Personalized oncology, ethics and adherence to NCCN guidelines.

Successful personalized oncology today depends on clinicians taking advantage of the extensive, evidence-based information provided by the National Comprehensive Cancer Network (NCCN) Guidelines, which arguably represent the most important advance in cancer care occurring in the last many decades. Personalized oncology also demands that clinicians present guideline information to each patient in a thorough, comprehendible and unbiased manner. Finally, the patient's ability to process that information for shared decision-making about whether an intervention is consistent with their personal preferences, goals and values is perhaps the most important ingredient in truly personalized oncology care. Here, the ethics of sometimes transgressing from the NCCN guidelines with the aim of more personalized care is discussed.

Impact of the Step-by-Step on febrile infants.

OBJECTIVE: To evaluate the impact of introducing the Step-by-Step approach on care quality in young febrile infants. DESIGN: Observational study including infants ≤90 days old with fever without source seen in a paediatric emergency department 5 years before (n=1222) and after (n=1151) its introduction. Quality of care was evaluated in terms of adherence to recommendations, resource use and safety. RESULTS: Adherence: percentages of infants undergoing both urine and blood tests and infants <15 days old receiving full sepsis evaluation increased (84.7% vs 91.0% and 23.9% vs 63.3%, respectively; p<0.01). Resource use: lumbar puncture and admission rates decreased (24.1% vs 18.7% and 43.6% vs 38.3%, respectively; p<0.01), while the rate of antibiotic therapy increased (30.2% vs 43.2%; p<0.01). SAFETY: the invasive bacterial infection rate among infants managed as outpatients was unchanged (0.7% vs 0.3%; p=0.24). CONCLUSION: The introduction of the Step-by-Step increased the quality of care provided to young febrile infants.

Ethics of Implementing US Preventive Services Task Force Recommendations for Childhood Obesity.

Childhood obesity represents a serious and growing concern for the United States. Its negative consequences for health and well-being can be far-reaching, devastating, and intergenerational. In 2017, the US Preventive Services Task Force (USPSTF) issued a grade B recommendation for screening children and adolescents for obesity and offering or referring to comprehensive, intensive behavioral interventions as indicated. However, many communities in the United States have limited access to such interventions. The USPSTF's mission is to review and grade research evidence for clinical preventive services and does not include cost or population-based operationalization and implementation logistics considerations for its recommendations. Yet implementing recommendations without considering cost and operationalization may lead to equity and access challenges. These are essential considerations, but oversight of the implementation of these recommendations is not standardized or assigned to any one agency or organization. As such, a central ethical feature inherent to the implementation of USPSTF recommendations calls for stakeholder collaborations to take on the next step beyond the establishment of evidence-based recommendations: to ensure the ethical application of such guidelines across diverse populations. Furthermore, the screening-intervention relationship inherent to this USPSTF recommendation raises ethical concerns regarding US societal norms surrounding obesity, particularly when contrasted against other screening-intervention modalities. More efforts, such as increased incentives or expansion of clinical services in low-resource areas, should be taken to facilitate this recommended intervention by expanding access to childhood obesity interventions to fulfill ethical responsibilities to equity and to ensure the right to open futures for children.

Current Challenges in Labelling for Generic Medicinal Products: Company Core Data Sheet (CCDS) Development and Maintenance.

Labelling of pharmaceutical products plays a vital role in the safe and effective use of approved medicinal products. This information may be provided to end-users including patients and/or prescribers, and it needs to be made available in multiple formats including printed forms (patient information leaflets, pack inserts, etc.) or web portals of the product, based on national authority guidelines. The Company Core Data Sheet (CCDS) serves as a key document representing the pharmaceutical company's position on the product and is used as a reference document for national labels. Content from national labels may differ from the CCDS for different reasons including implementation of national authority requirements in the serving market and findings from local markets. In the current article, we discuss the process, challenges and key concepts in creating and maintaining CCDS documents for generic products. We highlight key parameters that are worthy of process improvement in generic products' CCDS updates. In addition, we argue that labelling harmonisation across multiple regions, especially safety section-related information, plays a key role in promoting end-user safety and would help communicate risks. We also strongly believe that the topic is worthy of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) consideration, and propose that this is the key area that requires standardisation and harmonisation.

Guideline-adherence regarding critical time intervals in the German Chest Pain Unit registry.

BACKGROUND: Since 2008, the German Cardiac Society certified 256 Chest Pain Units (CPUs). Little is known about adherence to recommended performance measures in patients with suspected acute coronary syndrome (ACS) presenting to CPUs. We investigated guideline-adherence regarding critical time intervals and selected performance measures in German Chest Pain Units. METHODS: From 2008 to 2014, 23,804 consecutive patients with suspected ACS were prospectively enrolled in the Chest Pain Unit registry of the German Cardiac Society. RESULTS: Median time from symptom onset to first medical contact was 2 h in patients with ST-elevation myocardial infarction (STEMI) and 4 h in patients with unstable angina and non-STEMI (NSTEMI). In patients with STEMI, median time from hospital admission to percutaneous coronary intervention (PCI) was 40 min and median time from first medical contact to PCI was 1 h 35 min. Primary PCI was performed in 94.7% of patients with STEMI, 70.0% of patients with NSTEMI and 37.4% of patients with unstable angina. PCI was performed during the first 24 h in 79.5% of patients with NSTEMI and the first 72 h in 89.0% of patients with unstable angina. Electrocardiograms were performed in 99.5% after a median of 6 min after admission and obtained within 10 min in 71%. Interestingly, 56.1% of patients were found to have non-ACS diagnoses, underlining the importance of access to additional diagnostic modalities including echocardiography, stress testing or computed tomography. CONCLUSIONS: Guideline-adherence regarding critical time intervals and primary PCI rates is good in German Chest Pain Units. More than half of patients admitted with suspected ACS had non-ACS diagnoses. Improvements in pre-hospital time delays through public awareness programmes are warranted.

The impact of new evidence on regional variation in paediatric tonsillectomy and adenoidectomy: a historical review.

BACKGROUND: Tonsillectomy and adenoidectomy have been among the most commonly performed procedures in children for approximately 100 years. These procedures were the first for which unwarranted regional variation was discovered, in 1938. Indications for these procedures have become stricter over time, which might have reduced regional practice variation. METHODS: This paper presents a historical review on practice variation in paediatric tonsillectomy and adenoidectomy rates. Data on publication year, region, level of variation, methodology and outcomes were collected. RESULTS: Twenty-one articles on practice variation in paediatric tonsil surgery were included, with data from 12 different countries. Significant variation was found throughout the years, although a greater than 10-fold variation was observed only in the earliest publications. CONCLUSION: No evidence has yet been found that better indications for tonsillectomy and adenoidectomy have reduced practice variation. International efforts are needed to reconsider why we are still unable to tackle this variation.

Secondary cardiovascular prevention in clinical practice: what do we need today?

In the last decades, the post-hospital mortality from coronary artery disease (CAD) has significantly increased. This new trend in the epidemiology of CAD has been largely attributed to the improvement of survival from acute coronary syndromes that generated increasing incidence of population at high risk of recurrences and rehospitalization for major adverse cardiovascular events (MACE) and heart failure (HF). Thus, much longer after the acute event than we had thought, we have now been facing with higher complexity of "chronic" CAD phenotypes which deserve high clinical attention and more and more intricate pharmacological management. Although the guidelines recommend implementing secondary prevention programs through cardiac rehabilitation (CR) facilities in order to achieve a better outcome, i.e. decreased morbidity, re-hospitalization and increased adherence to evidence-based interventions, the referral rate to CR is paradoxically scarce. The Italian Association of Clinical Preventive Cardiology and Rehabilitation (AICPR) has been launching a survey involving the Network of Italian CR centers, which will make possible to observe trends, implement guidelines recommendations and then verify the effectiveness of the interventions and outcomes in post-acute and chronic CAD.

Challenges with study procedure fidelity when conducting household survey: reports from the field.

OBJECTIVES: The aim of the study was to identify reasons for protocol deviations during conduct of large epidemiological surveys despite training of field workers, validating clinicians, and providing field supervisory support. Enquiries focused on breaches of recruitment procedures, privacy, confidentiality, and informed consent. The case study was a household survey conducted in Ile-Ife, Nigeria. RESULTS: The study reveals that despite training of field workers, providing supervisory support, and conducting validation exercises, protocol deviation still occurred. Measures to improve internal research validity during the conduct of surveys can minimise but not eliminate protocol deviations. Individual and environmental factors increase the risk for protocol deviation. Individual factors include personal bias against adherence to elements of the protocols, and pressure to meet personal recruitment targets to maximise remuneration. These pressures increase the risk of breaching study participants' recruitment process. Environmental pressures resulted from low research literacy that made it possible for field workers not to consent participants and for participants not to prioritise privacy. The use of electronic data collection enhanced data security. A key recommendation from the study was that improved field supervision will reduce the risk for protocol violation.

Potential ethical pitfalls and dilemmas in the promotion and use of American Psychological Association-recommended treatments for posttraumatic stress disorder.

A variety of potential unrecognized ethical concerns arise from the American Psychological Association's (APA, 2017) Clinical Practice Guideline for the Treatment of PTSD in Adults. In privileging short-term treatments that underscore symptom reduction as the predominant index of outcome, such as cognitive processing therapy and prolonged exposure, there is a susceptibility to mislead mental health professionals and clients alike to believe that lasting improvements in socioemotional well-being, and a time-intensive approach, are unrealistic, rather than realistic psychotherapy expectations. There are ethical implications to incompletely addressing clients' preferences and clinicians' judgments on matters such as preferred socioemotional outcomes, and desirable qualities in a therapist and therapy. As regard combat veterans, treating trauma-related guilt and shame as symptoms to be eliminated, rather than moral feelings to be acknowledged, expressed, and self-forgiven, warrants special ethical consideration. The high dropout rates of cognitive processing therapy and prolonged exposure raise questions as to whether their protocol-driven methods alienate substantial numbers of traumatized clients. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Analysis of diagnosis announcements in Abidjan pediatric oncology unit 2 years after introduction of the African Pediatric Cancer Announcement Guideline.

INTRODUCTION: Announcing the diagnosis allows the therapeutic alliance between physicians and patients to be sealed and it prevents abandonment of treatment. To compensate for the deficit in information received by the families, the Franco-African Group of Pediatric Oncology (FAGPO) has published an "African Pediatric Cancer Announcement Guide" for the group's pediatric oncology units. OBJECTIVE: To analyze the announcements made to parents and children 2 years after the provision of this guide. METHODS: Cross-sectional survey conducted from March to July 2016. In total, 69 parents of children followed up in the pediatric oncology unit of Abidjan were interviewed regarding the characteristics of the announcement that was made to them and the information given to the sick child. RESULTS: Of all the accompanying individuals, 91% reported having benefited from the announcement made with empathy, mainly by a physician. In approximately one quarter of the cases the information had been given to a third party. The main barriers to information were: the negative experiences of parents, the medical terminology, and communication problems. The sick child was rarely informed. DISCUSSION: The information given was in accordance, in content and form, with the data from Western and African literature. The lack of information given to the child has a dual explanation: the primacy of the community over the individual advocated by African culture and the non-integration of the rights of children in the current code of ethics. CONCLUSION: The information provided could be improved by practical training of physicians in the technique of breaking bad news to patients and their families and the use of a code of ethics in accordance with the principle of autonomy.

Implementing a Central IRB Model in a Multicenter Research Network.

Implementing the National Institutes of Health's (NIH's) new single institutional review board (IRB) policy has caused a paradigm shift in IRB review across the country. IRBs and human research protection programs are looking more closely at their processes for ceding review and developing procedures to handle local review when relying on a single IRB. This article describes an NIH-funded network that proactively instituted a central IRB (CIRB) in 2012, anticipating the NIH future mandate. Lessons learned are described. There was a steep learning curve for IRBs and participating sites. IRB submission workload burden shifted from study teams to the data coordinating center, which created new workflow challenges, especially preparing hundreds of consent documents centrally. Despite difficulties encountered with CIRB review, this network is now fully functioning under a CIRB model. Further review and experience are needed to determine whether this shift in IRB review has eliminated duplicative review or regulatory burden from study teams.

Responsible data sharing in international health research: a systematic review of principles and norms.

BACKGROUND: Large-scale linkage of international clinical datasets could lead to unique insights into disease aetiology and facilitate treatment evaluation and drug development. Hereto, multi-stakeholder consortia are currently designing several disease-specific translational research platforms to enable international health data sharing. Despite the recent adoption of the EU General Data Protection Regulation (GDPR), the procedures for how to govern responsible data sharing in such projects are not at all spelled out yet. In search of a first, basic outline of an ethical governance framework, we set out to explore relevant ethical principles and norms. METHODS: We performed a systematic review of literature and ethical guidelines for principles and norms pertaining to data sharing for international health research. RESULTS: We observed an abundance of principles and norms with considerable convergence at the aggregate level of four overarching themes: societal benefits and value; distribution of risks, benefits and burdens; respect for individuals and groups; and public trust and engagement. However, at the level of principles and norms we identified substantial variation in the phrasing and level of detail, the number and content of norms considered necessary to protect a principle, and the contextual approaches in which principles and norms are used. CONCLUSIONS: While providing some helpful leads for further work on a coherent governance framework for data sharing, the current collection of principles and norms prompts important questions about how to streamline terminology regarding de-identification and how to harmonise the identified principles and norms into a coherent governance framework that promotes data sharing while securing public trust.

Management of postpartum hemorrhage in a rural hospital in Kenya: a best practice implementation project.

INTRODUCTION: Postpartum hemorrhage accounts for 34% of maternal deaths in Kenya. The World Health Organization guidelines on postpartum hemorrhage are not always followed despite being prominently promoted in hospitals. OBJECTIVES: The objectives of this study were to assess the current practice of health workers in the prevention and management of postpartum hemorrhage and to implement strategies to promote best practice. METHODS: A baseline audit with five evidence-based audit criteria was conducted using the Joanna Briggs Institute Practical Application of Clinical Evidence System. Strategies to improve compliance were implemented and a follow-up audit was carried out using the same data collection methods. Results of both audits were compared. RESULTS: The baseline audit showed that 90% of health workers were aware of the existence and location of the national guidelines. Almost two thirds (65%) of staff had received education on postpartum hemorrhage within the last two years. Only 30% had received specific training on the use of the guidelines and compliance with the guidelines was 0%. At the follow-up audit, the proportion of health workers who had received recent education on postpartum hemorrhage and specific training on the use of a protocol increased to 90%. The use and documentation of a protocol for postpartum hemorrhage increased to 100%. Compliance in prenatal risk assessment for postpartum hemorrhage decreased from 65% to 35%. CONCLUSIONS: Knowledge of the guidelines did not translate into their use during management of patients with postpartum hemorrhage. The introduction of a tool and staff education and training improved compliance.

The Accuracy and Perception of Test-Based Management of Malaria at Private Licensed Chemical Shops in the Middle Belt of Ghana.

The sale of artemisinin-based combination therapy (ACT) by private licensed chemical shops (LCS) without testing is contrary to current policy recommendations. This study assessed the accuracy and perception of test-based management of malaria using malaria rapid diagnostic test (mRDT) kits at private LCS in two predominantly rural areas in the middle part of Ghana. Clients presenting at LCS with fever or other signs and symptoms suspected to be malaria in the absence of signs of severe malaria were tested with mRDT by trained attendants and treated based on the national malaria treatment guidelines. Using structured questionnaires, exit interviews were conducted within 48 hours and a follow-up interview on day 7 (±3 days). Focus group discussions and in-depth interviews were also conducted to assess stakeholders' perception on the use of mRDT at LCS. About 79.0% (N = 1,797) of clients reported with a fever. Sixty-six percent (947/1,426) of febrile clients had a positive mRDT result. Eighty-six percent (815/947) of clients with uncomplicated malaria were treated with the recommended ACT. About 97.8% (790/808) of clients with uncomplicated malaria treated with ACT were reported to be well by day 7. However, referral for those with negative mRDT results was very low (4.1%, 27/662). A high proportion of clients with a positive mRDT result received the recommended malaria treatment. Test-based management of malaria by LCS attendants was found to be feasible and acceptable by the community members and other stakeholders. Successful implementation will however require effective referral, supervision and quality control systems.