Reduction In Risk Of Failure Research Articles

Modeling the flood protection services of levee setbacks, a nature-based solution

Levee setbacks are an intuitive nature-based solution that can improve the flood protection services provided by levees and help rehabilitate levee-stressed ecosystems. Their application in professional practice is in part limited by a lack of guidance on how to size setbacks to balance different interests in floodplain land use. To help address this application barrier, we demonstrate how flood hazard and levee failure risk reduction may be modeled with a numerical hydraulic model of a leveed river in the Midwestern USA, as well as how to calculate scaling relationships between levee failure risk reduction and setback size. Our results suggest setbacks can greatly reduce the severity of flood hazards, for example, by alleviating flow bottlenecks and lowering flood heights. Our results also suggest that improvements in levee reliability scale non-linearly with setback size and exhibit diminishing returns. We conclude with a discussion of design insights and cautions to support the application of setbacks in practice.

Effect of carvedilol versus placebo on cardiac function in anthracycline-exposed survivors of childhood cancer (PREVENT-HF): a randomised, controlled, phase 2b trial

Carvedilol improves cardiac function in patients with heart failure but remains untested as cardioprotective therapy in long-term childhood cancer survivors (ie, those who have completed treatment for childhood cancer and are in remission) at risk for heart failure due to high-dose anthracycline exposure. We aimed to evaluate the activity and safety of low-dose carvedilol for heart failure risk reduction in childhood cancer survivors at highest risk for heart failure. PREVENT-HF was a randomised, double-blind, phase 2b trial done at 30 hospitals in the USA and Canada. Patients were eligible if they had any cancer diagnosis that resulted in at least 250 mg/m2 cumulative exposure to anthracycline by age 21 years; completed their cancer treatment at least 2 years previously; an ejection fraction of at least 50% or fractional shortening of at least 25%, or both; and bodyweight of at least 40 kg. Patients were randomly assigned (1:1) with automated computer-generated permuted block randomisation (block size of 4), stratified by age at diagnosis, time since diagnosis, and history of chest-directed radiotherapy, to carvedilol (up-titrated from 3·125 g per day to 12·5 mg per day) or placebo orally for 2 years. Participants, staff, and investigators were masked to study group allocation. The primary endpoint was to establish the effect of carvedilol on standardised left ventricular wall thickness-dimension ratio Z score (LVWT/Dz). Treatment effects were analysed with a linear mixed-effects model for normally distributed data with a linear time effect and testing the significance of treatment*time interaction in the modified intention-to-treat (mITT) cohort (ie, all randomly assigned participants who had a baseline and at least one subsequent echocardiogram measurement). Safety was assessed in the ITT population (ie, all randomly assigned participants). This trial was registered with ClinicalTrials.gov, NCT027175073, and enrolment and follow-up are complete. Between July 3, 2012, and June 22, 2020, 196 participants were enrolled, of whom 182 (93%) were eligible and randomly assigned to either carvedilol (n=89) or placebo (n=93; ITT population). Median age was 24·7 years (IQR 19·6-36·6), 91 (50%) participants were female, 91 (50%) were male, and 119 (65%) were non-Hispanic White. As of data cutoff (June 10, 2022), median follow-up was 725 days (IQR 378-730). 151 (n=75 in the carvedilol group and n=76 in the placebo group) of 182 participants were included in the mITT population, among whom LVWT/Dz was similar between the two groups (-0·14 [95% CI -0·43 to 0·16] in the carvedilol group vs -0·45 [-0·77 to -0·13] in the placebo group; difference 0·31 [95% CI -0·10 to 0·73]; p=0·14). Two (2%) of 89 patients in the carvedilol group two adverse events of grade 2 or higher (n=1 shortness of breath and n=1 arthralgia) and none in the placebo group. There were no adverse events of grade 3 or higher and no deaths. Low-dose carvedilol appears to be safe in long-term childhood cancer survivors at risk for heart failure, but did not result in significant improvement of LVWT/Dz compared with placebo. These results do not support the use of carvedilol for secondary heart failure prevention in anthracycline-exposed childhood cancer survivors. National Cancer Institute, Leukemia & Lymphoma Society, St Baldrick's Foundation, Altschul Foundation, Rally Foundation, American Lebanese Syrian Associated Charities.

Risk evolution of crude oil pipeline under periodic maintenance based on dynamic bayesian network

Pipeline failure can result in a chain reaction of accidents, including oil and gas leaks. Traditional risk analysis methods fail to fully capture the degradation and imperfect maintenance processes of multi-state systems. The model utilizes a hybrid failure rate recursive rule to accurately depict the changes in system reliability under varying maintenance intervals. The robustness of the model was validated through a case study of crude oil pipelines and the probability of pipeline failure under different maintenance strategies was predicted. The results suggest that semi-annual maintenance can significantly reduce the probability of pipeline failure compared to annual maintenance. If the equipment has experienced multiple instances of imperfect maintenance, it will accumulate excessive fatigue damage, leading to a gradual increase in the growth rate of the hazard rate function. Therefore, after 36 months, the advantage of semi-annual incomplete maintenance gradually diminishes, indicating that there is an upper limit to the number of equipment maintenance actions. To maximize failure risk reduction and minimize losses, a combined maintenance strategy (semi-annual and annual maintenance) should be implemented. Finally, through sensitivity and diagnostic analysis, key factors leading to pipeline failure were identified and appropriate measures to prevent pipeline failure were proposed.

Evaluating the heterogeneity of hippocampal avoidant whole brain radiotherapy treatment effect: A secondary analysis of NRG CC001.

Hippocampal avoidant whole brain radiotherapy (HA-WBRT) is the standard of care for patients needing WBRT for brain metastases. This study, using existing data from NRG Oncology CC001 including baseline tumor characteristics and patient-reported MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT) scores, sought to identify subgroups of patients that demonstrate differential neuroprotective treatment response to HA-WBRT. An exploratory analysis of NRG CC001, a phase 3 trial in which 518 patients were randomly assigned to WBRT plus memantine or HA-WBRT plus memantine, was performed. Rates of neurocognitive function failure (NCFF) were estimated between subgroups and stratified by arm. Covariate and subgroup interaction with differential treatment response were calculated. The benefit of HA-WBRT on decreasing NCFF was seen in patients living ≥ 4 months (HR 0.75, 95% CI: 0.58-0.97, P = .03), whereas patients living < 4 months derived no significant neurocognitive benefit. A significant association between baseline MDASI-BT cognitive factor and treatment response (interaction P = .03) was identified. Patients with lower MDASI-BT scores (less patient-reported cognitive impairment) derived significantly greater benefit (HR = 0.64, 95% CI: 0.48-0.85, P = .002) compared to those with highest MDASI-BT scores (HR = 1.24, 95% CI: 0.76-2.04, P = .39). Tumor histology also had a significant interaction (P = .01) with treatment response. Primary lung histology patients derived cognitive failure risk reduction (HR = 0.58, 95% CI: 0.43-0.77, P = .0007) from HA-WBRT, in contrast to nonlung primary histology patients (HR = 1.15, 95% CI: 0.78-1.50, P = .48). Differential neuroprotective response to HA-WBRT was identified in this analysis. Patients surviving ≥ 4 months derived benefit from HA-WBRT. There is evidence of heterogeneity of treatment effect for patients with less severe patient-reported cognitive impairment at baseline and those with primary lung histology.

SGLT-2 inhibitors improve cardiovascular and renal outcomes in patients with CKD: a systematic review and meta-analysis

The effect of sodium-glucose co-transporter-2 (SGLT-2) inhibitors on cardiovascular and renal outcomes has not been systematically reviewed across baseline kidney function groups. We conducted a systematic review and meta-analysis of randomized control trials (RCTs) with SGLT-2 inhibitors in patients with and without CKD. We performed a PubMed/Medline search of randomized, placebo-controlled, event-driven outcome trials of SGLT-2 inhibitors versus active or placebo control in patients with and without diabetes from inception to November 2022. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m2 (PROSPERO registration CRD4202016054). The primary outcome was cardiovascular death. Secondary outcomes included hospitalization for heart failure, major adverse cardiovascular events, CKD progression, all-cause mortality, treatment discontinuation, and acute kidney injury (AKI). The relative risk (RR) was estimated using a random-effects model. Twelve RCTs were included in this meta-analysis (89,191 patients, including 38,949 with eGFR < 60 ml/min/1.73m2). Use of an SGLT-2 inhibitor in patients with CKD was associated with a lower incidence of cardiovascular death (RR 0.87; 95% CI 0.79–0.95) and of heart failure (RR 0.67; 95% CI 0.61–0.75), compared with placebo. Heart failure risk reduction with SGLT-2 inhibitors was larger among patients with CKD compared with patients without CKD (RR for the interaction 0.87, 95% CI 0.75–1.02, and p-value for interaction 0.08). SGLT-2 inhibitors were associated with a lower incidence of CKD progression among patients with pre-existing CKD: RR 0.77 (95% CI 0.68–0.88), compared with placebo. Among patients with CKD, a lower risk of AKI (RR 0.82; 95% CI 0.72–0.93) and treatment discontinuation was seen with SGLT-2 inhibitors compared with placebo. SGLT-2 inhibitors offer substantial protection against cardiovascular and renal outcomes in patients with CKD. These results strongly advocate in favor of using them in patients with CKD and keeping them as kidney function declines.

Biomechanical analysis of different osteosynthesis configurations in the pin and plate fixation method for distal humerus fractures

Distal humerus fractures commonly occur in adults with low bone mineral density causing major technical challenges for orthopedic surgeons. Persian fixation method was introduced as a novel technique to stabilize small fragments in comminuted distal humerus fractures using a set of K-wires and a reconstruction plate. The present study aims to measure this technique's stiffness and stability of this technique and analyze the effect of influential parameters with numerical simulation and biomechanical testing on a cadaveric specimen. Validation of the finite element (FE) model was conducted based on results of experiments. The results indicated that Delta configuration mainly led to a higher stiffness in the case of axial loading and anterior bending compared to L configuration. Analyzing the influential factors of this technique suggests that changes in diameter and number of K-wires have a similarly significant effect on the construct stiffness while the height of plate had a slight influence. Also, the diameter of wires was the most effective parameter for implant failure, particularly in the 3-pin construct, which caused a reduction in failure risk by about 60%. The results revealed that the Persian fixation method would achieve suitable stability compared to the dual-plating technique.

Failure risk assessment of deepwater HTHP well completion test string based on uncertainty analysis

In deepwater HTHP well completion test, the stress of the test string changes violently under the influence of HTHP environment, which is easy to cause the string failure. To solve this problem, the test string is simplified as a thick-wall cylinder model with uniform loads under the influence of high temperature. Then, the failure risk assessment method of the string is established based on the generalized stress-strength interference theory, and the influence of gas production, bottom hole pressure and test fluid density on the failure risk of a case well are analyzed. The results show that the failure mode in this well is internal pressure resistance failure, and the risk positions are mainly concentrated near wellhead. Gas production increasing leads to the intensification of radial heat transfer, increases the annular pressure and reduce the pressure difference of the string, resulting in the reduction of failure risk. Increasing the bottom hole pressure will increase the positive pressure difference of string, which will increase its internal pressure resistance failure risk. The test fluid density has low impact on failure risk. This method can provide theoretical reference for ensuring the reliability of deepwater HTHP well completion test.

Comparison of the effects of empagliflozin and glimepiride on endothelial function in patients with type 2 diabetes: A randomized controlled study.

Patients with type 2 diabetes who have cardiovascular disease and are receiving empagliflozin have a lower rate of primary composite cardiovascular outcomes. In contrast, glimepiride increases cardiovascular hospitalization when combined with metformin. Here, we assessed the effects of empagliflozin and glimepiride on endothelial function using flow-mediated dilation (FMD). In this prospective, open-label, randomized, parallel-group study, 63 patients with type 2 diabetes received metformin and insulin glargine U100 for 12 weeks. This was followed by additional treatment with empagliflozin or glimepiride for 12 weeks. The primary outcome was the change in the FMD measurement (ΔFMDs) at 24 weeks of additional treatment. Secondary outcomes comprised changes in metabolic markers and body composition. The empagliflozin group (n = 33) and glimepiride group (n = 30) showed no significant differences in ΔFMDs (empagliflozin, −0.11 [95%CI: -1.02, 0.80]%; glimepiride, −0.34 [95%CI: -1.28, 0.60]%; P = 0.73). Additionally, changes in glycated hemoglobin were similar between the two groups. However, a significant difference in body weight change was observed (empagliflozin, −0.58 [95%CI: -1.60, 0.43] kg; glimepiride, 1.20 [95%CI: 0.15, 2.26] kg; P = 0.02). Moreover, a body composition analysis revealed that body fluid volume significantly decreased after empagliflozin treatment (baseline, 35.8 ± 6.8 L; after 12 weeks, −0.33 ± 0.72 L; P = 0.03). Hence, although empagliflozin did not improve endothelial function compared with glimepiride for patients with type 2 diabetes, it did decrease body fluid volumes. Thus, the coronary-protective effect of empagliflozin is not derived from endothelial function protection, but rather from heart failure risk reduction.Trial registration: This trial was registered on September 13, 2016; UMIN000024001.

A Randomized Open-Label Study of Two Methods of Proton Pump Inhibitors Discontinuation.

BackgroundProton pump inhibitors (PPIs) are effective in treating gastroesophageal reflux disease (GERD). Unfortunately, they are often inappropriately prescribed and long-term use has potential adverse effects. A single best method for discontinuation of PPIs does not currently exist. The objective of this study was to determine if there is a significant difference in successfully discontinuing PPI use at 12 months between patients discontinuing abruptly or tapering first.MethodologyWe conducted a randomized trial with 38 patients diagnosed with GERD. We collected six weekly and then monthly surveys of symptoms based on the Dyspepsia Symptom Severity Index. Chart review at 12 months determined whether the patient was able to discontinue PPI.ResultsA Kaplan-Meier survival analysis at 12 months did not show a statistically significant difference between the abrupt and taper groups for discontinuation of PPI medication (p = 0.75). Cox regression analysis showed no association of alcohol use, smoking, or caffeine use with failure to discontinue PPI, but H2 blocker use was associated with a 79% reduction in risk of failure to discontinue PPI (p = 0.004). The taper group had significantly less symptoms 14, 18, 22, and 30 weeks after discontinuation.ConclusionsOur study suggests that there is no difference in successful discontinuation of PPIs between abrupt and taper methods at 12 months; however, there are less symptoms in the taper method, and H2 blocker use is associated with success. Further study is needed with larger numbers of participants and randomization of H2 blocker use.

The Development of a Quantitative RCM/MSG Application using Microsoft Office

The number of small to medium scale industries makes the development of a low cost and easy to use application to support maintenance programs development is necessary. Besides for industries, the developed application can be used also in the academic field for research. For cost reasons, the application is developed using Microsoft Access and Microsoft Excel. The development of the application is carried out in three steps, i.e. the determination of application specifications, the programming in Microsoft Access and Microsoft Excel, and the validation and user-friendly test. The application is developed by considering the relationship between the risk quantification of a failure effect and the selection of a maintenance task and its interval. The effectiveness assessments are based on the failure risk reduction up to an acceptable level. The developed application is named "Quantitative RCM/MSG". The application can conduct a database management according to the steps of the RCM/MSG method. The application can determine the required maintenance tasks and intervals for the category of evident and hidden failure effects by taking the safety and financial aspects into account. This application does its functions correctly and easy to use. For further application development, application can be developed using series and combination systems. Application with module redesign on default action

Non-steroidal mineralocorticoid antagonists: Prospects for renoprotection in diabetic kidney disease.

Diabetic kidney disease (DKD) is the major cause of kidney failure in the world and the combination of DKD and diabetes mellitus contributes to an additive incidence of worsening cardiovascular mortality rates. Angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) remain the mainstay of therapy and have reduced kidney function decline in DKD from 8 to 10 to ~4 mL/min/y. Sodium-glucose co-transporter-2 (SGLT2) inhibitors, in the presence of ACE inhibitors or ARB agents, further slowdown DKD progression by an additional 58% to 1.8 mL/min/y. Moreover, SGLT2 inhibitors reduce heart failure risk. However, the normal rate of kidney function decline in humans is between 0.7 and 0.9 mL/min/y, hence, there is still room for improvement. Mineralocorticoid receptor antagonists (MRAs) already have a track record of benefit in heart failure risk reduction, and efficacy in reducing albuminuria and treating resistant hypertension; however hyperkalaemia and other adverse effects preclude their routine use in DKD. Novel non-steroidal MRAs offer a reduced risk of hyperkalaemia, and yet have many benefits that they share with their steroidal cousins. This paper reviews the data for both steroidal and non-steroidal MRAs in DKD and presents some data from soon-to-be-completed ongoing renal and cardiovascular outcome trials in DKD.

CBS gene polymorphism and promoter methylation-mediating effects on the efficacy of folate therapy in patients with hyperhomocysteinemia.

A decrease in cystathionine beta-synthase (CBS) enzyme activity could lead to hyperhomocysteinemia (HHcy). Studies have revealed that DNA methylation has a mediating effect on the development of diseases. The present study aimed to explore CBS promoter methylation-mediating effects on the efficacy of folate treatment for HHcy. HHcy patients were treated with folate (5 mg/day) for 90 days and then divided into a failure group (Hcy ≥ 15 μmol/l) and a success group (Hcy < 15 μmol/l) according to post-treatment plasma Hcy levels. Genotyping of CBS gene (rs2851391 and rs706209) in patients (n = 638) was detected using a MassArray system (Sequenom, San Diego, CA, USA). The baseline DNA methylation levels of patients (n = 299) were detected using MethylTarget™ technology (Genesky Biotechnologies Inc., Shanghai, China). The CBS rs2851391 TC + CC genotype was related to a 57% reduction of failure risk in HHcy treatment compared to the TT genotype (95% confidence interval [CI] = 0.19-0.97). The CBS rs706209 CT + TT genotype had a 2.97-fold increased risk of failure to treatment compared to the CC genotype (95% CI = 1.52-5.80). After adjustment for confounding factors, the odds ratio (95% CI) for the risk of failure in HHcy treatment in total and male patients was 0.55 (0.32-0.93) and 0.34 (0.16-0.69), respectively, for patients with higher methylation levels (≥ methylation median). Additionally, baseline CBS promoter methylation mediated 33.39% of the effect of rs2851391 on the efficacy of folate treatment for HHcy (ACME [average causal mediation effects]: -0.05, 95% CI = -0.11 to 0.00, p = 0.046). The present study indicates that CBS gene polymorphism and promoter methylation could affect the efficacy of HHcy. There were potentially causal effects of genetic, epigenetic variations at the CBS rs2851391 locus on the efficacy of HHcy therapy with folate.

The Intention-to-Treat Effect of Bridging Treatments in the Setting of Milan Criteria-In Patients Waiting for Liver Transplantation.

In patients with hepatocellular carcinoma (HCC) meeting the Milan criteria (MC), the benefit of locoregional therapies (LRTs) in the context of liver transplantation (LT) is still debated. Initial biases in the selection between treated and untreated patients have yielded conflicting reported results. The study aimed to identify, using a competing risk analysis, risk factors for HCC-dependent LT failure, defined as pretransplant tumor-related delisting or posttransplant recurrence. The study was registered at www.clinicaltrials.gov (identification number NCT03723304). In order to offset the initial limitations of the investigated population, an inverse probability of treatment weighting (IPTW) analysis was used: 1083 MC-in patients (no LRT=182; LRT=901) were balanced using 8 variables: age, sex, Model for End-Stage Liver Disease (MELD) value, hepatitis C virus status, hepatitis B virus status, largest lesion diameter, number of nodules, and alpha-fetoprotein (AFP). All the covariates were available at the first referral. After the IPTW, a pseudo-population of 2019 patients listed for LT was analyzed, comparing 2 homogeneous groups of untreated (n=1077) and LRT-treated (n=942) patients. Tumor progression after LRT was the most important independent risk factor for HCC-dependent failure (subhazard ratio [SHR], 5.62; P<0.001). Other independent risk factors were major tumor diameter, AFP, MELD, patient age, male sex, and period of wait-list registration. One single LRT was protective compared with no treatment (SHR, 0.51; P<0.001). The positive effect was still observed when 2-3 treatments were performed (SHR, 0.66; P=0.02), but it was lost in the case of ≥4 LRTs (SHR, 0.80; P=0.27). In conclusion, for MC-in patients, up to 3 LRTs are beneficial for success in intention-to-treat LT patients, with a 49% to 34% reduction in failure risk compared with untreated patients. This benefit is lost if more LRTs are required. A poor response to LRT is associated with a higher risk for HCC-dependent transplant failure.

Development of forming tool concept validator with variable stiffness blank-holder for high strength steel applications

This paper presents numerical and experimental results of a prototype tool that includes blank-holder elements of variable stiffness. The application is developed for high-strength steel applications aiming to achieve improvements in the forming operation, namely expand the limits of formability for the tested materials. A numerical model was built including material constitutive models description for the high-strength steel grades used while a forming tool was designed and constructed in order to evaluate the proposed concept. The obtained experimental and numerical results show a positive geometry control and reduction of failure risk. These results are a contribution to the validation of a variable-stiffness blank-holder concept for this particular case study.

Development of intervention programs for inland waterway networks using genetic algorithms

Inland waterways often consist of large numbers of man-made objects to ensure navigability. These objects are of many different types, ages and sizes, and deteriorate in uncountable of different ways. In order to ensure that the deterioration of the objects does not result in a loss of navigability, interventions must be executed. This, however, produces costs, in terms of both labour and material costs and costs of loss of service if the waterway is rendered non-navigable during intervention. In this paper, a methodology is presented to determine optimal multiple time period intervention programmes for inland waterways. The optimal intervention programme is the one that has highest net benefit, i.e. overall benefits minus overall costs, where benefits are the reduction in risk of failure. A genetic algorithm is used to overcome the problem of combinatorial explosion when many objects, in many states, over many time periods are to be considered. The exact formulation of the genome, as well as the genetic fitness function, are presented. They are used to determine an optimal intervention programme for a fictive inland waterway network. The results are presented and discussed, and an outlook is provided on further steps to improve this methodology.

Prostate Specific Antigen Bounce Is Related to Overall Survival in Prostate Brachytherapy

To investigate the association between prostate specific antigen (PSA) bounce and disease outcome after prostate brachytherapy. We analyzed 975 patients treated with (125)I implantation monotherapy between 1992 and 2006. All patients had tumor Stage ≤ 2c, Gleason score ≤ 7 prostate cancer, a minimum follow-up of 2 years with at least four PSA measurements, and no biochemical failure in the first 2 years. Median follow-up was 6 years. Bounce was defined as a PSA elevation of +0.2 ng/mL with subsequent decrease to previous nadir. We used the Phoenix +2 ng/mL definition for biochemical failure. Additional endpoints were disease-specific and overall survival. Multivariate Cox regression analysis was performed to adjust for potential confounding factors. Bounce occurred in 32% of patients, with a median time to bounce of 1.6 years. More than 90% of bounces took place in the first 3 years after treatment and had disappeared within 2 years of onset. Ten-year freedom from biochemical failure, disease-specific survival, and overall survival rates were, respectively, 90%, 99%, and 88% for the bounce group and 70%, 93%, and 82% for the no-bounce group. Only 1 patient (0.3%) died of prostate cancer in the bounce group, compared with 40 patients (6.1%) in the no-bounce group. Adjusted for confounding, a 70% biochemical failure risk reduction was observed for patients experiencing a bounce (hazard ratio 0.31; 95% confidence interval 0.20-0.48). A PSA bounce after prostate brachytherapy is strongly related to better outcome in terms of biochemical failure, disease-specific survival, and overall survival.

Effect of laxatives and pharmacological therapies in chronic idiopathic constipation: systematic review and meta-analysis

BackgroundThere has been no definitive systematic review and meta-analysis to date examining the effect of laxatives and pharmacological therapies in chronic idiopathic constipation (CIC).ObjectiveTo assess efficacy of these therapies systematically...

Determining the optimal maintenance action for a deteriorating repairable system

This paper develops a decision model for risk management of the deterioration of a repairable system. When a failure occurs in a deteriorating system, an optimal maintenance decision that includes the possibility of system replacement, as compared to mere deterioration reduction, should be made. There are many uncertainties associated with deterioration, however, so the decision may require a probabilistic analysis. Here, a well-known nonhomogeneous Poisson process with a power law intensity function is used to model the uncertain behavior of the deteriorating system. A Bayesian statistical approach is adopted to allow for the uncertainty of the parameters of the power law intensity function, which imposes a conjugate prior distribution of the parameters. A power law maintenance cost function and the failure cost are analyzed to determine the magnitude of failure risk reduction by minimizing the expected cost incurred from the maintenance action and future failures. A numerical example is given.

Post Placement Affects Survival of Endodontically Treated Premolars

Clinical evidence is lacking regarding the influence of the amount of residual coronal dentin and of post placement on the failure risk of endodontically compromised teeth. The aim of this prospective clinical trial was to assess whether these factors significantly affect the two-year survival of restored pulpless premolars. A sample of 210 individuals provided six experimental groups of 40 premolars in need of endodontic treatment. Groups were defined based on the amount of dentin left at the coronal level. Within each group, in half of the teeth selected at random, a fiber post was inserted inside the root canal, whereas in the remaining half of the premolars, no post was placed. All teeth were covered with a crown. The Cox regression analysis revealed that post placement resulted in a significant reduction of failure risk (p < 0.001). Failure risk was increased for teeth under the "no ferrule" (p = 0.001) and "ferrule effect" conditions (p = 0.004).

Blood pressure reduction in stable angina by nifedipine was related to stroke and heart failure reduction but not to coronary interventions

Background and Objective Whether blood pressure (BP) reduction is a necessary prerequisite for cardiovascular risk reduction or an epiphenomenon has not been definitively established. We used an innovative analytic method to address this question. Methods For 7,287 participants in a stable angina trial comparing long-acting nifedipine to placebo, we estimated the BP response after 2 weeks of treatment corrected for regression-to-the mean, and then related the latter and assigned treatment to subsequent cardiovascular outcomes. Results Subsequent stroke and heart failure was strongly related to 2-week corrected systolic BP response, but coronary angiography and bypass surgery was not. Adjustment for the 2-week corrected systolic BP response changed nifedipine effect estimates (relative to placebo) for subsequent stroke from 28% ( P = 0.04) to 21% ( P = 0.13) risk reduction, and for heart failure from 30% ( P = 0.02) to 21% ( P = 0.11) risk reduction; but did not alter the effect estimates for coronary angiography (27% reduction, P < 0.001), and coronary bypass surgery (22% reduction, P = 0.002). Conclusion The stroke and heart failure risk reduction by nifedipine GITS in patients with stable angina can be attributed partly to its BP lowering effect, whereas effects on coronary procedures are likely to be related almost entirely to its antianginal effects.