Prognostic implications of clinical practice guidelines among hemodialysis patients

Although the National Kidney Foundation (NKF) has published clinical practice guidelines for the management of risk factors for cardiovascular disease, these guidelines have not been tested rigorously for their effectiveness. We conducted an observational study among patients with end-stage kidney disease to examine the prognostic impact of threshold levels recommended by the NKF for blood pressure, hemoglobin, calcium-phosphate product, parathyroid hormone, low-density lipoprotein, and glycosylated hemoglobin. The study population (N = 197) was assembled from a previously completed randomized trial examining arteriovenous graft thrombosis. Cox proportional hazard analysis was used to calculate hazard ratios for the association of levels outside guideline recommended targets and death, adjusting for age, comorbidity, race, and albumin. The proportion of patients outside guideline targets ranged from 33% to 81%, and the impact of levels outside guideline targets on mortality varied substantially. Elevated calcium-phosphate product and glycosylated hemoglobin had harmful effects, with adjusted hazard ratios of 1.58 (95% CI 1.00-2.50; p = 0.050) and 2.21 (95% CI 0.99-4.97; p = 0.054), respectively. Nontarget levels for blood pressure, hemoglobin, and parathyroid hormone had little effect, with adjusted hazard ratios of 1.15 (95% CI 0.74-1.78; p = 0.542), 1.04 (95% CI 0.65-1.68; p = 0.866), and 0.90 (95% CI 0.50-1.61; p = 0.722), respectively. Elevated low-density lipoprotein had a paradoxically beneficial effect, with an adjusted hazard ratio of 0.48 (95% CI 0.23-1.00; p = 0.049). These results suggest that the prognostic impact of current threshold levels recommended by select NKF guidelines on mortality is variable. Accordingly, the development and implementation of clinical practice guidelines should be accompanied by corresponding efforts to confirm their impact on patient outcomes. Such efforts are essential for the improvement of guidelines and to inform health policy optimally.     

A new database of the references on international clinical practice guidelines: a facility for the evaluation of clinical research

Scientometrics - Although there are now several bibliographic databases of research publications, such as Google Scholar, Pubmed, Scopus, and the Web of Science (WoS), and some also include counts...     

Good clinical laboratory practice (GCLP): the need for a hybrid of good laboratory practice and good clinical practice guidelines/standards for medical testing laboratories conducting clinical trials in developing countries.

There has been a significant increase in the number of clinical drug trials (particularly phase III) being conducted in developing countries for infectious diseases such as HIV, malaria, and tuberculosis. Laboratory results provided by medical testing laboratories in the region are critical to ensuring the safety of patients and the generation of good quality data. A number of well accepted Good Clinical Practice (GCP) and Good Laboratory Practice (GLP) guidelines govern the conduct of clinical trials internationally. Good Clinical Practice guidelines remain too vague with respect to sample analysis to ensure practical implementation in these laboratories. In their strictest sense, Good Laboratory Practice guidelines refer to the analysis of samples from non-clinical studies. A specific set of minimum standards or requirements for practical implementation of clinical trial requirements in medical testing laboratories in the developing world is urgently required.     

Sample-size guidelines for recalibrating crash prediction models: Recommendations for the highway safety manual

The Highway Safety Manual (HSM) prediction models are fitted and validated based on crash data collected from a selected number of states in the United States. Therefore, for a jurisdiction to be able to fully benefit from applying these models, it is necessary to calibrate or recalibrate them to local conditions. The first edition of the HSM recommends calibrating the models using a one-size-fits-all sample-size of 30–50 locations with total of at least 100 crashes per year. However, the HSM recommendation is not fully supported by documented studies. The objectives of this paper are consequently: (1) to examine the required sample size based on the characteristics of the data that will be used for the calibration or recalibration process; and, (2) propose revised guidelines. The objectives were accomplished using simulation runs for different scenarios that characterized the sample mean and variance of the data. The simulation results indicate that as the ratio of the standard deviation to the mean (i.e., coefficient of variation) of the crash data increases, a larger sample-size is warranted to fulfill certain levels of accuracy. Taking this observation into account, sample-size guidelines were prepared based on the coefficient of variation of the crash data that are needed for the calibration process. The guidelines were then successfully applied to the two observed datasets. The proposed guidelines can be used for all facility types and both for segment and intersection prediction models.     

Thermographic nondestructive evaluation: Data inversion procedures

A data inversion procedure is presented, for the one-dimensional case, to retrieve the subsurface defect depth and thermal resistance from the time evolution of the surface temperature distribution as recorded by a thermographic camera (thermal “defectometry”). The inversion algorithm is based on the global minimization of a specific functional (nonlinear least squares problem) through an iterational routine taking into account simultaneously all of the defect variables and their effects on the values of the observable parameters. Surface losses are included as an unknown Biot number in the inversion routine. This paper deals with one-dimensional thermal flow. Part II, in this same issue, covers the two-dimensional theory and the experimental results.     

Discussions about safety criteria and guidelines for radioactive waste management

In Japan, the clearance levels for uranium-bearing waste have been established by the Nuclear Safety Commission (NSC). The criteria for uranium-bearing waste disposal are also necessary; however, the NSC has not concluded the discussion on this subject. Meanwhile, the General Administrative Group of the Radiation Council has concluded the revision of its former recommendation 'Regulatory exemption dose for radioactive solid waste disposal', the dose criteria after the institutional control period for a repository. The Standardization Committee on Radiation Protection in the Japan Health Physics Society (The Committee) also has developed the relevant safety criteria and guidelines for existing exposure situations, which are potentially applicable to uranium-bearing waste disposal. A new working group established by The Committee was initially aimed at developing criteria and guidelines specifically for uranium-bearing waste disposal; however, the aim has been shifted to broader criteria applicable to any radioactive wastes.     

Ensuring measurement uniformity in commercial evaluation of petroleum gas

Translated from Izmeritel'naya Tekhnika, No. 7, pp. 44–46, July, 1992.     

Comparison of an effect-model-law-based method versus traditional clinical practice guidelines for optimal treatment decision-making: application to statin treatment in the French population

Healthcare authorities make difficult decisions about how to spend limited budgets for interventions that guarantee the best cost-efficacy ratio. We propose a novel approach for treatment decision-making, OMES—in French: Objectif thérapeutique Modèle Effet Seuil (in English: Therapeutic Objective–Threshold–Effect Model; TOTEM). This approach takes into consideration results from clinical trials, adjusted for the patients'' characteristics in treatment decision-making. We compared OMES with the French clinical practice guidelines (CPGs) for the management of dyslipidemia with statin in a computer-generated realistic virtual population, representing the adult French population, in terms of the number of all-cause deaths avoided (number of avoided events: NAEs) under treatment and the individual absolute benefit. The total budget was fixed at the annual amount reimbursed by the French social security for statins. With the CPGs, the NAEs was 292 for an annual cost of 122.54 M€ compared with 443 with OMES. For a fixed NAEs, OMES reduced costs by 50% (60.53 M€ yr⁻¹). The results demonstrate that OMES is at least as good as, and even better than, the standard CPGs when applied to the same population. Hence the OMES approach is a practical, useful alternative which will help to overcome the limitations of treatment decision-making based uniquely on CPGs.     

The cooling performance of a cryoprobe: Establishing guidelines for the safety margins in cryosurgery

Cryosurgery is a minimally invasive surgical technique that uses cryoprobes or cryoneedles to freeze and destroy tumors or undesirable tissues. It is supported by non-invasive monitoring technologies such as MRI and ultrasonography, which make it possible to distinguish frozen regions in tissues and organs. However, the application of an ice ball to a cancerous tissue cannot guarantee the eradication of the complete tumor. Exposing all cancer cells to the lethal temperature, while minimizing the exposure of the healthy tissue to avoid side effects, is necessary. Therefore, the size of the ice ball is a key issue in cryosurgery. However, no data on the performance of clinically used cryoprobes are available in the open literature. The objective of this study was to experimentally validate the cooling performance of a widely used Joule–Thomson cryoprobe, to investigate the growth of the ice ball and cooling power of the probe, and to suggest guidelines for establishing the safety margin at the ice periphery. A numerical simulation was also carried out, and the results were compared with the experimental findings.     

Appraising clinical practice guidelines in England and Wales: the development of a methodologic framework and its application to policy.

BACKGROUND: Clinical guidelines are pervading all aspects of health care. Their potential benefits are vast--from decreasing unjustified variation in treatment, to improving outcomes for patient, to containing escalating costs. However, there is increasing concern that many of the guidelines produced may be of low quality and recommend ineffective treatment. A framework to appraise the methodologic quality of clinical guidelines, commissioned by the NHS in 1997, was developed and validated in the United Kingdom (UK) under the auspices of the National Research and Development Programme. THE INDEPENDENT APPRAISAL SERVICE: This framework is now used to assess all national guidelines funded by the National Health Service (NHS) in the UK as part of an independent appraisal service. The appraisal provides a basis for policymakers to decide which guidelines should be commended for use in the NHS. Each guideline is appraised by a minimum of six appraisers. Twenty-one guidelines had been appraised as of July 1999. The mean time for completion of the appraisals, from receipt of the guidelines to dispatch of the reports, was just over ten weeks. There has been a marked improvement in the quality of documentation for national guidelines--including the search strategy and synthesis of evidence--in the past three years, although some areas of development remain inadequately reported. POLICY IMPLICATIONS: Ensuring that the clinical guidelines are sound before recommending their use is essential to policymakers responsible for guideline programs, and a formal appraisal should be an integral part of those programs.     

A systems model for safety program evaluation

A system of program evaluation is presented that examines organizational and programmatic aspects of countermeasures as well as three levels of outcome. Level one outcomes include changes in skills, knowledge, attitudes and resources. Change in behavior is the level two outcome. The ultimate or level three outcomes are increased cost effectiveness and reduction in death, disability, discomfort, dissatisfaction and deleterious side effects. Evaluation often requires assessment of level one and two outcomes for gatekeepers as well as for the ultimate population to be reached. Attention also must be paid to separate analysis of high vs low risk situations for injury events. The time series approach to evaluation should be used only on those rare occasions where it is not feasible to apply two by two design or its modifications.     

Efficacy and safety of Cinacalcet on secondary hyperparathyroidism in Chinese chronic kidney disease patients receiving hemodialysis

Introduction Secondary hyperparathyroidism (SHPT) develops in patients with chronic renal failure. Cinacalcet hydrochloride has been used successfully in U.S., Europe, and Japan in the treatment of SHPT, while maintaining serum levels of calcium and phosphorus. The efficacy and safety profile of Cinacalcet treatment vs. conventional treatments has been of great interest in clinical practice. In this recent phase III study conducted in China, efficacy and safety of a calcimimetic agent, Cinacalcet (Kyowa Hakko Kirin Co., Ltd.), were assessed for SHPT treatment in stable chronic renal disease patients on hemodialysis. Methods In this double‐blind, multicenter, placebo‐controlled, randomized phase III study, 238 subjects were enrolled in 12 centers and randomly divided into a Cinacalcet group and a placebo group. The percentage of patients achieving a serum parathyroid hormone (PTH) level ≤250 pg/mL was the primary efficacy end point. Serum calcium and phosphorus levels were measured. Adverse events and serious adverse events were recorded, and causal analysis performed. Findings In primary analysis, 25.4% of the Cinacalcet group and 3.5% of the placebo group achieved the primary end point (PTH ≤250 pg/mL). Calcium and phosphorus levels and calcium–phosphorus product were lower in the Cinacalcet group compared with the placebo group. Eleven serious adverse events were reported and considered to be not related to study drugs. Mild to moderate hypocalcemia and reduced calcium levels were reported and considered to be Cinacalcet related. Discussion This phase III study demonstrated that Cinacalcet is effective and well tolerated in treating SHPT in Chinese chronic kidney disease patients on hemodialysis, and in a patient population with much higher baseline PTH levels.     

Quality assurance (QA) procedures for software: evaluation of an ADC quality system

Image viewing and processing software in computed radiography manipulates image contrast in such a way that all relevant image features are rendered to an appropriate degree of visibility, and improves image quality using enhancement algorithms. The purpose of this study was to investigate procedures for the quality assessment of image processing software for computed radiography with the use of existing test objects and to assess the influence that processing introduces on physical image quality characteristics. Measurements of high-contrast resolution, low-contrast resolution, spatial resolution, greyscale (characteristic curve) and geometric distortion were performed 'subjectively' by three independent observers and 'objectively' by the use of criteria based on pixel intensity values. Results show quality assessment is possible without the need for human evaluators, using digital images. It was discovered that the processing software evaluated in this study was able to improve some aspects of image quality, without introducing geometric distortion.     

Economic evaluation of traffic safety measures for transport companies

This paper addresses the economic feasibility of measures to reduce the material damage of transport companies. Results are presented of a series of interviews among transport companies as well as from a postal questionnaire survey. Next, calculations are presented for three types of companies: a small family company, a large family company and a large formalised company. From the viewpoint of costs and benefits, damage prevention measures appear to be particularly interesting to larger companies. Small companies, being the largest group, tend to have an informal culture in which measures are less effective. Especially those measures for which no large investments are needed, which influence the behaviour of drivers and need not to be contracted out, are perceived as attractive by the transport companies.     

A comparative evaluation of sequential set point adjustment procedures for tolerance control

The machining of complex parts typically involves a logical and chronological sequence of n operations on m machine tools. Because manufacturing datums cannot always match design datums, some of the design specifications imposed on the part are usually satisfied by distinct subsets of the n operations prescribed in the process plan. Conventional tolerance control specifies a fixed set point for each operation and permissible variation about this set point to insure compliance with the specifications. Sequential tolerance control (STC) uses real-time measurement information at the completion of one stage to exploit the available space inside a dynamic feasible zone and reposition the set point for subsequent operations. This paper introduces an extension of STC that utilizes the variability of the operations to scale the problem data and further enhance the ability of STC to optimize the production of an acceptable part.     

Design and evaluation of shock-absorbing rubber tile for playground safety

Rubber tiles are commonly used in playgrounds as protective surfacing to reduce the incidence of head injuries in children caused by falling from equipment. This paper presents a newly designed rubber tile consisting of a surface layer of solid and a base layer of honeycomb shape plate-cell. This tile was applied to investigate head injury protective performance. A validated technique combined with experimental and numerical methods was utilized to perform head impact on the rubber tile. The peak acceleration and head injury criterion (HIC) were employed to assess the shock-absorbing capability of the tile. The better protective ability of the honeycomb-core was attributed to its lower transverse shearing stiffness. As a result, the likelihood of establishing safe protection in playground and reducing severe child head injuries could be magnified.