Development and Delphi consensus validation of the Medication-Related Fall screening and scoring tool.

BACKGROUND: Falls are a significant public health problem and constitute a major cause of injuries and mortality. Risk factors for falls are multifactorial and include medication use. AIM: To develop and investigate the content validity of the Medication-Related fall (MRF) screening and scoring tool. METHOD: The MRF tool was developed from clinical practice guidelines addressing medication-related problems, and additional medications identified by specialist pharmacists across a region of the United Kingdom (Northern Ireland). Medication classes were categorised according to their 'potential to cause falls' as: high-risk (three points), moderate-risk (two points) or low-risk (one point). The overall medication-related falls risk for the patient was determined by summing the scores for all medications. The MRF was validated using Delphi consensus methodology, whereby three iterative rounds of surveys were conducted using SurveyMonkey®. Twenty-two experts from 10 countries determined their agreement with the falls risk associated with each medication on a 5-point Likert scale. Only medications with at least 75% of respondents agreeing or strongly agreeing were retained in the next round. RESULTS: Consensus was reached for 19 medications/medication classes to be included in the final version of the MRF tool; ten were classified as high-risk, eight as moderate-risk and one as low-risk. CONCLUSION: The MRF tool is simple and has the potential to be integrated into medicines optimisation to reduce falls risk and negative fall-related outcomes. The score from the MRF tool can be used as a clinical parameter to assess the need for medication review and clinical interventions.

Discrepancies Between the Electronic Medical Record and Website Access to the Prescription Drug Monitoring Program.

The US opioid crisis has affected many patients across the age spectrum. Yet little has been reported on the effects of this crisis on cancer patients. Prescription drug monitoring programs have emerged as potential tools to mitigate risks of opioid prescribing, but they are not without limitations. We present a case of missing opioid prescriptions on EMR integrated PDMP versus the web based PDMP. A full review of PDMP integration is needed to identify gaps as these pose a significant patient safety issue.

Physical and Psychosocial Symptoms of Young Adult Patients Referred to the Supportive Care Mobile Team.

Young adult (YA) aged cancer patients have unique psychosocial needs with studies indicating more symptoms and emotional distress compared to older patients. Our study aimed to compare clinical characteristics and symptom distress between YAs and older adults. We retrospectively studied 896 randomly selected patients across 3 age groups: 18-39 YAs (n = 297), 40-64 (n = 300), and 65 and older (n = 299). We compared medical, psychosocial history, Morphine Equivalent Daily Dose (MEDD), Edmonton Symptom Assessment Scale (ESAS) scores, and Eastern Cooperative Oncology Group (ECOG) scores at the time of initial inpatient consultation with supportive care. YAs were more frequently female and white, with higher ECOG scores, had more self-reported psychiatric history and worse ESAS sleep scores compared to the other age cohort groups. YAs had higher pain expression than those of 65 years and older. YAs were more likely to have children younger than 18 years old, which was associated with worse pain, sleep, and financial distress. In general, YAs did not report higher symptoms distress, with the exception of insomnia and self-reported psychiatric history. Importantly, YAs with children was associated with higher ratings of pain, sleep difficulties, and financial distress. Overall, results suggest YAs may benefit from specialized services to address their unique psychosocial needs.

Hyponatremia with Antidepressant: A Rare Side Effect from Duloxetine in a Child with Acute Leukemia.

Duloxetine is indicated for the treatment of chemotherapy-induced neuropathic pain in adults. It is also indicated for anxiety, depression, and fibromyalgia in children. A rare side effect of syndrome of inappropriate antidiuretic hormone (SIADH) secretion has been reported in adults, but not in pediatrics or pediatric oncology patients. We present the case of a 10-year-old child with acute lymphoblastic leukemia, who developed SIADH after duloxetine was given for chemotherapy-induced neuropathic pain and comorbid anxiety. The SIADH resolved after duloxetine was stopped. This case highlights a rare side effect of duloxetine and caution should be taken when prescribing duloxetine to children.

Pediatric Palliative Care Pharmacy Pearls-A Focus on Pain and Sedation.

Determining the optimal dosing regimen for pediatric patients is a challenge due to the lack of dosing guidelines and studies. In addition, many developmental pharmacology changes that occur throughout childhood that have profound impacts on the absorption, distribution, metabolism, and elimination of medications are commonly used in palliative care. Adding to that complexity, certain medications have different effects in the pediatric patient compared to the adult patient. Being aware of the pharmacokinetic changes, impact on neurodevelopment and unique medication factors that are present in pediatric patients helps clinicians treat the pediatric palliative care patient in the best and safest way possible.

Patterns of Storage, Use, and Disposal of Prescription Opioids by Young Adults with Cancer.

Studies have demonstrated that adults with cancer and parents of children with cancer do not use and store prescription opioids safely. Most YAs (135/146, 92%) unsafely stored opioids. Fifty-two of 146 patients (36%) unsafely used, and 16 of 146 patients (11%) unsafely disposed of opioids. YAs with hematologic malignancies (p < 0.05) were more likely to use opioids safely compared with YAs with other types of malignancies. More research is necessary to understand the scope of this issue. Our data suggest that universal educational interventions regarding the safe storage, use, and disposal of opioids are justified for YAs.

Frequency of Concomitant Use of Gabapentinoids and Opioids among Patients with Cancer-Related Pain at an Outpatient Palliative Care Clinic.

Background: Patients with cancer-related pain use opioids for nociceptive pain, while gabapentinoids are common to treat neuropathic pain. The simultaneous use of opioids with gabapentinoids has been associated with an increased risk of opioid-related death. Objectives: Determine the frequency of combined use of gabapentinoids among patients receiving opioids for cancer-related pain. We also examined if concomitant use of opioids and gabapentinoids together was associated with increased scores of fatigue and drowsiness on the Edmonton Symptom Assessment Scale (ESAS) compared to patients on opioids. Design: Retrospective study of patients on opioids and opioids plus gabapentinoids at their third visit to the outpatient Supportive Care Center. Results: We found that 48% (508/1059) of patients were on opioids. Of these patients, 51% (257/508) were on opioids only, and 49% (251/508) were on opioids plus gabapentinoids. The median (interquartile range [IQR]) morphine equivalent daily dose for patients on opioids was 75 (45, 138) mg, and opioids plus gabapentinoids was 68 (38, 150) mg (p = 0.94). The median (IQR) gabapentinoid equivalent daily dose was 900 (300, 1200) mg. The median (IQR) for ESAS-fatigue in patients on opioids was 5 (3, 7), and opioids plus gabapentinoids was 5 (3, 7) (p = 0.27). The median (IQR) for ESAS-drowsiness in patients on opioids was 3 (0, 5), and opioids plus gabapentinoids was 3 (0, 6) (p = 0.11). Conclusion: Almost 50% of advanced cancer patients receiving opioids for pain were exposed to gabapentinoids. Maximal efforts should be made to minimize potential complications from the concomitant use of opioids with gabapentinoids.

Clinically Significant Drug-Drug Interaction Between Methadone and Cannabidiol.

The use of cannabidiol products in pediatric patients is becoming more frequent because of the increased ease of accessibility. This case report illustrates the potential for cannabidiol to interact with stable medication regimens. A 13-year-old girl with metastatic cancer and chronic pain presented with increased sleepiness and fatigue. She had been started on 7.5 mg of methadone by mouth twice daily 4 months earlier. Unbeknownst to her physicians, her parents had commenced her on cannabidiol and subsequently increased the dose leading up to her presentation, thinking it would result in tumor shrinkage. The initial serum methadone level was 271 ng/mL, which decreased to 125 ng/mL 14 days after discontinuing cannabidiol. The reduced serum methadone level coincided with improved sleepiness and fatigue. Cannabidiol inhibits CYP3A4 and CYP2C19, both of which are involved in the metabolism of methadone. Pediatricians should be aware of this potential interaction and inquire if their patients are receiving cannabidiol.

Patterns of Storage, Use, and Disposal of Prescription Opioids by Parents of Children With Cancer.

CONTEXT: Multiple studies have demonstrated that adults do not store prescription opioids safely. Increased prescription opioid rates have led to an increased incidence of opioid poisonings in children and adolescents. OBJECTIVES: We investigated whether parents practiced safe storage, use, and disposal techniques of opioids that were prescribed to their child with cancer-related pain. METHODS: We conducted a prospective cross-sectional survey of parents whose children were prescribed opioids and asked them about their patterns of storage, use, and disposal of prescription opioids. RESULTS: Virtually, all parents (106 of 109; 97%) completed the survey. Most parents (95 of 106; 90%) did not store opioids safely. Six of 106 parents (6%) gave their child's opioid pain medication to someone else with pain, and three of 106 parents (3%) personally took some of their child's opioid. Parents who personally took their child's opioid (P = 0.01) or gave it to another person (P < 0.001) were more likely to use opioids unsafely with their child. A minority of parents (22 of 106; 21%) did not use opioids safely in their child. A small number of parents (3 of 22; 14%) did not dispose of opioids safely. CONCLUSION: Universal education about the safe use and disposal of opioids should be adopted when prescribing opioids. Pediatricians need to maintain vigilance about the nonmedical use of prescription opioid use by parents of children.

Corrected QT Interval Prolongation in Pediatric and Young Adult Patients on Methadone for Cancer-Related Pain.

CONTEXT: Methadone has been reported to prolong the corrected QT (QTc) interval and increase the risk of torsades de pointes. OBJECTIVES: Our study examined the frequency of QTc prolongation among pediatric and young adult patients starting methadone for cancer pain. METHODS: All patients followed a standardized protocol. Electrocardiograms (ECGs) were obtained at baseline (methadone starting day to 14 days prior), 1-2 weeks, and 4-6 weeks later. QTc values were manually calculated using the Bazett formula. QTc prolongation was defined as ≥460 milliseconds (ms) for prepubertal children, ≥470 ms for pubertal males, and ≥480 ms for pubertal females. RESULTS: Baseline ECGs were completed in 42 patients. Follow-up ECGs were completed in 38 of 42 (91%) and 31 of 42 (74%) patients at 1-2 weeks and 4-6 weeks, respectively. No patients had prolongation of the QTc at baseline, and 1 of 38 (3%) patients had a prolonged QTc at weeks 1-2. This patient had a history of prolonged QTc that the family did not initially report. No patients had prolongation of the QTc at weeks 4-6. No patients had torsades de pointes or ventricular fibrillation, and none died suddenly. Median (interquartile range [IQR]) baseline QTc was 391 (377-400) ms; median (IQR) 1-2 week follow-up QTc was 399 (374-411) ms (P = .05), and median (IQR) 4-6 week follow-up QTc was 393 (379-423) ms (P = .01). CONCLUSION: Clinically significant prolongation of the QTc interval occurred only in one patient who had a history of prolonged QTc. Prolonged QTc is rare in this population.

Systematic Symptom Reporting by Pediatric Palliative Care Patients with Cancer: A Preliminary Report.

Background: Systematic symptom assessment is not a standard of care in children with cancer. Many well-known symptom assessment tools are lengthy or difficult to integrate into a daily pediatric palliative care practice. We created a series of brief and simple questions to be systematically given to children and their caregivers. Objective: The primary objective was to determine the percentage of eligible children and caregivers exposed to the questions that were able to complete the assessment. Secondary objectives included documenting the symptom burden at the time of consultation, evaluating the level of agreement in symptom reporting between children and caregivers, as well as between children/caregivers and the referring medical team. Design: A series of systematic questions were presented to all caregivers (if present) and children who were seven years of age or older at the time of initial consultation with pediatric palliative care. Results: One hundred twenty-two consecutive children/caregiver dyads were given the survey. One hundred seven of 108 (99%) eligible caregivers and 83 of 97 (86%) eligible children completed the survey. Lack of appetite (child-72/83, 87%; caregiver-89/107, 83%) and pain (child-71/83, 86%; caregiver-86/107, 80%) were the most commonly reported symptoms. Caregivers reported irritability (p = 0.005) and nervousness (p < 0.001) more frequently than children. Referring medical teams significantly underdiagnosed psychological and other less clinically evident symptoms such as lack of appetite, fatigue, and sleep disturbance (p < 0.001). Conclusions: Our series of questions is easy to complete by children and caregivers. Systematic symptom assessment of children with cancer referred to palliative care should become a true standard of care.

Attitudes, Beliefs, and Practices of Pediatric Palliative Care Physicians Regarding the Use of Methadone in Children With Advanced Cancer.

CONTEXT: Methadone is a long-acting opioid known for its unique pharmacokinetic and pharmacodynamic properties. Most research on methadone in children is limited to its effect on the prolongation of the corrected QT (QTc) interval. OBJECTIVES: To better understand the attitudes, beliefs, and practices of pediatric palliative care physicians regarding the use of methadone in children with advanced cancer. METHODS: A survey was sent to the American Academy of Pediatrics Section of Hospice and Palliative Medicine LISTSERV. Information on demographics, dosing of methadone, and the use of electrocardiograms (ECGs) was collected. RESULTS: One-hundred and five respondents (91%) provide palliative care to children ≥ 50% of the time, and a majority (81, 77%) prescribe methadone. Most (62, 77%) physicians were board certified in Hospice and Palliative Medicine, and most (39, 63%) certified via the direct pathway ("grandfathering"). Most physicians (57, 70%) do not use loading doses of methadone. Board-certified physicians trended toward decreasing methadone dose more (40% ± 19%) than non-board-certified physicians (28%, ±20%) when changing from the oral to intravenous route (P = 0.07). Respondents defined a QTc interval as "prolonged" (mean ± SD) at 444 milliseconds (±68 milliseconds). The percentage of patients receiving a baseline ECG was 65% (±33%). The most common reason for not performing a baseline ECG was that the patient was on hospice (13, 36%). CONCLUSIONS: There are consistent practices, attitudes, and beliefs of pediatric palliative care providers with regard to methadone. More education is needed on the accurate value of a prolonged QTc interval.

Practices, Attitudes, and Beliefs of Palliative Care Physicians Regarding the Use of Methadone and Other Long-Acting Opioids in Children with Advanced Cancer.

BACKGROUND: Palliative care physicians often assist with pain management in children with cancer, but little is known about how they use long-acting opioids for chronic pain with these patients. OBJECTIVE: To determine the practices, attitudes, and beliefs of palliative care physicians toward the use of long-acting opioids in children with advanced cancer. DESIGN: An electronic survey was sent to all members of The American Academy of Pediatrics (AAP) Section of Hospice and Palliative Medicine (SOHPM) and those identified as physicians who provide palliative care to children on the AAP SOHPM LISTSERV®. RESULTS: The response rate to the survey was 62% (116/188). A majority (66% [77/116]) of physicians are board certified in both pediatrics and hospice and palliative medicine. This represents 28% of all board-certified pediatric palliative care physicians. Most palliative care physicians report comfort in using long-acting opioids in children (84-94%), with the exception of long-acting hydromorphone (37%). Physicians perceived methadone as least costly (3%) but associated it with a higher perceived family resistance (51%). As compared with pediatric palliative care fellowship-trained physicians, nonpediatric fellowship-trained physicians perceived titration of oxycodone ER and morphine ER to be easier (p = 0.06, p = 0.07) and less likely to agree that the main reason for starting methadone is that the existing formulations of other long-acting opioids are unsuitable for children (p = 0.05). CONCLUSIONS: Most physicians who provide palliative care to children are comfortable using opioids but there is significant variation in the level of comfort with different opioids. This information will be helpful in developing targeted education for palliative care providers.

Methadone as the Initial Long-Acting Opioid in Children with Advanced Cancer.

BACKGROUND: Methadone is an attractive medication for treating children with advanced cancer with pain as it is the only long-acting opioid available as a liquid. However, it is not frequently used due to concerns about potential toxicities and side effects. OBJECTIVE: Evaluate the efficacy and safety of methadone as the first long-acting opioid in children with advanced cancer. DESIGN: Retrospective chart review of 52 consecutive patients referred to Pediatric Supportive Care for pain management started on methadone as their first long-acting opioid. Data collected at baseline, follow-up visits #1 (F1) and #2 (F2) included child and parent-reported outcomes for various physical and psychological symptoms, opioid side effects and other clinical data. Symptoms were rated on a 0 (not at all) to 4 (a lot) scale. RESULTS: Pain (mean ± standard deviation [SD]) scored by the child was 3.6 (±0.6)/4 at baseline and 1.8 (±1.1)/4 at F1 (p < 0.0001). Compared to baseline, pain scored by the child at F2 was 1.2 (±1.3)/4 (p < 0.0001). Pain scored by the parent was 3.5 (±0.7)/4 at baseline and 1.4 (±1.3)/4 at F1 (p < 0.0001). Compared to baseline, pain scored by the parent at F2 was 1.0 (±1.2)/4 (p < 0.0001). Thirty-three (70%) patients at F1 and 23 (79%) patients at F2 did not need a change in dose of methadone. No cardiac arrhythmias or opioid neurotoxicity was observed. CONCLUSIONS: Initiation of methadone was effective and safe as the first long-acting opioid in children with pain.

Adolescent-young adults (AYA) with cancer seeking integrative oncology consultations: demographics, characteristics, and self-reported outcomes.

PURPOSE: Integrative Oncology (IO) consultations offer cancer patients counseling regarding complementary integrative medicine (CIM). We explored the CIM interests and symptom burden of AYA cancer patients presenting for an IO consultation. METHODS: Patients referred for an IO physician consultation at an academic medical center from September 1, 2009 to December 31, 2013 completed an assessment on presentation: MYCaW, ESAS (10 symptoms, 0-10, 10 worst possible), CIM use survey, and SF-12 QOL survey. We compared findings of AYA patients (ages 15-39) with a control sample of adult patients (age ≥ 40). RESULTS: Of the total 2474 consecutive patients, 286 (12%) were AYA, 73.1% female, with the most common diagnosis of breast cancer (30%). Areas of greatest interest for both AYA and adult patients included developing a holistic approach, herbals, and diet, with no significant difference between groups. Comparing groups, AYA patients had significantly higher anxiety (3.4 vs 3.1, p = 0.042). AYA physical health was significantly higher (37.5 vs 35, p = 0.001), with no significant between group differences in mental health. AYA patients were more likely to have participated in yoga (22 vs 11%, p = 0.001) and pilates (9.2 vs 4.5%, p = 0.04), with no significant difference regarding overall CIM use. Differences persisted after correcting for stage. CONCLUSION: AYA patients make up a small number of overall referrals to an IO consultation, presenting with a low to moderate symptom burden. Physical CIM interventions such as yoga and pilates are of greater interest to the AYA population, suggesting the importance of making such interventions available in cancer programs serving this population.

Very-Low-Dose Methadone To Treat Refractory Neuropathic Pain in Children with Cancer.

BACKGROUND: Compared with nociceptive pain, neuropathic pain is a challenging diagnosis to make and successfully treat in children with cancer. OBJECTIVE: The objective of this case report was to see whether very-low-dose methadone (VLDM) (defined as <50% of accepted starting analgesic dose of methadone for children) would be an effective strategy to treat refractory neuropathic pain due to vincristine in two children with acute lymphoblastic leukemia. METHODS: This case report is based on the clinical experience and parent-reported outcomes of two children with refractory neuropathic pain who received VLDM. RESULTS: Based on parent/caregiver-reported outcome scores over a one-year period, both children's refractory neuropathic pain syndrome was successfully treated with the addition of VLDM to their pre-existing regimen of gabapentin. Neither child suffered any adverse effects from methadone. CONCLUSIONS: VLDM shows promise as an effective, safe, and inexpensive way to treat refractory neuropathic pain in children with cancer.

The frequency of QTc prolongation among pediatric and young adult patients receiving methadone for cancer pain.

INTRODUCTION: A prolonged corrected QT (QTc) interval in pediatric patients is defined as ≥470 msec. Methadone can cause a prolonged QTc interval that can lead to ventricular arrhythmias. The risk of methadone-induced prolongation of the QTc interval in children and young adults is unknown. The purpose of the study was to determine the frequency of QTc prolongation among pediatric and young adult patients with cancer pain on methadone treatment. METHODS: We retrospectively reviewed data for all patients on methadone during the study period. Qualifying patient data were reviewed to determine whether these patients had an electrocardiogram (ECG) while on methadone. The QTc values for analysis were manually calculated using the standard formula described by Bazett. RESULTS: Twenty-five patients were identified that met eligibility criteria. The median QTc decreased from baseline after initiation of methadone. QTc prolongation occurred in four of 25 (16%) patients and only one patient had a QTc greater than 500 msec. This patient had 17 normal QTc intervals on methadone prior to the prolongation. After resolution of electrolyte abnormalities, six subsequent ECGs on methadone had a normal QTc interval. CONCLUSIONS: Prolongation of the QTc interval is infrequent. The only observed case was transient during multiple comorbid conditions. A prospective study is justified to better understand what role methadone plays as one of many risk factors for prolongation of the QTc interval in children and young adults.

Pediatric Palliative Care in the Intensive Care Unit.

The chronicity of illness that afflicts children in Pediatric Palliative Care and the medical technology that has improved their lifespan and quality of life make prognostication extremely difficult. The uncertainty of prognostication and the available medical technologies make both the neonatal intensive care unit and the pediatric intensive care unit locations where many children will receive Pediatric Palliative Care. Health care providers in the neonatal intensive care unit and pediatric intensive care unit should integrate fundamental Pediatric Palliative Care principles into their everyday practice.

Recurrent delirium after surgery for congenital heart disease in an infant.

OBJECTIVE: The objective of this article is to describe a case of recurrent delirium after cardiac surgery in an infant. DESIGN: Case report. The institutional review board at Children's Hospital Los Angeles waived the need for informed consent. SETTING: Cardiothoracic intensive care unit in a freestanding children's hospital. PATIENT: A male infant with hypoplastic left heart syndrome who developed delirium on consecutive admissions to the cardiothoracic intensive care unit after cardiac surgery. INTERVENTION: Pharmacologic intervention using the atypical antipsychotic olanzapine. MEASUREMENTS AND MAIN RESULTS: The symptoms of delirium resolved with the initiation and continuation of olanzapine on both occasions. CONCLUSION: Delirium is a common, but often unrecognized, diagnosis in the intensive care unit. Its early recognition and treatment may prevent unnecessary use of narcotics and benzodiazepines, decrease length of stay and may improve long-term neurocognitive function. This case report describes an infant who developed discrete, consecutive episodes of delirium following surgery for congenital heart disease. Both episodes were treated effectively with olanzapine.

An integrative expression vector for Actinosynnema pretiosum.

BACKGROUND: The Actinomycete Actinosynnema pretiosum ssp. auranticum has commercial importance due to its production of ansamitocin P-3 (AP-3), a potent antitumor agent. One way to increase AP-3 production would be to constitutively express selected genes so as to relieve bottlenecks in the biosynthetic pathway; however, an integrative expression vector for A. pretiosum is lacking. The aim of this study was to construct a vector for heterologous gene expression in A. pretiosum. RESULTS: A series of integrative expression vectors have been made with the following features: the IS117 transposase from Streptomyces coelicolor, the constitutive ermE* promoter from Saccharopolyspora erythraea, different ribosome-binding site (RBS) sequences and xylE as a translational reporter. Positive E. coli clones and A. pretiosum transconjugants were assayed by catechol. pAP42, containing an E. coli consensus RBS, and pAP43, containing an asm19 RBS, gave strong and moderate gene expression, respectively. In addition, an operon construct capable of multi-gene expression was created. Plasmid integration sites in transconjugants were investigated and four different sites were observed. Although the most common integration site was within a putative ORF with sequence similarity to NADH-flavin reductase, AP-3 levels and cell growth of transconjugants were unaffected. CONCLUSION: A set of integrative vectors for constitutive gene expression in A. pretiosum has been constructed. Gene translation is easily determined by colorimetric assay on an agar plate. The vectors are suitable for studies relating to AP-3 biosynthesis as they do not affect AP-3 production.