The complex issue of medication management in older persons: a challenge for nurses

With increasing life expectancy, the share of older persons with coexisting multiple chronic degenerative diseases (comorbidity / multimorbidity) is expanding. These conditions require the use of multiple drugs, leading to polypharmacy, which plays a central role in making the therapeutic approach to the elderly particularly complex, together with age-related changes in pharmacokinetics and pharmacodynamics. Physicians and nurses both are challenged by polypharmacy and by the other drug-related issues involving older patients, in all care settings. In particular, nurses should be aware of the main issues of pharmacotherapy in older persons, because they are often the frontline for older patients care, especially in nursing homes. This review addresses the main issues related to pharmacotherapy in late life, such as pharmacokinetics and pharmacodynamics changes, limitations of evidence-based medicine, polypharmacy, drug interactions, adverse drug reactions, and lack of adherence. Focus will be on how these problems may impact on nursing, and on what nurses should know and do to improve drug treatment of older patients. In the last decade, the role and responsibilities of nurses in the management of drug therapy have significantly changed in most countries. There is consensus in educational programs and legislation that the preparation and administration of medications are essential aspects of nursing practice. These are considered as collaborative tasks with physicians and not purely mechanistic tasks. The nurse must intervene in the event of a perceived error, and he/she must report doubts about congruity or relevance of the therapy. Although nursing students gain knowledge and develop skills on drug therapy during their education, these are often perceived as insufficient. The need for post-graduation continuing education should be also emphasized. Thus, graduate and post-graduate educational programs should be developed, in order to offer adequate answers to the increasing and challenging share of older patients seen in clinical practice

How future surgery will benefit from SARS-COV-2-related measures: a SPIGC survey conveying the perspective of Italian surgeons

COVID-19 negatively affected surgical activity, but the potential benefits resulting from adopted measures remain unclear. The aim of this study was to evaluate the change in surgical activity and potential benefit from COVID-19 measures in perspective of Italian surgeons on behalf of SPIGC. A nationwide online survey on surgical practice before, during, and after COVID-19 pandemic was conducted in March-April 2022 (NCT:05323851). Effects of COVID-19 hospital-related measures on surgical patients' management and personal professional development across surgical specialties were explored. Data on demographics, pre-operative/peri-operative/post-operative management, and professional development were collected. Outcomes were matched with the corresponding volume. Four hundred and seventy-three respondents were included in final analysis across 14 surgical specialties. Since SARS-CoV-2 pandemic, application of telematic consultations (4.1% vs. 21.6%; p < 0.0001) and diagnostic evaluations (16.4% vs. 42.2%; p < 0.0001) increased. Elective surgical activities significantly reduced and surgeons opted more frequently for conservative management with a possible indication for elective (26.3% vs. 35.7%; p < 0.0001) or urgent (20.4% vs. 38.5%; p < 0.0001) surgery. All new COVID-related measures are perceived to be maintained in the future. Surgeons' personal education online increased from 12.6% (pre-COVID) to 86.6% (post-COVID; p < 0.0001). Online educational activities are considered a beneficial effect from COVID pandemic (56.4%). COVID-19 had a great impact on surgical specialties, with significant reduction of operation volume. However, some forced changes turned out to be benefits. Isolation measures pushed the use of telemedicine and telemetric devices for outpatient practice and favored communication for educational purposes and surgeon-patient/family communication. From the Italian surgeons' perspective, COVID-related measures will continue to influence future surgical clinical practice

Imatinib treatment inhibit IL-6, IL-8, NF-KB and AP-1 production and modulate intracellular calcium in CML patients

Imatinib (IM) is considered the gold standard for chronic myeloid leukemia (CML) treatment, although resistance is emerging as a significant problem. The proinflammatory cytokines interleukin-6 (IL-6) and interleukin-8 (IL-8) play an important role in cell proliferation, survival, and resistance to glucocorticoid-mediated cell death. Several transcription factors such as NF-KB and AP-1 are activated in response to physiopathological increases and modulation of intracellular calcium levels. Our previous study demonstrated that lymphocytes from CML patients showed dysregulated calcium homeostasis and oxidative stress. Alteration in ionized calcium concentration in the cytosol has been implicated in the initiation of secretion, contraction, and cell proliferation. In this study, we hypothesized that IL-6, IL-8, NF-kB, AP-1, and intracellular calcium may be used as selective and prognostic factors to address the follow-up in CML patients treated with imatinib. Our results demonstrated a significant down-regulation in IL-6 and IL-8 release as well as NF-kB and AP-1 activation in lymphomonocytes from Imatinib-treated patients, compared to samples from untreated patients. In parallel, IM treatment, in vivo and in vitro, were able to modulate the intracellular calcium concentration of peripheral blood mononuclear cells of CML patients by acting at the level of InsP(3) receptor in the endoplasmic reticulum and at the level of the purinergic receptors on plasma membrane. The results of this study show that measurements of NF-kB, AP-1, IL-6, IL-8, and intracellular calcium in CML patients treated with Imatinib may give important information to the hematologist on diagnostic criteria and are highly predictive in patients with newly diagnosed CML

Performance Evaluation of Lower Limb Exoskeletons: A Systematic Review

Benchmarks have long been used to verify and compare the readiness level of different technologies in many application domains. In the field of wearable robots, the lack of a recognized benchmarking methodology is one important impediment that may hamper the efficient translation of research prototypes into actual products. At the same time, an exponentially growing number of research studies are addressing the problem of quantifying the performance of robotic exoskeletons, resulting in a rich and highly heterogeneous picture of methods, variables and protocols. This review aims to organize this information, and identify the most promising performance indicators that can be converted into practical benchmarks. We focus our analysis on lower limb functions, including a wide spectrum of motor skills and performance indicators. We found that, in general, the evaluation of lower limb exoskeletons is still largely focused on straight walking, with poor coverage of most of the basic motor skills that make up the activities of daily life. Our analysis also reveals a clear bias towards generic kinematics and kinetic indicators, in spite of the metrics of human-robot interaction. Based on these results, we identify and discuss a number of promising research directions that may help the community to attain a comprehensive benchmarking methodology for robot-assisted locomotion more efficiently

Psychopharmacology in children and adolescents:unmet needs and opportunities

Psychopharmacological treatment is an important component of the multimodal intervention approach to treating mental health conditions in children and adolescents. Currently, there are many unmet needs but also opportunities, alongside possible risks to consider, regarding the pharmacological treatment of mental health conditions in children and adolescents. In this Position Paper, we highlight and address these unmet needs and opportunities, including the perspectives of clinicians and researchers from the European College of Neuropsychopharmacology–Child and Adolescent Network, alongside those of experts by lived experience from national and international associations, via a survey involving 644 participants from 13 countries, and of regulators, through representation from the European Medicines Agency. We present and discuss the evidence base for medications currently used for mental disorders in children and adolescents, medications in the pipeline, opportunities in the development of novel medications, crucial priorities for the conduct of future clinical studies, challenges and opportunities in terms of the regulatory and legislative framework, and innovations in the way research is conducted, reported, and promoted.</p

The future of child and adolescent clinical psychopharmacology: A systematic review of phase 2, 3, or 4 randomized controlled trials of pharmacologic agents without regulatory approval or for unapproved indications

International audienceWe aimed to identify promising novel medications for child and adolescent mental health problems. We systematically searched https://clinicaltrials.gov/ and https://www.clinicaltrialsregister.eu/ (from 01/01/2010–08/23/2022) for phase 2 or 3 randomized controlled trials (RCTs) of medications without regulatory approval in the US, Europe or Asia, including also RCTs of dietary interventions/probiotics. Additionally, we searched phase 4 RCTs of agents targeting unlicensed indications for children/adolescents with mental health disorders. We retrieved 234 ongoing or completed RCTs, including 26 (11%) with positive findings on ≥ 1 primary outcome, 43 (18%) with negative/unavailable results on every primary outcome, and 165 (70%) without publicly available statistical results. The only two compounds with evidence of significant effects that were replicated in ≥ 1 additional RCT without any negative RCTs were dasotraline for attention-deficit/hyperactivity disorder, and carbetocin for hyperphagia in Prader-Willi syndrome. Among other strategies, targeting specific symptom dimensions in samples stratified based on clinical characteristics or established biomarkers may increase chances of success in future development programmes

Tocilizumab for patients with COVID-19 pneumonia. The single-arm TOCIVID-19 prospective trial

BackgroundTocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients.MethodsA multicenter, single-arm, hypothesis-driven trial was planned, according to a phase 2 design, to study the effect of tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints, a priori expected rates being 20 and 35%, respectively). A further prospective cohort of patients, consecutively enrolled after the first cohort was accomplished, was used as a secondary validation dataset. The two cohorts were evaluated jointly in an exploratory multivariable logistic regression model to assess prognostic variables on survival.ResultsIn the primary intention-to-treat (ITT) phase 2 population, 180/301 (59.8%) subjects received tocilizumab, and 67 deaths were observed overall. Lethality rates were equal to 18.4% (97.5% CI: 13.6-24.0, P=0.52) and 22.4% (97.5% CI: 17.2-28.3, P&lt;0.001) at 14 and 30 days, respectively. Lethality rates were lower in the validation dataset, that included 920 patients. No signal of specific drug toxicity was reported. In the exploratory multivariable logistic regression analysis, older age and lower PaO2/FiO2 ratio negatively affected survival, while the concurrent use of steroids was associated with greater survival. A statistically significant interaction was found between tocilizumab and respiratory support, suggesting that tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline.ConclusionsTocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Possibly, this effect could be limited to patients not requiring mechanical respiratory support at baseline.Registration EudraCT (2020-001110-38); clinicaltrials.gov (NCT04317092)