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At low concentrations, both isomers of tubulozole (C, T) inhibit Plasmodium falciparum but only tubulozole C inhibits mammalian cells. Since tubulozole C prevents polymerization of mammalian tubulin whereas tubulozole T does not, the antimalarial action of tubulozoles may not involve microtubules. The present study concerns the inhibition of parasite protein synthesis by the tubulozoles. While tubulozoles took 3-4 h to kill parasites in erythrocytic culture, they inhibited protein synthesis within 10 min. The concentrations of the drug required were, however, too high for this to account for their antimalarial action. The microtubule inhibitor colcemid inhibited protein synthesis rapidly and at relevant concentrations, but vinblastine did not inhibit protein synthesis. Tubulozole T and colcemid inhibited protein synthesis posttranscriptionally since they had little effect on RNA synthesis. Analysis of labelled parasite proteins by two-dimensional gel electrophoresis showed that while it inhibited synthesis of most proteins to the same degree, tubulozole T super-inhibited the synthesis of certain proteins. This may cause its antimalarial effect at low concentrations. [ABSTRACT FROM AUTHOR]

Background: The present study sought to determine the prevalence of chronic non-cancer pain (CNCP) among older adult inpatients with polypharmacy. It also aimed to analyse prescription patterns and assess the therapy adequacy and patient complexity for those with and without CNCP., Methods: This 4-year longitudinal study examined data from an exhaustive acute care hospital register on home-dwelling older adult patients (≥65) with polypharmacy. Commonly known combinations of potentially inappropriate medications were used to estimate therapy adequacy. Patient complexity was evaluated by comparing number of comorbidities and investigating physical and cognitive deficits., Results: We determined a prevalence of CNCP of 9.7% among all older adult inpatients with polypharmacy, rising to 11.3% for those aged ≥85. Overall, CNCP patients were prescribed more drugs and had more comorbidities and physical and cognitive deficits than patients without CNCP. Older adult patients with CNCP received more analgesics, greater quantities of opioids, paracetamol and co-analgesics and elevated opioid dosages. Older adult patients with CNCP aged ≥85 received fewer analgesics, opioids, non-steroidal anti-inflammatory drugs and co-analgesics but more paracetamol. Older adult patients with CNCP were prescribed more potentially inappropriate medications involving opioids. In particular, 24.5% received an opioid and a hypnotic (benzodiazepine or Z-drug), and 8.6% received an opioid and a gabapentinoid., Conclusion: Observed differences in medication use between older adult inpatients with or without CNCP may be relevant for clinical practice. Potentially inadequate co-prescribing (such as hypnotics and opioids) affects a higher proportion of patients with CNCP and may have serious unintended consequences., Significance Statement: This study describes differences in prescription patterns between people with and without chronic non-cancer pain in a large dataset of 20,422 discharges. The differences found may be relevant to clinical practice. In particular, high co-prescribing of opioids and hypnotics may have serious unintended consequences. Greater physical and cognitive deficits may indicate greater patient complexity, and appropriate interventions need to be developed to improve the management of this vulnerable patient group., (© 2024 The Author(s). European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation ‐ EFIC ®.)

Background: Frailty is a widespread geriatric syndrome among older adults, including hospitalized older inpatients. Some countries use electronic frailty measurement tools to identify frailty at the primary care level, but this method has rarely been investigated during hospitalization in acute care hospitals. An electronic frailty measurement instrument based on population-based hospital electronic health records could effectively detect frailty, frailty-related problems, and complications as well be a clinical alert. Identifying frailty among older adults using existing patient health data would greatly aid the management and support of frailty identification and could provide a valuable public health instrument without additional costs., Objective: We aim to explore a data-driven frailty measurement instrument for older adult inpatients using data routinely collected at hospital admission and discharge., Methods: A retrospective electronic patient register study included inpatients aged ≥65 years admitted to and discharged from a public hospital between 2015 and 2017. A dataset of 53,690 hospitalizations was used to customize this data-driven frailty measurement instrument inspired by the Edmonton Frailty Scale developed by Rolfson et al. A 2-step hierarchical cluster procedure was applied to compute e-Frail-CH (Switzerland) scores at hospital admission and discharge. Prevalence, central tendency, comparative, and validation statistics were computed., Results: Mean patient age at admission was 78.4 (SD 7.9) years, with more women admitted (28,018/53,690, 52.18%) than men (25,672/53,690, 47.81%). Our 2-step hierarchical clustering approach computed 46,743 inputs of hospital admissions and 47,361 for discharges. Clustering solutions scored from 0.5 to 0.8 on a scale from 0 to 1. Patients considered frail comprised 42.02% (n=19,643) of admissions and 48.23% (n=22,845) of discharges. Within e-Frail-CH's 0-12 range, a score ≥6 indicated frailty. We found a statistically significant mean e-Frail-CH score change between hospital admission (5.3, SD 2.6) and discharge (5.75, SD 2.7; P<.001). Sensitivity and specificity cut point values were 0.82 and 0.88, respectively. The area under the receiver operating characteristic curve was 0.85. Comparing the e-Frail-CH instrument to the existing Functional Independence Measure (FIM) instrument, FIM scores indicating severe dependence equated to e-Frail-CH scores of ≥9, with a sensitivity and specificity of 0.97 and 0.88, respectively. The area under the receiver operating characteristic curve was 0.92. There was a strong negative association between e-Frail-CH scores at hospital discharge and FIM scores (r s =-0.844; P<.001)., Conclusions: An electronic frailty measurement instrument was constructed and validated using patient data routinely collected during hospitalization, especially at admission and discharge. The mean e-Frail-CH score was higher at discharge than at admission. The routine calculation of e-Frail-CH scores during hospitalization could provide very useful clinical alerts on the health trajectories of older adults and help select interventions for preventing or mitigating frailty., (©Boris Wernli, Henk Verloo, Armin von Gunten, Filipa Pereira. Originally published in JMIR Aging (https://aging.jmir.org), 28.10.2024.)

Objective: This study aimed to investigate medication management among polymedicated, home-dwelling older adults after discharge from a hospital centre in French-speaking Switzerland and then develop a model to optimise medication management and prevent adverse health outcomes associated with medication-related problems (MRPs)., Design: Explanatory, sequential, mixed methods study based on detailed quantitative and qualitative findings reported previously., Setting: Hospital and community healthcare in the French-speaking part of Switzerland., Participants: The quantitative strand retrospectively examined 3 years of hospital electronic patient records (n=53 690 hospitalisations of inpatients aged 65 years or older) to identify the different profiles of those at risk of 30-day hospital readmission and unplanned nursing home admission. The qualitative strand explored the perspectives of older adults (n=28), their informal caregivers (n=17) and healthcare professionals (n=13) on medication management after hospital discharge., Results: Quantitative results from older adults' profiles, affected by similar patient-related, medication-related and environment-related factors, were enhanced and supported by qualitative findings. The combined findings enabled us to design an interprofessional, collaborative medication management model to prevent MRPs among home-dwelling older adults after hospital discharge. The model comprised four interactive fields of action: listening to polymedicated home-dwelling older adults and their informal caregivers; involving older adults and their informal caregivers in shared, medication-related decision-making; empowering older adults and their informal caregivers for safe medication self-management; optimising collaborative medication management practices., Conclusion: By linking the retrospective and prospective findings from our explanatory sequential study involving multiple stakeholders' perspectives, we created a deeper comprehension of the complexities and challenges of safe medication management among polymedicated, home-dwelling older adults after their discharge from hospital. We subsequently designed an innovative, collaborative, patient-centred model for optimising medication management and preventing MRPs in this population., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To investigate patient characteristics and the available health and drug data associated with unplanned nursing home admission following an acute hospital admission or readmission., Design: A population-based hospital registry study., Setting: A public hospital in southern Switzerland (Valais Hospital)., Participants: We explored a population-based longitudinal dataset of 14 705 hospital admissions from 2015 to 2018., Outcome Measures: Sociodemographic, health and drug data, and their interactions predicting the risk of unplanned nursing home admission., Results: The mean prevalence of unplanned nursing home admission after hospital discharge was 6.1% (n=903/N=14 705). Our predictive analysis revealed that the oldest adults (OR=1.07 for each additional year of age; 95% CI 1.05 to 1.08) presenting with impaired functional mobility (OR=3.22; 95% CI 2.67 to 3.87), dependency in the activities of daily living (OR=4.62; 95% CI 3.76 to 5.67), cognitive impairment (OR=3.75; 95% CI 3.06 to 4.59) and traumatic injuries (OR=1.58; 95% CI 1.25 to 2.01) had a higher probability of unplanned nursing home admission. The number of International Classification of Diseases, 10th version diagnoses had no significant impact on nursing home admissions, contrarily to the number of prescribed drugs (OR=1.17; 95% CI 1.15 to 1.19). Antiemetics/antinauseants (OR=2.53; 95% CI 1.21 to 5.30), digestives (OR=1.78; 95% CI 1.09 to 2.90), psycholeptics (OR=1.76; 95% CI 1.60 to 1.93), antiepileptics (OR=1.49; 95% CI 1.25 to 1.79) and anti-Parkinson's drugs (OR=1.40; 95% CI 1.12 to 1.75) were strongly linked to unplanned nursing home admission., Conclusions: Numerous risk factors for unplanned nursing home admission were identified. To prevent the adverse health outcomes that precipitate acute hospitalisations and unplanned nursing home admissions, ambulatory care providers should consider these risk factors in their care planning for older adults before they reach a state requiring hospitalisation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

This study explored and compared the functional status of polymedicated and non-polymedicated geriatric inpatients at hospital discharge. We used a cross-sectional registry of geriatric patients' hospital records from a multi-site public hospital center in Switzerland. The analysis included all inpatients aged 65 years old or more admitted between 1 January 2015 and 31 December 2017 (n = 53,690), of whom 67.5% were polymedicated at hospital discharge, 52.1% were women (n = 18,909), and 42.7% were 75-84 years old (n = 15,485). On average, the polymedicated patients' hospital lengths of stay were six days longer, they presented with more than three comorbidities, and they were prescribed more than nine medications at hospital discharge ( p < 0.001). They showed more frequent general mobility decline (43.2% vs. 41.9%), gait disorders (46.2% vs. 43%), fatigue (48.6% vs. 43.4%) and dependence on lower-body care (49.7% vs. 47.6%), and presented a higher malnutrition risk (OR = 1.411; 95%CI 1.263-1.577; p < 0.001). However, the non-polymedicated inpatients had proportionally more physical and cognitive impairments. The comparison of the functional status of polymedicated and non-polymedicated geriatric inpatients at hospital discharge is important for clinicians trying to identify and monitor those who are most vulnerable to functional decline, and to design targeted strategies for the prevention of functional impairment and related adverse health outcomes.

Objectives: The present study analysed 4 years of a hospital register (2015-2018) to determine the risk of 30-day hospital readmission associated with the medical conditions and drug regimens of polymedicated, older inpatients discharged home., Design: Registry-based cohort study., Setting: Valais Hospital-a public general hospital centre in the French-speaking part of Switzerland., Participants: We explored the electronic records of 20 422 inpatient stays by polymedicated, home-dwelling older adults held in the hospital's patient register. We identified 13 802 hospital readmissions involving 8878 separate patients over 64 years old., Outcome Measures: Sociodemographic characteristics, medical conditions and drug regimen data associated with risk of readmission within 30 days of discharge., Results: The overall 30-day hospital readmission rate was 7.8%. Adjusted multivariate analyses revealed increased risk of hospital readmission for patients with longer hospital length of stay (OR=1.014 per additional day; 95% CI 1.006 to 1.021), impaired mobility (OR=1.218; 95% CI 1.039 to 1.427), multimorbidity (OR=1.419 per additional International Classification of Diseases, 10th Revision condition; 95% CI 1.282 to 1.572), tumorous disease (OR=2.538; 95% CI 2.089 to 3.082), polypharmacy (OR=1.043 per additional drug prescribed; 95% CI 1.028 to 1.058), and certain specific drugs, including antiemetics and antinauseants (OR=3.216 per additional drug unit taken; 95% CI 1.842 to 5.617), antihypertensives (OR=1.771; 95% CI 1.287 to 2.438), drugs for functional gastrointestinal disorders (OR=1.424; 95% CI 1.166 to 1.739), systemic hormonal preparations (OR=1.207; 95% CI 1.052 to 1.385) and vitamins (OR=1.201; 95% CI 1.049 to 1.374), as well as concurrent use of beta-blocking agents and drugs for acid-related disorders (OR=1.367; 95% CI 1.046 to 1.788)., Conclusions: Thirty-day hospital readmission risk was associated with longer hospital length of stay, health disorders, polypharmacy and drug regimens. The drug regimen patterns increasing the risk of hospital readmission were very heterogeneous. Further research is needed to explore hospital readmissions caused solely by specific drugs and drug-drug interactions., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Background: Hospital patient registries provide substantial longitudinal data sets describing the clinical and medical health statuses of inpatients and their pharmacological prescriptions. Despite the multiple advantages of routinely collecting multidimensional longitudinal data, those data sets are rarely suitable for advanced statistical analysis and they require customization and synthesis., Objective: The aim of this study was to describe the methods used to transform and synthesize a raw, multidimensional, hospital patient registry data set into an exploitable database for the further investigation of risk profiles and predictive and survival health outcomes among polymorbid, polymedicated, older inpatients in relation to their medicine prescriptions at hospital discharge., Methods: A raw, multidimensional data set from a public hospital was extracted from the hospital registry in a CSV (.csv) file and imported into the R statistical package for cleaning, customization, and synthesis. Patients fulfilling the criteria for inclusion were home-dwelling, polymedicated, older adults with multiple chronic conditions aged ≥65 who became hospitalized. The patient data set covered 140 variables from 20,422 hospitalizations of polymedicated, home-dwelling older adults from 2015 to 2018. Each variable, according to type, was explored and computed to describe distributions, missing values, and associations. Different clustering methods, expert opinion, recoding, and missing-value techniques were used to customize and synthesize these multidimensional data sets., Results: Sociodemographic data showed no missing values. Average age, hospital length of stay, and frequency of hospitalization were computed. Discharge details were recoded and summarized. Clinical data were cleaned up and best practices for managing missing values were applied. Seven clusters of medical diagnoses, surgical interventions, somatic, cognitive, and medicines data were extracted using empirical and statistical best practices, with each presenting the health status of the patients included in it as accurately as possible. Medical, comorbidity, and drug data were recoded and summarized., Conclusions: A cleaner, better-structured data set was obtained, combining empirical and best-practice statistical approaches. The overall strategy delivered an exploitable, population-based database suitable for an advanced analysis of the descriptive, predictive, and survival statistics relating to polymedicated, home-dwelling older adults admitted as inpatients. More research is needed to develop best practices for customizing and synthesizing large, multidimensional, population-based registries., International Registered Report Identifier (irrid): RR2-10.1136/bmjopen-2019-030030., (©Zhivko Taushanov, Henk Verloo, Boris Wernli, Saviana Di Giovanni, Armin von Gunten, Filipa Pereira. Originally published in JMIR Medical Informatics (https://medinform.jmir.org), 11.05.2021.)

Introduction: Optimal medication management is one of the basic conditions necessary for home-dwelling older adults living with multiple chronic conditions (OAMCC) to be able to remain at home and preserve their quality of life. Currently, the reasons for such high numbers of emergency department visits and the very significant rate of hospitalisations for OAMCC, due to medication-related problems (MRPs), is poorly explored. This study aims to reveal the current state of the medication management practices of polymedicated, home-dwelling OAMCC and to make proposals for improving clinical and medication pathways through an innovative and integrated model for supporting medication management and preventing adverse health outcomes., Methods and Analysis: A mixed-methods study will address the medication management of polymedicated, home-dwelling OAMCC. Its explanatory sequential design will involve two major phases conducted sequentially over time. The quantitative phase will consist of retrospectively exploiting the last 5 years of electronic patient records from a local hospital (N ≈ 50 000) in order to identify the different profiles-made up of patient-related, medication-related and environment-related factors-of the polymedicated, home-dwelling OAMCC at risk of hospitalisation, emergency department visits, hospital readmission (notably for MRPs), institutionalisation or early death. The qualitative study will involve: (a) obtaining and understanding the medication management practices and experiences of the identified profiles extracted from the hospital data of OAMCC who will be interviewed at home (N ≈ 30); (b) collecting and analysing the perspectives of the formal and informal caregivers involved in medication management at home in order to cross-reference perspectives about this important dimension of care at home. Finally, the mixed-methods findings will enable the development of an innovative, integrated model of medication management based on the Agency for Clinical Innovation framework and Bodenheimer and Sinsky's quadruple aim., Ethics and Dissemination: Ethical approval has been obtained from the Human Research Ethics Committee of the Canton Vaud (2018-02196). Findings will be disseminated in peer-reviewed journals, professional conferences and other knowledge transfer activities with primary healthcare providers, hospital care units, informal caregivers' and patients' associations., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Isotopic analyses of radioactive materials such as irradiated nuclear fuel are of major importance for the optimization of the nuclear fuel cycle and for safeguard aspects. Among the mass-spectrometric techniques available, inductively coupled plasma mass spectrometry (ICP-MS) and thermal ionization mass spectrometry are the most frequently applied methods for nuclear applications. Because of the low detection limits, the ability to analyze the isotopic composition of the elements and the applicability of the techniques for measuring stable as well as radioactive nuclides with similar sensitivity, both mass-spectrometric techniques are an excellent amendment to classical radioactivity counting methods. The paper describes selected applications of multicollector ICP-MS in combination with chromatographic separation techniques and laser ablation for the isotopic analysis of irradiated nuclear fuels. The advantages and limitations of the selected analytical technique for the characterization of such a heterogeneous sample matrix are discussed.

Calcium-dependent protein kinases play a pivotal role in calcium signalling in plants and some protozoa, including the malaria parasites. They are found in various subcellular locations, suggesting an involvement in multiple signal transduction pathways. Recently, Plasmodium falciparum calcium-dependent protein kinase 1 (PfCDPK1) has been found in the membrane and organelle fraction of the parasite. The kinase contains three motifs for membrane binding at its N-terminus, a consensus sequence for myristoylation, a putative palmitoylation site and a basic motif. Endogenous PfCDPK1 and the in vitro translated kinase were both shown to be myristoylated. The supposed membrane attachment function of the basic cluster was experimentally verified and shown to participate together with N-myristoylation in membrane anchoring of the kinase. Using immunogold electron microscopy, the protein was detected in the parasitophorous vacuole and the tubovesicular system of the parasite. Mutagenesis of the predicted acylated residues and the basic motif confirmed that dual acylation and the basic cluster are required for correct targeting of Aequorea victoria green fluorescent protein to the parasitophorous vacuole, suggesting that PfCDPK1 as the leishmanial hydrophilic acylated surface protein B is a representative of a novel class of proteins whose export is dependent on a 'non-classical' pathway involving N-myristoylation/palmitoylation.

Precise and accurate isotope ratio measurements are an important task in many applications such as isotope-dilution mass spectrometry, bioavailability studies, or the determination of isotope variations in geological or nuclear samples. The technique of MC-ICP-MS has attracted much attention because it permits the precise measurement of isotope compositions for a wide range of elements combined with excellent detection limits due to high ionisation efficiencies. However, the results are based mainly on measurements using continuous sample introduction. In the present study the determination of isotope ratios on various transient signals with a time duration of 30 to 60 s has been achieved by coupling high-performance liquid chromatography to a multicollector inductively coupled plasma mass spectrometer. In order to investigate the origin of ratio drifts across the transient signals for this hyphenated technique, measurements with the same standard solutions were also carried out using a flow-injection device for sample introduction. As a result of this application it could be concluded that the main source of the bias in the measured isotope ratios is within the ICP-MS instead of fractionation effects on the chromatographic column material. Preliminary studies on short transient signals of gaseous samples (dry plasma) showed a reverse fractionation effect compared with wet plasma conditions (flow injection and HPLC).

PfPK4, a protein kinase gene from the human malarial parasite Plasmodium falciparum, has been cloned utilizing oligonucleotide probing. The gene encodes a protein of a predicted length of 1123 amino acids, and within this amino acid sequence all the conserved regions characteristic of protein kinases can be identified. The catalytic kinase domain possesses highest identities (34-37%) with eukaryotic initiation factor-2alpha (eIF-2alpha) kinases, especially haem-regulated inhibitory (HRI) protein kinases. There are two kinase inserts in PfPK4, located at positions common to eIF-2alpha kinases. The first insert separates kinase subdomains IV and VI by 559 amino acids, and the second subdomains VII and VIII by 41 amino acids. Both inserts are larger than their homologues in eIF-2alpha kinases. The sequence of PfPK4 has one putative haemin-binding site. The recombinant protein, expressed in Escherichia coli, phosphorylates a synthetic peptide representing a substrate of eIF-2alpha kinases. Autophosphorylation and substrate phosphorylation are inhibited by haemin. Thus PfPK4 appears to be the first protozoan protein kinase related to eIF-2alpha kinases and might be the first non-mammalian HRI kinase. Western blots indicated that the protein is expressed as major forms of 80 and 90 kDa. Whereas the 80 kDa form is present throughout the intraerythrocytic development and in merozoites, the two 90 kDa forms are only found in mature parasites. One of the latter is also present in the membrane fraction of erythrocytes harbouring segmenters. Confocal microscopy detected the protein distributed throughout the trophozoite, whereas it was found in discrete foci (punctate distribution) in segmenters. PfPK4 co-localizes with P. falciparum 83 kDa antigen/apical membrane antigen-1 at the apical complex in segmenters and merozoites, but does not co-localize with rhoptry-associated protein-1.

Sera from 16 echinococcosis patients were analyzed with respect to polyclonal B cell activation and autoantibody formation. At least 8 of the sera were from patients who were never in tropical countries and therefore their cases were not complicated by other parasitic diseases. In comparison with a group of 52 healthy controls, these patients had significant levels of antibodies to DNP and haemocyanin, indicators of polyclonal B cell activation. There were also significant differences between control and patient groups with respect to antibodies to dsDNA, histones, actin, vimentin, and desmin. This is the first report of autoantibodies in echinococcosis.

Serum pools from mice undergoing lethal infection with Plasmodium berghei inhibit the growth of an IL2-dependent mouse cytotoxic T cell line (CTLL). A partially purified preparation of the inhibitory factor specifically inhibited IL2-mediated events such as IL2-dependent CTLL growth and the Con A mitogenic response of normal mouse spleen cells. Production of and response to IL1, as well as growth of myeloma lines, was not affected. Administration of the partially purified preparation to normal mice resulted in a significant depression in IL2 production, thereby indicating a role for the inhibitory factor in maintaining immune depression in malaria-infected mice.