Multilayers coating are needed for large optical components performances, but the thickness non-uniformities over the useful aperture can generate spatial and chromatic variations of the reflectance, ...the transmittance and the wavefront errors. Although these dependences can be measured, they are difficult to anticipate if the underlying thickness variations are unknown. We present a model to retrieve these variations from wavefront error measurements that enables the computation of any optical properties over the useful aperture at any wavelength, angle of incidence or polarization.
Epidermal necrolysis (EN)—either Stevens–Johnson syndrome (SJS) or toxic EN (TEN)—is a severe drug reaction. We constructed and evaluated a specific algorithm, algorithm of drug causality for EN ...(ALDEN), in order to improve the individual assessment of drug causality in EN. ALDEN causality scores were compared with those from the French pharmacovigilance method in 100 cases and the case–control results of the EuroSCAR study. Scores attributed by ALDEN segregated widely. ALDEN pointed to a “probable” or “very probable” causality in 69/100 cases as compared to 23/100 with the French method (P < 0.001). It scored “very unlikely” causality for 64% of medications vs. none with the French method. Results of ALDEN scores were strongly correlated with those of the EuroSCAR case–control analysis for drugs associated with EN (r = 0.90, P < 0.0001), with probable causality being reported in 218/329 exposures. ALDEN excluded causality in 321 drugs that the case–control analysis had described as “probably not associated” and in 22/233 drugs that had been described as inconclusive exposures. Being more sensitive than a general method, ALDEN, which correlates well with case–control analysis results, can be considered a reference tool in SJS/TEN.
Clinical Pharmacology & Therapeutics (2010) 88 1, 60–68. doi: 10.1038/clpt.2009.252
Summary
Background
The proportion of severe cutaneous adverse reactions (SCARs) that could be avoided if medication use was consistent with good medical practice is unknown.
Objectives
To estimate ...the proportion of SCARs related to inappropriate medication use.
Methods
We carried out a retrospective study of all validated SCARs collected in a French registry between 2003 and 2016. For each case, all plausible drugs suspected of inducing SCARs (i.e. not just the drug regarded as ‘the most probable’) were considered with regard to (i) prescription for an inappropriate indication, (ii) unintentional rechallenge despite a previous allergy to the drug or (iii) self‐medication with prescription medicines.
Results
In total, 602 cases were included in the analyses. Antibiotics, anticonvulsants and allopurinol were the drugs most frequently involved, accounting for more than 50% of all cases. All suspected medications were considered to have been appropriately used for 417 of the 602 individuals included in the study population 69·3%, 95% confidence interval (CI) 65·6–73·0 and inappropriately used for 144 individuals (23·9%, 95% CI 20·5–27·3). These inappropriate uses were due mainly to prescriptions for an inappropriate indication (65·8%, 95% CI 58·4–73·2) or unintentional rechallenge (20·9%, 95% CI 14·6–27·2). Allopurinol and co‐trimoxazole were the drugs most frequently involved in inappropriate indications. Antibiotics were the largest group involved in unintentional rechallenge. Nonsteroidal anti‐inflammatory drugs, available on prescription, were most frequently involved in inappropriate self‐medication.
Conclusions
Our results underline the need for respecting the appropriate indication for drugs in order to reduce the incidence of SCARs. Reducing unintentional rechallenge also seems to be a necessary preventive measure.
What's already known about this topic?
Severe cutaneous adverse reactions (SCARs) carry high morbidity and mortality.
Evidence is limited regarding the proportion of SCARs that could be avoided if medication prescriptions were consistent with good medical practice.
What does this study add?
This cohort study found that one‐quarter of SCARs could be avoided if indications for medication use were consistent with current good medical practice.
Adherence to guidelines regarding the use of allopurinol and co‐trimoxazole is a decisive factor in preventing SCARs.
Linked Comment: Walsh and Creamer. Br J Dermatol 2018; 179:242–243.
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Summary
Background
Corticosteroids (CS) with or without adjuvant immunosuppressant agents are standard treatment for pemphigus vulgaris (PV). The efficacy of adjuvant therapies in minimizing ...steroid‐related adverse events (AEs) is unproven.
Objectives
To utilize data collected in a French investigator‐initiated, phase III, open‐label, randomized controlled trial to demonstrate the efficacy and safety of rituximab and seek approval for its use in PV.
Methods
This was an independently conducted post hoc analysis of the moderate‐to‐severe PV subset enrolled in the Ritux 3 study. Patients were randomized to rituximab plus 0·5 or 1·0 mg kg−1 per day prednisone tapered over 3 or 6 months, or 1·0 or 1·5 mg kg−1 per day prednisone alone tapered over 12 or 18 months, respectively (according to disease severity). The primary end point was complete remission at month 24 without CS (CRoff) for ≥ 2 months, and 24‐month efficacy and safety results were also reported.
Results
At month 24, 34 of 38 patients (90%) on rituximab plus prednisone achieved CRoff ≥ 2 months vs. 10 of 36 patients (28%) on prednisone alone. Median total cumulative prednisone dose was 5800 mg in the rituximab plus prednisone arm vs. 20 520 mg for prednisone alone. Eight of 36 patients (22%) who received prednisone alone withdrew from treatment owing to AEs; one rituximab‐plus‐prednisone patient withdrew due to pregnancy. Overall, 24 of 36 patients (67%) on prednisone alone experienced a grade 3/4 CS‐related AE vs. 13 of 38 patients (34%) on rituximab plus prednisone.
Conclusions
In patients with moderate‐to‐severe PV, rituximab plus short‐term prednisone was more effective than prednisone alone. Patients treated with rituximab had less CS exposure and were less likely to experience severe or life‐threatening CS‐related AEs.
What's already known about this topic?
Pemphigus vulgaris (PV) is the most common type of pemphigus.
Corticosteroids, a standard first‐line treatment for PV, have significant side‐effects.
Although their effects are unproven, adjuvant corticosteroid‐sparing agents are routinely used to minimize steroid exposure and corticosteroid‐related side‐effects.
There is evidence that the anti‐CD20 antibody rituximab is effective in the treatment of patients with severe recalcitrant pemphigus and in patients with newly diagnosed pemphigus.
What does this study add?
This study provides a more detailed analysis of patients with PV enrolled in an investigator‐initiated trial.
Rituximab plus prednisone had a steroid‐sparing effect and more patients achieved complete remission off prednisone.
Fewer patients experienced grade 3 or grade 4 steroid‐related adverse events than those on prednisone alone.
This collaboration between academia and industry, utilizing independent post hoc analyses, led to regulatory authority approvals of rituximab in moderate‐to‐severe PV.
Linked Comment: Scorer et al. Br J Dermatol 2020; 182:1078–1079.
The treatment of stage I Merkel cell carcinoma (MCC) usually includes wide local excision (WLE) combined with irradiation of the tumor bed (ITB). No randomized study has ever been conducted in MCC. ...The purpose of this study was to assess the efficacy and safety of prophylactic adjuvant radiotherapy on the regional nodes.
In this randomized open controlled study, patients for a stage I MCC treated by WLE and ITB were randomly assigned to regional adjuvant radiotherapy versus observation. Overall survival (OS) and probability of regional recurrence (PRR) were primary end points. Progression-free survival (PFS) and tolerance of irradiation were secondary end points.
Eighty-three patients were included before premature interruption of the trial, due to a drop in the recruitment mainly due to the introduction of the sentinel node dissection in the management of MCC. No significant improvement in OS (P = 0.989) or PFS (P = 0.4) could be demonstrated after regional irradiation, which, however, significantly reduced the PRR (P = 0.007) with 16.7% regional recurrence rate in the observation arm versus 0% in the treatment arm. The treatment was well tolerated.
The adjuvant regional irradiation significantly decreased the PRR in MCC, but benefit in survival could not be demonstrated.
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