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1.  Mild hypoglycemia is strongly associated with increased intensive care unit length of stay 
Background
Hypoglycemia is associated with increased mortality in critically ill patients. The impact of hypoglycemia on resource utilization has not been investigated. The objective of this investigation was to evaluate the association of hypoglycemia, defined as a blood glucose concentration (BG) < 70 mg/dL, and intensive care unit (ICU) length of stay (LOS) in three different cohorts of critically ill patients.
Methods
This is a retrospective investigation of prospectively collected data, including patients from two large observational cohorts: 3,263 patients admitted to Stamford Hospital (ST) and 2,063 patients admitted to three institutions in The Netherlands (NL) as well as 914 patients from the GLUCONTROL trial (GL), a multicenter prospective randomized controlled trial of intensive insulin therapy.
Results
Patients with hypoglycemia were more likely to be diabetic, had higher APACHE II scores, and higher mortality than did patients without hypoglycemia. Patients with hypoglycemia had longer ICU LOS (median [interquartile range]) in ST (3.0 [1.4-7.1] vs. 1.2 [0.8-2.3] days, P < 0.0001), NL (5.2 [2.6-10.3] vs. 2.0 [1.3-3.2] days, P < 0.0001), and GL (9 [5-17] vs. 5 [3-9] days, P < 0.0001). For the entire cohort of 6,240 patients ICU LOS was 1.8 (1.0-3.3) days for those without hypoglycemia and 3.0 (1.5-6.7) days for those with a single episode of hypoglycemia (P < 0.0001). This was a consistent finding even when patients were stratified by severity of illness or survivor status. There was a strong positive correlation between the number of episodes of hypoglycemia and ICU LOS among all three cohorts.
Conclusions
This multicenter international investigation demonstrated that hypoglycemia was consistently associated with significantly higher ICU LOS in heterogeneous cohorts of critically ill patients, independently of severity of illness and survivor status. More effective methods to prevent hypoglycemia in these patients may positively impact their cost of care.
doi:10.1186/2110-5820-1-49
PMCID: PMC3273438  PMID: 22115519
hypoglycemia; intensive care unit; length of stay; resource utilization; APACHE II; mortality; intensive insulin therapy
2.  High levels of cellular proliferation predict pseudoprogression in glioblastoma patients 
International Journal of Oncology  2011;40(4):923-928.
Radiochemotherapy (RT) with concomitant followed by monthly temozolomide (TMZ) chemotherapy is the gold standard for the treatment of glioblastoma (GBM) patients. GBM patients can experience transient radiological deterioration after concurrent RT/TMZ that stabilizes or even resolves after additional cycles of adjuvant TMZ, a phenomenon defined as radiological pseudoprogression. The aim of this retrospective study was to identify a reliable marker associated with pseudoprogression processes. Patients with histologically proven newly diagnosed GBM were identified from a retrospective database between 2005 and 2009. Predictive factors for pseudoprogression were analyzed from clinical, radiological and biological data. Of the 130 analyzed patients, 63 underwent RT/TMZ treatment followed by cycles of TMZ and were evaluated for radiological responses every two months by magnetic resonance imaging. Early progression was confirmed in 52% (33/63) of the patients, and, within this group, 21% (7/33) displayed evidence of pseudo-progression. The predictive factors were evidenced in terms of clinical or radiological findings. In GBM patients, the level of cellular proliferation (Ki67 indices) emerged as a statistically significant prognostic marker for distinguishing pseudoprogression from actual progression. Our observation, suggesting that GBM associated with a high level of cellular proliferation may differentiate tumor progression from pseudoprogression, warrants further investigation in a large multi-center prospective study.
doi:10.3892/ijo.2011.1260
PMCID: PMC3584626  PMID: 22086066
cellular proliferation; glioblastoma; Ki67; pseudo-progression; radiochemotherapy
3.  Mild hypoglycemia is independently associated with increased mortality in the critically ill 
Critical Care  2011;15(4):R173.
Introduction
Severe hypoglycemia (blood glucose concentration (BG) < 40 mg/dL) is independently associated with an increased risk of mortality in critically ill patients. The association of milder hypoglycemia (BG < 70 mg/dL) with mortality is less clear.
Methods
Prospectively collected data from two observational cohorts in the USA and in The Netherlands, and from the prospective GLUCONTROL trial were analyzed. Hospital mortality was the primary endpoint.
Results
We analyzed data from 6,240 patients: 3,263 admitted to Stamford Hospital (ST), 2,063 admitted to three institutions in The Netherlands (NL) and 914 who participated in the GLUCONTROL trial (GL). The percentage of patients with hypoglycemia varied from 18% to 65% among the different cohorts. Patients with hypoglycemia experienced higher mortality than did those without hypoglycemia even after stratification by severity of illness, diagnostic category, diabetic status, mean BG during intensive care unit (ICU) admission and coefficient of variation (CV) as a reflection of glycemic variability. The relative risk (RR, 95% confidence interval) of mortality associated with minimum BG < 40, 40 to 54 and 55 to 69 mg/dL compared to patients with minimum BG 80 to 109 mg/dL was 3.55 (3.02 to 4.17), 2.70 (2.31 to 3.14) and 2.18 (1.87 to 2.53), respectively (all P < 0.0001). The RR of mortality associated with any hypoglycemia < 70 mg/dL was 3.28 (2.78 to 3.87) (P < 0.0001), 1.30 (1.12 to 1.50) (P = 0.0005) and 2.11 (1.62 to 2.74) (P < 0.0001) for the ST, NL and GL cohorts, respectively. Multivariate regression analysis demonstrated that minimum BG < 70 mg/dL, 40 to 69 mg/dL and < 40 mg/dL were independently associated with increased risk of mortality for the entire cohort of 6,240 patients (odds ratio (OR) (95% confidence interval (CI)) 1.78 (1.39 to 2.27) P < 0.0001), 1.29 (1.11 to 1.51) P = 0.0011 and 1.87 (1.46 to 2.40) P < 0.0001) respectively.
Conclusions
Mild hypoglycemia was associated with a significantly increased risk of mortality in an international cohort of critically ill patients. Efforts to reduce the occurrence of hypoglycemia in critically ill patients may reduce mortality
doi:10.1186/cc10322
PMCID: PMC3387616  PMID: 21787410
4.  The association between isoinertial trunk muscle performance and low back pain in male adolescents 
European Spine Journal  2009;19(4):624-632.
The literature reports inconsistent findings regarding the association between low back pain (LBP) and trunk muscle function, in both adults and children. The strength of the relationship appears to be influenced by how LBP is qualified and the means by which muscle function is measured. The aim of this study was to examine the association between isoinertial trunk muscle performance and consequential (non-trivial) low back pain (LBP) in male adolescents. Healthy male adolescents underwent anthropometric measurements, clinical evaluation, and tests of trunk range of motion (ROM), maximum isometric strength (STRENGTH) and peak movement velocity (VEL), using an isoinertial device. They provided information about their regular sporting activities, history and family history of LBP. Predictors of “relevant/consequential LBP” were examined using multivariable logistic regression. LBP status was reassessed after 2 years and the change from baseline was categorised. At baseline, 33/95 (35%) subjects reported having experienced consequential LBP. BMI, a family history of LBP, and regularly playing sport were each significantly associated with a history of consequential LBP (p < 0.05). 85/95 (89%) boys participated in the follow-up: 51 (60%) reported no LBP at either baseline or follow-up (never LBP); 5 (6%) no LBP at baseline, but LBP at follow-up (new LBP); 19 (22%) LBP at baseline, but none at follow-up; and 10 (12%) LBP at both time-points (recurrent/persistent LBP). The only distinguishing features of group membership in these small groups were: fewer sport-active in the “never LBP” group); worse trunk mobility, in the “persistent LBP” group, lower baseline sagittal ROM in the “never LBP” and “new LBP” (p < 0.05). Regular involvement in sport was a consistent predictor of LBP. Isoinertial trunk performance was not associated with LBP in adolescents.
doi:10.1007/s00586-009-1168-5
PMCID: PMC2899830  PMID: 19771455
Muscle strength; Range of motion; Sports; Adolescents; Low back pain

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