Human fetal brain self-organizes into long-term expanding organoids.

Human brain development involves an orchestrated, massive neural progenitor expansion while a multi-cellular tissue architecture is established. Continuously expanding organoids can be grown directly from multiple somatic tissues, yet to date, brain organoids can solely be established from pluripotent stem cells. Here, we show that healthy human fetal brain in vitro self-organizes into organoids (FeBOs), phenocopying aspects of in vivo cellular heterogeneity and complex organization. FeBOs can be expanded over long time periods. FeBO growth requires maintenance of tissue integrity, which ensures production of a tissue-like extracellular matrix (ECM) niche, ultimately endowing FeBO expansion. FeBO lines derived from different areas of the central nervous system (CNS), including dorsal and ventral forebrain, preserve their regional identity and allow to probe aspects of positional identity. Using CRISPR-Cas9, we showcase the generation of syngeneic mutant FeBO lines for the study of brain cancer. Taken together, FeBOs constitute a complementary CNS organoid platform.

Genotype-dependent N-glycosylation and newly exposed O-glycosylation affect plasmin-induced cleavage of histidine-rich glycoprotein (HRG).

Histidine-rich glycoprotein (HRG) is an abundant plasma protein harboring at least three N-glycosylation sites. HRG integrates many biological processes, such as coagulation, antiangiogenic activity, and pathogen clearance. Importantly, HRG is known to exhibit five genetic variants with minor allele frequencies of more than 10%. Among them, Pro204Ser can induce a fourth N-glycosylation site (Asn202). Considerable efforts have been made to reveal the biological function of HRG, whereas data on HRG glycosylation are scarcer. To close this knowledge gap, we used C18-based LC-MS/MS to study the glycosylation characteristics of six HRG samples from different sources. We used endogenous HRG purified from human plasma and compared its glycosylation to that of the recombinant HRG produced in Chinese hamster ovary cells or human embryonic kidney 293 cells, targeting distinct genotypic isoforms. In endogenous plasma HRG, every N-glycosylation site was occupied predominantly with a sialylated diantennary complex-type glycan. In contrast, in the recombinant HRGs, all glycans showed different antennarities, sialylation, and core fucosylation, as well as the presence of oligomannose glycans, LacdiNAcs, and antennary fucosylation. Furthermore, we observed two previously unreported O-glycosylation sites in HRG on residues Thr273 and Thr274. These sites together showed more than 90% glycan occupancy in all HRG samples studied. To investigate the potential relevance of HRG glycosylation, we assessed the plasmin-induced cleavage of HRG under various conditions. These analyses revealed that the sialylation of the N- and O-glycans as well as the genotype-dependent N-glycosylation significantly influenced the kinetics and specificity of plasmin-induced cleavage of HRG.

The pleiotropic phenotype of FlbA of Aspergillus niger is explained in part by the activity of seven of its downstream-regulated transcription factors.

Inactivation of flbA in Aspergillus niger results in thinner cell walls, increased cell lysis, abolished sporulation, and an increased secretome complexity. A total of 36 transcription factor (TF) genes are differentially expressed in ΔflbA. Here, seven of these genes (abaA, aslA, aslB, azf1, htfA, nosA, and srbA) were inactivated. Inactivation of each of these genes affected sporulation and, with the exception of abaA, cell wall integrity and protein secretion. The impact on secretion was strongest in the case of ΔaslA and ΔaslB that showed increased pepsin, cellulase, and amylase activity. Biomass was reduced of agar cultures of ΔabaA, ΔaslA, ΔnosA, and ΔsrbA, while biomass was higher in liquid shaken cultures of ΔaslA and ΔaslB. The ΔaslA and ΔhtfA strains showed increased resistance to H2O2, while ΔaslB was more sensitive to this reactive oxygen species. Together, inactivation of the seven TF genes impacted biomass formation, sporulation, protein secretion, and stress resistance, and thereby these genes explain at least part of the pleiotropic phenotype of ΔflbA of A. niger.

Glycoproteomics-Compatible MS/MS-Based Quantification of Glycopeptide Isomers.

Glycosylation is an essential protein modification occurring on the majority of extracellular human proteins, with mass spectrometry (MS) being an indispensable tool for its analysis, that not only determines glycan compositions, but also the position of the glycan at specific sites via glycoproteomics. However, glycans are complex branching structures with monosaccharides interconnected in a variety of biologically relevant linkages, isomeric properties that are invisible when the readout is mass alone. Here, we developed an LC-MS/MS-based workflow for determining glycopeptide isomer ratios. Making use of isomerically defined glyco(peptide) standards, we observed marked differences in fragmentation behavior between isomer pairs when subjected to collision energy gradients, specifically in terms of the galactosylation/sialylation branching and linkage. These behaviors were developed into component variables that allowed for relative quantification of isomerism within mixtures. Importantly, at least for small peptides, the isomer quantification appeared to be largely independent from the peptide portion of the conjugate, allowing a broad application of the method.

Estimating incidence and prevalence of hip osteoarthritis using electronic health records: a population-based cohort study.

OBJECTIVE: To determine the incidence and prevalence of hip osteoarthritis (OA) in electronic health records (EHRs) of Dutch general practices by using narrative and codified data. METHOD: A retrospective cohort study was conducted using the Integrated Primary Care Information database. An algorithm was developed to identify patients with narratively diagnosed hip OA in addition to patients with codified hip OA. Incidence and prevalence estimates among people aged ≥30 were assessed from 2008 to 2019. The association of comorbidities with codified hip OA diagnosis was analysed using multivariable logistic regression. RESULTS: Using the hip OA narrative data algorithm (positive predicted value = 72%) in addition to codified hip OA showed a prevalence of 1.76-1.95 times higher and increased from 4.03% in 2008 to 7.34% in 2019. The incidence was 1.83-2.41 times higher and increased from 6.83 to 7.78 per 1000 person-years from 2008 to 2019. Among codified hip OA patients, 39.4% had a previous record of narratively diagnosed hip OA, on average approximately 1.93 years earlier. Hip OA patients with a previous record of spinal OA, knee OA, hypertension, and hyperlipidaemia were more likely to be recorded with a hip OA code. CONCLUSION: This study using Dutch EHRs showed that epidemiological estimates of hip OA are likely to be an underestimation. Using our algorithm, narrative data can be added to codified data for more realistic epidemiological estimates based on routine healthcare data. However, developing a valid algorithm remains a challenge, possibly due to the diagnostic complexity of hip pain in general practice.

Direct comparison of predictive performance of PRECISE-DAPT versus PARIS versus CREDO-Kyoto: a subanalysis of the ReCre8 trial.

BACKGROUND: Multiple scores have been proposed to guide risk stratification after percutaneous coronary intervention. This study assessed the performance of the PRECISE-DAPT, PARIS and CREDO-Kyoto risk scores to predict post-discharge ischaemic or bleeding events. METHODS: A total of 1491 patients treated with latest-generation drug-eluting stent implantation were evaluated. Risk scores for post-discharge ischaemic or bleeding events were calculated and directly compared. Prognostic performance of both risk scores was assessed with calibration, Harrell's c­statistics net reclassification index and decision curve analyses. RESULTS: Post-discharge ischaemic events occurred in 56 patients (3.8%) and post-discharge bleeding events in 34 patients (2.3%) within the first year after the invasive procedure. C­statistics for the PARIS ischaemic risk score was marginal (0.59, 95% confidence interval (CI) 0.51-0.68), whereas the CREDO-Kyoto ischaemic risk score was moderate (0.68, 95% CI 0.60-0.75). With regard to post-discharge bleeding events, CREDO-Kyoto displayed moderate discrimination (c-statistic 0.67, 95% CI 0.56-0.77), whereas PRECISE-DAPT (0.59, 95% CI 0.48-0.69) and PARIS (0.55, 95% CI 0.44-0.65) had a marginal discriminative capacity. Net reclassification index and decision curve analysis favoured CREDO-Kyoto-derived bleeding risk assessment. CONCLUSION: In this contemporary all-comer population, PARIS and PRECISE-DAPT risk scores were not resilient to independent testing for post-discharge bleeding events. CREDO-Kyoto-derived risk stratification was associated with a moderate predictive capability for post-discharge ischaemic or bleeding events. Future studies are warranted to improve risk stratification with more focus on robustness and rigorous testing.

Incidence, prevalence, natural course and prognosis of patellofemoral osteoarthritis: the Cohort Hip and Cohort Knee study.

OBJECTIVE: To examine the proportion of isolated patellofemoral osteoarthritis (PFOA) compared to tibiofemoral osteoarthritis (TFOA) in middle-aged participants with early osteoarthritis (OA) symptoms of the knee; to describe the natural course of PFOA compared with that of TFOA and to identify whether patients with PFOA have a different phenotype compared to patients with TFOA, or with combined PFOA and TFOA (combined osteoarthritis (COA)). DESIGN: Participants with early OA symptoms of the knee were selected, completed questionnaires, underwent physical examination, and had knee radiographs at baseline, and at 2 and 5 years follow-up. Based on radiographs, participants were classified as having isolated TFOA, isolated PFOA, COA, or no radiographic OA. Multivariate logistic regression was used to identify participant characteristics associated with a specific group of OA at 2 years follow-up. RESULTS: The cohort comprised 845 participants (mean age 55.9 years). At baseline, 116 had PFOA, none had TFOA or COA. Of these 116 participants, 66.3% had developed COA at 5 years follow-up. At 2 years follow-up, PFOA, TFOA and COA were present in 77 (10.8%), 39 (5.5%) and 83 (11.6%) participants, respectively. Multivariate regression analyses at 2 years follow-up showed that participants with radiographic PFOA or TFOA were not significantly different from each other with respect to signs and symptoms. CONCLUSIONS: These results suggest that OA is more likely to start in the patellofemoral joint and then progress to COA in individuals with symptoms of early knee OA. No differences in TFOA and PFOA phenotypes were determined with respect to signs and symptoms.

Defining hip pain trajectories in early symptomatic hip osteoarthritis--5 year results from a nationwide prospective cohort study (CHECK).

OBJECTIVE: To define distinct hip pain trajectories in individuals with early symptomatic hip osteoarthritis (OA) and to determine risk factors for these pain trajectories. METHOD: Data were obtained from the nationwide prospective Cohort Hip and Cohort Knee (CHECK) study. Participants with hip pain or stiffness and a completed 5-year follow-up were included. Baseline demographic, anamnestic, physical examination characteristics were assessed. Outcome was annually assessed by the Numeric Rating Scale (NRS) for pain. Pain trajectories were retrieved by latent class growth analysis (LCGA). Multinomial logistic regression was used to calculate risk ratios. RESULTS: 545 participants were included. Four distinct pain trajectories were uncovered by LCGA. We found significant differences in baseline characteristics, including body mass index (BMI); symptom severity; pain coping strategies and in criteria for clinical hip OA (American College of Rheumatology (ACR)). Lower education, higher activity limitation scores, frequent use of pain transformation as coping strategy and painful internal hip rotation were more often associated with trajectories characterized by more severe pain. No association was found for baseline radiographic features. CONCLUSION: We defined four distinct pain trajectories over 5 years follow-up in individuals with early symptomatic hip OA, suggesting there are differences in symptomatic progression of hip OA. Baseline radiographic severity was not associated with the pain trajectories. Future research should be aimed at measuring symptomatic progression of hip OA with even more frequent symptom assessment.

Development and measurement of perioperative patient safety indicators.

BACKGROUND: To improve perioperative patient safety, hospitals are implementing evidence-based perioperative safety guidelines. To facilitate this process, it is important to provide insight into current practice. For this purpose, we aimed to develop patient safety indicators. METHODS: The RAND-modified Delphi method was used to develop a set of patient safety indicators based on the perioperative guidelines. First, a core group of experts systematically selected recommendations from the guidelines. Then, an expert panel of representative professionals appraised the recommendations against safety criteria, prioritized them and reached consensus about 11 patient safety indicators. Measurability, applicability, improvement potential (based on current practice) and discriminatory capacity of each indicator were pilot tested in eight hospitals. RESULTS: Seven structure, two process and two outcome indicators were developed covering the entire perioperative care process. Most indicators showed good applicability (N=11), improvement potential (N=6) and discriminatory capacity (N=7). Four indicators were difficult to measure. Improvement opportunities concerned the use of perioperative stops, timely administration of antibiotics, availability of protocols on perioperative anticoagulants and on prospective risk analysis of medical equipment, presence of a surveillance system for postoperative wound infections, and a morbidity and mortality registration. CONCLUSIONS: Using a systematic, stepwise method 11 patient safety indicators were developed for internal assessment, monitoring and improvement of the perioperative care process. There was large variation in guideline adherence between and within hospitals, identifying opportunities for improvement in the quality of perioperative care.

Inter-observer reliability for radiographic assessment of early osteoarthritis features: the CHECK (cohort hip and cohort knee) study.

OBJECTIVE: To calculate inter-observer reliability between four different trained readers and an experienced reader on early radiographic osteoarthritis (OA) features in our early OA cohort hip and cohort knee (CHECK) cohort. METHODS: Four readers were trained by a radiologist and experienced reader to score radiographic OA features. After this training they scored the CHECK cohort. Of the 1002 participants, 38 were scored by all readers. Five different angle radiographs (three for the knee, two for the hip) at three different time points were scored and compared. Inter-observer reliability was evaluated between each of the four trained readers and the experienced reader. Separate radiographic OA features and of overall Kellgren & Lawrence (K&L) scores. In addition, reliability of progression of radiographic was determined in K&L scores and joint space narrowing (JSN). RESULTS: For hip and knee there was substantial inter-observer reliability on overall K&L scores. In the knee, JSN was scored with fair to moderate reliability, osteophytes with moderate to nearly perfect reliability, and other features with fair to substantial reliability. In the hip, reliability ranged from substantial to nearly perfect. Moderate inter-observer reliability was found for progression of OA in both knee and hip, with slightly better reliability for progression based on K&L scores than on separate features. CONCLUSION: Good inter-observer reliability can be achieved between trained readers and an experienced reader. Although JSN in the knee is scored with lower inter-observer reliability than osteophytes, this does not seem to influence overall K&L scoring. In the hip all features showed good reliability.

Meta-analysis of operative mortality and complications in patients from minority ethnic groups.

BACKGROUND: Insight into the effects of ethnic disparities on patients' perioperative safety is necessary for the development of tailored improvement strategies. The aim of this study was to review the literature on safety differences between patients from minority ethnic groups and those from the ethnic majority undergoing surgery. METHODS: PubMed, CINAHL, the Cochrane Library and Embase were searched using predefined inclusion criteria for available studies from January 1990 to January 2013. After quality assessment, the study data were organized on the basis of outcome, statistical significance and the direction of the observed effects. Relative risks for mortality were calculated. RESULTS: After screening 3105 studies, 26 studies were identified. Nine of these 26 studies showed statistically significant higher mortality rates for patients from minority ethnic groups. Meta-analysis demonstrated a greater risk of mortality for these patients compared with patients from the Caucasian majority in studies performed both in North America (risk ratio 1·22, 95 per cent confidence interval 1·05 to 1·42) and outside (risk ratio 2·25, 1·40 to 3·62). For patients from minority groups, the length of hospital or intensive care unit stay was significantly longer in five studies, and complication rates were significantly higher in ten. Methods used to identify patient ethnicity were not described in 14 studies. CONCLUSION: Patients from minority ethnic groups, in North America and elsewhere, have an increased risk of perioperative death and complications. More insight is needed into the causes of ethnic disparities to pursue safer perioperative care for patients of minority ethnicity.

Patterns of knee osteoarthritis management in general practice: a retrospective cohort study using electronic health records.

OBJECTIVE: This study determined patterns of knee osteoarthritis (OA) management by general practitioners (GPs) using routine healthcare data from Dutch general practices from 2011 to 2019. DESIGN: A retrospective cohort study was conducted using the Integrated Primary Care Information database between 2011 and 2019. Electronic health records (EHRs) of n = 750 randomly selected knee OA patients (with either codified or narrative diagnosis) were reviewed against eligibility criteria and n = 503 patients were included. Recorded information was extracted on GPs' management from six months before to three years after diagnosis and patterns of management were analysed. RESULTS: An X-ray referral was the most widely recorded management modality (63.2%). The next most widely recorded management modalities were a referral to secondary care (56.1%) and medication prescription or advice (48.3%). Records of recommendation of/referral to other primary care practitioners (e.g. physiotherapists) were found in only one third of the patients. Advice to lose weight was least common (1.2%). Records of medication prescriptions or recommendation of/referral to other primary care practitioners were found more frequently in patients with an X-ray referral compared to patients without, while records of secondary care referrals were found less frequently. Records of an X-ray referral were often found in narratively diagnosed knee OA patients before GPs recorded a code for knee OA in their EHR. CONCLUSION: These findings emphasize the importance of better implementing non-surgical management of knee OA in general practice and on initiatives for reducing the overuse of X-rays for diagnosing knee OA in general practice.

Skin pentosidine in very early hip/knee osteoarthritis (CHECK) is not a strong independent predictor of radiographic progression over 5 years follow-up.

OBJECTIVES: Age-related changes in articular cartilage are likely to play a role in the etiology of osteoarthritis (OA). One of the major age-related changes in cartilage is the accumulation of advanced glycation end products (AGEs). The present study evaluates whether pentosidine can predict radiographic progression and/or burden over 5 years follow-up in a cohort of early knee and/or hip OA. DESIGN: The 5 years follow-up data of 300 patients from cohort hip & cohort knee (CHECK) were used. Radiographic progression and burden were assessed by X-rays of both knees and hips (Kellgren and Lawrence (K&L) and Altman scores). Baseline pentosidine levels (and urinary CTXII as a comparator) were measured by high-performance-liquid-chromatography (HPLC) and enzyme linked immunosorbent assay (ELISA). Univariable and multivariable associations including baseline radiographic damage, age, gender, body mass index (BMI) and kidney function were performed. RESULTS: Both pentosidine and urinary C-terminal telopeptide of type II collagen (uCTXII) correlated with radiographic progression and burden. In general pentosidine did not have an added predictive value to uCTXII for progression nor burden of the disease. The best prediction was obtained for burden of radiographic damage (R(2) = 0.60-0.88), bus this was predominantly determined by baseline radiographic damage (without this parameter R(2) = 0.07-0.17). Interestingly, pentosidine significantly added to prediction of osteophyte formation, whereas uCTXII significantly added to prediction of JSN in multivariable analysis. CONCLUSION: Pentosidine adds to prediction of radiographic progression and burden of osteophyte formation and uCTXII to radiographic progression and burden of JSN, but overall skin pentosidine did not perform better that uCTXII in predicting radiographic progression or burden. Burden of damage over 5 years is mainly determined by radiographic joint damage at baseline.

Novel Components of the Stress Assembly Sec Body Identified by Proximity Labeling.

Sec bodies are membraneless stress-induced assemblies that form by the coalescence of endoplasmic reticulum exit sites (ERES). Through APEX2 tagging of Sec24AB, we biotinylated and identified the full complement of Sec body proteins. In the presence of biotin-phenol and H2O2 (APEX on), APEX2 facilitates the transfer of a biotin moiety to nearby interactors of chimeric Sec24AB. Using this unbiased approach comparing APEX on and off (-H2O2) conditions, we identified 52 proteins specifically enriched in Sec bodies. These include a large proportion of ER and Golgi proteins, packaged without defined stoichiometry, which we could selectively verify by imaging. Interestingly, Sec body components are neither transcriptionally nor translationally regulated under the conditions that induce Sec body formation, suggesting that incorporation of these proteins into granules may be driven instead by the aggregation of nucleating proteins with a high content of intrinsically disordered regions. This reinforces the notion that Sec bodies may act as storage for ERES, ER and Golgi components during stress.

GAGE mediates radio resistance in cervical cancers via the regulation of chromatin accessibility.

Radiotherapy (RT) resistance is a major cause of treatment failure in cancers that use definitive RT as their primary treatment modality. This study identifies the cancer/testis (CT) antigen G antigen (GAGE) as a mediator of radio resistance in cervical cancers. Elevated GAGE expression positively associates with de novo RT resistance in clinical samples. GAGE, specifically the GAGE12 protein variant, confers RT resistance through synemin-dependent chromatin localization, promoting the association of histone deacetylase 1/2 (HDAC1/2) to its inhibitor actin. This cumulates to elevated histone 3 lysine 56 acetylation (H3K56Ac) levels, increased chromatin accessibility, and improved DNA repair efficiency. Molecular or pharmacological disruption of the GAGE-associated complex restores radiosensitivity. Molecularly, this study demonstrates the role of GAGE in the regulation of chromatin dynamics. Clinically, this study puts forward the utility of GAGE as a pre-screening biomarker to identify poor responders at initial diagnosis and the therapeutic potential of agents that target GAGE and its associated complex in combination with radiotherapy to improve outcomes.

A dual role for Src homology 2 domain-containing inositol-5-phosphatase (SHIP) in immunity: aberrant development and enhanced function of b lymphocytes in ship -/- mice.

In this report, we demonstrate that the Src homology 2 domain-containing inositol-5-phosphatase (SHIP) plays a critical role in regulating both B cell development and responsiveness to antigen stimulation. SHIP(-/-) mice exhibit a transplantable alteration in B lymphoid development that results in reduced numbers of precursor B (fraction C) and immature B cells in the bone marrow. In vitro, purified SHIP(-/)- B cells exhibit enhanced proliferation in response to B cell receptor stimulation in both the presence and absence of Fcgamma receptor IIB coligation. This enhancement is associated with increased phosphorylation of both mitogen-activated protein kinase and Akt, as well as with increased survival and cell cycling. SHIP(-/)- mice manifest elevated serum immunoglobulin (Ig) levels and an exaggerated IgG response to the T cell-independent type 2 antigen trinitrophenyl Ficoll. However, only altered B cell development was apparent upon transplantation into nonobese diabetic-severe combined immunodeficient (NOD/SCID) mice. The in vitro hyperresponsiveness, together with the in vivo findings, suggests that SHIP regulates B lymphoid development and antigen responsiveness by both intrinsic and extrinsic mechanisms.

Cysteine Deprivation Targets Ovarian Clear Cell Carcinoma Via Oxidative Stress and Iron-Sulfur Cluster Biogenesis Deficit.

Aims: Current treatment options for ovarian clear cell carcinoma (OCCC) are limited to combination of platinum-based and other cytotoxic agents to which patients respond poorly due to intrinsic chemoresistance. There is therefore an urgent need to develop alternative therapeutic strategies for OCCC. Results: Cysteine deprivation suppresses OCCC growth in vitro and in vivo with no apparent toxicity. Modes of cell death induced by cysteine deprivation in OCCC are determined by their innate metabolic profiles. Cysteine-deprived glycolytic OCCC is abolished primarily by oxidative stress-dependent necrosis and ferroptosis, which can otherwise be prevented by pretreatment with antioxidative agents. Meanwhile, OCCC that relies on mitochondria respiration for its bioenergetics is suppressed through apoptosis, which can otherwise be averted by pretreatment with cysteine precursor alone, but not with antioxidative agents. Cysteine deprivation induces apoptosis in respiring OCCC by limiting iron-sulfur (Fe-S) cluster synthesis in the mitochondria, without which electron transport chain may be disrupted. Respiring OCCC responds to Fe-S cluster deficit by increasing iron influx into the mitochondria, which leads to iron overload, mitochondria damage, and eventual cell death. Innovation/Conclusion: This study demonstrates the importance of cysteine availability in OCCC that is for its antioxidative property and its less appreciated role in mitochondria respiration. Regardless of OCCC metabolic profiles, cysteine deprivation abolishes both glycolytic and respiring OCCC growth in vitro and in vivo. Conclusion: This study highlights the therapeutic potential of cysteine deprivation for OCCC.

[Prevention of perioperative cardiac complications in non-cardiac surgery: an evidence-based guideline]. / De preventie van perioperatieve cardiale complicaties bij niet-cardiale chirurgie: een evidence-based richtlijn.

Approximately 2.5% of the patients undergoing non-cardiac surgery suffer from perioperative cardiac complications. These are associated with a mortality of 20.60%, a longer stay in hospital and higher costs. The risk factors for perioperative cardiac complications are: high-risk surgery, ischaemic heart disease, a history of congestive heart failure, cerebrovascular disease, diabetes, and renal failure. Recently, the scope of medical management has shifted from assessing and treating underlying culprit coronary lesions toward coronary plaque stabilisation and prevention of myocardial oxygen supply demand mismatch. Currently, the prevention of cardiac problems consists of identification of the patients at risk, optimisation of the preoperatieve condition by modification of underlying risk factors, optimisation of the perioperative medication with adrenergic beta-antagonists, statins, and acetylsalicylic acid, adequate perioperative monitoring and measures to prevent myocardial ischaemia. These include adequate sedation and analgesia, adequate oxygenation, oxygen transport, and ventilation, and if necessary additional cardiac medication.

Development and validation of a Self-assessment Instrument for Perioperative Patient Safety (SIPPS).

BACKGROUND: Patient safety is a fundamental value of healthcare to avoid patient harm. Non-compliance with patient safety standards may result in patient harm and is therefore a global concern. A Self-assessment Instrument for Perioperative Patient Safety (SIPPS) monitoring and benchmarking compliance to safety standards was validated in a multicentre pilot study. METHODS: A preliminary questionnaire, based on the Dutch perioperative patient safety guidelines and covering international patient safety goals, was evaluated in a first digital RAND Delphi round. The results were used to optimize the questionnaire and design the SIPPS. For measurement and benchmarking purposes, SIPPS was categorized into seven main patient safety domains concerning all care episode phases of the perioperative trajectory. After consensus was reached in a face-to-face Delphi round, SIPPS was pilot-tested in five hospitals for five characteristics: measurability, applicability, improvement potential, discriminatory capacity and feasibility. RESULTS: The results of the first Delphi round showed moderate feasibility for the preliminary questionnaire (81·6 per cent). The pilot test showed good measurability for SIPPS: 99·8 per cent of requested information was assessable. Some 99·9 per cent of SIPPS questions were applicable to the selected respondents. With SIPPS, room for improvement in perioperative patient safety compliance was demonstrated for all hospitals, concerning all safety domains and all care episode phases of the perioperative trajectory (compliance 76·1 per cent). SIPPS showed mixed results for discriminatory capacity. SIPPS showed good feasibility for all items (range 91·9-95·7 per cent). CONCLUSION: A self-assessment instrument for measuring perioperative patient safety (SIPPS) compliance meeting international standards was validated. With SIPPS, improvement areas for perioperative patient safety and best practices across hospitals could be identified.

Development of the Surgical Patient safety Observation Tool (SPOT).

BACKGROUND: A Surgical Patient safety Observation Tool (SPOT) was developed and tested in a multicentre observational pilot study. The tool enables monitoring and benchmarking perioperative safety performance across departments and hospitals, covering international patient safety goals. METHODS: Nineteen perioperative patient safety observation topics were selected from Dutch perioperative patient safety guidelines, which also cover international patient safety goals. All items that measured these selected topics were then extracted from available local observation checklists of the participating hospitals. Experts individually prioritized the best measurement items per topic in an initial written Delphi round. The second (face to face) Delphi round resulted in consensus on the content of SPOT, after which the measurable elements (MEs) per topic were defined. Finally, the tool was piloted in eight hospitals for measurability, applicability, improvement potential, discriminatory capacity and feasibility. RESULTS: The pilot test showed good measurability for all 19 patient safety topics (range of 8-291 MEs among topics), with good applicability (median 97 (range 11·8-100) per cent). The overall improvement potential appeared to be good (median 89 (range 72·5-100) per cent), and at topic level the tool showed good discriminatory capacity (variation 27·5 per cent, range in compliance 72·5-100 per cent). Overall scores showed relatively little variation between the participating hospitals (variation 13 per cent, range in compliance 83-96 per cent). All eight auditors considered SPOT a straightforward and easy-to-use tracer tool. CONCLUSION: A comprehensive tool to measure safety of care was developed and validated using a systematic, stepwise method, enabling hospitals to monitor, benchmark and improve perioperative safety performance.