Loop Ileostomy Closure as a 23-Hour Stay Procedure With Preoperative Efferent Limb Enteral Stimulation: A Randomized Controlled Trial.

BACKGROUND: Loop ileostomy closure is a common procedure in colorectal surgery. Often seen as a simple operation associated with a low complication rate, it still leads to lengthy hospitalizations. Reducing postoperative complications and ileus rates could lead to a shorter length of stay and even ambulatory surgery. OBJECTIVES: This study aimed to assess the safety and feasibility of ileostomy closure performed in a 23-hour hospitalization setting using a standardized enhanced recovery pathway. DESIGN: Randomized controlled trial. SETTINGS: Two high-volume colorectal surgery centers. PATIENTS: Healthy adults undergoing elective ileostomy closure from July 2019 to January 2022. INTERVENTION: All patients were enrolled in a standardized enhanced recovery pathway specific to ileostomy closure, including daily irrigation of efferent limb with a nutritional formula for 7 days before surgery. Patients were randomly allocated to either conventional hospitalization (n = 23) or a 23-hour stay (n = 24). MAIN OUTCOME MEASURES: Primary outcome was total length of stay and secondary outcomes were 30-day rates of readmission, postoperative ileus, surgical site infections, and postoperative morbidity and mortality. RESULTS: A total of 47 patients were ultimately randomly allocated. Patients in the 23-hour hospitalization arm had a shorter median length of stay (1 vs 2 days, p = 0.02) and similar rates of readmission (4% vs 13%, p = 0.35), postoperative ileus (none in both arms), surgical site infection (0% vs 4%, p = 0.49), postoperative morbidity (21% vs 22%, p = 1.00), and mortality (none in both arms). LIMITATIONS: Due to coronavirus disease 2019, access to surgical beds was greatly limited, leading to a shift toward ambulatory surgery for ileostomy closure. The study was terminated early, which affected its statistical power. CONCLUSION: Loop ileostomy closures as 23-hour stay procedures are feasible and safe. Ileus rate might be reduced by preoperative intestinal stimulation with nutritional formula through the stoma's efferent limb, although specific randomized controlled trials are needed to confirm this association. See Video Abstract . CIERRE DE ILEOSTOMA EN ASA COMO PROCEDIMIENTO AMBULATORIO DE HORAS CON ESTMULO PREOPERATORIO ENTERAL EFERENTE ESTUDIO ALEATORIO CONTROLADO: ANTECEDENTES:El cierre de la ileostomía en asa es un procedimiento común en la cirugía colorrectal. A menudo vista como una operación simple asociada con bajas tasas de complicaciones, aún conduce a largas hospitalizaciones. La reducción de las complicaciones postoperatorias y las tasas de íleo podría conducir a una estadía hospitalaria más corta o incluso a una cirugía ambulatoria.OBJETIVOS:El presente estudio pretende evaluar la seguridad y la viabilidad del cierre de ileostomía realizadas en un entorno de hospitalización de 23 horas utilizando una vía de recuperación mejorada y estandarizada.DISEÑO:Estudio aleatorio controladoAJUSTES:Dos centros de cirugía colorrectal de gran volúmenPACIENTES:Adultos sanos sometidos a cierre electivo de ileostomía, desde Julio de 2019 hasta Enero de 2022.INTERVENCIÓN:Todos los pacientes fueron inscritos en una vía de recuperación mejorada y estandarizada específica para el cierre de la ileostomía, incluyendo la irrigación diaria de la extremidad eferente del intestino asociada a una fórmula nutricional durante 7 días previos a la cirugía. Los pacientes fueron asignados aleatoriamente en hospitalización convencional (n = 23) o a una estadía de 23 horas (n = 24).PRINCIPALES MEDIDAS DE RESULTADO:El resultado primario fue la duración total de la estadía hospitalaria y los resultados secundarios fueron las tasas de reingreso a los 30 días, el íleo postoperatorio, las infecciones de la herida quirúrgica, la morbilidad y mortalidad postoperatorias.RESULTADOS:Finalmente fueron randomizados un total de 47 pacientes. Aquellos que se encontraban en el grupo de hospitalización de 23 horas tuvieron una estadía media más corta (1 día versus 2 días, p = 0,02) y tasas similares de reingreso (4% vs 13%, p = 0,35), de íleo postoperatorio (ninguno en ambos brazos), de infección del sitio quirúrgico (0 vs 4%, p = 0,49), de morbilidad postoperatoria (21% vs 22%, p > 0,99) y de mortalidad (ninguna en ambos brazos).LIMITACIONES:Debido a la pandemia SARS CoV-2, el acceso a las camas quirúrgicas fue muy limitado, lo que llevó a un cambio hacia la cirugía ambulatoria para el cierre de ileostomías. El estudio finalizó anticipadamente, lo que afectó su poder estadístico.CONCLUSIÓN:Los cierres de ileostomía en asa como procedimientos de estadía de 23 horas son factibles y seguros. La tasa de íleo podría reducirse mediante la estimulación intestinal preoperatoria a través de la rama eferente del estoma asociada a fórmulas nutricionales, por lo que se necesitan estudios randomizados específicos para confirmar esta asociación. (Traducción-Dr. Xavier Delgadillo ).

Validating Health Economic Models With the Probabilistic Analysis Check dashBOARD.

OBJECTIVES: Health economic (HE) models are often considered as "black boxes" because they are not publicly available and lack transparency, which prevents independent scrutiny of HE models. Additionally, validation efforts and validation status of HE models are not systematically reported. Methods to validate HE models in absence of their full underlying code are therefore urgently needed to improve health policy making. This study aimed to develop and test a generic dashboard to systematically explore the workings of HE models and validate their model parameters and outcomes. METHODS: The Probabilistic Analysis Check dashBOARD (PACBOARD) was developed using insights from literature, health economists, and a data scientist. Functionalities of PACBOARD are (1) exploring and validating model parameters and outcomes using standardized validation tests and interactive plots, (2) visualizing and investigating the relationship between model parameters and outcomes using metamodeling, and (3) predicting HE outcomes using the fitted metamodel. To test PACBOARD, 2 mock HE models were developed, and errors were introduced in these models, eg, negative costs inputs, utility values exceeding 1. PACBOARD metamodeling predictions of incremental net monetary benefit were validated against the original model's outcomes. RESULTS: PACBOARD automatically identified all errors introduced in the erroneous HE models. Metamodel predictions were accurate compared with the original model outcomes. CONCLUSIONS: PACBOARD is a unique dashboard aiming at improving the feasibility and transparency of validation efforts of HE models. PACBOARD allows users to explore the working of HE models using metamodeling based on HE models' parameters and outcomes.

Cost-effectiveness analysis of transthoracic echocardiographic assessment in patients with ischemic stroke or TIA of undetermined cause.

BACKGROUND: The multicenter ATTEST study recently assessed 1084 patients with ischemic stroke or transient ischemic attack (TIA) of undetermined cause and found that routine transthoracic echocardiography (TTE) detects abnormalities with treatment implications (i.e., major cardiac sources of embolism) in only 1% of patients, of whom most (91%) also had major electrocardiographic (ECG)-abnormalities. In this study, we performed a cost-effectiveness analysis of different TTE strategies. METHODS: We compared the cost-effectiveness of three strategies of TTE assessment: (1) TTE in all patients; (2) TTE only in patients with major ECG-abnormalities; and (3) TTE not performed. Input data were derived from ATTEST and systematic literature reviews. A Markov model was developed that simulated recurrent ischemic stroke or TIA and intracranial and gastro-intestinal bleeding complications in patients with ischemic stroke or TIA of undetermined cause. Primary outcome was the additional costs per additional quality-adjusted life-year (QALY) from a Dutch societal perspective. RESULTS: Performing TTE only in patients with major ECG-abnormalities led to 0.0083 additional QALYs and €108 additional costs per patient as compared with not performing TTE (€12,987/QALY). Performing TTE in all patients resulted in 0.0005 additional QALYs and €422 additional costs per patient as compared with performing TTE only in case of major ECG-abnormalities (€805,336/QALY). CONCLUSIONS: In patients with ischemic stroke or TIA of undetermined cause, a strategy of performing TTE only in patients who also had major ECG-abnormalities resulted in the most favorable ratio of additional costs per additional QALY. This supports performing TTE only in patients, who also have major ECG-abnormalities.

Dynamic generation of photonic spatial quantum states with an all-fiber platform.

Photonic spatial quantum states are a subject of great interest for applications in quantum communication. One important challenge has been how to dynamically generate these states using only fiber-optical components. Here we propose and experimentally demonstrate an all-fiber system that can dynamically switch between any general transverse spatial qubit state based on linearly polarized modes. Our platform is based on a fast optical switch based on a Sagnac interferometer combined with a photonic lantern and few-mode optical fibers. We show switching times between spatial modes on the order of 5 ns and demonstrate the applicability of our scheme for quantum technologies by demonstrating a measurement-device-independent (MDI) quantum random number generator based on our platform. We run the generator continuously over 15 hours, acquiring over 13.46 Gbits of random numbers, of which we ensure that at least 60.52% are private, following the MDI protocol. Our results show the use of photonic lanterns to dynamically create spatial modes using only fiber components, which due to their robustness and integration capabilities, have important consequences for photonic classical and quantum information processing.

Opportunities and Barriers to the Development and Use of Open Source Health Economic Models: A Survey.

OBJECTIVES: Health economic (HE) models are routinely used to support health policy and resource allocation decisions but are often considered "black boxes" that may be prone to error and bias. Open source models (OSMs) have been advocated to increase the transparency, credibility, and reuse of HE models. Previous studies have demonstrated interest in OSMs among the health economics and outcomes research community, but the number of OSMs remains low. METHODS: We conducted an online survey of ISPOR (the leading professional society for health economics and outcomes research) members' perspectives on the usefulness of OSMs and barriers to their development and implementation. RESULTS: Respondents (N = 230) included academics (27%), pharmaceutical (or related) industry representatives (23%), health research or consulting representatives (21%), governmental or nonprofit agency representatives (10%), and others (19%). Respondents were generally not familiar with barriers to the development and adoption of OSMs. Most agreed that OSMs would improve transparency (92%), efficiency (76%), and HE model reuse (86%) and promote confidence in using HE models (75%). The use of OSMs by health technology assessment authorities was considered a very important indicator of the usefulness of OSMs by 49% of respondents. Three-quarters of respondents perceived legal concerns and the ability to transfer data as important barriers to the development and use of OSMs. CONCLUSIONS: Respondents believe that OSMs could increase the transparency, efficiency, and credibility of HE models, but that several barriers hamper their widespread adoption. Our results suggest that fundamental changes may be needed across the health economics and outcomes research community if OSMs are to become widely adopted.

Results of a randomized phase 3 study of oral sapacitabine in elderly patients with newly diagnosed acute myeloid leukemia (SEAMLESS).

BACKGROUND: Acute myeloid leukemia (AML) is fatal in elderly patients who are unfit for standard induction chemotherapy. The objective of this study was to evaluate the survival benefit of administering sapacitabine, an oral nucleoside analogue, in alternating cycles with decitabine, a low-intensity therapy, to elderly patients with newly diagnosed AML. METHODS: This randomized, open-label, phase 3 study (SEAMLESS) was conducted at 87 sites in 11 countries. Patients aged ≥70 years who were not candidates for or chose not to receive standard induction chemotherapy were randomized 1:1 to arm A (decitabine in alternating cycles with sapacitabine) received 1-hour intravenous infusions of decitabine 20 mg/m2 once daily for 5 consecutive days every 8 weeks (first cycle and subsequent odd cycles) and sapacitabine 300 mg twice daily on 3 consecutive days per week for 2 weeks every 8 weeks (second cycle and subsequent even cycles) or to control arm C who received 1-hour infusions of decitabine 20 mg/m2 once daily for 5 consecutive days every 4 weeks. Prior hypomethylating agent therapy for preexisting myelodysplastic syndromes or myeloproliferative neoplasms was an exclusion criterion. Randomization was stratified by antecedent myelodysplastic syndromes or myeloproliferative neoplasms, white blood cell count (<10 × 109 /L and ≥10 × 109 /L), and bone marrow blast percentage (≥50% vs <50%). The primary end point was overall survival (OS). Secondary end points were the rates of complete remission (CR), CR with incomplete platelet count recovery, partial remission, hematologic improvement, and stable disease along with the corresponding durations, transfusion requirements, number of hospitalized days, and 1-year survival. The trial is registered at ClinicalTrials.gov (NCT01303796). RESULTS: Between October 2011 and December 2014, 482 patients were enrolled and randomized to receive decitabine administered in alternating cycles with sapacitabine (study arm, n = 241) or decitabine monotherapy (control arm, n = 241). The median OS was 5.9 months on the study arm versus 5.7 months on the control arm (P = .8902). The CR rate was 16.6% on the study arm and 10.8% on the control arm (P = .1468). In patients with white blood cell counts <10 × 109 /L (n = 321), the median OS was higher on the study arm versus the control arm (8.0 vs 5.8 months; P = .145), as was the CR rate (21.5% vs 8.6%; P = .0017). CONCLUSIONS: The regimen of decitabine administered in alternating cycles with sapacitabine was active but did not significantly improve OS compared with decitabine monotherapy. Subgroup analyses suggest that patients with baseline white blood cell counts <10 × 109 /L might benefit from decitabine alternating with sapacitabine, with an improved CR rate and the convenience of an oral drug. These findings should be prospectively confirmed.

Polarization-independent single-photon switch based on a fiber-optical Sagnac interferometer for quantum communication networks.

An essential component of future quantum networks is an optical switch capable of dynamically routing single photons. Here we implement such a switch, based on a fiber-optical Sagnac interferometer design. The routing is implemented with a pair of fast electro-optical telecom phase modulators placed inside the Sagnac loop, such that each modulator acts on an orthogonal polarization component of the single photons, in order to yield polarization-independent capability that is crucial for several applications. We obtain an average extinction ratio of more than 19 dB between both outputs of the switch. Our experiment is built exclusively with commercial off-the-shelf components, thus allowing direct compatibility with current optical communication systems.

An economic evaluation of eribulin for advanced breast cancer treatment based on the Southeast Netherlands advanced breast cancer registry.

Background: In 2013, eribulin was reimbursed under a coverage with evidence development (CED) as third or later chemotherapy line for advanced breast cancer (ABC) patients in the Netherlands because of uncertain cost effectiveness. In 2016, the final decision of reimbursing eribulin was taken without considering the evidence collected during CED research. We analysed the cost effectiveness of eribulin versus non-eribulin chemotherapy, using real-world data.Methods: A three health states (progression-free, progressed disease, dead) partitioned survival model was developed. The SOuth East Netherlands Advanced BREast Cancer (SONABRE) registry informed the effectiveness and costs inputs. Health state utility values were obtained from the literature. Incremental cost-effectiveness ratio (ICER) between the eribulin and matched non-eribulin chemotherapy was estimated. Deterministic and probabilistic sensitivity analyses and scenario analyses were performed. The financial risk (i.e., the expected value of perfect information (EVPI) plus the expected monetary loss (eML) associated with reimbursing eribulin) and budget impact associated with reimbursing eribulin were calculated.Results: Eribulin led to higher health benefits (0.07 quality-adjusted life year (QALY)) and costs (€15,321) compared with non-eribulin chemotherapy. This resulted in an ICER of €220,608. At a €80,000 per QALY threshold, the risk of reimbursing eribulin was €9,791 per patient (EVPI €13, eML €9,778). Scaled up to the Dutch population, the estimated annual budget impact was €1.9 million and the annual risk of reimbursing eribulin was €2.7 million.Conclusion: From a Dutch societal perspective, eribulin is not cost effective when considering its list price as third and later chemotherapy line for ABC patients.

Uncertainty and Coverage With Evidence Development: Does Practice Meet Theory?

OBJECTIVES: In theory, a successful coverage with evidence development (CED) scheme is one that addresses the most important uncertainties in a given assessment. We investigated the following: (1) which uncertainties were present during the initial assessment of 3 Dutch CED cases, (2) how these uncertainties were integrated in the initial assessments, (3) whether CED research plans included the identified uncertainties, and (4) issues with managing uncertainty in CED research and ways forward from these issues. METHODS: Three CED initial assessment dossiers were analyzed and 16 stakeholders were interviewed. Uncertainties were identified in interviews and dossiers and were categorized in different causes: unavailability, indirectness, and imprecision of evidence. Identified uncertainties could be mentioned, described, and explored. Issues and ways forward to address uncertainty in CED schemes were discussed during the interviews. RESULTS: Forty-two uncertainties were identified. Thirteen (31%) were caused by unavailability, 17 (40%) by indirectness, and 12 (29%) by imprecision. Thirty-four uncertainties (81%) were only mentioned, 19 (45%) were described, and the impact of 3 (7%) uncertainties on the results was explored in the assessment dossiers. Seventeen uncertainties (40%) were included in the CED research plans. According to stakeholders, research did not address the identified uncertainty, but CED research should be designed to focus on these. CONCLUSIONS: In practice, uncertainties were neither systematically nor completely identified in the analyzed CED schemes. A framework would help to systematically identify uncertainty, and this process should involve all stakeholders. Value of information analysis, and the uncertainties that are not included in this analysis should inform CED research design.

Tunable entanglement distillation of spatially correlated down-converted photons.

We report on a new technique for entanglement distillation of the bipartite continuous variable state of spatially correlated photons generated in the spontaneous parametric down-conversion process (SPDC), where tunable non-Gaussian operations are implemented and the post-processed entanglement is certified in real-time using a single-photon sensitive electron multiplying CCD (EMCCD) camera. The local operations are performed using non-Gaussian filters modulated into a programmable spatial light modulator and, by using the EMCCD camera for actively recording the probability distributions of the twin-photons, one has fine control of the Schmidt number of the distilled state. We show that even simple non-Gaussian filters can be finely tuned to a ∼67% net gain of the initial entanglement generated in the SPDC process.

Quantum random number generation enhanced by weak-coherent states interference.

We propose and demonstrate a technique for quantum random number generation based on the random population of the output spatial modes of a beam splitter when both inputs are simultaneously fed with indistinguishable weak coherent states. We simulate and experimentally validate the probability of generation of random bits as a function of the average photon number per input, and compare it to the traditional approach of a single weak coherent state transmitted through a beam-splitter, showing an improvement of up to 32%. The ensuing interference phenomenon reduces the probability of coincident counts between the detectors associated with bits 0 and 1, thus increasing the probability of occurrence of a valid output. A long bit string is assessed by a standard randomness test suite with good confidence. Our proposal can be easily implemented and opens attractive performance gains without a significant trade-off.

Five Measurement Bases Determine Pure Quantum States on Any Dimension.

A long-standing problem in quantum mechanics is the minimum number of observables required for the characterization of unknown pure quantum states. The solution to this problem is especially important for the developing field of high-dimensional quantum information processing. In this work we demonstrate that any pure d-dimensional state is unambiguously reconstructed by measuring five observables, that is, via projective measurements onto the states of five orthonormal bases. Thus, in our method the total number of different measurement outcomes (5d) scales linearly with d. The state reconstruction is robust against experimental errors and requires simple postprocessing, regardless of d. We experimentally demonstrate the feasibility of our scheme through the reconstruction of eight-dimensional quantum states, encoded in the momentum of single photons.

Increased expression of miR-187 in human islets from individuals with type 2 diabetes is associated with reduced glucose-stimulated insulin secretion.

AIMS/HYPOTHESIS: Type 2 diabetes is characterised by progressive beta cell dysfunction, with changes in gene expression playing a crucial role in its development. MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression and therefore alterations in miRNA levels may be involved in the deterioration of beta cell function. METHODS: Global TaqMan arrays and individual TaqMan assays were used to measure islet miRNA expression in discovery (n = 20) and replication (n = 20) cohorts from individuals with and without type 2 diabetes. The role of specific dysregulated miRNAs in regulating insulin secretion, content and apoptosis was subsequently investigated in primary rat islets and INS-1 cells. Identification of miRNA targets was assessed using luciferase assays and by measuring mRNA levels. RESULTS: In the discovery and replication cohorts miR-187 expression was found to be significantly increased in islets from individuals with type 2 diabetes compared with matched controls. An inverse correlation between miR-187 levels and glucose-stimulated insulin secretion (GSIS) was observed in islets from normoglycaemic donors. This correlation paralleled findings in primary rat islets and INS-1 cells where overexpression of miR-187 markedly decreased GSIS without affecting insulin content or apoptotic index. Finally, the gene encoding homeodomain-interacting protein kinase-3 (HIPK3), a known regulator of insulin secretion, was identified as a direct target of miR-187 and displayed reduced expression in islets from individuals with type 2 diabetes. CONCLUSIONS/INTERPRETATION: Our findings suggest a role for miR-187 in the blunting of insulin secretion, potentially involving regulation of HIPK3, which occurs during the pathogenesis of type 2 diabetes.

Multivariate and subgroup analyses of a randomized, multinational, phase 3 trial of decitabine vs treatment choice of supportive care or cytarabine in older patients with newly diagnosed acute myeloid leukemia and poor- or intermediate-risk cytogenetics.

BACKGROUND: Compared with younger patients, older adults with acute myeloid leukemia (AML) generally have poorer survival outcomes and less benefit from clinical trials. A recent phase 3 trial demonstrated a trend toward improved overall survival (OS) with decitabine, a hypomethylating agent, compared with treatment choice of either cytarabine or supportive care (7.7 months, 95% CI: 6.2-9.2 vs 5.0 months, 95% CI: 4.3-6.3, respectively) in older adults with newly diagnosed AML. The current analyses investigated prognostic factors for outcomes in this trial and examined OS and responses in prespecified subgroups. METHODS: A multivariate Cox proportional hazards model was used to investigate effects of demographic and baseline characteristics, including age, sex, cytogenetic risk, AML type, ECOG Performance Status, geographic region, bone marrow blasts, platelets, and white blood cells on OS, based on mature data. Similar analyses were conducted with a logistic regression model to predict response rates. Prespecified subgroup analyses were performed for OS and response rates, also using mature data. RESULTS: Patient characteristics that appeared to negatively influence OS included more advanced age (hazard ratio [HR] 1.560 for ≥75 vs <70 years; p = 0.0010), poorer performance status at baseline (HR 0.771 for 0 or 1 vs 2; p = 0.0321), poor cytogenetics (HR 0.699 for intermediate vs poor; p = 0.0010), higher bone marrow blast counts (HR 1.355 for >50% vs ≤50%; p = 0.0045), low baseline platelet counts (HR 0.775 for each additional 100 × 109/L; p = 0.0015), and high white blood cell counts (HR 1.256 for each additional 25 × 109/L; p = 0.0151). Regarding geographic regions, patients from Western Europe had the longest median OS. Response rates favored decitabine for all subgroups investigated, including patients ≥75 years (odds ratio 5.94, p = 0.0006). CONCLUSION: Response to decitabine in AML is associated with known prognostic factors related to both patient demographics and disease characteristics. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT00260832.

Phenotypic and molecular fingerprinting of fast growing rhizobia of field-grown pigeonpea from the eastern edge of the Brazilian Pantanal.

The aim of this study was to evaluate the diversity of rhizobial isolates obtained from root nodules of pigeonpea plants grown at the eastern edge of the Brazilian Pantanal. The bacterial isolates were isolated from root nodules from field-growing pigeonpea grown in two rural settlements of the Aquidauana municipality. The bacterial isolates were characterized phenotypically by means of cultural characterization, intrinsic antibiotic resistance (IAR), salt and high incubation temperature tolerance, and amylolytic and cellulolytic activities. The molecular characterization of the bacterial isolates was carried out using amplified ribosomal DNA restriction analysis (ARDRA) and Box-polymerase chain reaction (PCR) techniques. In addition, the symbiotic performance of selected rhizobial isolates was evaluated in a greenhouse experiment using sterile substrate. The phenotypic characterization revealed that the bacterial strains obtained from pigeonpea root nodules presented characteristics that are uncommon among rhizobial isolates, indicating the presence of new species nodulating the pigeonpea plants in the Brazilian Pantanal. The molecular fingerprinting of these bacterial isolates also showed a highly diverse collection, with both techniques revealing less than 25% similarity among bacterial isolates. The evaluation of symbiotic performance also indicated the presence of microorganisms with high potential to increase the growth and nitrogen content at the shoots of pigeonpea plants. The results obtained in this study indicate the presence of a highly diversified rhizobial community nodulating the pigeonpea at the eastern edge of the Brazilian Pantanal.

Introducing Open Science in Teaching Health Economic Modelling.

Open Science is gaining ground in all research fields, including health economics and outcomes research (HEOR). However, teaching Open Science is still in its infancy. This paper describes the design, implementation and evaluation of a teaching activity focusing on introducing Open Science during a Master's course during which participants have to develop a discrete event simulation. The teaching activity was organised as a series of lectures introducing different aspects of the Open Science philosophy and practices, such as good software coding practices, version control systems and reproducible research. The participants' increase in Open Science knowledge was elicited through a survey before and after the teaching innovation. After the teaching innovation, participants' knowledge of Open Science increased and they reported an improvement in Open Science-related skills, such as using a script-based statistical software, identifying and re-using open data, and collaborative script development. During the evaluation at the end of the course, the course participants mentioned that the Open Science-related content was interesting but would fit better within a course in which broader research-related content is taught. Based on this feedback, we will most likely narrow the scope of the Open-Science-related content in this course to Open Source Modelling which may better fit the scope of the course. This paper contains links to the teaching activities we developed and other resources which may be used to design teaching activities on Open Science. Herewith, we hope to inspire other teachers in including Open Science into their teaching.

Cost-effectiveness of screening for chronic kidney disease: existing evidence and knowledge gaps.

It is well known that the worldwide prevalence of chronic kidney disease (CKD) has risen to over 10% of the general population during the past decades. Patients with CKD are at increased risk of both kidney failure and cardiovascular disease (CVD), posing a substantial health challenge. Therefore, screening for CKD is warranted to identify and treat patients early to prevent progression and complications. In this issue of the Journal, Yeo and colleagues provide an updated systematic review of the cost-effectiveness of screening for CKD in the general adult population. They show that screening for CKD in high-risk populations is cost-effective and that there is limited evidence for screening the general population. It should be noted that most studies they discuss do not consider the benefit of screening to prevent CVD in addition to preventing kidney failure, the treatment effect of novel therapeutic agents such as SGLT2 inhibitors, and the possibility of screening in a home-based setting. These three aspects will likely improve the cost-effectiveness of CKD screening, making it feasible to move towards general population screening for CKD.

Cost-effectiveness of home-based screening of the general population for albuminuria to prevent progression of cardiovascular and kidney disease.

Background: Chronic kidney disease (CKD) is often detected late, leading to substantial health loss and high treatment costs. Screening the general population for albuminuria identifies individuals at high risk of kidney events and cardiovascular disease (CVD) who may benefit from early start of preventive interventions. Previous studies on the cost-effectiveness of albuminuria population screening were inconclusive, but were based on survey or cohort data rather than an implementation study, modelled screening as performed by general practitioners rather than home-based screening, and often included only benefits with respect to kidney events. We evaluated the cost-effectiveness of home-based general population screening for increased albuminuria based on real-world data obtained from a prospective implementation study taking into account prevention of CKD as well as CVD events. Methods: We developed an individual-level simulation model to compare home-based screening using a urine collection device with usual care (no home-based screening) in individuals of the general population aged 45-80, based on the THOMAS study (Towards HOMe-based Albuminuria Screening). Cost-effectiveness was assessed from the Dutch healthcare perspective with a lifetime horizon. The costs of the screening process and benefits of preventing CKD progression (dialysis and kidney transplantation) and CVD events (non-fatal myocardial infarction, non-fatal stroke, fatal CVD event) were reflected. Albuminuria detection led to treatment of identified risk factors. The model subsequently simulated CKD progression, the occurrence of CVD events, and death. The risks of experiencing CVD events were calculated using the SCORE2 CKD risk prediction model and individual-level data from the THOMAS study. Relative treatment effectiveness, quality of life scores, resource use, and cost inputs were obtained from literature. Model outcomes were the number of CKD and CVD-related events, total costs, quality-adjusted life years (QALYs), and the incremental cost-effectiveness ratio (ICER) per QALY gained by screening versus usual care. All results were obtained through probabilistic analysis. Findings: The absolute difference between screening versus usual care in lifetime probability of dialysis, kidney transplantation, non-fatal myocardial infarction, non-fatal stroke, and fatal CVD events were 0.2%, 0.05%, 0.6%, 0.6%, and 0.2%, respectively. This led to relative decreases compared to usual care in lifetime incidence of these events of 10.7%, 11.1%, 5.1%, 4.1%, and 1.6%, respectively. The incremental costs and QALYs of screening were €1607 and 0.17 QALY, respectively, which led to a corresponding ICER of €9225/QALY. The probability of screening being cost-effective for the Dutch willingness-to-pay threshold for preventive population screening of €20,000/QALY was 95.0%. Implementing the screening in the subgroup of 45-64 years old reduced the ICER (€7946/QALY), whereas implementing screening in the subgroup of 65-80 years old increased the ICER (€10,310/QALY). A scenario analysis assuming treatment optimization in all individuals with newly diagnosed risk factors or known risk factors not within target range reduced the ICER to €7083/QALY, resulting from the incremental costs and QALY gain of €2145 and 0.30, respectively. Interpretation: Home-based screening for increased albuminuria to prevent CVD and CKD events is likely cost-effective. More health benefits can be obtained by screening younger individuals and better optimization of care in individuals identified with newly diagnosed or known risk factors outside target range. Funding: Dutch Kidney Foundation, Top Sector Life Sciences & Health of the Dutch Ministry of Economic Affairs.

Ultralow-Dose Intraoperative Computed Tomography During Endoscopic Stone Surgery: A Quality Improvement Project.

Objectives: To improve care in patients with large kidney stones using advanced intraoperative imaging techniques to reduce perioperative radiation exposure, improve stone-free rates (SFRs), and reduce the number of surgical interventions in a quality improvement project. Patients and Methods: Patients with kidney stones appropriate for percutaneous nephrolithotomy (PCNL) treatment were scheduled into a hybrid operating room for endoscopic surgery (PCNL and/or ureteroscopy) with intent to perform intraoperative CT (ICT). Imaging was performed using an Artis Zeego Care+Clear™ (Siemens) robotic-armed multiplanar fluoroscopy system with collimation to the level of the affected kidney(s). After the initial case, the proprietary CARE™ (combined applications to reduce exposure) protocol was used. When the hybrid room was unavailable, a mobile CT scanner (O-Arm; Medtronics) was used in the traditional room (n = 2). Results: Thirty-one ICTs were performed in 23 consecutive patients during endoscopic stone procedures with a median effective radiation dose of 1.39 mSv per scan, significantly less than the preoperative noncontrast CT (12.02 mSv) in the same patients (p < 0.001). Longitudinal radiation exposure associated with stone treatment significantly decreased by 83% (15.80 to 2.68 mSv, p < 0.001) compared with a similar historical PCNL cohort. Clinically significant residual stones (≥3 mm) were identified at initial ICT in eight patients (35%) and further treated in six patients. One patient had missed residual stone diagnosed 34 days after surgery, which was apparent on re-review of the ICT. Thus, final verified SFR was 87% for all stages. Mean number of procedures improved from 1.77 to 1.30 (p = 0.05) and rate of postoperative CT scans improved from 82% to 26% (p < 0.001). Conclusion: Ultralow-dose ICT was demonstrated to simultaneously improve SFR and number of staged treatments, and greatly reduce the perioperative radiation dose for our patients. The findings support the continued use of this modality to benefit all patients with large stones.