Drug-Drug Interactions Involving Dexamethasone in Clinical Practice: Myth or Reality?

Concomitant administration of multiple drugs frequently causes severe pharmacokinetic or pharmacodynamic drug-drug interactions (DDIs) resulting in the possibility of enhanced toxicity and/or treatment failure. The activity of cytochrome P450 (CYP) 3A4 and P-glycoprotein (P-gp), a drug efflux pump sharing localization and substrate affinities with CYP3A4, is a critical determinant of drug clearance, interindividual variability in drug disposition and clinical efficacy, and appears to be involved in the mechanism of numerous clinically relevant DDIs, including those involving dexamethasone. The recent increase in the use of high doses of dexamethasone during the COVID-19 pandemic have emphasized the need for better knowledge of the clinical significance of drug-drug interactions involving dexamethasone in the clinical setting. We therefore aimed to review the already published evidence for various DDIs involving dexamethasone in vitro in cell culture systems and in vivo in animal models and humans.

Infliximab for the Treatment of Inflammatory Labyrinthitis: A Retrospective Cohort Study.

Inflammatory labyrinthitis is defined as a fluctuant vestibulo-cochlear syndrome associated with an impairment of the blood-labyrinthine barrier (BLB) on delayed FLAIR MRI sequences. Systemic and intratympanic corticosteroids are the gold standard treatment but their effect is frequently insufficient. The objective is here to determine whether infliximab could be of value in the treatment of bilateral inflammatory labyrinthitis. A retrospective monocentric study was conducted between January 2013 and December 2021. All patients included in the study were affected with a bilateral vestibulo-cochlear syndrome associated with bilateral blood-labyrinthine barrier impairment. Patients were administered infliximab at the dose of 5 mg/kg every 6 weeks for 6 months. Audiometry, MRI with delayed FLAIR sequences on the labyrinth, and corticosteroid doses still required were assessed both before and after treatment with infliximab was completed. Pure-tone average (PTA) was the primary outcome. The secondary outcomes were the speech recognition threshold (SRT), the Dizziness Handicap Inventory (DHI) score, and the corticosteroid (CS) dose. A total of nine patients including five men and four women were enrolled in the study. Thirteen ears were analyzed. After a 6-month period of treatment, the mean PTA (54 ± 24 db versus 66 ± 22 db; p = 0.027), SRT (54 ± 37 db versus 66 ± 32 db; p = 0.041) and DHI score (27 ± 15 versus 9 ± 2; p = 0.032) significantly improved. After the 6-month treatment period, the mean CS dose decreased from 38 ± 33 to 6 ± 5 mg/day (p = 0.003). We conclude that infliximab substantially improves the vestibulo-cochlear function in patients with bilateral inflammatory labyrinthitis and could be of value in corticosteroid-dependent cases.

18-Fluorodeoxyglucose positron emission tomography/computed tomography for large vessel vasculitis in clinical practice.

Diagnosis, prognostic assessment, and monitoring disease activity in patients with large vessel vasculitis (LVV) can be challenging. Early recognition of LVV and treatment adaptation is essential because vascular complications (aneurysm, dilatations, ischemic complications) or treatment related side effects can occur frequently in these patients. 18-fluorodeoxyglucose positron emission tomography/computed tomography (2-[18F]FDG-PET/CT) is increasingly used to diagnose, follow, and evaluate treatment response in LVV. In this review, we aimed to summarize the current evidence on the value of 2-[18F]FDG-PET/CT for diagnosis, follow, and treatment monitoring in LVV.

Etiologies and Management of Aseptic Meningitis in Patients Admitted to an Internal Medicine Department.

Several studies have focused on the clinical and biological characteristics of meningitis in order to distinguish between bacterial and viral meningitis in the emergency setting. However, little is known about the etiologies and outcomes of aseptic meningitis in patients admitted to Internal Medicine.The aim of the study is to describe the etiologies, characteristics, and outcomes of aseptic meningitis with or without encephalitis in adults admitted to an Internal Medicine Department.A retrospective cohort study was conducted in the Internal Medicine Department of the Lariboisière Hospital in Paris, France, from January 2009 to December 2011. Clinical and biological characteristics of aseptic meningitis were recorded. These included cerebrospinal fluid analysis, results of polymerase chain reaction testing, final diagnoses, and therapeutic management.The cohort included 180 patients fulfilling the criteria for aseptic meningitis with (n = 56) or without (n = 124) encephalitis. A definitive etiological diagnosis was established in 83 of the 180 cases. Of the cases with a definitive diagnosis, 73 were due to infectious agents, mainly enteroviruses, Herpes Simplex Virus 2, and Varicella Zoster Virus (43.4%, 16.8%, and 14.5% respectively). Inflammatory diseases were diagnosed in 7 cases. Among the 97 cases without definitive diagnoses, 26 (26.8%) remained free of treatment throughout their management whereas antiviral or antibiotic therapy was initiated in the emergency department for the remaining 71 patients. The treatment was discontinued in only 10 patients deemed to have viral meningitis upon admission to Internal Medicine.The prevalence of inflammatory diseases among patients admitted to internal medicine for aseptic meningitis is not rare (4% of overall aseptic meningitis). The PCR upon admission to the emergency department is obviously of major importance for the prompt optimization of therapy and management. However, meningitis due to viral agents or inflammatory diseases could also be distinguished according to several clinical and biological characteristics highlighted in this retrospective study. As recommendations are now available concerning the prescriptions of antiviral agents in viral meningitis, better therapeutic management is expected in the future.

Effects of chronic low-dose exposure to ionizing radiation on physician microvascular structure revealed by nail fold capillaroscopy.

The aim of this study was to assess the long-term asymptomatic effects of low-dose radiation on microvascular structure among interventional physicians, whose hands are exposed to ionizing radiation during daily practice. The study, approved by the national ethics committee, included 186 radiation-exposed (surgeons, cardiologists, radiologists) and 35 unexposed physicians, all of whom had provided written consent. The subjects completed a questionnaire describing their current and past daily practice, from which tentative estimates of current and cumulative radiation exposure estimates were computed. Subject dermal microcirculation state was assessed by capillaroscopy of the nail fold of eight fingers (thumbs excluded) based on photographs. Two quantitative scores characterizing extravasation and morphological abnormalities based on seven semiquantitative indices were obtained from post hoc coding of the photographs by five capillaroscopists. These evaluations were randomized and blind to the exposure. The effect of the radiation exposure on both abnormality scores was modelled using multilevel proportional odds regression adjusted for potential confounders. The proportion of physicians for which the most frequent act is close to the radiation source was highest among surgeons, but with fewer weekly acts. The median duration of exposure was highest among radiologists and cardiologists. No exposure effect could be detected on the extravasation score. The morphological anomaly score increased significantly with duration of exposure and estimated cumulative exposure among surgeons and interventional radiologists, unlike cardiologists among whom no effect could be detected. It is concluded that the shown effects of chronic low-dose exposure to ionizing radiation on physician microvascular structure reveal the importance of increased exposure monitoring and prevention.

Optimizing the use of intravenous therapy in internal medicine.

BACKGROUND: We aimed to evaluate the impact of physicians' educational programs in the reduction of inappropriate intravenous lines in internal medicine. METHODS: Fifty-six French internal medicine units were enrolled in a nationwide, prospective, blinded, randomized controlled trial. Forms describing the patients with an intravenous line and internal medicine department characteristics were filled out on 2 separate days in January and April 2007. Following the first visit, all units were randomly assigned to either a specific education program on the appropriate indications of an intravenous line, during February and March 2007, or no training (control group). The Investigators' Committee then blindly evaluated the clinical relevance of the intravenous line according to pre-established criteria. The primary outcome was the percentage of inappropriate intravenous lines. RESULTS: During January 2007, intravenous lines were used in 475 (24.9%) of the 1910 hospitalized patients. Of these, 80 (16.8%) were considered inappropriate. In April 2007, 416 (22.8%) of the 1823 hospitalized patients received an intravenous line, which was considered in 10.2% (21/205) of patients managed by trained physicians, versus 16.6% (35/211) of patients in the control group (relative difference 39%; 95% confidence interval, -0.6-13.3; P = .05). Reduced intravenous administration of fluids, antibiotics, and analgesics accounted for the observed decrease. CONCLUSION: The use of a simple education program reduced the rate of inappropriate intravenous lines by almost 40% in an internal medicine setting (NCT01633307).

Efficacy of early clinical evaluation in predicting direct home discharge of elderly patients after hospitalization in internal medicine.

OBJECTIVES: Early evaluation of direct home discharge (DHD) after hospitalization of elderly patients is important to organize discharge planning quickly. Many scores, scales, and indices have been developed to improve discharge planning. Is clinical judgment better than functional status, comorbidity, or cognitive function scales in predicting DHD of elderly patients after hospitalization? METHODS: Ninety-seven patients, aged 75 years or older, admitted from the emergency department to an internal medicine department in a French teaching hospital between December 1, 2006 and May 1, 2007, were enrolled prospectively in the study. Demographic, clinical, and laboratory characteristics and functional status, comorbidity, and cognitive function scales were determined. The primary outcome was the percentage of correct discharge prediction made by junior and senior doctors within the first 48 hours upon admission. Univariate analysis and logistic regression were assessed to determine predictive variables of patients' discharge. RESULTS: Junior and senior doctors obtained correct prediction in 74.2% and 73.2% of cases, respectively (P > 0.99). Activities of daily living, instrumental activities of daily living, and duration of hospitalization were predictive of DHD (95% confidence interval [CI] -6.1 to 0.2, P = 0.037; 95% CI -2.1 to 9.9, P = 0.003; 95% CI -3 to 9.1, P = 0.0001, respectively) in the univariate analysis. Instrumental activities of daily living was an independent predictive variable of patients' discharge in a logistic regression. No difference between clinical evaluation and the use of an independent predictive variable regarding the prediction of DHD was found. CONCLUSIONS: Early clinical evaluation is as effective as the use of functional status scales to predict DHD of hospitalized elderly patients.

In vivo discrimination of hip fracture with quantitative computed tomography: results from the prospective European Femur Fracture Study (EFFECT).

In assessing osteoporotic fractures of the proximal femur, the main objective of this in vivo case-control study was to evaluate the performance of quantitative computed tomography (QCT) and a dedicated 3D image analysis tool [Medical Image Analysis Framework--Femur option (MIAF-Femur)] in differentiating hip fracture and non-hip fracture subjects. One-hundred and seven women were recruited in the study, 47 women (mean age 81.6 years) with low-energy hip fractures and 60 female non-hip fracture control subjects (mean age 73.4 years). Bone mineral density (BMD) and geometric variables of cortical and trabecular bone in the femoral head and neck, trochanteric, and intertrochanteric regions and proximal shaft were assessed using QCT and MIAF-Femur. Areal BMD (aBMD) was assessed using dual-energy X-ray absorptiometry (DXA) in 96 (37 hip fracture and 59 non-hip fracture subjects) of the 107 patients. Logistic regressions were computed to extract the best discriminates of hip fracture, and area under the receiver characteristic operating curve (AUC) was calculated. Three logistic models that discriminated the occurrence of hip fracture with QCT variables were obtained (AUC = 0.84). All three models combined one densitometric variable--a trabecular BMD (measured in the femoral head or in the trochanteric region)--and one geometric variable--a cortical thickness value (measured in the femoral neck or proximal shaft). The best discriminant using DXA variables was obtained with total femur aBMD (AUC = 0.80, p = .003). Results highlight a synergistic contribution of trabecular and cortical components in hip fracture risk and the utility of assessing QCT BMD of the femoral head for improved understanding and possible insights into prevention of hip fractures.

Influence of patient education on exercise compliance in rheumatoid arthritis: a prospective 12-month randomized controlled trial.

OBJECTIVE: To determine the effect of education on the exercise habits of patients with rheumatoid arthritis (RA) after 6 and 12 months. METHODS: We studied 208 outpatients recruited between June 2001 and December 2002. This was a prospective controlled randomized trial. The active group received a multidisciplinary education program, including training in home-based exercises and guidelines for leisure physical activity (PA). The control group received a booklet added to usual medical care. Compliance with home-based exercises was defined as a practice rate >or= 30% of the prescribed training. Compliance with leisure PA was defined as >or= 20% increase in Baecke questionnaire score. Additional assessments involved possible predictors of compliance and changes with regard to the compliance. RESULTS: At 6-month followup, home-based exercise and leisure PA compliance were significantly higher [13.5% vs 1%, respectively (p = 0.001); and 28.2% vs 13.8% (p = 0.02)], but were not at 12 months. Predictors of leisure PA compliance at 6 months included participating in the active group (odds ratio 2.74, 95% CI 1.17 to 6.38) and previous low leisure PA (OR 6.01, 95% CI 2.47 to 14.61), with decreased fatigue (FACIT-F mean -2.94 +/- 8.04 vs -0.1 +/- 7.25 for noncompliant subjects; p = 0.04) and improved psychological status (Arthritis Impact Measurement Scale mean -1.25 +/- 3.12 vs 0.11 +/- 3.39; p = 0.03). CONCLUSION: Education of patients with RA may increase compliance especially with leisure PA, particularly when it is poor at baseline, but these effects are limited and short-term.

Effect of a collective educational program for patients with rheumatoid arthritis: a prospective 12-month randomized controlled trial.

OBJECTIVE: To evaluate the effect on health and functional status of an 8-week group-education program for rheumatoid arthritis (RA) in addition to usual medical care. METHODS: All consecutive inpatients and outpatients with RA (ACR criteria) were asked to participate in this randomized, prospective, controlled trial. The educational intervention consisted of 8 weekly ambulatory sessions, each lasting 6 hours. Followup was undertaken after 1 year. The primary criterion for judging effectiveness was the Health Assessment Questionnaire (HAQ) score; secondary criteria consisted of coping, medical knowledge, patient global satisfaction, and quality of life scores before the intervention and after 1 year. RESULTS: We asked 1242 inpatients and outpatients to participate in the study: 208 (16.75%) agreed (104 in each group). At baseline, there was no statistically significant difference between the 2 groups. After 1 year, no statistically significant difference was observed between the 2 groups in change in HAQ score: -0.04 +/- 0.46 (education group) vs -0.06 +/- 0.47 (control group) (p = 0.79). Statistically significant differences were found in 3 domains: patient coping (-1.22 +/- 5.55 vs -0.22 +/- 3.81; p = 0.03), knowledge (3.42 +/- 4.73 vs 0.73 +/- 3.78; p < 0.0001), and satisfaction (10.07 +/- 11.70 vs 5.72 +/- 13.77; p = 0.02), all of which were better for the group attending the education sessions. CONCLUSION: Despite improvements in patient coping, knowledge, and satisfaction, the education program was not found to be effective at 1 year. There may have been methodological problems relating to the sensitivity of questionnaires and patient selection, and tailored educational interventions should be considered.

[Follow-up brain imaging after strokes in internal medicine: frequently requested but rarely used for diagnosis or treatment]. / Imagerie cérébrale supplémentaire après un accident vasculaire cérébral en médecine interne: fréquemment demandée mais une rare implication diagnostique ou thérapeutique.

OBJECTIVE: To assess the interest of a second computed tomography (CT) scan of the brain during hospitalization of stroke patients in an internal medicine department and study the characteristics of these patients. METHOD: This retrospective study included 110 patients diagnosed with stroke between January 1, 2002, and August 31, 2004 in an internal medicine department. RESULT: All patients had a brain CT scan soon after admission - within three hours, on average, of arrival at the hospital; however, the mean delay between the onset of symptoms and hospital arrival was 40 hours. Mean hospital stay was 19 days. Eighty patients (73%) had at least one more scan. Indications for these scans were: no acute cerebral ischemia on the initial image (34%), routine follow-up or reason not specified (34%), worsening of neurologic status (15%), before oral anticoagulation (5%), to search a tumor (5%), to look for a cause (4%), and clinic-radiologic discordance (3%). Only 29% of the indications had any diagnostic or therapeutic reason. Among these 80 patients, the repeat brain scan resulted in a change in the initial diagnosis for 4 patients (5%) and in a change of therapy for 11 (14%). CONCLUSION: In our study, repeat CT imaging was frequently ordered in ischemic stroke, despite the not uncommon absence of any diagnostic or therapeutic reasons. To optimize the use of medical resources and avoid unnecessary imaging, it would be useful to identify subgroups of patients for whom repeat imaging might be of interest.

[Use and misuse of intravenous drug administration in a department of internal medicine]. / Usage et mésusage de la voie intraveineuse pour l'administration de médicaments en médecine interne.

AIM: Numerous intravenously-administered medications are also available in equally effective oral forms. To assess the number of avoidable intravenous infusions, we retrospectively analyzed consecutive infusions prescribed in a department of internal medicine. METHODS: Between November and December 2004, we analyzed all patients who received at least one intravenous drug during hospitalization. Intravenous administration was considered unavoidable when prescribed for no more than 2 days in a patient unstable at admission, when oral administration or feeding was impossible, or when the drug was not available in oral form. RESULTS: During the study period 133 patients were admitted to the department. In all, 65 infusions were prescribed, 30% of which lasted more than 2 days for no medical reason. Four intravenous antibiotics were prescribed in patients when their antibiotic susceptibility tests indicated that another oral antibiotic could easily be given. Infusions for 16 other patients continued longer than 48 hours, although the oral route was not contraindicated in these patients and the medication was available in oral form. CONCLUSION: Systematic analysis of the daily prescriptions may be helpful in preventing or shortening use of intravenous medications and thereby decreasing iatrogenic infections and injuries, length of hospitalization, and costs.

Comparative effect of aspirin and clopidogrel on arterial function in CHF.

BACKGROUND: By inhibiting prostaglandins, aspirin may be deleterious in congestive heart failure (CHF) and/or partially counteract the efficacy of angiotensin-converting enzyme inhibitors (ACEI). Conversely, clopidogrel has no effect on prostaglandin metabolism. The aim of this study was to prospectively investigate the effect of aspirin and clopidogrel on arterial functional properties in CHF patients treated with ACEI. METHODS: Forty-five patients with stable NYHA class II-IV CHF (64.0+/-15.5 years), ejection fraction <40%, were included in this prospective double-blind study and randomized to receive aspirin 325 mg/day or clopidogrel 75 mg/day for 14 days. Reflected wave assessed by radial applanation tonometry and pulse wave velocity (PWV) were measured at day 0 and day 14. RESULTS: Aspirin resulted in an increase in the augmentation index of the reflected wave (Delta=+3.5+/-5.2%, p=0.005) and the height above the shoulder of the reflected wave (Delta=+1.7+/-3.1 mm Hg, p=0.023), without statistically variation in PWV. Conversely, clopidogrel had no effect on the same parameters (p=0.512, p=0.677 and 0.801, respectively). Overall, variations in the augmentation index of reflected wave significantly differed when compared aspirin with clopidogrel (p=0.0261). CONCLUSION: This study demonstrates the existence of a negative effect of aspirin 325 mg/day when compared to clopidogrel 75 mg/day on arterial functional properties in CHF patients treated with ACEI.

Disseminated extrapulmonary tuberculosis revealed by humeral osteomyelitis with chronic unremarkable pain.

Disseminated extrapulmonary tuberculosis is uncommon, particularly among immunocompentent individuals. We report the case of a 38-year-old woman from the Ivory Coast who had osteomyelitis in the right humerus, a cold abscess in the pectoralis major muscle, T11 spondylitis, deep lymphadenopathies, peritoneal nodules, and hepatitis. She had no evidence of immune deficiency, and her only risk factor for tuberculosis was her origin from an endemic area. The outcome was favorable after treatment with antitubercular drugs. This case illustrates the recent changes in the epidemiology of tuberculosis in France, where the incidence among immigrants is rising. It also serves as a reminder that tuberculosis can run a chronic and extremely insidious course. At diagnosis, our patient had a 2-year history of chronic pain in her right shoulder and back, suggestive of a minor mechanical disorder.

Association of Takayasu's arteritis and Crohn's disease. Results of a study on 44 Takayasu patients and review of the literature.

Takayasu's arteritis and Crohn's colitis are exceptionally associated and characteristics of patients affected with both diseases have not been fully described. In a group of 44 consecutive Takayasu patients, 4 also had Crohn's disease. This 9% prevalence (95% confidence interval=2.5-21.7%) of Crohn's disease in the group is significantly greater than the highest reported prevalence of the disease in the general population. In these 4 patients, fulfilling 5 or more ACR criteria for Takayasu's disease, Crohn's disease was confirmed with colonoscopic examination and biopsies. Takayasu-Crohn patients were younger at diagnosis and tended to have systemic symptoms more frequently. Other clinical, radiological and biological characteristics were not different between the 2 groups. In the literature, 16 cases of this unusual association have been reported. The diagnosis of Takayasu's disease was simultaneous or posterior to Crohn's disease in 87%. Data on vascular lesions was available in 6 out of 16 patients and in the 4 patients of the present study: the distribution of vascular lesions in Takayasu-Crohn patients did not appear to be different from Takayasu patients. Our results and previous reports suggest that this association of rare diseases is not fortuitous. With respect to the indolent course of Takayasu's arteritis, early diagnosis of vascular lesions in Crohn patients is encouraged.