A venetoclax and azacitidine bridge-to-transplant strategy for NPM1-mutated acute myeloid leukaemia in molecular failure.

NPM1-mutated acute myeloid leukaemia (NPM1mut AML) represents a mostly favourable/intermediate risk disease that benefits from allogeneic haematopoietic stem cell transplantation (HSCT) in case of measurable residual disease (MRD) relapse or persistence after induction chemotherapy. Although the negative prognostic role of pre-HSCT MRD is established, no recommendations are available for the management of peri-transplant molecular failure (MF). Based on the efficacy data of venetoclax (VEN)-based treatment in NPM1mut AML older patients, we retrospectively analysed the off-label combination of VEN plus azacitidine (AZA) as bridge-to-transplant strategy in 11 NPM1mut MRD-positive fit AML patients. Patients were in MRD-positive complete remission (CRMRDpos ) at the time of treatment: nine in molecular relapse and two in molecular persistence. After a median number of two cycles (range 1-4) of VEN-AZA, 9/11 (81.8%) achieved CRMRD -negative (CRMRDneg ). All 11 patients proceeded to HSCT. With a median follow-up from treatment start of 26 months, and a median post-HSCT follow-up of 19 months, 10/11 patients are alive (1 died from non-relapse mortality), and 9/10 patients are in MRDneg status. This patient series highlights the efficacy and safety of VEN-AZA to prevent overt relapse, achieve deep responses and preserve patient fitness before HSCT, in patients with NPM1mut AML in MF.

A rapid review of time management strategies among nurse managers.

Background: Time management practice is the act of influencing one's behavioural dimensions to complete as many tasks as possible within a specified amount of time. These behavioural dimensions include work organization and the continued application of time management techniques. Good time management, such as setting goals and priorities, as well as planning and delegating tasks, can facilitate productivity and success, contributing to work effectiveness, maintaining balance and job satisfaction. Conversely, poor time management has been associated with poor quality of work, low productivity, negative influence on the career path, and high levels of stress. Aim: The study aims to identify the strategies used by middle nurse managers in time management. Methods: A rapid review of biomedical databases was undertaken during the month of June 2021. The included studies were published in English and in Italian. Results: Findings reveal that the most used and effective time management strategies for nurse managers are setting goals, and priorities and delegating tasks. Other useful strategies also found to be fundamental are discussed in detail. Conclusion: A manager should prioritize the concept of planning, which can be counted as an efficient time management technique and educate himself on delegating. Time management has an impact not only on productivity and organizational success, but also on the balance between private and working life of managers.

The diurnal cortisol cycle and cognitive performance in the healthy old.

Associations between cognitive performance and cortisol have variously been reported for measures of both cortisol level and change, and for some domains of cognitive functioning more than others. In this study, associations between cortisol secretion measures and cognitive performance were examined in 50 healthy older people (mean age 74 years; 34 F /16 M). Participants provided 16 accurately timed saliva samples over 2 consecutive days to determine diurnal profiles of cortisol secretion. Overall cognitive performance (OCP) was measured as the principal component of a comprehensive battery of cognitive tests. Across a 30 year age range, there was a strong inverse correlation between age and OCP. Age and poorer OCP were also associated with an attenuated cortisol awakening response (CAR), defined as the rise from 0-30 min after awakening, and a subsequent less steep fall in cortisol level over the rest of the day. Partialling analyses, suggested that the correlation between fall in cortisol over the day and OCP was independent of age. Both older age and less cortisol change were particularly related to poorer performance on tests of declarative memory and executive functioning. Our conclusions are that during the short post-awakening period, an exception exists to the generally pertaining association between higher levels of cortisol and poorer cognitive performance. Consequentially dynamic measures reflecting the rise (CAR) and fall from the post-awakening peak may be particularly salient in helping to explain links between cortisol and cognitive performance. Finally our pattern of results across different cognitive tests suggests an association between cortisol and those domains of cognitive functioning which depend crucially on the integrity of the hippocampus and pre-frontal cortex.

Incidence of class A extended-spectrum beta-lactamases in Champagne-Ardenne (France): a 1 year prospective study.

OBJECTIVES: To assess the frequency and diversity of extended spectrum beta-lactamases (ESBLs) in the Champagne-Ardenne region France, and to identify genetic elements associated with the bla(CTX-M) genes. METHODS: During 2004, all the non-duplicate isolates of Pseudomonas aeruginosa and Acinetobacter baumannii resistant to ceftazidime and of Enterobacteriaceae intermediate or resistant to ceftazidime and/or cefotaxime, screening samples excluded, were collected in 10 public hospitals and 3 private clinics. bla genes were sequenced and bla(CTX-M) environment characterized by PCR mapping. RESULTS: In Enterobacteriaceae (138/21 861; 0.6%), ESBLs were predominantly TEM-24 (n = 52; 37.7%) and CTX-M-15 (n = 37; 26.8%). Three new enzymes were identified, CTX-M-61 (CTX-M-1 group), TEM- and SHV-type. A. baumannii (n = 5) produced VEB-1 and P. aeruginosa (n = 2) SHV-2a. ISEcp1 was detected in 22/27 strains, disrupted in 7 of them. The IS903-like element was downstream of bla(CTX-M-14) and bla(CTX-M-16). ISCR1 was found upstream of bla(CTX-M-2) and bla(CTX-M-9), and ISCR1 and bla(CTX-M-2) were located on a sul1-type class 1 integron. In comparison with 2001-02, ESBL distribution among Enterobacteriaceae showed an increase in CTX-M-type (44.9% vs 3.7% P < 10(-7)) due to Escherichia coli CTX-M-15 and to the almost total disappearance of TEM-3 (0.9% vs 51.2%). E. coli was the most frequent species (50.0% vs 5.1% in 1998) despite a similar prevalence to that in 1998 (0.5% vs 0.2%). CONCLUSIONS: A careful detection of bla(CTX-M)-type spread to other species would help to anticipate clonal endemics such as those observed in Enterobacter aerogenes TEM-24.

Cortisol secretory activity in older people in relation to positive and negative well-being.

Secretion of the hormone cortisol, a physiological correlate of affect, has been studied mostly in relation to negative states, especially stress. By contrast, policy initiatives aimed at older populations now routinely emphasise well-being and a 'positive ageing' perspective. In this study, we examined diurnal salivary cortisol profiles from 50 active seniors recruited into a wider community research project (mean age 74 years; 34 F/16 M). Participants' wrist activity was continuously monitored by actimeters in their homes over a 48 h period. During this time two diurnal cycles of cortisol data were collected (8 samples per day); with actimeter data providing a compliance check in regard to timing of self-administered saliva collections. Prior to the trial, participants had completed the GHQ-30 which was scored separately to yield both positive and negative well-being scores which matched closely normative data from over 6000 cases in a large survey. Our data suggest that positive and negative psychological well-being are quite strongly and inversely correlated. However, neither on their own was associated with basal levels of cortisol. Rather, for cortisol secretion in the 45-min period following awakening, but not during the rest of the day, we found a significant interaction between positive and negative well-being (p<0.024). Further analysis of this interaction showed that among participants low on negative well-being, higher positive well-being was significantly associated with lower cortisol; equally, among participants high on positive well-being, lower negative well-being was significantly associated with lower cortisol. Thus, a powerful synergy seemed to be operating in this early morning period such that cortisol secretion was 27% lower in participants with both higher-than-average positive well-being and lower-than-average negative well-being (comprising 34% of the sample). We conclude that cortisol secretion in the first 45 min following awakening is distinct from the rest of the day and most able to discriminate well-being states.

Linear estimates of disease progression predict survival in patients with amyotrophic lateral sclerosis.

We have shown that linear estimates of rates of disease progression (LEP), derived from isometric myometry [grip or foot dorsiflexion (FD) strength] and forced vital capacity (FVC%), are clinically and statistically significant predictors of survival of patients with amyotrophic lateral sclerosis (ALS) from date of disease onset and, except those based on grip strength, of survival from the date of measurement. We tested these results in 2 additional groups of patients: 1) those who participated in a previously reported Protropin (GH) study; and 2) those enrolled in two other clinical trials (group 2). The LEP were derived and tested as predictors of survival. In a Cox proportional hazards model, LEP based on all measures predicted survival from disease onset in both groups of patients. Using cutoff points determined within the original group to stratify patients in the validation groups into faster and slower progressing subgroups resulted in statistically significant separation of survival curves from disease onset in group 2 for all LEP and in group 1 (the GH group) for LEP derived from FD strength; and, for survival from date of measurement in group 2, when stratified by LEP based on FD strength or FVC%. LEP based on data generated by myometry or pulmonary function studies have now been shown to predict survival in 3 unrelated groups of patients with ALS entering clinical trials. Their precise use in clinical trial design needs to be explored further.

Practice guidelines for clinical prevention: do patients, physicians and experts share common ground?

BACKGROUND: Clinical practice guidelines, such as those of the Canadian Task Force on Preventive Health Care, although based on sound evidence, may conflict with the perceived needs and expectations of patients and physicians. This may jeopardize the implementation of such guidelines. This study was undertaken to explore patients' and family physicians' acceptance of the task force's recommendations and the values and criteria upon which the opinions of these 2 groups are based. METHODS: Focus groups were used to collect study data. In total, 35 physicians (in 7 groups) and 75 patient representatives (in 9 groups) participated in the focus groups. An inductive approach was used to develop coding grids and to generate themes from the transcripts of the interviews. RESULTS: Physicians expressed resistance to discontinuing the annual check-up, which they viewed as an organizational strategy to counteract the many barriers to preventive care that they encounter. They reported difficulties in explaining to their patients the recommendations of the Canadian Task Force on Preventive Health Care, which they found complex and inconsistent with popular wisdom. Both patients and physicians attributed high value to the detection of insidious diseases, even in the absence of proof of the effectiveness of such activity. INTERPRETATION: The patients and family physicians who participated in this study shared many opinions on the value of preventive activities that depart from the values used by "prevention experts" such as the Canadian Task Force on Preventive Health Care in establishing their recommendations. A better understanding of the values of patients and physicians would help guideline developers to create better targeted communication strategies to take these discrepancies into account.

An audit of measuring equipment in elderly care.

Accurate monitoring of weight and height is a vital element of nutritional assessment. Specialist equipment may be required for older patients. Accuracy depends upon calibration and maintenance of equipment.

Cytometric DNA ploidy after different types of urinary diversions.

Patients undergoing uterosigmoidostomy (USS) have a high risk of developing colon cancer, while no evidence of an increased risk associated with rectal bladder (RB) has been reported. The purpose of the present study was to monitor the presence of aneuploidy by flow cytometry in patients who have undergone USS and RB as a possible basis for the identification of patients with an increased risk of malignant tumor occurrence. We have observed that 31% Of USS and 27% of RB cases were aneuploid. Data from the present investigation confirm that follow up studies may be useful in patients after urinary diversion.

Community-based breast cancer intervention program for older African American women in beauty salons.

African American women are at high risk for morbidity and mortality from breast cancer. African American women ages 50 and older have been a difficult group to reach through conventional breast cancer intervention programs. Cultural and health beliefs that differ from mainstream society are reported to be factors contributing to the low rates of breast screening among this group. In addition to these attitudinal factors, older African American women are disproportionately represented among uninsured and under-insured Americans. As a result, cost becomes a barrier to mammography screening for many of these women. This project proposes to increase breast cancer screening awareness and provide a referral or free breast screening, or both, for African American women ages 50 and older. This information will be offered in the culturally familiar setting of local beauty salons. The culturally sensitive educational pamphlets developed by the National Cancer Institute (NCI) and video developed by the NCI-funded project, Cancer Prevention Research Unit, will be used to promote mammography, clinical breast examinations, and breast self-examination. Providers staffing a mobile mammography van provided by Dr. Anitha Mitchell of the Association of Black Women Physicians through a grant from the Breast and Cervical Cancer Control Program, funded by the Centers for Disease Control and Prevention, will perform mammograms for women on site during scheduled intervals. A followup telephone survey will be conducted.

Cellular effects of image diagnostic ultrasound on murine spermatogenesis monitored by flow cytometry.

A study has been carried out to evaluate the possible cellular effects induced by image diagnostic ultrasound on murine spermatogenetic cells. Exposure to ultrasound was carried out using a commercial diagnostic instrument that operates in B-mode. Male hybrid F1 mice, aged 8-10 weeks, were exposed to ultrasound for 30 min and observed from 7 to 35 days after treatment. Flow cytometric analysis has been used to monitor the relative frequency of the different types of spermatogenetic cells. This analytical approach showed changes in cell frequency in the compartment containing elongated spermatids which was used as an endpoint. A statistically significant decrease in the frequency of this cell type was observed 21, 28 and 35 days after exposure. These changes suggest that there may be a cytotoxic and/or cytostatic effect on spermatocytes and spermatogonia. These results showed that image diagnostic ultrasound induces effects on murine spermatogenesis at cellular level and that the flow cytometric approach makes it possible to identify quantitative cellular changes with reference to specific cell type.

Aneuploid cells in benign breast-lesions monitored by flow-cytometry.

It has been observed that various types of benign breast disease are associated to an increased risk of breast cancer. The biological significance of this association remains unclear: both benign and malignant lesions could independently have a common set of risk factors. The cellular DNA content of biopsy samples from 47 breast benign lesions was analyzed by flow cytometry. Flow cytometric measurements evidenced that 11/47 cases showed at least one aneuploid cell subpopulation. The presence of aneuploid subpopulations in benign lesions could be related to an unknown cellular alteration predisponding the developement of benign and malignant lesions independently.

Cellular effects of diagnostic Doppler ultrasound on murine spermatogenic cells monitored by flow cytometry.

A study has been carried out to investigate the possible effects caused by Doppler diagnostic ultrasound on murine spermatogenesis. The frequency of the different types of cells has been analyzed using flow cytometry. Exposure to ultrasound was carried out using a commercial device used in diagnostic conditions. Male hybrid mice were exposed to ultrasound for 30 min and observed from 7 to 35 days after treatment. Flow cytometrical analysis showed changes in the relative frequency of the elongated spermatids and this was used as an end-point. A statistically significant decrease in the frequency of this cell type was observed after 7 and 35 days with both pulsed and continuous ultrasound. With the former, a decrease was also seen in this compartment after 14 and 21 days. Our results have shown that diagnostic ultrasound used in the Doppler technique induces effects on specific cell types of murine spermatogenesis.

Biological and clinical implication of cellular DNA content in renal cell carcinomas.

DNA flow cytometric analysis (FCM) was performed on surgical bioptic samples taken from 82 renal cell carcinomas. FCM has evidenced that 35% (29/82) of renal carcinomas resulted diploid, 65% (53/82) aneuploid and of the latter 22% (12/53) multiclonal. Our results do not indicate any relationship among cytometric ploidy, Fuhrman grading, Robson and pTNM staging. A possible interesting increase of aneuploidy frequency was observed between the NMV (66%) subgroup and the no zero NMV (90%) subgroup, while in diploid patients these values were 40% and 10%, respectively. Follow-up data evidence a significant difference in survival pattern of patients between diploid and aneuploid groups. In conclusion, our results show that cytometric ploidy is a potential important prognostic parameter in survival term.

The prognostic value of DNA content in patients with prostatic carcinoma.

In 80 patients with pathologically proven prostatic cancer, DNA content was correlated to grade, stage and survival. The survival curve and duration of response to therapy in these patients was examined. At the end of follow-up the cumulative survival curve in the aneuploid patients was 0.40, according to the Kaplan-Meier method, while in the diploid population it was 0.65. Differences between the two groups, aneuploid and diploid, were observed within the various histological subgroups: survival in the G2 population was 0.57 for the diploid and 0.30 for the aneuploid whereas in the G3 patients it was respectively 0.69 for the diploid and 0.05 for the aneuploid patients.

Cellular DNA content and proliferative activity evaluated by flow cytometry versus histopathological and staging classifications in human bladder tumors.

Flow cytometric analysis of cellular DNA content was performed on 78 biopsy bladder samples obtained from 61 patients with bladder tumors. All 6 normal tissue samples and 1 benign papilloma exhibited a cytometrically diploid DNA distribution, while 39 of 60 bladder carcinomas exhibited at least one aneuploid cell subpopulation. Furthermore, 13 of 39 aneuploid tumors were characterized by the presence of more than one aneuploid cell subpopulation. The results indicate a significant relationship between cytometric ploidy and morphological classification and stage: the occurrence of subpopulations with abnormal DNA content is associated with the increase in differentiation grade and stage. A significant statistical difference in the survival pattern between the diploid and aneuploid groups was observed. The percent of S cells extracted from DNA content distribution histograms indicates a statistically significant difference (p less than 0.01) between normal tissue (3.7 +/- 1.8), diploid tumor (8.4 +/- 3.9) and aneuploid tumor (14.9 +/- 6.0). Moreover the percent of S-phase cells increases with grade in only the aneuploid subgroup. Our results suggest that cytometric parameters in association with morphological and clinical criteria can contribute to a more accurate characterization of bladder tumors in prognostic terms.