Steve Su

Intensive versus conventional glucose control in critically ill patients

BACKGROUND The optimal target range for blood glucose in critically ill patients remains unclear. METHODS Within 24 hours after admission to an intensive care unit (ICU), adults who were expected to require treatment in the ICU on 3 or more consecutive days were randomly assigned to undergo either intensive glucose control, with a target blood glucose range of 81 to 108 mg per deciliter (4.5 to 6.0 mmol per liter), or conventional glucose control, with a target of 180 mg or less per deciliter (10.0 mmol or less per liter). We defined the primary end point as death from any cause within 90 days after randomization. RESULTS Of the 6104 patients who underwent randomization, 3054 were assigned to undergo intensive control and 3050 to undergo conventional control; data with regard to the primary outcome at day 90 were available for 3010 and 3012 patients, respectively. The two groups had similar characteristics at baseline. A total of 829 patients (27.5%) in the intensive-control group and 751 (24.9%) in the conventional-control group died (odds ratio for intensive control, 1.14; 95% confidence interval, 1.02 to 1.28; P=0.02). The treatment effect did not differ significantly between operative (surgical) patients and nonoperative (medical) patients (odds ratio for death in the intensive-control group, 1.31 and 1.07, respectively; P=0.10). Severe hypoglycemia (blood glucose level, < or = 40 mg per deciliter [2.2 mmol per liter]) was reported in 206 of 3016 patients (6.8%) in the intensive-control group and 15 of 3014 (0.5%) in the conventional-control group (P<0.001). There was no significant difference between the two treatment groups in the median number of days in the ICU (P=0.84) or hospital (P=0.86) or the median number of days of mechanical ventilation (P=0.56) or renal-replacement therapy (P=0.39). CONCLUSIONS In this large, international, randomized trial, we found that intensive glucose control increased mortality among adults in the ICU: a blood glucose target of 180 mg or less per deciliter resulted in lower mortality than did a target of 81 to 108 mg per deciliter. (ClinicalTrials.gov number, NCT00220987.)

Intensity of Continuous Renal-Replacement Therapy in Critically Ill Patients

BACKGROUND The optimal intensity of continuous renal-replacement therapy remains unclear. We conducted a multicenter, randomized trial to compare the effect of this therapy, delivered at two different levels of intensity, on 90-day mortality among critically ill patients with acute kidney injury. METHODS We randomly assigned critically ill adults with acute kidney injury to continuous renal-replacement therapy in the form of postdilution continuous venovenous hemodiafiltration with an effluent flow of either 40 ml per kilogram of body weight per hour (higher intensity) or 25 ml per kilogram per hour (lower intensity). The primary outcome measure was death within 90 days after randomization. RESULTS Of the 1508 enrolled patients, 747 were randomly assigned to higher-intensity therapy, and 761 to lower-intensity therapy with continuous venovenous hemodiafiltration. Data on primary outcomes were available for 1464 patients (97.1%): 721 in the higher-intensity group and 743 in the lower-intensity group. The two study groups had similar baseline characteristics and received the study treatment for an average of 6.3 and 5.9 days, respectively (P=0.35). At 90 days after randomization, 322 deaths had occurred in the higher-intensity group and 332 deaths in the lower-intensity group, for a mortality of 44.7% in each group (odds ratio, 1.00; 95% confidence interval [CI], 0.81 to 1.23; P=0.99). At 90 days, 6.8% of survivors in the higher-intensity group (27 of 399), as compared with 4.4% of survivors in the lower-intensity group (18 of 411), were still receiving renal-replacement therapy (odds ratio, 1.59; 95% CI, 0.86 to 2.92; P=0.14). Hypophosphatemia was more common in the higher-intensity group than in the lower-intensity group (65% vs. 54%, P<0.001). CONCLUSIONS In critically ill patients with acute kidney injury, treatment with higher-intensity continuous renal-replacement therapy did not reduce mortality at 90 days. (ClinicalTrials.gov number, NCT00221013.)

An observational study fluid balance and patient outcomes in the Randomized Evaluation of Normal vs. Augmented Level of Replacement Therapy trial

Objective:To examine associations between mean daily fluid balance during intensive care unit study enrollment and clinical outcomes in patients enrolled in the Randomized Evaluation of Normal vs. Augmented Level (RENAL) replacement therapy study. Design:Statistical analysis of data from multicenter, randomized, controlled trials. Setting:Thirty-five intensive care units in Australia and New Zealand. Patients:Cohort of 1453 patients enrolled in the RENAL study. Interventions:We analyzed the association between daily fluid balance on clinical outcomes using multivariable logistic regression, Cox proportional hazards, time-dependent analysis, and repeated measure analysis models. Measurements and Main Results:During intensive care unit stay, mean daily fluid balance among survivors was –234 mL/day compared with +560 mL/day among nonsurvivors (p < .0001). Mean cumulative fluid balance over the same period was –1941 vs. +1755 mL (p = .0003). A negative mean daily fluid balance during study treatment was independently associated with a decreased risk of death at 90 days (odds ratio 0.318; 95% confidence interval 0.24–0.43; p < .000.1) and with increased survival time (p < .0001). In addition, a negative mean daily fluid balance was associated with significantly increased renal replacement-free days (p = .0017), intensive care unit-free days (p < .0001), and hospital-free days (p = .01). These findings were unaltered after the application of different statistical models. Conclusions:In the RENAL study, a negative mean daily fluid balance was consistently associated with improved clinical outcomes. Fluid balance may be a target for specific manipulation in future interventional trials of critically ill patients receiving renal replacement therapy.

Glucosamine and chondroitin for knee osteoarthritis: a double-blind randomised placebo-controlled clinical trial evaluating single and combination regimens

Objective To determine if the dietary supplements, glucosamine and/or chondroitin, result in reduced joint space narrowing (JSN) and pain among people with symptomatic knee osteoarthritis. Methods A double-blind randomised placebo-controlled clinical trial with 2-year follow-up. 605 participants, aged 45–75 years, reporting chronic knee pain and with evidence of medial tibio-femoral compartment narrowing (but retaining >2 mm medial joint space width) were randomised to once daily: glucosamine sulfate 1500 mg (n=152), chondroitin sulfate 800 mg (n=151), both dietary supplements (n=151) or matching placebo capsules (n=151). JSN (mm) over 2 years was measured from digitised knee radiographs. Maximum knee pain (0–10) was self-reported in a participant diary for 7 days every 2 months over 1 year. Results After adjusting for factors associated with structural disease progression (gender, body mass index (BMI), baseline structural disease severity and Heberdens nodes), allocation to the dietary supplement combination (glucosamine–chondroitin) resulted in a statistically significant (p=0.046) reduction of 2-year JSN compared to placebo: mean difference 0.10 mm (95% CI 0.002 mm to 0.20 mm); no significant structural effect for the single treatment allocations was detected. All four allocation groups demonstrated reduced knee pain over the first year, but no significant between-group differences (p=0.93) were detected. 34 (6%) participants reported possibly-related adverse medical events over the 2-year follow-up period. Conclusions Allocation to the glucosamine–chondroitin combination resulted in a statistically significant reduction in JSN at 2 years. While all allocation groups demonstrated reduced knee pain over the study period, none of the treatment allocation groups demonstrated significant symptomatic benefit above placebo. Trial Registration ClinicalTrials.gov identifier: NCT00513422; http://www.clinicaltrials.gov

Numerical maximum log likelihood estimation for generalized lambda distributions

This paper presents a two-step procedure using the method of moment or percentile to find initial values and then maximize the numerical log likelihood to fit the appropriate generalized lambda distribution to data. This paper demonstrates the use of this procedure to fit well-known statistical distributions as well as some empirical data. Overall, the use of numerical maximum log likelihood estimation is a valuable alternative among existing methods of fitting. It provides not only convincing results in terms of quantile plots and goodness of fit tests but also has the advantage of a lower variability in its parameter estimation compared to the existing starship (King and MacGillivray, 1999) and method of moment (Karian and Dudewicz, 2000) fitting schemes.

The high prevalence of knee osteoarthritis in a rural Chinese population: the Wuchuan osteoarthritis study.

OBJECTIVE To estimate the prevalence of radiographic and symptomatic knee osteoarthritis (OA) in a remote rural region of northern China, and compare them with those reported in Beijing and with data from the Framingham (Massachusetts) cohort. METHODS A population-based cross-sectional survey was conducted among 1,030 residents of Wuchuan County, Inner Mongolia, age > or =50 years. Survey participants, mostly farmers reporting heavy physical occupational activity, completed an interviewer-based questionnaire, and bilateral weight-bearing posteroanterior semiflexed knee radiographs were obtained. RESULTS Whereas the overall prevalence of radiographic knee OA was similar to that demonstrated in the Beijing OA study, men in Wuchuan had approximately double the prevalence of severe radiographic knee OA (prevalence ratio [PR] 2.5, 95% confidence interval [95% CI] 1.6-3.8) and symptomatic knee OA (PR 1.9, 95% CI 1.3-2.9). Women in Wuchuan also had a higher prevalence of both severe radiographic (PR 1.4, 95% CI 1.0-2.0) and symptomatic knee OA (PR 1.6, 95% CI 1.2-2.1) compared with their Beijing counterparts. The prevalence of bilateral OA and lateral compartment disease were 2-3 times higher in both Chinese cohorts compared with estimates from the Framingham OA study. CONCLUSION The prevalence of symptomatic knee OA in rural areas of China is much higher than reported from urban regions of China or in the Framingham cohort. The higher representation of bilateral and lateral compartment disease in China suggests a unique phenotype to OA. These findings will be useful for guiding the distribution of future health care resources and preventive strategies.

Reducing the burden of road traffic injury: translating high-income country interventions to middle-income and low-income countries

Objective: To increase seat belt restraint use in Guangzhou City, People’s Republic of China. Design: Comparison group pre-test, post-test design. Setting: Guangzhou City. Interventions: Interventions to increase the prevalence of seat belt use in high-income countries (enhanced training and enforcement practices along with raising of public awareness) were adapted and implemented in Guangzhou. The prevalence of seat belt use was determined before and after the introduction of the 12-month intervention. Seat belt prevalence was also examined over the same time period in the neighboring city of Nanning, and an incremental cost-effectiveness analysis of the intervention was undertaken. Main outcome measures: Prevalence rates and incremental cost effectiveness ratios. Results: A 12% increase in seat belt use was observed in Guangzhou over the study period, increasing from a prevalence of 50% before (error range 30–62%) to 62% after (error range 60–67%) (p<0.001) the intervention; an absolute change difference between the intervention and reference city of 20% was achieved. The incremental cost-effectiveness ratio of the intervention was ¥3246 (US

Confidence intervals for quantiles using generalized lambda distributions

418) per disability-adjusted life year saved. Conclusions: This city-wide intervention demonstrates that it is possible to increase the prevalence of seat belt use using similar methods to those used in high-income countries and, importantly, that such an approach is cost-effective.

A Statistical Activity Cost Analysis of Engineering Assets

Generalized lambda distributions (GLD) can be used to fit a wide range of continuous data. As such, they can be very useful in estimating confidence intervals for quantiles of continuous data. This article proposes two simple methods (Normal-GLD approximation and the analytical-maximum likelihood GLD approach) to find confidence intervals for quantiles. These methods are used on a range of unimodal and bimodal data and on simulated data from ten well-known statistical distributions (Normal, Students T, Exponential, Gamma, Log Normal, Weibull, Uniform, Beta, F and Chi-square) with sample sizes n=10,25,50,100 for five different quantiles q=5%,25%,50%,75%,95%. In general, the analytical-maximum likelihood GLD approach works better with shorter confidence intervals and has closer coverage probability to the nominal level as long as the GLD models the data with sufficient accuracy. This technique can also be used to find confidence interval for the mode of a continuous data as well as comparing two data sets in terms of quantiles.

A longitudinal study of knee pain in older men: Concord Health and Ageing in Men Project

In this paper, Statistical Activity Cost Analysis (SACA) is used to identify the interaction of mutually dependent physical and financial aspects of a fixed asset-like system configuration. The novelty of the approach is, having established a rational description of the uncertainty inherent in both domains, the analysis of their interaction. Little research to date has investigated the duality of engineering and accounting aspects, in a statistical setting. Our approach is conceptual rather than empirical. We use an illustrative 4-component model, a) to explain the concept of SACA by means of a software demonstration tool, b) to relate financial issues of cost to engineering asset capacity to perform specified tasks, and c) to demonstrate how to produce quantified measures of return and risk, both of which are relevant in areas of life-cycle analysis, budgeting and planning decision-making.