Objective To improve patient safety and clinical outcomes by reducing the risk of prescribing errors, we tested the accuracy of a hybrid clinical decision support system in prioritizing prescription checks. Materials and Methods Data from electronic health records were collated over a period of 18 months. Inferred scores at a patient level (probability of a patient’s set of active orders to require a pharmacist review) were calculated using a hybrid approach (machine learning and a rule-based expert system). A clinical pharmacist analyzed randomly selected prescription orders over a 2-week period to corroborate our findings. Predicted scores were compared with the pharmacist’s review using the area under the receiving-operating characteristic curve and area under the precision-recall curve. These metrics were compared with existing tools: computerized alerts generated by a clinical decision support (CDS) system and a literature-based multicriteria query prioritization technique. Data from 10 716 individual patients (133 179 prescription orders) were used to train the algorithm on the basis of 25 features in a development dataset. Results While the pharmacist analyzed 412 individual patients (3364 prescription orders) in an independent validation dataset, the areas under the receiving-operating characteristic and precision-recall curves of our digital system were 0.81 and 0.75, respectively, thus demonstrating greater accuracy than the CDS system (0.65 and 0.56, respectively) and multicriteria query techniques (0.68 and 0.56, respectively). Discussion Our innovative digital tool was notably more accurate than existing techniques (CDS system and multicriteria query) at intercepting potential prescription errors. Conclusions By primarily targeting high-risk patients, this novel hybrid decision support system improved the accuracy and reliability of prescription checks in a hospital setting.

Study Objectives: Previous case reports of intravenous immunoglobulins (IVIg) in pediatric narcolepsy have shown contradictory results. Methods: This was a nonrandomized, open-label, controlled, longitudinal observational study of IVIg use in pediatric narcolepsy with retrospective data collection from medical files obtained from a single pediatric national reference center for the treatment of narcolepsy in France. Of 56 consecutively referred patients with narcolepsy, 24 received IVIg (3 infusions administered at 1-mo intervals) in addition to standard care (psychostimulants and/or anticataplectic agents), and 32 continued on standard care alone (controls). Results: For two patients in each group, medical files were unavailable. Of the 22 IVIg patients, all had cerebrospinal fluid (CSF) hypocretin ≤ 110 pg/mL and were HLA-DQB1*06:02 positive. Of the 30 control patients, 29 were HLA-DQB1*06:02 positive and of those with available CSF measurements, all 12 had hypocretin ≤ 110 pg/mL. Compared with control patients, IVIg patients had shorter disease duration, shorter latency to sleep onset, and more had received H1N1 vaccination. Mean (standard deviation) follow-up length was 2.4 (1.1) y in the IVIg group and 3.9 (1.7) y in controls. In multivariate-adjusted linear mixed-effects analyses of change from baseline in Ullanlinna Narcolepsy Scale (UNS) scores, high baseline UNS, but not IVIg treatment, was associated with a reduction in narcolepsy symptoms. On time-to-event analysis, among patients with high baseline UNS scores, control patients achieved a UNS score < 14 (indicating remission) less rapidly than IVIg patients (adjusted hazard ratio 0.18; 95% confidence interval: 95% confidence interval: 0.03, 0.95; p = 0.043). Shorter or longer disease duration did not influence treatment response in any analysis. Conclusions: Overall, narcolepsy symptoms were not significantly reduced by IVIg. However, in patients with high baseline symptoms, a subset of IVIgtreated patients achieved remission more rapidly than control patients. I NTRO DUCTI O NNarcolepsy is a debilitating and currently an incurable neurological condition with a characteristic constellation of symptoms, including excessive daytime sleepiness (EDS), cataplexy, sleep paralysis, hypnagogic hallucinations, and disturbed nocturnal sleep.Until recently, and at the time patients in this study were treated, the disorder was categorized into narcolepsy with cataplexy and narcolepsy without cataplexy according to the revised second edition of the International Classification of Sleep Disorders (ICSD).1 ICSD-2-revised has now been replaced by ICSD-3, which classifies narcolepsy into type 1 and type 2 narcolepsy. 2The majority of patients with type 1 narcolepsy have hypocretin deficiency (cerebrospinal fluid [CSF] hypocretin-1 level ≤ 110 pg/ mL), which is considered to result from an autoimmune-mediated loss of hypocretin-secreting neurons in those who are genetically predisposed (most commonly those with human leucocyte antigen [HLA] DQB1*06:02 haplotype). The...

Nivolumab for the treatment of advanced nonsmall cell lung cancer (NSCLC) evaluated in phase III trials showed 50% progression at first evaluation, but better overall survival (OS), suggesting regained efficacy of treatments given thereafter. We aimed to evaluate the efficacy of nivolumab and of next treatment received after nivolumab progression in patients with advanced NSCLC.Our multicentre retrospective study included all patients receiving nivolumab between January and December 2015. The primary end-point was progression-free survival (PFS) of treatment given after nivolumab.The 303 patients had the following characteristics: median age 63 years, 69% males, 92% smokers, 67% performance status 0–1 and 61% adenocarcinoma. Nivolumab was given as second-line treatment in 40% of patients. With 13.7 months of median follow-up, nivolumab PFS and OS were 2.6 and 11.3 months, respectively. At the cut-off analysis 18% were controlled under nivolumab, 14% were deceased and 5% were lost to follow-up under nivolumab. Among the 191 (63%) patients eligible for post-nivolumab (PN) treatment, 115 (38%) received further treatment and were characterised by better performance status (p=0.028) and by receiving more injections of nivolumab (p=0.001). Global PN-OS and PN-PFS were 5.2 and 2.8 months, respectively. Drugs most frequently used after nivolumab were gemcitabine (23%), docetaxel (22%) and erlotinib (16%), with median PFS of 2.8, 2.7 and 2.0 months, respectively.Nivolumab produced similar efficacy as in phase III trials, although patients received nivolumab later and had worse performance status. 38% received treatment after nivolumab progression with efficacy comparable to historical second-line trials.

Highlights  Hyper progressive disease is a new form of progression in patients treated with immunotherapy  The definition of HPD is yet to be consensual  We suggest a clinical definition of patients refractory to immunotherapy based on the number of nivolumab injections