Critical review of the use of erythropoietin in the treatment of anaemia during therapy for chronic hepatitis C

Combined pegylated interferon (PegIFN) and ribavirin represents the standard therapy for patients with chronic hepatitis C (CHC), which allows for sustained viral response (SVR) in up to 90% of patients depending on certain viral and host factors. Clinical studies have demonstrated the importance of adherence to therapy, that is, the ability of patients to tolerate and sustain a fully dosed therapy regimen. Adherence is markedly impaired by treatment-related adverse effects. In particular, haemolytic anaemia often requires dose reduction or termination of ribavirin treatment, which compromises treatment efficacy. Recent evidence points to a beneficial role of recombinant erythropoietin (EPO) in alleviating ribavirin-induced anaemia thereby improving quality of life, enabling higher ribavirin dosage and consequently improving SVR. However, no general consensus exists regarding the use of EPO for specific indications: its optimal dosing, treatment benefits and potential risks or cost efficiency. The Swiss Association for the Study of the Liver (SASL) has therefore organized an expert meeting to critically review and discuss the current evidence and to phrase recommendations for clinical practice. A consensus was reached recommending the use of EPO for patients infected with viral genotype 1 developing significant anaemia below 100 g/L haemoglobin and a haematocrit of <30% during standard therapy to improve quality of life and sustain optimal ribavirin dose. However, the evidence supporting its use in patients with pre-existing anaemia, non-1 viral genotypes, a former relapse or nonresponse, liver transplant recipients and cardiovascular or pulmonary disease is considered insufficient.

Clitics, affixes, and wordhood in Garifuna (Arawak): A multidimensional continuum of morphosyntactic boundness

Recent research on wordhood and morphosyntactic boundness suggests that the domains word and clitic do not lend themselves to cross-linguistic categorization but must be defined language specifically. In most languages, it is necessary to define word on two separate levels, the phonological word (p-word) and the grammatical word (g-word), and to describe mismatches between the two. This paper defines those domains for Garifuna, an Arawak language spoken in Honduras, Central America. Garifuna has auxiliary and classifier constructions which make up two p-words, and only one g-word. P-words made up of more than one g-word involve second position enclitics, word scope clitics, and proclitic connectives and prepositions. Garifuna clitics are typically unstressed, able to attach to hosts of any word class and able to string together into clusters. Enclitics are used to express tense-aspect, modality, and adverbial meanings, among others. In other languages, clitic clusters tend to display a fixed order; Garifuna clitic order seems quite free, although certain orders are preferred. Also, contrary to cross-linguistic tendencies, proclitic connectives can act as hosts for enclitic clusters, contradicting the commonly used definition of clitics as phonologically weak elements that need to attach to a host to form a p-word; such clitic-only p-words are problematic for traditional definitions of clitics.