Interactions between glucocorticoids and warfarin in chronic inflammatory (autoimmune) diseases

Glucocorticosteroids are still very important part of the treatment of chronic inflammatory disorders. Their use is often accompanied by unpleasant adverse effects, problems associated with withdrawal during their long-term use and interactions with concomitantly administered drugs. One of the important interactions that may often occur in clinical practice is interaction with warfarin. Despite the fact that as glucocorticosteroids so warfarin are used for many years and seem to be completely known, their co-administration is still accompanied by uncertainties. The interaction may have pharmacodynamic or pharmacokinetic character and both types result in increased risk of bleeding. The pharmacodynamic interaction can be expected to increase a risk of gastrointestinal bleeding to which a gastrotoxicity of glucocorticosteroids contributes. A pharmacokinetic interaction is considered to influence a hepatic metabolism of warfarin and to increase its availability. The exact mechanism is still not fully understood. Manifestations of both types of interactions are taken up with a delay. Co-administration requires increased attention and close monitoring of international normalized ratio. At higher doses of glucocorticosteroids proton pump inhibitors are also effective in prevention of gastrotoxicity.     

Systematic Serological Testing for Hepatitis E Virus in Kidney Transplant Recipients

Hepatitis E virus (HEV) genotype 3 is endemic in Europe and hyperendemic in southern France. Recent reports of a high prevalence of HEV RNA in blood donations and in culinary specialties from this geographical area confirmed the endemicity of HEV and sources of viral transmission in this geographical area. HEV causes acute and chronic hepatitis in solid organ transplant recipients. Since March 2012, we have implemented systematic HEV serological testing in our cohort of kidney transplant recipients (KTRs) in Marseille in southeastern France. The aim of our study was to assess HEV exposure in this cohort between March 2012 and May 2014. During these 27 months, we found that 39% of the patients who underwent kidney transplantation had an anti-HEV IgG response using a sensitive microplate enzyme immunoassay. This seroprevalence was approximately 43% at both 1 and 8 years after, using the same assay. In addition, systematic HEV serological testing detected 6 cases of HEV infection among 578 KTRs (1%) during the 27 months of the study, with 5 at an acute stage and 1 at a chronic stage. In conclusion, continuous HEV monitoring in this population is useful for better understanding the epidemiology of HEV in France, because these patients are a well-monitored population. Moreover, HEV monitoring in KTRs is clinically relevant because HEV represents a clinical threat in these patients. Nevertheless, HEV serological testing may be more fruitful for identifying HEV infections when performed in cases of biological liver abnormalities than when performed systematically.     

Acute myelogenous leukaemia following cytotoxic therapy: five cases and a review

Acute myelogenous leukaemia (AML) following cytotoxic chemotherapy has been reported increasingly. Five new cases are presented including the first described following treatment for immune thrombocytopaenia. A review of the literature has revealed 226 case reports of treatment-linked AML with sufficient detail to permit further study. Of the total of 231 patients, 76 (33 per cent) followed Hodgkin's disease, 59 (25.5 per cent) multiple myeloma, 22 (9.5 per cent) non-Hodgkin's lymphoma, 32 (14 per cent) other solid tumours and 42 (18 per cent) non-malignant diseases. The time interval from the start of chemotherapy to the diagnosis of AML was similar in all disease groups whether the patients had received radiotherapy or not. Differences emerged when the duration of exposure to chemotherapy was analysed in the individual disease groups; exposure was shorter in those patients treated for Hodgkin's disease and solid tumours than with the others suggesting that the pattern of administration of chemotherapy may be important. The effects of radiotherapy in addition to chemotherapy could not be defined precisely, but the study highlights the particular risk that appears to arise from alkylating agents, and the need to define optimal methods of administration of chemotherapy with minimal risk of inducing leukaemia.     

Association between antiphospholipid antibodies and recurrent fetal loss in women without autoimmune disease: a metaanalysis

OBJECTIVE: To assess the strength of association between recurrent fetal loss (RFL) and presence of antiphospholipid antibodies (aPL) in women without autoimmune disease, and to examine whether magnitude of association varies according to type or titer of antibody and timing of fetal loss. METHODS: We searched Medline and Current Contents for articles published between 1975 and 2003 with terms denoting early (less than 13 weeks) and late (less than 24 weeks) RFL associated with various aPL. Published case-control, cohort, and cross-sectional studies rated moderate or strong were included in our metaanalysis. Pooled odds ratios with 95% CI were generated using the random-effects models with Cochrane Review Manager software. RESULTS: Our analysis included 25 studies. Lupus anticoagulant (LAC) was associated with late RFL (OR 7.79, 95% CI 2.30-26.45); the association of LAC was stronger than that of any other aPL. IgG anticardiolipin antibodies (aCL), when combining all titers, were associated with both early (OR 3.56, 95% CI 1.48-8.59) and late RFL (OR 3.57, 95% CI 2.26-5.65). Restricting analysis to include only women with moderate to high titers increased the strength of association (OR 4.68, 95% CI 2.96-7.40). It was not possible to extract data on isolated low IgG aCL positivity. IgM aCL were associated with late RFL (OR 5.61, 95% CI 1.26-25.03). There was no association found between early RFL and anti-Beta2-glycoprotein I antibodies (OR 2.12, 95% CI 0.69-6.53). CONCLUSION: The magnitude of the association between aPL and RFL varies according to type of aPL. More data on the relationship between recurrent fetal loss and isolated IgM aCL as well as with low titer IgG aCL would be useful. The place of testing for anti-Beta2-glycoprotein I antibodies remains to be determined.     

What do general practitioners do differently when consulting with a medical student?

Objectives The practice of having medical students see patients in a general practice setting, in their own consulting rooms, prior to the GP preceptor joining the consultation does not increase general practitioner (GP) consultation time. How do GPs meet the needs of both patient and student without extending consultation time? This study sought to quantify and compare GP consultation activities with and without students. Methods This was a prospective cohort study of 523 videotaped consultations. Consultations were analysed in 15‐second intervals using a modified Davis observation code to define GP activity. Estimated marginal means were calculated using mixed model analysis accounting for confounding factors. Results In comparison with consulting alone, GPs precepting a student spent 37 seconds less time examining patients (P = 0.001), 41 seconds less on patient management, and 1 minute, 31 seconds less on clerical and other activities (P < 0.001). This created time for GPs to take a history from both the student and patient (39 seconds longer; P = 0.002) and to teach students (1 minute, 10 seconds; P < 0.001). Discussion General practitioner activity in the consultation changes significantly when precepting a student; GPs spend longer exploring the history in order to unpack the student’s clinical reasoning, verify the patient’s story and resynthesise the information. They spend less time on examination, management and clerical activities and presumably delegate or defer these activities. Conclusions This organising of clinical activities in order to meet the needs of both patient and student is likely to require different processing skills to solo consulting.