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Conflicting results come from epidemiological studies on the correlations between gender and pain in hospitalized patients. No specific data are reported in patients admitted to Internal Medicine Units (IMUs). Post-hoc analysis of the FADOI-DOMINO study, performed in 26 IMUs in Italy, with two cross-sectional surveys interspersed with an educational program. The 5200 medical charts of the FADOI-DOMINO study were re-analyzed. The following sex differences were highlighted: i) a greater pain prevalence was evidenced in women in the Pre-phase; ii) among patients with chronic pain, anxiety and depression were significantly more present in women compared with men; iii) oncologic pain was more prevalent in men; in a specular way, nononcologic pain showed a greater prevalence in women in both phases; iv) strong opioids therapy was higher for men. Some sex differences in pain seem to exist in IMUs, although less evident if compared with those previously reported in other settings. A more careful assessment of coexisting conditions such as anxiety, depression or cognitive impairment can result in a better management of these problems.