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At least 19 recordsLinked to original sources
PubMed1996

Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene. Hemophilia Growth and Development Study, Multicenter AIDS Cohort Study, Multicenter Hemophilia Cohort Study, San Francisco City Cohort, ALIVE Study.

The chemokine receptor 5 (CKR5) protein serves as a secondary receptor on CD4(+) T lymphocytes for certain strains of human immunodeficiency virus-type 1 (HIV-1). The CKR5 structural gene was mapped to human chromosome 3p21, and a 32-base pair deletion allele (CKR5Delta32) was identified that is present at a frequency of approximately0.10 in the Caucasian population of the United States. An examination of 1955 patients included among six well-characterized acquired immunodeficiency syndrome (AIDS) cohort studies revealed that 17 deletion homozygotes occurred exclusively among 612 exposed HIV-1 antibody-negative individuals (2.8 percent) and not at all in 1343 HIV-1-infected individuals. The frequency of CKR5 deletion heterozygotes was significantly elevated in groups of individuals that had survived HIV-1 infection for more than 10 years, and, in some risk groups, twice as frequent as their occurrence in rapid progressors to AIDS. Survival analysis clearly shows that disease progression is slower in CKR5 deletion heterozygotes than in individuals homozygous for the normal CKR5 gene. The CKR5Delta32 deletion may act as a recessive restriction gene against HIV-1 infection and may exert a dominant phenotype of delaying progression to AIDS among infected individuals.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Contrasting genetic influence of CCR2 and CCR5 variants on HIV-1 infection and disease progression. Hemophilia Growth and Development Study (HGDS), Multicenter AIDS Cohort Study (MACS), Multicenter Hemophilia Cohort Study (MHCS), San Francisco City Cohort (SFCC), ALIVE Study.

The critical role of chemokine receptors (CCR5 and CXCR4) in human immunodeficiency virus-type 1 (HIV-1) infection and pathogenesis prompted a search for polymorphisms in other chemokine receptor genes that mediate HIV-1 disease progression. A mutation (CCR2-64I) within the first transmembrane region of the CCR2 chemokine and HIV-1 receptor gene is described that occurred at an allele frequency of 10 to 15 percent among Caucasians and African Americans. Genetic association analysis of five acquired immunodeficiency syndrome (AIDS) cohorts (3003 patients) revealed that although CCR2-64I exerts no influence on the incidence of HIV-1 infection, HIV-1-infected individuals carrying the CCR2-64I allele progressed to AIDS 2 to 4 years later than individuals homozygous for the common allele. Because CCR2-64I occurs invariably on a CCR5-+-bearing chromosomal haplotype, the independent effects of CCR5-Delta32 (which also delays AIDS onset) and CCR2-64I were determined. An estimated 38 to 45 percent of AIDS patients whose disease progresses rapidly (less than 3 years until onset of AIDS symptoms after HIV-1 exposure) can be attributed to their CCR2-+/+ or CCR5-+/+ genotype, whereas the survival of 28 to 29 percent of long-term survivors, who avoid AIDS for 16 years or more, can be explained by a mutant genotype for CCR2 or CCR5.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Genetic restriction of AIDS pathogenesis by an SDF-1 chemokine gene variant. ALIVE Study, Hemophilia Growth and Development Study (HGDS), Multicenter AIDS Cohort Study (MACS), Multicenter Hemophilia Cohort Study (MHCS), San Francisco City Cohort (SFCC)

Stromal-derived factor (SDF-1) is the principal ligand for CXCR4, a coreceptor with CD4 for T lymphocyte cell line-tropic human immunodeficiency virus-type 1 (HIV-1). A common polymorphism, SDF1-3'A, was identified in an evolutionarily conserved segment of the 3' untranslated region of the SDF-1 structural gene transcript. In the homozygous state, SDF1-3'A/3'A delays the onset of acquired immunodeficiency syndrome (AIDS), according to a genetic association analysis of 2857 patients enrolled in five AIDS cohort studies. The recessive protective effect of SDF1-3'A was increasingly pronounced in individuals infected with HIV-1 for longer periods, was twice as strong as the dominant genetic restriction of AIDS conferred by CCR5 and CCR2 chemokine receptor variants in these populations, and was complementary with these mutations in delaying the onset of AIDS.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Trends in smoking by birth cohort for births between 1940 and 1975: a reconstructed cohort analysis of the 1990 Ontario Health Survey.

BACKGROUND: Smoking patterns have changed markedly over the past 70 years. Previous studies have shown that examination of smoking patterns within birth cohorts can identify important changes in tobacco adoption and cessation. This paper examines temporal trends in the prevalence of smoking and the age of smoking adoption and cessation for birth cohorts born between 1940 and 1975. METHODS: The underlying data were obtained from the Ontario Health Survey (conducted in 1990), which used a multistage stratified area sampling strategy to obtain interviews on 29,843 people age 12 or older. Self-reported smoking histories were used as the basis for a reconstructed cohort analysis of prevalence rates. A life events methodology was employed to examine the age at starting smoking and the time of smoking cessation. RESULTS: There has been a steady drop in peak smoking prevalence for men. This trend appears to be continuing among the most recent cohorts. However, for women, peak smoking prevalence increased until the 1960 birth cohort, after which time the peak prevalence has been dropping. Prevalence of smoking was much higher for men then for women among the earlier birth cohorts but, by the 1960 cohort, the prevalence for men and women was essentially the same. Examination of the age of smoking onset reveals that there was a statistically significant interaction between sex and birth cohort on the relative risk of starting smoking. The rate of smoking cessation has increased uniformly across all birth cohorts among both men and women. CONCLUSIONS: This study confirms recent trends in smoking reduction and provides no evidence to suggest a diminution of the effect. Trends in recent birth cohorts of women are encouraging. There is a clear need for public health initiatives directed at older children and teenagers in order to further reduce the onset of smoking. Efforts to prohibit advertising directed toward minors, sponsorship of sporting and cultural events, and the sale of tobacco to minors should receive high priority.

Adolescent↗
PubMed2005

Socio-economic position across the life course and hysterectomy in three British cohorts: a cross-cohort comparative study.

OBJECTIVE: To examine the association between indicators of lifetime socio-economic position and rates of hysterectomy in three British cohorts. DESIGN: Cross-cohort comparative study. SETTING: Two cohorts: England, Scotland and Wales. Third cohort: Aberdeen, Scotland. POPULATION: Three thousand two hundred and eight women born between 1919 and 1940, participating in the British Women's Heart and Health Study (BWHHS); 1394 women from the MRC National Survey of Health and Development (NSHD), followed up since birth in 1946; 3208 women born between 1950 and 1955, participating in the Aberdeen Children of the 1950s study, all with complete information on lifetime socio-economic position and hysterectomy status. METHODS: Relative indices of inequality were derived for markers of socio-economic position in childhood and adulthood. Cox's regression models were used to test the association between these markers and hysterectomy. MAIN OUTCOME MEASURE: Self-reported hysterectomy with or without oophorectomy. RESULTS: Adverse socio-economic position in childhood and as indicated by educational status was associated with reduced rates of hysterectomy in the oldest of the three cohorts (BWHHS), whereas conversely in the NSHD and Aberdeen cohorts it was associated with increased rates of hysterectomy. The unadjusted hazards ratios for hysterectomy comparing worst to best socio-economic position for father's social class were 0.73 (0.56, 0.96) for women from the BWHHS, 1.77 (1.19, 2.65) for those from the NSHD and 2.06 (1.46, 2.89) for those from the Aberdeen cohort. Associations between markers of adult socio-economic position and hysterectomy tended to be weaker in all three cohorts and often did not reach conventional levels of statistical significance. CONCLUSIONS: Our results show that hysterectomy rates are influenced by childhood socio-economic position and educational attainment, but that the nature of this association varies across these three British cohorts born in different decades of the 20th century. That there were no consistent or strong associations between adult SEP and hysterectomy rates suggest that social factors influencing rates of hysterectomy are likely to be those experienced or which develop in early life rather than those which develop later.

Adult↗
PubMed2004

A comparison of socio-economic differences in long-term sickness absence in a Japanese cohort and a British cohort of employed men.

OBJECTIVES: To compare the magnitude of socio-economic differences in sickness absence rates between a Japanese cohort and a British cohort. To assess the effects of self-rated health and behavioural risk factors on sickness absence in the two cohorts, and whether they explain socio-economic differences in sickness absence within and between cohorts. METHODS: An 8 year follow up study of sickness absence in 2504 Japanese male employees in a factory in Japan and 6290 British male employees in civil service departments in London. The rates of first occurrences of long-term (>7 calendar days) sickness absence were determined and compared between these cohorts. Socio-economic status was measured with hierarchical employment grades. RESULTS: The first time sickness absence rates were about two times higher among British men as compared with Japanese men. The rate ratio of lower to higher employment grade was 1.2, 1.3 and 2.1 among Japanese white-collar, Japanese blue-collar and British white-collar employees respectively. Baseline self-rated health and smoking habit predicted sickness absence in both cohorts. After adjusting for these factors a significant difference between the Japanese and British cohorts, and between employment grades remained. CONCLUSIONS: The rate of long-term sickness absence was higher in the British cohort than the Japanese cohort.

Absenteeism↗
PubMed2003

Associations of aging and birth cohort with body mass index in a biethnic cohort.

OBJECTIVE: To examine associations of aging and birth cohort with body mass index (BMI) in a biethnic cohort. RESEARCH METHODS AND PROCEDURES: This was a longitudinal closed cohort study of 14,500 white and African-American men and women, 45 to 64 years of age, followed for 9 years. Aging was defined as the length of the interval in years between baseline and following visits. Birth cohort was defined by the year in which participants were born. Mixed model analyses were used to examine associations of aging, birth cohort, and BMI in four ethnicity-gender groups. RESULTS: We found that aging was associated with an increase in BMI in white and African-American men and women. The associations between aging and BMI were stronger in the younger birth cohorts. Except for white women, younger birth cohort was associated with a higher BMI. After adjusting for aging, birth cohort was associated with an increase in BMI of 0.1 kg/m(2) [95% confidence interval (95% CI): -0.1, 0.3] among white women. The corresponding values for African-American women, white men, and African-American men are 0.5 kg/m(2) (95% CI: 0.1, 0.9), 0.6 kg/m(2) (95% CI: 0.4, 0.8), and 0.6 kg/m(2) (95% CI: 0.2, 1.0), respectively. DISCUSSION: Our analyses show that, in all except white women, people in this age range who were born later have a higher BMI at the same attained age. In all groups, people who are born later gained more weight as they aged. In general, subjects ages 45 to 64 years gained weight as they aged 9 years.

Aged↗
PubMed2005

[Case-cohort studies: an effective design for the investigation of biomarkers as risk factors for chronic diseases--demonstrated by the example of the MONICA/KORA Augsburg Case-Cohort Study 1984-2002].

As it is often not possible to determine specific measures of exposure in all participants of a prospective cohort study due to financial or other restrictions, new study designs have been developed. The aim of these designs is to obtain valid results even though expensive measurements are restricted to a limited number of participants of the original cohort study. The case-cohort study is a design that has recently become interesting as an alternative to the well known nested case-control study. The following article describes the case-cohort design considering as an example data from the MONICA/KORA Augsburg cohort study 1984-2002 and the outcomes of type 2 diabetes mellitus and acute myocardial infarction. Furthermore, results obtained in the full cohort for selected exposures are compared with results obtained in the case-cohort study.

Adult↗
PubMed1989

Lung cancer risk comparison among male smokers between the "six-prefecture cohort" in Japan and the British physicians' cohort.

We estimated the effective duration of cigarette smoking using the data of lung cancer mortality among male smokers of a large-scale cohort study in Japan and evaluated its role in the lung cancer risk difference between male smokers of the Japanese cohort and the British physicians' cohort. By selecting male cohort members who answered that they had started smoking at ages 18-22 (average = 20.3), the subjects of our analysis, which numbered 49,013, were made relatively homogeneous in terms of age at which smoking was started. Assuming lung cancer mortality to be proportional to the 4.5th power of the effective duration of cigarette smoking, i.e., (age-theta)4.5, as was proposed on the basis of the British cohort study by Doll and Peto, the parameter theta was estimated to be 29.4 for male smokers aged 40-64 in 1966; therefore, the estimated duration of cigarette smoking was, on average, 9.1 years (95% confidence interval = 5.8-11.6) shorter than that calculated from the reported age at which smoking was started. Our findings suggested that the low lung cancer mortality relative to daily cigarette consumption in Japan resulted from the shorter duration of cigarette smoking in the Japanese cohort, possibly due to the severe shortage of cigarettes during and shortly after World War II. Once the effective duration of cigarette smoking was adjusted, lung cancer mortality in the range of 5-34 cigarettes per day was fairly comparable to that observed among the cohort of male British physicians.

Adult↗
PubMed2007

Demographic and clinical characteristics of chronic prostatitis: prospective comparison of the University of Sciences Malaysia Cohort with the United States National Institutes of Health Cohort.

PURPOSE: We compared demographic and clinical characteristics of the University of Sciences Malaysia Chronic Prostatitis Cohort to the United States National Institutes of Health Chronic Prostatitis Cohort. MATERIALS AND METHODS: Participants met the same definition of chronic prostatitis/chronic pelvic pain syndrome. Each participant had extensive demographic, medical history, previous treatment, clinical and laboratory evaluations. RESULTS: The University of Sciences Malaysia and National Institutes of Health cohorts proved similar in most respects. National Institutes of Health-Chronic Prostatitis Symptom Index total scores, pain and urinary subscores were similar for the 332 University of Sciences Malaysia Chronic Prostatitis Cohort and 488 National Institutes of Health Chronic Prostatitis Cohort participants. Differences included worse quality of life subscore for the University of Sciences Malaysia Chronic Prostatitis Cohort, differences in the location, number of sites, and types of pain/discomfort between the 2 populations, and that the University of Sciences Malaysia participants had received less previous treatment. CONCLUSIONS: The demographic characteristics and clinical presentation of chronic prostatitis/chronic pelvic pain syndrome proved remarkably similar in these diverse populations. Both cohorts experienced major reduction in their quality of life from chronic pelvic pain and urinary symptoms. Comparison of diverse populations using standard clinical, laboratory and assessment instruments is feasible, and may provide important insights into chronic prostatitis/chronic pelvic pain syndrome and the factors that determine clinical outcome.

Adult↗
PubMed1996

Early undifferentiated connective tissue disease. IV.Musculoskeletal manifestations in a large cohort of patients with undifferentiated connective tissue diseases compared with cohorts of patients with well-established connective tissue diseases: followup analyses in patients with unexplained polyarthritis and patients with rheumatoid arthritis at baseline.

OBJECTIVES: To examine the musculoskeletal manifestations in a large cohort of patients (n = 410) diagnosed with either a well-established connective tissue disease (CTD) (n = 197) or an early undifferentiated CTD (n = 213) with a symptom duration of <1 year. This study was aimed at determining the predictive value of demographic, clinical, and laboratory features on outcome in patients with unexplained polyarthritis (UPA) (from the early undifferentiated CTD cohort; n = 67) or rheumatoid arthritis (RA) (from the well-established CTD cohort; n = 57), over a 5-year followup period. METHODS: Patients from both cohorts were assessed at years 1, 3, and 5. At the study visits, clinical data were collected in a standardized manner, and sera were obtained and stored. A priori criteria were established for patient ascertainment and diagnosis over the duration of the study. Standard statistics were used for comparisons of baseline characteristics in patients diagnosed as having systemic lupus erythematosus, RA, undifferentiated CTD, and UPA at entry into the cohorts. Baseline features in patients with UPA were examined according to the different subsequent outcomes (RA, CTD, or undifferentiated CTD, remission [nonpersistent], or persistent or active UPA). Baseline features in patients with RA whose disease remained active versus those in whom remission was attained were also examined. Two multivariable analyses, classification trees and polychotomous logistic regression, were performed to predict disease outcomes over time. RESULTS: The overall rate of ascertainment for the 410 patients ranged from 90 % at year 1 to 71 % at year 5. Patients with established CTDs showed a tendency for more stable diagnoses than those with early undifferentiated CTDs (90-100% versus 45-70%). Consistent baseline predictors of persistent active disease among patients with RA, in both univariate and multivariable analyses, were higher joint counts for pain and tenderness and higher erythrocyte sedimentation rate (ESR). In approximately 20% of patients who were classified as having RA when they originally entered the cohort, the disease was in remission at 5 years. Twenty percent of the patients originally classified as having UPA developed RA over the duration of the study. These patients tended to be older and to have swelling of small joints at baseline. However, a consistent pattern of predictive variables could not be identified in the multivariable analyses, other than at year 1 (higher small joint counts for swelling and higher ESR). CONCLUSION: Baseline features (joint counts, and ESR) among RA patients were variously predictive of persistently active disease at years 1-5. Consistent baseline predictors of outcome among patients with UPA only emerged at year 1. Remission occurred in approximately 20% of RA patients, whereas a similar percentage of patients with UPA developed RA. These findings have implications with regard to treatment decisions in patients with early RA and/or UPA.

Adult↗
PubMed2001

Cohort studies: history of the method. I. Prospective cohort studies.

The term "cohort study" was introduced by Frost in 1935 to describe a study that compared the disease experience of people born at different periods, in particular the sex and age specific incidence of tuberculosis and the method was extended to the study of non-communicable disease by Korteweg who used it 20 years later to analyse the epidemic of lung cancer in the Netherlands. Such studies are now best described as generation studies or generation cohort studies to distinguish them from the common type of study that is now carried out that consists in defining groups of individuals distinguished by some variable (such as place of residence, occupation, behaviour, or environmental exposure) and following them up to see if the incidence or mortality rates vary with the selected variable. This type of study is now one of the most important tools for epidemiological investigation. Initially called prospective studies, because the information characterising the individuals in the cohorts was recorded before the onset of disease, they are now preferably called cohort studies and distinguished as prospective cohort studies, If the information obtained relates to the subjects at the time the study is started and they are then followed, or retrospective cohort studies, if the information characterising the individuals was recorded sometime in the past (for example, the receipt of radiotherapy, or entry to a specific occupation). Studies of either type have the great advantage that they avoid all the most important sources of bias that may affect case-control-studies, but the disadvantage that because incidence rates and more specifically mortality rates are commonly low, large numbers of subjects have to be followed for several (if not many) years to obtain statistically significant results. Several early prospective studies are described: Namely, those of 34,000 male British doctors, 190,000 male and female American citizens with different smoking habits, some 5,000 middle aged residents of Framingham with different blood pressures, blood cholesterol levels, etc, and 13,000 children born in the UK in one week in 1946 with different family backgrounds.

Cohort Studies↗
PubMed1997

Comparison of two procedures to estimate the hospital stay attributable to nosocomial infection: matched cohort study versus analysis of covariance of the total unmatched cohort.

We compare the results of a matched cohort study with those yielded by analysis of covariance (ANCOVA) in the cohort where the matched study was nested to assess whether the matching design underestimates (as it has been assumed) the extra length of hospitalization due to nosocomial infection. A total of 218 patients developed hospital infection in a cohort of 1483 general surgery patients; 161 were successfully matched 1:1 for surgical procedure, ASA score, age (+/-10 years), emergency-scheduled surgery, preoperative stay, and, whenever possible, number of diagnoses and sex. Unmatched infected patients (57, 23.1%) were different from matched ones. There were no differences for the variables between matched infected patients and their pairs. The matched cohort study overestimates the extra LOH due to hospital infection. The use of ANCOVA in the total cohort obviates the selection bias of the matched cohort design.

Adult↗
PubMed1987

Age, period and cohort analysis of trends in mortality from major diseases in Japan, 1955 to 1979: peculiarity of the cohort born in the early Showa Era.

Japanese researchers have reported that recent mortality rates from diabetes mellitus, ischemic heart disease, peptic ulcer, cirrhosis of the liver and suicide for middle-aged Japanese men have increased by comparison with those for other age groups. There has been some controversy over the etiology of this unusual trend, and in particular whether it is due primarily to recent undesirable socio-economic factors (period effects) or to factors specific to these cohorts born in the early Showa Era, around 1925 to 1940 (cohort effects). A possible source of this controversy lies in the methods which have been used to describe the trends; these are mostly descriptive and graphical. To elucidate which factors are responsible for these trends, we analysed the mortality data quantitatively applying an age-period-cohort model modified so that period effects remain constant within certain age groups but may vary from one age group to the next. Although the identifiability problem still occurs in the modified model, estimable curvature components of time effects may be used to examine these unusual trends. In fact, the peculiarity of the cohort born in the early Showa Era was clearly detected by the curvature components of cohort effects for these major diseases. These findings are consistent with the 'cohort hypothesis' for the recent peculiar trend in Japanese male mortality.

Adult↗
PubMed2003

Validity and reproducibility of a self-administered food frequency questionnaire in the JPHC Study Cohort II: study design, participant profile and results in comparison with Cohort I.

The objective of this study was to evaluate the validity and reproducibility of a self-administered food frequency questionnaire (FFQ) to estimate nutrient and food intake in the subjects of the Japan Public Health Center-based prospective Study on Cancer and Cardiovascular Diseases (JPHC Study Cohort II). The FFQ was originally developed to estimate intake in the JPHC Study Cohort I. A total of 392 subjects were recruited from the entire cohort participants in the 6 areas of Cohort II on a voluntary basis. The subjects completed the FFQ used for the 5-year follow-up survey twice at approximately a 1-year interval. Seven-day dietary records (DR) and blood samples were collected 4 times at 3-month intervals over a year. Daily nutrient and food intakes from FFQ and DR were estimated. The Spearman correlation coefficients for estimated intakes were calculated between FFQ and DR for validity, and between 2 identical FFQs for reproducibility. Correlation coefficients for the validity ranged from 0.09 to 0.82 among various nutrients and food groups. The correlation coefficients for most of the nutrients and food groups were improved to a level comparable to that of Cohort I by energy-adjustment. Correlation coefficients for reproducibility ranged from 0.42 to 0.82, similar to those of Cohort I.

Diet Records↗
PubMed1989

Age, period, and cohort models. Non-overlapping cohorts don't resolve the identification problem.

Age, period, and cohort models have generally been applied to rates from tabulated national statistics, and it is known that such models suffer from an identification problem. When individual records, including date of birth, are available, however, a unique solution has been proposed which uses non-overlapping cohorts. We have shown that the identification problem exists in continuous time, so that even perfect information on the three variables will fail to resolve it. It is important to recognize clearly the assumptions that are implicit in the non-overlapping cohort formulation of the age-period-cohort model. The value of the solution proposed depends critically on their appropriateness or otherwise. It should always be remembered that the assumptions determine much of the final solution, including the apportionment of trend to the different components, age, period, or cohort.

Age Factors↗
PubMed1999

Use of observational databases to evaluate the effectiveness of antiretroviral therapy for HIV infection: comparison of cohort studies with randomized trials. EuroSIDA, the French Hospital Database on HIV and the Swiss HIV Cohort Study Groups.

OBJECTIVES: It is important to assess the extent of bias when comparing the clinical efficacy of antiretroviral regimens in observational databases because, with the current lack of planned large trials, such analyses may represent the only means of assessing the risk of serious clinical events associated with new regimens. We aimed to compare the results from observational databases with those from randomized trials. METHODS: Three treatment comparisons from randomized trials [Delta, AIDS Clinical Trials Group (ACTG) 175, Community Programs for Clinical Research on AIDS (CPCRA) 007 and ACTC 320] were mimicked in cohorts: (i) zidovudine monotherapy versus combination regimens of two nucleoside analogues; (ii) zidovudine combined with either didanosine or zalcitabine; and (iii) a dual combination versus a triple regimen including a protease inhibitor. Data for over 10 000 patients from the French Hospital Database on HIV, the EuroSIDA study and the Swiss HIV cohort study were analysed for each of the comparisons. Progression to AIDS disease or death was analysed in Cox models, adjusting for baseline differences, and results compared with randomized trials. RESULTS: For comparison (i) the adjusted relative risk estimates from cohorts were between 0.61 and 0.84, favouring combinations over monotherapy, compared with 0.57 to 0.63 for trials. For comparison (ii) relative risk estimates from cohorts ranged from 0.81 to 1.01 compared with 0.77 to 0.92 for trials. For comparison (iii), two of the cohorts showed similar results to the ACTG 320 trial but one indicated a higher risk of progression on triple therapy [relative risk 1.20, 95% confidence interval (CI) 1.01-1.441, in direct contrast to the trial result (relative risk 0.50, 95% CI 0.33-0.76). CONCLUSION: Serious biases can be present when comparing outcomes from the use of antiretroviral regimens in observational studies. However, such bias is not inevitable and careful interpretation of the results from several observational studies considered together is likely to be informative, guiding the design of new trials.

Anti-HIV Agents↗