Physicians Report Barriers to Deliver Best Practice Care for Asplenic Patients: A Cross-Sectional Survey

Background: Current management of asplenic patients is not in compliance with best practice standards, such as defined by the British Committee for Standards in Haematology. To improve quality of care, factors inhibiting best practice care delivery need to be identified first. With this study, we aimed to identify and quantify physicians' barriers to adhere to best practice management of asplenic patients in the Netherlands. Methods and Principal Findings: A cross-sectional survey, preceded by multiple focus group discussions, was performed among Dutch physicians responsible for prevention of infections in asplenic patients, including specialists ( of Internal medicine and Surgery) and general practitioners (GPs). Forty seven GPs and seventy three hospital specialists returned the questionnaire, yielding response rates of 47% and 36,5% respectively. Physicians reported several barriers to deliver best practice. For both GPs and specialists, the most frequently listed barriers were: poor patient knowledge (> 80% of hospital specialists and GPs) and lack of clarity about which physician is responsible for the management of asplenic patients (50% of Internists, 46% of Surgeons, 55% of GPs). Both GPs and hospital specialists expressed to experience a lack of mutual trust: specialists were uncertain whether the GP would follow their advice given on patient discharge (33-59%), whereas half of GPs was not convinced that specialists' discharge letters contained the correct recommendations. Almost all physicians (> 90%) indicated that availability of a national guideline would improve adherence to best practice, especially if accessible online. Conclusion: This study showed that, in accordance with reports on international performance, care delivery for asplenic patients in the Netherlands is suboptimal. We identified and quantified perceived barriers by physicians that prevent adherence to post-splenectomy guidelines for the first time. Better transmural collaboration and better informed patients are likely to improve the quality of care of the asplenic patient population. A national, online-available guideline is urgently require

Quenched phosphorescence as alternative detection mode in the chiral separation of methotrexate by electrokinetic chromatography

Quenched phosphorescence was used, for the first time, as detection mode in the chiral separation of methotrexate (MTX) enantiomers by electrokinetic chromatography. The detection is based on dynamic quenching of the strong emission of the phosphorophore 1-bromo-4-naphthalene sulfonic acid (BrNS) by MTX under deoxygenated conditions. The use of a background electrolyte with 3 mg/mL 2-hydroxypropyl-β-cyclodextrin and 20% MeOH in 25 mM phosphate buffer (pH 7.0) and an applied voltage of 30 kV allowed the separation of l-MTX and its enantiomeric impurity d-MTX with sufficient resolution. In the presence of 1 mM BrNS, a detection limit of 3.2 × 10−7 M was achieved, about an order of magnitude better than published techniques based on UV absorption. The potential of the method was demonstrated with a degradation study and an enantiomeric purity assessment of l-MTX. Furthermore, l-MTX was determined in a cell culture extract as a proof-of-principle experiment to show the applicability of the method to biological samples

Diagnostic criteria and long-term outcomes in AIH-PBC variant syndrome under combination therapy

Background &amp; Aims: Autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) can co-exist in AIH-PBC, requiring combined treatment with immunosuppression and ursodeoxycholic acid (UDCA). The Paris criteria are commonly used to identify these patients; however, the optimal diagnostic criteria are unknown. We aimed to evaluate the use and clinical relevance of both Paris and Zhang criteria. Methods: Eighty-three patients with a clinical suspicion of AIH-PBC who were treated with combination therapy were included. Histology was re-evaluated. Characteristics and long-term outcomes were retrospectively compared to patients with AIH and PBC. Results: Seventeen (24%) patients treated with combination therapy fulfilled the Paris criteria. Fifty-two patients (70%) fulfilled the Zhang criteria. Patients who met Paris and Zhang criteria more often had inflammation and fibrosis on histology compared to patients only meeting the Zhang criteria. Ten-year liver transplant (LT)-free survival was 87.3% (95% CI 78.9–95.7%) in patients with AIH-PBC. This did not differ in patients in or outside the Paris or Zhang criteria (p = 0.46 and p = 0.40, respectively) or from AIH (p = 0.086). LT-free survival was significantly lower in patients with PBC and severe hepatic inflammation – not receiving immunosuppression – compared to those with AIH-PBC (65%; 95% CI 52.2–77.8% vs. 87%; 95% CI 83.2–90.8%; hazard ratio 0.52; p = 0.043). Conclusions: In this study, patients with AIH-PBC outside Paris or Zhang criteria were frequently labeled as having AIH-PBC and were successfully treated with combination therapy with similar outcomes. LT-free survival was worse in patients with PBC and hepatic inflammation than in those treated as having AIH-PBC. More patients may benefit from combination therapy. Impact and implications: This study demonstrated that patients with AIH-PBC variant syndrome treated with combined therapy consisting of immunosuppressants and ursodeoxycholic acid often do not fulfill the Paris criteria. They do however have comparable response to therapy and long-term outcomes as patients who do fulfill the diagnostic criteria. Additionally, patients with PBC and additional signs of hepatic inflammation have poorer long-term outcomes compared to patients treated as having AIH-PBC. These results implicate that a larger group of patients with features of both AIH and PBC may benefit from combined treatment. With our results, we call for improved consensus among experts in the field on the diagnosis and management of AIH-PBC variant syndrome.</p

Diagnostic criteria and long-term outcomes in AIH-PBC variant syndrome under combination therapy

Background &amp; Aims: Autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) can co-exist in AIH-PBC, requiring combined treatment with immunosuppression and ursodeoxycholic acid (UDCA). The Paris criteria are commonly used to identify these patients; however, the optimal diagnostic criteria are unknown. We aimed to evaluate the use and clinical relevance of both Paris and Zhang criteria. Methods: Eighty-three patients with a clinical suspicion of AIH-PBC who were treated with combination therapy were included. Histology was re-evaluated. Characteristics and long-term outcomes were retrospectively compared to patients with AIH and PBC. Results: Seventeen (24%) patients treated with combination therapy fulfilled the Paris criteria. Fifty-two patients (70%) fulfilled the Zhang criteria. Patients who met Paris and Zhang criteria more often had inflammation and fibrosis on histology compared to patients only meeting the Zhang criteria. Ten-year liver transplant (LT)-free survival was 87.3% (95% CI 78.9–95.7%) in patients with AIH-PBC. This did not differ in patients in or outside the Paris or Zhang criteria (p = 0.46 and p = 0.40, respectively) or from AIH (p = 0.086). LT-free survival was significantly lower in patients with PBC and severe hepatic inflammation – not receiving immunosuppression – compared to those with AIH-PBC (65%; 95% CI 52.2–77.8% vs. 87%; 95% CI 83.2–90.8%; hazard ratio 0.52; p = 0.043). Conclusions: In this study, patients with AIH-PBC outside Paris or Zhang criteria were frequently labeled as having AIH-PBC and were successfully treated with combination therapy with similar outcomes. LT-free survival was worse in patients with PBC and hepatic inflammation than in those treated as having AIH-PBC. More patients may benefit from combination therapy. Impact and implications: This study demonstrated that patients with AIH-PBC variant syndrome treated with combined therapy consisting of immunosuppressants and ursodeoxycholic acid often do not fulfill the Paris criteria. They do however have comparable response to therapy and long-term outcomes as patients who do fulfill the diagnostic criteria. Additionally, patients with PBC and additional signs of hepatic inflammation have poorer long-term outcomes compared to patients treated as having AIH-PBC. These results implicate that a larger group of patients with features of both AIH and PBC may benefit from combined treatment. With our results, we call for improved consensus among experts in the field on the diagnosis and management of AIH-PBC variant syndrome.</p

Adverse drug events caused by three high-risk drug–drug interactions in patients admitted to intensive care units:A multicentre retrospective observational study

Aims: Knowledge about adverse drug events caused by drug–drug interactions (DDI-ADEs) is limited. We aimed to provide detailed insights about DDI-ADEs related to three frequent, high-risk potential DDIs (pDDIs) in the critical care setting: pDDIs with international normalized ratio increase (INR+) potential, pDDIs with acute kidney injury (AKI) potential, and pDDIs with QTc prolongation potential. Methods: We extracted routinely collected retrospective data from electronic health records of intensive care units (ICUs) patients (≥18 years), admitted to ten hospitals in the Netherlands between January 2010 and September 2019. We used computerized triggers (e-triggers) to preselect patients with potential DDI-ADEs. Between September 2020 and October 2021, clinical experts conducted a retrospective manual patient chart review on a subset of preselected patients, and assessed causality, severity, preventability, and contribution to ICU length of stay of DDI-ADEs using internationally prevailing standards. Results: In total 85 422 patients with ≥1 pDDI were included. Of these patients, 32 820 (38.4%) have been exposed to one of the three pDDIs. In the exposed group, 1141 (3.5%) patients were preselected using e-triggers. Of 237 patients (21%) assessed, 155 (65.4%) experienced an actual DDI-ADE; 52.9% had severity level of serious or higher, 75.5% were preventable, and 19.3% contributed to a longer ICU length of stay. The positive predictive value was the highest for DDI-INR+ e-trigger (0.76), followed by DDI-AKI e-trigger (0.57). Conclusion: The highly preventable nature and severity of DDI-ADEs, calls for action to optimize ICU patient safety. Use of e-triggers proved to be a promising preselection strategy.</p

Adverse drug events caused by three high-risk drug–drug interactions in patients admitted to intensive care units:A multicentre retrospective observational study

Aims: Knowledge about adverse drug events caused by drug–drug interactions (DDI-ADEs) is limited. We aimed to provide detailed insights about DDI-ADEs related to three frequent, high-risk potential DDIs (pDDIs) in the critical care setting: pDDIs with international normalized ratio increase (INR+) potential, pDDIs with acute kidney injury (AKI) potential, and pDDIs with QTc prolongation potential. Methods: We extracted routinely collected retrospective data from electronic health records of intensive care units (ICUs) patients (≥18 years), admitted to ten hospitals in the Netherlands between January 2010 and September 2019. We used computerized triggers (e-triggers) to preselect patients with potential DDI-ADEs. Between September 2020 and October 2021, clinical experts conducted a retrospective manual patient chart review on a subset of preselected patients, and assessed causality, severity, preventability, and contribution to ICU length of stay of DDI-ADEs using internationally prevailing standards. Results: In total 85 422 patients with ≥1 pDDI were included. Of these patients, 32 820 (38.4%) have been exposed to one of the three pDDIs. In the exposed group, 1141 (3.5%) patients were preselected using e-triggers. Of 237 patients (21%) assessed, 155 (65.4%) experienced an actual DDI-ADE; 52.9% had severity level of serious or higher, 75.5% were preventable, and 19.3% contributed to a longer ICU length of stay. The positive predictive value was the highest for DDI-INR+ e-trigger (0.76), followed by DDI-AKI e-trigger (0.57). Conclusion: The highly preventable nature and severity of DDI-ADEs, calls for action to optimize ICU patient safety. Use of e-triggers proved to be a promising preselection strategy.</p

Adverse drug events caused by three high-risk drug-drug interactions in patients admitted to intensive care units: a multicentre retrospective observational study

Aims: Knowledge about adverse drug events caused by drug–drug interactions (DDI-ADEs) is limited. We aimed to provide detailed insights about DDI-ADEs related to three frequent, high-risk potential DDIs (pDDIs) in the critical care setting: pDDIs with international normalized ratio increase (INR+) potential, pDDIs with acute kidney injury (AKI) potential, and pDDIs with QTc prolongation potential. Methods: We extracted routinely collected retrospective data from electronic health records of intensive care units (ICUs) patients (≥18 years), admitted to ten hospitals in the Netherlands between January 2010 and September 2019. We used computerized triggers (e-triggers) to preselect patients with potential DDI-ADEs. Between September 2020 and October 2021, clinical experts conducted a retrospective manual patient chart review on a subset of preselected patients, and assessed causality, severity, preventability, and contribution to ICU length of stay of DDI-ADEs using internationally prevailing standards. Results: In total 85 422 patients with ≥1 pDDI were included. Of these patients, 32 820 (38.4%) have been exposed to one of the three pDDIs. In the exposed group, 1141 (3.5%) patients were preselected using e-triggers. Of 237 patients (21%) assessed, 155 (65.4%) experienced an actual DDI-ADE; 52.9% had severity level of serious or higher, 75.5% were preventable, and 19.3% contributed to a longer ICU length of stay. The positive predictive value was the highest for DDI-INR+ e-trigger (0.76), followed by DDI-AKI e-trigger (0.57). Conclusion: The highly preventable nature and severity of DDI-ADEs, calls for action to optimize ICU patient safety. Use of e-triggers proved to be a promising preselection strategy