to more severe or chronic forms of the disease 5,6 and avoid The objective of this study is to present and validate a the occurrence of new episodes, including some cases of clinical scale for the diagnosis of drug-induced liver injury fulminant hepatic failure. 7 (DILI). Five components were selected to be included in the Because there are no specific markers or tests for DILI, the scale: temporal relationship between drug intake and the ondiagnosis is usually based on circumstantial evidence. 8 It set of clinical picture, exclusion of alternative causes, extraherelies on a great deal of speculation by the clinician, the patic manifestations, rechallenge or accidental re-exposure, collection of a detailed pharmacological history, the estaband previous report in medical literature. The relative imporlishment of a consistent relationship between drug intake tance of each component was weighed, and arbitrary scores and the onset of the clinical picture, and the exclusion of were attributed. The probability of the diagnosis of DILI was alternative causes. Clinical improvement following drug expressed as a final score, which could vary from 06 to 20.withdrawal is another element that may indicate a drugContent validity, criterion validity, construct validity, and inrelated cause, although there is an increased recognition of ter-rater reliability were studied. To analyze validity and reliaprolonged cholestatic hepatitis, sometimes lasting for more bility, a random sample of 50 cases of suspected DILI was than 6 months, after drug withdrawal. 9 Rechallenge is fredrawn from a series of 120 cases reported to our unit. The quently considered to be the most reliable test in the diagnoclassification of the 50 cases by three experts in DILI was sis of suspected cases of DILI, 10 but it is clearly dangerous used as the external standard in the study of criterion validity.and is best avoidable. 7 Agreement between the scale and the standard, and agreement This complex process of diagnosis usually requires an exbetween two independent raters (inter-rater reliability) was perienced clinician who is deeply aware of the critical compoanalyzed by weighted k coefficient. There was agreement benents to be weighed for an accurate diagnosis, including a tween the scale and the standard in 42 cases (84%) with a good knowledge of the published literature. The translation weighted k coefficient of 0.90. A good discriminatory capacity of such experience and subjective clinical judgment into a of the scale was found when construct validity was studied.quantitative measurement to define, by more objective criteAgreement between raters was observed in 86% of the cases, ria, the probability of an adverse event being related to a corresponding to the weighted k of 0.93. In conclusion, the drug, is of major importance. The complexity of the clinical clinical scale was shown to have a high-level of validity and diagnosis has led to attempts to improve in vitro diagnostic inter-rater reliability as well as a good discriminatory capacity tests to...

Background-Diagnosis of drug induced liver injury is usually based on a temporal relation between drug intake and clinical picture as well as on the exclusion of alternative causes. More precise diagnosis has been attempted by using in vitro specific T cell reactivity to drugs but the test has never reached general acceptability because of frequent negative results which could be explained, in part, by prostaglandin producing suppressor cells (PPSC). Results-When PBMC were stimulated with drugs alone, lymphocyte sensitisation to drugs (SI>2) was detected in 26% of the cases. This was noticeably increased (56%) when a prostaglandin inhibitor was added to the cultures. No reactivity was found in controls. In patients with possible sensitivity to several drugs, lymphocyte reactivity was detected to only one drug. The severity of the lesions, as assessed by aminotransferase concentrations and disease duration, was lower in patients with evidence of PPSC. Conclusions-This new approach is useful for the diagnosis of drug induced liver injury, particularly in patients exposed to more than one drug; furthermore, the presence of putative PPSC is associated with less severe forms of drug induced hepatitis. (Gut 1997; 41: 534-540) Aim-To

No abstract

Background In 2015, Portugal was the OECD country with the highest reported consumption of BZD. Physician’s perceptions and attitudes regarding BZD are main determinants of related prescription habits. This study aimed to characterize beliefs and attitudes of Portuguese physicians regarding the prescription, management challenges, benefits, risks and withdrawal effects of BZD. Methods A cross-sectional, observational study with online data collection through anonymous self-administered questionnaire. Physicians registered with the Portuguese Medical Association were invited to participate through direct e-mail message. Physicians were asked to give their opinion (using a 5-points Likert scale) regarding the prescription of BZD, their benefits and risks in the management of insomnia and anxiety, the possible adverse effects of chronic use and alternative non-pharmacologic approaches. Descriptive statistics were used and groups were compared through logistic regression. Results A total of 329 physicians participated in the study (56% family physicians). Mean age was 44.10 ± 15.2 years, with 19.03 ± 14.9 years of clinical experience. Fifty eight percent of participants were female. Physicians reported BZD’s negative impact on cognitive function (89%), association with road traffic accidents (88%) and falls (79%). Also, 58% shared the belief that chronic use is justified if the patient feels better and without adverse events. Although 68% reported to feel capable of helping patients to reduce or stop BZD, 55% recognized difficulties in motivating them. Compared to other medical specialists (altogether), family physicians were significantly more aware about the adverse effects of BZD and considered that chronic use may not be justified. Conversely, more family physicians expressed concerns about their skills to motivate patients engaging in withdrawal programs and to support them during the process. Conclusion Our results show that physicians’ awareness about risks of BZD chronic use is adequate though their attitudes and self-perceived skills towards promoting BZD withdrawal can be improved. Interventions in primary care are needed to capacitate physicians to better motivate patients for BZD withdrawal.