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1.
bioRxiv ; 2023 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-38077022

RESUMO

Autophagy is an essential cellular recycling process that maintains protein and organelle homeostasis. ATG9A vesicle recruitment is a critical early step in autophagy to initiate autophagosome biogenesis. The mechanisms of ATG9A vesicle recruitment are best understood in the context of starvation-induced non-selective autophagy, whereas less is known about the signals driving ATG9A vesicle recruitment to autophagy initiation sites in the absence of nutrient stress. Here we demonstrate that loss of ATG9A or the lipid transfer protein ATG2 leads to the accumulation of phosphorylated p62 aggregates in the context of basal autophagy. Furthermore, we show that p62 degradation requires the lipid scramblase activity of ATG9A. Lastly, we present evidence that poly-ubiquitin is an essential signal that recruits ATG9A and mediates autophagy foci assembly in nutrient replete cells. Together, our data support a ubiquitin-driven model of ATG9A recruitment and autophagosome formation during basal autophagy.

2.
J Clin Oncol ; 41(36): 5482-5492, 2023 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-38100992

RESUMO

PURPOSE: Most patients with advanced pancreas cancer experience pain and must limit their daily activities because of tumor-related symptoms. To date, no treatment has had a significant impact on the disease. In early studies with gemcitabine, patients with pancreas cancer experienced an improvement in disease-related symptoms. Based on those findings, a definitive trial was performed to assess the effectiveness of gemcitabine in patients with newly diagnosed advanced pancreas cancer. PATIENTS AND METHODS: One hundred twenty-six patients with advanced symptomatic pancreas cancer completed a lead-in period to characterize and stabilize pain and were randomized to receive either gemcitabine 1,000 mg/m2 weekly x 7 followed by 1 week of rest, then weekly x 3 every 4 weeks thereafter (63 patients), or to fluorouracil (5-FU) 600 mg/m2 once weekly (63 patients). The primary efficacy measure was clinical benefit response, which was a composite of measurements of pain (analgesic consumption and pain intensity), Karnofsky performance status, and weight. Clinical benefit required a sustained (> or = 4 weeks) improvement in at least one parameter without worsening in any others. Other measures of efficacy included response rate, time to progressive disease, and survival. RESULTS: Clinical benefit response was experienced by 23.8% of gemcitabine-treated patients compared with 4.8% of 5-FU-treated patients (P = .0022). The median survival durations were 5.65 and 4.41 months for gemcitabine-treated and 5-FU-treated patients, respectively (P = .0025). The survival rate at 12 months was 18% for gemcitabine patients and 2% for 5-FU patients. Treatment was well tolerated. CONCLUSION: This study demonstrates that gemcitabine is more effective than 5-FU in alleviation of some disease-related symptoms in patients with advanced, symptomatic pancreas cancer. Gemcitabine also confers a modest survival advantage over treatment with 5-FU.

3.
J Chem Theory Comput ; 19(20): 7242-7259, 2023 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-37796868

RESUMO

The calculation of the origin-independent density of the dynamic electric dipole polarizability, previously presented for uncorrelated and density functional theory (DFT)-based methods, has been developed and implemented at the coupled cluster singles and doubles (CCSD) level of theory. A pointwise analysis of polarizability densities calculated for a number of molecules at Hartree-Fock (HF) and CCSD clearly shows that the electron correlation effect is much larger than one would argue considering the integrated dipole electric polarizability alone. Large error compensations occur during the integration process, which hide fairly large deviations mainly located in the internuclear regions. The same is observed when calculated CCSD and B3LYP polarizability densities are compared, with the remarkable feature that positive/negative deviations between CCSD and HF reverse sign, becoming negative/positive when comparing CCSD to B3LYP.

4.
Anaesthesia ; 78(12): 1465-1471, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37864459

RESUMO

The effects of oral dexamethasone on peripheral nerve blocks have not been investigated. We randomly allocated adults scheduled for forearm or hand surgery to oral placebo (n = 61), dexamethasone 12 mg (n = 61) or dexamethasone 24 mg (n = 57) about 45 min before lateral infraclavicular block. Mean (SD) time until first pain after block were: 841 (327) min; 1171 (318) min; and 1256 (395) min, respectively. Mean (98.3%CI) differences in time until first postoperative pain for dexamethasone 24 mg vs. placebo and vs. dexamethasone 12 mg were: 412 (248-577) min, p < 0.001; and 85 (-78 to 249) min, p = 0.21, respectively. Mean (98.3%CI) difference in time until first postoperative pain for dexamethasone 12 mg vs. placebo was 330 (186-474) min, p < 0.001. Both 24 mg and 12 mg of oral dexamethasone increased the time until first postoperative pain compared with placebo in patients having upper limb surgery under infraclavicular brachial plexus block.


Assuntos
Analgesia , Bloqueio do Plexo Braquial , Adulto , Humanos , Dexametasona , Dor Pós-Operatória , Extremidade Superior/cirurgia , Anestésicos Locais
5.
J Biomech ; 152: 111587, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37080081

RESUMO

Markerless motion capture has improved physical screening efficiency in sport and occupational settings; however, reliability of kinematic measurements from commercial systems must be established. Further, the impact of torso-borne equipment on these measurements is unclear. The purpose of this study was to evaluate the reliability of HumanTrak, a markerless motion capture system, for estimating peak trunk flexion in squat movements with and without a weighted vest. Eighteen participants completed body weight squats (BWSQ) and overhead squats (OHSQ) to their maximum depth (unrestricted-range) and to a plyometric box (fixed-range) while wearing no body armour (NBA) or 9 kg body armour (BA9). Peak trunk flexion was measured using HumanTrak. Testing was performed in two sessions on one day (intra-day) and one session on a separate day (inter-day) to assess reliability. HumanTrak had a standard error of measurement < 3.74° across all movements and conditions. Reliability was good to excellent (ICC = 0.82-0.96) with very large to nearly perfect Pearson correlations (r > 0.80) for all comparisons except unrestricted-range BWSQ with BA9 (ICC = 0.60-0.71, r = 0.71). HumanTrak was more reliable for intra- than inter-day, but reliability was still excellent for almost all inter-day comparisons (ICC > 0.82). HumanTrak is reliable for detecting differences in peak trunk flexion > 8.5° when body armour is not worn and > 10.5° when body armour is worn. Practitioners can assess meaningful changes in sagittal plane trunk motion when screening squat movements regardless of whether body armour is worn.


Assuntos
Captura de Movimento , Postura , Humanos , Reprodutibilidade dos Testes , Movimento , Amplitude de Movimento Articular , Fenômenos Biomecânicos
6.
J Cutan Pathol ; 50(5): 441-449, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36794511

RESUMO

BACKGROUND: To minimize the risk of incomplete excision of basal cell carcinomas (BCC) the macroscopic tumor margins should be adequately defined. Optical coherence tomography (OCT) is a non-invasive imaging tool that can provide structural and vascular information about skin cancer lesions. The study objective was to compare the presurgical delineation of facial BCC by clinical examination, histopathology, and OCT imaging in tumors undergoing full excision. METHODS: Ten patients with BCC lesions on the face were examined clinically, with OCT and histopathology at 3-mm intervals, from the clinical lesion border and beyond the resection line. The OCT scans were evaluated blinded and a delineation estimate of each BCC lesion was made. The results were compared to the clinical and histopathologic results. RESULTS: OCT evaluations and histopathology were in agreement in 86.6% of the collected data points. In three cases the OCT scans estimated a reduction of the tumor size compared to the clinical tumor border set by the surgeon. CONCLUSION: The results of this study support the notion that OCT can have a role in the clinical daily practice by aiding clinicians in delineating BCC lesions before surgery.


Assuntos
Carcinoma Basocelular , Neoplasias Cutâneas , Humanos , Tomografia de Coerência Óptica/métodos , Carcinoma Basocelular/diagnóstico por imagem , Carcinoma Basocelular/cirurgia , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/cirurgia , Cirurgia de Mohs/métodos
7.
J Mol Biol ; 435(2): 167890, 2023 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-36402225

RESUMO

14-3-3s are abundant proteins that regulate essentially all aspects of cell biology, including cell cycle, motility, metabolism, and cell death. 14-3-3s work by docking to phosphorylated Ser/Thr residues on a large network of client proteins and modulating client protein function in a variety of ways. In recent years, aided by improvements in proteomics, the discovery of 14-3-3 client proteins has far outpaced our ability to understand the biological impact of individual 14-3-3 interactions. The rate-limiting step in this process is often the identification of the individual phospho-serines/threonines that mediate 14-3-3 binding, which are difficult to distinguish from other phospho-sites by sequence alone. Furthermore, trial-and-error molecular approaches to identify these phosphorylations are costly and can take months or years to identify even a single 14-3-3 docking site phosphorylation. To help overcome this challenge, we used machine learning to analyze predictive features of 14-3-3 binding sites. We found that accounting for intrinsic protein disorder and the unbiased mass spectrometry identification rate of a given phosphorylation significantly improves the identification of 14-3-3 docking site phosphorylations across the proteome. We incorporated these features, coupled with consensus sequence prediction, into a publicly available web app, called "14-3-3 site-finder". We demonstrate the strength of this approach through its ability to identify 14-3-3 binding sites that do not conform to the loose consensus sequence of 14-3-3 docking phosphorylations, which we validate with 14-3-3 client proteins, including TNK1, CHEK1, MAPK7, and others. In addition, by using this approach, we identify a phosphorylation on A-kinase anchor protein-13 (AKAP13) at Ser2467 that dominantly controls its interaction with 14-3-3.


Assuntos
Proteínas 14-3-3 , Mapas de Interação de Proteínas , Humanos , Proteínas 14-3-3/metabolismo , Sítios de Ligação , Proteínas Fetais/metabolismo , Aprendizado de Máquina , Proteína Quinase 7 Ativada por Mitógeno/metabolismo , Fosforilação , Proteínas Tirosina Quinases/metabolismo , Proteoma/metabolismo , Serina/metabolismo , Treonina/metabolismo
8.
Public Health ; 210: 16-25, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35863158

RESUMO

OBJECTIVE: To systematically appraise the existing published literature on cervical cancer screening utilization, and associated barriers and facilitators, in Nepal. STUDY DESIGN: Systematic literature review and meta-analysis. METHODS: PubMed/MEDLINE, CINAHL, Scopus, Embase, and, Google Scholar were systematically searched using Preferred Reporting Items for Systematic Review and Meta-Analysis guideline. All quantitative and qualitative studies reporting cervical cancer screening (using the Pap smear test or visual inspection with acetic acid or human papillomavirus test) utilization, barriers, and facilitators for screening were identified. A meta-analysis was performed to estimate Nepal's pooled cervical cancer screening utilization proportion. RESULTS: The search yielded 97 records, of which 17 studies were included. Fifteen studies were quantitative and two were qualitative. Of the 17 studies, six were hospital-based and six were community-based. The pooled cervical cancer screening utilization proportion (using Pap smear test) among Nepalese women was 17% from the studies in the hospital settings, and 16% in the community. Six studies reported barriers to cervical cancer screening, of which four reported embarrassments related to the gynecological examination and a low level of knowledge on cervical cancer. Three (of four) studies reported health personnel, and two studies reported screening services-related facilitators for cervical cancer screening. CONCLUSION: Our review reported that cervical cancer screening utilization (16%) is more than four times lower than the national target (70%) in Nepal. Multiple barriers such as low levels of knowledge and embarrassment are associated with cervical cancer screening utilization. Health personnel's gender, counseling, and privacy of screening services were commonly reported facilitators. These findings could help to inform future research, and policy efforts to increase cervical cancer screening utilization in Nepal.


Assuntos
Detecção Precoce de Câncer , Neoplasias do Colo do Útero , Feminino , Humanos , Programas de Rastreamento , Nepal , Teste de Papanicolaou , Neoplasias do Colo do Útero/prevenção & controle , Esfregaço Vaginal
9.
BMC Med Res Methodol ; 22(1): 155, 2022 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-35637426

RESUMO

BACKGROUND: Natalizumab and fingolimod are used as high-efficacy treatments in relapsing-remitting multiple sclerosis. Several observational studies comparing these two drugs have shown variable results, using different methods to control treatment indication bias and manage censoring. The objective of this empirical study was to elucidate the impact of methods of causal inference on the results of comparative effectiveness studies. METHODS: Data from three observational multiple sclerosis registries (MSBase, the Danish MS Registry and French OFSEP registry) were combined. Four clinical outcomes were studied. Propensity scores were used to match or weigh the compared groups, allowing for estimating average treatment effect for treated or average treatment effect for the entire population. Analyses were conducted both in intention-to-treat and per-protocol frameworks. The impact of the positivity assumption was also assessed. RESULTS: Overall, 5,148 relapsing-remitting multiple sclerosis patients were included. In this well-powered sample, the 95% confidence intervals of the estimates overlapped widely. Propensity scores weighting and propensity scores matching procedures led to consistent results. Some differences were observed between average treatment effect for the entire population and average treatment effect for treated estimates. Intention-to-treat analyses were more conservative than per-protocol analyses. The most pronounced irregularities in outcomes and propensity scores were introduced by violation of the positivity assumption. CONCLUSIONS: This applied study elucidates the influence of methodological decisions on the results of comparative effectiveness studies of treatments for multiple sclerosis. According to our results, there are no material differences between conclusions obtained with propensity scores matching or propensity scores weighting given that a study is sufficiently powered, models are correctly specified and positivity assumption is fulfilled.


Assuntos
Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Cloridrato de Fingolimode/uso terapêutico , Humanos , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Natalizumab/uso terapêutico , Resultado do Tratamento
10.
Am J Hosp Palliat Care ; 39(6): 687-694, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35040688

RESUMO

BACKGROUND: Neurocritical care (NCC) and neuropalliative care (NPC) clinicians provide care in specialized intensive care units (ICU). There is a paucity of data regarding the impact of NCC and NPC collaboration in smaller, community-focused settings. OBJECTIVE: To determine the clinical impact of introducing a NCC/NPC collaborative model in a mixed ICU community-based teaching hospital. DESIGN: Retrospective pre/post cohort study. SUBJECTS: Patients ≥18 years of age admitted to the ICU who received neurology and palliative care consultations between September 1, 2015 and August 31, 2017 at a 300 bed community-focused hospital were included. INTERVENTION: The addition of a NCC/NPC collaborative model took place in September of 2016. The time periods before (9/1/2015 to 8/31/2016) and after (9/1/2016 to 8/31/2017) the addition were compared. RESULTS: A total of 274 admissions (pre: 130, post: 144) were included. There were significantly more NCC consultations provided in the post-period (44.6% vs 57.6%; P = .03). NPC consultation increased (55.4% vs 66.7%; P = .056) Median LOS was significantly shorter after implementation of the collaborative model (11 vs 8 days; P = .01). Median ICU LOS was also shorter by 1 ICU-day in the post-period, though this was not statistically significant (P = .23). Mortality rates were similar (P = .95). CONCLUSIONS: Our findings suggest NCC/NPC collaboration in a community-focused teaching hospital was associated with more NCC consultations, as well as shorter LOS without increasing mortality. These data highlight the importance of supporting collaborative models of care in community settings. Further research is warranted.


Assuntos
Hospitalização , Unidades de Terapia Intensiva , Estudos de Coortes , Mortalidade Hospitalar , Humanos , Tempo de Internação , Estudos Retrospectivos
11.
BMC Health Serv Res ; 21(1): 980, 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34535148

RESUMO

BACKGROUND: People with musculoskeletal pain seek more healthcare than the general population, however little is known about the long-term effect on healthcare use. The aim of this study was to examine the consequences of number of musculoskeletal pain sites on long-term care-seeking and healthcare-related costs and explore how health anxiety influences this relationship. METHODS: We conducted a Danish population-based longitudinal cohort study of 4883 participants combining self-reported survey data from 2008 with ten-year follow-up data from national health registers. Using a causal inference framework, we examined associations between number of pain sites (range 0-7)/level of health anxiety (high/low level) and face-to-face healthcare contacts/healthcare-related costs. Data were analyzed using negative binomial regression with generalized estimating equations. Regression models were adjusted for sex, age, duration of pain, level of education, comorbidity, personality traits, risk of depression, marital status, physical job exposure, and previous healthcare utilization. RESULTS: For each additional pain site general healthcare contacts (Incidence Rate Ratio (IRR): 1.04 (95% CI: 1.03-1.05)), healthcare-related costs (IRR: 1.06 (95% CI: 1.03-1.08) and musculoskeletal healthcare contacts (IRR: 1.11 (95% CI:1.09-1.14) increased. Those with high levels of health anxiety at baseline had a slightly higher number of general healthcare contacts (IRR 1.06 (1.01-1.11), independent of number of pain sites. However, level of anxiety did not influence the effect of number of pain sites on any healthcare use or cost outcomes. CONCLUSIONS: We found evidence for a causal association between increasing number of pain sites and greater healthcare use and cost, and high levels of health anxiety did not increase the strength of this association. This suggests that number of pain sites could be a potential target for biopsychosocial interventions in order to reduce the need for future care-seeking.


Assuntos
Dor Musculoesquelética , Estudos de Coortes , Atenção à Saúde , Dinamarca/epidemiologia , Humanos , Estudos Longitudinais , Dor Musculoesquelética/epidemiologia , Dor Musculoesquelética/terapia
12.
Health Qual Life Outcomes ; 19(1): 198, 2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34412630

RESUMO

BACKGROUND: The COVID-19 pandemic has caused significant disruptions in the implementation of programs across educational institutions. Nursing students, being both young adults and by practical training, part of the health care system, may be particularly vulnerable during the COVID-19 pandemic. The purpose of this study was to explore the associations between self-reported fear of COVID-19, general health, psychological distress and overall quality of life (QoL) in a sample of Norwegian baccalaureate nursing students compared to reference data. METHODS: The survey targeted baccalaureate nursing students from five universities in February 2021. An electronic questionnaire consisted of the Fear of COVID-19 Scale (FCV-19S), the Hopkins Symptom Checklist 5 (SCL-5), one general health and one overall QoL question. The respondents' mean scores were compared to reference data. Hierarchical regression analyses were conducted, and effect sizes (Cohen's d) were evaluated. RESULTS: In total, 2605 out of 6088 (43%) students responded. Their FCV-19S scores (mean 2.45, CI 2.42, 2.48) were significantly higher than those of the reference population (mean 1.8, P < 0.001). Nursing students scores showed significantly lower general health (mean 3.50 ± 0.93 SD, population mean = 3.57, Cohen's d = 0.07), higher levels of psychological distress (mean 2.68 ± 1.03 SD, population mean = 2.12, Cohen's d = 0.55) and lower overall QoL (mean 5.50 ± 2.16 SD, population mean = 8.00, Cohen's d = 1.16) compared to pre-pandemic reference data. FCV-19S scores were significantly associated with levels of general health (Cohen's d = 0.26), psychological distress (Cohen's d = 0.76) and overall QoL (Cohen's d = 0.18). CONCLUSIONS: Baccalaureate nursing students reported worse outcomes during the Covid-19 pandemic on general health, psychological distress and overall QoL compared to the reference population. Level of fear of Covid-19, however, accounted for few of these differences. Other factors related to the pandemic may have reduced nursing students' overall QoL.


Assuntos
COVID-19/psicologia , Medo/psicologia , Qualidade de Vida/psicologia , Estudantes de Enfermagem/psicologia , COVID-19/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pandemias , SARS-CoV-2 , Universidades , Adulto Jovem
13.
Hum Reprod ; 36(9): 2429-2442, 2021 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-34324672

RESUMO

In recent years, the amount of data produced in the field of ART has increased exponentially. The diversity of data is large, ranging from videos to tabular data. At the same time, artificial intelligence (AI) is progressively used in medical practice and may become a promising tool to improve success rates with ART. AI models may compensate for the lack of objectivity in several critical procedures in fertility clinics, especially embryo and sperm assessments. Various models have been developed, and even though several of them show promising performance, there are still many challenges to overcome. In this review, we present recent research on AI in the context of ART. We discuss the strengths and weaknesses of the presented methods, especially regarding clinical relevance. We also address the pitfalls hampering successful use of AI in the clinic and discuss future possibilities and important aspects to make AI truly useful for ART.


Assuntos
Inteligência Artificial , Clínicas de Fertilização , Instituições de Assistência Ambulatorial , Humanos
14.
J Prof Nurs ; 37(3): 578-587, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34016317

RESUMO

BACKGROUND: Tenure is a hallmark of higher education, but its value and relevance is questioned. PURPOSE: This study examined faculty perceptions of the value of tenured and non-tenured nursing faculty appointments. METHODS: A descriptive correlational design using an anonymous survey was sent to members of the American Association of College of Nursing. Participants (N = 542) from 44 states completed the survey. RESULTS: Significant differences in workload were found in teaching, administrative responsibilities, scholarship, and academic service. Compared to non-tenured faculty, tenured faculty had higher scores on Career Opportunities (p < 0.001), lower Life Balance scores (p = 0.001) and higher Academic Support scores (p = 0.014). Non-tenured faculty were less likely to agree than tenured faculty that tenure improves quality of education (χ2 = 86.48, p < 0.001) or is relevant to the modern university (χ2 = 75.20, p < 0.001). Narrative responses revealed six themes about tenure. Faculty on both tracks questioned the value of tenure. CONCLUSIONS: Faculties in schools of nursing nationwide need to re-evaluate the purpose of tenure and the tenure criteria in light of each institution's unique mission and expectations to determine how they are meeting the needs of both academic institution and nursing faculty. Although the idea of tenure is institutional, implementation is initiated at the school level. Our study revealed naivete about tenure among nursing faculty at the school level.


Assuntos
Mobilidade Ocupacional , Docentes de Medicina , Docentes de Enfermagem , Humanos , Inquéritos e Questionários , Estados Unidos , Universidades
15.
Epidemiol Psychiatr Sci ; 30: e28, 2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33820580

RESUMO

AIMS: Antipsychotics are primarily labelled for the treatment of severe mental illness and have documented clinical utility in certain neurological disorders or palliative care. However, off-label use of antipsychotics is common and increasing, and prior studies on antipsychotic utilisation have not specifically assessed users in neurology, palliative care or general practice. We aimed to explore diagnoses associated with antipsychotic use, treatment patterns and characteristics of users without diagnoses relevant to antipsychotic treatment. METHODS: Population-based study identifiying all users of antipsychotics in Denmark (pop 5.7 mio.) 1997-2018 in the Danish National Prescription Register (DNPR). Possible indications for antipsychotic therapy were evaluated using in- and outpatient contacts from the DNPR. Users were divided hierarchically into six groups: severe mental disorders (schizophrenia, bipolar-spectrum disorders), chronic mental disorders (dementias, mental retardation, autism), other mental disorders (depression-spectrum, anxiety and personality disorders, etc.), selected neurological diseases, cancer and antipsychotic users without any of these diagnoses. This last group was characterised regarding demographics, antipsychotic use, health care utilisation and likely antipsychotic treatment initiator in 2018. RESULTS: Altogether, 630 307 antipsychotic users were identified, of whom 127 649 had filled prescriptions during 2018. Users without diagnoses relevant to antipsychotic treatment comprised of the largest group (37%), followed by schizophrenia and bipolar-spectrum disorders (34%), other mental disorders (15%), dementia, autism and mental retardation (11%), cancer (2.2%) and neurological diagnoses (2.0%). Of 37 478 incident users in 2018, 39% had no diagnosis relevant to antipsychotic treatment, 7.9% had major depression, 7.7% neurotic/stress-related disorders and 7.5% dementia. Quetiapine was most commonly used, both overall (51%) and among users without diagnoses relevant to antipsychotic treatment (58%). Of 14 474 incident users in 2018 without diagnoses relevant to antipsychotic treatment, treatment was most likely initiated by a general practitioner (65%), with only 17% seeing a psychiatrist during the following year. As many as 18% of patients with adjustment disorders and 14% of those without relevant diagnoses for antipsychotic use, remained on antipsychotic treatment 5 years after their first prescription. CONCLUSIONS: Over one-third of antipsychotic users in Denmark did not have psychiatric, neurological or cancer diagnoses as possible indications for antipsychotic therapy. Many antipsychotics are initiated or prescribed in general practice, and a concerningly large subgroup without documented diagnoses relevant for antipsychotics continued to receive them. Rational prescribing, adequate side effect monitoring and further research into reasons for the observed antipsychotic use patterns and their risk-benefit ratio are needed.


Assuntos
Antipsicóticos , Uso de Medicamentos , Transtornos Mentais , Uso Off-Label , Antipsicóticos/uso terapêutico , Dinamarca/epidemiologia , Uso de Medicamentos/estatística & dados numéricos , Humanos , Transtornos Mentais/diagnóstico , Transtornos Mentais/tratamento farmacológico , Transtornos Mentais/epidemiologia , Uso Off-Label/estatística & dados numéricos
16.
J Orthop ; 24: 216-221, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33746422

RESUMO

BACKGROUND: Revision TKA is a serious adverse event with substantial consequences for the patient. As revision is becoming increasingly common in patients under 65 years, the need for improved preoperative patient selection is imminently needed. Therefore, this study aimed to identify the most important factors of early revision and to develop a prediction model of early revision including assessment of the effect of incorporating data on patient-reported outcome measures (PROMs). MATERIAL AND METHODS: A cohort of 538 patients undergoing primary TKA was included. Multiple logistic regression using forward selection of variables was applied to identify the best predictors of early revision and to develop a prediction model. The model was internally validated with stratified 5-fold cross-validation. This procedure was repeated without including data on PROMs to develop a model for comparison. The models were evaluated on their discriminative capacity using area under the receiver operating characteristic curve (AUC). RESULTS: The most important factors of early revision were age (OR 0.63 [0.42, 0.95]; P = 0.03), preoperative EQ-5D (OR 0.07 [0.01, 0.51]; P = 0.01), and number of comorbidities (OR 1.01 [0.97, 1.25]; P = 0.15). The AUCs of the models with and without PROMs were 0.65 and 0.61, respectively. The difference between the AUCs was not statistically significant (P = 0.32). CONCLUSIONS: Although more work is needed in order to reach a clinically meaningful quality of the predictions, our results show that the inclusion of PROMs seems to improve the quality of the prediction model.

17.
Osteoarthritis Cartilage ; 29(7): 986-994, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33676014

RESUMO

OBJECTIVE: To investigate acute changes in biochemical markers of cartilage turnover in response to moderate intensity exercise with and without joint impact in humans with knee osteoarthritis. DESIGN: We conducted a randomized, cross-over, exploratory clinical study. Twenty subjects with knee osteoarthritis (OA) were randomized, of which twenty completed 30 min of cycling and 15 completed 30 min of running on days 1 week apart. Fasting blood samples were taken before, immediately after and 1, 2, 3, and 24 h after activity was initiated. Midstream spot urine was sampled before and after activity. Serum samples were analyzed for concentrations of fragment of type II collagen degradation, C2M, fragment of type VI collagen degradation, C6M, cartilage oligomeric matrix protein, COMP, marker of type II collagen formation, PRO-C2, and urine for marker of crosslinked type II collagen degradation, CTX-II. To establish a reference, all subjects had similar samples taken during rest on a separate day. Data was analyzed in a restricted maximum likelihood based random effects linear mixed model. RESULTS: C2M trended to increase after cycling compared running (13.49%, 95%CI: -0.36-27.34%) and resting (12.88%, 95%CI: 0.2-25.6%) and the type II collagen formation/degradation ratio switched towards degradation after cycling, but not running. C6M trended to decrease after cycling (-8.1%, 95%CI: -14.8 to -1.4%) and running (-6.8%, 95%CI: -14.16-0.55%). CONCLUSION: In persons with knee OA moderate intensity exercise without joint impact may induce acute changes in circulating levels of biochemical markers reflecting type II and VI collagen degradation.


Assuntos
Colágeno Tipo II/sangue , Exercício Físico , Metaloproteases/sangue , Osteoartrite do Joelho/sangue , Adulto , Idoso , Biomarcadores , Estudos Cross-Over , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
18.
Occup Med (Lond) ; 70(7): 496-502, 2020 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-32804235

RESUMO

BACKGROUND: There is a growing body of research on operational stress injuries (OSIs) among police officers and first responders. Most studies focus on operational stressors' contribution to OSI and the development of post-traumatic stress disorder. However, preliminary research shows that organizational stressors may uniquely contribute to OSI and depression, and thus should be examined more closely. AIMS: This study explored the influence of organizational stress on symptoms of depression in a sample of police officers from a large urban region. METHODS: Front-line (n = 109) police officers completed questionnaires measuring police organizational and operational stress, depression, anxiety, hostility, rumination, perceived social support and social desirability. Using negative binomial regression (NBR), a best subset model of self-reported depression symptoms was derived from the full model (a function of gender, age, police experience (years), organizational stress, operational stress, anxiety, anger, rumination and social support), based on Akaike Information Criterion (AIC) goodness of fit. RESULTS: Organizational stress and anxiety were positively associated with self-reported depression symptoms. A paired t-test revealed no significant difference between reported organizational and operational stress levels. CONCLUSIONS: Organizational stress may uniquely contribute to OSI and depressive symptoms and should be examined in future research. Findings support prior literature suggesting that initiatives to treat OSI among police should address workplace environment and organizational stressors. Addressing organizational issues in police culture and developing long-lasting initiatives is key in the future of OSI prevention and treatment for police officers.


Assuntos
Ansiedade/epidemiologia , Depressão/epidemiologia , Estresse Ocupacional/psicologia , Polícia , Adulto , Ira , Feminino , Humanos , Masculino , Ontário/epidemiologia , Ruminação Cognitiva , Apoio Social , Estresse Psicológico/epidemiologia , Inquéritos e Questionários
19.
J Hosp Infect ; 2020 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-32380030

RESUMO

Contaminated hands may contribute to the transmission of pathogens. In the prevention of healthcare-associated infections the effect of disinfection methods should ideally be possible to measure in a simple way. Microbial cultivation is the reference standard, but it is a rather complicated and time-consuming procedure, and the use of swabs for measuring adenosine triphosphate (ATP) has become a much-used proxy measurement (bioluminescence). We evaluated the effect of three hand-disinfection methods on eradication of Escherichia coli from artificially contaminated hands, using cultivation and ATP measurements in parallel. ATP measurement was found to be an unsuitable method as this reflects the total amount of cellular material left on the hands, not only the viable bacteria.

20.
J Hosp Infect ; 105(2): 213-215, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32229145

RESUMO

The effect of alcohol hand rub was tested in eradicating Escherichia coli, and compared with hand wash using ozonized tap water or soap and water. Alcohol eradicated all bacteria in 10 out of 35 participants, but with an average (SD) of 2330 (4227) cfu/mL left after disinfection, whereas ozonized water removed all bacteria in 10 out of 55 participants, with an average of only 538 (801) cfu/mL left (P = 0.045). Soap washing was the most effective with total removal of bacteria in six out of 20 participants, with an average of 98 (139) cfu/mL (P = 0.048 and 0.018 versus ozonized water and alcohol, respectively).


Assuntos
Bactérias/efeitos dos fármacos , Desinfetantes/farmacologia , Desinfecção das Mãos/métodos , Higienizadores de Mão/farmacologia , Sabões/farmacologia , Água/farmacologia , 2-Propanol/farmacologia , Adulto , Idoso , Contagem de Colônia Microbiana , Desinfetantes/classificação , Etanol/farmacologia , Feminino , Pessoal de Saúde/estatística & dados numéricos , Humanos , Controle de Infecções/métodos , Masculino , Pessoa de Meia-Idade , Ozônio/farmacologia , Adulto Jovem
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