What influences physician opioid prescribing for children with acute pain?

Background: Pain is one of the most common symptoms encountered in the healthcare system, and opioids are among the top three medications used to treat it. Understanding the reasoning behind physicians' opioid prescribing practices is vital to safe practice. The primary objective of our study was to describe pediatric emergency physicians' decision-making process when prescribing opioids for children's acute pain management. Methods: This study employed qualitative methodology, using one-on-one semi-structured interviews within a grounded theory analytic framework. We employed purposeful sampling to recruit pediatric emergency physicians from across Canada. Interviews were conducted by telephone (December 2019-January 2021). Transcript analysis occurred concurrently with data collection, supporting data saturation and theory development considerations. Results: Eleven interviews were completed with participants representing each of Canada's geographic regions. Nine major themes emerged: (1) practice setting and outpatient opioid use, (2) condition-specific considerations, (3) physician confidence in medical evidence, (4) pain assessment challenges, (5) patient and family perspectives, (6) opioid safety concerns, (7) personal biases and experiences, (8) personal practice context, and (9) the Opioid Crisis/media influence. Most clinicians felt that they limited opioid use to those who needed it most; all participants described challenges managing acute pain, emphasizing the need for accurate pain measurement and better guidelines, evidence-based data, and knowledge translation. Clinicians were more comfortable treating pain in the emergency department, compared to discharge prescribing. They recognized the importance of co-therapy with non-opioids and the need for opioid risk assessment when prescribing. A family centered approach was recognized as the goal of practice. Conclusion: Clinicians are less comfortable prescribing opioids to children for at-home use and find pain assessment and lack of clear guidelines to be barriers to pain care. Knowledge translation strategies for safer practice and optimal acute pain management could support responsible and judicious opioid use.

A two-centre survey of caregiver perspectives on opioid use for children's acute pain management.

BACKGROUND: Given the current opioid crisis, caregivers have mounting fears regarding the use of opioid medication in their children. We aimed to determine caregivers' a) willingness to accept, b) reasons for refusing, and c) past experiences with opioids. METHODS: A novel electronic survey of caregivers of children aged 4 to 16 years who had an acute musculoskeletal injury and presented to two Canadian paediatric emergency departments (ED) (March to November 2017). Primary outcome was caregiver willingness to accept opioids for moderate pain for their children. RESULTS: Five hundred and seventeen caregivers participated; mean age was 40.9 (SD 7.1) years with 70.0% (362/517) mothers. Children included 62.2% (321/516) males with a mean age of 10.0 (SD 3.6) years. 49.6% of caregivers (254/512) reported willingness to accept opioids for ongoing moderate pain in the ED, while 37.1% (190/512) were 'unsure'; 33.2% (170/512) of caregivers would accept opioids for at-home use, but 45.5% (233/512) were 'unsure'. Caregivers' primary concerns were side effects, overdose, addiction, and masking of diagnosis. Caregiver fear of addiction (odds ratio [OR] 1.12, 95% confidence interval [CI] 1.01 to 1.25) and side effects (OR 1.25, 95% CI 1.11 to 1.42) affected willingness to accept opioids in the emergency department; fears of addiction (OR 1.19, 95% CI 1.07 to 1.32), and overdose (OR 1.15, 95% CI 1.04 to 1.27) affected willingness to accept opioids for at-home use. CONCLUSIONS: Only half of the caregivers would accept opioids for moderate pain, despite ongoing pain following nonopioid analgesics. Caregivers' fears of addiction, side effects, overdose, and masking diagnosis may have influenced their responses. These findings are a first step in understanding caregiver analgesic decision making.

Sensitive detection of Cre-mediated recombination using droplet digital PCR reveals Tg(BGLAP-Cre) and Tg(DMP1-Cre) are active in multiple non-skeletal tissues.

In humans, somatic activating mutations in PIK3CA are associated with skeletal overgrowth. In order to determine if activated PI3K signaling in bone cells causes overgrowth, we used Tg(BGLAP-Cre) and Tg(DMP1-Cre) mouse strains to somatically activate a disease-causing conditional Pik3ca allele (Pik3caH1047R) in osteoblasts and osteocytes. We observed Tg(BGLAP-Cre);Pik3caH1047R/+ offspring were born at the expected Mendelian frequency. However, these mice developed cutaneous lymphatic malformations and died before 7 weeks of age. In contrast, Tg(DMP1-Cre);Pik3caH1047R/+ offspring survived and had no cutaneous lymphatic malformations. Assuming that Cre-activity outside of the skeletal system accounted for the difference in phenotype between Tg(BGLAP-Cre);Pik3caH1047R/+ and Tg(DMP1-Cre);Pik3caH1047R/+ mice, we developed sensitive and specific droplet digital PCR (ddPCR) assays to search for and quantify rates of Tg(BGLAP-Cre)- and Tg(DMP1-Cre)-mediated recombination in non-skeletal tissues. We observed Tg(BGLAP-Cre)-mediated recombination in several tissues including skin, muscle, artery, and brain; two CNS locations, hippocampus and cerebellum, exhibited Cre-mediated recombination in >5% of cells. Tg(DMP1-Cre)-mediated recombination was also observed in muscle, artery, and brain. Although we cannot preclude that differences in phenotype between mice with Tg(BGLAP-Cre)- and Tg(DMP1-Cre)-mediated PIK3CA activation are due to Cre-recombination being induced at different stages of osteoblast differentiation, differences in recombination at non-skeletal sites are the more likely explanation. Since unanticipated sites of recombination can affect the interpretation of data from experiments involving conditional alleles, we recommend ddPCR as a good first step for assessing efficiency, leakiness, and off-targeting in experiments that employ Cre-mediated or Flp-mediated recombination.

Ocular Manifestations of Chordin-like 1 Knockout Mice.

PURPOSE: In humans, loss-of-function mutations in the gene encoding Chordin-like 1 (CHRDL1) cause X-linked megalocornea (MGC1), characterized by bilateral corneal enlargement, decreased corneal thickness, and increased anterior chamber depth (ACD). We sought to determine whether Chrdl1 knockout (KO) mice would recapitulate the ocular findings found in patients with MGC1. METHODS: We generated mice with a Chrdl1 KO allele and confirmed that male Chrdl1 hemizygous KO mice do not express Chrdl1 mRNA. We examined the eyes of male mice that were hemizygous for either the wild-type (WT) or KO allele and measured corneal diameter, corneal area, corneal thickness, endothelial cell density, ACD, tear volume, and intraocular pressure. We also harvested retinas and counted retinal ganglion cell numbers. Eye segregation pattern in the dorsal lateral geniculate nucleus were also compared between male Chrdl1 KO and WT mice. RESULTS: Male Chrdl1 KO mice do not have larger cornea diameters than WT mice. KO mice have significantly thicker central corneas (116.5 ± 3.9 vs. 100.9 ± 4.2 µm, P = 0.013) and smaller ACD (325.7 ± 5.7 vs. 405.6 ± 6.3 µm, P < 0.001) than WT mice, which is the converse of what occurs in patients who lack CHRDL1. Retinal-thalamic projections and other ocular measurements did not significantly differ between KO and WT mice. CONCLUSIONS: Male Chrdl1 KO mice do not have the same anterior chamber abnormalities seen in humans with CHRDL1 mutations. Therefore, Chrdl1 KO mice do not recapitulate the human MGC1 phenotype. Nevertheless, Chrdl1 plays a role during mouse ocular development because corneas in KO mice differ from those in WT mice.

Knowledge, attitudes and practices of Canadian pediatric emergency physicians regarding short-term opioid use: a descriptive, cross-sectional survey.

BACKGROUND: In the midst of the current opioid crisis, physicians are caught between balancing children's optimal pain management and the risks of opioid therapy. This study describes pediatric emergency physicians' practice patterns for prescribing, knowledge and attitudes regarding, and perceived barriers to and facilitators of short-term use of opioids. METHODS: We created a survey tool using published methodology guidelines and distributed it from October to December 2017 to all physicians in the Pediatric Emergency Research Canada database using Dillman's tailored design method for mixed-mode surveys. We performed bivariable binomial logistic regressions to ascertain the effects of clinically significant variables (e.g., training, age, sex, degree of worry regarding severe adverse events) on use of opioids as a first-line treatment for moderate pain in the emergency department, and prescription of opioids for moderate or severe pain for at-home use in children. RESULTS: Of the 224 physicians in the database, 136 (60.7%) completed the survey (60/111 [54.1%] women; median age 44 yr). Of the 136, 74 (54.4%) had subspecialty training. Intranasally administered fentanyl was the most commonly selected opioid for first-line treatment of moderate (47 respondents [34.6%]) and severe (82 [60.3%]) pain due to musculoskeletal injury. On a scale of 0 (not worried) to 100 (extremely worried), physicians' median score for worry regarding physical dependence was 6.0 (25th percentile 0.0, 75th percentile 16.0), for worry regarding addiction 10.0 (25th percentile 2.0, 75th percentile 20.0) and for worry regarding diversion of opioids 24.5 (25th percentile 14.0, 75th percentile 52.0). On a scale of 0 (not at all) to 100 (extremely), the median score for influence of the opioid crisis on willingness to prescribe opioids was 22.0 (25th percentile 8.0, 75th percentile 49.0). The top 3 reported barriers to prescribing opioids were parental reluctance (57 [41.9%]), lack of clear guidelines for pediatric opioid use (35 [25.7%]) and concern about adverse effects (33 [24.3%]). Binomial logistic regression did not identify any statistically significant variables affecting use of opioids in the emergency department or prescribed for use at home. INTERPRETATION: Emergency department physicians appeared minimally concerned about physical dependence, addiction risk and the current opioid crisis when prescribing opioids to children. Evidence-based development of guidelines and protocols for use of opioids in children may improve physicians' ability to manage pain in children responsibly and adequately.