Medroxyprogesterone acetate (MPA) is widely used in the hormonal therapy of breast cancer. So far, oral formulations of MPA commercially available present a very low bioavailability, with a less than ...10% extent of oral absorption. A new oral preparation of MPA has been recently developed. Based on a pilot study, an open, randomized, crossover trial has been performed on 22 breast and endometrial cancer patients to evaluate the relative bioavailability of this new oral formulation (200-mg sachet, twice daily) as compared with a standard formulation (Farlutal, 500-mg tablet, twice daily). The bioavailability evaluation was mainly based on the area under the curve measured between two administrations at steady state, after 15 days of continuous therapy. Wide interpatient variability of MPA plasma levels after oral MPA administration was confirmed. The MPA plasma levels were higher in patients treated with the new formulation than in patients treated with Farlutal. The relative bioavailability of the new preparation was 3.5 times higher than that of the standard. This new formulation represents a great improvement in the extent of oral absorption of MPA and could lead to better management of hormone-responsive tumors by hormonal therapy.
Selective digestive tract decontamination (SDD) and selective oropharyngeal decontamination (SOD) eradicate gram-negative bacteria (GNB) from the intestinal and respiratory tract in intensive care ...unit (ICU) patients, but their effect on antibiotic resistance remains controversial.
We quantified the effects of SDD and SOD on bacterial ecology in 13 ICUs that participated in a study, in which SDD, SOD, or standard care was used during consecutive periods of 6 months (de Smet AM, Kluytmans JA, Cooper BS, Mascini EM, Benus RF, van der Werf TS, van der Hoeven JG, Pickkers P, Bogaers-Hofman D, van der Meer NJ, et al. N Engl J Med 2009;360:20-31).
Point prevalence surveys of rectal and respiratory samples were performed once monthly in all ICU patients (receiving or not receiving SOD/SDD). Effects of SDD on rectal, and of SDD/SOD on respiratory tract, carriage of GNB were determined by comparing results from consecutive point prevalence surveys during intervention (6 mo for SDD and 12 mo for SDD/SOD) with consecutive point prevalence data in the pre- and postintervention periods.
During SDD, average proportions of patients with intestinal colonization with GNB resistant to either ceftazidime, tobramycin, or ciprofloxacin were 5, 7, and 7%, and increased to 15, 13, and 13% postintervention (P < 0.05). During SDD/SOD resistance levels in the respiratory tract were not more than 6% for all three antibiotics but increased gradually (for ceftazidime; P < 0.05 for trend) during intervention and to levels of 10% or more for all three antibiotics postintervention (P < 0.05).
SOD and SDD have marked effects on the bacterial ecology in an ICU, with rising ceftazidime resistance prevalence rates in the respiratory tract during intervention and a considerable rebound effect of ceftazidime resistance in the intestinal tract after discontinuation of SDD.
The study described herein was conducted to analyze the relationship between tumor exposure to 5-FU and clinical response. Six patients were placed on continuous 5-day intrahepatic 5-FU chemotherapy ...for colorectal cancer metastasized to the liver. The starting dose was 600-800 mg/m2 per day; cycles were repeated at 4-week intervals. The 5-FU dose was increased by 250 mg/day at each cycle. All six patients received 3 or more cycles, for a total of 37 cycles. Response was evaluated after each cycle by ultrasonography or computed tomography (CT). Pharmacokinetic data revealed a high individual cycle-to-cycle variability for all six patients in the 5-FU area under the curve (AUC day 1 to day 5) corrected for the dose. These variations in drug biodisposition, reflecting hepatic 5-FU uptake, were significantly related to measurable modifications in the tumor mass in 71% of cycles. The correlation between the reduction in local drug exposure and tumor regrowth was better than that between the increase in local drug exposure and tumor reduction. These findings constitute an original illustration in humans of the experimental concept of the drug exposure/tumor response relationship for 5-FU.
We compared SimoaTM and EllaTM immunoassays to assess serum neurofilament‐light chain levels in 203 multiple sclerosis patients from the OFSEP HD study. There was a strong correlation (ρ = 0.86, ...p < 0.0001) between both platforms. The EllaTM instrument overestimated values by 17%, but as the data were linear (p = 0.57), it was possible to apply a correction factor to EllaTM results. As for SimoaTM, serum neurofilament‐light chain levels measured by EllaTM were correlated with age and EDSS and were significantly higher in active multiple sclerosis, suggesting that these assays are equivalent and can be used in routine clinical practice.
We compared Simoa
and Ella
immunoassays to assess serum neurofilament-light chain levels in 203 multiple sclerosis patients from the OFSEP HD study. There was a strong correlation (ρ = 0.86, ...p < 0.0001) between both platforms. The Ella
instrument overestimated values by 17%, but as the data were linear (p = 0.57), it was possible to apply a correction factor to Ella
results. As for Simoa
, serum neurofilament-light chain levels measured by Ella
were correlated with age and EDSS and were significantly higher in active multiple sclerosis, suggesting that these assays are equivalent and can be used in routine clinical practice.
We compared Simoa and Ella immunoassays to assess serum neurofilament-light chain levels in 203 multiple sclerosis patients from the OFSEP HD study. There was a strong correlation (ρ = 0.86, ...p < 0.0001) between both platforms. The Ella instrument overestimated values by 17%, but as the data were linear (p = 0.57), it was possible to apply a correction factor to Ella results. As for Simoa , serum neurofilament-light chain levels measured by Ella were correlated with age and EDSS and were significantly higher in active multiple sclerosis, suggesting that these assays are equivalent and can be used in routine clinical practice.
Objectives
The aim of this study was to investigate whether the quadrivalent human papillomavirus (HPV) vaccine Gardasil is associated with a change in the risk of autoimmune disorders (ADs) in young ...female subjects.
Design
Systematic case–control study of incident ADs associated with quadrivalent HPV vaccination in young women across France.
Participants and setting
A total of 113 specialised centres recruited (from December 2007 to April 2011) females aged 14–26 years with incident cases of six types of ADs: idiopathic thrombocytopenic purpura (ITP), central demyelination/multiple sclerosis (MS), Guillain–Barré syndrome, connective tissue disorders (systemic lupus erythematosus, rheumatoid arthritis/juvenile arthritis), type 1 diabetes mellitus and autoimmune thyroiditis. Control subjects matched to cases were recruited from general practice.
Analysis
Multivariate conditional logistic regression analysis; factors included age, geographical origin, smoking, alcohol consumption, use of oral contraceptive(s) or vaccine(s) other than Gardasil received within 24 months before the index date and personal/family history of ADs.
Results
Overall, 211 definite cases of ADs were matched to 875 controls. The adjusted odds ratio (OR) for any quadrivalent HPV vaccine use was 0.9 95% confidence interval (CI) 0.5–1.5. The individual ORs were 1.0 (95% CI 0.4–2.6) for ITP, 0.3 (95% CI 0.1–0.9) for MS, 0.8 (95% CI 0.3–2.4) for connective disorders and 1.2 (95% CI 0.4–3.6) for type 1 diabetes. No exposure to HPV vaccine was observed in cases with either Guillain–Barré syndrome or thyroiditis.
Conclusions
No evidence of an increase in the risk of the studied ADs was observable following vaccination with Gardasil within the time periods studied. There was insufficient statistical power to allow conclusions to be drawn regarding individual ADs.
Summary Background Previously, we assessed selective digestive tract decontamination (SDD) and selective oropharyngeal decontamination (SOD) on survival and prevention of bacteraemia in patients in ...intensive-care units. In this analysis, we aimed to assess effectiveness of these interventions for prevention of respiratory tract colonisation and bacteraemia with highly resistant microorganisms acquired in intensive-care units. Methods We did an open-label, clustered group-randomised, crossover study in 13 intensive-care units in the Netherlands between May, 2004, and July, 2006. Participants admitted to intensive-care units with an expected duration of mechanical ventilation of more than 48 h or an expected stay of more than 72 h received SOD (topical tobramycin, colistin, and amphotericin B in the oropharynx), SDD (SOD antibiotics in the oropharynx and stomach plus 4 days' intravenous cefotaxime), or standard care. The computer-randomised order of study regimens was applied by an independent clinical pharmacist who was masked to intensive-care-unit identity. We calculated crude odds ratios (95% CI) for rates of bacteraemia or respiratory tract colonisation with highly resistant microorganisms in patients who stayed in intensive-care units for more than 3 days (ie, acquired infection). This trial is registered at http://isrctn.org , number ISRCTN35176830. Findings Data were available for 5927 (>99%) of 5939 patients, of whom 5463 (92%) were in intensive-care units for more than 3 days. 239 (13%) of 1837 patients in standard care acquired bacteraemia after 3 days, compared with 158 (9%) of 1758 in SOD (odds ratio 0·66, 95% CI 0·53–0·82), and 124 (7%) of 1868 in SDD (0·48, 0·38–0·60). Eight patients acquired bacteraemia with highly resistant microorganisms during SDD, compared with 18 patients (with 19 episodes) during standard care (0·41, 0·18–0·94; rate reduction RR 59%, absolute risk reduction ARR 0·6%) and 20 during SOD (0·37, 0·16–0·85; RR 63%, ARR 0·7%). Of the patients staying in intensive-care units for more than 3 days, we obtained endotracheal aspirate cultures for 881 (49%) patients receiving standard care, 886 (50%) receiving SOD, and 828 (44%) receiving SDD. 128 (15%) patients acquired respiratory tract colonisation with highly resistant microorganisms during standard care, compared with 74 (8%) during SDD (0·58, 0·43–0·78; RR 38%, ARR 5·5%) and 88 (10%) during SOD (0·65, 0·49–0·87; RR 32%, ARR 4·6%). Acquired respiratory tract colonisation with Gram-negative bacteria or cefotaxime-resistant and colistin-resistant pathogens was lowest during SDD. Interpretation Widespread use of SDD and SOD in intensive-care units with low levels of antibiotic resistance is justified. Funding None.
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