Causal association reversibility

A causal association has been shown between the hepatotoxicity of ciclosporin and cold ischemic liver damage that can occur during preservation before liver transplantation (85). This presents a problem when ciclosporin is used after liver transplantation. In more than 1000 patients there was an incidence of mild reversible hepatotoxicity of 40% in patients taking 5-fluorouracil and levamisole as adjuvants for more than 1 year the incidence of mild hepatotoxicity in those taking levamisole alone and amongst those receiving no treatment at all was the same, a little over 16% (86). 

Secondary health effects indoors are less adverse, and mostly characterized by being reversible, and with no severe consequences for the occupants. The effects may have high prevalence. For these effects the causality may not be exactly known but an association to IAQ has been documented. Exact quantification may not be possible and indicators or substitute measures may have to be used. For secondary effects strict guidelines cannot be set and a strict compound-by-compound evaluation is not possible (or needed). 

It is very difficult to find a causal relation between topiramate and this patient s hemiparesis. An alternative interpretation is that he had complex partial status (as suggested by his electroencephalogram) when carbamazepine was withdrawn, associated with reversible hemiparesis. 

NTP had the same concern as EPA (2012) that the association of BLL with ALS was influenced by reverse causality and by bias dne to the increase in survival time with higher BLL (Kamel et al. 2008 Fang et al. 2010). NTP s conclusion that there was sufficient evidence of an association between essential tremor and BLLs under 10 pg/dL was based on case-control studies conducted in two countries (Louis et al. 2003, 2005, 2011 Dogu et al. 2007). The evidence that essential tremor is associated with a BLL of 3 pg/dL is based on a small sample (300 essential tremor patients) in the two stndies. Thus, NTP concluded that evidence of an association with a concurrent BLL nnder 5 pg/dL was limited. 

The results of prospective or cohort studies of homocysteine and vascular disease (where blood for homocysteine determinations was collected before the onset of disease in cases) in the late 1990s were less extreme than those of retrospective studies (where blood for homocysteine determinations was collected after the onset of vascular disease) (Danesh and Lewington 1998). In 1998, Danesh and Lewington reported that a 5 pmol/L higher measured homocysteine was associated with an odds ratio for CHD of 1.6 (1.4-1.7) in retrospective studies but only 1.3 (95%CI 1.1-1.5) in prospective studies (Danesh and Lewington 1998). The discrepancy between the results of retrospective and prospective studies was interpreted to indicate reverse causality i.e. the effect of vascular disease on homocysteine concentrations) (Danesh and Lewington 1998). 

Cardiovascular A 64-year-old woman treated for macular degeneration with intraocular injections of bevacizumab presented with chest pain, nausea and vomiting. After an initial diagnosis of acute coronary syndrome and anticoagulation treatment with intravenous heparin, she remained stable without chest pain or shortness of breath and with no evidence of arrhythmias. This may be the first report of an association between intraocular bevacizumab and reversible myocardial dysfunction with a pattern similar to stress-induced cardiomyopathy (also called Takotsubo cardiomyopathy or apical ballooning), although clear evidence for a causal relationship is lacking [97 ]. 

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