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1.
Environ Mol Mutagen ; 65(1-2): 4-24, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38545858

RESUMO

ToxTracker is a mammalian cell reporter assay that predicts the genotoxic properties of compounds with high accuracy. By evaluating induction of various reporter genes that play a key role in relevant cellular pathways, it provides insight into chemical mode-of-action (MoA), thereby supporting discrimination of direct-acting genotoxicants and cytotoxic chemicals. A comprehensive interlaboratory validation trial was conducted, in which the principles outlined in OECD Guidance Document 34 were followed, with the primary objectives of establishing transferability and reproducibility of the assay and confirming the ability of ToxTracker to correctly classify genotoxic and non-genotoxic compounds. Reproducibility of the assay to predict genotoxic MoA was confirmed across participating laboratories and data were evaluated in terms of concordance with in vivo genotoxicity outcomes. Seven laboratories tested a total of 64 genotoxic and non-genotoxic chemicals that together cover a broad chemical space. The within-laboratory reproducibility (WLR) was up to 98% (73%-98% across participants) and the overall between-laboratory reproducibility (BLR) was 83%. This trial confirmed the accuracy of ToxTracker to predict in vivo genotoxicants with a sensitivity of 84.4% and a specificity of 91.2%. We concluded that ToxTracker is a robust in vitro assay for the accurate prediction of in vivo genotoxicity. Considering ToxTracker's robust standalone accuracy and that it can provide important information on the MoA of chemicals, it is seen as a valuable addition to the regulatory in vitro genotoxicity battery that may even have the potential to replace certain currently used in vitro battery assays.


Assuntos
Dano ao DNA , Mamíferos , Animais , Humanos , Testes de Mutagenicidade , Reprodutibilidade dos Testes , Genes Reporter
2.
BMJ Open Qual ; 13(1)2024 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-38216295

RESUMO

BACKGROUND: Non-adherence to antihypertensive agents is common, mainly because of the low perceived burden of high blood pressure. General practitioners (GPs) are unable to predict whether patients are adhering to a recommended treatment. Knowledge about adherence might be of clinical interest in patients non-responding to antihypertensive treatment. AIM: To assess the usefulness of an Adherence Monitoring Package (AMoPac) to identify non-adherence in patients non-responding to antihypertensive treatment. METHODS: AMoPac consists of (1) 4 weeks of electronic adherence monitoring, (2) pharmacist's feedback on patient's intake behaviour and (3) adherence metrics including clinical-pharmaceutical recommendations to the GP. AMoPac-HYP ('Adherence Monitoring Package to identify non-adherence in ambulatory HYPertensive patients') is an observational study among GPs and ambulatory patients with hypertension in a real-world setting. The primary outcome was GPs' perceived usefulness of AMoPac. Secondary outcomes were (1) frequency of medication problems and prescribing errors; (2) types of pharmacist's' recommendations; (3) acceptance of the recommendations by GPs; (4) medication adherence and (5) patients' satisfaction. Outcomes are reported descriptively. Data were collected with questionnaires and electronic monitoring of medicine intake. RESULTS: Fifteen GPs and 15 patients with hypertension participated in the AMoPac-HYP Study. Patients were on average 62 years old, and mean blood pressure was 137/83 mmHg. All GPs rated AMoPac as useful. The most frequently mentioned use was excluding non-adherence in patients with hypertension (93%). Medication problems and prescribing errors were observed in 80% of the patients. The study pharmacist recommended adherence support (N=9 patients) and treatment optimisation (N=8 patients). The recommendations were accepted and implemented in 10 of 17 cases by the GP. Patients' mean taking and timing adherence were 90% and 86%, respectively. Satisfaction with the study procedures among patients was high. CONCLUSION: AMoPac was rated as useful for identifying and excluding non-adherence in patients with hypertension and was highly accepted among patients. Including adherence data in clinical decision-making could contribute to optimising patient care.


Assuntos
Clínicos Gerais , Hipertensão , Humanos , Pessoa de Meia-Idade , Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Adesão à Medicação , Satisfação do Paciente
3.
Clin Microbiol Infect ; 30(3): 353-359, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38000535

RESUMO

OBJECTIVES: The aim of this study was to evaluate antibiotic prescribing of medium-to-high prescribing primary care physicians being followed up after the completion of a Swiss national intervention trial of antibiotic prescription audit and feedback in the first SARS-CoV-2 pandemic year. METHODS: We used health insurer based claims data to calculate monthly antibiotic prescription rates per 100 consultations (primary endpoint) and applying interrupted time series (ITS) analysis methods, we estimated the immediate (step change) and sustained effects (slope) of the SARS-CoV-2 epidemic in 2020 on antibiotic prescribing compared to the pre-pandemic trial period from 2017-2019. RESULTS: We analysed data of 2945 of 3426 physicians (86.0%) from the trial with over 4 million consultations annually, who were in 2020 still in practice. Consultations dropped by 43% during the first pandemic year compared with 2017. Median monthly antibiotic prescription rates per 100 consultations in 2017 were 8.44 (Interquartile range [IQ] 6.32-11.50) and 8.35 (6.34-11.74) in the intervention and control groups, respectively, and increased to 15.63 (10.69-23.81) and 16.31 (10.65-24.72) per 100 consultations in 2020. ITS-derived incidence rate ratios for overall antibiotic prescriptions were 2.32 (95% CI 2.07-2.59) for the immediate pandemic effect, and 0.96 (0.95-0.98) for the sustained effect (change in slope in 2020 compared with 2017-2019). DISCUSSION: The SARS-CoV-2 pandemic had a major impact on antibiotic prescription patterns in primary care in Switzerland. For future viral pandemics, intervention plans with timely activation steps to minimize unjustified antibiotic consumption in primary care should be prepared.


Assuntos
COVID-19 , Médicos de Atenção Primária , Humanos , Pandemias , Suíça/epidemiologia , Antibacterianos/uso terapêutico , COVID-19/epidemiologia , SARS-CoV-2 , Atenção Primária à Saúde , Padrões de Prática Médica
4.
Environ Mol Mutagen ; 2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-38115239

RESUMO

Quantitative risk assessments of chemicals are routinely performed using in vivo data from rodents; however, there is growing recognition that non-animal approaches can be human-relevant alternatives. There is an urgent need to build confidence in non-animal alternatives given the international support to reduce the use of animals in toxicity testing where possible. In order for scientists and risk assessors to prepare for this paradigm shift in toxicity assessment, standardization and consensus on in vitro testing strategies and data interpretation will need to be established. To address this issue, an Expert Working Group (EWG) of the 8th International Workshop on Genotoxicity Testing (IWGT) evaluated the utility of quantitative in vitro genotoxicity concentration-response data for risk assessment. The EWG first evaluated available in vitro methodologies and then examined the variability and maximal response of in vitro tests to estimate biologically relevant values for the critical effect sizes considered adverse or unacceptable. Next, the EWG reviewed the approaches and computational models employed to provide human-relevant dose context to in vitro data. Lastly, the EWG evaluated risk assessment applications for which in vitro data are ready for use and applications where further work is required. The EWG concluded that in vitro genotoxicity concentration-response data can be interpreted in a risk assessment context. However, prior to routine use in regulatory settings, further research will be required to address the remaining uncertainties and limitations.

5.
Mutat Res Rev Mutat Res ; 792: 108469, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37777464

RESUMO

Over the past thirty years, the International Workshops on Genotoxicity Testing (IWGT) became one of the leading groups in the field of regulatory genotoxicology, not only due to the diversity of participants with respect to geography and professional affiliation, but also due to the unique setup of recurring IWGT meetings every four years. The hallmarks of the IWGT process have been diligent initial planning approaches of the working groups, collection of data so as to stimulate data-driven discussions and debate, and striving to reach consensus recommendations. The scientific quality of the Working Groups (WGs) has been exceptional due to the selection of highly regarded experts on each topic. As a result, the IWGT working group reports have become important documents. The deliberations and publications have provided guidance on test systems and testing protocols that have influenced the development or revision of test guidelines of the Organisation for Economic Co-operation and Development (OECD), guidance by the International Council for Harmonisation (ICH), and strategic testing or data analysis approaches in general. This article summarizes the history of the IWGT, identifies some of its major achievements, and provides an outlook for the future.


Assuntos
Testes de Mutagenicidade , Humanos , Testes de Mutagenicidade/métodos
6.
Geriatr Nurs ; 53: 12-18, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37399613

RESUMO

Unplanned hospitalizations from nursing homes (NHs) may be considered potentially avoidable and can result in adverse resident outcomes. There is little information about the relationship between a clinical assessment conducted by a physician or geriatric nurse expert before hospitalization and an ensuing rating of avoidability. This study aimed to describe characteristics of unplanned hospitalizations (admitted residents with at least one night stay, emergency department visits were excluded) and to examine this relationship. We conducted a cohort study in 11 Swiss NHs and retrospectively evaluated data from the root cause analysis of 230 unplanned hospitalizations. A telephone assessment by a physician (p=.043) and the need for further medical clarification and treatment (p=<0.001) were the principal factors related to ratings of avoidability. Geriatric nurse experts can support NH teams in acute situations and assess residents while adjudicating unplanned hospitalizations. Constant support for nurses expanding their clinical role is still warranted.


Assuntos
Hospitais , Casas de Saúde , Humanos , Idoso , Estudos de Coortes , Estudos Retrospectivos , Suíça , Hospitalização , Serviço Hospitalar de Emergência
7.
Ther Umsch ; 80(2): 46-47, 2023.
Artigo em Alemão | MEDLINE | ID: mdl-37067086
8.
Environ Mol Mutagen ; 2023 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-37097075

RESUMO

Historical negative control data (HCD) have played an increasingly important role in interpreting the results of genotoxicity tests. In particular, Organisation for Economic Co-operation and Development (OECD) genetic toxicology test guidelines recommend comparing responses produced by exposure to test substances with the distribution of HCD as one of three criteria for evaluating and interpreting study results (referred to herein as "Criterion C"). Because of the potential for inconsistency in how HCD are acquired, maintained, described, and used to interpret genotoxicity testing results, a workgroup of the International Workshops for Genotoxicity Testing was convened to provide recommendations on this crucial topic. The workgroup used example data sets from four in vivo tests, the Pig-a gene mutation assay, the erythrocyte-based micronucleus test, the transgenic rodent gene mutation assay, and the in vivo alkaline comet assay to illustrate how the quality of HCD can be evaluated. In addition, recommendations are offered on appropriate methods for evaluating HCD distributions. Recommendations of the workgroup are: When concurrent negative control data fulfill study acceptability criteria, they represent the most important comparator for judging whether a particular test substance induced a genotoxic effect. HCD can provide useful context for interpreting study results, but this requires supporting evidence that (i) HCD were generated appropriately, and (ii) their quality has been assessed and deemed sufficiently high for this purpose. HCD should be visualized before any study comparisons take place; graph(s) that show the degree to which HCD are stable over time are particularly useful. Qualitative and semi-quantitative assessments of HCD should also be supplemented with quantitative evaluations. Key factors in the assessment of HCD include: (i) the stability of HCD over time, and (ii) the degree to which inter-study variation explains the total variability observed. When animal-to-animal variation is the predominant source of variability, the relationship between responses in the study and an HCD-derived interval or upper bounds value (i.e., OECD Criterion C) can be used with a strong degree of confidence in contextualizing a particular study's results. When inter-study variation is the major source of variability, comparisons between study data and the HCD bounds are less useful, and consequentially, less emphasis should be placed on using HCD to contextualize a particular study's results. The workgroup findings add additional support for the use of HCD for data interpretation; but relative to most current OECD test guidelines, we recommend a more flexible application that takes into consideration HCD quality. The workgroup considered only commonly used in vivo tests, but it anticipates that the same principles will apply to other genotoxicity tests, including many in vitro tests.

9.
JAMA Intern Med ; 183(3): 213-220, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36745412

RESUMO

Importance: Antibiotics are commonly prescribed in primary care, increasing the risk of antimicrobial resistance in the population. Objective: To investigate the effect of quarterly audit and feedback on antibiotic prescribing among primary care physicians in Switzerland with medium to high antibiotic prescription rates. Design, Setting, and Participants: This pragmatic randomized clinical trial was conducted from January 1, 2018, to December 31, 2019, among 3426 registered primary care physicians and pediatricians in single or small practices in Switzerland who were among the top 75% prescribers of antibiotics. Intention-to-treat analysis was performed using analysis of covariance models and conducted from September 1, 2021, to January 31, 2022. Interventions: Primary care physicians were randomized in a 1:1 fashion to undergo quarterly antibiotic prescribing audit and feedback with peer benchmarking vs no intervention for 2 years, with 2017 used as the baseline year. Anonymized patient-level claims data from 3 health insurers serving roughly 50% of insurees in Switzerland were used for audit and feedback. The intervention group also received evidence-based guidelines for respiratory tract and urinary tract infection management and community antibiotic resistance information. Physicians in the intervention group were blinded regarding the nature of the trial, and physicians in the control group were not informed of the trial. Main Outcomes and Measures: The claims data used for audit and feedback were analyzed to assess outcomes. Primary outcome was the antibiotic prescribing rate per 100 consultations during the second year of the intervention. Secondary end points included overall antibiotic use in the first year and over 2 years, use of quinolones and oral cephalosporins, all-cause hospitalizations, and antibiotic use in 3 age groups. Results: A total of 3426 physicians were randomized to the intervention (n = 1713) and control groups (n = 1713) serving 629 825 and 622 344 patients, respectively, with a total of 4 790 525 consultations in the baseline year of 2017. In the entire cohort, a 4.2% (95% CI, 3.9%-4.6%) relative increase in the antibiotic prescribing rate was noted during the second year of the intervention compared with 2017. In the intervention group, the median annual antibiotic prescribing rate per 100 consultations was 8.2 (IQR, 6.1-11.4) in the second year of the intervention and was 8.4 (IQR, 6.0-11.8) in the control group. Relative to the overall increase, a -0.1% (95% CI, -1.2% to 1.0%) lower antibiotic prescribing rate per 100 consultations was found in the intervention group compared with the control group. No relevant reductions in specific antibiotic prescribing rates were noted between groups except for quinolones in the second year of the intervention (-0.9% [95% CI, -1.5% to -0.4%]). Conclusions and Relevance: This randomized clinical trial found that quarterly personalized antibiotic prescribing audit and feedback with peer benchmarking did not reduce antibiotic prescribing among primary care physicians in Switzerland with medium to high antibiotic prescription rates. Trial Registration: ClinicalTrials.gov Identifier: NCT03379194.


Assuntos
Antibacterianos , Padrões de Prática Médica , Humanos , Antibacterianos/uso terapêutico , Retroalimentação , Atenção Primária à Saúde , Prescrições , Prescrição Inadequada
10.
BMJ Open Qual ; 12(1)2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36849193

RESUMO

BACKGROUND: Adherence to pharmacotherapy is crucial to prevent symptom deterioration in chronic diseases. However, non-adherence to chronic treatments is prevalent, especially in polypharmacy. Practical tools to assess adherence to polypharmacy in primary care are missing. AIMS: We aimed to develop an Adherence Monitoring Package (AMoPac) for general practitioners (GPs) to identify patient non-adherence. We tested the feasibility and acceptance of AMoPac in the primary healthcare setting. METHODS: AMoPac was developed based on peer-reviewed literature. It consists in (1) electronic monitoring of patients' medication intakes for 4 weeks, (2) receiving feedback on intake behaviour by the pharmacist and (3) generating an adherence report to communicate to the GPs. A feasibility study was conducted with heart failure patients. GPs' acceptance of AMoPac was explored with semistructured interviews. Electronic transmission of the reports into the GP's electronic health record along with laboratory reports stating N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels was analysed. RESULTS: We developed AMoPac and tested its feasibility with six GPs and seven heart failure patients. GPs were satisfied with the adherence report including the pharmaceutical-clinical recommendations. Integrated transmission of adherence reports to GPs was not feasible due to technical incompatibilities. Mean taking adherence was 86.4%±12.8% and three patients had low correct dosing-days (69%, 38% and 36%, respectively). NT-proBNP ranged from 102 to 8561 pg/mL and four patients had elevated values (>1000 pg/mL). CONCLUSION: AMoPac is feasible in the primary healthcare setting, excluding the integrated transmission of adherence reports to GPs. The procedure was highly accepted by GPs and patients. AMoPac fills a gap by combining clinical values with adherence data, and therefore, delivers a multifaceted picture of the patient's behaviour. In case of unmet adherence, our tool might facilitate the selection of patient-centred approaches to optimise pharmacological therapies in chronic heart failure patients. TRIAL REGISTRATION NUMBER: NCT04326101.


Assuntos
Insuficiência Cardíaca , Polimedicação , Humanos , Estudos de Viabilidade , Insuficiência Cardíaca/tratamento farmacológico , Adesão à Medicação , Atenção Primária à Saúde
12.
PLoS One ; 17(12): e0278767, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36542596

RESUMO

BACKGROUND: Evaluations of integrated care models for home-dwelling frail older adults have shown inconclusive results on health and service outcomes. However, limited research has focused on the implementation of integrated care models. Applying implementation science methods may facilitate uptake of integrated care models, thus generating positive outcomes e.g., reduced hospital admissions. This paper describes the protocol to assess the feasibility of an integrated care model (featuring a four-step comprehensive geriatric assessment: screening, a multi-dimensional assessment, a coordinated individualized care plan and follow-up) designed for a new community-based center for home-dwelling older adults in Switzerland. The study includes the following objectives: 1) to assess implementation by a) monitoring respondents to the outreach strategies and describing the Center's visitors; b) assessing implementation outcomes related to the care model (i.e., adoption, acceptability, feasibility, fidelity) and implementation processes related to collaboration; and 2) assessing implementation costs. METHODS: For objective 1a, we will use a descriptive design to assess respondents to the outreach strategies and describe the Center's visitors. We will use a parallel convergent mixed methods design for objective 1b. Implementation outcomes data will be collected from meetings with the Center's staff, interviews with older adults and their informal caregivers, and reviewing older adults' health records at the Center. Implementation processes related to collaboration will be assessed through a questionnaire to external collaborators (e.g., GPs) towards the end of the study. For objective 2, implementation costs will be calculated using time-driven activity-based costing methods. Data collection is anticipated to occur over approximately six months. DISCUSSION: This study of a contextually adapted integrated care model will inform adaptations to the outreach strategies, care model and implementation strategies in one community center, prior to evaluating the care model effectiveness and potentially scaling out the intervention. TRIAL REGISTRATION: Feasibility study registration ID with clinicaltrials.gov: NCT05302310; registration ID with BMC: ISRCTN12324618.


Assuntos
Prestação Integrada de Cuidados de Saúde , Idoso Fragilizado , Humanos , Idoso , Estudos de Viabilidade , Cuidadores , Hospitalização
13.
Health Qual Life Outcomes ; 20(1): 166, 2022 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-36544173

RESUMO

BACKGROUND: HRQoL is an indicator of individuals' perception of their overall health, including social and environmental aspects. As a multidimensional concept, HRQoL can be influenced by a multitude of factors. Studies of HRQoL and factors associated with it among home-dwelling older adults have often been limited to inpatient settings or to a sub-population with a chronic disease. Studying HRQoL and its correlating factors among this population, by providing an ecological lens on factors beyond the individual level, can provide a better understanding of the construct and the role of the environment on how they perceive their HRQoL. Thus, we aimed to assess the HRQoL and investigate the correlates of HRQOL among home-dwelling older adults, guided by the levels of the ecological model. METHODS: This is a cross-sectional population survey conducted in 2019 in Canton Basel-Landschaft, in northwestern Switzerland, and includes a sample of 8786 home-dwelling older adults aged 75 and above. We assessed HRQoL by using the EQ-index and the EQ-VAS. The influence of independent variables at the macro, meso and micro level on HRQoL was tested using Tobit multiple linear regression modelling. RESULTS: We found that having a better socio-economic status as denoted by higher income, having supplementary insurance and a higher level of education were all associated with a better HRQoL among home-dwelling older adults. Furthermore, being engaged in social activities was also related to an improved HRQoL. On the other hand, older age, female gender, presence of multimorbidity and polypharmacy as well as social isolation and loneliness were found to all have a negative impact on HRQoL. CONCLUSIONS: Understanding factors related to HRQoL by using an ecological lens can help identify factors beyond the individual level that impact the HRQoL of home-dwelling older adults. Our study emphasises the importance of social determinants of health and potential disparities that exists, encouraging policymakers to focus on policies to reduce socio-economic disparities using a life-course approach, which consequently could also impact HRQoL in later stages of life.


Assuntos
Qualidade de Vida , Humanos , Feminino , Idoso , Estudos Transversais , Suíça , Inquéritos e Questionários , Modelos Lineares
14.
BMC Geriatr ; 22(1): 857, 2022 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-36376806

RESUMO

BACKGROUND: Home-dwelling frail older adults are often faced with multimorbidity and complex care needs, requiring health and social care systems that support frail older adults to age in place. The objective of this paper was to investigate the types of formal health and social care as well as informal care and social support used by home-dwelling frail older adults; whether they perceive their support as sufficient; and their experience with and preferences for care and support. METHODS: Using an explanatory sequential mixed methods design, we first conducted a secondary analysis of a subset of cross-sectional data from the ImplemeNtation of a community-baSed care Program for home dwelling senIoR citizEns (INSPIRE) population survey using descriptive analysis. Subsequently, we analyzed existing data from interviews in the parent study to help explain the survey results using applied thematic analysis. Results were organized according to adapted domains and concepts of the SELFIE framework and integrated via a joint display table. RESULTS: Of the parent population survey respondents, 2314 older adults indicating frailty were included in the quantitative arm of this study. Interview data was included from 7 older adults who indicated frailty. Support from health and social, formal and informal caregivers is diverse and anticipated to increase (e.g., for 'care and assistance at home' and 'meal services'). Informal caregivers fulfilled various roles and while some older adults strongly relied on them for support, others feared burdening them. Most participants (93.5%) perceived their overall support to meet their needs; however, findings suggest areas (e.g., assessment of overall needs) which merit attention to optimize future care. CONCLUSIONS: Given the anticipated demand for future care and support, we recommend efforts to prevent fragmentation between health and social as well as formal and informal care.


Assuntos
Idoso Fragilizado , Fragilidade , Humanos , Idoso , Fragilidade/diagnóstico , Fragilidade/epidemiologia , Fragilidade/terapia , Estudos Transversais , Suíça/epidemiologia , Apoio Social , Cuidadores
15.
Geriatr Nurs ; 48: 280-286, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36334468

RESUMO

Aim of this study was to test the reliability and validity of the life-space measures and walking speed delivered by the MOBITEC-GP app. Participants underwent several supervised walking speed assessments as well as a 1-week life-space assessment during two assessment sessions 9 days apart. Fifty-seven older adults (47.4% male, mean age= 75.3 (±5.9) years) were included in the study. The MOBITEC-GP app showed moderate to excellent test-retest reliability (ICCs between 0.584 and 0.920) and validity (ICCs between 0.468 and 0.950) of walking speed measurements of 50 meters and above and of most 1-week life-space parameters, including life-space area, time spent out-of-home, and action range. The MOBITEC-GP app for Android is a reliable and valid tool for the assessment of real-life walking speed (at distances of 50 metres and above) and life-space parameters of older adults. Future studies should look into technical issues more systematically in order to avoid invalid measurements.


Assuntos
Aplicativos Móveis , Humanos , Masculino , Idoso , Feminino , Reprodutibilidade dos Testes , Velocidade de Caminhada , Psicometria , Caminhada , Marcha
16.
Artigo em Inglês | MEDLINE | ID: mdl-35914859

RESUMO

It is often assumed that genotoxic substances will be detected more easily by using in vitro rather than in vivo genotoxicity tests since higher concentrations, more cytotoxicity and static exposures can be achieved. However, there is a paucity of data demonstrating whether genotoxic substances are detected at lower concentrations in cell culture in vitro than can be reached in the blood of animals treated in vivo. To investigate this issue, we compared the lowest concentration required for induction of chromosomal damage in vitro (lowest observed effective concentration, or LOEC) with the concentration of the test substance in blood at the lowest dose required for biologically relevant induction of micronuclei in vivo (lowest observed effective dose, or LOED). In total, 83 substances were found for which the LOED could be identified or estimated, where concentrations in blood and micronucleus data were available via the same route of administration in the same species, and in vitro chromosomal damage data were available. 39.8 % of substances were positive in vivo at blood concentrations that were lower than the LOEC in vitro, 22.9 % were positive at similar concentrations, and 37.3 % of substances were positive in vivo at higher concentrations. Distribution analysis showed a very wide scatter of > 6 orders of magnitude across these 3 categories. When mode of action was evaluated, the distribution of clastogens and aneugens across the 3 categories was very similar. Thus, the ability to detect induction of micronuclei in bone marrow in vivo regardless of the mechanism for micronucleus induction, is clearly not solely determined by the concentration of test substance which induced chromosomal damage in vitro.


Assuntos
Aneugênicos , Mutagênicos , Animais , Meios de Cultura , Dano ao DNA , Testes para Micronúcleos , Mutagênicos/toxicidade
17.
Acta Diabetol ; 59(9): 1189-1200, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35780277

RESUMO

AIM: Management of diabetes care can be affected by COVID-19 pandemic control measures. This study aimed to determine the impact of the pandemic, during 17.03.2020-16.03.2021, on quality outcomes of diabetes care in general practice in Switzerland. METHODS: In this retrospective cohort study, diabetes mellitus patients (≥ 18 years) with at least one consultation at a general practitioner, during 17.03.2018-16.03.2019 (cohort 1) and 17.03.2019-16.03.2020 (cohort 2) were included and followed-up for two years. Quality indicators and outcomes of diabetes care, at patient and practitioner level, were compared before and during the pandemic. Logistic regression was performed to identify patient's risk factors for dropout from follow-up. RESULTS: Data from 191 practices, 23,903 patients, cohort 1 and 25,092 patients, cohort 2, were analyzed. The fraction of patients lost to follow-up, attributable to the pandemic, was 28% (95% confidence interval: 25%, 30%). During the pandemic, compared to the previous year, regular measurement of weight, HbA1c, blood pressure and serum creatinine were less frequent and less patients per practitioner reached HbA1c and blood pressure target outcomes. Factors associated with continuity of care during the pandemic were: patient age 41-80 years, longer diabetes duration, diagnosis of hypertension or dyslipidemia, influenza vaccination during the last year. Risk factors for dropout were age > 80 and receiving only insulin as anti-diabetic medication. CONCLUSION: A considerable quality reduction in diabetes mellitus care could be observed during the pandemic. Though the most vulnerable patients were not the most affected by the pandemic, key factors that might reduce dropout from follow-up were identified.


Assuntos
COVID-19 , Diabetes Mellitus Tipo 2 , Diabetes Mellitus , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/epidemiologia , Estudos de Coortes , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/terapia , Hemoglobinas Glicadas , Humanos , Pessoa de Meia-Idade , Pandemias , Atenção Primária à Saúde , Estudos Retrospectivos
18.
Swiss Med Wkly ; 152: w30196, 2022 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-35752965

RESUMO

INTRODUCTION: General practitioners (GPs) play a key role in the delivery of health care in Switzerland. Assessing GPs' workload over time is essential to meet the population's health service demand and for future health care planning. METHODS: The study involved four questionnaire-based cross-sectional studies among a representative sample of Swiss GPs on a five-yearly basis since 2005. Data on GPs' self-estimated workload and practice administration (face-to-face consultations, house calls, nursing home visits and clinical administrative work) were analysed in hours per week (h/week) or full-time equivalents (FTE; 100% = 55 h/week). RESULTS: The mean age of GPs (n = 2,037) in 2020 was 54.9 years, significantly higher than in 2005 (51.4 years, p <0.001, n = 1,780). The proportion of female GPs increased gradually from 16.5% in 2005 to 36.2% in 2020 (p <0.001). The GPs' workload significantly decreased over the last 15 years from 50.2 h/week to 43.4 h/week or from 90.9% FTE in 2005 to 78.9% FTE in 2020 (p <0.001). The decreased average workload across years was less pronounced in women (-4.4% FTE) than in men (-9.0% FTE, p = 0.015). Across all survey years, women worked on average 12.7 h/week or 23.2% FTE less than men (p <0.001). The time spent with patients gradually decreased, whereas the amount of time spent on clinical administrative work remained stable since 2005 (9 h/week). In 2020, GPs were working more frequently in group practices compared to 2005 (45.0% vs. 12.4%, p <0.001). CONCLUSION: This study demonstrates a decrease in GPs' overall workload from 2005 to 2020, indicating that the "new" generation of GPs prefers to work part-time. This decrease is at the expense of direct face-to-face encounters with patients. Over the last 15 years, a clear trend exists towards more women in the Swiss general practice, persisting over-ageing of GPs, replacement of single-handed practices by group practices, and increasing burden of administrative tasks, a risk factor for burnout and reduced job satisfaction. To maintain an efficient healthcare system in the future, substantial efforts are crucial to provide a positive and motivating insight into general practice to pre- and postgraduate students and improve the operational working conditions of GPs.


Assuntos
Medicina Geral , Clínicos Gerais , Atitude do Pessoal de Saúde , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Autorrelato , Inquéritos e Questionários , Suíça , Carga de Trabalho
19.
BMC Geriatr ; 22(1): 496, 2022 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-35681157

RESUMO

BACKGROUND: Health economic evaluations of the implementation of evidence-based interventions (EBIs) into practice provide vital information but are rarely conducted. We evaluated the health economic impact associated with implementation and intervention of the INTERCARE model-an EBI to reduce hospitalisations of nursing home (NH) residents-compared to usual NH care. METHODS: The INTERCARE model was conducted in 11 NHs in Switzerland. It was implemented as a hybrid type 2 effectiveness-implementation study with a multi-centre non-randomised stepped-wedge design. To isolate the implementation strategies' costs, time and other resources from the NHs' perspective, we applied time-driven activity-based costing. To define its intervention costs, time and other resources, we considered intervention-relevant expenditures, particularly the work of the INTERCARE nurse-a core INTERCARE element. Further, the costs and revenues from the hotel and nursing services were analysed to calculate the NHs' losses and savings per resident hospitalisation. Finally, alongside our cost-effectiveness analysis (CEA), a sensitivity analysis focused on the intervention's effectiveness-i.e., regarding reduction of the hospitalisation rate-relative to the INTERCARE costs. All economic variables and CEA were assessed from the NHs' perspective. RESULTS: Implementation strategy costs and time consumption per bed averaged 685CHF and 9.35 h respectively, with possibilities to adjust material and human resources to each NH's needs. Average yearly intervention costs for the INTERCARE nurse salary per bed were 939CHF with an average of 1.4 INTERCARE nurses per 100 beds and an average employment rate of 76% of full-time equivalent per nurse. Resident hospitalisation represented a total average loss of 52% of NH revenues, but negligible cost savings. The incremental cost-effectiveness ratio of the INTERCARE model compared to usual care was 22'595CHF per avoided hospitalisation. As expected, the most influential sensitivity analysis variable regarding the CEA was the pre- to post-INTERCARE change in hospitalisation rate. CONCLUSIONS: As initial health-economic evidence, these results indicate that the INTERCARE model was more costly but also more effective compared to usual care in participating Swiss German NHs. Further implementation and evaluation of this model in randomised controlled studies are planned to build stronger evidential support for its clinical and economic effectiveness. TRIAL REGISTRATION: clinicaltrials.gov ( NCT03590470 ).


Assuntos
Papel do Profissional de Enfermagem , Casas de Saúde , Análise Custo-Benefício , Hospitalização , Humanos , Instituições de Cuidados Especializados de Enfermagem
20.
Curr Med Res Opin ; 38(8): 1459-1466, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35369836

RESUMO

BACKGROUND: Cough is one of the most common health issues for which medical attention is sought. A chronic cough (CC) is understood as a cough that lasts longer than 8 weeks. CC encompasses two subsets referred to as refractory chronic cough (RCC) and unexplained chronic cough (UCC). This study aims to assess the current understanding and perceptions of a RCC and UCC, from a physician's perspective in Switzerland and how this understanding and practical work leads to the relevant diagnosis and treatment. METHODS: In October 2020, 549 GPs and 338 pulmonologists in Switzerland, received an invite to participate in the online-based quantitative survey. Data collection was carried out through a 25-minute online survey. The questionnaire was based on structured questions, and conducted on a randomized sample of doctors (general practitioners -GPs and pulmonologists) in the German- and French-speaking part of Switzerland. RESULTS: Overall, 33 pulmonologists and 52 GPs participated in the online survey. Only 39% of GPs, but 73% of pulmonologists, defined chronic cough as a cough lasting 8 weeks or longer. The majority of physicians (72%), especially pulmonologists (88%), perceived a clinical gap regarding the treatment of persistent cough. 74% of the sampled physicians agreed that persistent cough is a high burden of disease for patients. Based on the answers, the annual number of new patients with RCC and UCC in Switzerland is estimated at 9322 patients. CONCLUSIONS: Results of this study have highlighted differences in the terminology used to describe CC (RCC and UCC), in the diagnostic tests used and, in the treatments used between GPs and pulmonologists. These findings suggest the need to align the current language regarding the disease to facilitate a standardized approach for diagnosis and treatment and towards improving patient care and reduce burden of disease for CC (RCC and UCC) patients.


Assuntos
Carcinoma de Células Renais , Clínicos Gerais , Neoplasias Renais , Doença Crônica , Tosse/tratamento farmacológico , Tosse/terapia , Humanos , Percepção , Inquéritos e Questionários , Suíça
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