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More than 250 Pleistocene vertebrate trace fossil sites have been identified on the Cape south coast of South Africa in aeolianites and cemented foreshore deposits. These discoveries, representing the epifaunal tracks of animals that moved over these sand substrates, complement traditional body fossil studies, and contribute to palaeo-environmental reconstruction. Not described in detail until now, but also important faunal components, are the infaunal traces of animals that moved within these sandy substrates. Six golden mole burrow trace sites (Family Chrysochloridae) have been identified on the Cape south coast. In addition, three sites, including one on the Cape southeast coast, have been identified that show evidence of sand-swimming, probably by a golden mole with a means of locomotion similar to that of the extant Eremitalpa genus. Such traces have not been described in detail in the global ichnology record, and merit the erection of a new ichnogenus Natatorichnus, with two ichnospecies, N. subarenosa ichnosp. nov and N. sulcatus ichnosp. nov. Care is required in the identification of such traces, and the orientation of the trace fossil surface needs to be determined, to avoid confusion with hatchling turtle tracks. Substantial regional Pleistocene dune environments are inferred from these sand-swimming traces.
Clozapine is mainly used in patients with treatment-resistant schizophrenia and may lead to potentially severe haematologic adverse events, such as agranulocytosis. Whether clozapine might be associated with haematologic malignancies is unknown. We aimed to assess the association between haematologic malignancies and clozapine using Vigibase®, the WHO pharmacovigilance database.
We performed a disproportionality analysis to compute reporting odds-ratio adjusted for age, sex and concurrent reporting of antineoplastic/immunomodulating agents (aROR) for clozapine and structurally related drugs (loxapine, olanzapine and quetiapine) compared with other antipsychotic drugs. Cases were malignant lymphoma and leukaemia reports. Non-cases were all other reports including at least one antipsychotic report.
Of the 140 226 clozapine-associated reports, 493 were malignant lymphoma cases, and 275 were leukaemia cases. Clozapine was significantly associated with malignant lymphoma (aROR 9.14, 95% CI 7.75–10.77) and leukaemia (aROR 3.54, 95% CI 2.97–4.22). Patients suffering from those haematologic malignancies were significantly younger in the clozapine treatment group than patients treated with other medicines (p < 0.001). The median time to onset (available for 212 cases) was 5.1 years (IQR 2.2–9.9) for malignant lymphoma and 2.5 years (IQR 0.6–7.4) for leukaemia. The aROR by quartile of dose of clozapine in patients with haematologic malignancies suggested a dose-dependent association.
Clozapine was significantly associated with a pharmacovigilance signal of haematologic malignancies. The risk-benefit balance of clozapine should be carefully assessed in patients with risk factors of haematologic malignancies. Clozapine should be used at the lowest effective posology.