metaplasia, abnormalities of lipoprotein metabolism have been demonstrated. To determine whether similar abnormalities in lipoprotein cholesterol concentrations could be identified in patients with sarcoidosis, we studied total cholesterol, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol as well as triglyceride levels in 52 patients with biopsy-proven sarcoidosis., Patients and Methods: Patients had no other medical disorders and were not being treated with corticosteroids or antimalarial agents. Blood samples were collected by venipuncture after an overnight fast. Plasma total cholesterol and triglyceride levels were measured using enzymatic techniques. Lipoprotein cholesterol was quantified by lipoprotein fractionation. HDL cholesterol was measured as cholesterol remaining in the supernatant after precipitation of LDL and very-low-density lipoprotein from whole plasma by the heparin-maganese chloride method. Computation was used to determine the level of LDL cholesterol., Results: We found significantly reduced levels of total cholesterol (183.9 +/- 27.6 versus 194.3 +/- 16.5 mg/dl, mean +/- SD, p = 0.021) and HDL cholesterol (41.2 +/- 13.0 versus 51.9 +/- 6.1 mg/dl, p = 0.0001) in sarcoid patients versus an age-, sex-, and race-matched reference group. Differences were not observed in triglyceride or LDL cholesterol levels (p greater than 0.05)., Conclusion: These findings are similar to those observed in the myeloproliferative diseases, Gaucher's disease, and rheumatoid arthritis and suggest a functional role for monocytes-macrophages in the regulation of serum lipoprotein cholesterol levels.