Ker-Ai Lee

Predictive value of bone resorption and formation markers in cancer patients with bone metastases receiving the bisphosphonate zoledronic acid.

PURPOSEnThree large, randomized trials of patients with bone metastases recently demonstrated that zoledronic acid reduces the risk of skeletal-related events. These trials provide an opportunity for investigating the correlation between bone metabolism and clinical outcome during bisphosphonate therapy.nnnPATIENTS AND METHODSnUrinary measurements of N-telopeptide (Ntx) and serum bone alkaline phosphatase (BAP) were obtained in 1,824 bisphosphonate-treated patients-1,462 with zoledronic acid (breast, 490; prostate, 411; myeloma, 210; non-small-cell lung, 183; other, 168) and 362 with pamidronate (breast, 254; myeloma, 108). This exploratory cohort analysis grouped patients by baseline and most recent levels of Ntx as low (< 50 nmol/mmol creatinine), moderate (50 to 99 nmol/mmol creatinine), or high (> or = 100 nmol/mmol creatinine), and BAP as low (< 146 U/L) or high (> or = 146 U/L). The relative risks for negative clinical outcomes were estimated for each group using multiple-event and Cox regression models with time-varying covariates.nnnRESULTSnPatients with high and moderate Ntx levels had 2-fold increases in their risk of skeletal complications and disease progression compared with patients with low Ntx levels (P < .001 for all). High Ntx levels in each solid tumor category were associated with a 4- to 6-fold increased risk of death on study, and moderate Ntx levels a 2- to 4-fold increased risk compared with low Ntx levels (P < .001 for all). Bone alkaline phosphatase also showed some correlation with risk of negative clinical outcomes.nnnCONCLUSIONnThe bone resorption marker Ntx provides valuable prognostic information in patients with bone metastases receiving bisphosphonates.

Multiple organ dysfunction: baseline and serial component scores.

Objective The multiple organ dysfunction score (MODS) describes and quantifies organ-specific physiology. The objective of this study was to examine the relation between six components of MODS (cardiovascular, respiratory, renal, central nervous system, hepatic, and hematologic) measured at admission to the intensive care unit (ICU) and during the ICU stay, with time to death in the ICU. Design Prospective observational cohort study. Setting Sixteen Canadian ICUs. Patients A total of 1,200 patients were mechanically ventilated for >48 hrs. Measurements and Main Results The six organ systems comprising MODS were measured at ICU admission (baseline scores) and daily thereafter. The change in organ dysfunction each day (serial scores) were calculated as daily component scores minus the corresponding baseline component scores. In Cox regression analyses, the independent explanatory variables were the MODS components measured at baseline and serially, and the dependent variable was the time from admission to ICU mortality. When each organ system was analyzed individually, both the baseline and serial MODS for the cardiovascular, respiratory, renal, central nervous system, and hematologic components were significantly associated with ICU mortality. After adjusting for the serial hepatic score, the baseline hepatic score was unrelated to mortality. After adjusting for all baseline and serial MODS components in aggregate, four organ systems were significantly associated with ICU mortality: cardiovascular (baseline relative risk [RR], 1.5; serial RR, 1.4); respiratory (baseline RR, 1.4; serial RR, 1.4); renal (baseline RR, 1.3; serial RR, 1.5); and central nervous system (baseline RR, 1.6; serial RR, 1.7). We found that the relative risk of mortality related to organ dysfunction varied significantly over time and among organ systems. Baseline respiratory function was not associated with mortality until the second ICU week (week 1: RR, 1.1 [0.9–1.4]; week 2 onward: RR, 1.9 [1.5–2.4]); the same was true for the change in respiratory function as measured by the serial respiratory score (week 1: RR, 1.2 [1.0–1.5]; week 2 onward: RR, 1.7 [1.4–2.1]). The serial hepatic score was not associated with mortality until the fourth ICU week (weeks 1–3: RR, 0.9 [0.7–1.1]; week 4 onward: RR, 1.4 [1.0–2.0]). Conclusions Organ dysfunction scores describe physiology at ICU admission and during ICU stay. Although patterns vary by system, daily MODS component scores provide additional prognostic value over baseline MODS.

Frequency, predictors, and prognosis of sustained minimal disease activity in an observational psoriatic arthritis cohort

To establish the frequency and predictors of minimal disease activity in psoriatic arthritis (PsA) and to investigate the prognostic ability of minimal disease activity criteria to predict future joint damage.

Disease and host characteristics as predictors of time to first bone metastasis and death in men with progressive castration‐resistant nonmetastatic prostate cancer

The natural history of castration‐resistant nonmetastatic prostate cancer is poorly defined.

Consensus on the utility of bone markers in the malignant bone disease setting

Biochemical markers of bone turnover provide insight into ongoing rates of skeletal metabolism and tumor-bone interactions in patients with malignant bone disease. This article reviews the available recent evidence assessing the potential of bone markers for detecting and monitoring malignant bone lesions in patients with advanced cancers, and for assessing overall skeletal health and response to antiresorptive therapies in patients at all stages of cancer progression. Most data thus far are for urinary N-terminal cross-linked telopeptide of type I collagen (NTX) in predicting risks of skeletal morbidity and death and monitoring response to zoledronic acid in patients with bone metastases. Ongoing studies are evaluating such correlations for other markers and therapies. Emerging evidence suggests that bone markers may help identify patients at high risk for bone metastasis or bone lesion progression, thereby allowing improved follow-up. Results from ongoing clinical trials evaluating such potential applications of bone markers are awaited.

Predictors of response to intra-articular steroid injection in psoriatic arthritis

OBJECTIVESnTo assess the effectiveness of IA corticosteroid (IAS) injections in PsA and to determine the association between macrophage migration inhibition factor (MIF) gene polymorphism and response to IAS injections.nnnMETHODSnA cohort analysis of PsA patients who were followed prospectively was performed. Clinical response was defined as no tenderness or effusion in the injected joint at 3 months. Relapse was defined as re-occurrence of joint pain or effusion. MIF 173C > G genotyping (rs755622) was performed.nnnRESULTSnTwo hundred and twenty patients with 245 IAS injections were included in the study. The probability of responding at 3 months was 41.6%. Within 12 months, 25.5% of the joints relapsed. Clinical factors that were associated with response included duration of psoriasis [Odds ratio (OR) 1.03] and the use of MTX or anti-TNF agents at the time of injection (OR 2.68). Factors that were associated with relapse included injection into large joints (OR 4.58) and elevated sedimentation rate (OR 15.0), whereas absence of clinical and/or radiographic damage (OR 0.23) and duration of PsA (OR 0.92) reduced risk of relapse. MIF polymorphism was not associated with clinical response, but was associated with relapse (OR 3.2). On multivariate analysis including clinical covariates, the association between MIF polymorphism and relapse was lost.nnnCONCLUSIONSnIAS injections are effective in PsA. MIF gene polymorphism is associated with relapse. However, this effect is explained by clinical variables that reflect disease activity, suggesting that MIF gene polymorphism influences inflammatory activity.

A multicenter pilot-randomized controlled trial of the feasibility of an augmented red blood cell transfusion strategy for patients treated with induction chemotherapy for acute leukemia or stem cell transplantation

BACKGROUND: Anemia may be an important factor contributing to an increased risk of bleeding, particularly in patients with thrombocytopenia.

Robust Estimation of Mean Functions and Treatment Effects for Recurrent Events Under Event-Dependent Censoring and Termination: Application to Skeletal Complications in Cancer Metastatic to Bone

In clinical trials featuring recurrent clinical events, the definition and estimation of treatment effects involves a number of interesting issues, especially when loss to follow-up may be event-related and when terminal events such as death preclude the occurrence of further events. This paper discusses a clinical trial of breast cancer patients with bone metastases where the recurrent events are skeletal complications, and where patients may die during the trial. We argue that treatment effects should be based on marginal rate and mean functions. When recurrent event data are subject to event-dependent censoring, however, ordinary marginal methods may yield inconsistent estimates. Incorporating correctly specified inverse probability of censoring weights into analyses can protect against dependent censoring and yield consistent estimates of marginal features. An alternative approach is to obtain estimates of rate and mean functions from models that involve some conditioning to render censoring conditionally independent. We consider three methods of estimating mean functions of recurrent event processes and examine the bias and efficiency of unweighted and inverse probability weighted versions of the methods with and without a terminating event. We compare the methods via simulation and use them to analyse the data from the breast cancer trial.

A Multistate Model for Bivariate Interval‐Censored Failure Time Data

SUMMARYnInterval-censored life-history data arise when the events of interest are only detectable at periodic assessments. When interest lies in the occurrence of two such events, bivariate-interval censored event time data are obtained. We describe how to fit a four-state Markov model useful for characterizing the association between two interval-censored event times when the assessment times for the two events may be generated by different inspection processes. The approach treats the two events symmetrically and enables one to fit multiplicative intensity models that give estimates of covariate effects as well as relative risks characterizing the association between the two events. An expectation-maximization (EM) algorithm is described for estimation in which the maximization step can be carried out with standard software. The method is illustrated by application to data from a trial of HIV patients where the events are the onset of viral shedding in the blood and urine among individuals infected with cytomegalovirus.

The Incidence and Risk Factors for Psoriatic Arthritis in Patients With Psoriasis: A Prospective Cohort Study

To estimate the incidence of psoriatic arthritis (PsA) in patients with psoriasis, and to identify risk factors for its development.