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Background: The World Health Organisation reports that melanoma had an incidence of 331,722 cases worldwide in 2022, ranking it 17th on the list of the most prevalent malignancies. This disease is a threat to public health as years of potential life lost from melanoma deaths constitute an economic and social burden; it is, however, curable if detected early. This study aims to show current trends in clinical trials for melanoma screening., Materials and Methods: The analysis was conducted using data from clinicaltrials.gov. The analysis considered both interventional and observational studies on melanoma screening. Only the studies with complete and active statutes by 4 September 2024 were included in the analysis., Results: Out of 25 studies registered in clinical trial databases regarding melanoma screening, 20% research advanced imagining techniques employing innovative machine learning algorithms, while 16% explore behavioural interventions., Conclusions: Intensification of behavioural interventions and health promotion activities is recommended.

In 2020 it is estimated that 281 million people were international migrants. Migrants constitute a potentially vulnerable population in terms of facing discrimination, poor living and housing conditions, and insufficient access to healthcare services. Due to the armed conflict in Ukraine in 2022, almost 10 million people crossed the Polish border within a year of the outbreak of the conflict. The objective of this paper is to present the use of primary healthcare services by people migrating from Ukraine to Poland and identify the barriers in access to healthcare by this group of persons. This study used a qualitative research technique in the form of an expert interview using individual in-depth interviews (IDI). The study group consisted of professionally active primary healthcare providers (doctors, nurses, and facility managers) in Poland. Research was carried out in the areas regarding the availability of healthcare, the potential threats and challenges, and possible system solutions. The results showed that the most common cause for doctor's appointments among migrants are respiratory infections, including COVID-19. Many cases were related to back pain, mainly resulting from the physical work of the patients. Additionally, some barriers to access and the provision of healthcare services for patients from Ukraine were identified. The majority (75%) of respondents indicated language as a significant barrier when providing services. Based on the study results, we recommend creating a dedicated website and telephone hotline for this group of persons as well as the use of traditional media to distribute information about access to healthcare services. It is also essential to focus on assistance for older people, since they may experience more difficulties with language and navigating the healthcare system.

Lung cancer is the leading cause of death among all the oncological diseases worldwide. This applies to both women and men; however, the incidence and mortality among women is on the rise. In 2020, lung cancer was responsible for 1.8 million deaths (18%). More than 90% of lung cancer cases and 77.1% of lung cancer deaths occur in countries with high and very high HDI (human development index) values. The aim of our study is to the present trends and most recent studies aimed at lung cancer screening. In the face of the persistently high mortality rate, conducting research aimed at extending already-implemented diagnostic algorithms and behavioural interventions focused on smoking cessation is recommended.

Alcohol addiction is characterized by extensive alcohol consumption that dominates other behaviours previously important to a patient. According to data from The State Agency for Prevention of Alcohol-Related Problems, up to 900,000 people in Poland are addicted to alcohol. On average, approximately 9.7 L of pure alcohol per capita was consumed in 2021. Alcohol addiction may cause severe health problems and is one the key risk factors for various diseases. Stress plays an important role in the process of alcohol addiction and is also a predictor for lower enjoyment in life. On the other hand, sense of coherence may be a stronger protective factor. The aim of our study was to verify the relation between the level of perceived stress among patients with alcohol addiction and satisfaction with life. Because sense of coherence is a disposition that allows for managing stress effectively, the latter should be reflected in the results of multivariate analyses that take both the level of stress and sense of coherence into account. In the present study, sense of coherence and perceived stress were negatively correlated; therefore, strengthening internal resources for managing difficult and stressful situations is recommended.

Introduction : Chronic obstructive pulmonary disease (COPD) is a common, preventable, and treatable disease. The first PREM (patient-reported outcome measure)-type questionnaire that has been dedicated to assess the experience of care in COPD is the PREM-C9. Aim : The aim of this study was to create a Polish version of the PREM-C9 and determine its psychometric characteristics. Methods : The validation procedure involved forward and back translation. We included 42 patients with COPD. The psychometric properties were assessed using Cronbach's alpha, Bartlett's test, the Kaiser-Meyer-Olkin test, and Spearman's correlation coefficient. The validity of the questionnaire was assessed using a principal component analysis for the extracted principal components. The validity of the factor analysis was demonstrated using Bartlett's sphericity test and the Kaiser-Meyer-Olkin (KMO) test. A factor analysis was performed using the Oblimin and Varimax rotation. The reliability of the questionnaire was assessed using Cronbach's alpha. Results : The Polish version of the analyzed questionnaire met all the validation criteria: face, translation, psychometric, functional, and reconstruction equivalence. Spearman's correlation results between the Polish PREM-C9 and CAT were as follows: rho = 0.44, p = 0.003539; HADS-Anxiety: rho = 0.370864, p = 0.015612; and HADS-Depression: rho = 0.387405, p = 0.011253. Conclusions : The developed Polish PREM-C9 questionnaire is a reliable and valid tool that assesses Polish COPD patients' experiences of their disease and the care they receive.

Pancreatic cancer (PC) is usually diagnosed at an advanced stage of its development, which results in lower overall survival (OS). Prognosis is also poor even with curative-intent surgery. Approximately 80% of patients with localized PDAC have micrometastases at the time of diagnosis, which leads to a worse prognosis than in other cancers. The objective of this study is to present the progress in the treatment of metastatic pancreatic cancer based on the recommendations of oncological scientific societies, such as ESMO, NCCN, ASCO, NICE and SEOM, over the last 5 years. Combined FOLFIRINOX therapy is mostly a recommended therapy among patients with good performance statuses, while gemcitabine is recommended for more fragile patients as a first-line treatment. The newest guidelines suggest that molecular profiling of the tumor should be the first step in determining the course of treatment. The use of modern molecular therapies in patients with specific gene mutations should extend the survival of patients with this disease.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with high morbidity and mortality in which long-term survival rates remain disastrous. Surgical resection is the only potentially curable treatment for early pancreatic cancer; however, the right patient qualification is crucial for optimizing treatment outcomes. With the rapid development of radiographic and surgical techniques, resectability decisions are made by a multidisciplinary team. Upfront surgery (Up-S) can improve the survival of patients with potentially resectable disease with the support of adjuvant therapy (AT). However, early recurrences are quite common due to the often-undetectable micrometastases occurring before surgery. Adopted by international consensus in 2017, the standardization of the definitions of resectable PDAC (R-PDAC) and borderline resectable PDAC (BR-PDAC) disease was necessary to enable accurate interpretation of study results and define which patients could benefit from neoadjuvant therapy (NAT). NAT is expected to improve the resection rate with a negative margin to provide significant local control and eliminate micrometastases to prolong survival. Providing information about optimal sequential multimodal NAT seems to be key for future studies. This article presents a multidisciplinary concept for the therapeutic management of patients with R-PDAC and BR-PDAC based on current knowledge and our own experience.

Alcohol consumption is linked to over 200 diseases and injuries. It is also classified as a risk factor for several types of neoplasms as well as infectious diseases (i.e., HIV and tuberculosis). In 2019, among people aged 25 to 49, alcohol use was the leading risk factor for attributable burden of disease. There are many factors that affect alcohol drinking patterns such as social and economic status, social norms, cultural customs, availability of alcohol, etc. Stress also plays a significant role in the process of developing alcohol addiction. The aim of our study was to examine health patterns and stress levels among patients undergoing alcohol addiction treatment. The study sample consisted of 104 patients who were treated in a hospital ward due to alcohol dependence. Three standardized questionnaire tools were used to measure the sense of coherence and the level of stress among those patients. The main results suggest that the level of perceived stress correlated negatively with all dimensions of sense of coherence and all indicators of health behaviors, however, age was positively correlated with positive mental attitude, proper eating habits, and health behaviors. In conclusion, it is worth noting that developing patterns for positive health behaviors will make it possible to avoid alcohol dependence or reinforce the treatment results if alcohol dependence syndrome occurs.

Patients with pancreatic cancer who develop irreversible cancer cachexia have a life expectancy of less than 3 months. Therefore, it is extremely important to evaluate the patient's nutritional status as early as possible and to implement an appropriate nutritional intervention in order to reduce the risk of further weight loss and/or muscle loss, which affect the outcomes of cancer treatment and the correct nutritional treatment in patients with pancreatic cancer. A literature review was performed by using the PubMed and Cochrane quick search methodology. The main purpose of this review was to present the current approach to nutritional treatment in pancreatic cancer. The review included publications, most of which concerned clinical nutrition as part of the phase of treatment of patients with pancreatic cancer, nutritional and metabolic disorders in pancreatic cancer, and the period after pancreatic resection. Some of the publications concerned various nutritional interventions in patients with pancreatic cancer undergoing chemotherapy or surgical treatment (nutritional support before surgery, after surgery, or during palliative treatment). There is an unmet need for integrated nutritional therapy as a key part of the comprehensive care process for PC patients. Nutritional counseling is the first line of nutritional treatment for malnourished cancer patients, but pancreatic enzyme replacement therapy also constitutes the cornerstone of nutritional treatment for relieving symptoms of indigestion and maintaining or improving nutritional status.

(1) Background: Acceptance of illness is a process in which a person with an illness accepts its presence and treats it as an integral part of their life. With regard to alcoholism, acceptance of illness is one of the important elements of the healing process. (2) Methods: The study group consisted of 104 residents in an addiction treatment ward. Questionnaires SOC-29, AIS and PSS-10 were used to check levels of coherence, stress and acceptance of illness. The analysis was based on regression analysis. Patient age was analysed as a moderator of correlations between perceived indicators. Moderation analysis was based on the simple moderation model. (3) Results: The level of perceived stress correlated negatively with all areas of the sense of coherence and with acceptance of illness. All areas of the sense of coherence correlated with acceptance of illness positively. (4) Conclusions: The acceptance of illness by the patient is a factor that can be motivating for further treatment, through a positive approach to illness and strengthening the sense of control in experiencing it. The combination of strengthening behavioural, cognitive and motivational resources can be used in the treatment of people experiencing the challenges of addiction to alcohol.

Pancreatic cancer is the seventh most common cause of death in the group of oncological diseases. Due to the asymptomatic course, early diagnosis is difficult. Currently, early detection methods are only used in high-risk groups. A literature review based on the available results of observational studies on patients with pancreatic cancer and people from high-risk groups was used to summarize the knowledge on risk factors. The GLOBOCAN 2020 data were used to assess the epidemiological situation in Europe. A summary of screening recommendations was prepared based on the available documents from medical organizations and associations. Pancreatic cancer risk factors are divided into two main groups: non-modifiable factors, e.g., hereditary factors and age, which increase the risk of developing this disease, and modifiable factors-BMI, smoking, and alcohol consumption. Hereditary factors account for 10% of pancreatic cancer cases. The highly specialized methods of early detection, (MRI, CT, or EUS) are used for screening high-risk populations. Of all the imaging methods, EUS is considered the most sensitive for pancreatic cancer and allows an accurate assessment of the size of even small lesions (<30 mm) and the extent of tumour infiltration into blood vessels. The available studies vary on the level of sensitivity and specificity of these methods for the diagnosis of pancreatic cancer. EUS, MRI, and CT are also expensive procedures and in some patients can be invasive, which is one of the arguments against the introduction of population screening programs based on imaging methods. Therefore, it is important to look for viable solutions that would improve early detection. This is important from the point of view of healthcare systems in Europe, where almost 29% of all global pancreatic cancer cases are reported.

Healthcare effectiveness measurement and value in health have been common topics in public health literature since 2006 when value-based healthcare (VBHC) was first defined by Porter and Teisberg. The aim of this study was to identify the barriers and challenges related to the implementation of VBHC solutions in the example of Poland. A case presentation was used as a method. The national integrated care programs (KOS-Infarction, POZ-Plus, and comprehensive treatment of chronic wounds) were used to present general challenges, along with the Integrated Care Model (ICM) for patients with advanced chronic obstructive pulmonary disease (COPD), to determine specific difficulties. ICM has been operating since 2012 in Gdańsk and gradually adapted the value-based integrated care (VBIC) approach. An analysis of the available data showed that the greatest difficulties related to the implementation of the VBHC and VBIC concepts are a lack of legal and reimbursement solutions, staff shortages, a lack of educational standards for some members of the multidisciplinary team, and insufficient awareness of the role of integrated care. As the level of preparation to implement VBHC policies varies between individual countries, the conclusions drawn from the experience of ICM and other Polish projects may be a valuable voice in discussion.

(1) Background: Pancreatic cancer is the cancer with the third-highest mortality rate, and forecasts indicate its growing share in morbidity. The basis of treatment is inpatient chemotherapy and there is a strong focus on palliative care. (2) Methods: A literature review was conducted based on the rapid review methodology in PubMed and Cochrane databases. The search was supplemented with publications from the snowball search. Qualitative assessment of included publications was performed using AMSTAR2 modified scheme. (3) Results: The review included 17 publications, of which majority concerned direct costs related to the adopted treatment regimen. Most of the publications focused on comparing the cost-effectiveness of drug therapies and the costs of palliative treatment. Other publications concerned indirect costs generated by pancreatic cancer. They particularly focused on the economic burden of lost productivity due to sickness absence. (4) Conclusion: The increase in the incidence of pancreatic cancer translates into an increase in the costs of the health care system and indirect costs. Due to the significant share of hospitalization in the health care structure, direct costs are increasing. The inpatient treatment regimen and side effects translate into a loss of productivity for patients with pancreatic cancer. Among gastrointestinal cancers, pancreatic cancer generates the second largest indirect costs, although it has a much lower incidence rate than the dominant colorectal cancer. This indicates a significant problem of the economic burden of this cancer.

Pancreatic cancer is the malignant disease with the highest mortality rate, and it ranks third in the world after lung and colon cancer. Identified factors that increase the risk of developing pancreatic cancer include chronic pancreatitis, radiation therapy to the pancreatic area due to another cancer, diabetes mellitus, obesity, smoking, and age. The objective of this study was to present the current state of knowledge on the quality of life of patients diagnosed with pancreatic cancer, factors that determine QoL, and ways of coping with the disease. The low curability and low survival rates of pancreatic cancer significantly affect the quality of life of patients, often in the form of significant deterioration, especially in terms of mental changes, cognitive functions, and coping with the disease. Cognitive decline with comorbid depression is also typical for patients with this type of cancer. Research has shown that the health-related quality of life of patients with pancreatic cancer is low, so further research is needed to improve the situation in this area.

Background: The COVID-19 pandemic has significantly contributed to accelerating the development of telemedicine and eHealth. The main aim of this study was to assess the attitudes of patients towards remote care implemented in general practice (GP) during the pandemic., Methods: The study was a pilot study conducted in March-April 2021, considering technical aspects of using teleconsultations, and evaluating the difficulties, advantages and disadvantages for patients. When assessing opinions, a simple Likert scale was used, where a value of 1 meant the worst possible assessment or strong disagreement and the upper value the best or full agreement of the respondent., Results: The study covered 408 respondents. Their biggest organizational challenge reaching GPs by telephone, regardless of the patients' home location ( p = 0.23698). Obtaining e-documents was not problematic but was rated as worse by men ( p = 0.048295). Respondents rated the overall effectiveness of teleconsultations more highly if they could speak directly with a doctor ( p = 0.0005). There were no differences in willingness to recommend teleconsultations based on gender ( p = 0.2432), place of residence ( p = 0.7878), age ( p = 0.290355) or education ( p = 0.9109), but people assessing the overall effectiveness of telemedicine more highly were more willing to recommend it ( p = 0.000)., Conclusions: Respondents assess teleconsultations in a differentiated way, noticing both positive and negative features of the remote form of providing health services.

Background: The aim of the study is to analyze the prevalence of using patients’ reported outcomes measures and experiences (PROMs and PREMs) in relation to integrated care (IC). Material and methods: To select eligible studies (<10 years, full-text), PubMed was used. The general subject of the articles referring to the type of disease was indicated on the basis of a review of all full-text publications discussing the effectiveness of IC (N = 6518). The final search included MeSH headings related to outcomes measures and IC. Full-text screening resulted in including 73 articles (23 on COPD, 40 on diabetes/obesity and 10 on depression) with 93.391 participants. Results: Analysis indicated that authors used multiple outcome measures, with 54.8% of studies including at least one patient reported. PROMs were more often used than PREMs. Specific (disease or condition/dimension) outcome measures were reported more often than general, especially those dedicated to self-assessment of health in COPD and depression. PROMs and PREMs were most commonly used in studies from the USA and Netherlands. Conclusion: Using PROMS/PREMS is becoming more popular, although it is varied, both due to the place of research and type of disease.

Background: According to the World Health Organization's statistics, 7 of the 10 main causes of death in 2019 were noncommunicable diseases. Health indicators are measures used to evaluate public health system effectiveness and functioning. Monitoring mortality rates from leading causes, life expectancy and other health indicators is essential to address their causes and adapt health systems to react adequately. The aim of this study is to present the dependencies of selected health care indicators and health outcomes., Methods: Based on the literature review conducted, selected health indicators, along with healthcare system data, were analyzed using Pearson's r correlation. The analyses included data from the Organization for Economic Cooperation and Development (OECD) presented in statistics and the Health at a Glance 2021 report and data collected as part of the preparation of the Financing Global Health 2020 report by the Institute for Health Metrics and Evaluation., Results: Health system resources are linked to health outcomes. The number of medical consultations, the number of nurses per patient or the level of financing of services under general health insurance are related to life expectancy and deaths due to causes that could have been avoided or treated., Conclusions: Life expectancy is positively correlated with access to general health insurance and public expenditure on healthcare. There is a need for all countries to provide their citizens with broad access to healthcare services.

The 2019 worldwide sales of Orphan Drugs were estimated at $136 billion USD, which constituted 16% of the global pharmaceutical prescription market and is expected to grow by 12% in the next 5 years. A better understanding of Orphan Drug pricing may contribute to on-going discussions on Orphan Drug Act (ODA) corrections in US or modifications of price setting mechanisms in EU. The objective of the study was comparison and analysis of the prices of Orphan Drugs in US and EU. All drugs with Orphan Drug status were compared in the US and EU. For the US prices, the US Department of Veterans Affairs (VA) was sourced. The EU List Prices came from six EU countries: Denmark, France, Germany, Greece, Poland, Spain. We found US prices to be higher than the six selected EU countries. The average Price Ratio was 1.64. The prices across EU countries were more homogeneous, while the number of the reimbursed and therefore available to patient medicines varied and was correlated with GDP per capita r = 0.87. Considered implementation of the External Reference Price system in US may generate significant savings in the US but may result in upward pressure on pricing of Orphan Drugs in EU. Centralization of the Orphan Drugs pricing negotiations in EU may prevent such development and offer a win-win opportunity for all involved parties.

Maintaining body balance is a complex function based on the information deriving from the vestibular, visual, and proprioceptive systems. The aim of the study was to evaluate quiet single stance stability in young adults with lumbar derangement syndrome (LDS) and in the control group of the healthy subjects. The second aim of this study was to determine whether pain intensity, degree of disability, and the level of physical activity can influence postural control in patients with LDS. It is important to underline that selecting a homogeneous group of LBP patients using, for example, mechanical diagnosis and therapy method and Quebec Task Force Classification, can result in an increased sensitivity of the study. The study included 126 subjects: 70 patients with LDS (37 women, 33 men) and the control group 56 healthy volunteers (36 women, 20 men). In case of multiple group comparisons for variables with normal distribution, ANOVA post hoc test was used or, as the nonparametric equivalent, Kruskal-Wallis test. In all these calculations, the statistical significance level was set to p < 0.05. The stability index eyes open for the study group was 88.34 and for the control group 89.86. There was no significant difference in the level of postural control between the study and control groups ( p > 0.05). The level of stability index eyes closed (SI EC) for the study group was 71.44 and for the control group 77.1. SI EC results showed significant differences in proprioceptive control during single leg stance between the study and control groups ( p < 0.05). The level of pain intensity, the degree of disability, and physical activity level did not influence postural control in the study group with LDS. In summary, patients with LDS showed significantly worse proprioceptive control., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2021 Marzena Olszewska-Karaban et al.)

Background: Obesity and overweight, including childhood obesity and overweight, pose a public health challenge worldwide. According to the available research findings, long-term interventions focusing on dietary behavior, physical activity, and psychological support are the most effective in reducing obesity in children aged 6-18 years. There are limited studies showing the financial effectiveness of such interventions., Objective: The objective of the present study was to evaluate cost-effectiveness of the 6-10-14 for Health weight management program using pharmacoeconomic indicators, i.e., cost-effectiveness analysis using the incremental cost-effectiveness ratio., Methods: We used anthropometric data of 3,081 children included in a 1-year-long intervention with a full financial cost assessment., Results: The cost of removing a child from the overweight group (BMI >85th percentile) was PLN 27,758 (EUR 6,463), and the cost of removing a child from the obese group (BMI >95th percentile) was slightly lower, i.e., PLN 23,601 (EUR 5,495). Given the obesity-related medical costs calculated in the life-long perspective, these results can be considered encouraging. At the same time, when comparing the total costs per participant with the costs of other interventions, it can be noted that they are similar to the costs of school programs containing more than 1 type of intervention., Conclusions: The 6-10-14 for Health program can be considered cost-effective. As a result of committing financial resources in the approximate amount of EUR 1,790 per child, around half of the children participating in the program have improved their weight indicators., (© 2020 The Author(s) Published by S. Karger AG, Basel.)

BACKGROUND Chronic obstructive pulmonary disease (COPD) is a common disease that occurs all over the world. Models of care, initially accessed from the clinical point of view, must also be evaluated in terms of their economic effectiveness, as health care systems are limited. The Integrated Care Model (ICM) is a procedure dedicated to patients suffering from advanced COPD that offers home-oriented support from a multidisciplinary team. The main aim of the present study was to evaluate the cost-effectiveness of the ICM. MATERIAL AND METHODS We included 44 patients in the study (31 males, 13 females) with an average age 72 years (Me=71). Costs of care were estimated based on data received from public payer records and included general costs, COPD-related costs, and exacerbation-related costs. To evaluate cost-effectiveness, cost-effectiveness analysis (CEA) was used. The incremental cost-effectiveness ratio (ICER) was calculated based on changes in health care resources utilization and the value of costs observed in 2 consecutive 6-month periods before and after introducing ICM. RESULTS Costs of care of all types decreased after introducing ICM. Demand for ambulatory visits changed significantly (p=0.037) together with a substantial decrease in the number of emergency department appointments and hospitalizations (p=0.033). ICER was more profitable for integrated care than for standard care when assessing costs of avoiding negative parameters such as hospitalizations (-227 EUR), exacerbations-related hospitalizations (-312 EUR), or emergency procedures (-119 EUR). CONCLUSIONS ICM is a procedure that meets the criteria of cost-effectiveness. It allows for avoiding negative parameters such as unplanned hospitalizations with higher economic effectiveness than the standard type of care used in managing COPD.

BACKGROUND Chronic obstructive pulmonary disease (COPD) is a commonly diagnosed condition in people older than 50 years of age. In advanced stage of this disease, integrated care (IC) is recommended as an optimal approach. IC allows for holistic and patient-focused care carried out at the patient's home. The aim of this study was to analyze the impact of IC on costs of care and on demand for medical services among patients included in IC. MATERIAL AND METHODS The study included 154 patients diagnosed with advanced COPD. Costs of care (general, COPD, and exacerbations-related) were evaluated for 1 year, including 6-months before and after implementing IC. The analysis included assessment of the number of medical procedures of various types before and after entering IC and changes in medical services providers. RESULTS Direct medical costs of standard care in advanced COPD were 886.78 EUR per 6 months. Costs of care of all types decreased after introducing IC. Changes in COPD and exacerbation-related costs were statistically significant (p=0.012492 and p=0.017023, respectively). Patients less frequently used medical services for respiratory system and cardiovascular diseases. Similarly, the number of hospitalizations and visits to emergency medicine departments decreased (by 40.24% and 8.5%, respectively). The number of GP visits increased after introducing IC (by 7.14%). CONCLUSIONS The high costs of care in advanced COPD indicate the need for new forms of effective care. IC caused a decrease in costs and in the number of hospitalization, with a simultaneous increase in the number of GP visits.

Aim: The aim of this study was to evaluate the quality of nursing care in psychiatric wards and compare it between hospitals of different types., Results: Significant differences between hospitals were found in: personnel benevolence (p=0,006219) and response to patient needs (p=0,011446) as well as patients' sense of safety (p=0,020042). In both hospitals, patients were equally dissatisfied with the quality of information concerning treatment side effects (p=0,207804). In both hospitals patients were equally satisfied regarding the level of respect for their dignity and psychological support (p=0,176928)., Conclusion: General patient perception of nursing care in psychiatry wards seems to be positive. Some tasks carried out by nurses in psychiatric care still require improvement, especially regarding providing information to patients., (Copyright © 2016 Elsevier Inc. All rights reserved.)