[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.

Performance of crisis standards of care guidelines in a cohort of critically ill COVID-19 patients in the United States.

Many US states published crisis standards of care (CSC) guidelines for allocating scarce critical care resources during the COVID-19 pandemic. However, the performance of these guidelines in maximizing their population benefit has not been well tested. In 2,272 adults with COVID-19 requiring mechanical ventilation drawn from the Study of the Treatment and Outcomes in Critically Ill Patients with COVID-19 (STOP-COVID) multicenter cohort, we test the following three approaches to CSC algorithms: Sequential Organ Failure Assessment (SOFA) scores grouped into ranges, SOFA score ranges plus comorbidities, and a hypothetical approach using raw SOFA scores not grouped into ranges. We find that area under receiver operating characteristic (AUROC) curves for all three algorithms demonstrate only modest discrimination for 28-day mortality. Adding comorbidity scoring modestly improves algorithm performance over SOFA scores alone. The algorithm incorporating comorbidities has modestly worse predictive performance for Black compared to white patients. CSC algorithms should be empirically examined to refine approaches to the allocation of scarce resources during pandemics and to avoid potential exacerbation of racial inequities.

The Effect of Drug Pricing on Outpatient Payments and Treatment for Three Soil-Transmitted Helminth Infections in the United States, 2010-2017.

The price of certain antiparasitic drugs (e.g., albendazole and mebendazole) has dramatically increased since 2010. The effect of these rising prices on treatment costs and use of standard of care (SOC) drugs is unknown. To measure the impact of drug prices on overall outpatient cost and quality of care, we identified outpatient visits associated with ascariasis, hookworm, and trichuriasis infections from the 2010 to 2017 MarketScan Commercial Claims and Encounters and Multi-state Medicaid databases using Truven Health MarketScan Treatment Pathways. Evaluation was limited to members with continuous enrollment in non-capitated plans 30 days prior, and 90 days following, the first diagnosis. The utilization of SOC prescriptions was considered a marker for quality of care. The impact of drug price on the outpatient expenses was measured by comparing the changes in drug and nondrug outpatient payments per patient through Welch's two sample t-tests. The total outpatient payments per patient (drug and nondrug), for the three parasitic infections, increased between 2010 and 2017. The increase was driven primarily by prescription drug payments, which increased 20.6-137.0 times, as compared with nondrug outpatient payments, which increased 0.3-2.2 times. As prices of mebendazole and albendazole increased, a shift to alternative SOC and non-SOC drug utilization was observed. Using parasitic infection treatment as a model, increases in prescription drug prices can act as the primary driver of increasing outpatient care costs. Simultaneously, there was a shift to alternative SOC, but also to non-SOC drug treatment, suggesting a decrease in quality of care.

Changing clinical characteristics of infants treated for hypoxic-ischaemic encephalopathy in England, Wales and Scotland: a population-based study using the National Neonatal Research Database.

BACKGROUND: Therapeutic hypothermia is standard of care for babies with moderate/severe hypoxic-ischaemic encephalopathy and is increasingly used for mild encephalopathy. OBJECTIVE: Describe temporal trends in the clinical condition of babies diagnosed with hypoxic-ischaemic encephalopathy who received therapeutic hypothermia. DESIGN: Retrospective cohort study using data held in the National Neonatal Research Database. SETTING: National Health Service neonatal units in England, Wales and Scotland. PATIENTS: Infants born from 1 January 2010 to 31 December 2017 with a recorded diagnosis of hypoxic-ischaemic encephalopathy who received therapeutic hypothermia for at least 3 days or died in this period. MAIN OUTCOMES: Primary outcomes: recorded clinical characteristics including umbilical cord pH; Apgar score; newborn resuscitation; seizures and treatment on day 1. SECONDARY OUTCOMES: recorded hypoxic-ischaemic encephalopathy grade. RESULTS: 5201 babies with a diagnosis of hypoxic-ischaemic encephalopathy received therapeutic hypothermia or died; annual numbers increased over the study period. A decreasing proportion had clinical characteristics of severe hypoxia ischaemia or a diagnosis of moderate or severe hypoxic-ischaemic encephalopathy, trends were statistically significant and consistent across multiple clinical characteristics used as markers of severity. CONCLUSIONS: Treatment with therapeutic hypothermia for hypoxic-ischaemic encephalopathy has increased in England, Scotland and Wales. An increasing proportion of treated infants have a diagnosis of mild hypoxic-ischaemic encephalopathy or have less severe clinical markers of hypoxia. This highlights the importance of determining the role of hypothermia in mild hypoxic-ischaemic encephalopathy. Receipt of therapeutic hypothermia is unlikely to be a useful marker for assessing changes in the incidence of brain injury over time.

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.

Technical Standards for Nursing Education Programs in the 21st Century.

PURPOSE: The Institute of Medicine (2000, 2002) exposed serious safety problems in the health system and called for total qualitative system change. The Institute of Medicine (2011, 2015) also calls for improving the education of nurses to provide leadership for a redesigned health system. Intertwined with improving education is the need to recruit and retain diverse highly qualified students. Disability is part of diversity inclusion, but current technical standards (nonacademic requirements) for admission to many nursing programs are a barrier to the entry of persons with disabilities. Rehabilitation nurse leaders are in a unique position to improve disability diversity in nursing. The purpose of this paper is to discuss the importance of disability diversity in nursing. DESIGN: The history of existing technical standards used in many nursing programs is reviewed along with examples. METHODS: On the basis of the concept that disability inclusion is a part of diversity inclusion, we propose a new model of technical standards for nursing education. CONCLUSION AND CLINICAL RELEVANCE: Rehabilitation nurse leaders can lead in eliminating barriers to persons with disabilities entering nursing.

Current and evolving standards of care for patients with ARDS.

Care for patients with acute respiratory distress syndrome (ARDS) has changed considerably over the 50 years since its original description. Indeed, standards of care continue to evolve as does how this clinical entity is defined and how patients are grouped and treated in clinical practice. In this narrative review we discuss current standards - treatments that have a solid evidence base and are well established as targets for usual care - and also evolving standards - treatments that have promise and may become widely adopted in the future. We focus on three broad domains of ventilatory management, ventilation adjuncts, and pharmacotherapy. Current standards for ventilatory management include limitation of tidal volume and airway pressure and standard approaches to setting PEEP, while evolving standards might focus on limitation of driving pressure or mechanical power, individual titration of PEEP, and monitoring efforts during spontaneous breathing. Current standards in ventilation adjuncts include prone positioning in moderate-severe ARDS and veno-venous extracorporeal life support after prone positioning in patients with severe hypoxemia or who are difficult to ventilate. Pharmacotherapy current standards include corticosteroids for patients with ARDS due to COVID-19 and employing a conservative fluid strategy for patients not in shock; evolving standards may include steroids for ARDS not related to COVID-19, or specific biological agents being tested in appropriate sub-phenotypes of ARDS. While much progress has been made, certainly significant work remains to be done and we look forward to these future developments.

Cardiopatías congénitas del adulto en España: estructura, actividad y características clínicas / Adult congenital heart disease in Spain: health care structure and activity, and clinical characteristics

INTRODUCCIÓN Y OBJETIVOS: Analizar la estructura asistencial y las características clínicas de las cardiopatías congénitas del adulto en España. MÉTODOS: En 2014 se realizó una encuesta entre 32 centros que se clasificaron como nivel 1 o 2 en función de su estructura asistencial. En 2017 se realizó un registro clínico de todos los pacientes asistidos consecutivamente en cada centro durante un periodo de 2 meses. RESULTADOS: Un total de 31 centros (97%) respondieron la encuesta. Se excluyó a 7 por no disponer de consulta especializada. Hasta el año 2005 solo había 5 centros con dedicación específica, pero en 2014 había 10 centros de nivel 1 y 14 de nivel 2 con un total de 19.373 pacientes en seguimiento. La estructura institucional era completa en la mayoría de los centros, pero solo el 33% disponía de enfermería propia y el 29%, de unidad de transición estructurada. La actividad terapéutica específica supuso el 99 y el 91% de la publicada en los registros nacionales de cirugía y cateterismo terapéutico. Del total, el 44% de los pacientes tenían cardiopatía de complejidad moderada y el 24%, de gran complejidad. Aunque el 46% de los pacientes atendidos en centros de nivel 2 tenían cardiopatías simples, el 17% eran cardiopatías de gran complejidad. CONCLUSIONES: La estructura y la actividad de los centros españoles cumplen las recomendaciones internacionales y son comparables a las de otros países desarrollados. El espectro de cardiopatías en seguimiento muestra una concentración de lesiones de complejidad moderada y gran complejidad incluso en centros de nivel 2. Sería aconsejable reordenar el seguimiento de los pacientes en función de las recomendaciones internacionales

INTRODUCTION AND OBJECTIVES: To assess the structure of health care delivery and the clinical characteristics of adults with congenital heart disease (ACHD) attending specialized centers in Spain. METHODS: A survey was conducted among 32 Spanish centers in 2014. The centers were classified into 2 levels based on their resources. In 2017, a clinical dataset was collected of all consecutive patients attended for a 2-month period at these centers. RESULTS: A total of 31 centers (97%) completed the survey. Seven centers without specialized ACHD clinics were excluded from the analysis. In 2005, only 5 centers met the requirements for specific care. In 2014, there were 10 level 1 and 14 level 2 centers, with a total of 19 373 patients under follow-up. Health care structure was complete in most centers but only 33% had ACHD nurse specialists on staff and 29% had structured transition programs. Therapeutic procedures accounted for 99% and 91% of those reported by National Registries of Cardiac Surgery and Cardiac Catheterization, respectively. Among attended patients, 48% had moderately complex lesions and 24% had highly complex lesions. Although 46% of patients attending level 2 centers had simple lesions, 17% had complex lesions. CONCLUSIONS: The structure for ACHD health care delivery in Spain complies with international recommendations and is similar to that of other developed countries. Congenital heart diseases under specialized care consist mostly of moderately and highly complex lesions, even in level 2 centers. It would be desirable to reorganize patient follow-up according to international recommendations in clinical practice

National Children's Hospitals Bereavement Network standards for supporting families following the death of a child.

In England, a child death review process must be undertaken when a child dies, regardless of the cause of death. Scotland and Wales have their own version of the child death review process, while it is the author's understanding that Northern Ireland are still developing their process. An important aspect of this process is family engagement and bereavement support. This article is an introduction to the bereavement support standards developed by the National Children's Hospitals Bereavement Network, a newly formed group of specialist children's nurses and allied health professionals interested in bereavement care. These standards translate the statutory requirements into practical guidance for healthcare professionals working in children's hospitals in the UK or district general hospitals that offer services for children and families. They also apply to NHS trusts that care for children and need to develop a local policy and workforce with the appropriate skills to provide bereavement care, thereby improving the experiences of families and healthcare professionals. The standards would also be applicable to other NHS trusts and healthcare services in the UK who want to develop an approach to bereavement care and support for families.

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.

Biomarkers of sepsis: time for a reappraisal.

INTRODUCTION: Sepsis biomarkers can have important diagnostic, therapeutic, and prognostic functions. In a previous review, we identified 3370 references reporting on 178 different biomarkers related to sepsis. In the present review, we evaluate the progress in the research of sepsis biomarkers. METHODS: Using the same methodology as in our previous review, we searched the PubMed database from 2009 until September 2019 using the terms "Biomarker" AND "Sepsis." There were no restrictions by age or language, and all studies, clinical and experimental, were included. RESULTS: We retrieved a total of 5367 new references since our previous review. We identified 258 biomarkers, 80 of which were new compared to our previous list. The majority of biomarkers have been evaluated in fewer than 5 studies, with 81 (31%) being assessed in just a single study. Apart from studies of C-reactive protein (CRP) or procalcitonin (PCT), only 26 biomarkers have been assessed in clinical studies with more than 300 participants. Forty biomarkers have been compared to PCT and/or CRP for their diagnostic value; 9 were shown to have a better diagnostic value for sepsis than either or both of these biomarkers. Forty-four biomarkers have been evaluated for a role in answering a specific clinical question rather than for their general diagnostic or prognostic properties in sepsis. CONCLUSIONS: The number of biomarkers being identified is still increasing although at a slower rate than in the past. Most of the biomarkers have not been well-studied; in particular, the clinical role of these biomarkers needs to be better evaluated.

Progressing toward specialty certification as the National Standard for Nursing.

Nursing specialty certification is an objective measure that assures the public that nurses demonstrate the highest level of professional knowledge in their field. Many nurses do not seek specialty certification, as evidenced by low certification rates. In this creative controversy article, we build a case that progressing toward nursing specialty certification as a national standard will increase overall nursing professionalism while better preparing nurses to meet the needs of their specialty patient populations and the changing health care system.

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.

Safe and competent nursing care: An argument for a minimum standard?

There is no agreed minimum standard with regard to what is considered safe, competent nursing care. Limited resources and organizational constraints make it challenging to develop a minimum standard. As part of their everyday practice, nurses have to ration nursing care and prioritize what care to postpone, leave out, and/or omit. In developed countries where public healthcare is tax-funded, a minimum level of healthcare is a patient right; however, what this entails in a given patient's actual situation is unclear. Thus, both patients and nurses would benefit from the development of a minimum standard of nursing care. Clarity on this matter is also of ethical and legal concern. In this article, we explore the case for developing a minimum standard to ensure safe and competent nursing care services. Any such standard must encompass knowledge of basic principles of clinical nursing and preservation of moral values, as well as managerial issues, such as manpower planning, skill-mix, and time to care. In order for such standards to aid in providing safe and competent nursing care, they should be in compliance with accepted evidence-based nursing knowledge, based on patients' needs and legal rights to healthcare and on nurses' codes of ethics. That is, a minimum standard must uphold a satisfactory level of quality in terms of both professionalism and ethics. Rather than being fixed, the minimum standard should be adjusted according to patients' needs in different settings and may thus be different in different contexts and countries.

Caring for Pregnant Patients with COVID-19: Practical Tips Getting from Policy to Practice.

Novel coronavirus disease 2019 (COVID-19) is a pandemic with most American cases in New York. As an institution residing in a high-prevalence zip code, with over 8,000 births annually, we have cared for over 80 COVID-19-infected pregnant women, and have encountered many challenges in applying new national standards for care. In this article, we review how to change outpatient and inpatient practices, develop, and disseminate new hospital protocols, and we highlight the psychosocial challenges for pregnant patients and their providers. KEY POINTS: · Novel coronavirus disease 2019 (COVID-19) information rapidly changes.. · Multidisciplinary communication is key.. · This study addresses psychosocial challenges..

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 Ebola-related critical illness.

PURPOSE: To explore contemporary clincial case management of patients with Ebola virus disease. METHODS: A narrative review from a clinical perspective of clinical features, diagnostic tests, treatments and outcomes of patients with Ebola virus disease. RESULTS: Substantial advances have been made in the care of patients with Ebola virus disease (EVD), precipitated by the unprecedented extent of the 2014-2016 outbreak. There has been improved point-of-care diagnostics, improved characterization of the clinical course of EVD, improved patient-optimized standards of care, evaluation of effective anti-Ebola therapies, administration of effective vaccines, and development of innovative Ebola treatment units. A better understanding of the Ebola virus disease clinical syndrome has led to the appreciation of a central role for critical care clinicians-over 50% of patients have life-threatening complications, including hypotension, severe electrolyte imbalance, acute kidney injury, metabolic acidosis and respiratory failure. Accordingly, patients often require critical care interventions such as monitoring of vital signs, intravenous fluid resuscitation, intravenous vasoactive medications, frequent diagnostic laboratory testing, renal replacement therapy, oxygen and occasionally mechanical ventilation. CONCLUSION: With advanced training and adherence to infection prevention and control practices, clinical interventions, including critical care, are feasible and safe to perform in critically ill patients. With specific anti-Ebola medications, most patients can survive Ebola virus infection.