Weight Matching Research Articles

Renin–angiotensin system inhibition and mortality in patients undergoing dialysis with coronary artery disease: insights from a multi-center observational study

ABSTRACT Background While the survival benefits of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) are firmly established in the general population, their efficacy within patient undergoing dialysis with coronary artery disease (CAD) remains controversial. Methods Between January 2015 and June 2021, 1168 patients undergoing dialysis with CAD were assessed from 30 tertiary medical centers. The primary outcome was all-cause death, and the secondary outcome was cardiovascular death. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for between-group differences. Results Overall, ACEI or ARB were prescribed to 518 patients (44.3%) upon discharge. After a median follow-up of 22.2 months, 361 (30.9%) patients died, including 243 cardiovascular deaths. The use of ACEI or ARB was associated with a significantly lower risk of all-cause (25.3% vs 35.4%, hazard ratio [HR] 0.65, 95% confidence interval [CI] 0.52–0.82, p < 0.001) and cardiovascular death (17.0% vs 23.8%; HR 0.64, 95% CI 0.48–0.83, p = 0.001). These findings remained consistent across IPTW and PSM analyses. Sensitivity analyses for ACEI and ARB use separately yielded similar results. Conclusions Our findings suggested that among patients undergoing dialysis with CAD, ACEI or ARB use was associated with a lower risk of all-cause and cardiovascular death.

Evaluating the impact of brachytherapy duration on therapeutic outcomes in patients with cervical cancer

The total duration of radiotherapy for patients with cervical cancer should be limited to 56 days to optimize treatment outcomes. This study aimed to statistically evaluate the effects of extended radiotherapy duration on survival and complications in 649 patients with cervical cancer treated with brachytherapy at our institution from 2014 to 2019. All patients had undergone intensity-modulated external beam radiation therapy, with 525 receiving two-dimensional (2D) brachytherapy and 124 receiving three-dimensional (3D) brachytherapy. Using the inverse probability of treatment weighting (IPTW) and propensity score matching (PSM), clinical data regarding treatment duration, survival outcomes, and complications were analyzed. PSM revealed that overall survival (OS) did not significantly differ between patients receiving prolonged treatment (&gt;56 days) and those receiving treatment for a standard duration (&lt;56 days) (P &gt; 0.05). However, among patients who had received 2D brachytherapy, prolonged treatment correlated with increased recurrence and metastasis risks (P &lt; 0.001); this trend was not evident in patients receiving 3D brachytherapy (P = 0.287). Higher FIGO stages were associated with worse OS and higher progression risks, which persisted post-IPTW adjustment. Extended radiotherapy duration was linked to a higher incidence of rectal and bladder reactions, particularly in the 2D group. Consequently, strictly controlling radiotherapy duration for patients receiving 2D brachytherapy is essential to reduce recurrence and metastasis risks. Close monitoring of rectal and bladder reactions is also recommended.

Experience-based transition to robotic surgery in an experienced program in minimally invasive hepatobiliary surgery.

The adoption of robotic techniques in liver surgery introduces significant challenges for their safe integration within hepatobiliary surgery units. This study is designed to investigate the complexities associated with establishing a robotic surgery program. Data on robotic hepatobiliary surgeries were prospectively collected from October 2021 to October 2023. Historical cohorts from the institutional experiences for comparison were hand-assisted (HALS) and purely laparoscopic procedures (PLS). Inverse probability of treatment weighting and propensity score matching were employed to compare outcomes between PLS and robotic resections. The learning curve for robotic surgeries was evaluated by the cumulative sum method. In this study, 454 patients were enrolled (113 robotic surgeries, 157 HALS, and 184 PLS). The posterosuperior segments resections were significantly higher in the robotic group (47.8%) compared to PLS (31.5%) and HALS (35.7%). There were no conversions in the robotic group, in PLS 2.7% and HALS 3.8%. The degree of difficulty according to the median of the IWATE score and IMM score was significantly higher in the robot group (p < 0.001 and p = 0.008, respectively). No significant differences in short-term outcomes were observed between robotic procedures and PLS in a matched subset of patients. Operative efficiency and blood loss improved significantly after the 75th robotic surgery patient, with high-difficulty cases (IWATE ≥ 10) incorporated from the beginning. This study suggests that robotic liver surgery in units with prior experience in minimally invasive liver surgery offers benefits, such as a lower conversion rate and a higher rate of successful difficult resections.

Percutaneous coronary intervention vs. medical therapy in patients on dialysis with coronary artery disease in China.

The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [n=278] vs. 43.7% [n=142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs. 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.

A Multi-Criteria Decision Making for Employee Selection Using SAW and Profile Matching

Multi-criteria decision making process has been one of the fastest growing areas during the last decades depending on the change in the business sector. Multi-criteria decision making is the most important branch of operation research by which people make complex decision daily life. The major steps in the decision- making approach are selecting the most preferred alternative for the decision-maker, ranking alternatives in order of importance for selection problems, and screening alternatives for the final decision. Employees are an important element of a company that determines its progress. Conventional (manual) recruitment methods are vulnerable to non-technical factors, such as frequent duplication or invalid data. In this study, simple additive weighting and profile matching are proposed to solve the employee selection problem. This study was conducted at the (UPT) Career Development and Entrepreneurship Universitas Brawijaya Malang using data collected from written test selection in 2019. The effectiveness of both methods was analyzed using confusion matrix. The SAW method provides an accuracy rate of 94.7%, a precision rate of 87.5%, Recall rate of 91.3% and F-measure rate of 89.4%. On the other hand, profile matching method obtained the Accuracy rate of 90.4%, Precision rate of 81.4%, Recall rate of 81.4% and F-measure rate of 81.4%. Thus, it can be concluded that both methods have high accuracy values accompanied by high precision values when used for the selection process. This system can also effectively reduce the bias rate of the same data very well, as can be seen from the high recall and F-measure rates.

Red Blood Cell Transfusion for Incidence of Retinopathy of Prematurity: Prospective Multicenter Cohort Study.

Retinopathy of prematurity (ROP) is a leading cause of visual impairment and blindness in preterm infants. This study sought to investigate the association between red blood cell (RBC) transfusion and ROP in very preterm infants (VPIs) to inform clinical strategies for ROP prevention and treatment. We designed a prospective multicenter cohort study that included VPIs and follow-up data from January 2017 to December 2022 at 3 neonatal clinical medicine centers. They were categorized into a transfusion group (infants who received an RBC transfusion within 4 wk) and a nontransfusion group. The relationship between RBC transfusion and ROP incidence was assessed using binary logistic regression, with subgroup analyses based on gestational age, birth weight, sex, and sepsis status. Inverse probability of treatment weighting and propensity score matching were applied to account for all potential confounding factors that could affect ROP development, followed by sensitivity analysis. The study included 832 VPIs, including 327 in the nontransfusion group and 505 in the transfusion group. The transfusion group had a lower average birth weight and gestational age and a greater incidence of ROP, ≥stage 2 ROP, and severe ROP. Logistic regression analysis revealed that the transfusion group had a significantly greater risk of ROP (adjusted odds ratio [aOR] 1.70, 95% CI 1.14-2.53, P=.009) and ≥stage 2 ROP (aOR 1.68, 95% CI 1.02-2.78, P=.04) but not severe ROP (aOR 1.75, 95% CI 0.61-5.02, P=.30). The trend analysis also revealed an increased risk of ROP with an increasing number of transfusions and a larger volume of blood transfused (P for trend<.001). Subgroup analyses confirmed a consistent trend, with the transfusion group at a higher risk for ROP across all subgroups. Inverse probability of treatment weighting and propensity score matching analyses supported the initial findings. For VPIs, RBC transfusion significantly increases the risk of ROP, and the risk increases with an increasing number of transfusions and volume of blood transfused.

Extended Prone Position and 90-Day Mortality in Mechanically Ventilated Patients With COVID-19.

Prone positioning (PP) has demonstrated its potential for improving outcomes in patients with ARDS who require invasive mechanical ventilation. However, the ability of prolonged proning to reduce mortality in patients with COVID-19 specifically, sessions lasting > 24 h remains uncertain. In this retrospective cohort study, we examined 158 subjects with COVID-19 pneumonia who required mechanical ventilation due to moderate-to-severe ARDS. Seventy-six subjects were placed in standard PP and 82 in extended PP, defined as prone sessions lasting at least 32 h. Our primary aim was to evaluate the effect of EPP on 90-d survival in subjects with COVID-19 with acute severe respiratory failure. To ensure the reliability of our findings and to minimize bias, we applied 3 adjustment approaches: cardinality matching (CM), matching weighting (MW), and inverse probability of treatment weighting with stabilized and trimmed weights (SW). We used Kaplan-Meier curves and Cox proportional hazard models to analyze the effects of EPP on 90-d mortality and sensitivity analysis by calculating E-values. The overall crude 90-d mortality rate was 31.7%. The unadjusted 90-d mortality rates were 19.5% in the EPP group and 44.7% in the SPP group (hazard ratio [HR] 0.35 [95% CI 0.19- 0.63], P < .001). After adjustment for confounding factors using CM, MW, and SW, baseline covariates were balanced between the 2 groups. Subjects in the EPP group exhibited lower 90-d mortality rates after adjustment using CM (HR 0.42 [95% CI 0.23-0.79], P = .007), MW (HR 0.45 [95% CI 0.21-0.95], P = .036), or SW (HR 0.29 [95% CI 0.15-0.56], P < .001). Extended PP was associated with improved 90-d survival in subjects with COVID-19 undergoing mechanical ventilation for severe ARDS. These findings suggest the potential benefit of EPP in the management of COVID-19-related respiratory failure. Further research and prospective studies are warranted to confirm and elucidate the underlying mechanisms of this association.

Kidney Paired Donation-European Transnational Experience in Adults and Opportunities for Pediatric Kidney Transplantation.

Live donor kidney transplantation is considered the optimal choice for renal replacement therapy, providing established benefits, such as superior patient survival and improved quality of life. However, immunological challenges, including ABO blood group incompatibility and, particularly, donor-specific HLA antibodies, may impact long-term outcomes considerably or even prevent safe direct transplantation with the intended donor. In this review, the authors discuss kidney paired donation (KPD) as a viable strategy to overcome immunological barriers to living donation through organ exchanges. We thereby lay special focus on the Czech-Austrian transnational KPD program. While the benefits of KPD programs are well established for adult recipients, recent data suggest that this may hold true also for pediatric patients. Complex algorithms, considering factors like the intricate patterns of HLA sensitization, play a pivotal role in predicting suitable matches, but for pediatric patients also non-immunological factors including age and weight match may play a role. As pool size proves crucial for program efficacy, several countries in Europe have now initiated transnational collaborations to maximize match rates. Among those, the Czech-Austrian transnational joint program, established in 2015 and now expanded to a cooperation with the Israel transplant program to further increase transplant rates, represents a successful example. KPD programs, with their innovative approaches and international partnerships, hold promise for enhancing outcomes and addressing the increasing demand for kidney transplantation.

Minimizing confounding in comparative observational studies with time-to-event outcomes: An extensive comparison of covariate balancing methods using Monte Carlo simulation.

Observational studies are frequently used in clinical research to estimate the effects of treatments or exposures on outcomes. To reduce the effects of confounding when estimating treatment effects, covariate balancing methods are frequently implemented. This study evaluated, using extensive Monte Carlo simulation, several methods of covariate balancing, and two methods for propensity score estimation, for estimating the average treatment effect on the treated using a hazard ratio from a Cox proportional hazards model. With respect to minimizing bias and maximizing accuracy (as measured by the mean square error) of the treatment effect, the average treatment effect on the treated weighting, fine stratification, and optimal full matching with a conventional logistic regression model for the propensity score performed best across all simulated conditions. Other methods performed well in specific circumstances, such as pair matching when sample sizes were large (n = 5000) and the proportion treated was < 0.25. Statistical power was generally higher for weighting methods than matching methods, and Type I error rates were at or below the nominal level for balancing methods with unbiased treatment effect estimates. There was also a decreasing effective sample size with an increasing number of strata, therefore for stratification-based weighting methods, it may be important to consider fewer strata. Generally, we recommend methods that performed well in our simulations, although the identification of methods that performed well is necessarily limited by the specific features of our simulation. The methods are illustrated using a real-world example comparing beta blockers and angiotensin-converting enzyme inhibitors among hypertensive patients at risk for incident stroke.

Does pretrial detention influence time until re-involvement with the criminal legal system?

PurposeThe current study was designed to evaluate the effects of time spent in pretrial detention on the number of days from release until experiencing an arrest for a new offense and a new violent offense. MethodsUsing a sample of 31,598 individuals from three counties in the United States, the evaluation estimated the effects of spending 2–3 days, 3–7 days, and >7 days in pretrial detention – compared to admitted to jail and released on the same or next day (0 to 1 day– on the number of days from release until a new criminal arrest and new violent criminal arrest. The primary models were replicated using inverse probability weighting and propensity score matching. ResultsThe results of the study suggest that spending 2–3 days, 3–7 days, and >7 days in pretrial detention was associated with an increased probability of a new criminal arrest and new violent criminal arrest earlier when compared to spending 0 to 1 day in pretrial detention. ConclusionsThis research is consistent with the prior literature, suggesting that spending more time in pretrial detention might be criminogenic and contribute to an increased rate of churn through the criminal legal system.

Association of Pringle maneuver with postoperative recurrence and survival following hepatectomy for hepatocellular carcinoma: a multicenter propensity score and competing-risks regression analysis.

The application of Pringle maneuver (PM) during hepatectomy reduces intraoperative blood loss and the need for perioperative transfusion, but its effect on long-term recurrence and survival for patients with hepatocellular carcinoma (HCC) remains controversial. We sought to determine the association between the application of PM and post-hepatectomy oncologic outcomes for patients with HCC. Patients who underwent curative hepatectomy for HCC at 9 Chinese hospitals from January 2010 to December 2018 were identified. Using two propensity score methods [propensity score matching (PSM) and inverse probability of treatment weight (IPTW)], cumulative recurrence rate and cancer-specific mortality (CSM) were compared between the patients in the PM and non-PM groups. Multivariate competing-risks regression models were performed to adjust for the effect of non-cancer-specific mortality and other prognostic risk factors. Of the 2,798 included patients, 2,404 and 394 did and did not adopt PM (the PM and non-PM groups), respectively. The rates of intraoperative blood transfusion, postoperative 30-day mortality and morbidity were comparable between the two groups (all P>0.05). In the PSM cohort by the 1:3 ratio, compared to 382 patients in the non-PM group, 1,146 patients in the PM group also had the higher cumulative 5-year recurrence rate and CSM (63.9% and 39.1% vs. 55.3% and 31.6%, both P<0.05). Similar results were also yielded in the entire cohort and the IPTW cohort. Multivariate competing-risks regression analyses demonstrated that no application of the PM was independently associated with lower recurrence rate and CSM based on various analytical cohorts [hazard ratio (HR), 0.82 and 0.77 in the adjusted entire cohort, HR 0.80 and 0.73 in the PSM cohort, and HR 0.80 and 0.76 in the IPTW cohort, respectively]. The findings suggested that no application of PM during hepatectomy for patients with HCC reduced the risk of postoperative recurrence and cancer-specific death by approximately 20-25%.

#2020 The use of the target trial approach in kidney failure: a systematic methodological review

Abstract Background and Aims The concept of target trial emulation has recently been introduced and implemented in nephrology as a complement to when randomized trials may not be feasible. Thereby critical questions in the comparative effectiveness and safety of interventions during kidney failure can be addressed. This methodological systematic review aims to evaluate the scope, validity and robustness of the target trial approach for studying outcomes in patients with kidney disease. Method MEDLINE, Embase, and reference lists were searched up until 1st June 2023 to identify studies on kidney disease patients that use target trial emulation. Dual study selection (AA, PK) was undertaken, with a third reviewer settling disagreements (JP). Interventional observational studies were eligible that used target trial emulation to mimic a hypothetical trial where the conduct of a randomized trial was unfeasible, unethical, or untimely. We included studies across the range of chronic kidney diseases, i.e., predialysis, dialysis and transplantation; studies assessing acute disease states (including acute kidney injury) were excluded as well as non-primary research (i.e., case series/editorials/reports/narrative reviews). The quality of reporting and risk of bias was assessed independently by three reviewers and differences resolved through consensus with a fourth reviewer. The critical appraisal was piloted using a previously published reporting checklist and refined throughout the process. Results The systematic search yielded 2883 studies, of which 649 duplicates were removed. From 2232 studies, 367 full-text studies were assessed for eligibility according to target trial emulation criteria and 74 studies were included. A large number of studies (47) focused on patients with kidney failure undergoing renal replacement therapy, mainly haemodialysis. 30 studies were reported before 2019. Of the 74 studies, 46 focused on pharmacological interventions, six on surgical interventions, four on transplantation and 18 on other interventions. Studies used either registries (41), health administration data (4), insurance data (5), electronic health records (15), study databases (8) or other (1). It should be noted that in multiple instances more than one data source was used. The majority (66) of studies did not explicitly mention target trial emulation in the title or abstract. Only a minority (8) of studies explicitly prespecified a target trial protocol. To mitigate confounding, studies mainly focused on exact matching of the groups by using inverse probability weighting and propensity score matching. Conclusion In the past decade the use of the target trial emulation framework in nephrology has substantially increased. However, reporting and quality of study conduct is variable and shows the clear need for a reporting framework to increase clarity and reliability, and to understand to what extent study findings are generalisable into clinical practice to improve health outcomes

Forecasting vaping health risks through neural network model prediction of flavour pyrolysis reactions

Vaping involves the heating of chemical solutions (e-liquids) to high temperatures prior to lung inhalation. A risk exists that these chemicals undergo thermal decomposition to new chemical entities, the composition and health implications of which are largely unknown. To address this concern, a graph-convolutional neural network (NN) model was used to predict pyrolysis reactivity of 180 e-liquid chemical flavours. The output of this supervised machine learning approach was a dataset of probability ranked pyrolysis transformations and their associated 7307 products. To refine this dataset, the molecular weight of each NN predicted product was automatically correlated with experimental mass spectrometry (MS) fragmentation data for each flavour chemical. This blending of deep learning methods with experimental MS data identified 1169 molecular weight matches that prioritized these compounds for further analysis. The average number of discrete matches per flavour between NN predictions and MS fragmentation was 6.4 with 92.8% of flavours having at least one match. Globally harmonized system classifications for NN/MS matches were extracted from PubChem, revealing that 127 acute toxic, 153 health hazard and 225 irritant classifications were predicted. This approach may reveal the longer-term health risks of vaping in advance of clinical diseases emerging in the general population.

Intravenous Acetaminophen Versus Ketorolac for Prehospital Analgesia: A Retrospective Data Review

BackgroundParenteral ketorolac and intravenous (IV) acetaminophen have been used for prehospital analgesia, yet limited data exist on their comparative effectiveness. Study ObjectivesTo evaluate the comparative effectiveness of IV acetaminophen and parenteral ketorolac for analgesia in the prehospital setting. MethodsWe conducted a retrospective cross-sectional evaluation of patients receiving IV acetaminophen or parenteral ketorolac for pain management in a large suburban EMS system between 1/1/2019 and 11/30/2021. The primary outcome was change in first to last pain score. Subgroup analysis was performed on patients with traumatic pain. We used inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) to estimate the treatment effect of acetaminophen versus ketorolac among all patients and the subgroup of those with traumatic pain. ResultsOf 2178 patients included, 856 (39.3%) received IV acetaminophen and 1322 (60.7%) received parenteral ketorolac. The unadjusted mean change in pain score was −1.9 (SD 2.4) for acetaminophen group and −2.4 (SD 2.4) for ketorolac. In the propensity score analyses, there was no statistically significant difference in pain score change for the acetaminophen group versus ketorolac among all patients (mean difference, IPTW: 0.11, 95% confidence interval [CI] −0.16, 0.37; PSM: 0.15, 95% CI −0.13, 0.43) and among those with traumatic pain (unadjusted: 0.18, 95% CI −0.35, 0.72; IPTW: 0.23, 95% CI −0.25, 0.71; PSM: −0.03, 95% CI −0.61, 0.54). ConclusionsWe found no statistically significant difference in mean pain reduction of IV acetaminophen and parenteral ketorolac for management of acute pain.

The association between low serum calcium level and new-onset atrial fibrillation after coronary artery bypass grafting.

This study aims to investigate the relationship between serum calcium (SC) levels and the incidence of postoperative atrial fibrillation (POAF) in patients undergoing coronary artery bypass graft surgery. This retrospective, observational cohort study consecutively enrolled patients undergoing isolated coronary artery bypass grafting in Beijing Anzhen Hospital from January 2018 to December 2021. Patients with a previous history of atrial fibrillation or atrial flutter or requiring concomitant cardiac surgery were excluded. A logistic regression model was used to determine predictors of POAF. Multivariable adjustment, inverse probability of treatment weighting and propensity score matching were used to adjust for confounders. Moreover, we conducted univariable and multivariable logistic regression analyses on preoperative and postoperative SC and ionized SC levels. The analysis encompassed 12 293 patients. The POAF rate was significantly higher in patients with low SC level than those without (1379 [33.9%] vs 2375 [28.9%], P < 0.001). Low SC level was associated with an increased odds ratio of POAF (odds ratio [95% confidence interval]: 1.27 [1.18-1.37], P < 0.001). Inverse probability of treatment weighting and propensity score matching analyses confirmed the results. The increased POAF rate in low SC level group still existed among subgroup analysis based on different age, sex, body mass index, hypertension, hyperlipidaemia, CHA2DS2-VASc and magnesium. Low SC level indicates elevated POAF risk in patients undergoing isolated coronary artery bypass graft surgery even after the adjustment for age, sex, cardiovascular risk factors, echocardiographic parameters and laboratory markers.

Intra-islet glucagon signalling regulates beta-cell connectivity, first-phase insulin secretion and glucose homoeostasis

ObjectiveType 2 diabetes (T2D) is characterised by the loss of first-phase insulin secretion. We studied mice with β-cell selective loss of the glucagon receptor (Gcgrfl/fl X Ins-1Cre), to investigate the role of intra-islet glucagon receptor (GCGR) signalling on pan-islet [Ca2+]I activity and insulin secretion. MethodsMetabolic profiling was conducted on Gcgrβ-cell−/− and littermate controls. Crossing with GCaMP6f (STOP flox) animals further allowed for β-cell specific expression of a fluorescent calcium indicator. These islets were functionally imaged in vitro and in vivo. Wild-type mice were transplanted with islets expressing GCaMP6f in β-cells into the anterior eye chamber and placed on a high fat diet. Part of the cohort received a glucagon analogue (GCG-analogue) for 40 days and the control group were fed to achieve weight matching. Calcium imaging was performed regularly during the development of hyperglycaemia and in response to GCG-analogue treatment. ResultsGcgrβ-cell−/− mice exhibited higher glucose levels following intraperitoneal glucose challenge (control 12.7 mmol/L ± 0.6 vs. Gcgrβ-cell−/− 15.4 mmol/L ± 0.0 at 15 min, p = 0.002); fasting glycaemia was not different to controls. In vitro, Gcgrβ-cell−/− islets showed profound loss of pan-islet [Ca2+]I waves in response to glucose which was only partially rescued in vivo. Diet induced obesity and hyperglycaemia also resulted in a loss of co-ordinated [Ca2+]I waves in transplanted islets. This was reversed with GCG-analogue treatment, independently of weight-loss (n = 8). ConclusionThese data provide novel evidence for the role of intra-islet GCGR signalling in sustaining synchronised [Ca2+]I waves and support a possible therapeutic role for glucagonergic agents to restore the insulin secretory capacity lost in T2D.

Low-Intensity Statin Plus Ezetimibe Versus Moderate-Intensity Statin for Primary Prevention: A Population-Based Retrospective Cohort Study in Asian Population.

While moderate-intensity statin therapy is recommended for primary prevention, statins may not be utilized at a recommended intensity due to dose-dependent adverse events, especially in an Asian population. However, evidence supporting the use of low-intensity statins in primary prevention is limited. We sought to compare clinical outcomes between a low-intensity statin plus ezetimibe and a moderate-intensity statin for primary prevention. This population-based retrospective cohort study used the Korean nationwide claims database (2002-2019). We included adults without atherosclerotic cardiovascular diseases who received moderate-intensity statins or low-intensity statins plus ezetimibe. The primary outcome was a composite of all-cause mortality, myocardial infarction, and ischemic stroke. The safety outcomes were liver and muscle injuries and new-onset diabetes mellitus (DM). We used standardized inverse probability of treatment weighting (sIPTW) and propensity score matching (PSM). In the sIPTW model, 1717 and 36 683 patients used a low-intensity statin plus ezetimibe and a moderate-intensity statin, respectively. In the PSM model, each group included 1687 patients. Compared with moderate-intensity statin use, low-intensity statin plus ezetimibe use showed similar risks of the primary outcome (hazard ratio [HR] = 0.92, 95% CI = 0.81-1.12 in sIPTW and HR = 1.16, 95% CI = 0.87-1.56 in PSM model). Low-intensity statin plus ezetimibe use was associated with decreased risks of liver and muscle injuries (subHR [sHR] = 0.84, 95% CI = 0.74-0.96 and sHR = 0.87, 95% CI = 0.77-0.97 in sIPTW; sHR = 0.84, 95% CI = 0.72, 0.96 and sHR = 0.82, 95% CI = 0.72-0.94 in PSM model, respectively). For new-onset DM and hospitalization of liver and muscle injuries, no difference was observed. Low-intensity statin plus ezetimibe may be an alternative to moderate-intensity statin for primary prevention. Our findings provide evidence on safety and efficacy of statin therapy in Asian population.

Risk of acute kidney injury in critically-ill patients with COVID-19 compared with seasonal influenza: a retrospective cohort study

The SARS-CoV-2 virus can bind to angiotensin-converting enzyme 2 receptors on host renal cells and may cause acute kidney injury (AKI). The comparative risks of AKI in patients severely ill with COVID-19 and influenza A have not been examined. This is a retrospective cohort study including patients with positive PCR results for SARS-CoV-2 or influenza A virus admitted to the intensive care units (ICUs) of 15 public hospitals in Hong Kong between 1st January 2013 and 30th April 2023. Patients who were already on chronic dialysis or had missing values in the confounder model were excluded. Data were retrieved from Hong Kong Hospital Authority's electronic healthcare records. The primary outcome was incident AKI during ICU stay. Secondary outcomes included acute kidney disease (AKD) and hospital mortality. All analyses were examined in multivariable regression adjusting for potential confounders (age, sex, baseline eGFR, PaO2/FiO2 ratio, baseline comorbidities, APACHE IV predicted risk of death, Charlson Comorbidity Index, emergent hospital admission, admission from elderly home, reason for ICU admission, presence of bacterial co-infections, use of medications [including vasopressors, antiviral medications, steroids and nephrotoxic antibiotics], as well as anaemia and leucocytosis). Patients were matched in a 1:1 ratio using a propensity score generated based on the full confounder model. The analyses were repeated using inverse probability weighting and in propensity-score matched cohorts. A total of 5495 ICU patients were identified. After excluding 1093 (19.9%) patients who met the exclusion criteria and 74 (1.3%) patients who had one or more missing values in the logistic regression model, a total of 4328 patients were included in the final analysis, with 2787 (64.4%) patients who tested positive for SARS-CoV-2 reverse transcription (RT)-PCR and 1541 (35.6%) patients who tested positive for influenza A virus RT-PCR. The comorbidity burden was greater in patients with COVID-19 (Charlson Comorbidity Index 3 [2-4] vs. 3 [1-4]), but the median APACHE IV predicted risk of death was significantly lower (0.19 [0.08-0.38] vs. 0.25 [0.11-0.52]). A total of 1053 (37.8%) patients with COVID-19 and 828 (53.7%) patients with influenza A developed AKI of any stage during ICU stay. In adjusted analysis, the risk of AKI was significantly lower in patients with COVID-19 compared with influenza A (adjusted odds ratio 0.51, 95% confidence interval 0.42-0.61, P<0.0001]. The risk of stage 3 AKI and AKD were also significantly lower in patients with COVID-19. These results remained robust in multiple pre-planned sensitivity analyses including inverse probability weighting and propensity score matching. Our results suggest that the risk of AKI in patients severely ill with COVID-19 was lower than in patients with influenza A. The burden of concurrent organ failure complicating respiratory viral infections, such as the higher disease-attributable risk of AKI associated with influenza, should be clarified. An unrestricted philanthropic donation from Mr and Mrs Laurence Tse, The Wai Im Charitable Foundation, Chan Sui Kau Family Benefits and Charitable Foundation, So Ka Wing and Lee Sau Ying Charitable Foundation, Mr & Mrs Tam Wing Fun Edmund Renal Research Fund, the Theme-Based Research Scheme of the Research Grants Council, Hong Kong Special Administrative Region, The Government of the Hong Kong Special Administrative Region; Programme of Enhancing Laboratory Surveillance and Investigation of Emerging Infectious Diseases and Antimicrobial Resistance for the Department of Health of the Hong Kong Special Administrative Region Government; Emergency COVID-19 Project, Major Projects on Public Security, National Key Research and Development Program; Emergency Collaborative Project of Guangzhou Laboratory; the National Key Research and Development Program of China; Sanming Project of Medicine in Shenzhen China; and the High Level-Hospital Program, Health Commission of Guangdong Province, China.

Improving ranking quality and fairness in Swiss-system chess tournaments

Abstract The International Chess Federation (FIDE) imposes a voluminous and complex set of player pairing criteria in Swiss-system chess tournaments and endorses computer programs that are able to calculate the prescribed pairings. The purpose of these formalities is to ensure that players are paired fairly during the tournament and that the final ranking corresponds to the players’ true strength order. We contest the official FIDE player pairing routine by presenting alternative pairing rules. These can be enforced by computing maximum weight matchings in a carefully designed graph. We demonstrate by extensive experiments that a tournament format using our mechanism (1) yields fairer pairings in the rounds of the tournament and (2) produces a final ranking that reflects the players’ true strengths better than the state-of-the-art FIDE pairing system.

Adjuvant Chemotherapy and Outcomes in Older Adult Patients With Biliary Tract Cancer

The association of adjuvant chemotherapy (AC) with survival in the general population of patients with resected biliary tract cancer (BTC) remains controversial. As such, the role of this treatment in the treatment of older adult patients (aged ≥70 years) needs to be evaluated. To describe the patterns of use of AC and compare survival outcomes of AC and observation in older adult patients following resection of BTC. This retrospective cohort study included 8091 older adult patients with resected BTC with data available in the National Cancer Database from January 1, 2004, to December 31, 2019. Patients were divided into 2 cohorts: AC and observation. The AC cohort was subdivided into single-agent and multiagent AC treatment. Adjuvant chemotherapy vs observation following BTC resection. The primary outcome was overall survival (OS) of patients who received AC compared with observation following resection of BTC as evaluated using Kaplan-Meier estimates and multivariable Cox proportional hazards regression models. Inverse probability of treatment weighting and propensity score matching were performed to address indication bias. Between 2004 and 2019, of 8091 older adult patients with resected BTC identified (median [range] age, 77 [70-90] years; 5136 women [63.5%]; 2955 men [36.5%]), only one-third (2632 [32.5%]) received AC. There was an increase in the use of AC across the study period from 20.7% (n = 495) in 2004 to 2009 to 41.2% (n = 856) in 2016 to 2019. Age 80 years or older (odds ratio, 0.29; 95% CI, 0.25-0.33; P < .001) and gallbladder primary site (odds ratio, 0.71; 95% CI, 0.61-0.83; P < .001) were associated with a lower odds of AC. Following inverse probability of treatment weighting, as a composite, AC was not associated with improved survival (median OS, 20.5 months; 95% CI, 19.2-21.7 months) compared with observation (median OS, 19.0 months; 95% CI, 18.1-20.3 months). A longer median OS was associated with single-agent AC (21.5 months; 95% CI, 19.9-24.0 months) but not multiagent AC (19.1 months; 95% CI, 17.5-21.1 months) compared with observation (median OS, 17.3 months; 95% CI, 16.1-18.4 months). This improvement in OS with single-agent AC was not apparent on multivariable analysis (hazard ratio [HR], 0.97; 95% CI, 0.89-1.05; P = .44). However, age at diagnosis of 80 years or older (HR, 1.35; 95% CI, 1.28-1.42; P < .001) and treatment at nonacademic centers (HR, 1.14; 95% CI, 1.07-1.20, P < .001) were associated with worse OS. In this cohort study of older adult patients, AC was not associated with an improvement in survival compared with observation following BTC resection. These findings suggest the need for further study of AC for older adult patients who may benefit after curative intent surgery for BTC.