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Often postdropout responses (PDR) in study dropouts are identified from death/disease registries or other medical records. If all dropout is random, then use of postdropout responses while censoring other subjects at date of dropout (CDO/PDR) will bias non-parametric survival probability estimates downward. Censoring all individuals at the last date of study contact, ignoring postdropout information (CDO) will produce unbiased nonparametric survival estimates. As onset of the response sometimes incapacitates the individual, preventing further study participation, dropout is often positively correlated with response. In this case CDO/PDR tends to prevent nonparametric survival overestimation but could lead to underestimation. When all of the responses in dropouts are identified, then regardless of dropout cause, use of all postdropout information, together with censoring all other subjects at time of analysis (CTA/PDR) will produce unbiased minimum variance estimates. We analyze the bias properties of nonparametric survival estimates produced using CDO/PDR, CDO, and CTA/PDR censoring mechanisms under various causes of study dropout and degrees of postdropout response recovery. The goal is to identify which of these censoring methods best incorporates postdropout information. Postdropout information may create interval-censored data. To facilitate statistical analysis of such data, the likelihood function is formulated in terms of the hazard. This results in computationally simple nonparametric estimates and covariances for interval-censored and left-truncated data. An application to estimation of acquired immune deficiency (AIDS)-free time after human immunodeficiency virus (HIV)-l seroconversion using data from a long-term cohort study with considerable dropout is presented. Upper and lower bound estimates for AIDS-free survival probabilities derived using CDO and CDO/PDR are shown to be quite close when compared to the underlying variance of these estimates. KEY WORDS: Censoring method; Dropout; Interval censoring; Nonparametric survival analysis; Postdropout response; Truncation., Accurate projection of the future impact of the acquired immune deficiency (AIDS) epidemic requires knowledge of the hazard of AIDS as a function of time elapsed from human immunodeficiency virus [...]

Background: The coronavirus disease 2019 (COVID-19) global pandemic drastically impacted the health system and the research community. As a result, research institutions and funding agencies recommended a moratorium on conducting in-person research and study enrollment until protocol changes to protect participant safety were approved and implemented. We detail the operational modifications made to the Lupus Intervention Fatigue Trial (LIFT) protocol and summarize how we met the varied challenges created by COVID-19., Methods: We evaluated study protocols and determined that scheduling, acquiring consent, in-person assessments and intervention baseline visits, patient reported outcomes, and data processing procedures needed modification., Results: Operational modifications were made to ensure study progress while adhering to COVID-19 restrictions. Major changes included electronic consent, remote baseline visits for those in the intervention, self-report outcome measures at home via emailed weblinks, and telemedicine physician assessment visits. The collection of safety labs presented the largest challenge since this required an in-person visit to a laboratory. The study team elected to delay this up to one month after the physician assessment. All follow-up visits were completed, and no participants withdrew from the study., Conclusion: LIFT was severely impacted by COVID-19. We provide insight into how our study protocol was modified without compromising the integrity of the primary and secondary outcomes of the study. The modifications utilized by the LIFT study resulted in efficiencies that will be included in a revised protocol and may serve as a useful example for other behavioral interventions to adapt their research studies., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: DKH, RRG, JSC, AY, LB, AC, DE, HM, AK, and LR have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. LEJ would like to disclose consulting work with Zimmer Biomet for training of Community Health Workers in motivational interviewing for a project to increase physical activity in disadvantaged populations of women with osteoarthritis., (Published by Elsevier Inc.)

Objective: Examine associations of hip abductor strength with (1) cartilage damage worsening in the tibiofemoral and patellofemoral compartments 2 years later, and (2) poor function and disability outcomes 5 years later., Methods: Participants had knee osteoarthritis (K/L ≥ 2) in at least one knee. Hip abductor strength was measured using Biodex Dynamometry. Participants underwent 3.0T MRI of both knees at baseline and 2 years later. Baseline-to-2-year cartilage damage progression, defined as any worsening of WORMS cartilage damage score, was assessed at each tibiofemoral and patellofemoral surface. LLFDI (Late-Life Function and Disability Instrument) and Chair-Stand-Rate were recorded at baseline and 5-year follow-up; outcomes analyzed using quintiles. Poor outcomes were defined as remaining in the same low-function quintiles or being in a worse quintile at 5-year follow-up. We analyzed associations of baseline hip abductor strength with cartilage damage worsening and function and disability outcomes using multivariable log-binomial models., Results: 275 knees from 164 persons [age = 63.7 (SD = 9.8) years, 79.3% women] comprised the structural outcome sample, and 187 persons [age = 64.2 (9.7), 78.6% women] the function and disability outcomes sample. Greater baseline hip abductor strength was associated with reduced risks of baseline-to-2-year medial patellofemoral and lateral tibiofemoral cartilage damage worsening [adjusted relative risks (RRs) range: 0.80-0.83) and with reduced risks of baseline-to-5-year poor outcomes for Chair-Stand-Rate and LLFDI Basic Lower-Extremity Function and Disability Limitation (adjusted RRs range: 0.91-0.94)., Conclusion: Findings support a beneficial role of hip abductor strength for disease modification and for function and disability outcomes, and as a potential therapeutic target in managing knee osteoarthritis., (Copyright © 2019 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objective: Among high risk individuals, whether knee lesions in tissues involved in osteoarthritis (OA) can improve prediction of knee OA is unclear. We hypothesized that models predicting (1) incident osteophytes and (2) incident osteophytes and joint space narrowing can be improved by including symptoms or function, and further improved by lesion status., Design: In Osteoarthritis Initiative (OAI) participants with normal knee X-rays, we assessed cartilage damage, bone marrow lesions (BMLs), and menisci. Cox proportional hazards models were used to develop risk prediction models for risk of each outcome. Nested models (increasingly larger baseline covariable sets) were compared using likelihood ratio tests and Schwarz Bayesian Information Criterion (SBC). Model discrimination used receiver operating characteristic (ROC) curves and area under the curve (AUC)., Results: In 841 participants [age 59.6, body mass index (BMI) 26.7, 55.9% women] over up to 7 years follow-up, each larger set improved prediction (+hand OA, injury, surgery, activities; +symptoms/function). Prediction was further improved by including cartilage damage both compartments, BMLs both compartments, meniscal tear, meniscal extrusion, sum of lesion types, number of subregions with cartilage damage, number of subregions with BMLs, and (concurrently) subregion number with cartilage damage, subregion number with BMLs, and meniscal tear. AUCs were ≥0.80 for both outcomes for number of subregions with cartilage damage and the combined model., Conclusions: Among persons at higher risk for knee OA with normal X-rays, MRI tissue lesions improved prediction of mild as well as moderate disease. These findings support that disease onset is likely occurring during the "high-risk" period and encourage a reorientation of approach., (Copyright © 2017 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objective: Knee sagittal dynamic joint stiffness (DJS) describes the biomechanical interaction between change in external knee flexion moment and flexion angular excursion during gait. In theory, greater DJS may particularly stress the patellofemoral (PF) compartment and thereby contribute to PF osteoarthritis (OA) worsening. We hypothesized that greater baseline knee sagittal DJS is associated with PF cartilage damage worsening 2 years later., Methods: Participants all had OA in at least one knee. Knee kinematics and kinetics during gait were recorded using motion capture systems and force plates. Knee sagittal DJS was computed as the slope of the linear regression line for knee flexion moments vs angles during the loading response phase. Knee magnetic resonance imaging (MRI) scans were obtained at baseline and 2 years later. We assessed the association between baseline DJS and baseline-to-2-year PF cartilage damage worsening using logistic regression with generalized estimating equations (GEE)., Results: Our sample had 391 knees (204 persons): mean age 64.2 years (SD 10.0); body mass index (BMI) 28.4 kg/m 2 (5.7); 76.5% women. Baseline knee sagittal DJS was associated with baseline-to-2-year cartilage damage worsening in the lateral (OR = 5.35, 95% CI: 2.37-12.05) and any PF (OR = 2.99, 95% CI: 1.27-7.04) compartment. Individual components of baseline DJS (i.e., change in knee moment or angle) were not associated with subsequent PF disease worsening., Conclusion: Capturing the concomitant effect of knee kinetics and kinematics during gait, knee sagittal DJS is a potentially modifiable risk factor for PF disease worsening., (Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objective: Test the hypothesis that greater baseline peak external knee adduction moment (KAM), KAM impulse, and peak external knee flexion moment (KFM) during the stance phase of gait are associated with baseline-to-2-year medial tibiofemoral cartilage damage and bone marrow lesion progression, and cartilage thickness loss., Methods: Participants all had knee OA in at least one knee. Baseline peak KAM, KAM impulse, and peak KFM (normalized to body weight and height) were captured and computed using a motion analysis system and six force plates. Participants underwent MRI of both knees at baseline and 2 years later. To assess the association between baseline moments and baseline-to-2-year semiquantitative cartilage damage and bone marrow lesion progression and quantitative cartilage thickness loss, we used logistic and linear regressions with generalized estimating equations (GEE), adjusting for gait speed, age, gender, disease severity, knee pain severity, and medication use., Results: The sample consisted of 391 knees (204 persons): mean age 64.2 years (SD 10.0); BMI 28.4 kg/m(2) (5.7); 156 (76.5%) women. Greater baseline peak KAM and KAM impulse were each associated with worsening of medial bone marrow lesions, but not cartilage damage. Higher baseline KAM impulse was associated with 2-year medial cartilage thickness loss assessed both as % loss and as a threshold of loss, whereas peak KAM was related only to % loss. There was no relationship between baseline peak KFM and any medial disease progression outcome measures., Conclusion: Findings support targeting KAM parameters in an effort to delay medial OA disease progression., (Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objective: Varus thrust visualized during walking is associated with a greater medial knee load and an increased risk of medial knee osteoarthritis (OA) progression. Little is known about how varus thrust presence determined by visual observation relates to quantitative gait kinematic data. We hypothesized that varus thrust presence is associated with greater knee frontal plane dynamic movement during the stance phase of gait., Methods: Participants had knee OA in at least one knee. Trained examiners assessed participants for varus thrust presence during ambulation. Frontal plane knee motion during ambulation was captured using external passive reflective markers and an 8-camera motion analysis system. To examine the cross-sectional relationship between varus thrust and frontal plane knee motion, we used multivariable regression models with the quantitative motion measures as dependent variables and varus thrust (present/absent) as predictor; models were adjusted for age, gender, body mass index (BMI), gait speed, and knee static alignment., Results: 236 persons [mean BMI: 28.5 kg/m(2) (standard deviation (SD) 5.5), mean age: 64.9 years (SD 10.4), 75.8% women] contributing 440 knees comprised the study sample. 82 knees (18.6%) had definite varus thrust. Knees with varus thrust had greater peak varus angle and greater peak varus angular velocity during stance than knees without varus thrust (mean differences 0.90° and 6.65°/s, respectively). These patterns remained significant after adjusting for age, gender, BMI, gait speed, and knee static alignment., Conclusion: Visualized varus thrust during walking was associated with a greater peak knee varus angular velocity and a greater peak knee varus angle during stance phase of gait., (Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

A common severe complication of human immunodeficiency virus (HIV) infection has been Pneumocystis carinii pneumonia (PCP). Recently, with increasing use of PCP prophylaxis and multidrug antiretroviral therapy, the clinical manifestations of HIV infection have changed dramatically and the predictors of inpatient mortality for PCP may have also changed. We developed a new staging system for predicting inpatient mortality for patients with HIV-associated PCP admitted between 1995 and 1997. Trained abstractors performed chart reviews of 1,660 patients hospitalized with HIV-associated PCP between 1995 and 1997 at 78 hospitals in seven metropolitan areas in the United States. The overall inpatient mortality rate was 11.3%. Hierarchically optimal classification tree analysis identified an ordered five-category staging system based on three predictors: wasting, alveolar-arterial oxygen gradient (AaPO(2)), and serum albumin level. The mortality rate increased with stage: 3.7% for Stage 1, 8.5% for Stage 2, 16.1% for Stage 3, 23.3% for Stage 4, and 49.1% for Stage 5. This new staging system may be useful for severity of illness adjustment in the current era while exploring current variation in HIV-associated PCP inpatient mortality rates among hospitals and across cities.

A homozygous 32-bp deletion in the gene encoding CCR5, a major coreceptor for HIV-1, leads to resistance to infection with HIV-1, and heterozygosity for the deletion is associated with delayed disease progression in persons infected with HIV-1. We investigated the effect of CCR5 heterozygosity on disease progression as measured by both CD4+ T-cell count decline and the occurrence of clinical AIDS symptoms. Using a unified statistical model for CD4 count progression and AIDS development, we examined whether the effect of CCR5 heterozygosity on clinical AIDS is direct or indirect through its effect on CD4 counts. Based on data from the Multicenter AIDS Cohort Study, we noted a protective effect of CCR5 heterozygosity on both CD4 cell count progression and on AIDS occurrence. Furthermore, we found that this protective effect on the occurrence of AIDS was completely mediated through an effect on the CD4 marker. Additional adjustment for the effect of an initial viral load measurement indicate that CCR5 heterozygosity did not have predictive value for either CD4 progression or the development of AIDS beyond its association with early viral load.

Effective HIV-1 therapies may directly or indirectly impact the development of AIDS-associated malignancies. Using data from the Multicenter AIDS Cohort Study, a longitudinal cohort study of the natural history of HIV-1 infection among homosexual men, the incidence rates of Kaposi's sarcoma (KS) and non-Hodgkin's lymphoma (NHL) over calendar time were determined for the 1813 HIV-1-seropositive men enrolled in 1984 through 1985. Poisson regression models were used to identify statistically significant temporal trends. Nested case control studies were used to assess whether recent cases of these malignancies represented treatment breakthroughs. The incidence of KS as a presenting AIDS illness significantly (p = .003) declined from 25.6 cases per 1000 person-years (95% confidence interval [CI], 21.8-29.9) in the early 1990s to an average incidence of 7.5 per 1000 person-years (95% CI, 3.4-16.7) in 1996 through 1997. In contrast, the incidence of NHL has continued to increase significantly (p < .001) at a rate of 21% per year since 1985, although a possible recent decrease is suggested. None of the recent KS cases and only 1 of 8 NHL cases had used the potent antiretroviral therapies, compared with >70 percent of the HIV-1-seropositive men who were free of malignancies and observed over the same time period. These results may be due to an indirect protection against developing KS by the boosting of the immune system by antiretroviral therapies. However, it is important to clarify the direct therapeutic effect on the pathogenic disease mechanism of human herpesvirus type 8 (HHV-8), the agent postulated to be important in the causal pathway of KS. The absence of a similar effect on NHL may be due to a lack of effect on its pathogenesis or because potent antiretroviral therapies need to be administered early in the disease process and the cases that have occurred represent outcomes following a long latency period. With additional follow-up, an impact on NHL may yet be observed.

Objective: To determine whether race is associated with health insurance coverage and health service use among gay and bisexual men in the Baltimore center of the Multicenter AIDS Cohort Study., Methods: Data from eight semiannual study visits between 1991 and 1996 were used. Descriptive, stratified, and logistic regression analyses were conducted to determine whether race is associated with insurance coverage, medical, or dental service use, after controlling for socioeconomic variables., Results: No difference was found between blacks' and whites' likelihood of having health insurance, private insurance, using inpatient, emergency department services, or antiretroviral medications. Whites were more likely to use outpatient services, particularly if CD4 cell counts were high, and were more likely to use dental services, although blacks were more likely to have dental insurance., Conclusions: Further research must be conducted to examine cultural, social, and psychological factors that help explain why white gay men use more outpatient and dental services, when other service use is unrelated to race. Investigators should be precise when using race as a variable in health services and epidemiologic research, emphasizing when racial differences truly exist versus when the variable race is a surrogate for another factor.

The second AIDS-defining condition diagnosed chronologically is referred to in this report as the secondary AIDS diagnosis. In this study, we examined survival following a secondary AIDS diagnosis using demographic and clinical factors known within 1 year before secondary AIDS diagnosis. In a prospective cohort of 2412 HIV-seropositive homosexual men observed in the Multicenter AIDS Cohort Study (MACS), 609 presented with a secondary AIDS diagnosis between January 1, 1988 and March 31, 1995. To analyze the data, we used survival analysis methods including the Kaplan-Meier product-limit estimator and extended Cox models that allow for nonproportional hazards. The median survival time after a secondary diagnosis was 10.3 months. Rapidity of progression from an initial AIDS diagnosis to a secondary diagnosis was not associated with survival. Drug treatment did not show a beneficial effect because of confounding by indication (i.e., selection bias) and limited efficacy on advanced disease of treatments available prior to 1995. However, a beneficial effect was captured by the use of calendar periods as a proxy measure for the relative exposure to drug treatments. Later calendar year of secondary diagnosis, secondary Kaposi's sarcoma, and higher CD4+ cell count were found to be significantly (p < .05) associated with longer survival time. However, secondary AIDS diagnosis was a significant factor only in the short term. Using secondary Pneumocystis carinii pneumonia as the reference diagnosis, the relative hazard of death 3 months after the time of secondary Kaposi's sarcoma diagnosis was 0.56 (95% confidence interval [CI] = 0.36-0.89) whereas the relative hazard after concurrently diagnosed multiple secondary illnesses was 2.06 (95% CI = 1.26-3.38). After approximately 1 year from the secondary diagnosis, the type of diagnosis was no longer significantly associated with survival.

Despite much investigation of zidovudine, little has been reported regarding its effect on the development of most individual AIDS-defining illnesses, including Kaposi's sarcoma (KS). We used observational data from the Multicenter AIDS Cohort Study (MACS) to estimate the effect of zidovudine use on the subsequent incidence of KS. To do this, we examined and adjusted for predictors of zidovudine use. CD4 lymphocyte counts, the development of HIV-related symptoms and AIDS, and changes in these factors were important predictors of zidovudine use. We used these associations to control for confounding by these and other factors with the G-estimation approach. We found no evidence that zidovudine use affected the time to KS in the MACS; the point estimate (95% confidence interval [CI]) for increase in time to KS was zero (-28%-68%). The relative risk was 1.0 (95% CI, 0.54-1.84). Randomized trials suggest that zidovudine may prevent KS. We discuss possible explanations for differences between results.

Objective: To investigate the dependence of the hazard of symptomatic AIDS on various markers using a non-parametric method. The markers we consider are measures of time (time since infection and calendar date), measures of immune function (numbers and percentage of CD4 T cells) and serological activation markers (neopterin and beta 2-microglobulin)., Methods: We adapted a non-parametric statistical method to estimate the hazard of AIDS. We considered both univariate analyses, in which each marker was considered separately and bivariate analyses of pairs of markers., Conclusions: Using data from 356 seroconverters from the Multicenter AIDS Cohort Study, we found that in the univariate analyses the hazard of AIDS is dependent on all markers, with the strongest dependence for CD4 count and CD4 percentage. In the bivariate analyses we found that the time since infection is of little importance in determining the hazard of AIDS if the CD4 count or percentage are known, and is of minor additional value if one of the serological markers is known. In contrast, we found that both beta 2-microglobulin and neopterin do add some additional information to the hazard of AIDS if CD4 count or CD4 percentage are known.

It is widely assumed that the time since human immunodeficiency virus (HIV) infection is an important indicator of HIV disease stage, yet for most infected individuals the date of infection is unknown. We consider whether marker values, such as CD4 lymphocyte number or percent and levels of serum beta2 microglobulin or serum neopterin, render time since infection unimportant for predicting the residual time to acquired immunodeficiency syndrome (AIDS) diagnosis. The Multicenter AIDS Cohort Study (MACS) contains a subsample of homosexual men whose date of HIV seroconversion is known within +/-6 months and who provide data for this analysis. From this subsample, we extract two overlapping data subsets. The first subset consists of 370 persons whose 3,723 study visits include complete data on the cellular markers CD4 lymphocyte number and percent for a period of 9 years. The second consists of 272 persons whose 1,593 visits include complete information on cellular markers and on the serological markers beta2-microglobulin and neopterin for a period of 5 1/2 years. We model the residual time to AIDS diagnosis with a regression model, in which cellular and serologic markers are the explanatory covariates (independent variables) and the residual time to AIDS is the responses variable (dependent variable). A robust estimate of the variance-covariance matrix corrects for the dependence of repeated measurements in the same individual. In the case of CD4 number and percent, the results indicate that time since infection is of none or at most little importance if the marker value is known, suggesting that time since infection can be adequately replaced by the combination of marker values. However, the serological markers alone do not eliminate the importance of the time since infection.

Background: The Commission on Cancer of the American College of Surgeons conducted a large, national survey to assess methods of diagnosis, American Joint Commission on Cancer staging, treatment, and outcome of patients with adenocarcinoma of the pancreas., Study Design: The survey questionnaire contained 160 questions and covered two study periods, 1983 to 1985 and 1990, for time-trend analysis. Nine hundred seventy-eight institutions throughout the United States voluntarily participated, contributing 8917 case reports for 1983 to 1985 and 8025 reports for 1990, resulting in a total of 16,942 patient reports. Most, but not all, of the participating hospitals maintain approval status with the Commission on Cancer of the American College of Surgeons., Results: The ratio of male-to-female cases was 1:1. Patient characteristics including age, ethnicity, neighborhood income, type of insurance coverage, and hospital characteristics--including annual caseload and type of facility (e.g., teaching, community)--appeared to influence surgical multimodality treatment patterns. The most common presenting symptom was abdominal pain. The reported history of smoking for these patients with pancreatic cancer was higher than U.S. population averages. The frequency of using abdominal computed tomography scans, endoscopic retrograde cholangiopancreatography, carcinoembryonic antigen, and CA 19-9 during patient evaluation all increased. Time trends toward lower operative mortality and more extirpative surgery were reported, as was a slightly higher survival for those patients who were resected surgically., Conclusions: Pancreatic cancer continues to be a disease of older patients. There were slight improvements in operative mortality. For a highly selective category of patients, cancer-directed surgery offers a chance for cure with excellent operative mortality and acceptable complication rates, especially when performed in institutions that have a 20 or greater case per year experience.

The purpose of this study was to characterize the epidemiologic, clinical, and laboratory parameters of a cohort of men at risk of AIDS-associated toxoplasmic encephalitis. One hundred seventeen (11%) of the 1,073 participants at the time of enrollment into the Chicago Multicenter AIDS Cohort Study (MACS) were seropositive for Toxoplasma antibodies. Significant differences in prevalence of antibodies between African-American, Hispanic, or white men were not observed (p = 0.49). One hundred one (86%) of the 117 antibody-positive participants had at least one follow-up serology performed and 6 (6%) of the 101 had a significant rise in IgG antibody titer on subsequent visits. Five of six participants with a significant rise in titer were also seropositive for HIV-1 at entry or seroconverted during the study. A trend toward higher IgG Toxoplasma titers and prevalence of IgM antibodies in participants seropositive for HIV-1 was observed, but the differences did not reach statistical significance. There was no evidence that the presence of Toxoplasma infection predisposed to development of CD4+ depletion or AIDS. None of the 183 individuals in the cohort who developed AIDS and who were seronegative for Toxoplasma antibodies developed toxoplasmic encephalitis. In contrast, of the 13 persons who developed AIDS and who were positive for Toxoplasma antibodies, 5 (38%) developed toxoplasmic encephalitis. Prevalence of Toxoplasma antibodies in the MACS population was independent of HIV-1 serostatus. Toxoplasma infection does not appear to predispose to progression of HIV-1 infection. The risk of development of toxoplasmic encephalitis in persons with AIDS and chronic Toxoplasma infection may have been underestimated by previous retrospective studies.

Paraffin-embedded surgical specimens from 69 patients who underwent resections of otherwise untreated Dukes stage C adenocarcinoma of the colon were examined for proliferative activity, DNA aneuploidy, DNA index, and proportion of aneuploid cells by flow cytometry. Results were correlated to clinical characteristics of the patients and to overall survival times. DNA aneuploid tumors were identified in 60 cases (87%), diploid tumors in 9 cases (13%). The mean S-phase fraction for all cases was 17.6%, with a standard deviation (SD) of 7.8. In univariate statistical analysis, younger patient age, lower tumor proliferative activity, DNA index less than or equal to 1.2, and presence of only 1-4 lymph nodes with tumor involvement were found to be significant predictors of improved patient survival. In multivariate Cox regression analysis, low tumor proliferative activity, younger patient age, and location of the tumor in the right or transverse colon were found to be significant independent predictors of increased patient survival. When tumor proliferative activity was stratified into statistically defined subgroups, patients with tumors of low proliferative activity (S-phase less than mean - 0.5 SD) had significantly longer survival than patients with tumors of moderate proliferative activity (S-phase value greater than mean - 0.5 SD and less than mean +0.5 SD) or high proliferative activity (S-phase greater than mean +0.5 SD). These results suggest that tumor proliferative activity in Dukes C colon carcinoma may be an important biological factor in determining patient prognosis.

A cohort of 2915 HIV-1-seronegative men from the four centers of the Multicenter AIDS Cohort Study (MACS) was followed at 6 month intervals for 24 months to identify men who developed antibodies to HIV-1. Two hundred thirty-two men (8%) seroconverted. The highest attack rate was among men who reported practicing both receptive and insertive anal-genital intercourse. The attack rate among men who reported practicing receptive but not insertive intercourse was 3.6 times higher than among men practicing insertive intercourse although those practicing insertive only reported 38% more different partners. Only two men seroconverted who reported not practicing analgenital intercourse in the 12 month prior to the first antibody-positive visit. Because men were followed every 6 months, one of these men could have been infected within 6 months of the actual development of HIV-1 antibodies. The seroconversion rate was significantly lower among men who reported using condoms with all their partners. The results of this study (a) reaffirm that receptive anal-genital intercourse is the major route of infection among homosexual men of HIV-1, (b) suggest that there is a low risk of HIV-1 infection to the insertive partner in anal-genital intercourse, (c) suggest that infection may rarely occur through sexual activities other than anal-genital intercourse, (d) provide evidence that condoms as currently used by men in the MACS provide significant but not complete protection against HIV-1 infection, and (e) suggest that the number of men in the homosexual community engaging in high-risk behavior is declining.

Twenty homosexual men who reported having sexual contact with homosexual men who had the acquired immunodeficiency syndrome (AIDS) or the AIDS-related complex were examined to determine their clinical status, immunologic profiles, and the presence of antibody to the human T-cell lymphotropic virus type III (HTLV-III). Of the 20, eight men had one or more signs or symptoms of the AIDS-related complex and 12 were asymptomatic. Antibodies to HTLV-III were present in 14 (70%) of 20 of the sexual contacts as compared with four (10%) of 40 healthy homosexuals without known contact with a patient who had AIDS (P less than .0001). Seropositive contacts had significantly higher mean counts of suppressor lymphocytes and lower helper: suppressor ratios (P less than .05 and .005, respectively) and higher serum levels of IgG than seronegative contacts (P less than .05). It was not possible to determine significant differences in sexual practices, drug use, length of relationship, or numbers of different sexual partners between symptomatic and asymptomatic contacts or between seropositive and seronegative contacts in this study.

We evaluated the usefulness of both the Walter Reed (WR) staging classification and the component criteria used in the system in predicting progression to AIDS. The WR classification was applied to a cohort of 431 men who were seropositive for the human immunodeficiency virus on entry into a prospective study. The WR classification was of limited usefulness, as only 133 men (31%) could be assigned to a WR stage. Among men who could be WR classified, only individuals in WR stage 5 were found to have a significantly more rapid progression to AIDS. The seropositive cohort was also classified based on initial CD4 cell number. Low CD4 counts (less than 400 cells/mm3) were significantly associated with progression to AIDS, and grouping seropositive men by CD4 number alone provided as much prognostic information as the WR classification. Skin test anergy was also a significant predictor for progression to AIDS, but only in individuals with low CD4 counts.