What decline in pain intensity is meaningful to patients with acute pain?

Despite widespread use of the 0-10 numeric rating scale (NRS) of pain intensity, relatively little is known about the meaning of decreases in pain intensity assessed by means of this scale to patients. We aimed to establish the meaning to patients of declines in pain intensity and percent pain reduction. Upon arrival to the postanesthesia care unit, postsurgical patients rated their baseline pain intensity on both a 0-10 NRS and on a 4-point verbal scale. Patients whose NRS was higher than 4/10 received intravenous opioids until their pain intensity declined to 4/10 or lower. During opioid titration, patients were asked every 10 min to rate pain intensity on a NRS and to indicate the degree of pain improvement on a 5-point Likert scale from 'no improvement' to 'complete pain relief'. Seven hundred adult patients were enrolled. For patients with moderate pain, a decrease of 1.3 units (20% reduction) corresponded to 'minimal' improvement, a decrease of 2.4 (35% reduction) to 'much' improvement, a decrease of 3.5 units (45% reduction) corresponded to 'very much' improvement. For patients with severe pain, the decrease in NRS pain score and the percentage of pain relief had to be larger to obtain similar degrees of pain relief. The change in pain intensity that is meaningful to patients increases as the severity of their baseline pain increases. The present findings are applicable in the clinical setting and research arena to assess treatment efficacy.     

Estimated number of adults with prediabetes in the US in 2000: opportunities for prevention

OBJECTIVE: To estimate the percent and number of overweight adults in the U.S. with prediabetes who would be potential candidates for diabetes prevention as per the American Diabetes Association Position Statement (12). RESEARCH DESIGN AND METHODS: We analyzed data from the Third National Health and Nutrition Examination Survey (NHANES III; 1988-1994) and projected our estimates to the year 2000. We defined impaired glucose tolerance (IGT; 2-h glucose 140-199 mg/dl), impaired fasting glucose (IFG; fasting glucose 110-125 mg/dl), and prediabetes (IGT or IFG) per American Diabetes Association (ADA) criteria. The ADA recently recommended that all overweight people (BMI >or=25 kg/m(2)) who are >or=45 years of age with prediabetes could be potential candidates for diabetes prevention, as could prediabetic people aged >25 years with risk factors. In NHANES III, 2-h postload glucose concentrations were done only among subjects aged 40-74 years. Because we were interested in overweight people who had both the 2-h glucose and fasting glucose tests, we limited our estimates of IGT, IFG, and prediabetes to those aged 45-74 years. RESULTS-Overall, 17.1% of overweight adults aged 45-74 years had IGT, 11.9% had IFG, 22.6% had prediabetes, and 5.6% had both IGT and IFG. Based on those data, we estimated that in the year 2000, 9.1 million overweight adults aged 45-74 had IGT, 5.8 million had IFG, 11.9 million had prediabetes, and 3.0 million had IGT and IFG. CONCLUSIONS: Almost 12 million overweight individuals aged 45-74 years in the U.S. may benefit from diabetes prevention interventions. The number will be substantially higher if estimation is extended to individuals aged >75 and 25-44 years.     

Utility of Tumor Burden Score to Stratify Prognosis of Patients with Hepatocellular Cancer: Results of 4759 Cases from ITA.LI.CA Study Group

Background

Dichotomous models like Milan Criteria represent the routinely used tools for predicting the outcome of patients with hepatocellular carcinoma (HCC). However, a paradigm shift from a dichotomous to continuous prognostic stratification should represent a good strategy for improving the prediction process. Recently, the tumor burden score (TBS) has been proposed for selecting patients with colorectal liver metastases. To date, TBS has not been validated in a large HCC population. The main objective of this study was to evaluate the prognostic power of TBS in an HCC population treated with different curative and palliative modalities.

Methods

Prospectively collected data from consecutive HCC patients managed in 24 institutions participating in the ITA.LI.CA group between Jan 2002 and Mar 2015 were analyzed (n?=?4759). A sub-analysis focused on 3909 patients with the radiological evidence of vascular invasion or metastatic disease was also performed.

Results

TBS demonstrated the best discriminative ability when compared to MC and other tumor-specific scores. At multivariable Cox regression analysis, TBS was an independent risk factor of overall survival, with a 6% increased risk for patient death for each point increase in TBS. At survival analysis, when TBS?≥?8 was connected with MELD?≥?15 and alpha-fetoprotein ≥?1000 ng/mL, patients presenting all these three risk factors presented the worst results (p value <?0.0001).

Conclusions

Survival prediction of HCC patients was very well done using TBS model, even stratifying the population in relation to the presence of metastases and/or vascular invasion. TBS model was the best in terms of discriminatory ability and goodness of fit when compared with other continuous or binary variables. Its incorporation in a model composed by tumor- and liver function-related variables further increases its survival prediction.

     

β subunits influence the biophysical and pharmacological differences between P- and Q-type calcium currents expressed in a mammalian cell line

Human epithelial kidney cells (HEK) were prepared to coexpress α1A, α2δ with different β calcium channel subunits and green fluorescence protein. To compare the calcium currents observed in these cells with the native neuronal currents, electrophysiological and pharmacological tools were used conjointly. Whole-cell current recordings of human epithelial kidney α1A-transfected cells showed small inactivating currents in 80 mM Ba²⁺ that were relatively insensitive to calcium blockers. Coexpression of α1A, βIb, and α2δ produced a robust inactivating current detected in 10 mM Ba²⁺, reversibly blockable with low concentration of ω-agatoxin IVA (ω-Aga IVA) or synthetic funnel-web spider toxin (sFTX). Barium currents were also supported by α1A, β2a, α2δ subunits, which demonstrated the slowest inactivation and were relatively insensitive to ω-Aga IVA and sFTX. Coexpression of β3 with the same combination as above produced inactivating currents also insensitive to low concentration of ω-Aga IVA and sFTX. These data indicate that the combination α1A, βIb, α2δ best resembles P-type channels given the rate of inactivation and the high sensitivity to ω-Aga IVA and sFTX. More importantly, the specificity of the channel blocker is highly influenced by the β subunit associated with the α1A subunit.     

Selective purging by human interleukin-2 activated lymphocytes of bone marrows contaminated with a lymphoma line or autologous leukaemic cells

The ability of recombinant interleukin 2 (rIL2) activated lymphocytes (LAK) to purge BM samples contaminated by tumour cells was evaluated. Human BM mononuclear cells were contaminated with 10% of the lymphoma line CA46 and then cultured in liquid medium containing 1000 U/ml of rIL2 and/or LAK autologous to the used BM. At the end of coculture the growth of residual tumour cells and of CFU-GM were evaluated by clonogenic assay. No tumour cell growth was observed in 5/5 independent experiments after 18 h of coculture with LAK. No significant inhibition of CFU-GM growth was also noted. Subsequently, the effect of LAK on BM obtained from four leukaemic patients and contaminated with 20-50% of their own AML and ALL cells was studied using MAb as a tool for identifying leukaemic cells. LAK eliminated 24-78% of contaminating cryopreserved uncultured autologous leukaemic cells. In five cases the BM was contaminated by a low (2%) amount of ALL cells. In these patients the monoclonal heavy chain rearrangement typical of ALL was no longer visible after coculture with LAK. Evidence for selective tumour cytotoxicity by LAK was confirmed by using autologous BM cells as hot and cold targets in a 51Cr release assay. Finally, successful haematologic reconstitution of lethally irradiated BALB/c mice was obtained using syngeneic BM cocultured with LAK. These results support the investigational use of rIL2 and LAK in the treatment of human leukaemia.     

Catheter motion during atrial ablation due to the beating heart and respiration: impact on accuracy and spatial referencing in three-dimensional mapping.

BACKGROUND: The accuracy of three-dimensional mapping systems is affected by cardiac contraction and respiration. OBJECTIVE: The study sought to determine relative motion of cardiac and thoracic structures to assess positional errors and guide the choice of an optimized spatial reference. METHODS: Motion of catheters placed at the coronary sinus (CS), pulmonary vein (PV) ostia, left atrial (LA) isthmus and roof, cavotricuspid isthmus (CTI), and right atrial appendage (RAA) were recorded for 30 patients using Ensite-NavX. The right subclavian vein, left brachiocephalic vein, azygos vein, pulmonary arteries, and a static reference were included. The displacement from a mean position was calculated for each pair of sites. Respiration effects were assessed by the shift of the motion curve during in- and expiration phases. RESULTS: The PVs showed a mean interpair displacement of 4.1 +/- 0.2 mm and a shift of 5.0 +/- 0.5 mm. Proximal CS references for all LA structures (4.0 +/- 1.1 mm) were superior to the static reference (4.9 +/- 0.7 mm; P = .01). In addition, the shift due to respiration was less pronounced at 3.5 +/- 0.8 mm versus 4.9 +/- 0.5 mm (P = .004), respectively. Motion of extracardiac vessels was influenced by a mean shift of 6.8 +/- 1 mm. The remote subclavian and brachiocephalic veins were more affected (7.6 +/- 0.7 mm) than the pulmonary arteries (5.9 +/- 0.4 mm; P = .002). For the CTI, a minimized mean displacement of less than 4.6 +/- 2.0 mm relative to the proximal CS, RAA, and azygos vein was found. CONCLUSION: Respiration is the major source of relative motion, which increases with distance from the heart. For LA procedures, a proximal CS reference position is superior to a static reference position.     

The revascular active percutaneous interventional device for coronary total occlusions study

Background. Despite the well‐documented benefit of recanalization of an occluded vessel in some symptomatic patients, attempt is only performed in a minority of them. Percutaneous coronary intervention (PCI) of CTO is associated with high incidence of complications and unsuccessful procedure, mainly due to inability to cross the lesion. We sought to evaluate the efficacy and safety of the novel RVT CTO Guidewire Device? (RVT‐GDW?, ReVascular Therapeutics, Sunnyvale, CA) in this complex scenario. Methods. The RAPID‐CTO study is a non‐randomized, single center, first‐in‐man evaluation of a new guidewire system for treatment of CTO. The RVT‐GDW is a new device designed to provide enhanced penetration and positioning control for crossing CTO via: (1) an 0.014 “guidewire with a mechanically active distal end; (2) a handle attached proximally to the guidewire, with an adjustable torquer, and interfaced to (3) a non‐disposable, battery‐operated, control unit, that provides activation control and audio feedback during the CTO crossing procedure. Per protocol, the RVT‐GDW device was only used after at least 5 min (fluoroscopy time) of attempt with commercially available conventional guidewires to cross the target lesion. Results. A total of 16 patients (16 lesions) were treated with the RVT‐GDW. Mean age was 56.25 years, 56.2% were men, and 25% diabetics. The average duration of occlusion was 4.7 ± 2.1 months. The mean vessel reference diameter was 2.76 ± 0.31 mm and the mean lesion length was 16.64 ± 7.70 mm (range 4.37–35.0 mm). Thirteen patients (81.2%) had “tapered stump” morphology at the proximal end of the occlusion, and a side branch was involved in 12 (75.0%). All lesions had contralateral circulation; bridging collaterals were seen in three (18.7%). Procedural success was achieved in 10 lesions (62.5%), with an average procedural time of 111.43 ± 35.76 min. There were no major adverse cardiac events at both in‐hospital and 30‐day clinical follow‐up. Conclusions. The first‐in‐man RAPID‐CTO study suggests that the novel RVT‐GDW device is technically feasible, safe and effective in crossing chronically occluded coronary arteries. Larger studies are warranted. © 2008 Wiley‐Liss, Inc.