Effectiveness of a vitamin D regimen in deficient multiple myeloma patients and its effect on peripheral neuropathy.

PURPOSE: Peripheral neuropathy (PN) is common in multiple myeloma (MM) patients. More insight has been gained concerning the role of vitamin D in preventing PN. However, studies evaluating the effects of vitamin D3 supplementation on PN are lacking. The aims of this study are to (1) evaluate the effectiveness of a vitamin D3 regimen on achieving adequate vitamin D levels in deficient MM patients and to (2) exploratively evaluate the effect of vitamin D3 supplementation on PN. METHODS: Thirty-nine MM patients with inadequate (< 75 nmol/L [= 30 ng/mL]) 25-hydroxyvitamin D (25(OH)D) levels were included in this multicenter, prospective, single-arm study, of whom 35 patients completed the study. They received oral vitamin D3 for 6 months according to a dose escalation regimen that consisted of one or two loading doses of 200,000 international units (IU), and maintenance doses of 800, 1600, or 3200 IU/day depending on the 25(OH)D level. A validated questionnaire was used to measure PN. RESULTS: Median 25(OH)D increased from 38 (IQR 32-52) nmol/L at baseline to 77 (IQR 72-87) nmol/L after 6 months (P < 0.001). Adequate 25(OH)D levels were achieved by 66% of the subjects, and 34% were within the range of 50-75 nmol/L. Furthermore, in 37% of the participants, PN severity decreased (P = 0.007). CONCLUSION: The use of substantially higher vitamin D3 doses than recommended in current guidelines resulted in a significant increase in vitamin D levels in MM patients. Furthermore, evaluation of PN showed a significant decrease in PN grading. However, this exploratory evaluation needs further confirmatory research.

Cumulative corticosteroid-sparing effect of anti-interleukin-5/5Ra in eosinophilic asthma.

BACKGROUND: Anti-interleukin (IL)-5/IL-5 receptor α (IL-5Ra) therapy has been shown to reduce maintenance oral corticosteroid (OCS) dose in severe eosinophilic asthma. However, the effect on cumulative OCS exposure is currently unknown. Neither is it known how prior OCS exposure affects response to anti-IL-5/5Ra treatment. We aimed primarily to compare the cumulative OCS exposure over a 2-year period before and after anti-IL-5/5Ra initiation, and secondarily to investigate whether duration and cumulative OCS exposure prior to anti-IL-5/5Ra influence the ability to discontinue OCS within 2 years of anti-IL-5/5Ra therapy. METHODS: This real-world nationwide observational registry-based study evaluated all dispensed OCS from 389 adults with severe eosinophilic asthma included in the Dutch Severe Asthma Registry (RAPSODI) 2 years before and 2 years after initiating anti-IL-5/5Ra. The Wilcoxon signed-rank test and multivariable regression analyses were used. RESULTS: Median (interquartile range) cumulative OCS exposure in the 2 years before and after anti-IL-5/5Ra initiation decreased from 2.715 (1.150-5.539) to 1.050 (0.300-3.640) g (p<0.001). 52% of patients were able to discontinue OCS within 2 years after anti-IL-5/5Ra therapy, which was independently predicted by lower and shorter prior OCS exposure. CONCLUSIONS: This real-world study showed that anti-IL-5/5Ra therapy leads to a significant reduction in cumulative OCS exposure over a 2-year period. Patients with lower and shorter OCS exposure were more likely to completely eliminate OCS. Since cumulative exposure increased progressively prior to anti-IL-5/5Ra initiation, our data suggest that early intervention leads to a better long-term prognosis in patients with severe eosinophilic asthma.

Pharmacology, particle deposition and drug administration techniques of intranasal corticosteroids for treating allergic rhinitis.

This review presents an overview of the available literature regarding intranasal corticosteroids (INCs) for the treatment of allergic rhinitis (AR). Various treatment options exist for AR including INCs, antihistamines and leucotriene antagonists. INCs are considered to be the most effective therapy for moderate-to-severe AR, as they are effective against nasal and ocular symptoms and improve quality of life. Their safety has been widely observed. INCs are effective and safe for short-term use. Local adverse events are observed but generally well-tolerated. The occurrence of (serious) systemic adverse events is unlikely but cannot be ruled out. There is a lack of long-term safety data. INC may cause serious eye complications. The risk of INCs on the hypothalamic-pituitary-adrenal axis, on bone mineral density reduction or osteoporosis and on growth in children, should be considered during treatment. Pharmacological characteristics of INCs (e.g. the mode of action and pharmacokinetics) are well known and described. We sought to gain insight into whether specific properties affect the efficacy and safety of INCs, including nasal particle deposition, which the administration technique affects. However, advances are lacking regarding the improved understanding of the effect of particle deposition on efficacy and safety and the effect of the administration technique. This review emphasizes the gaps in knowledge regarding this subject. Advances in research and health care are necessary to improve care for patients with AR.

Clinical view versus guideline adherence in ferritin monitoring and initiating iron chelation therapy in patients with myelodysplastic syndromes.

OBJECTIVES: In patients with myelodysplastic syndromes (MDS) with >20 transfusions and ferritin levels >1000 µg/L, international guidelines recommend iron chelation therapy (ICT). The study's objective was to determine guideline adherence and the intensity of ferritin monitoring in clinical practice. METHODS: We performed an observational population-based study using the HemoBase Registry, which contains data of all MDS patients diagnosed since 2005 in Friesland, the Netherlands. Clinical information on transfusions, ferritin measurements, ICT, and clinical performance as defined by age ≤ 80 years, Charlson Comorbidity Index <2 and lower-risk MDS was collected from health records. RESULTS: Two hundred and thirty seven of 292 patients (81.1%) received ≥1 transfusion, and 121 (41.4%) received >20 transfusions. In 57 of these 121 patients (47.1%), ferritin measurements were performed at least once. Clinical performance was significantly associated with monitoring ferritin around the 20th transfusion (RR: 2.49, p = .016). Clinical performance was also associated with initiating ICT (RR: 5.99, p < .001). ICT was offered to 22.3% (n = 25) of eligible patients. CONCLUSIONS: In this population-based study, ferritin levels were measured in <50% of MDS patients who received >20 transfusions, and clinical performance was significantly associated with measuring ferritin. Our study suggests that in heavily transfused MDS patients, ferritin monitoring is primarily based on patients' clinical performance rather than guideline recommendations.

Patterns of transfusion burden in an unselected population of patients with myelodysplastic syndromes: A population-based study.

BACKGROUND: Ineffective hematopoiesis in patients with myelodysplastic syndromes (MDS) often results in transfusion dependence. The burden of frequent transfusions in the real-world MDS population is largely unknown. STUDY DESIGN AND METHODS: An observational, retrospective, population-based study, using the HemoBase registry, was performed including all patients diagnosed with MDS between 2005 and 2017 in Friesland, a province in the Netherlands with approximately 650,000 inhabitants. Detailed clinical information was collected from the electronic health records. Transfusion burden was classified according to the International Working Group 2018 criteria: not transfusion dependent, low (LTB), or high transfusion burden (HTB). Univariate and multivariable regression analyses were performed. RESULTS: Of 292 patients, 136 (46.6%) had a HTB of ≥8 units/16 weeks and 17 (5.8%) had a LTB of 3-7 units/16 weeks. This was present in all types of MDS patients, but patients aged 75-84 years (odds ratio [OR] 4.02, 95% confidence interval [CI]: 1.84-8.82), high-risk MDS patients (OR 2.88, 95% CI: 1.08-7.68) and MDS-EB-2 patients (OR 7.07, 95% CI: 2.17-22.90) were particularly at risk for a HTB. DISCUSSION: This study provides a reliable estimate of the transfusion burden in real-world MDS patients, with almost half of the patients having a HTB. A HTB was observed in all MDS subtypes and both low- and high-risk MDS. Therefore, we conclude that the entire MDS population might benefit from novel agents that reduce the transfusion need and that might have beneficial effects on patient outcomes and healthcare utilization outcomes.

Applicability of somatic monitoring instructions in clinical practice guidelines on antipsychotic drug use.

BACKGROUND: Clinical practice guidelines (CPGs) recommend the monitoring of somatic parameters in patients treated with antipsychotic drugs in order to detect adverse effects. The objective of this study was to assess, in adult and (frail) elderly populations, the consistency and applicability of the somatic monitoring instructions recommended by established CPGs prior to and during antipsychotic drug use. METHODS: A search for national and international CPGs was performed by querying the electronic database PubMed and Google. Somatic monitoring instructions were assessed for adult and (frail) elderly populations separately. The applicability of somatic monitoring instructions was assessed using the Systematic Information for Monitoring (SIM) score. Somatic monitoring instructions were considered applicable when a minimum SIM score of 3 was reached. RESULTS: In total, 16 CPGs were included, with a total of 231 somatic monitoring instructions (mean: 14; range: 0-47). Of the somatic monitoring instructions, 87% were considered applicable, although critical values and how to respond to aberrant values were only present in 28 and 52% of the available instructions respectively. Only 1 CPG presented an instruction specifically for (frail) elderly populations. CONCLUSIONS: We emphasize the need for a guideline with somatic monitoring instructions based on the SIM definition for both adult and (frail) elderly populations using antipsychotic drugs. In addition, CPGs should state that clear agreements should be made regarding who is responsible for interventions and somatic monitoring prior to and during antipsychotic drug use.

Design and methods of the 'monitoring outcomes of psychiatric pharmacotherapy' (MOPHAR) monitoring program - a study protocol.

BACKGROUND: At many outpatient departments for psychiatry worldwide, standardized monitoring of the safety of prescribed psychotropic drugs is not routinely performed in daily clinical practice. Therefore it is unclear to which extent the drugs used by psychiatric outpatients are prescribed effectively and safely. These issues warrant structured monitoring of medication use, (pre-existing) co-morbidities, effectiveness and side effects during psychiatric outpatient treatment. Improvement of monitoring practices provides an opportunity to ensure that somatic complications and adverse drug effects are detected and dealt with in a timely manner. Structural support for data collection and follow-up tests seems essential for improvement of monitoring practices in psychiatric outpatients. The implementation of a structured somatic monitoring program as part of routine clinical practice, as we describe in this study protocol, may be a solution. METHODS: In order to address these issues, we developed the innovative program 'Monitoring Outcomes of Psychiatric Pharmacotherapy (MOPHAR)'. MOPHAR is an infrastructure for implementation of standardized routine outcome monitoring (ROM; including standardized monitoring of treatment effect), monitoring of adverse psychotropic medication effects in psychiatric outpatients, encompassing both somatic adverse effects (e.g. metabolic disturbances) and subjective adverse effects (e.g. sedation or sexual side effects) and medication reconciliation. DISCUSSION: In the MOPHAR monitoring program, a nurse performs general and psychotropic drug-specific somatic screenings and provides the treating mental health care providers with more and better information on somatic monitoring for treatment decisions. Given our experience regarding implementation of the MOPHAR program, we expect that the MOPHAR program is feasible and beneficial for patients in any MHS organisation. This paper describes the objectives, target population, setting and the composition and roles of the treatment team. It also indicates what measurements are performed at which time points during outpatient treatment in the MOPHAR monitoring program, as well as the research aspects of this project. TRIAL REGISTRATION: MOPHAR research has been prospectively registered with the Netherlands Trial Register on 19th of November 2014. ( NL4779 ).

Relapse in stage I(E) diffuse large B-cell lymphoma.

Despite a general favourable outcome in limited stage diffuse large B-cell lymphoma (DLBCL), relapses occur in about 10 to 20% of patients. Prognostic models only partially identify patients at risk for relapse. Moreover, it is not known whether the outcome after such a relapse is similar to the outcome after relapse in advanced stages. From January 2004 through December 2012, all newly diagnosed patients with stage I(E) DLBCL were retrospectively analysed from 2 clinical databases to investigate the relapse pattern and outcome in relation to initial treatment and clinical characteristics. In 126 patients (median age 64 years), histologically confirmed stage I(E) DLBCL was diagnosed. With a median follow-up of 53 months (range 5-132 months), 1 progressive disease and 18 relapses occurred. The 5-year time to tumour progression and disease-specific survival were 85% (95% CI 79-91%) and 92% (95% CI 87%-97%), respectively. We observed no significant difference in relapse localization, time to tumour progression, and disease-specific survival between patients treated with abbreviated R-CHOP plus involved field radiotherapy or with 6 to 8 cycles of R-CHOP. Analysis of relapses showed relapse >5 years after initial treatment (late relapse) in 5 of 19 patients (26%). Six of 19 patients (32%) had central nervous system relapse. Three of 11 relapsed cases available for analysis (28%) showed an MYC translocation, suggesting an overrepresentation in the relapse group. Outcome of patients with a relapse was poor with a median survival after relapse of 8 months. Only 1 patient (5%) underwent successful autologous stem cell transplantation. To improve outcome in these patients, early identification of new biological factors such as a MYC translocation or a high risk for CNS dissemination might be helpful. Moreover, treatment of any relapse after stage I disease should be taken seriously. Salvage treatment should be similar to relapses after advanced DLBCL.

Non-invasive bladder volume measurement for the prevention of postoperative urinary retention: validation of two ultrasound devices in a clinical setting.

Ultrasound scanning of bladder volume is used for prevention of postoperative urinary retention (POUR). Accurate assessment of bladder volume is needed to allow clinical decision-making regarding the need for postoperative catheterization. Two commonly used ultrasound devices, the BladderScan® BVI 9400 and the newly released Prime® (Verathon Medical®, Bothell, WA, USA), with or without the 'pre-scan' option, have not been validated in clinical practice. The aim of this study was to assess the performance of these devices in daily clinical practice. Between June and September 2016 a prospective observational study was conducted in 318 surgical patients (18 years or older) who needed a urinary catheter perioperatively for clinical reasons. For acceptable performance, we required that the volume as estimated by the BladderScan® differs by no more than 5% from the actual urine volume after catheterization. The Schuirmann's two one-sided test was performed to assess equivalence between the BladderScan® estimate and catheterization. The BVI 9400® overestimated the actual bladder volume by + 17.5% (95% CI + 8.8 to + 26.3%). The Prime® without pre-scan underestimated by - 4.1% (95% CI - 8.8 to + 0.5%) and the Prime® with pre-scan underestimated by - 6.3% (95% CI - 11.6 to - 1.1%). This study shows that while both ultrasound devices were able to approximate current bladder volume, both BVI 9400® and Prime®-with and without pre-scan-were not able to measure the actual bladder volume within our predefined limit of ± 5%. Using the pre-scan feature of the Prime® did not further improve accuracy.

Influence of bariatric surgery on the use of medication.

PURPOSE: Bariatric surgery can influence the prevalence and incidence of comorbidities, as well as the pharmacokinetics of drugs. This might lead to changes in the use of drugs. This study aimed to assess the influence of bariatric surgery on the use of medication in patients before and after surgery, focusing on type, number of medications, and daily dosage. METHODS: In a retrospective and prospective observational study, drug dispensing data from pharmacies of patients undergoing their first bariatric surgery between January 2008 and September 2011 was collected. Dispensing data from 1 month before until 12 months after surgery was analyzed. Drugs were classified according to the WHO-ATC classification system. Dosages of drugs were compared using defined daily dose (DDD). RESULTS: Among 450 patients, 12 months after surgery, the mean number of drugs per patient for antidiabetics, drugs acting on the cardiovascular system, anti-inflammatory and antirheumatic drugs, and drugs for obstructed airway diseases decreased by, respectively, 71.3 % (95 % CI 57.2 to 85.4), 34.5 % (95 % CI 28.2 to 43.0), 45.5 % (95 % CI 13.3 to 72.6), and 33.1 % (95 % CI 15.3 to 53.2). Patients used lower median DDD of oral antidiabetics, beta-blocking agents, and lipid-modifying drugs. CONCLUSIONS: For some major drug classes 12 months after bariatric surgery, the use of drugs decreases in terms of mean number per patient. A reduction in dose intensity was observed for oral antidiabetics, beta-blocking agents, and lipid-modifying drugs. Dispensing data from pharmacies may provide detailed information on the use of medications by patients after bariatric surgery.

Vitamin D reduces eosinophilic airway inflammation in nonatopic asthma.

BACKGROUND: Low levels of vitamin D are associated with asthma severity, airway remodeling, and exacerbation rate increase, especially in nonatopic asthma. Reduced steroid responsiveness or impaired antimicrobial defense might be underlying mechanisms. OBJECTIVE: We sought to evaluate the effect of vitamin D supplementation on eosinophilic and neutrophilic airway inflammation in patients with nonatopic asthma. METHODS: In a double-blind, randomized, placebo-controlled trial, we investigated the effect of long-acting vitamin D3 (400,000 IU) on sputum neutrophils and eosinophils in 44 patients with nonatopic asthma with neutrophilic (≥53%) and/or eosinophilic (≥3%) airway inflammation. Sputum induction was performed at baseline and after 9 weeks. Other measurements included questionnaires, blood samples, and pulmonary function. RESULTS: Treatment with vitamin D did not significantly affect sputum neutrophils or eosinophils compared with treatment with placebo in the total group. Regarding sputum eosinophils, the effect of vitamin D appeared to be dependent on baseline sputum eosinophil levels (interaction P = .015). In patients with eosinophil levels of 26.2% or more (median in patients with sputum eosinophilia, >3%), eosinophils decreased from a median of 41.0% to 11.8% after vitamin D treatment as compared with an increase from 51.8% to 63.3% in patients receiving placebo (P = .034). Vitamin D treatment also resulted in slightly better Asthma Control Questionnaire scores (P = .08). CONCLUSIONS: Vitamin D supplementation reduced eosinophilic airway inflammation in patients with nonatopic asthma with severe eosinophilic airway inflammation, but did not affect sputum neutrophils. Also, a small effect on asthma control was observed. These findings suggest that vitamin D might have potential as an add-on treatment option in eosinophilic asthma.

Postoperative bladder catheterization based on individual bladder capacity: a randomized trial.

BACKGROUND: Untreated postoperative urinary retention can result in permanent lower urinary tract dysfunction and can be prevented by timely bladder catheterization. The author hypothesized that the incidence of postoperative bladder catheterization can be decreased by using the patient's own maximum bladder capacity (MBC) instead of a fixed bladder volume of 500 ml as a threshold for catheterization. METHODS: Randomized parallel-arm and single-blinded comparative effectiveness trial conducted in 1,840 surgical patients, operated under general or spinal anesthesia without an indwelling urinary catheter. Patients were randomized to either use their individual MBC (index) or a fixed bladder volume of 500 ml (control) as a threshold for postoperative bladder catheterization. Preoperatively, the MBC was determined at home by voiding in a calibrated bowl. All other bladder volumes were measured by ultrasound. Postoperatively, bladder catheterization was performed when spontaneous voiding was impossible, and the ultrasound measurement exceeded the threshold for the group in which the patient was randomized (500 or MBC). The primary outcome was the incidence of bladder catheterization. RESULTS: The average MBC in the control group was 582 ml (±199 ml) and in the index group 611 ml (±209 ml). The incidence of catheterization decreased from 11.8% (107 of 909 patients) in the control group to 8.6% (80 of 931) in the index group (relative risk 0.73, 95% CI 0.55 to 0.96, P = 0.025). There were no adverse events in either group. CONCLUSIONS: In patients undergoing surgery under general or spinal anesthesia using the MBC rather than a fixed 500 ml threshold for bladder catheterization is a safe approach that significantly reduces the incidence of postoperative bladder catheterizations.

Comorbidity is an independent prognostic factor in patients with advanced-stage diffuse large B-cell lymphoma treated with R-CHOP: a population-based cohort study.

An observational population-based cohort study was performed to investigate the role of comorbidity on outcome and treatment-related toxicity in patients with newly diagnosed advanced-stage diffuse large B-cell lymphoma (DLBCL) treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). Data for the clinical characteristics of 154 patients (median age 69 years), including Charlson Comorbidity Index (CCI), treatment, toxicity and outcome were evaluated. Forty-five percent of the patients had an International Prognistic index ≥3 and 16% had a CCI ≥2. The planned R-CHOP schedule was completed by 84% and 75% reached complete remission (CR). In those with CCI ≥2, 67% completed treatment with 46% CR. In patients with a CCI <2, overall survival (OS) after 1, 2 and 5 years was 84%, 79% and 65% respectively and it was 64%, 48% and 48% for those with CCI ≥2. Grade III/IV toxicity was documented in 53%, most frequently febrile neutropenia (27%) and infections (23%). In multivariate analysis CCI ≥2 and IPI ≥3 were independent risk indicators for OS and grade III/IV toxicity. In conclusion, comorbidity is an independent risk indicator for worse OS in patients with advanced DLBCL treated with R-CHOP by interference with intensive treatment schedules and more grade III/IV toxicity. Future studies are warranted to determine the optimal treatment approach in patients with significant comorbidities.

Low-dose ketamine or opioids combined with propofol for procedural sedation in the emergency department: a systematic review.

Procedural sedation is routinely performed for procedures in the emergency department (ED). Propofol is a commonly used sedative, frequently combined with an opioid or low-dose ketamine as an analgesic. However, there is still controversy on the optimal combination of agents in current guidelines. The objective of this systematic review is to identify and present studies comparing low-dose ketamine to opioids when combined with propofol for procedural sedation in the ED and to describe the dosing regimen, observed efficacy, and side effects. For this systematic review, following the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines, EMBASE and PubMed databases were searched. Studies comparing propofol with opioids versus propofol with low-dose (es)ketamine in patients undergoing procedural sedation for procedures in the ED were included. Analyses were descriptive because of the high heterogeneity among included studies. The outcomes were dosing regimen, efficacy of analgesia, efficacy of sedation depth, efficacy of recovery and (adverse) events. We included four out of 2309 studies found in the literature search. Overall, the studies had a low risk of bias, but the Grading of Recommendations Assessment, Development, and Evaluation evidence profile was downgraded due to the imprecision and inconsistency of the studies. All studies compared low-dose ketamine with fentanyl. Dosing ranged from 0.3 to 1.0 mg/kg (ketamine), 1.0-1.5 µg/kg (fentanyl) and 0.4-1.0 mg/kg (propofol). The efficacy of analgesia was measured by two studies, one favoring the fentanyl group, and one favoring the ketamine group. The efficacy of sedation depth was measured by one study, with the fentanyl group having a deeper sedation score. Two studies showed shorter recovery time with low-dose ketamine. One study showed a higher incidence of cardio-respiratory clinical events and interventions in the fentanyl group. Two studies showed significant differences of overall sedation events in the fentanyl group. One study did not find any significant differences of the incidence of sedation events. This systematic review did not provide sufficient evidence that the combination of low-dose ketamine and propofol is associated with a shorter recovery time and fewer sedation events compared to the combination of opioids and propofol.

[After bariatric surgery effects of medication are not always predictable]. / Farmacotherapie na bariatrische chirurgie: niet altijd voorspelbaar.

Bariatric surgery is widely used as an effective treatment for obesity. Changes in the anatomy of the digestive tract as a result of these operations may lead to changes in drug availability. This is illustrated by three cases in which problems arose with calcium metabolism, thyroid hormone substitution or weight. Effects on medication after bariatric surgery are not always predictable and there are no uniform guidelines how to handle. We advocate therefore a proactive attitude of physicians by monitoring direct effects (such as blood pressure, glucose, or mood) or determining drug concentrations, to prevent treatment failure or toxicity.

Clinical response to benralizumab can be predicted by combining clinical outcomes at 3†months with baseline characteristics.

Background: Benralizumab is highly effective in many, but not all, patients with severe asthma. Baseline characteristics alone are insufficient to predict an individual's probability of long-term benralizumab response. The objectives of the present study were to: 1) study whether parameters at 3 months, in addition to baseline characteristics, contribute to the prediction of benralizumab response at 1 year; and 2) develop an easy-to-use prediction tool to assess an individual's probability of long-term response. Methods: We assessed the effect of benralizumab treatment in 192 patients from the Dutch severe asthma registry (RAPSODI). To investigate predictors of long-term benralizumab response (≥50% reduction in maintenance oral corticosteroid (OCS) dose or annual exacerbation frequency) we used logistic regression, including baseline characteristics and 3-month Asthma Control Questionnaire (ACQ-6) score and maintenance OCS dose. Results: Benralizumab treatment significantly improved several clinical outcomes, and 144 (75%) patients were classified as long-term responders. Response prediction improved significantly when 3-month outcomes were added to a predictive model with baseline characteristics only (area under the receiver-operating characteristic (AUROC) 0.85 versus 0.72, p=0.001). Based on this model, a prediction tool using sex, prior biologic use, baseline blood eosinophils, forced expiratory volume in 1 s, and at 3 months OCS dose and ACQ-6 was developed which classified patients into three categories with increasing probability of long-term response (95% CI): 25% (3-65%), 67% (57-77%) and 97% (91-99%), respectively. Conclusion: In addition to baseline characteristics, treatment outcomes at 3 months contribute to the prediction of benralizumab response at 1 year in patients with severe eosinophilic asthma. Prediction tools as proposed in this study may help physicians optimise the use of costly biologics.

Acute kidney injury associated with nephrotoxic drugs in critically ill patients: a multicenter cohort study using electronic health record data.

Background: Nephrotoxic drugs frequently cause acute kidney injury (AKI) in adult intensive care unit (ICU) patients. However, there is a lack of large pharmaco-epidemiological studies investigating the associations between drugs and AKI. Importantly, AKI risk factors may also be indications or contraindications for drugs and thereby confound the associations. Here, we aimed to estimate the associations between commonly administered (potentially) nephrotoxic drug groups and AKI in adult ICU patients whilst adjusting for confounding. Methods: In this multicenter retrospective observational study, we included adult ICU admissions to 13 Dutch ICUs. We measured exposure to 44 predefined (potentially) nephrotoxic drug groups. The outcome was AKI during ICU admission. The association between each drug group and AKI was estimated using etiological cause-specific Cox proportional hazard models and adjusted for confounding. To facilitate an (independent) informed assessment of residual confounding, we manually identified drug group-specific confounders using a large drug knowledge database and existing literature. Results: We included 92 616 ICU admissions, of which 13 492 developed AKI (15%). We found 14 drug groups to be associated with a higher hazard of AKI after adjustment for confounding. These groups included established (e.g. aminoglycosides), less well established (e.g. opioids) and controversial (e.g. sympathomimetics with α- and ß-effect) drugs. Conclusions: The results confirm existing insights and provide new ones regarding drug associated AKI in adult ICU patients. These insights warrant caution and extra monitoring when prescribing nephrotoxic drugs in the ICU and indicate which drug groups require further investigation.

Adverse Drug Reactions of Intranasal Corticosteroids in the Netherlands: An Analysis from the Netherlands Pharmacovigilance Center.

BACKGROUND: Intranasal corticosteroids are one of the cornerstone treatment options for allergic rhinitis and chronic sinusitis complaints. Safety information in the summary of product characteristics may not be representative for observations in daily clinical practice. The Netherlands Pharmacovigilance Center (Lareb) collects post-marketing safety information, using spontaneous reporting systems. OBJECTIVE: Our objective was to analyse reports of adverse drug reactions associated with intranasal corticosteroids reported in the Dutch spontaneous reporting database of the Netherlands Pharmacovigilance Center Lareb to obtain insight into real-world safety data. METHODS: We retrospectively examined all adverse drug reactions of intranasal corticosteroids reported to the Netherlands Pharmacovigilance Center Lareb, entered into the database from 1991 until 1 July, 2020. RESULTS: In total, 2263 adverse drug reactions after intranasal corticosteroid use were reported in 1258 individuals. Headache (n = 143), epistaxis (n = 124) and anosmia (n = 57) were reported most frequently. Nasal septum perforation (reporting odds ratio 463.2; 95% confidence interval: 186.7-1149.7) had the highest reporting odds ratio, followed by nasal mucosal disorder (reporting odds ratio 104.5; 95% confidence interval 36.3-301.3) and hyposmia (reporting odds ratio 90.8; 95% confidence interval 45.1-182.7). Moreover, 101 (4.5%) reports were classified as serious by Lareb, including reports of Cushing's syndrome, adrenal cortical hypofunction and growth retardation. CONCLUSIONS: Many side effects are consistent with the safety information in the summary of product characteristics of intranasal corticosteroids. Several serious (systemic) side effects are reported and it is important to realise that intranasal corticosteroids may contribute to the development. Healthcare providers and patients should be aware of the potential (individual) adverse drug reactions of intranasal corticosteroids. This information could help in discussing treatment options.

A clinical effect of disease-modifying treatment on alloimmunisation in transfused patients with myelodysplastic syndromes: data from a population-based study.

BACKGROUND: Alloimmunisation against blood products is an adverse event, causing time-consuming compatibility testing. Current literature has not yet identified the influence of treatment on the risk of alloimmunisation in patients with myelodysplastic syndromes (MDS). MATERIALS AND METHODS: An observational, population-based study, using the HemoBase registry, was performed including all transfused patients who were diagnosed with MDS between 2005 and 2017 in Friesland, a province in the Netherlands. Information about transfusion dates, types, and treatment regimens was collected from the health records. Blood products were matched for ABO and Rhesus D. The effect of disease-modifying treatment was estimated with incidence rates and a Cox time-dependent analysis. RESULTS: 233 patients were included in this study, with a median follow-up of 13.0 months. Alloimmunisation occurred in 21 patients (9.0%) and predominantly occurred early in follow-up. Three (5%) and 18 (11%) alloimmunisation events occurred in patients with and without disease-modifying treatment, respectively. The hazard ratio for alloimmunisation without treatment compared to during treatment was 2.7 (95% CI: 0.35-20.0), with incidence rates of 7.18 and 2.41 per 100 patient-years, respectively. DISCUSSION: In a non-selected real-world population of MDS patients receiving blood transfusions, the percentage of patients with alloimmunisation was below 10%. The results of this study support the hypothesis that disease-modifying treatment affects the ability of the immune system to mount an antibody response to non-self blood group antigens.