J. D. F. Habbema

Screening for colorectal cancer: randomised trial comparing guaiac-based and immunochemical faecal occult blood testing and flexible sigmoidoscopy

Background: Screening for colorectal cancer (CRC) is widely accepted, but there is no consensus on the preferred strategy. We conducted a randomised trial comparing participation and detection rates (DR) per screenee of guaiac-based faecal occult blood test (gFOBT), immunochemical FOBT (FIT), and flexible sigmoidoscopy (FS) for CRC screening. Methods: A representative sample of the Dutch population (n = 15 011), aged 50–74 years, was 1:1:1 randomised prior to invitation to one of the three screening strategies. Colonoscopy was indicated for screenees with a positive gFOBT or FIT, and for those in whom FS revealed a polyp with a diameter ⩾10 mm; adenoma with ⩾25% villous component or high grade dysplasia; serrated adenoma; ⩾3 adenomas; ⩾20 hyperplastic polyps; or CRC. Results: The participation rate was 49.5% (95% confidence interval (CI) 48.1 to 50.9%) for gFOBT, 61.5% (CI, 60.1 to 62.9%) for FIT and 32.4% (CI, 31.1 to 33.7%) for FS screening. gFOBT was positive in 2.8%, FIT in 4.8% and FS in 10.2%. The DR of advanced neoplasia was significantly higher in the FIT (2.4%; OR, 2.0; CI, 1.3 to 3.1) and the FS arm (8.0%; OR, 7.0; CI, 4.6 to 10.7) than the gFOBT arm (1.1%). FS demonstrated a higher diagnostic yield of advanced neoplasia per 100 invitees (2.4; CI, 2.0 to 2.8) than gFOBT (0.6; CI, 0.4 to 0.8) or FIT (1.5; CI, 1.2 to 1.9) screening. Conclusion: This randomised population-based CRC-screening trial demonstrated superior participation and detection rates for FIT compared to gFOBT screening. FIT screening should therefore be strongly preferred over gFOBT screening. FS screening demonstrated a higher diagnostic yield per 100 invitees than both FOBTs.

Screening for colorectal cancer: random comparison of guaiac and immunochemical faecal occult blood testing at different cut-off levels

Immunochemical faecal occult blood testing (FIT) provides quantitative test results, which allows optimisation of the cut-off value for follow-up colonoscopy. We conducted a randomised population-based trial to determine test characteristics of FIT (OC-Sensor micro, Eiken, Japan) screening at different cut-off levels and compare these with guaiac-based faecal occult blood test (gFOBT) screening in an average risk population. A representative sample of the Dutch population (n=10 011), aged 50–74 years, was 1 : 1 randomised before invitation to gFOBT and FIT screening. Colonoscopy was offered to screenees with a positive gFOBT or FIT (cut-off 50 ng haemoglobin/ml). When varying the cut-off level between 50 and 200 ng ml−1, the positivity rate of FIT ranged between 8.1% (95% CI: 7.2–9.1%) and 3.5% (95% CI: 2.9–4.2%), the detection rate of advanced neoplasia ranged between 3.2% (95% CI: 2.6–3.9%) and 2.1% (95% CI: 1.6–2.6%), and the specificity ranged between 95.5% (95% CI: 94.5–96.3%) and 98.8% (95% CI: 98.4–99.0%). At a cut-off value of 75 ng ml−1, the detection rate was two times higher than with gFOBT screening (gFOBT: 1.2%; FIT: 2.5%; P<0.001), whereas the number needed to scope (NNscope) to find one screenee with advanced neoplasia was similar (2.2 vs 1.9; P=0.69). Immunochemical faecal occult blood testing is considerably more effective than gFOBT screening within the range of tested cut-off values. From our experience, a cut-off value of 75 ng ml−1 provided an adequate positivity rate and an acceptable trade-off between detection rate and NNscope.

Hip fracture in elderly patients: outcomes for function, quality of life, and type of residence.

A prospective study was done to investigate functional outcome, quality of life, and type of residence after hip fracture in patients 65 years of age and older. One hundred two patients admitted consecutively to a university and a general hospital were followed up as long as 4 months after admission. The mean age of the participants was 83 years; 58% of patients came from their own home, and 42% of patients came from institutions. Nearly 70% of patients had two or more diagnoses other than the hip fracture. Cumulative mortality was 20% at 4 months after fracture. Of surviving patients, 57% were back in their original situation for accommodation, 43% reached the same level of walking ability, and 17% achieved the same level of activities of daily living as before fracture. Patients experienced on average three complications, 26% of which were severe. Quality of life improved in the followup period of 4 months; however, the quality of life at 4 months was worse than the quality of life reported in a reference population. Average costs amounted to ε (Euro) 15.338 (which at the time was nearly equivalent to the US dollar) per patient, with nearly 50% of the costs attributable to hospital costs and 30% attributable to nursing home costs. The results of this study show a poor outcome after hip fracture in elderly patients.

Epidemiological evidence for age-dependent regression of pre-invasive cervical cancer

Data from the screening programme in British Columbia are used to test hypotheses about the natural history of cervical cancer, especially about progression and regression of preclinical lesions (dysplasia and carcinoma in situ). Three models are considered. A model without regression does not give an adequate fit of the data (P less than 0.001), and results in an implausible estimate of 33 years for the mean duration of pre-invasive lesions. A model with an equal regression rate at all ages still does not result in a good reproduction of the data. A good fit is achieved for a model with different regression rates in lesions that develop under and over age 34. Under age 34, 84% of the new lesions will regress spontaneously, with a 95% confidence interval of 76-92% regression. Over age 34, we estimate that 40% of the new lesions will regress. The average duration of dysplasia + CIS is 11.8 years, and the sensitivity of the Pap-smear is 80%. It is concluded that a considerable proportion of pre-invasive lesions in young women do not progress. The findings about progression and duration of pre-invasive lesions do not support the still prevailing tendency of frequently making Pap smears in young women.

Spatial and temporal variations of malaria epidemic risk in Ethiopia: factors involved and implications

The aim of this study was to describe spatial and temporal variations in malaria epidemic risk in Ethiopia and to examine factors involved in relation to their implications for early warning and interpretation of geographical risk models. Forty-eight epidemic episodes were identified in various areas between September 1986 and August 1993 and factors that might have led to the events investigated using health facility records and weather data. The study showed that epidemics in specific years were associated with specific geographical areas. A major epidemic in 1988 affected the highlands whereas epidemics in 1991 and 1992 affected highland-fringe areas on the escarpments of the Rift Valley and in southern and north-western parts of the country. Malaria epidemics were significantly more often preceded by a month of abnormally high minimum temperature in the preceding 3 months than based on random chance, whereas frequency of abnormally low minimum temperature prior to epidemics was significantly lower than expected. Abnormal increases of maximum temperature and rainfall had no positive association with the epidemics. A period of low incidence during previous transmission seasons might have aggravated the events, possibly due to low level of immunity in affected populations. Epidemic risk is a dynamic phenomenon with changing geographic pattern based on temporal variations in determinant factors including weather and other eco-epidemiological characteristics of areas at risk. Epidemic early warning systems should take account of non-uniform effects of these factors by space and time and thus temporal dimensions need to be considered in spatial models of epidemic risks.

Can ivermectin mass treatments eliminate onchocerciasis in Africa

OBJECTIVE To elucidate the conditions in which mass treatment with ivermectin reduces the transmission of Onchocerca volvulus sufficiently to eliminate infection from an African community. METHODS ONCHOSIM, a microsimulation model for onchocerciasis transmission, was used to explore the implications of different treatment intervals, coverage levels and precontrol endemicities for the likelihood of elimination. FINDINGS Simulations suggested that control strategies based exclusively on ivermectin mass treatments could eliminate onchocerciasis. The duration of treatment required to eliminate infection depended heavily on the treatment programme and precontrol endemicity. In areas with medium to high levels of infection, annual mass treatments with 65% coverage for at least 25 years were necessary. Model predictions suggested that durations exceeding 35 years would be required if there were much heterogeneity in exposure to vector bites and, consequently, wide individual variation in microfilaria counts. If the treatment interval were reduced from 12 to 6 months the time for completion of the programme could be more than halved and elimination could be accomplished in areas of hyperendemicity, provided that the effects of each treatment would be the same as with annual treatments. However, it was doubtful whether high coverage levels could be sustained long enough to achieve worldwide eradication. CONCLUSION Elimination of onchocerciasis from most endemic foci in Africa appears to be possible. However, the requirements in terms of duration, coverage, and frequency of treatment may be prohibitive in highly endemic areas.

The MISCAN-COLON simulation model for the evaluation of colorectal cancer screening

A general model for evaluation of colorectal cancer screening has been implemented in the microsimulation program MISCAN-COLON. A large number of fictitious individual life histories are simulated in each of which several colorectal lesions can emerge. Next, screening for colorectal cancer is simulated, which will change some of the life histories. The demographic characteristics, the epidemiology and natural history of the disease, and the characteristics of screening are defined in the input. All kinds of assumptions on the natural history of colorectal cancer and screening and surveillance strategies can easily be incorporated in the model. MISCAN-COLON gives detailed output of incidence, prevalence and mortality, and the results and effects of screening. It can be used to test hypotheses about the natural history of colorectal cancer, such as the duration of progressive adenomas, and screening characteristics, such as sensitivity of tests, against empirical data. In decision making about screening, the model can be used for evaluation of screening policies, and for choosing between competing policies by comparing their simulated incremental costs and effectiveness outcomes.

The reproductive lifespan of Onchocerca volvulus in West African savanna.

The epidemiological model ONCHOSIM--a model and computer simulation program for the transmission and control of onchocerciasis--has been used to determine the range of plausible values for the reproductive lifespan of Onchocerca volvulus. Model predictions based on different lifespan quantifications were compared with the results of longitudinal skin-snip surveys undertaken in 4 reference villages during 13 to 14 years of successful vector control in the Onchocerciasis Control Programme in West Africa. Good fits between predicted and observed trends in skin microfilarial loads could be obtained for all villages. It is concluded that the reproductive lifespan of the savanna strain of O. volvulus lies between 9 and 11 years, and that 95% of the parasites reach the end of reproduction before the age of 13 to 14 years.

The MISCAN simulation program for the evaluation of screening for disease

The computer program MISCAN is developed for use in evaluation of mass screening for disease. The program uses Monte Carlo simulation. It produces output on the results of screening projects and on the effects of screening on morbidity and mortality on the individual and population level. The calculations are based on models of the natural history of the disease and of the impact of screening on the natural history. The approach is such that considerable flexibility exists in specifying the structure of the model and its parameters. The program consists of two parts. The DISEASE part can be used for simulating the epidemiology of the disease when no screening is taking place; it requires input on the population and on the disease process. The SCREENING part is to be used in combination with the DISEASE part. It is intended for simulation of the results and effects of a screening project. It requires input on the properties of the screening tests, the consequences of early detection by screening, and the policy (ages and intervals between screens) of the project. MISCAN can be used for finding model assumptions regarding the disease process and the impact of screening that give a good explanation of the observed results of a screening project. Such an analysis proceeds in two steps. First, MISCAN is used to calculate simulated results of the project, based on specific assumptions. Next, these results are tested against the observed results, in order to assess the acceptability of the assumptions. MISCAN can also be used for optimization of the screening policy by simulating the cost and benefit components of a large number of different screening policies.

ONCHOSIM: A model and computer simulation program for the transmission and control of onchocerciasis

ONCHOSIM is a computer program for modelling the transmission and control of the tropical parasitic disease onchocerciasis, or river blindness. It is developed in collaboration with the Onchocerciasis Control Programme in West Africa (OCP), and is used as a tool in the evaluation and planning of control operations. The model comprises a detailed description of the life history of the parasite Onchocerca volvulus and of its transmission from person to person by Simulium flies. The effects of different control strategies, based on larvicide application and chemotherapy (ivermectin), on the transmission and on the disease symptoms can be evaluated and predicted. In the program two simulation techniques are mixed. Stochastic microsimulation is used to calculate the life events of individual persons and inhabitant parasites, while the dynamics of the Simulium population and the development of the parasite in the flies are simulated deterministically. Output of ONCHOSIM conforms to the format in which data collected by the OCP are reported. This enables detailed checking of model specifications against empirical data. Output can also consist of summarizing key indices for the intensity of onchocerciasis infection, which is especially useful for comparing the effectivity of control strategies.