Treatment of breakthrough and prevention of refractory chemotherapy-induced nausea and vomiting in pediatric cancer patients: Clinical practice guideline update.

This clinical practice guideline update provides recommendations for treating breakthrough chemotherapy-induced nausea and vomiting (CINV) and preventing refractory CINV in pediatric patients. Two systematic reviews of randomized controlled trials in adult and pediatric patients informed the recommendations. In patients with breakthrough CINV, escalation of antiemetic agents to those recommended for chemotherapy of the next higher level of emetogenic risk is strongly recommended. A similar recommendation to escalate therapy is made to prevent refractory CINV in patients who did not experience complete breakthrough CINV control and are receiving minimally or low emetogenic chemotherapy. A strong recommendation to use antiemetic agents that controlled breakthrough CINV for the prevention of refractory CINV is also made.

Prevention of acute and delayed chemotherapy-induced nausea and vomiting in pediatric cancer patients: A clinical practice guideline.

This clinical practice guideline provides recommendations for preventing acute and delayed phase chemotherapy-induced nausea and vomiting (CINV) in pediatric patients. The recommendations are based on two systematic reviews of randomized controlled trials evaluating interventions to prevent (1) acute phase CINV and (2) delayed phase CINV. Recommendations for acute phase and delayed phase CINV prophylaxis are made for patients receiving chemotherapy of varying emetogenicity, as well as for patients not able to receive dexamethasone or a neurokinin-1 receptor antagonist. Evidence gaps, including antiemetic safety and optimal dosing, were identified.

Interventions for the prevention of acute phase chemotherapy-induced nausea and vomiting in adult and pediatric patients: a systematic review and meta-analysis.

PURPOSE: To identify effective and safe interventions to prevent acute phase chemotherapy-induced nausea and vomiting (CINV) in adult and pediatric patients. METHODS: We conducted a systematic review of randomized trials evaluating interventions to prevent acute CINV. Outcomes assessed were complete chemotherapy-induced vomiting (CIV) control, complete chemotherapy-induced nausea (CIN) control, complete CINV control, and discontinuation of antiemetics due to adverse effects. RESULTS: The search identified 65,172 citations; 744 were evaluated at full-text, and 295 (25 pediatric) met eligibility criteria. In patients receiving highly emetogenic chemotherapy (HEC), complete CIV (risk ratio (RR) 1.23, 95% confidence interval (CI) 1.05-1.44) and CIN (RR 1.34, 95% CI 1.10-1.62) control improved when olanzapine was added. The addition of a neurokinin-1 receptor antagonist (NK1RA) to a corticosteroid plus a serotonin-3 receptor antagonist (5HT3RA) also improved complete CIV (RR 1.11, 95% CI 1.08-1.14) and CIN (RR 1.05, 95% CI 1.01-1.08) control. Compared to granisetron/ondansetron, palonosetron provided improved complete CIV control when the 5HT3RA was given alone or when combined with dexamethasone. In patients receiving moderately emetogenic chemotherapy (MEC), dexamethasone plus a 5HT3RA improved complete CIV control compared to a 5HT3RA alone (RR 1.29, 95% CI 1.21-1.39). Only a single meta-analysis evaluating the safety outcome was possible. CONCLUSIONS: For patients receiving HEC, various antiemetic regimens improved CIV and CIN control. For patients receiving MEC, administration of a 5HT3RA plus dexamethasone improved CIV control. Analysis of antiemetic safety was constrained by lack of data.

Prevention and treatment of anticipatory chemotherapy-induced nausea and vomiting in pediatric cancer patients and hematopoietic stem cell recipients: Clinical practice guideline update.

This 2021 clinical practice guideline update provides recommendations for preventing anticipatory chemotherapy-induced nausea and vomiting (CINV) in pediatric patients. Recommendations are based on systematic reviews that identified (1) if a history of acute or delayed CINV is a risk factor for anticipatory CINV, and (2) interventions for anticipatory CINV prevention and treatment. A strong recommendation to optimize acute and delayed CINV control in order to prevent anticipatory CINV is made. Conditional recommendations are made for hypnosis, systematic desensitization, relaxation techniques, and lorazepam for the secondary prevention of anticipatory CINV. No recommendation for the treatment of anticipatory CINV can be made.

Classification of the acute emetogenicity of chemotherapy in pediatric patients: A clinical practice guideline.

This clinical practice guideline (CPG) provides clinicians with recommendations regarding chemotherapy emetogenicity classification in pediatric oncology patients. This information is critically important for the appropriate selection of antiemetic prophylaxis. Recommendations are based on a systematic review limited to pediatric patients and a framework for classification when antiemetic prophylaxis is provided. Findings of 87 publications informed the emetogenicity classification of 49 single-agent and 13 combination-agent regimens. Information required for the classification of many chemotherapies commonly administered to pediatric patients is lacking. In the absence of pediatric data, consultation of methodologically sound CPGs aimed at adult oncology patients may be appropriate.

Guideline for the prevention of acute chemotherapy-induced nausea and vomiting in pediatric cancer patients: A focused update.

This update of the 2013 clinical practice guideline provides clinicians with guidance regarding the use of aprepitant and palonosetron for the prevention of acute chemotherapy-induced nausea and vomiting (CINV) in children. The recommendations were based on three systematic reviews. Substantive changes were made to the guideline recommendations including the inclusion of palonosetron to the 5-HT3 antagonists recommended for children receiving highly emetogenic chemotherapy (HEC) and the recommendation of aprepitant for children 6 months of age or older receiving HEC. To optimize CINV control in children, future work must focus on closing critical research gaps.

Disclosing neuroimaging incidental findings: a qualitative thematic analysis of health literacy challenges.

BACKGROUND: Returning neuroimaging incidental findings (IF) may create a challenge to research participants' health literacy skills as they must interpret and make appropriate healthcare decisions based on complex radiology jargon. Disclosing IF can therefore present difficulties for participants, research institutions and the healthcare system. The purpose of this study was to identify the extent of the health literacy challenges encountered when returning neuroimaging IF. We report on findings from a retrospective survey and focus group sessions with major stakeholders involved in disclosing IF. METHODS: We surveyed participants who had received a radiology report from a research study and conducted focus groups with participants, parents of child participants, Institutional Review Board (IRB) members, investigators and physicians. Qualitative thematic analyses were conducted using standard group-coding procedures and descriptive summaries of health literacy scores and radiology report outcomes are examined. RESULTS: Although participants reported high health literacy skills (m = 87.3 on a scale of 1-100), 67 % did not seek medical care when recommended to do so; and many participants in the focus groups disclosed they could not understand the findings described in their report. Despite their lack of understanding, participants desire to have information about their radiology results, and the investigators feel ethically inclined to return findings. CONCLUSIONS: The language in clinically useful radiology reports can create a challenge for participants' health literacy skills and has the potential to negatively impact the healthcare system and investigators conducting imaging research. Radiology reports need accompanying resources that explain findings in lay language, which can help reduce the challenge caused by the need to communicate incidental findings.

Guideline for the Treatment of Breakthrough and the Prevention of Refractory Chemotherapy-Induced Nausea and Vomiting in Children With Cancer.

This clinical practice guideline provides an approach to the treatment of breakthrough chemotherapy-induced nausea and vomiting (CINV) and the prevention of refractory CINV in children. It was developed by an international, interprofessional panel and is based on systematic literature reviews. Evidence-based interventions for the treatment of breakthrough and prophylaxis of refractory CINV are recommended. Gaps in the evidence used to support the recommendations made in this clinical practice guideline were identified. The contribution of these recommendations to breakthrough and refractory CINV control in children requires prospective evaluation.

Evolution of universal review and disclosure of MRI reports to research participants.

BACKGROUND: Although incidental findings (IF) are commonly encountered in neuroimaging research, there is no consensus regarding what to do with them. Whether researchers are obligated to review scans for IF, or if such findings should be disclosed to research participants at all, is controversial. Objective data are required to inform reasonable research policy; unfortunately, such data are lacking in the published literature. This manuscript summarizes the development of a radiology review and disclosure system in place at a neuroimaging research institute and its impact on key stakeholders. METHODS: The evolution of a universal radiology review system is described, from inception to its current status. Financial information is reviewed, and stakeholder impact is characterized through surveys and interviews. RESULTS: Consistent with prior reports, 34% of research participants had an incidental finding identified, of which 2.5% required urgent medical attention. A total of 87% of research participants wanted their magnetic resonance imaging (MRI) results regardless of clinical significance and 91% considered getting an MRI report a benefit of study participation. A total of 63% of participants who were encouraged to see a doctor about their incidental finding actually followed up with a physician. Reasons provided for not following-up included already knowing the finding existed (14%), not being able to afford seeing a physician (29%), or being reassured after speaking with the institute's Medical Director (43%). Of those participants who followed the recommendation to see a physician, nine (38%) required further diagnostic testing. No participants, including those who pursued further testing, regretted receiving their MRI report, although two participants expressed concern about the excessive personal cost. The current cost of the radiology review system is about $23 per scan. CONCLUSIONS: It is possible to provide universal radiology review of research scans through a system that is cost-effective, minimizes investigator burden, and does not overwhelm local healthcare resources.

Risk-based strategy for outpatient pharmacy practice: Focus on opioids.

OBJECTIVES: To highlight the limitations of community pharmacy practice and to propose a system change by implementing a risk-assessment method and management strategy for opioids in this arena. DATA SOURCES: Selected by the author. SUMMARY: Numerous studies show that the U.S. health care system is subject to a high rate of drug misadventures involving primarily low therapeutic index drugs, especially opioids. Currently proposed approaches to managing opioids focus on access control, but without a broader consideration of patient-use problems that lead to morbidity and mortality. While pharmacists are well-trained health professionals, their primary focus has been on drug distribution rather than proper use. This article highlights the limitations in contemporary community pharmacy practice that likely contribute to the problem of opioid misuse and resultant morbidity. CONCLUSION: A new model of practice is proposed whereby the most dangerous agents such as opioids are preidentified for a more formalized risk-based strategy focused upon optimal patient education and required follow-up.

'Ethical responsibility' or 'a whole can of worms': differences in opinion on incidental finding review and disclosure in neuroimaging research from focus group discussions with participants, parents, IRB members, investigators, physicians and community members.

PURPOSE: To identify the specific needs, preferences and expectations of the stakeholders impacted by returning neuroimaging incidental findings to research participants. METHODS: Six key stakeholder groups were identified to participate in focus group discussions at our active neuroimaging research facility: Participants, Parents of child participants, Investigators, Institutional Review Board (IRB) Members, Physicians and Community Members. A total of 151 subjects attended these discussions. Transcripts were analysed using principles of Grounded Theory and group consensus coding. RESULTS: A series of similar and divergent themes were identified across our subject groups. Similarities included beliefs that it is ethical for researchers to disclose incidental findings as it grants certain health and emotional benefits to participants. All stakeholders also recognised the potential psychological and financial risks to disclosure. Divergent perspectives elucidated consistent differences between our 'Participant' subjects (Participants, Parents, Community Members) and our 'Professional' subjects (IRB Members, Investigators and Physicians). Key differences included (1) what results should be reported, (2) participants' autonomous right to research information and (3) the perception of the risk-benefit ratio in managing results. CONCLUSIONS: Understanding the perceived impact on all stakeholders involved in the process of disclosing incidental findings is necessary to determine appropriate research management policy. Our data further demonstrate the challenge of this task as different stakeholders evaluate the balance between risk and benefit related to their unique positions in this process. These findings offer some of the first qualitative insight into the expectations of the diverse stakeholders affected by incidental finding disclosure.

Root Cause Analysis Design and Its Application to Pharmacy Education.

Objective. To evaluate third-year pharmacy students' ability to effectively design and apply root cause analysis (RCA) to a sentinel event and to analyze student responses for areas of proficiency and deficiency. Methods. This study involved a comprehensive review of RCA key assessments from 82 students in spring 2014. The performance assessments consisted of a review of each student's RCA worksheet and flow diagram as well as the 1-2 page narrative reflection. Results. The majority of students were able to successfully design an RCA, but had challenges with 3 components: fact-finding session, disclosure plan, and a flow diagram. Several students perceived challenges to conducting a formal RCA in certain health care settings, which included assembling an RCA team and gathering relevant facts, a lack of transparency/safe environment within organizations, and creating a plan for multiple/sequential errors. Conclusion. Most students were able to design an RCA process, but encountered difficulty with some components. Students also identified challenges in applying the approach in certain health care arenas.

Stakeholder Opinions And Ethical Perspectives Support Complete Disclosure Of Incidental Findings In MRI Research.

How far does a researcher's responsibility extend when an incidental finding is identified? Balancing pertinent ethical principles such as beneficence, respect for persons, and duty to rescue is not always straightforward, particularly in neuroimaging research where empirical data that might help guide decision-making is lacking. We conducted a systematic survey of perceptions and preferences of 396 investigators, research participants and IRB members at our institution. Using the partial entrustment model as described by Richardson, we argue that our data supports universal reading by a neuroradiologist of all research MRI scans for incidental findings and providing full disclosure to all participants.

Guideline for the prevention and treatment of anticipatory nausea and vomiting due to chemotherapy in pediatric cancer patients.

This guideline provides an approach to the prevention and treatment of anticipatory chemotherapy-induced nausea and vomiting (CINV) in children. It was developed by an international, inter-professional panel using AGREE II methods and is based on systematic literature reviews. Evidence-based recommendations for pharmacological and non-pharmacological interventions to prevent and treat anticipatory CINV in children receiving antineoplastic agents are provided. Gaps in the evidence used to support the recommendations are identified. The contribution of this guideline to anticipatory CINV control in children requires prospective evaluation.

Evidence of psittacine beak and feather disease virus spillover into wild critically endangered Orange-bellied Parrots (Neophema chrysogaster).

We report the recent emergence of a novel beak and feather disease virus (BFDV) genotype in the last remaining wild population of the critically endangered Orange-bellied Parrot (Neophema chrysogaster). This virus poses a significant threat to the recovery of the species and potentially its survival in the wild. We used PCR to detect BFDV in the blood of three psittacine beak and feather disease (PBFD)-affected wild Orange-bellied Parrot fledglings captured as founders for an existing captive breeding recovery program. Complete BFDV genome sequence data from one of these birds demonstrating a 1,993-nucleotide-long read encompass the entire circular genome. Maximum-likelihood (ML) and neighbor-joining (NJ) phylogenetic analysis supported the solitary position of this viral isolate in a genetically isolated branch of BFDV. On Rep gene sequencing, a homologous genotype was present in a second wild orange-bellied parrot and the third bird was infected with a distantly related genotype. These viruses have newly appeared in a population that has been intensively monitored for BFDV for the last 13 yr. The detection of two distinct lineages of BFDV in the remnant wild population of Orange-bellied Parrots, consisting of fewer than 50 birds, suggests a role for other parrot species as a reservoir for infection by spillover into this critically endangered species. The potential for such a scenario to contribute to the extinction of a remnant wild animal population is supported by epidemiologic theory.

Mutability dynamics of an emergent single stranded DNA virus in a naïve host.

Quasispecies variants and recombination were studied longitudinally in an emergent outbreak of beak and feather disease virus (BFDV) infection in the orange-bellied parrot (Neophema chrysogaster). Detailed health monitoring and the small population size (<300 individuals) of this critically endangered bird provided an opportunity to longitudinally track viral replication and mutation events occurring in a circular, single-stranded DNA virus over a period of four years within a novel bottleneck population. Optimized PCR was used with different combinations of primers, primer walking, direct amplicon sequencing and sequencing of cloned amplicons to analyze BFDV genome variants. Analysis of complete viral genomes (n = 16) and Rep gene sequences (n = 35) revealed that the outbreak was associated with mutations in functionally important regions of the normally conserved Rep gene and immunogenic capsid (Cap) gene with a high evolutionary rate (3.41×10(-3) subs/site/year) approaching that for RNA viruses; simultaneously we observed significant evidence of recombination hotspots between two distinct progenitor genotypes within orange-bellied parrots indicating early cross-transmission of BFDV in the population. Multiple quasispecies variants were also demonstrated with at least 13 genotypic variants identified in four different individual birds, with one containing up to seven genetic variants. Preferential PCR amplification of variants was also detected. Our findings suggest that the high degree of genetic variation within the BFDV species as a whole is reflected in evolutionary dynamics within individually infected birds as quasispecies variation, particularly when BFDV jumps from one host species to another.

Current approaches to punitive action for medication errors by boards of pharmacy.

BACKGROUND: To increase disclosure of errors and lead to system improvements, publications recommend a nonpunitive approach to medication errors. To our knowledge there is no published information regarding the extent or bases on which boards of pharmacy invoke punitive action against pharmacists involved in medication errors. OBJECTIVE: To determine how often and on what bases boards of pharmacy determine punitive action to be taken against pharmacists involved in medication error events. METHODS: The policies, procedures, and practices regarding medication errors by pharmacists for 49 of the 50 US boards of pharmacy were reviewed by pharmacy students at the University of New Mexico as a Safe Medication Practices class assignment. RESULTS: Most boards of pharmacy invoke punitive action against pharmacists involved in medication errors. Most states do not have specific rules or regulations that stipulate errors as actual violations and most determinations are made on a case-by-case basis. The major determinants of punitive action were error severity, actual patient injury, patient complaints, and factors related to the pharmacist. The most common types of punitive action include license suspension, probation, or revocation, and fines. In at least 17 states, incarceration was also a possible punitive action. The most common bases for punitive action were to address public safety/health and public complaints. CONCLUSIONS: Despite the fact that punitive action is not recommended as best practice for addressing medication errors made by health care practitioners, most state boards of pharmacy use punitive measures against pharmacists involved in medication errors. Based on current recommendations, such actions would not be expected to lead to improvements in the health care system.

Guideline for the prevention of acute nausea and vomiting due to antineoplastic medication in pediatric cancer patients.

This guideline provides an approach to the prevention of acute antineoplastic-induced nausea and vomiting (AINV) in children. It was developed by an international, inter-professional panel using AGREE and CAN-IMPLEMENT methods. Evidence-based interventions that provide optimal AINV control in children receiving antineoplastic agents of high, moderate, low, and minimal emetogenicity are recommended. Recommendations are also made regarding selection of antiemetic agents for children who are unable to receive corticosteroids for AINV control, the role of aprepitant and optimal doses of antiemetic agents. Gaps in the evidence used to support the recommendations were identified. The contribution of this guideline to AINV control in children requires prospective evaluation.

Reduction of methyl isothiocyanate atmospheric emissions after application of metam sodium by shank injection.

Regulatory initiatives in the United States have created the impetus to reassess application methods for metam sodium (sodium -methyldithiocarbamate), a methyl isothiocyanate (MITC) generator, to reduce flux to the atmosphere. This paper compares flux rates in the years 1990 through 2002 with flux rates based on four studies conducted during the period 2008 through 2010 in California, Michigan, Wisconsin, and Washington using current shank-injection/compaction methods. Up to a 100-fold reduction in peak flux rates and total loss of MITC have been observed. A combination of the following factors led to these reductions in flux: soil moisture goals set at 70% of the field water holding capacity; improved design of shank-injection systems to break up the voids after injection; effective shank compaction to further reduce volatilization; and the use of water sealing, where applicable. These refinements in the application methods for metam sodium provide a means to merge environmental and agricultural goals in the United States and in other countries that use metam sodium. This paper documents the reduced atmospheric emissions of MITC under commercial production conditions when applied using good agricultural practices. This research also shows that MITC flux can be effectively managed without the use of high barrier tarp material.

Deep-vein thrombosis: a United States cost model for a preventable and costly adverse event.

Preventable venous thromboembolism (VTE) and "appropriate" type, dose, and duration of prophylaxis are emerging concepts. Contemporary definitions by key quality organisations, including the World Health Organization, have shifted towards "preventable" VTE being considered an adverse event or adverse drug event. A decision tree and cost model were developed to estimate the United States health care costs for total deep-vein thrombosis (DVT), total hospital-acquired DVT, and total "preventable" DVT. Annual cost ranges were obtained in 2010 US dollars for total ($7.5 to $39.5 billion), hospital-acquired ($5 to $26.5 billion), and preventable ($2.5 to $19.5 billion) DVT costs. When the sensitivity analysis was applied--taking into consideration higher incidence rates and costs - annual US total, hospital-acquired, and "preventable" DVT costs ranged from $9.8 to $52 billion, $6.8 to $36 billion, and $3.4 to $27 billion, respectively.