The R package BiDAG implements Markov chain Monte Carlo (MCMC) methods for structure learning and sampling of Bayesian networks. The package includes tools to search for a maximum a posteriori (MAP) ...graph and to sample graphs from the posterior distribution given the data. A new hybrid approach to structure learning enables inference in large graphs. In the first step, we define a reduced search space by means of the PC algorithm or based on prior knowledge. In the second step, an iterative order MCMC scheme proceeds to optimize the restricted search space and estimate the MAP graph. Sampling from the posterior distribution is implemented using either order or partition MCMC. The models and algorithms can handle both discrete and continuous data. The BiDAG package also provides an implementation of MCMC schemes for structure learning and sampling of dynamic Bayesian networks.
Aberrant regulation of the Wnt/β-catenin pathway has an important role during the onset and progression of colorectal cancer, with over 90% of cases of sporadic colon cancer featuring mutations in ...APC or β-catenin. However, it has remained a point of controversy whether these mutations are sufficient to activate the pathway or require additional upstream signals. Here we show that colorectal tumours express elevated levels of Wnt3 and Evi/Wls/GPR177. We found that in colon cancer cells, even in the presence of mutations in APC or β-catenin, downstream signalling remains responsive to Wnt ligands and receptor proximal signalling. Furthermore, we demonstrate that truncated APC proteins bind β-catenin and key components of the destruction complex. These results indicate that cells with mutations in APC or β-catenin depend on Wnt ligands and their secretion for a sufficient level of β-catenin signalling, which potentially opens new avenues for therapeutic interventions by targeting Wnt secretion via Evi/Wls.
Secondary hyperparathyroidism (sHPTH) is common in patients with end-stage chronic kidney disease. If drug therapy fails, total parathyroidectomy with autotransplantation of parathyroid tissue into ...the forearm (PTX-AT) is the most widely used procedure. High recurrence rates of sHPTH following PTX-AT are reported in the literature.
The aim of this study was to evaluate recurrences of sHPTH following PTX-AT in detail in order to develop strategies to prevent recurrences in the future.
This retrospective study analysed a single-centre cohort of 42 patients who underwent PTX-AT for sHPTH at a tertiary centre in Switzerland. Postoperative PTH levels were evaluated to determine the recurrence and persistence rates and the time to recurrence. Furthermore, the peri- and postoperative outcomes were assessed. Patients on dialysis and patients with a functioning kidney transplant suffering tertiary HPTH were analysed separately.
Intraoperative measurements showed that serum PTH decreased to 6.9% (3.3-15.0%) of the preoperative baseline level. After a median follow-up of 89.5 months (IQR 31.9-152.9), persistence of sHPTH was found in five patients (11.9%) and recurrence in four patients (9.5%), giving a total recurrence rate of 21.4%.
Recurrence of sHPTH after PTX remains a problem, occurring in every fifth patient. In our experience, the introduction of intraoperative PTH measurement has helped to lower the rates of persistence and recurrence. Further reductions in the recurrence rate might be achieved with novel, more accurate pre- and intraoperative imaging techniques.
Adjusting for covariates is a well-established method to estimate the total causal effect of an exposure variable on an outcome of interest. Depending on the causal structure of the mechanism under ...study, there may be different adjustment sets, equally valid from a theoretical perspective, leading to identical causal effects. However, in practice, with finite data, estimators built on different sets may display different precisions. To investigate the extent of this variability, we consider the simplest non-trivial non-linear model of a v-structure on three nodes for binary data. We explicitly compute and compare the variance of the two possible different causal estimators. Further, by going beyond leading-order asymptotics, we show that there are parameter regimes where the set with the asymptotically optimal variance does depend on the edge coefficients, a result that is not captured by the recent leading-order developments for general causal models. As a practical consequence, the adjustment set selection needs to account for the relative magnitude of the relationships between variables with respect to the sample size and cannot rely on purely graphical criteria.
High bed-occupancy (capacity utilization) rates are commonly thought to increase in-hospital mortality; however, little evidence supports a causal relationship between the two. This observational ...study aimed to assess three time-varying covariates-capacity utilization, patient turnover and clinical complexity level- and to estimate causal effect of time-varying high capacity utilization on 14 day in-hospital mortality.
This retrospective population-based analysis was based on routine administrative data (n = 1,152,506 inpatient cases) of 102 Swiss general hospitals. Considering the longitudinal nature of the problem from available literature and expert knowledge, we represented the underlying data generating mechanism as a directed acyclic graph. To adjust for patient turnover and patient clinical complexity levels as time-varying confounders, we fitted a marginal structure model (MSM) that used inverse probability of treatment weights (IPTWs) for high and low capacity utilization. We also adjusted for patient age and sex, weekdays-vs-weekend, comorbidity weight, and hospital type.
For each participating hospital, our analyses evaluated the ≥85th percentile as a threshold for high capacity utilization for the higher risk of mortality. The mean bed-occupancy threshold was 83.1% (SD 8.6) across hospitals and ranged from 42.1 to 95.9% between hospitals. For each additional day of exposure to high capacity utilization, our MSM incorporating IPTWs showed a 2% increase in the odds of 14-day in-hospital mortality (OR 1.02, 95% CI: 1.01 to 1.03).
Exposure to high capacity utilization increases the mortality risk of inpatients. Accurate monitoring of capacity utilization and flexible human resource planning are key strategies for hospitals to lower the exposure to high capacity utilization.
Celotno besedilo
Dostopno za:
CEKLJ, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Directed acyclic graphs are the basic representation of the structure underlying Bayesian networks, which represent multivariate probability distributions. In many practical applications, such as the ...reverse engineering of gene regulatory networks, not only the estimation of model parameters but the reconstruction of the structure itself is of great interest. As well as for the assessment of different structure learning algorithms in simulation studies, a uniform sample from the space of directed acyclic graphs is required to evaluate the prevalence of certain structural features. Here we analyse how to sample acyclic digraphs uniformly at random through recursive enumeration, an approach previously thought too computationally involved. Based on complexity considerations, we discuss in particular how the enumeration directly provides an exact method, which avoids the convergence issues of the alternative Markov chain methods and is actually computationally much faster. The limiting behaviour of the distribution of acyclic digraphs then allows us to sample arbitrarily large graphs. Building on the ideas of recursive enumeration based sampling we also introduce a novel hybrid Markov chain with much faster convergence than current alternatives while still being easy to adapt to various restrictions. Finally we discuss how to include such restrictions in the combinatorial enumeration and the new hybrid Markov chain method for efficient uniform sampling of the corresponding graphs.
Acyclic digraphs are the underlying representation of Bayesian networks, a widely used class of probabilistic graphical models. Learning the underlying graph from data is a way of gaining insights ...about the structural properties of a domain. Structure learning forms one of the inference challenges of statistical graphical models. Markov chain Monte Carlo (MCMC) methods, notably structure MCMC, to sample graphs from the posterior distribution given the data are probably the only viable option for Bayesian model averaging. Score modularity and restrictions on the number of parents of each node allow the graphs to be grouped into larger collections, which can be scored as a whole to improve the chain's convergence. Current examples of algorithms taking advantage of grouping are the biased order MCMC, which acts on the alternative space of permuted triangular matrices, and nonergodic edge reversal moves. Here, we propose a novel algorithm, which employs the underlying combinatorial structure of DAGs to define a new grouping. As a result convergence is improved compared to structure MCMC, while still retaining the property of producing an unbiased sample. Finally, the method can be combined with edge reversal moves to improve the sampler further. Supplementary materials for this article are available online.
Background
Centralization of care is an established concept in complex visceral surgery. Switzerland introduced case load requirements (CR) in 2013 in five areas of cancer surgery. The current study ...investigates the effects of CR on indication and mortality in liver surgery.
Methods
This is a retrospective analysis of a complete national in-hospital data set including all admissions between January 1, 2005, and December 31, 2015. Primary outcome variables were the incidence proportion and the 60-day in-hospital mortality of liver resections. Incidence proportion was calculated as the overall yearly number of liver resections performed in relation to the population living in Switzerland before and after the introduction of CR.
Results
Our analysis shows an increase number of liver resections compared to the period before introduction of CR from 2005–2012 (4.67 resections/100,000) to 2013–2015 (5.32 resections/100,000) after CR introduction. Age-adjusted incidence proportion increased by 14% (OR 1.14 95 CI 1.07–1.22). National in-hospital mortality remained stable before and after CR (4.1 vs 3.7%), but increased in high-volume institutions (3.6 vs 5.6%). The number of hospitals performing liver resections decreased after the introduction of CR from 86 to 43. Half of the resections were performed in institutions reaching the stipulated numbers (53% before vs 49% after introduction of CR). After implementation of CR, patients undergoing liver surgery had more comorbidities (88 vs 92%).
Conclusion
The introduction of CR for liver surgery in Switzerland in 2013 was accompanied by an increase in operative volume with limited effects on centralization of care.
ObjectiveTo describe the characteristics and the survival of patients with cancer with intended off-label use (OLU) cancer treatment and reimbursement request.DesignCohort study using medical record ...data.SettingThree major cancer centres in Switzerland.Participants519 patients with cancer and a reimbursement request for OLU between January 2015 and July 2018.Main outcomesCharacteristics of patients with cancer with and without access to intended OLU. Characteristics included the Glasgow prognostic score (GPS) which includes C reactive protein and albumin and discriminates prognostic groups.ResultsOLU was intended for 519 (17%) of 3046 patients with cancer, as first-line treatment in 51% (n=264) and second-line in 31% (n=162). Of the 519 patients, 63% (n=328) were male, 63% (n=329) had solid cancer and 21% (n=111) had a haematological malignancy. Their median overall survival was 23.6 months (95% CI: 19.0 to 32.5). Access to OLU had 389 (75%) patients who were compared with patients without access on average 4.9 years younger (mean; 95% CI: 1.9 to 7.9 years), had a better overall prognosis according to the GPS (51% with GPS of 0 vs 39%; OR: 1.62 (95% CI: 1.01 to 2.59)), had less frequently solid cancer (62% vs 71%; OR: 0.66 (95% CI: 0.41 to 1.05)) and advanced stage cancer (53% vs 70%; OR: 0.48 (95% CI: 0.30 to 0.75)), were more frequently treatment-naive (53% vs 43%; OR: 1.55 (95% CI 1.01 to 2.39)) and were more frequently in an adjuvant/neoadjuvant treatment setting (14% vs 5%; OR: 3.39 (95% CI: 1.45 to 9.93)). Patients with access to OLU had a median OS of 31.1 months versus 8.7 months for patients without access (unadjusted HR: 0.54; (95% CI: 0.41 to 0.70)).ConclusionContrary to the common assumption, OLU in oncology is typically not primarily intended for patients with exhausted treatment options. Patient characteristics largely differ between patients with and without access to intended OLU. More systematic evaluations of the benefits and harms of OLU in cancer care and the regulation of its access is warranted.
Abstract
Background
Observational studies have shown that dressings containing chlorhexidine gluconate (CHX) lower the incidence external ventricular drain (EVD)-associated infections (EVDAIs). This ...prospective, randomized controlled trial (RCT) studies the efficacy of CHX-containing dressings in reducing bacterial colonization.
Methods
In this RCT, patients aged ≥18 years undergoing emergency EVD placement were randomly given either a CHX-containing or an otherwise identical control dressing at the skin exit wound. The primary end-point was bacterial regrowth in cultured skin swab samples of the EVD exit wound. The secondary end-points were catheters processed by sonication, clinically diagnosed EVDAI and surgical treatment of hydrocephalus.
Results
From October 2013 to January 2016, a total of 57 patients were randomized to receive either a CHX or a control dressing (29 and 28 patients, respectively). Cutaneous bacterial regrowth at the EVD exit wound was significantly reduced over time (geometric mean ratio, 0.18; 95% confidence interval, .08-.42; P < .001). The incidence of colonized catheters was lower in the CHX group (5 of 28; 18%) than in the control group (10 of 27; 33%), with less microbial colonization on the subcutaneous portion. The infection rate was 4 of 28 (14%) in the CHX group, compared with 7 of 27 (26%) in the control group, with a substantially lower hydrocephalus treatment rate (7 of 28 25% vs 14 of 27 52%, respectively).
Conclusion
Our data support the use of CHX dressings to reduce EVD exit site contamination, potentially reducing EVDAIs and permanent cerebrospinal fluid diversion procedures for hydrocephalus.
Clinical Trials Registration
NCT02078830.
This prospective, randomized controlled trial studies the effectiveness of chlorhexidine-coated dressings in reducing bacterial colonization of external ventricular drains and supports their use to reduce exit site contamination and potentially reduce infections and permanent cerebrospinal fluid diversion procedures for hydrocephalus.
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