Improved efficiency of daratumumab treatment of multiple myeloma adopting the subcutaneous route: A micro-costing analysis in three Italian hematology centers.

BACKGROUND: Daratumumab is a humanized monoclonal antibody approved for the treatment of adult patients with newly diagnosed or relapsed/refractory multiple myeloma (RRMM). Subcutaneous (SC) formulation proved to be non-inferior in comparison with intravenous (IV) administration route. This study aimed at assessing the economic and time impact associated with the use of SC versus IV daratumumab in patients with RRMM from the perspective of the hematology center. METHODS: This was a 5-month multicenter time-and-motion cross-sectional micro-costing study conducted in three Italian hematology centers among adult patients diagnosed with RRMM with ongoing treatment with IV or SC daratumumab. Measurements were performed by an ad hoc App. RESULTS: Nineteen (20%) IV and 76 (80%) SC administration procedures were measured. Patients spent a mean of 4.85 ± 0.91 or 1.08 ± 0.56 h in the hematology center to receive IV or SC daratumumab, respectively. Healthcare professionals (HCPs) spent a mean of 49.38 ± 16.13 and 20.37 ± 7.88 min of active working time to manage IV and SC administrations, respectively. The infusion chair was occupied for a mean of 4.85 ± 0.91 and 0.99 ± 0.55 h during IV or SC administration, respectively. On average, considering the costs due to HCP and chair time, materials, and overhead costs, every IV and SC administration costed €80.33 and 34.90, respectively. CONCLUSIONS: In conclusion, as compared with IV administration, SC daratumumab was associated with 78%, 59%, 80% savings in terms of patient time, HCP active working time, and infusion chair, respectively, and 56.6% budget savings.

Point-of-care ultrasound for neonatal central catheter positioning: impact on X-rays and line tip position accuracy.

Objective of the study was to compare number of X-rays performed for neonatal central line tip positioning when real-time US is used compared to X-ray only, and to assess consequences on position accuracy, irradiation and cost. Retrospective monocentric cohort study conducted at Evelina London Children's Hospital Neonatal Unit over 6 months. Study was conducted during implementation of US for line tip localisation with formulation of US protocol. Tip position on X-ray was reviewed by one neonatologist and one radiologist and inter-rater agreement calculated. Criteria for good, satisfactory or inadequate position of the tip were defined. Estimated effective radiation dose and cost for each X-ray was determined. Two hundred seventy-four lines were inserted (nPICC, UVC, UAC). Eighty-three lines were scanned with US (US group); 191 lines were not (no-US group). Number of X-rays performed was significantly lower in the US group: 1.19 vs. 1.5 (p 0.001), related to a significantly lower percentage of lines requiring multiple X-rays (38.7% no-US group vs. 19.9% US group; p 0.004). Accuracy was higher in US group with more lines at cavoatrial junction (p 0.05) and was significantly increased with US use for lines inserted from lower limbs (22.9% and 76.2%, p 0.001). Inter-rater agreement was strong (k > 0.8). US group received lower mean radiation dose (p < 0.001) and cost related to X-ray was significantly reduced (p 0.001). CONCLUSION: Real-time US use for line tip positioning in the NICU significantly decreased the number of X-rays performed and was associated with better-positioned lines, decreased irradiation and cost. WHAT IS KNOWN: • The use of point-of-care ultrasound (PoCUS) by critical care providers in neonatology has increased in recent years. International guidelines advocate for the use of PoCUS as valid guidance to practical procedures in neonatology. • Central catheters (umbilical catheters and neonatal peripherally inserted central catheters) are among the most commonly used devices to support NICU patients. Proper positioning is crucial to avoid complications and PoCUS has high sensitivity and specificity in accurately determining line tip position. The current standard practice for line tip position confirmation in neonatology is still conventional radiography despite multiple evidence suggest significant inaccuracy of X-ray compared to ultrasound. WHAT IS NEW: • PoCUS implementation for line tip positioning leads to a significant decrease in the number of X-rays performed, in radiation effective dose and costs. PoCUS evaluation of central catheters significantly increases the accuracy of the final line tip position with more lines at the cavoatrial junction. • Training is fundamental for univocal interpretation of ultrasound images and an effective learning strategy is being proposed.

Testing for fecal gluten immunogenic peptides: a useful tool to evaluate compliance with gluten-free diet by celiacs.

BACKGROUND: Although experts agree that strict dietary compliance is fundamental for the health of celiac patients, there are no evidence-based recommendations on the best way to assess dietary compliance. Detection of gluten immunogenic peptides (GIPs) in feces was recently proposed as an effective method of assessing the dietary compliance of celiac patients. METHODS: Fifty-five consecutive celiac patients (27 adults and 28 children, age 6-72 years), who had been on a gluten-free diet for at least 2 years, were enrolled. All patients were evaluated clinically for symptoms, physical parameters and laboratory parameters. Dietary compliance was assessed with the Biagi questionnaire and serum anti-tissue transglutaminase (tTG) IgA antibodies were measured. GIPs were determined by immunoenzymatic assay on an automated Chorus analyzer (DIESSE Diagnostica Senese), after extraction of fecal samples by the method developed by DIESSE. RESULTS: Eight patients tested positive for GIPs (GIPs+); 71.4% of GIP-positive patients were asymptomatic; tTG antibodies were detected in 3/8 GIP+ patients. The Biagi score was significantly associated with fecal positivity for GIPs (P=0.02). However, according to the Biagi score, 57.1% of GIP+ patients followed the diet strictly and 5.4% of GIP- subjects did not comply with the diet or made substantial mistakes. CONCLUSIONS: Assay of fecal GIPs identified more patients who did not comply with the diet than did the Biagi questionnaire, evaluation of symptoms or anti-tTG antibodies. Detection of fecal GIPs offers a direct, objective, quantitative assessment of even occasional exposure to gluten and is confirmed as a practical way to check dietary compliance.

Fecal gluten immunogenic peptides as indicators of dietary compliance in celiac patients.

BACKGROUND: It is important to have methods for evaluating dietary compliance in patients with celiac disease (CD). Determination of fecal gluten immunogenic peptides (GIPs) was recently proposed as a method of detecting gluten intake. The aim of this study was to evaluate whether determination of GIPs can be used as an indicator of compliance with a gluten-free diet (GFD). METHODS: Twenty-five persons with CD on a gluten-free diet for at least one year were enrolled in the study. Compliance with the diet was assessed by the Biagi questionnaire, evaluation of symptoms and assay of IgA anti-tissue transglutaminase antibodies (IgA anti-tTG). GIPs were determined by iVYLISA GIP-S test (Biomedal S.L., Seville, Spain) on an automated Chorus analyzer (DIESSE Diagnostica Senese, Siena, Italy), after extraction of fecal samples by the method developed by DIESSE. RESULTS: Four patients tested positive for GIPs (GIP+), two of whom complied strictly with the gluten-free diet according to the Biagi questionnaire. None of the four GIP-positive patients manifested symptoms. IgA anti-tTG was significantly higher in GIP+ than in GIP- subjects. CONCLUSIONS: Assay of fecal GIPs identified more patients who were not complying with the diet than the Biagi questionnaire or evaluation of symptoms. The anti-tTG and GIP results agreed perfectly; however, since anti-tTG antibodies remain high for longer and are not a completely reliable marker of GFD intake, detection of fecal GIPs offers a direct, objective, quantitative assessment of exposure, even occasional, to gluten and could be used to check dietary compliance.

Antiepileptic drugs: Role in paediatric poisoning.

Intoxications, both accidental and intentional, are common in children and adolescents and often require hospitalisation and intensive treatment. Antiepileptic drugs are a possible cause of poisoning and intoxications because this category of medications has shown a rising trend in recent years. They might be responsible for multi-organ dysfunctions of variable severity, ranging from subtle symptoms to life-threatening complications. No guidelines on the management of these intoxications in the paediatric population are currently available, and treatment is mainly supportive. Activated charcoal administration and extracorporeal circulation techniques for drug removal have been proposed. Facing the complexity of this clinical scenario, it is of utmost importance to maintain a high index of suspicion to guarantee a prompt intervention and ensure the best possible management for the patient.

Massive lamotrigine poisoning. A case report.

Lamotrigine (LTG) represents the most commonly prescribed of the so-called new generation antiepileptic drugs. We describe a child who was admitted to the emergency room because of generalized tonic-clonic status epilepticus followed by a complex neurological picture with hyperkinesia and acute ataxia as a result of a LTG intoxication. The experience on acute LTG intoxication is very limited in pediatrics. The present case provides information on the clinical picture related to LTG overdose and confirms that drug intoxications should be considered in the differential diagnosis strategy when severe and polymorphic neurological symptoms occur acutely.

Celiac disease: is it really possible to overcome duodenal biopsy?

We report the case of a two-year-five-month-old child who underwent screening for celiac disease due to strong familiarity. During the first observation body weight and height were at 25th and 50th centile for gender and age. Physical examination did not reveal any sign of disease. Blood tests showed increased transaminases levels and antibodies research showed: tTG IgA: 100 UI/ml, tTG IgG: 36,6 UI/ml, EMA IgA: positive. HLA study revealed homozygous allelic combination DRB1*07;DQA102:01; DQB1* 02:02 with presence of a double copy of beta chain in the composition of the  DQ2 heterodymer. Biopsy with histological examination did find neither mucosal alteration  nor lymphocytic infiltrates (Marsh 0). During follow up with free diet the patient remained asymptomatic and all antibody titers decreased up to normalization. According to ESPGHAN guidelines the finding of hypertransaminasemia as sign of celiac hepatic inflammation, a more than 10-fold increase of tTG IgA and a high-risk HLA would permit diagnosis of celiac disease but histological examination done due to mismatch between paucity of clinical sings and a "multiple risk combination" excluded it, allowing diagnosis of potential celiac disease.  We believe that this case is interesting because of its being in contrast with current literature data that suggest a linear relationship between antibodies levels and histological damage with tTG IgA at the upper reference range in case of potential celiac disease. According to guidelines we could have avoided intestinal biopsy but we would have considered as celiac a patient who is maybe just potentially affected.

Raman database of amino acids solutions: a critical study of extended multiplicative signal correction.

The Raman spectra of biological materials always exhibit complex profiles, constituting several peaks and/or bands which arise due to the large variety of biomolecules. The extraction of quantitative information from these spectra is not a trivial task. While qualitative information can be retrieved from the changes in peaks frequencies or from the appearance/disappearance of some peaks, quantitative analysis requires an examination of peak intensities. Unfortunately in biological samples it is not easy to identify a reference peak for normalizing intensities, and this makes it very difficult to study the peak intensities. In the last decades a more refined mathematical tool, the extended multiplicative signal correction (EMSC), has been proposed for treating infrared spectra, which is also capable of providing quantitative information. From the mathematical and physical point of view, EMSC can also be applied to Raman spectra, as recently proposed. In this work the reliability of the EMSC procedure is tested by application to a well defined biological system: the 20 standard amino acids and their combination in peptides. The first step is the collection of a Raman database of these 20 amino acids, and subsequently EMSC processing is applied to retrieve quantitative information from amino acids mixtures and peptides. A critical review of the results is presented, showing that EMSC has to be carefully handled for complex biological systems.