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Biomedical subjects

R J Connor

Publications and source records attributed to R J Connor.

At least 19 recordsLinked to original sources
PubMed1991

Analysis of the temporal patterns of benefits in the Health Insurance Plan of Greater New York trial by stage and age.

Reductions in breast cancer mortality in the Health Insurance Plan of Greater New York trial are examined by age at entry and stage at diagnosis using a stage shift cancer screening model. The results indicate that for women aged 40-49 years at entry, benefits are associated with an internal stage shift of stage 1 cancers that have a prognosis poorer than the usual stage 1 cancers. Further, the results indicate that after 18 years of follow-up, of the reduction of 16 fewer deaths in the intervention group, 12-15 of the deaths are related to this internal shift. Given that stage 1 cases inherently have relatively good survival, the time required to see the screening benefit is substantial. For women aged 50-64 years at entry, the results suggest that benefits are associated primarily with shifts to or within stage 1. Further, the results indicate that after 6 years, of the reduction of 31 fewer deaths in the intervention group, 22 of the deaths are related to external shifts to stage 1. Given that stage 2 cancers have poorer survival than stage 1 cancers, screening benefit is seen sooner for the older cohort than for the younger cohort.

Adult↗
PubMed1991

The case-control design and the assessment of the efficacy of cancer screening.

Case-control studies have been used in recent years to evaluate the efficacy of cancer screening. However, relatively little work has been done to examine the methodology itself for this purpose. In this paper, it is demonstrated that because of self-selection bias the case-control study can yield a biased estimate of screening efficacy. Further, it is shown how this bias can be assessed using data from a randomized trial. Using data from the HIP breast cancer screening study, the magnitude of the self-selection bias is estimated and is seen to be substantial.

Breast Neoplasms↗
PubMed1990

Helminthosis in goats in southern Tanzania: investigations on epidemiology and control.

Investigations were conducted in naturally infected goats to determine the main epidemiological factors related to gastro-intestinal nematode infections in southern Tanzania with a view to making appropriate recommendations for control. Faecal worm egg counts rose during the single rainy season and then fell to remain low during the dry season. The beneficial effect of an anthelmintic treatment after the rains was demonstrated in weaner goats under traditional management and this should form the basis of rational control.

Animals↗
PubMed1990

Prospective evaluation of serum CA 125 levels in a normal population, phase I: the specificities of single and serial determinations in testing for ovarian cancer.

To determine the potential efficacy of the CA 125 assay as one component of a strategy for early detection of ovarian malignancy, serum CA 125 levels were determined in 1082 women 40 years of age or older in Stockholm. Initial serum CA 125 levels exceeded 35 U/ml in 36 women (3.3%) and 65 U/ml in 11 women (1.0%), placing the exact 95% upper confidence limits on false positive rates for a single screen at 4.3 and 1.7%, respectively. Follow-up CA 125 levels were obtained for those women with initially elevated levels and a group of age-matched controls. Mean CA 125 levels declined significantly for women with initially elevated levels (P = 0.0014). Interindividual variation and variation within individual subjects over the entire follow-up period were 52 and 35%, respectively. Of the 36 subjects with initially elevated serum CA 125 levels, only 2 showed a doubling of these levels; in only 1 of these 2 was this increase sustained. Intensive clinical follow-up with pelvic examination and ultrasonography, with investigators blinded to CA 125 results, led to the diagnosis of Stage III ovarian cancer in the latter individual. Diagnosis was made 21 months after the initially elevated serum CA 125 measurement and 15 months after the first measured doubling of that level. Because no other malignancies were identified at entry or during the follow-up period (median 560 days) in the women with elevated CA 125 levels, the specificity of the assay over that time period would have been 99.9% using the doubling of an initially elevated value as the criterion for determining positivity and 100% using as the criterion a sustained increase in level for those with initially elevated levels that doubled. These results support the continued investigation of longitudinally collected CA 125 levels to identify individuals at high risk for ovarian malignancy.

Adult↗
PubMed1990

Statistical considerations in cancer screening programs.

The goal of cancer screening is the early detection and treatment of disease, with a consequent reduction in the mortality rate. Evaluation of whether a particular screening program can achieve this goal is a difficult task. Two components of the screening process must be assessed. The first is the ability of the screening test to detect cancer early while minimizing the number of false-positive results. In this regard, the specificity of the test ordinarily must be very high, approaching 99%. No screening test for prostate cancer has yet been reported to have a specificity this high, indicating that any prostate cancer screening program using currently available tests will have to deal with the problem of a large number of false-positive findings. To evaluate the overall impact of a screening program, the best procedure is the randomized controlled trial with cancer-specific mortality as the endpoint. This endpoint is used because it avoids the lead time and length biases inherent in other outcome variables such as stage shift and case survival. The screening randomized controlled trial must be carefully planned and implemented, because it is lengthier and more costly than the usual therapy trial because of differences in study populations, trial design relative to the planned population intervention, and the extent of knowledge of disease natural history. A further important component of screening evaluation is cost. The decision to implement or continue a screening program can be aided by using cost-effectiveness analysis, which bases a decision on the ranking of cost-to-benefit ratios for the various programs contending for limited funds. Screening cost includes the cost of the test, the cost of side effects of the test, and the costs of biopsy and treatment, while screening benefit can be measured in terms of lives saved, life years saved, or quality-adjusted life years.

Cost-Benefit Analysis↗
PubMed1989

Bovine trypanosomiasis in southern Tanzania: investigation into the incidence of infection and duration of chemoprophylaxis.

Before implementing chemoprophylaxis to control bovine trypanosomiasis it is essential to have epidemiological data upon which to base control regimes. A study was conducted under natural tsetse challenge with two groups each of 12 calves grazing their first season. Group 1 received isometamidium treatments prophylactically at intervals during the rainy season and calves in group 2 were treated individually with diminazene as they become infected with trypanosomes. Infections were first detected in the unprotected calves and indicated that the onset of challenge was approximately four weeks after the rainy season began. Trypanosoma vivax accounted for 21 of the 30 infections detected in blood smears, and although one infection remained unspeciated, the remaining eight were T. congolense. It was concluded that a prophylactic regime beginning one month after the start of the rains with repeat treatments of isometamidium at 1 mg/kg at intervals of 10 weeks could be expected to give good control of trypanosomiasis at this location.

Age Factors↗
PubMed1989

Notes on the routine intravenous use of isometamidium in the control of bovine trypanosomiasis on the Kenya coast.

Various chemotherapeutic regimes were used to control trypanosomiasis in 3,000 Boran cattle on an estate on the Kenya coast. Recently the therapeutic use of isometamidium by the intravenous route was adopted to treat individual trypanosome-infected cattle. This was in order to overcome tissue reactions encountered after intramuscular injection and also to control a "thin cow" syndrome attributed to chronic trypanosomiasis. Toxic side effects were eliminated by careful attention to the intravenous technique which was safely used in calves, pregnant cattle and bulls. Weekly blood sampling and treatments of infected individuals resulted in a reduction of cases from 2,187 to 208 out of 46,495 and 46,329 samples examined in 1985 and 1986 respectively. The standard of management was very high and although this routine successfully controlled bovine trypanosomiasis on this estate its application elsewhere is likely to be limited.

Animals↗
PubMed1989

Stage-shift cancer screening model.

A stage-shift cancer screening model is developed in the context of a randomized controlled trial (RCT) of cancer screening. In the model, detection by screening causes the time of diagnosis of the cancer to be advanced so that either the stage at diagnosis is shifted from one stage to the next lower one or the stage of diagnosis is unchanged but the cancer is diagnosed earlier in the stage. These are called external and internal stage shifts, respectively. At each stage the extent of the external and internal shifts and any associated mortality benefits are estimated. Further, the model allows the interrelationships of these benefits within and between stages to be delineated. This then allows us to better understand the results of the RCT. Data from a completed breast cancer screening RCT are used to illustrate the application of the model and its value in improving our understanding of the trial's results.

Adult↗
PubMed1987

Bovine trypanosomiasis in southern Tanzania: parasitological and serological survey of prevalence.

In a survey for bovine trypanosomiasis blood smears from 1,617 cattle at 72 sites were examined. Trypanosomes were found in 93 cattle, representing 16% of the cattle in herds in which trypanosomiasis was confirmed. Of the positive cattle 56% had infections with T. congolense, 17% T. vivax and 2.2% T. brucei. Five cattle had mixed infections and in 18 cattle the species was not identified. Sera from 1,352 cattle were tested using microelisa. Ten out of 16 sites, at which no trypanosomes were found in blood smears and at which trypanocides were in use, had over 15% seropositive cattle compared with five of 19 sites at which trypanocides were not in use. It was concluded that the microelisa was a useful aid to the diagnosis of bovine trypanosomiasis and that there is a need for accurate records of drug use and livestock movements to be kept. The serious risk of drug resistant strains of trypanosomes emerging due to the uncontrolled use of trypanocides is emphasised.

Animals↗
PubMed1987

Comparing new and old screening tests when a reference procedure cannot be performed on all screenees. Example of automated cytometry for early detection of cervical cancer.

Direct determination of the sensitivity and specificity of a screening test requires use of a reference procedure (such as biopsy with histopathologic analysis) that provides an estimate of true disease status. The authors present a method for comparing the accuracy of a new screening test to an old one in situations when it is not feasible to apply the reference procedure to all screenees. This method requires that only those persons who test positive on old or new screening tests be further evaluated with the reference procedure. Ratios of sensitivities and specificities are derived for rapid comparison of the two screening tests. It is shown that McNemar's test can be used for significance testing of the differences in sensitivities and specificities between two screening tests. The required sample size for a study that compares the two tests is determined.

Female↗
PubMed1987

Sample size for testing differences in proportions for the paired-sample design.

Miettinen (1968, Biometrics 24, 339-352) presented an approximation for power and sample size for testing the differences between proportions in the matched-pair case. Duffy (1984, Biometrics 40, 1005-1015) gave the exact power for this case and showed that Miettinen's approximation tends to slightly overestimate the power or underestimate the sample size necessary for the design power. A simple alternative approximation that is more conservative is presented here. In many cases, the sample size for the independent-sample case provides a conservative approximation for the matched-pair design.

Research Design↗
PubMed1986

Concurrent outbreak of pseudo-lumpy skin disease and acute Trypanosoma vivax infection in cattle.

Pseudo-lumpy skin disease and acute Trypanosoma vivax infections occurred simultaneously in a dairy herd which had no previous history of trypanosomiasis. The onset of the outbreak was sudden and 29 out of the 40 adult Friesian and exotic x zebu cattle were found to have skin lesions. Five out of the nine animals sampled had fulminating T. vivax parasitaemias with packed red cell volumes ranging from 0.09 to 0.28 litres/litre. Whereas carried tsetse may have introduced T. vivax, the failure to trap tsetse and the presence of large numbers of biting flies strongly suggested that in this outbreak both aetiological agents were transmitted mechanically.

Animals↗
PubMed1979

Skin cancer development in mice exposed chronically to immunosuppressive agents.

Inbred female C3Hf/HeN, murine mammary tumor virus-negative mice exposed to either UV light or benzo[a]pyrene (BP), were subjected to four different chronic immunosuppressive regimens to determine their effect on skin cancer development. The immunosuppressive agents were cyclophosphamide, methotrexate, cortisone, and heterologous antilymphocyte globulin. Because of an unexpectedly high morbidity and mortality of mice exposed to chronic immunosuppressive measures, the dosages were kept at a level that permitted them to survive but did not prolong allogeneic skin graft survival and lower antibody titers, nor did this level diminish proliferative responses of lymphocytes to mitogens or allogeneic lymphocytes. Nevertheless, the latency periods (time interval between beginning of medication and appearance of skin tumors) of tumors in mice exposed to immunosuppressant measures were significantly shortened in several groups of mice exposed to UV and subjected to cyclophosphamide, cortisone, or antilymphocyte globulin and mice exposed to BP and subjected to cortisone acetate. In 3 groups, spindle cell tumors (fibrosarcomas) shifted to squamous cell carcinomas. A suppressed immune function would not be regarded as the mechanism for the observed responses because immunosuppression was not detected in the experimental mice.

Animals↗
PubMed1978

Use of the leukocyte migration inhibition assay to evaluate antigenic differences in human breast cancers and melanomas.

The leukocyte migration inhibition assay was used to compare the antigenic reactivity of 3 M KCl extracts of human tumors. Many extracts demonstrated strong reactivity with patient leukocytes, whereas others demonstrated weak or no reactivity, Extracts prepared from primary tumors or local recurrent tumors were more antigenic than extracts from involved lymph nodes or pleural effusions. The least reactive preparations were extracts made from specimens of liver metastases obtained at autopsy. A large standard extract tested at a standard concentration was useful for the evaluation of antigenic reactivity of human tumor extracts. It served as a point of reference in simultaneous tests with one blood sample from each individual, thus eliminating the influence of patient variation on extract reactivity.

Antigens, Neoplasm↗