[A decade of checkpoint inhibitors: current standard of care and future trends]. / Checkpoint-Inhibitoren ­ aktuelle Versorgungsstandards und Zukunftstrends.

Therapy with checkpoint inhibitors still revolutionizes the therapeutical landscape in oncology. Since the first approval of a checkpoint inhibitor for the therapy of malignant melanoma 2011, many other approvals in the field of hematology and oncology followed. Besides monotherapy, a rapidly increasing number of trials is investigating checkpoint inhibitors in different combination therapies for advanced disease. Cumulating evidence suggests checkpoint blockade also as promising option for (neo)-adjuvant treatment. Here we review the different treatment strategies of mono- and combination-therapies. Additionally, important biomarkers for the treatment with checkpoint inhibitors are discussed.

Hereditary hemorrhagic telangiectasia: systemic therapies, guidelines, and an evolving standard of care.

Hereditary hemorrhagic telangiectasia (HHT) management is evolving because of the emergence and development of antiangiogenic therapies to eliminate bleeding telangiectasias and achieve hemostasis. This progress is reflected in recent clinical recommendations published in the Second International Guidelines for the Diagnosis and Treatment of HHT, in which systemic therapies including antiangiogenics and antifibrinolytics are now recommended as standard treatment options for bleeding. This review highlights the new recommendations especially relevant to hematologists in managing bleeding, anticoagulation, and anemia in patients with HHT.

Identifying risk factors and optimizing standard of care for patients with acquired haemophilia A: Results from a Czech patient cohort.

INTRODUCTION: Acquired haemophilia A (AHA) is a rare autoimmune disorder, characterized by bleeds of varying severity caused by autoantibodies against factor VIII (FVIII). AIM: Identify risk factors associated with AHA-related deaths/relapses and assess the effect of increased corticosteroid doses. METHODS: AHA patients treated across two specialist centres in the Czech Republic, generally receiving first-line haemostatic therapy with rFVIIa and immunosuppression with corticosteroids/cyclophosphamide, were included. We analysed the association between early death (within 8 weeks of diagnosis [considered disease-related]) and age, malignancy, FVIII levels and bleeding severity. Risk factors associated with reduced 2-year survival and relapse incidence, and the effect of increased corticosteroid doses on early death and remission were also assessed. RESULTS: The demographics of the described cohort (n = 66) were similar to other AHA registries. Early death occurred in 20% of cases. Unlike age and malignancy, FVIII levels <1% and severe bleeding were associated significantly with early death (P = .010 and P = .046, respectively). Patients with underlying malignancy or requiring continued haemostatic therapy exhibited significantly decreased 2-year survival compared with those without these risk factors (P = .007 and P = .006, respectively). Patients with an underlying autoimmune disease relapsed significantly more than those without (P = .015). Higher corticosteroid doses were associated with a significantly increased incidence of early deaths (P < .001), but also with early remission (P < .001). CONCLUSION: Based on this rather large patient cohort, we were able to evaluate the significance of several risk factors associated with treatment outcomes in AHA and the effect of initial treatment with corticosteroids on survival and time to remission.

Standard Operating Procedures (SOPs) for Palliative Care in German Comprehensive Cancer Centers - an evaluation of the implementation status.

BACKGROUND: The working group for palliative medicine within the Comprehensive Cancer Center (CCC) network funded by the German Cancer Aid in Germany has developed and published 14 Standard Operating Procedures (SOPs) for palliative care in CCCs. This study analyzed to what extent these SOPs have been implemented in the clinical routine in the CCC network one year after their publication. METHODS: An online-based survey on the implementation status, limitations in daily practice and further themes was conducted between April and July 2018. In total, 125 health professionals in specialized palliative care from all 16 CCC locations were invited to participate. The data were analyzed descriptively using SPSS. RESULTS: The response rate was 52.8%. More than half of the respondents (57.6%) knew about the free availability of SOPs on the CCC network website. The extent to which each SOP was being used actively in practice by the survey respondents ranged from a low of 22.7% (for the "Fatigue" SOP) to a highest of 48.5% (for the "Palliative Sedation" and "Respiratory Distress" SOPs). The respondents became aware of the SOP through recommendations from colleagues, team meetings or from the head of the department. The SOPs "Respiratory distress of an adult palliative patient" and "Palliative sedation" were perceived as the most practically oriented and understandable. Barriers to use SOPs were mainly limited time resources and lack of knowledge of existence and availability. CONCLUSIONS: In practice, better knowledge about the SOPs and at the same time increased use can be achieved through systematic training or discussion of SOPs in regular team meetings. There is a need to take measures to optimize the implementation in clinical practice.

Reducing Readmissions Following Radical Cystectomy: Moving Beyond Enhanced Recovery.

OBJECTIVE: To assess readmission outcomes of a traditional ER pathway as well as a targeted postdischarge intervention aimed at reducing hospital readmissions following RC. METHODS: A prospectively maintained clinical database was used to identify patients undergoing RC before and after implementation of an ER protocol at our institution. An additional intervention aimed at reducing hospital readmission included close postdischarge follow-up and outpatient intravenous hydration (ER+). Inpatient length of stay (LOS) and readmission rates were compared between groups using Wilcoxon Rank Sum and chi-square, respectively. Univariate and multivariate logistic regression was used to identify factors associated with hospital readmission. RESULTS: A total of 320 patients underwent RC, including 111 and 209 patients before and after ER implementation. Median (IQR) LOS decreased from 8.0 (6.0-11.0) days to 5.0 (4.0-7.0) days following ER implementation (P <.0001). Readmissions, however, were unchanged following ER implementation (P = .49). An additional targeted readmission reduction intervention (ER+) was associated with significantly reduced hospital readmissions compared to traditional ER alone (ER+ 5.9%, traditional ER 20.3%, P = .017). CONCLUSION: ER protocols consistently demonstrate reductions in LOS, and should be the standard of care following RC. In order to reduce readmissions, the urologic community must expand beyond traditional ER pathways. We report significant reductions in hospital readmission among RC patients receiving a targeted postdischarge intervention beyond traditional ER alone.

Treatment of Primary in Metastatic Prostate Cancer: What Is the Standard of Care?

Until recently, men with metastatic prostate cancer were commenced on androgen deprivation therapy at diagnosis, followed by sequential lines of treatment with the development of castration resistance. However, the results of recent clinical trials, which revealed that the addition of radiotherapy to the prostate to a dose of 55 to 60 Gy in 20 fractions over 4 weeks in patients with low-volume metastatic hormone-sensitive prostate cancer, in addition to androgen deprivation therapy and another systemic treatment option, either docetaxel, abiraterone, enzalutamide, or apalutamide, has led to a paradigm change in the management of this disease.

Recent advances in understanding and managing myasthenia gravis.

Autoimmune myasthenia gravis (MG) is a neuromuscular junction disorder marked clinically by fatigable muscle weakness and serologically by the presence of autoantibodies against acetylcholine receptors (AChRs), muscle-specific kinase (MuSK), or lipoprotein-related protein 4 (LPR4). Over the past few decades, the mortality of patients with MG has seen a dramatic decline secondary to evolving interventions in critical care and medical management. In the past 2 to 3 years, there have been several changes in standard of care for the treatment of MG. These changes include confirmation of the benefit of thymectomy versus medical management alone in AChR patients and a new US Food and Drug Administration-approved medication for refractory MG. There are also several exciting new prospective drugs in the pipeline, which are in different stages of clinical trial testing.

Competence for basic midwifery practice: Updating the ICM essential competencies.

OBJECTIVE: To obtain consensus amongst midwifery experts globally about the essential competencies for basic midwifery practice. DESIGN: A modified Delphi approach, involving a three-round online survey. PARTICIPANTS: Midwifery leaders, educators and regulators in all ICM regions, along with representatives of organisations affiliated to ICM. METHODS: The research team worked closely with a Core Working Group and a Task Force. An initial set of competencies and components was developed through a content analysis of existing competency documents and presented to participants in Round 1 of the survey. Items identified as essential by at least 85% of participants were endorsed. Remaining items and new items identified by participants were returned to participants in Rounds 2 and 3 for further rating. FINDINGS: The study achieved a wide sample representative of midwifery experts across all ICM regions and countries, language groups, and income categories. Only a small number of competencies relating to the wider role of the midwife were endorsed as essential competencies. Competencies and components relating to professional and personal attributes were extended. Although most competencies and components relating to core midwifery practice were endorsed as essential competencies, several were rejected relating to abortion-related care, cancer screening, infertility, and gynaecology. Findings are, nevertheless, highly consistent with the scope of practice delineated in the current 2010/2013 version of the ICM Essential Competencies for Basic Midwifery Practice. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: The extension of professional and personal attributes reflects the recent emphasis on respectful midwifery care. The rejection of most of the additional competencies and components relating to the wider role of the midwife and endorsement of most of those considered to relate to core midwifery practice indicates that the scope of midwifery practice remains essentially unchanged through 2017.

Transitions in palliative care: conceptual diversification and the integration of palliative care into standard oncology care.

Palliative care acknowledges the historical origin of the hospice developed in the UK during the 20th century. Palliative care initially focused primarily on end-of-life care provided at hospices, but then changed to at-home care, leading to the formation of a support system provided by the palliative care team. The palliative care team further coordinated with acute care hospitals and became involved in earlier stages of care as well, such as providing symptomatic relief in conjunction with cancer treatment. On this backdrop, the concept of palliative care itself also evolved over time. In recent years, attempts at early-stage palliative care from the initial stages of treatment are being studied with respect to cases with complications such as advanced cancer. Early-stage palliative care has been reported to improve patient quality of life (QOL), improve depression, reduce the burden on the family, and possibly improve survival prognosis for some advanced cancers. Currently, efforts to integrate palliative care into standard oncology care regimens by providing specialist palliative care and cancer treatment as a single unit are anticipated to enter more widespread practice. Such a care approach differs from conventional palliative care, which is started around the time when the end of conventional cancer treatment, and consists of applying specialist palliative care from the stage where cancer treatments are administered to address with multiple problems. Many breast cancer patients have severe problems such as esthetic outcome, sexuality and psycho-social effects associated with breast cancer itself and treatment. And it effects their QOL for a long time not only during therapy but also having done therapy or recurrence. Therefore, it may be effectiveness for patients to integrate of palliative care into standard oncology care in breast cancer, but the effect of it for only breast cancer patients has not been reported on yet. In this paper, after reviewing the concepts and historical evolution of palliative care, we describe the integration of palliative care into standard oncology care that has been making progress recently.

A Step Toward Identifying Sources of Medical Errors: Modeling Standards of Care Deviations for Different Disease States.

Objective: To examine the feasibility of utilizing electronic health records (EHR) to determine a metric for identifying physician diagnostic and treatment deviations in standards of care for different disease states. Methods: A Boolean-rule-based model compared deviations in standards of care across four disease states: diabetes, cardiovascular disease, asthma, and rheumatoid arthritis. This metric was used to identify the relationship between physician deviations in standards of care procedures, before and after diagnosis, for 76 internal medicine physicians. Results: The Boolean-rule-based model identified patterns of standards of care deviation for the physicians before diagnosis and during treatment. The deviations identified for each of the four disease states were then related to Continuing Medical Education courses that could support further training. The rule-based model was extended and improved by including system and process aspects of medical care that are not specifically related to the physician, yet potentially have an impact on the physician's decision to deviate from the standards of care. Conclusion: The Boolean-rule-based approach provided a means to systematically mine EHRs and use these data to assess deviations in standards of care that could identify quality of care issues stemming from system processes or the need for specific CME for a physician.

The maternity ward of a teaching hospital: reconfiguration of maternal-child nursing care / Maternidad de un hospital-escuela: reconfiguración de la asistencia de enfermería materno-infantil / Maternidade de um hospital-escola: reconfiguração da assistência de enfermagem materno infantil

ABSTRACT Objective: to analyze the strategies used by nurses and nurse professors for a better position in the maternity ward of the teaching hospital of the Universidade Federal do Espírito Santo. Method: this is a social-historical study with a qualitative approach. The primary sources were written documents, such as official letters, memos, ordinances, standards and routines of the hospital; photographic material; and oral testimonies from seven participants. The interviews were performed using a semi-structured questionnaire, with questions regarding the adaptation from a sanatorium to a teaching hospital, the challenges faced, and the strategies adopted by the nursing department. Results: the results allowed us to understand the close link between the maternity ward and the nursing course of the Universidade Federal do Espírito Santo, which created a differentiated nursing care that integrated training and care with a broader and humanized look. Final considerations: the actions of the nurses were recognized and gave them professional visibility, influencing a new form of care in the maternity ward.

RESUMEN Objetivo: analizar las estrategias usadas por las enfermeras asistenciales y enfermeras docentes por una mejor posición en la maternidad del hospital-escuela de la Universidad Federal de Espírito Santo. Método: estudio de naturaleza histórico-social con abordaje cualitativo. Las fuentes primarias se constituyeron de documentos escritos, como los oficios, los memorandos, los decretos, las normas y las rutinas hospitalarias; el material fotográfico; y las declaraciones orales de siete participantes. La encuesta fue orientada por la ruta semiestructurada con cuestiones sobre la adaptación del sanatorio para hospital-escuela, los retos enfrentados y las estrategias adoptadas por la enfermería. Resultados: permitieron entender la estrecha vinculación de la maternidad con el curso de enfermería de la Universidad Federal de Espírito Santo, el que determinaba una asistencia de enfermería diferenciada, la cual integraba enseñanza y asistencia con una mirada más amplia y humanizada. Consideraciones finales: las acciones de las enfermeras fueron reconocidas y generaron visibilidad profesional, influenciando una nueva manera de cuidar en la maternidad.

RESUMO Objetivo: analisar as estratégias usadas pelas enfermeiras assistenciais e enfermeiras docentes por uma melhor posição na maternidade do hospital-escola da Universidade Federal do Espírito Santo. Método: estudo de natureza histórico-social com abordagem qualitativa. As fontes primárias constituíram-se de documentos escritos, como ofícios, memorandos, portarias, normas e rotinas hospitalares; material fotográfico; e depoimentos orais de sete participantes. A entrevista foi orientada por roteiro semiestruturado com questões sobre a adaptação do sanatório para hospital-escola, os desafios enfrentados e as estratégias adotadas pela enfermagem. Resultados: permitiram entender a estreita vinculação da maternidade com o curso de enfermagem da Universidade Federal do Espírito Santo, o que determinava uma assistência de enfermagem diferenciada, a qual integrava ensino e assistência com um olhar mais amplo e humanizado. Considerações finais: as ações das enfermeiras foram reconhecidas e geraram visibilidade profissional, influenciando uma nova forma de cuidar na maternidade.

Time trends (2006-2015) of quality indicators in EUSOMA-certified breast centres.

AIM OF THE STUDY: The European Society of Breast Cancer Specialists (EUSOMA) has fostered a voluntary certification process for breast centres to establish minimum standards and ensure specialist multidisciplinary care. Prospectively collected anonymous information on primary breast cancer cases diagnosed and treated in the units is transferred annually to a central EUSOMA data warehouse for continuous monitoring of quality indicators (QIs) to improve quality of care. Units have to comply with the EUSOMA Breast Centre guidelines and are audited by peers. The database was started in 2006 and includes over 110,000 cancers from breast centres located in Germany, Switzerland, Belgium, Austria, The Netherlands, Spain, Portugal and Italy. The aim of the present study is assessing time trends of QIs in EUSOMA-certified breast centres over the decade 2006-2015. MATERIALS AND METHODS: Previously defined QIs were calculated for 22 EUSOMA-certified breast centres (46122 patients) during 2006-2015. RESULTS: On the average of all units, the minimum standard of care was achieved in 8 of 13 main EUSOMA QIs in 2006 and in all in 2015. All QIs, except removal of at least 10 lymph nodes at axillary clearance and oestrogen receptor-negative tumours (T > 1 cm or N+) receiving adjuvant chemotherapy, improved significantly in this period. The desirable target was reached for two QIs in 2006 and for 7 of 13 QIs in 2015. CONCLUSION: The EUSOMA model of audit and monitoring QIs functions well in different European health systems and results in better performance of QIs over the last decade. QIs should be evaluated and adapted on a regular basis, as guidelines change over time.

Care path of person with stroke: from onset to rehabilitation / Camino que recorre la persona con accidente vascular encefálico: desde el acontecimiento hasta la rehabilitación / Percurso da pessoa com acidente vascular encefálico: do evento à reabilitação

ABSTRACT Objective: to describe the care path of the person with stroke goes through and to identify the important events in this path. Method: qualitative descriptive exploratory research, using the semi-structured interview technique based on Meleis's Middle-Range Theory. The sample was composed of 13 people who became dependent after a stroke and were admitted to two hospital units in the region of Vale do Ave, Portugal. Data were collected between January and October 2013. Content analysis was used to analyze the data. Results: The data revealed that the person's care path goes from recognition of the symptoms to preparation for hospital discharge. Adapting to the new situation of dependence brings the need for new competencies. Final considerations: The research aims to contribute to the improvement of nursing care regarding care for people with stroke including onset, recovery and rehabilitation, and home care.

RESUMEN Objetivo: Describir el camino que recorre la persona con Accidente Vascular Encefálico e identificar los acontecimientos significativos de ese camino. Método: se trata de un abordaje cualitativo de naturaleza exploratoria- descriptiva, con técnica de entrevista mixta basada en la Teoría de Mediano Alcance de Meleis. Participaron 13 personas que se volvieron dependientes debido a un Accidente Vascular Encefálico y recurrieron a dos Unidades de la región del Valle del Ave, Portugal. La recolección de datos se realizó durante el período comprendido entre enero y octubre de 2013 mediante el análisis de contenido. Resultados: Los datos rebelaron que el trayecto de la persona comienza con el reconocimiento de los síntomas y se extiende hasta la preparación del alta hospitalaria. La dependencia hace surgir la necesidad de adquirir competencias para adaptarse a la nueva situación. Consideraciones finales: Se espera contribuir para la mejoría de los cuidados de enfermería en la atención de los pacientes con Accidente Vascular Encefálico, desde el acontecimiento, durante la recuperación y la rehabilitación, hasta los cuidados domiciliares.

RESUMO Objetivo: Descrever o percurso da pessoa com Acidente Vascular Encefálico e identificar os acontecimentos significativos neste percurso. Método: Abordagem qualitativa e natureza exploratória- descritiva, valeu-se da técnica de entrevista semiestruturada baseada na Teoria de Médio Alcance de Meleis. Participaram 13 pessoas que se tornaram dependentes devido à Acidente Vascular Encefálico e recorreram a duas Unidades da região do Vale do Ave, Portugal. A colheita de dados deu-se durante Janeiro a Outubro de 2013. Para análise dos dados foi utilizada a análise de conteúdo. Resultados: Os dados revelaram que o trajeto da pessoa vai desde o reconhecimento dos sintomas até à preparação da alta hospitalar. A dependência traz a necessidade de adquirir competências para se adaptar à nova situação. Considerações finais: Espera-se contribuir para a melhoria dos cuidados de enfermagem no atendimento das pessoas acometidas com Acidente Vascular Encefálico, desde o acometimento, recuperação e reabilitação, até aos cuidados domiciliares.

Evolving standards of care for resected pancreatic cancer.

Pancreatic cancer is a devastating illness, and surgical resection offers the only chance of a cure for patients with the disease. Relatively few patients have resectable disease at diagnosis, however, and the cancer frequently recurs even after complete surgical resection. This review discusses clinical trials in which adjuvant therapy with chemotherapy or chemoradiation has prolonged survival in patients following surgery. It also highlights new data from the ESPAC-4 and JASPAC 01 studies that may change the current treatment paradigm for adjuvant therapy. The ESPAC-4 results support the use of adjuvant gemcitabine plus capecitabine in preference to the previous standard of gemcitabine alone, demonstrating that in this instance, more may be better. Finally, the review discusses ongoing trials and new approaches that aim to improve outcomes further for patients with resectable pancreatic cancer.

Combination Treatment of Patients with BRAF-Mutant Melanoma: A New Standard of Care.

Raf-mitogen-activated protein kinase (Raf-MAPK) pathway inhibition with the BRAF inhibitors vemurafenib and dabrafenib, alone or in combination with a MEK inhibitor, has become a standard therapeutic approach in patients with BRAF-mutated metastatic melanoma. Both vemurafenib and dabrafenib have shown good safety and efficacy as monotherapy compared with chemotherapy. However, the duration of response is limited in the majority of patients treated with BRAF inhibitor monotherapy because of the development of acquired resistance. The addition of a MEK inhibitor can improve blockade of the MAPK pathway and may help to overcome resistance and thereby prolong efficacy, as well as reduce cutaneous toxicity. Combinations of BRAF inhibitors and MEK inhibitors (dabrafenib plus trametinib and vemurafenib plus cobimetinib) have been approved for the treatment of BRAF-mutant metastatic melanoma and may become a new standard of care. However, acquired resistance is still a significant concern with BRAF and MEK inhibitor combination therapy, and other strategies are being investigated, including the use of sequential and intermittent schedules. The combination of BRAF or MEK inhibitors with immunotherapy has been shown to hold considerable promise, with several combinations being evaluated in clinical trials. Preliminary results from clinical trials involving triple combination therapy with BRAF-MEK inhibitors and anti-PD-L1 antibodies appear promising and may indicate a new strategy to treat patients with BRAF-mutated metastatic melanoma. Biomarkers are needed to help identify patients with BRAFV600 mutations most likely to benefit from first-line BRAF/MEK inhibitor therapy rather than immunotherapy and vice versa.

Helicobacter pylori therapy: a paradigm shift.

Helicobacter pylori (H. Pylori) is a leading cause of gastroduodenal disease, including gastric cancer. H. pylori eradication therapies and their efficacy are summarized. A number of current treatment regimens will reliably yield >90% or 95% cure rates with susceptible strains. None has proven to be superior. We show how to predict the efficacy of a regimen in any population provided one knows the prevalence of antibiotic resistance. As with other infectious diseases, therapy should always be susceptibility-based. Susceptibility testing should be demanded. We provide recommendations for empiric therapies when that is the only option and describe how to distinguish studies providing misinformation from those providing reliable and interpretable data. When treated as an infectious disease, high H. pylori cure rates are relatively simple to reliably achieve.

Receipt of Care Discordant with Practice Guidelines is Associated with Compromised Overall Survival in Nasopharyngeal Carcinoma.

AIMS: It is unknown whether receiving treatment that is discordant with practice guidelines is associated with improved survival in patients with nasopharyngeal carcinoma. The objectives of this study were to characterise national treatment patterns, analyse whether treatment outside of practice guidelines is associated with overall survival, and identify variables associated with receiving guidelines-discordant care in the USA. MATERIALS AND METHODS: This was a retrospective cohort study of 1741 nasopharyngeal carcinoma patients in the National Cancer Data Base (2003-2006). Treatment regimens were compared with the 2004-2006 National Comprehensive Cancer Network guidelines. Statistical analyses included chi-square, Kaplan-Meier, multivariable logistic, and Cox regression. RESULTS: Nearly 26% of our cohort received care discordant with practice guidelines. In multivariable analysis, patients with stage IVC disease (odds ratio 2.59, 95% confidence interval 1.66-4.04) were more likely to receive guidelines-discordant care when compared with those with stage II-IVB disease. The most common treatment deviation for those with stage I disease was overtreatment with chemoradiation therapy. Receiving guidelines-discordant care was associated with an increased risk of death (hazard ratio 1.46, 95% confidence interval 1.25-1.69). CONCLUSIONS: Many patients with stages I and IVC nasopharyngeal carcinoma do not receive care in accordance with practice guidelines. Receiving guidelines-discordant care is associated with compromised overall survival in the USA.