Generating Utilities for the Château-Santé Base: A Novel, Generic, and Patient-Centered Health-Outcome Measure.

OBJECTIVES: We have developed a new patient-centered, preference-based generic health-outcome measure, Château-Santé Base (CS-Base), which is based on a novel multiattribute preference response (MAPR) measurement framework. This study aimed to generate a first utility set for the CS-Base, making it suitable for use in health-economic evaluations. METHODS: CS-Base comprises 12 health attributes: mobility, vision, hearing, cognition, mood, anxiety, pain, fatigue, social functioning, daily activities, self-esteem, and independence, each with 4 levels. Our methodology to generate utilities for the CS-Base was 2-fold. First, we derived coefficients from patient MAPR data to calculate CS-Base values. Subsequently, these were normalized to a 0.0 to 1.0 utility scale, in which 0.0 signifies dead. The dead position was estimated using general population data from a discrete choice experiment (discrete choice experiment + dead), using a division-value strategy, which localize the position of states better or worse than dead. RESULTS: We analyzed MAPR data from 3222 patients and discrete choice experiment + dead data from 1995 respondents. All MAPR coefficients were negative, logically ordered, and significantly different from the reference level. The dead position was denoted by a division value of -148.385. Utility values spanned from -0.071 to 1.0, and only 53 of 16 777 216 states were deemed worse than dead. CONCLUSIONS: This study introduced the first CS-Base utility set, underlining a 2-step utility derivation method. This method, blending societal and patient views, surpasses traditional preference-based approaches, yielding firmer results. However, improvement of the normalization procedure is expected. Estimating CS-Base utilities is an ongoing process that gains precision over time.

Diagnostic value of transcranial doppler to predict delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage : To predict delayed cerebral ischemia.

BACKGROUND: Transcranial Doppler (TCD) is a technique to assess blood flow velocity in the cerebral arteries. TCD is frequently used to monitor aneurysmal subarachnoid hemorrhage (aSAH) patients. This study compares TCD-criteria for vasospasm and its association with Delayed Cerebral Ischemia (DCI). An overall score based on flow velocities of various intracranial arteries was developed and evaluated. METHODS: A retrospective diagnostic accuracy study was conducted between 1998 and 2017 with 621 patients included. Mean flow velocity (MFV) of the cerebral artery was measured between 2-5 days and between 6-9 days after ictus. Cutoff values from the literature, new cutoff values, and a new composite score (Combined Severity Score) were used to predict DCI. Sensitivity, specificity, and area under the curve (AUC) were determined, and logistic regression analysis was performed. RESULTS: The Combined Severity Score showed an AUC 0.64 (95%CI 0.56-.71) at days 2-5, with sensitivity 0.53 and specificity 0.74. The Combined Severity Score had an adjusted Odds Ratio of 3.41 (95CI 1.86-6.32) for DCI. MCA-measurements yielded the highest AUC to detect DCI at day 2-5: AUC 0.65 (95%CI 0.58-0.73). Optimal cutoff MFV of 83 cm/s for MCA resulted in sensitivity 0.73 and specificity 0.50 at days 2-5. CONCLUSION: TCD-monitoring of aSAH patients may be a valuable strategy for DCI risk stratification. Lower cutoff values can be used in the early phase after the ictus (day 2-5) than are commonly used now. The Combined Severity Score incorporating all major cerebral arteries may provide a meaningful contribution to interpreting TCD measurements.

Low revision rate throughout the adoption of the direct superior approach in primary total hip arthroplasty: an analysis based on 1551 total hip arthroplasties from the Dutch Arthroplasty Register.

BACKGROUND: Recently, surgeons introduced a minimally invasive modification on the classic posterolateral approach (PLA) in total hip arthroplasty (THA): the direct superior approach (DSA). We investigated the association between surgeon's experience and the risk of early revision of the DSA in primary THA, using data from the Dutch Arthroplasty Register (LROI). METHODS: We retrieved all primary THAs performed using the DSA in 4 hospitals between 2016 and 2022 (n = 1551). Procedures were sorted in 5 groups using the date of operation and number of previous procedures per surgeon: 1-25; 26-50; 51-75; 76-100; >100. Subsequently, data from different surgeons were pooled together and the risk of revision was calculated via a multilevel time-to-event analysis. RESULTS: The overall revision rate was 1.5% after a mean follow-up of 2 years. Patients from the 1-25 group had comparable risks of revision compared to patients in the >100 group (hazard ratio [HR] 1.0 [CI, 0.3-3.2]). The risk for patients in groups 26-50, 51-75 and 75-100 was also not statistically different from the >100 group (resp. HR 1.5 [CI, 0.5-5.0], 1.8 [CI, 0.5-6.4] and 0.5 [CI, 0.1-4.0]). Main reasons of revision were dislocation (0.5%) and infection (0.4%). CONCLUSIONS: We did not identify an association between the surgeon's experience and the early risk of revision for the DSA in primary THA in the Netherlands. The DSA seems safe in the early adoption phases with a low risk of revision due to dislocation and revision for all other causes.

A New Procedure-Based Assessment of Operative Skills in Gastric Bypass Surgery, Evaluated by Video Fragment Rating.

PURPOSE: Feedback on technical and procedural skills is essential during the training of residents and fellows. The aim of this study was to assess the performance of a newly created instrument for the assessment of operative skills using laparoscopic Roux-en-Y gastric bypass (LRYGB) video fragments. MATERIALS AND METHODS: A new procedure-based assessment (PBA) was created by combining LRYGB key steps with a 5-point independence scale. LRYGB performed by residents and surgeons with different levels of expertise were video recorded. Fragments of the pouch creation, gastro-jejunostomy and jejunojejunostomy, were review by 12 expert bariatric surgeons and the operative skills assessed with the PBA, Objective Structured Assessment of Technical Skill (OSATS), and the Bariatric OSATS (BOSATS). The PBA was compared to the OSATS and BOSATS. Mean scores for all items of the different assessments were summarized and compared using a T-test. RESULTS: The scores of the procedural steps were combined and compared for all levels. The mean scores for beginner, intermediate, and expert level were 2.71, 3.70, and 3.90 for the PBA; for the OSATS 1.84, 2.86, and 3.44; and for the BOSATS 2.78, 3.56, and 4.19. Each of these assessments differentiated between the three skill levels (all p < 0.05). CONCLUSION: The PBA discriminates well between different levels of operative skills. Similar patterns were found for the OSATS and BOSATS, showing that the randomly selected video fragments are representative samples for assessing skill level. Future research will demonstrate whether these results can be extrapolated to clinical training, and which scores allow for procedure certification.

Effect of Previous INR Control during VKA Therapy on Subsequent DOAC Adherence and Persistence, in Patients Switched from VKA to DOAC.

INTRODUCTION: Current guideline suggests a switch from vitamin K antagonist (VKA) to direct oral anticoagulant (DOAC) in patients with low time in therapeutic range (TTR < 70%). Poor international normalized ratio (INR) control may be the result of poor compliance, and might therefore be associated with subsequent DOAC intake. Therefore, this study evaluates the effect of previous TTR and other measures of INR control on DOAC nonadherence and nonpersistence, in patients who switched from VKA to DOAC. METHODS: A total of 437 patients who switched from VKA to DOAC between 2012 and 2019 were included using data from Certe Thrombosis Service, IADB.nl pharmacy community database University Groningen, and Statistics Netherlands. DOAC prescriptions were used to determine nonadherence and nonpersistence. INR control (i.e., TTR, time under therapeutic range [TUR], and INR variability) was assessed during the last 180 days of VKA use. Multivariable regression models were applied to determine the association between INR control and DOAC nonpersistence/nonadherence. RESULTS: On VKA, 67.7% of the patients had a TTR below 70%. DOAC nonpersistence was 39.8% (95% confidence interval [CI]: 33.4-45.5%) during a median follow-up of 34.4 months (interquartile range: 19.1-49.2). Approximately 80% of persistent patients were DOAC-adherent. Low TTR was not associated with DOAC nonpersistence (hazard ratio: 1.14, 95% CI: 0.69-1.87) and DOAC nonadherence (odds ratio: 1.38, 95% CI: 0.67-2.84), nor were TUR and INR variability. CONCLUSION: Previous INR control during VKA therapy is not associated with subsequent DOAC nonadherence and nonpersistence. This study suggests that INR control on VKA cannot, and therefore should not, be used for predicting DOAC adherence or persistence.

The Diagnostic Value of Near-Infrared Spectroscopy to Predict Delayed Cerebral Ischemia and Unfavorable Outcome After Subarachnoid Hemorrhage.

OBJECTIVE: Near-infrared spectroscopy (NIRS) is a noninvasive tool to monitor cerebral regional oxygen saturation. Impairment of microvascular circulation with subsequent cerebral hypoxia during delayed cerebral ischemia (DCI) is associated with poor functional outcome after subarachnoid hemorrhage (SAH). Therefore, NIRS could be useful to predict the risk for DCI and functional outcome. However, only limited data are available on NIRS regional cerebral tissue oxygen saturation (rSO2) distribution in SAH. The aim of this study was to compare the distribution of NIRS rSO2 values in patients with nontraumatic SAH with the occurrence of DCI and functional outcome at 2 months. In addition, the predictive value of NIRS rSO2 was compared with the previously validated SAFIRE grade (derived from Size of the aneurysm, Age, FIsher grade, World Federation of Neurosurgical Societies after REsuscitation). METHODS: In this study, the rSO2 distribution of patients with and without DCI after SAH was compared. The optimal cutoff points to predict DCI and outcome were assessed, and its predictive value was compared with the SAFIRE grade. RESULTS: Of 41 patients, 12 developed DCI, and 9 had unfavorable outcome at 60 days. Prediction of DCI with NIRS had an area under the curve of 0.77 (95% confidence interval 0.62-0.92; P = 0.0028) with an optimal cutoff point of 65% (sensitivity 1.00; specificity 0.45). Prediction of favorable outcome with NIRS had an area under the curve of 0.86 (95% confidence interval 0.74-0.98; P = 0.0003) with an optimal cutoff point of 63% (sensitivity 1.00; specificity 0.63). Regression analysis showed that NIRS rSO2 score is complementary to the SAFIRE grade. CONCLUSIONS: NIRS rSO2 monitoring in patients with SAH may improve prediction of DCI and clinical outcome after SAH.

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.

Assessment methods in laparoscopic colorectal surgery: a systematic review of available instruments.

BACKGROUND: Laparoscopic surgery has become the golden standard for many procedures, requiring new skills and training methods. The aim of this review is to appraise literature on assessment methods for laparoscopic colorectal procedures and quantify these methods for implementation in surgical training. MATERIALS AND METHODS: PubMed, Embase and Cochrane Central Register of Controlled Trials databases were searched in October 2022 for studies reporting learning and assessment methods for laparoscopic colorectal surgery. Quality was scored using the Downs and Black checklist. Included articles were categorized in procedure-based assessment methods and non-procedure-based assessment methods. A second distinction was made between capability for formative and/or summative assessment. RESULTS: In this systematic review, nineteen studies were included. These studies showed large heterogeneity despite categorization. Median quality score was 15 (range 0-26). Fourteen studies were categorized as procedure-based assessment methods (PBA), and five as non-procedure-based assessment methods. Three studies were applicable for summative assessment. CONCLUSIONS: The results show a considerable diversity in assessment methods with varying quality and suitability. To prevent a sprawl of assessment methods, we argue for selection and development of available high-quality assessment methods. A procedure-based structure combined with an objective assessment scale and possibility for summative assessment should be cornerstones.

Adherence to protocols for the use of reversal agents in patients treated with direct oral anticoagulants.

OBJECTIVES: This study aimed to evaluate the adherence to protocols for the use of reversal agents in direct oral anticoagulant (DOAC) users in Dutch hospitals. METHODS: A retrospective cohort study was conducted in seven hospitals in the Netherlands. Treatment protocols for bleeding and (urgent) procedures in patients on DOAC were collected from each hospital. All patient data on the use of reversal agents were retrospectively collected from September 2021 to April 2022 and compared to the protocols. The degree of per-protocol adherence (compliance score) was categorized into four levels as follows: poor (<45%), moderate (45-79%), high (80-89%), and full (> 90%) adherence rates. RESULTS: A total of 290 patients were included in our study. In patients with bleeding under DOAC, the protocol adherence for prothrombin complex concentrate (PCC) was "moderate" (61%). In the remaining cases (39%), non-adherence was mainly caused by underdosing (68%), overdosing (12%), and a lack of indication (14%). Furthermore, idarucizumab was administered for bleeding with "full" adherence (96%). For andexanet alfa, adherence to the hospital bleeding protocol was "moderate" (67%), with a lack of indication being the only reason for non-adherence. In case of reversal for an urgent procedure, the protocol adherence for PCC was "low" (45%), with underdosing, a lack of indication, and missing lab data being the main reasons for non-adherence. Missing lab data on dabigatran plasma concentration before reversal was the main reason for "low" adherence (26%) in idarucizumab. The adherence for andexanet alfa was also "low" (0%). CONCLUSION: In case of reversal for bleeding under DOAC, overall adherence to the protocol was "moderate"; however, in patients needing an urgent procedure, it was "low." The major reasons for non-adherence were underdosing, off-label use, and a lack of specific lab testing. The results of this study can assist in improving the implementation of hospital protocols.

Treatment patterns in older patients with myelodysplastic syndromes: A population-based analysis reflecting the real world.

INTRODUCTION: Treatment for myelodysplastic syndromes (MDS) is complex, options are limited, and insight into consecutive treatments is lacking. We performed this study to assess the outcomes in a real-world cohort of patients with MDS. MATERIALS AND METHODS: An observational population-based study was performed using the HemoBase registry. Treatment patterns and overall survival (OS) were analyzed with Kaplan-Meier analyses. RESULTS: In 144 of 280 (51.4%) patients with MDS >50 years, first-line treatment was initiated. The median age was 75.1 years (range: 52.6-92.0); the majority were male (72.2%). Hypomethylating agents (HMA), intensive chemotherapy, lenalidomide, and erythropoiesis-stimulating agents (ESA) were given as first-line treatment to 31.1% (n = 45), 12.5% (n = 18), 2.8% (n = 4), and 53.5% (n = 77) of the population, respectively. The median treatment duration was 5.8 months (95% Confidence Interval [CI]: 1.1-10.4) for HMA, 1.7 months (95%CI: 0.9-2.6) for intensive chemotherapy, 10.8 months (95%CI: 4.7-17.0) for lenalidomide, and 14.8 months (95%CI: 11.4-18.1) for ESA. Consecutive treatments were given to 27.2% of patients. The main reasons for first-line treatment discontinuation were treatment failure (45.8%), toxicity (6.9%), or death (20.1%). Median OS after termination of the initial, second, and third treatment was 5.8 months (95%CI: 3.2-8.5), 9.3 months (95%CI: 0.0-19.6), and 1.0 months (95%CI: 0.0-5.1), respectively. DISCUSSION: This study shows the treatment outcomes in a real-world population of older patients with MDS. Treatment duration and median OS after treatment discontinuation were relatively limited. There is still an urgent need for new treatment options, strategies to further optimize duration of existing treatments, and communication of realistic treatment goals and expectations, especially for older, higher-risk patients with MDS with a poor prognosis.

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.

Protocolized management of bleeding in hospitals in The Netherlands in patients treated with direct oral anticoagulants.

OBJECTIVE: To investigate and describe the protocolized treatment of DOAC-related bleeds in all Dutch hospitals. METHODS: From August to December 2020 a nationwide survey among all 70 hospitals in the Netherlands was conducted on their protocols for management of bleeding in patients treated with direct oral anticoagulants (DOACs, i.e. apixaban, edoxaban, rivaroxaban and dabigatran). The protocols were assessed the following characteristics: bleeding definitions (mild, moderate and severe bleed), diagnostic parameters (hemoglobin [Hb], loss of blood, surgical procedure needed, etc), first and second choice of treatment, effectiveness criteria and the level of evidence/references upon which protocols were based. RESULTS: All 70 hospitals responded (100%). We received 69 protocols in total, 6 of which were identical because hospitals worked together. In 35 (50%) of the protocols a definition of minor, moderate or severe bleeds was described. Diagnostic parameters for bleeds were present in 2%, 41% and 47% of protocols for a mild, moderate and severe bleed. While the first choice treatment for severe bleeding under dabigatran was idarucizumab in 96% of protocols, considerably more therapeutic options (mostly different prothrombin complex concentrate (PCC) doses) are described for Xa inhibitors. When considering criteria for effectiveness more than 90% of protocols did not have a clear description. CONCLUSION: This study provides an overview of the current state of protocols for management of DOAC-related bleeding in The Netherlands. Protocols vary in the content of information provided and often do not include information, especially for diagnostic criteria and criteria for establishing the effectiveness of the intervention. The results of this study can assist in improving and harmonizing the protocols.

Protocols for perioperative management of direct oral anticoagulants in hospitals: opportunities for improvement.

OBJECTIVES: To investigate and describe the protocolized perioperative management in patient using Direct oral anticoagulants (DOACs) in Dutch hospitals. METHODS: Between August and December 2020, a nationwide survey in 70 hospitals in the Netherlands was conducted. We asked hospital pharmacists to submit their protocols for perioperative management of DOAC (apixaban, dabigatran, edoxaban and rivaroxaban) users. The protocols were assessed for a number of parameters divided into categories: interruption and restart timetables DOACs for elective procedures, criteria for the start of an urgent procedure without antidotes, criteria for the use of antidotes and advised antidotes for urgent procedures. RESULTS: A total of 49 hospitals (70%) sent a protocol for perioperative management of DOACs. Two pairs of protocols were identical because hospitals cooperated closely, leaving 47 individual protocols for analysis. Thirty-five of these protocols contained a policy for both elective and urgent procedure; five protocols contained only a policy for elective and seven only for urgent procedures. In protocols for elective procedure, we found great variation in interruption and restart timetables intended for patients with renal impairment (Estimated Glomerular Filtration Ratio < 80 ml/min). In case of urgent procedures, there is variation in choice of antidote, criteria for administration of an antidote and antidote dosing. CONCLUSION: This study provides an overview of the current state of the perioperative protocols in the Netherlands in patients treated with direct oral anticoagulants. Protocols are often not complete and show important and unwanted variation. We have found that national guidelines do not provide unambiguous advice on all points (urgent procedures) and are therefore often elaborated at a local level. The results of this research can help in improving and harmonizing the perioperative protocols on a national level.

High-flow nasal cannula oxygen therapy for admitted COPD-patients. A retrospective cohort study.

BACKGROUND: The use of High-flow nasal cannula (HFNC) is increasing in admitted COPD-patients and could provide a step in between non-invasive ventilation (NIV) and standard oxygen supply. Recent studies demonstrated that HFNC is capable of facilitating secretion removal and reduce the work of breathing. Therefore, it might be of advantage in the treatment of acute exacerbations of COPD (AECOPD). No randomized trials have assessed this for admitted COPD-patients on a regular ward and only limited data from non-randomized studies is available. OBJECTIVES: The aim of our study was to identify the reasons to initiate treatment with HFNC in a group of COPD-patients during an exacerbation, further identify those most likely to benefit from HFNC treatment and to find factors associated with treatment success on the pulmonary ward. MATERIAL AND METHODS: This retrospective study included COPD-patients admitted to the pulmonary ward and treated with HFNC from April 2016 until April 2019. Only patients admitted with severe acute exacerbations were included. Patients who had an indication for NIV-treatment where treated with NIV and were included only if they subsequently needed HFNC, e.g. when they did not tolerate NIV. Known asthma patients were excluded. RESULTS: A total of 173 patients were included. Stasis of sputum was the indication most reported to initiate HFNC-treatment. Treatment was well tolerated in 83% of the patients. Cardiac and vascular co-morbidities were significantly associated with a smaller chance of successful treatment (Respectively OR = 0.435; p = 0.013 and OR = 0.493;p = 0.035). Clinical assessment judged HFNC-treatment to be successful in 61% of the patients. Furthermore, in-hospital treatment with NIV was associated with a higher chance of HFNC failure afterwards (OR = 0.439; p = 0.045). CONCLUSION: This large retrospective study showed that HFNC-treatment in patients with an AECOPD was initiated most often for sputum stasis as primary reason. Factors associated with improved outcomes of HFNC-treatment was the absence of vascular and/or cardiac co-morbidities and no need for in-hospital NIV-treatment.

Increased prescription rate of anti-infective agents after diagnosis of myelodysplastic syndromes.

The a priori risk for infections in patients with myelodysplastic syndromes (MDS) is unknown. This study examines prescription rates of anti-infective agents in MDS patients before and after diagnosis, in both in- and outpatient settings, to provide information on infection management in clinical practice. We performed a population-based study using the HemoBase registry, containing data of all MDS patients diagnosed since 2005 in Friesland, the Netherlands. Community and hospital pharmacies provided prescription data from 1995 to 2020. Data were obtained for 203 of 292 patients (70%). Patients received significantly more anti-infective agents, predominantly antibacterials (70%), after diagnosis compared to before: 148.7 defined daily dose/1000 days (DID) (95% CI: 146.9-150.5) and 55.1 DID (95% CI: 54.5-55.8, p < 0.01), respectively, corresponding to median 23.5 and 7.6 treatment days/year. Higher-risk (449.9 DID) and lower-risk patients (129.1 DID) both received significantly more anti-infective agents after diagnosis; comorbidities, neutropenia, and age did not show significant differences relative to prescription rates. Before diagnosis, 10% of patients had infection-related hospital admissions versus 38% after diagnosis. In conclusion, MDS patients received significantly more anti-infective agents compared to before diagnosis. This is the first study that has quantified the prescription rate of anti-infective agents within and beyond the clinical setting in MDS.

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.

Impact of minor bleeds on confidence in anticoagulation therapy, adherence to treatment and quality of life in patients using a non-vitamin K antagonist oral anticoagulant for atrial fibrillation.

OBJECTIVE: In a previous study on the reasons for discontinuation of novel oral anticoagulation therapy (NOAC) in patients with atrial fibrillation, we showed that minor bleeding was the second most important reason for NOAC discontinuation. This finding suggest that the impact of minor bleeds on the patient's perspective on NOACs cannot be ignored, especially those minor bleeds for which the patient searched medical care. We therefore performed a study in which we explored the impact of minor bleed (clinically relevant non-major bleeds) on patient confidence in therapy, adherence to treatment and quality of life in AF patients using NOAC's. METHODS: Details on NOAC therapy, level of confidence, adherence and quality of life were assessed using a semi-structured telephone interview. Questions related to annoyance, concern and trust were scored on a scale of 1-10, with score 10 representing the highest level of impact or trust. For the adherence to treatment before and after a minor bleed the Medication Adherence Rating Scale (MARS-5) questionnaire was used. The total MARS-5 score ranges from 5 to 25; score 5 is indicative of poor adherence and 25 suggest perfect adherence. Furthermore, the impact (restrictions) of a bleed on physical activities and daily life was assessed using a VAS score ranging from 1 to 10; score 10 representing the highest level of restriction. RESULTS: A total of 142 patients were included. During NOAC treatment, minor bleeds were reported by 87 patients (61%) of whom 16 (11%) suffered from a CRNMB. All patients that suffered from a CRNMB contacted their treating physician and 13 received treatment. The most frequently reported CRNMBs were epistaxis (n = 6), a bleed after injury (n = 3), rectal bleed (n = 2) and an eye bleed (n = 2). With regard to the impact of a CRNMB, the median level of annoyance was 8 (min-max 2-10)) and the level of concern 4 (min-max 1-10). The MARS-5 score for adherence to treatment was only marginally influenced. Also the level of trust remained high after the CRNMB. Out of 12 patients, only 2 patients reported a reduction of 1 and 8 points, respectively. Ten patients scored no change and one patient scored a 1 point increase in the level of trust. The mean reduction in trust was 0.7 (95%CI -0.8 to 2.2). With regard to the reported restrictions on physical activities, 8 out of 12 patients reported no (score 1) or only marginal impact (score 2), 2 patients reported a moderate impact (score 5 and 6) and 2 patients reported a high impact score 7 (mean score 2.9 (95%CI 1.3-4.5). For the daily life impact question, 5 out of 9 patients reported no or only marginal impact, 3 patients reported a moderate impact (scores 4 and 5) and 1 patient reported maximal impact (score 10) (mean score 3.2 (95%CI 0.9-5.5)). CONCLUSION: In our study the level of trust, annoyance and concern were not significantly impacted by the CRNMB, nor the adherence to treatment and impact on daily life and physical activities. However, on an individual basis, there were patients that reported a high impact. We hope that future data on impact of this type of minor bleeds will help us identify and guide suboptimaly adherent NOAC patients in shared decision manner.

Management of infection prophylaxis in Dutch patients with myelodysplastic syndromes, a web-based case vignette questionnaire: The MINDSET study.

OBJECTIVES: Infections are a major cause of morbidity and mortality in patients with myelodysplastic syndromes (MDS). The objective of the MINDSET study was to evaluate haematologists' management of infection prevention in MDS patients using a case vignette study and to assess the availability of guidelines. METHODS: We conducted a web-based, nationwide survey amongst haematologists in the Netherlands between September and December 2021. The survey included a set of case vignettes. In addition, the availability of protocols was evaluated. RESULTS: Sixty responses were obtained (23.6%). These responses were well distributed across hospital types as well as level of experience. No protocols regarding infection prophylaxis specifically for MDS patients were received. In the case vignette of a 75-year-old MDS patient, respondents would primarily prescribe infection prophylaxis in case of recurrent infections (96.7%) and neutropenia (75.0% for absolute neutrophil count [ANC] < 0.2 × 109 /L and 53.3% for ANC < 0.5 × 109 /L), especially in combination with hypomethylating agents (80.0%), lenalidomide (66.7%) or chemotherapy (51.7%). Respondents would predominantly choose antibacterial agents (85.0%), followed by antifungal agents (71.7%). CONCLUSIONS: This study showed diverse reasons and considerations of haematologists regarding whether to prescribe infection prophylaxis in MDS patients. Given the seriousness of infections in MDS patients, patient-tailored recommendations might be valuable in clinical decision-making.

Thromboembolic Events While Taking Direct Oral Anticoagulants: An Analysis of Post-market WHO Database Reports from 2012 to 2020.

BACKGROUND AND OBJECTIVE: Several cases of venous thromboembolism in patients treated with direct oral anticoagulants (DOACs) have been reported in the literature, but a quantative analysis of postmarketing reports is lacking. The objective of this study was to determine the post-marketing odds ratio (OR) and reporting odds ratio (ROR) of venous thromboembolism in patients receiving DOACs compared among each other and to vitamin K antagonists (VKAs). METHODS: The OR and ROR were used to determine the ratio of reports for deep vein thrombosis and pulmonary embolism between 1 January, 2012 and 15 November, 2020 using the World Health Organization VigiLyze database. This was performed using all venous thromboembolism events in which a DOAC or a VKA was the suspected medication. The OR and ROR including 95% confidence intervals were calculated for each DOAC drug in comparison to all VKAs as a group. RESULTS: The OR of deep vein thrombosis was highest for rivaroxaban compared with dabigatran and apixaban [2.63 (2.41-2.89); 1.84 (1.72-1.97)]. The OR of deep vein thrombosis was lowest for edoxaban compared with dabigatran, apixaban and rivaroxaban [0.44 (0.32-0.61); 0.31 (0.22-0.42); 0.17 (0.12-0.23)]. The OR of pulmonary embolism was also highest for rivaroxaban compared with dabigatran and apixaban [2.59 (2.37-2.83); 1.79 (1.68-1.92)]. The OR of pulmonary embolism was also lowest for edoxaban compared with dabigatran, apixaban and rivaroxaban [0.77 (0.60-0.97); 0.59 (0.41-0.67); 0.30 (0.23-0.37)]. Comparing RORs of various DOACs with VKAs, rivaroxaban had the highest RORs for deep vein thrombosis/pulmonary embolism, in comparison to apixaban, dabigatran and edoxaban. CONCLUSIONS: Our findings may indicate a higher association between rivaroxaban therapy and venous thromboembolism as compared with apixaban, dabigatran and edoxaban. These findings are uncertain owing to the reliability of a post-marketing registration system that is negatively influenced by a high level of under-reporting. However, based on pharmacodynamics, we cannot exclude the possibility that there is a real effect that may be driven by non-adherence.

Optical imaging compared to clinical examination in 484 rheumatoid arthritis patients: the Leeuwarden Handscan Registry.

The Handscan is a novel objective optical imaging device for disease follow-up and management in rheumatoid arthritis patients. We aim to examine the association between the baseline outcomes of the Handscan, disease activity levels and joint swelling. The Handscan measures differences in laser light absorption between joints of fingers and wrists and adjacent reference tissue, indicating the presence or absence of inflammation. The device gives an optical spectral transmission (OST) index per joint. The average of these indices is represented in the total optical score (TOS). Associations between TOS and DAS28 at subject level and OST and swelling at joint level were examined. 484 RA patients were included. Compared to patients with high disease activity (defined by DAS28), TOS was significantly lower in patients with moderate (estimated coefficient B: - 7.09, P < 0.001), low disease activity (B: - 6.99, P < 0.001) and patients in remission (B: - 7.72, P < 0.001) but could not distinguish between the latter three disease states. TOS was significantly lower in females (B: - 3.2, P < 0.001). OST was significantly higher in swollen than non-swollen joints (B: 0.28, P < 0.001). TOS was significantly higher in patients with high disease activity than in those in remission or with low and moderate disease activity. The difference in TOS between males and females should be accounted for in the interpretation of this outcome. The OST at joint level discriminates swollen from non-swollen joints and could be a more promising tool than the overall optical activity reflected in TOS.