This population-based registry was designed to provide robust and updated information on the characteristics and the epidemiology of chronic myeloid leukemia (CML). All cases of newly diagnosed ...Philadelphia positive, BCR-ABL1+ CML that occurred in a sample of 92.5 million adults living in 20 European countries, were registered over a median period of 39 months. 94.3% of the 2904 CML patients were diagnosed in chronic phase (CP). Median age was 56 years. 55.5% of patients had comorbidities, mainly cardiovascular (41.9%). High-risk patients were 24.7% by Sokal, 10.8% by EURO, and 11.8% by EUTOS risk scores. The raw incidence increased with age from 0.39/100,000/year in people 20-29 years old to 1.52 in those >70 years old, and showed a maximum of 1.39 in Italy and a minimum of 0.69 in Poland (all countries together: 0.99). The proportion of Sokal and Euro score high-risk patients seen in many countries indicates that trial patients were not a positive selection. Thus from a clinical point of view the results of most trials can be generalized to most countries. The incidences observed among European countries did not differ substantially. The estimated number of new CML cases per year in Europe is about 6370.
OBJECTIVE:The novel exercise computer-assisted high-frequency QRS-analysis (ex-HF/QRS) has demonstrated improved sensitivity and specificity over the conventional exercise-ST/ECG-segment-analysis ...(ex-ST/ECG) in the detection of myocardial ischemia. The aim of the present study was to test the implementation in diagnostic value of the ex-HF/QRS in patient with hypertension and chest pain (CP) versus the conventional ex-ST/ECG anlysis alone.
DESIGN AND METHOD:Patients with long-standing hypertension, CP, normal ECG, troponin and echocardiography were enrolled. All patients underwent the ex-ST/ECG and ex-HF/QRS. A decrease >/=50% of the signal of ex-HF/QRS intensity recorded in two contiguous leads, at least, was considered as index of ischaemia, as ST-segment depression >/=2 mm or >/=1 mm and CP on ex-ST/ECG. Exclusion criteria were QRS duration >/=120 msec and inability to exercise. The end-point was the composite of coronary stenosis >50% or acute coronary syndrome, revascularization, cardiovascular death at 3-month follow-up.
RESULTS:Six-hundred thirty-one patients were enrolled (age 61+/-15 y). The percentage of age-adjusted maximal predicted heart rate was 88+/-10 beat-per-minute and the maximal systolic blood pressure was 169+/-22 mmHg. Twenty-seven patients achieved the end-point. On multivariate analysis, both the ex-ST/ECG and ex-HF/QRS were predictors of the end-point. The ex-HF/QRS showed higher sensitivity (88% vs 50%; p = 0.003), lower specificity (77% vs 97%; p = 0.245) and comparable negative predictive value (99% vs 99%; p = NS) when compared to ex-ST/ECG. Receiver operator characteristics (ROC) analysis showed the incremental diagnostic value of the ex-HF/QRS (area0.64, 95% Confidence Intervals, CI 0.51–0.77) over conventional ex-ST/ECG (0.60, CI 0.52–0.66) and Chest Pain Score (0.53, CI 0.48–0.59); p = NS on pairwise C-statistic.
CONCLUSIONS:In patients with long-standing hypertension and CP submitted to risk stratification with exercise tolerance test, the novel ex-HF/QRS shows a valuable incremental diagnostic value over ex-ST/ECG.
OBJECTIVE:The novel exercise computer-assisted high-frequency QRS-analysis (ex-HF/QRS) has demonstrated improved sensitivity and specificity over the conventional ST/ECG-segment analysis (ex-ST/ECG) ...in the detection of myocardial ischemia. The aim of the present study was to compare the diagnostic value of the validated exercise-Echocardiography (ex-Echo), needing skilled cardiologist, with the novel low-cost ex-HF/QRS, including the conventional ST-segment analysis.
DESIGN AND METHOD:A prospective cohort study was conducted in the Emergency Department of a tertiary care teaching Hospital, and validated by the Propensity Score Model. Patients with chest pain (CP), normal resting ECGs, troponins, echocardiography and “intermediate-risk” for adverse coronary events underwent the ex-HF/QRS and ex-Echo. An ST-segment depression >/=2 mV or >/=1 mV when associated with CP were considered as index of ischemia, as a decrease >/=50% in HF/QRS intensity or new wall motion abnormalities on ex-Echo. Exclusion criteria were QRS duration >/=120 milliseconds, poor echo-acoustic window and inability to exercise. The endpoint was the composite of coronary stenoses >50% at angiography or acute coronary syndrome, revascularization and cardiovascular death on the six-month follow-up.
RESULTS:In 270 patients enrolled, the ex-HF/QRS and ex-Echo showed comparable predictive values with p = NS for all comparisons as followsnegative predictive value 97% vs 96%, respectively; sensitivity 63% versus 65%, respectively; specificity 64% versus 83%, respectively. The areas on Receiver Operator Characteristics analysis were comparable (ex-HF/QRS0.65, 95% CI 0.51–0.77 vs ex-Echo0.66, CI 0.56–0.86; C statistic p = NS). On multivariate analysis, both ex-HF/QRS and ex-Echo were predictors of the endpoint.
CONCLUSIONS:In “intermediate-risk” CP patients, the novel ex-HF/QRS was a valuable diagnostic tool in the crowed Emergency Departments. The test might be proposed to avoid additional costly imaging also because it did not require specialized personnel. However, additional study are needed before it can be recommended as a replacement for current techniques.
OBJECTIVE:Atrial fibrillation (AF), the most common cardiac-arrhythmia in critical-care, has reached a high prevalence in hypertensive patients. Prevention of systemic-embolism is mandatory; ...unfortunately, evidence to support the treatment of comorbidities as coronary artery disease (CAD) that contribute to excess mortality is lacking, and the mechanism underlying the troponin-rise during AF without acute coronary syndrome (ACS) is unclear. This study investigates the relationship between CAD, stroke and outcomes in patients with troponin-rise and AF.
DESIGN AND METHOD:Patients with a recent-onset AF and without severe comorbidities were enrolled. Baseline characteristics in those with troponin-rise versus those without were adjusted with propensity-score-matching for possible confounders. SPSS-software allowed estimation of the propensity-score using logistic-regression and specifying nearest-neighbor matching in prior-stroke, heart-rate, hypertension, TIMI-risk-score, GRACE-score, CHA2DS2Vasc-score. Patients with a troponin-rise or cardiovascular event (CVE) were considered for angiography. The primary endpoint was the composite of ACS, revascularization (with critical CAD>/ = 70%) and cardiac-death at the follow-up; the secondary endpoint was stroke.
RESULTS:Out of 6203 AF patients without severe comorbidities, 3541 with recent-onset AF completed the study; 202(6%) showed a troponin-rise, 91(3%) a CVE. After matching no difference existed in baseline characteristics. On multivariate analysis, in the entire cohort, troponin-rise, know-CAD and hypertension were predictors of the endpoint, whereas only troponin-rise (Odd Ratio, OR10, Confidence Interval 95%, CI4–22, p < 0.001) and TIMI-score > 2 (OR 4, CI 2–9, p < 0.001) in the matching cohort, suggesting the role of CAD in poor outcomes. Patients with or without troponin-rise achieved the endpoint in 38(19%) and 43(1%), respectively (p < 0.001). Stroke occurred in 4(2%) and 20 (1%), respectively (p = 0.018). Critical CAD account for 23(12%) and 15(1%), respectively (p < 0,001). In the matching cohort, only stroke did not reach the statistical significance. Interestingly, the best cut/off troponin level for decision-making was 0.30 ng/L which, on Receiver Operator Curve analysis, was associated with 68% of sensitivity and 60% specificity; the value > 0.50 ng/L with 55% and 75%, respectively.
CONCLUSIONS:Patients with a recent-onset AF and troponin-rise showed a high prevalence of CVE but not stroke, thus CAD might have a role in poor outcomes.
The term multidrug resistance (MDR) describes the observation that tumour cell lines can become cross-resistant to several structurally unrelated chemotherapeutic agents after exposure to a single ...cytotoxic drug. In hematological malignancies, MDR is most often associated with overexpression of P-gp, a 170-kd transmembrane glycoprotein encoded by the human MDR1 gene. Indeed, P-gp expression has been correlated with drug sensitivity and clinical outcome in several studies in acute myelogenous leukemia (AML), multiple myeloma (MM), and malignant lymphomas (NHL). A large number of compounds ‘off the shelf’ have been investigated for their ability to reverse the P-gp mediated MDR. However, most of these agents produced severe toxic effects at doses required to effectively block P-gp function, and modulation of P-gp in normal tissues can affect the pharmacokinetics and, thus, the toxicity of the associated chemotherapeutic agents. Phase I/IIa trials with third generation MDR modulators, such as valspodar, show that these new agents can be safely administered in combination with different chemotherapy regimens after dose adjustments of cytotoxic drugs that are P-gp substrates. Moreover, MDR reversal by valspodar has been demonstrated in the patients with AML, multiple myeloma, and non-Hodgkin's lymphoma. The definition of the clinical benefits of using MDR modulators in haematological malignancies and their full extent awaits the conclusion of the ongoing randomized phase III trials with valspodar in either newly diagnosed or resistant/relapsed AML patients, and in multiple myeloma patients who have failed front-line treatment.
Considerable progress has been made in adapting existing and developing new technologies to enable increasingly detailed phenotypic information to be obtained in embryonic and newborn mice. ...Sophisticated methods for imaging mouse embryos and newborns are available and include ultrasound and magnetic resonance imaging (MRI) for in vivo imaging, and MRI, vascular corrosion casts, microcomputed tomography, and optical projection tomography (OPT) for postmortem imaging. In addition, Doppler and M-mode ultrasound are useful noninvasive tools to monitor cardiac and vascular hemodynamics in vivo in embryos and newborns. The developmental stage of the animals being phenotyped is an important consideration when selecting the appropriate technique for anesthesia or euthanasia and for labeling animals in longitudinal studies. Study design also needs to control for possible differences between inter- and intralitter variability, and for possible long-term developmental effects caused by anesthesia and/or procedures. Noninvasive or minimally invasive intravenous or intracardiac injections or blood sampling, and arterial pressure and electrocardiography (ECG) measurements are feasible in newborns. Whereas microinjection techniques are available for embryos as young as 6.5 days of gestation, further advances are required to enable minimally invasive fluid or tissue samples, or blood pressure or ECG measurements, to be obtained from mouse embryos in utero. The growing repertoire of techniques available for phenotyping mouse embryos and newborns promises to accelerate knowledge gained from studies using genetically engineered mice to understand molecular regulation of morphogenesis and the etiology of congenital diseases.
Abstract
Background
Gamification, according to literature, is the use of game design elements in non-game contexts. Rewards (e.g. points, badges and rankings) are a gamification strategy to entice ...users to complete required tasks and could be useful for Public Health (PH) interventions to promote healthy lifestyles. This study aims to find out which gamification approaches are most useful in PH.
Methods
We investigated PubMed, Scopus and Web of Science databases to conduct our systematic review, including articles published up to February 3, 2023. Prisma Statement 2020 guidelines were used. No time limits were included. Only articles in Italian or English that discussed gamification interventions in PH, effectiveness and user satisfaction were taken into account. The quality of the studies will be assessed using the NIH quality assessment tool.
Results
327 articles were found, 27 of which were included in the review. Pre-post studies were the most included (n = 12), conducted in Europe (n = 7) and USA (n = 6). The target population was mainly young adults and teens (n = 7). Most gamification interventions involved physical activity (n = 13), nutrition (n = 5) and smoking cessation (n = 2). Overall, the interventions proved to be all effective, but the ones about physical activity were the most useful, engaging and with longer-lasting results over time. Where satisfaction was assessed (n = 16), users gave positive feedback.
Conclusions
The research outcomes have shown how gamification may engage not only individuals, but masses, using game design elements in different Public Health areas. The implementation of gamification tools in PH is an innovative intervention that often uses graphic language to simplify and deliver messages to all kinds of users. Gamification is easy to use and could be a good strategy for primary prevention, to support a sustainable behavior change following the game period. More large scale controlled trials are needed in order to confirm these results.
Key messages
• Gamification is an important tool in public health useful for primary prevention.
• The mass appeal of gamification can reach many users leading to healthier lifestyles, especially among young adults.
The aim of the present study was to evaluate the effect of the cyclosporine derivative valspodar (PSC 833; Amdray, Novartis Pharma, Basel, Switzerland) on the concentration of daunorubicin (dnr) in ...leukemic blast cells in vivo during treatment.
Ten patients with acute myeloid leukemia (AML) were included. Leukemic cells from seven of the patients were P-glycoprotein (Pgp)-positive. dnr 100 mg/m(2) was given as a continuous infusion over 72 hours. After 24 hours, a loading dose of valspodar was given, followed by a 36-hour infusion of 10 mg/kg per 24 hours. Blood samples were drawn at regular intervals, and concentrations of dnr and its main metabolite, daunorubicinol, in plasma and isolated leukemic cells were determined by high-pressure liquid chromatography.
The mean dnr concentrations in leukemic cells 24 hours after the start of infusion (before valspodar) were 18.8 micromol/L in Pgp-negative samples and 13.5 micromol/L in Pgp-positive samples. After 8 hours of valspodar infusion, these values were 25.8 and 24.0 micromol/L, respectively. The effect of valspodar was evaluated from the ratio of the area under the curve (AUC) for dnr concentration versus time in leukemic cells to the AUC for dnr concentration against time in the plasma. For the seven patients with Pgp-positive leukemia, the mean ratio increased by 52%, from 545 on day 1 to 830 on day 2 (P<.05) when valspodar was given. In the three patients with Pgp-negative leukemia, no significant difference was observed.
These results strongly suggest that valspodar, by interacting with Pgp, can increase the cellular uptake of dnr in leukemic blasts in vivo.
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