Cumulative incidence

New-onset DM after transplantation (NODAT) is a serious complication that often is underestimated by transplant practitioners.74 Kasiske and colleagues attempted to quantify the cumulative incidence of NODAT in renal transplant recipients and found that 8% of patients developed NODAT at 3 months after transplantation, 13% at 12 months, and... 

TMPT activity in human erythrocytes is transmitted as an autosomic codominant trait [15] and is trimodally distributed, with 89-94% of the individuals having high, 6-11% intermediate, and 0.3% low activity [7, 15-17] (Figure 14.2). The measurement of TPMT activity in erythrocytes closely reflects the ability of bone marrow to inactivate 6-MP. TPMT activity is inversely related to erythrocyte 6-TGN levels [7, 13, 18, 19], and children with low TPMT activity and very high 6-TGN levels experienced profound myelotoxicity [20, 21]. Moreover, TPMT phenotype in erythrocyte reflects that in leukemic blasts [22]. Patients with intermediate TPMT activity had a 5-fold greater cumulative incidence of dose reductions than subjects with high activity [13], and TPMT activity has been inversely related to the time of treatment withdrawal due to cytopenia [21]. 

Fig. 10.10. Cumulative incidence of invasive breast cancers during 8 years of treatment either with raloxifene (dotted line) or placebo (solid line) Reproduced with permission from Martino et al. (2004)...

Persons with aplastic anemia due to benzene exposure have been found to be at a much greater risk for developing leukemias. A follow-up of 51 benzene-exposed workers with pancytopenia revealed 13 cases of leukemia. The cumulative incidence of leukemia among individuals with clinically ascertained benzene hemopathy has ranged from 10% to 17% in various studies. ... 

It is usual to estimate and plot the probability of being event-free, but there will be occasions when interpretation is clearer when the opposite of this, cumulative incidence (or cumulative probability of experiencing the event by that time), is plotted. This is simply obtained as 1 - probability of being event-free. Pocock et al. (2002) discuss issues associated with the interpretation of these plots. These authors point out that interpretation in the conventional type of plot, when the event rates are low, can be exaggerated visually by a break in the y-axis, so take care ... 

The 8-year cumulative incidence of brain tumors among children with low TPMT activity was 42.9% (standard error 20.6) versus 8.3% (standard error 4.7) in TPMT wild-type patients. In the Scandinavian NOPHO ALL-92 trial, Thomsen and colleagues reported on a significantly higher risk of therapy-associated AML or myelodysplastic syndrome in patients with low TPMT activity and high erythrocyte 6-TGN levels and/or 6-MMPR (207). 

Fig. 3.2 Cumulative incidence of neoplasms of the liver and urinary bladder in female BALB/c mice exposed to 2 aoetylamino fluorene at various concentrations in the diet for up to 33 months (from Littlefield etaL, 1979).

First, the carcinogenic effects of radiation and chemicals are expressed as an increase in the age-spedfic incidence of particular neoplasms. Depending on the survival of the population at risk, the final cumulative incidence of neoplasms in the population may, or may not, be increased. 

Although the data are not sufficient to define the shapes of the dose incidence curves in most instances, a markedly increased risk of cancer has been noted in a number of more heavily exposed populations (Ikble 6.5). In 2-naphthylamine distillers, for example, the latency and incidence of bladder cancer have been observed to vary systematically in relation to the duration of exposure (Figure 6.2). In those with exposures lasting more than five years, the cumulative incidence approached 100 percent (Figures 6.2 6.3). 

Fig. 6.2 Lateiu and cumulative incidence of tumors of the urinary bladder in 78 distillers of 2-naphthylamine, in relation to duration of occupational exposure (reproduced from Saffiotti. 1973 based on data from Williams, 1958).

There have been conflicting reports on the incidence and severity of symptoms such as hot flushes (also known as hot flashes) during long-term treatment with raloxifene for the prevention of osteoporosis. In fact the difference between raloxifene and placebo does not seem to be very great. In a review of three identical randomized trials in which raloxifene 60 mg was given for long periods to healthy postmenopausal women of various ages it was concluded that after 30 months the cumulative incidence of hot flushes was 21% for placebo and 28% for raloxifene, but the difference in frequency was confined to the first 6 months of therapy (25). There was no difference... 

A graph of cumulative incidence from one of the studies (Wetzel et al, 1994) is shown in Figure 26.1. The principal effect of treatment in this study was to cause an earlier onset of tumor appearance, which was essentially matched by the control group after 24 months. Note also in Figure 26.1 the absence of tumor response in F-344 female rats, both in the control and treated groups. 

Figure 26.1 Cumulative incidence of mammary tumors in Sprague-Dawley and Fischer-344 female rats fed atrazine in the diet for 104 weeks. (Only palpated masses proven at necropsy to be mammary tumors were included. The incidence plot of 400ppm in the SD study was significantly different from the Oppm plot (p < 0.05), but the final incidence percentages were not different (N = 60 per dose)).

Fig. 9. Cumulative incidence of all confirmed breast cancers in the placebo and raloxifene groups (Cummings etal, 1999).

Cumulative incidence of gastric or duodenal ulcers in patients receiving long-term NSAID therapy. 

Effect of raloxifene on cumulative incidence of breast cancer in 7,705 postmenopausal women. 

The cumulative incidence of hepatic adverse reactions associated with antidepressant treatment has been estimated through spontaneous reports to the Spanish Pharmacovigilance System (12). For classical tricyclic antidepressants and SSRIs the estimated rate of adverse hepatic reactions was 1.28-4.00 per 100 000 patient years. However, the rate with nefazodone was much higher (29 per 100 000 patient years). This report supports concerns that nefazodone may be more hepatotoxic than other antidepressants. Significant hepatic reactions to nefazodone are relatively rare but can be serious. 

In one study, previous neuroleptic drug use at study entry was the only significant predictor of tardive dyskinesia (296). Psychiatric outpatients aged over 45 years, who had taken neuroleptic drugs for 0-30 days (n = 176), were compared with 131 who had taken neuroleptic drugs for more than 30 days. The cumulative incidences of tardive dyskinesia were 23% and 37% at the end of 12 months. In the patients who had never used neuroleptic drugs before (n = 87), the mean cumulative incidence of tardive dyskinesia after the use of typical neuroleptic drugs (median dose 68 mg/day of chlorpromazine equivalents) was 3.4% at baseline and 5.9% at 1 and 3 months. 

Tardive dyskinesia was studied in 330 elderly patients with dementia (mean age 83 years) (94). They were enrolled in a 1-year open study, in which the modal risperidone dose was 0.96 mg/day and the median duration of use was 273 days. The 1-year cumulative incidence of persistent tardive dyskinesia among the 225 patients without dyskinesia at baseline was 2.6%, and patients with dyskinesia at baseline had significant reductions in severity. 

FIGURE 24.4 Cumulative incidence of neuroleptic-induced tardive dyskinesia in old ( ) and young ( ) adults. (Reproduced lAuth permission from Jeste DV. J Clin Psychiatry 2000 61(suppl 4) 27-32.)... 

The National Wilms Tumor Study Group has reported the incidence of second malignant neoplasms in 5278 patients treated over 22 years (81). There were 43 second malignant neoplasms, whereas only five were expected. Fifteen years after the diagnosis of Wilms tumor, the cumulative incidence of a second malignant neoplasm was 1.6% and increasing steadily. Abdominal irradiation, given as part of the initial therapy, increased the risk, and... 

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