Hand grip strength in patients with advanced cancer: a prospective study

BACKGROUND: Hand grip strength (HGS) is a widely used functional test for the assessment of strength and functional status in patients with cancer, in particular with cancer cachexia. The aim was to prospectively evaluate the prognostic value of HGS in patients with mostly advanced cancer with and without cachexia and to establish reference values for a European-based population. METHODS: In this prospective study, 333 patients with cancer (85% stage III/IV) and 65 healthy controls of similar age and sex were enrolled. None of the study participants had significant cardiovascular disease or active infection at baseline. Repetitive HGS assessment was performed using a hand dynamometer to measure the maximal HGS (kilograms). Presence of cancer cachexia was defined when patients had ≥5% weight loss within 6 months or when body mass index was <20.0 kg/m(2) with ≥2% weight loss (Fearon's criteria). Cox proportional hazard analyses were performed to assess the relationship of maximal HGS to all-cause mortality and to determine cut-offs for HGS with the best predictive power. We also assessed associations with additional relevant clinical and functional outcome measures at baseline, including anthropometric measures, physical function (Karnofsky Performance Status and Eastern Cooperative of Oncology Group), physical activity (4-m gait speed test and 6-min walk test), patient-reported outcomes (EQ-5D-5L and Visual Analogue Scale appetite/pain) and nutrition status (Mini Nutritional Assessment). RESULTS: The mean age was 60 ± 14 years; 163 (51%) were female, and 148 (44%) had cachexia at baseline. Patients with cancer showed 18% lower HGS than healthy controls (31.2 ± 11.9 vs. 37.9 ± 11.6 kg, P < 0.001). Patients with cancer cachexia had 16% lower HGS than those without cachexia (28.3 ± 10.1 vs. 33.6 ± 12.3 kg, P < 0.001). Patients with cancer were followed for a mean of 17 months (range 6-50), and 182 (55%) patients died during follow-up (2-year mortality rate 53%) (95% confidence interval 48-59%). Reduced maximal HGS was associated with increased mortality (per -5 kg; hazard ratio [HR] 1.19; 1.10-1.28; P < 0.0001; independently of age, sex, cancer stage, cancer entity and presence of cachexia). HGS was also a predictor of mortality in patients with cachexia (per -5 kg; HR 1.20; 1.08-1.33; P = 0.001) and without cachexia (per -5 kg; HR 1.18; 1.04-1.34; P = 0.010). The cut-off for maximal HGS with the best predictive power for poor survival was <25.1 kg for females (sensitivity 54%, specificity 63%) and <40.2 kg for males (sensitivity 69%, specificity 68%). CONCLUSIONS: Reduced maximal HGS was associated with higher all-cause mortality, reduced overall functional status and decreased physical performance in patients with mostly advanced cancer. Similar results were found for patients with and without cancer cachexia

Malnutrition as assessed by nutritional risk index is associated with worse outcome in patients admitted with acute decompensated heart failure: an ACAP-HF data analysis

Malnutrition is common at hospital admission and tends to worsen during hospitalization. This controlled population study aimed to determine if serum albumin or moderate and severe nutritional depletion by Nutritional Risk Index (NRI) at hospital admission are associated with increased length of hospital stay (LOS) in patients admitted with acute decompensated heart failure (ADHF). Serum albumin levels and lymphocyte counts were retrospectively determined at hospital admission in 1740 consecutive patients admitted with primary and secondary diagnosis of ADHF. The Nutrition Risk Score (NRI) developed originally in AIDS and cancer populations was derived from the serum albumin concentration and the ratio of actual to usual weight, as follows: NRI = (1.519 × serum albumin, g/dL) + {41.7 × present weight (kg)/ideal body weight(kg)}. Patients were classified into four groups as no, mild, moderate or severe risk by NRI. Multiple logistic regressions were used to determine the association between nutritional risk category and LOS

Discovery and Fine-Mapping of Glycaemic and Obesity-Related Trait Loci Using High-Density Imputation

Reference panels from the 1000 Genomes (1000G) Project Consortium provide near complete coverage of common and low-frequency genetic variation with minor allele frequency ≥0.5% across European ancestry populations. Within the European Network for Genetic and Genomic Epidemiology (ENGAGE) Consortium, we have undertaken the fi

The relation between postural stability and weight distribution in healthy subjects.

Contains fulltext : 70693.pdf (publisher's version ) (Closed access)Knowledge of the effects of leg-loading asymmetry on postural control and control asymmetry during quiet upright standing in healthy young and middle-aged subjects is necessary before these relationships in patients with lateralized disorders can be assessed and understood. A posturographic procedure was developed, using a dual-plate force platform, during which 10 younger and 10 middle-aged healthy individuals were required to adopt various degrees of (a) symmetrical weight distributions (0, 5, 10, 20 and 30% of extra body weight loaded onto either leg). Postural control and control asymmetry were quantified by centre of pressure (CP) fluctuations in the lateral (LAT) and anterior-posterior (AP) directions under both feet together and individually. Subsequently, the relationship between weight distribution on one hand and postural control and control asymmetry on the other hand, was calculated. Results demonstrated that with increasing weight-bearing asymmetry (WBA), the overall control of postural sway velocity increased mainly in the LAT direction, where a first-order polynomial function fitted best. The asymmetry of control of postural sway velocity increased with increasing weight-bearing asymmetry in favour of the more loaded leg in LAT and AP directions. A first-order polynomial was used for both AP and LAT direction. Effects of weight-bearing asymmetry on postural control and control asymmetry are due to changes in the biomechanical constraints of upright standing. It was suggested that through increasing weight-bearing asymmetry the postural instability increased by reducing the efficiency of hip load/unload mechanisms and increasing the (compensatory) ankle moments

Stimulus-response characteristics of motor evoked potentials and silent periods in proximal and distal upper-extremity muscles.

Contains fulltext : 81487.pdf (publisher's version ) (Closed access)OBJECTIVE: To compare stimulus-response characteristics of both motor evoked potentials (MEP) and silent periods (SP) induced by transcranial magnetic stimulation (TMS) in proximal and distal upper-extremity muscles. METHODS: Stimulus-response curves of MEPs and SPs were obtained from the biceps brachii (BB) and abductor digiti minimi (ADM) muscles in 15 healthy participants. A nonlinear mixed model was used to fit the stimulus-response curves to a sigmoid Boltzmann function. Results : Small residuals of the function were found for MEPs and SPs in both muscles. Higher maximal MEP amplitudes were found for the BB compared to the ADM (p<0.01). The active motor threshold to obtain a SP was less for the ADM compared to the BB (p<0.01). The slope parameter of the function of the SP duration was steeper and more variable in the ADM than in the BB (p<0.01). For the MEP amplitude no difference in active motor threshold and slope of the function was found between both muscles. CONCLUSIONS: Excitatory (MEP) and inhibitory (SP) effects of TMS differ between proximal arm and distal hand muscles in healthy participants. The adequate fit of our model suggests that this model can be used to study between and within subject changes in future studies

Population pharmacokinetics and pharmacodynamics of Tranexamic acid in women undergoing caesarean delivery.

AIMS: The population pharmacokinetics (PK) and pharmacodynamics (PD) of tranexamic acid (TXA) have not been studied to prevent postpartum haemorrhage (PPH) in pregnant women. It is unclear which TXA dose assures sufficient PPH prevention. This study investigated population PK/PD of TXA in pregnant women who underwent caesarean delivery to determine the optimal prophylactic doses of TXA for future studies. METHODS: We analysed concentration (PK) and maximum lysis (PD) data from 30 pregnant women scheduled for caesarean delivery who received 5, 10 or 15 mg/kg of TXA intravenously using population approach. RESULTS: TXA PK was best described by a two-compartment model with first-order elimination and the following parameters: clearance (between-subject variability) of 9.4 L/h (27.7%), central volume of 10.1 L (47.4%), intercompartmental clearance of 22.4 L/h (66.7%), peripheral volume of 14.0 L (13.1%) and additive error of 1.4 mg/L. The relationship between TXA concentration and maximum lysis was characterized by a sigmoid Emax model with baseline lysis of 97%, maximum inhibition of 89%, IC CONCLUSION: This is the first population PK and PD study of TXA in pregnant women undergoing caesarean delivery. Our analysis suggests that a 650 mg dose provides adequate PPH prophylaxis up to 1 hour, which is less than the currently used 1000 mg of TXA in pregnant women

Application of a plasmin generation assay to define pharmacodynamic effects of tranexamic acid in women undergoing cesarean delivery

© 2020 International Society on Thrombosis and Haemostasis Essentials Tranexamic acid (TXA) is an antifibrinolytic drug used to reduce bleeding. Assaying plasmin generation (PG) in plasma detects clinically relevant TXA levels in vitro and ex vivo. 3.1-16.2 µg/mL TXA half-maximally inhibits PG in plasma from women undergoing cesarean delivery. PG velocity shows the strongest dose-relationship at low TXA concentrations (≤10 µg/mL). Abstract: Background Tranexamic acid (TXA) is used to reduce bleeding. TXA inhibits plasmin(ogen) binding to fibrin and reduces fibrinolysis. TXA antifibrinolytic activity is typically measured by clot lysis assays; however, effects on plasmin generation (PG) are unclear due to a lack of tools to measure PG in plasma. Aims Develop an assay to measure PG kinetics in human plasma. Determine effects of TXA on PG and compare with fibrinolysis measured by rotational thromboelastometry (ROTEM). Methods We characterized effects of plasminogen, tissue plasminogen activator, fibrinogen, and α2-antiplasmin on PG in vitro. We also studied effects of TXA on PG in plasma from 30 pregnant women administered intravenous TXA (5, 10, or 15 mg/kg) during cesarean delivery. PG was measured by calibrated fluorescence. PG parameters were compared with TXA measured by mass spectrometry and ROTEM of whole blood. Results The PG assay is specific for plasmin and sensitive to tissue plasminogen activator, fibrin(ogen), and α2-antiplasmin. Addition of TXA to plasma in vitro dose dependently prolonged the clot lysis time and delayed and reduced PG. For all doses of TXA administered intravenously, the PG assay detected delayed time-to-peak (≤3 hours) and reduced the velocity, peak, and endogenous plasmin potential (≤24 hours) in plasma samples obtained after infusion. The PG time-to-peak, velocity, and peak correlated significantly with TXA concentration and showed less variability than the ROTEM lysis index at 30 minutes or maximum lysis. Conclusions The PG assay detects pharmacologically relevant concentrations of TXA administered in vitro and in vivo, and demonstrates TXA-mediated inhibition of PG in women undergoing cesarean delivery