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Setting: Task sharing can fill health workforce gaps, improve access to care, and enhance health equity by redistributing health services to providers with less training. We report learnings from a demonstration project designed to assess whether lay student vaccinators can support community immunizations. Intervention: Between July 2022 and February 2023, 27 undergraduate and graduate students were recruited from the University of Toronto Emergency First Responders organization and operated 11 immunization clinics under professional supervision. Medical directives, supported with online and in-person training, enabled lay providers to administer and document vaccinations when supervised by nurses, physicians, or pharmacists. Participants were invited to complete a voluntary online survey to comment on their experience. Outcomes: Lay providers administered 293 influenza and COVID-19 vaccines without adverse events. A total of 141 participants (122 patients, 17 lay vaccinators, 1 nurse, and 1 physician) responded to our survey. More than 80% of patients strongly agreed to feeling safe and comfortable with lay providers administering vaccines under supervision, had no concerns with lay vaccinators, and would attend another lay vaccinator clinic. Content and thematic analysis of open-text responses revealed predominantly positive experiences, with themes about excellent vaccinators, organized and efficient clinics, and the importance of training, communication, and access to regulated professionals. The responding providers expressed comfort working in collaborative immunization teams. Implications: Lay student providers can deliver vaccines safely under a medical directive while potentially improving patient experiences. Rather than redeploying scarce professionals, task sharing strategies could position trained lay vaccinators to support immunizations, improve access, and foster community engagement.

BACKGROUND: Parents have reported that they want to learn how to reduce pain in infants during vaccinations. Our objective was to compare different levels of intensity of postnatal education about pain mitigation on parental self-reported use of interventions at future infant vaccinations. METHODS: We conducted a longitudinal, 3-group parallel, add-on, randomized controlled trial on the postnatal ward of a hospital. New mothers, unaware of the hypothesis, were randomly assigned to 1 of 3 intervention groups and 3 follow-up groups (i.e., 9 groups, 3 x 3). The 3 intervention groups were control (general immunization information), pain pamphlet (pain mitigation information), and pain pamphlet and pain video (pain mitigation information). Both pain mitigation education groups also received general immunization information. The 3 follow-up groups were 2-, 4- and 6-month infant vaccinations. Mothers reported use of breastfeeding, sucrose and topical anesthetics during infant vaccinations in a telephone survey. RESULTS: Of 3420 participants, follow-up was available for 2549 (75%): 36.1%, 34.2% and 29.7% reported on pain mitigation practices at 2-, 4- and 6-month vaccinations, respectively (p = 0.9). Maternal characteristics did not differ (p > 0.05): mean age, 33.6 years; 58% were primipara. Utilization of any intervention (breastfeeding, sucrose or topical anesthetics) was 53.2%, 61.4% and 63.0% for control, pain pamphlet, and pain pamphlet and pain video groups, respectively (p < 0.001); both pain education groups had higher utilization than the control group, but did not differ from one another. Uptake differed among intervention groups at 2 and 4 months but not at 6 months. INTERPRETATION: Hospital-based postnatal education increased parental use of pain interventions at infant vaccinations and can be added to existing education. Trial registration: ClinicalTrials. gov, no. NCT01937143., Vaccine injections are the most common recurring painful procedure in infancy. Pain experienced by infants during vaccinations can cause distress in infants, caregivers and health providers, contributing to a negative [...]

BACKGROUND: Vaccine injections can cause acute pain and distress in infants, which can contribute to dissatisfaction with the vaccination experience and vaccine hesitancy. We sought to compare the effectiveness of additive pain interventions administered consistently during vaccine injections in the first year of life. METHODS: We conducted a multicentre, longitudinal, double-blind, add-on, randomized controlled trial. Healthy infants were randomly assigned to 1 of 4 levels of pain management for all vaccine injections at 2, 4, 6 and 12 months: (i) placebo control; (ii) parent-directed video education about infant soothing; (iii) the video plus sucrose administered orally or (iv) the video plus sucrose plus liposomal lidocaine applied topically. All infants benefit from injection techniques that minimize pain. We used a double-dummy design; hence all parents watched a video (active psychological intervention or placebo) and all infants received oral solution (sucrose or placebo) and topical cream (lidocaine or placebo). We assessed infant distress during 3 phases--preinjection (baseline), vaccine injection (needle), and 1 minute postinjection (recovery)--using the Modified Behavioural Pain Scale (range 0-10). We compared scores between groups and across infant ages using a mixed-model repeated-measures analysis. RESULTS: A total of 352 infants participated in the study, from Jan. 17, 2012, to Feb. 2, 2016. Demographics did not differ among intervention groups (p > 0.05). Baseline pain scores did not differ among intervention groups (p = 0.4), but did differ across ages (p < 0.001). Needle pain scores differed among groups (p = 0.003) and across ages (p < 0.001). The mean ([+ or -] standard deviation) needle score was 6.3 ([+ or -] 0.8) in the video-sucrose-lidocaine group compared with 6.7 ([+ or -] 0.8) in each of the other groups. There were no other between-group differences. Recovery scores did not differ among groups (p = 0.98), but did differ across ages (p < 0.001). INTERPRETATION: Only liposomal lidocaine provided consistent analgesia within an additive pain intervention regimen during vaccinations in infants. Trial registration: ClinicalTrials.gov, no. NCT01503060, Vaccine injections are associated with acute distress in infants, (1,2) which can contribute to dissatisfaction with the vaccination experience and vaccine hesitancy. (3-5) Mitigating pain is therefore clinically relevant and [...]

CMAJ Podcasts: author interview at soundcloud.com/cmajpodcasts/150391-guide Pain from vaccine injections is common, and concerns about pain contribute to vaccine hesitancy across the lifespan. (1,2) Noncompliance with vaccination compromises the individual [...]

Breast cancer resistance protein (BCRP, ABCG2) is an efflux transporter that plays a crucial role in multidrug resistance to antineoplastic drugs. Ko143, an analogue of the natural product fumitremorgin C, is a potent inhibitor of ABCG2 but is rapidly hydrolyzed to an inactive metabolite in vivo. To identify ABCG2 inhibitors with improved metabolic stability, we have assessed a series of Ko143 analogues for their ability to inhibit ABCG2-mediated transport in ABCG2-transduced MDCK II cells and determined the stability of the most potent compounds in liver microsomes. The most promising analogues were evaluated in vivoby positron emission tomography. In vitro, three of the tested analogues were potent ABCG2 inhibitors and stable in microsomes. In vivo, they increased the distribution of the ABCG2/ABCB1 substrate [11C]tariquidar to the brain both in wild-type (with Abcb1a/b transport blocked by tariquidar) and Abcb1a/b(−/−) mice. One analogue was more potent than Ko143 in both animal models.

•Needle procedures are a significant source of pain and distress for individuals receiving health care.•This manuscript adds to the AAAPT taxonomy effort providing a standard definition for needle pain.•A total of 4 diagnostic criteria, with 2 modifiers to account for the influence of needle associated fear are proposed.

Introduction: We explored Canadian community pharmacists’ perceptions of the CARD (Comfort Ask Relax Distract) system, a vaccine delivery framework that integrates evidence-based interventions that reduce immunization stress-related responses (ISRRs). The objective was to introduce CARD to pharmacists and obtain their feedback to guide future implementation efforts for community pharmacy-based vaccinations.Methods: Eighteen pharmacists across all provinces participated in one-on-one moderated virtual interviews. A semistructured interview guide was used to guide the discussion and included questions about experiences with coronavirus disease 2019 (COVID-19) vaccine administration and perceptions of CARD as a framework for vaccination delivery in the pharmacy. In this report, we focus on feedback about CARD. Interviews were audio-recorded and transcribed verbatim and deductively coded using the Consolidated Framework for Implementation Research (CFIR).Results: The study was conducted from May 28 to August 16, 2021. Pharmacists’ responses were categorized in 3 CFIR domains: intervention characteristics, inner setting and characteristics of individuals. Overall, pharmacists were receptive towards CARD and thought it filled a current gap in practice, particularly for childhood vaccinations. Pharmacists reported learning techniques to make vaccinations more comfortable for their clients. They provided feedback on how specific interventions could be adapted for their practice (e.g., dissemination of client-directed education via appointment booking portals, provision of distraction items in waiting and vaccinating spaces).Discussion: This study provided preliminary evidence that pharmacists found CARD acceptable and appropriate for community pharmacy-based vaccinations. The data collected from this study were used to inform a small-scale implementation project with CARD during COVID-19 vaccine administration in children aged 5 to 11 years.

Introduction: The scope of practice for pharmacy technicians is expanding to include vaccine administration in some provinces. Vaccine training courses and programs currently do not include education about mitigating immunization stress-related responses (ISRR) and improving the vaccination experience. We obtained feedback from pharmacy technician students about a new e-module that addresses this identified knowledge gap, whereby learners are educated about CARD (Comfort Ask Relax Distract), a vaccine delivery framework that reduces ISRR and improves the vaccination experience.Methods: Mixed-methods design including second-year pharmacy technician students who elected to take an accredited vaccine injection training program. Students were given access to the CARD e-module after completing mandatory vaccine education components. Eight students answered a quantitative survey and 4 (50%) additionally participated in a focus group. Qualitative data were analyzed deductively using the Consolidated Framework for Implementation Research (CFIR).Results: The study was conducted between April 28 and June 12, 2022. Students reported positive attitudes about the CARD e-module across quantitative and qualitative measures. Qualitative feedback spanned 4 CFIR constructs: intervention characteristics, outer setting, inner setting and individual characteristics. Students reported the e-module was well designed and that the content was relevant. They believed CARD facilitated provision of vaccinations using a person-centred approach that promotes vaccination. They felt that CARD could potentially add time to the vaccination appointment and that it would need to be acceptable to pharmacy leaders because of implications for training and vaccination delivery. They suggested that CARD education should be mandatory. CARD improved their confidence in delivering vaccinations, and they planned to integrate CARD into their practice.Conclusion: The CARD e-module was well received by pharmacy technician students when coupled with usual vaccine injection training.

Introduction: CARD (Comfort Ask Relax Distract) is a vaccine delivery program demonstrated to reduce pain, fear and associated immunization stress-related responses (ISRR) in children undergoing vaccinations at school. This study evaluated CARD’s clinical impact when integrated into community pharmacy–based pediatric vaccinations.Methods: This was a before-and-after CARD implementation study in 5 independent pharmacies offering COVID-19 vaccinations to children aged 5-11 years. No changes were made to practices in the “before” phase. CARD interventions were integrated in the “after” phase (e.g., children prepared a coping plan using a checklist, distraction toolkits were placed in waiting and vaccination spaces, vaccinations were performed with privacy, needles were obscured). Children self-reported ISRR, including fear, pain and dizziness during vaccination, and both children and parents/caregivers (herein, parents) compared the child’s experience to their last needle (better, same, worse). In the “after” phase, parents and children reported how much CARD helped (not at all, a little bit, a moderate amount, a lot).Results: The study was conducted between January 16 and March 20, 2022. Altogether, 152 children participated (71 before and 81 after CARD); demographic characteristics did not differ. Children’s self-reported fear was lower after CARD, when assessed continuously (2.5 vs 3.7 out of 10; p= 0.02) or dichotomously, using a cut-off of 0 vs >0 (58% vs 80%; p= 0.01). Pain was lower when assessed dichotomously (<2 vs ≥2; p= 0.03). There was no difference in dizziness. After CARD, children and parents reported more positive experiences compared to the child’s last needle (p= 0.01, both analyses) and more children and parents reported that distraction and child participation in the process were helpful (p< 0.001, both analyses). Overall, 92% of children and 91% of parents said CARD helped.Conclusion: CARD reduced children’s fear and improved vaccination experiences for children and parents when integrated in community pharmacy–based vaccinations.

Background: Throughout the COVID-19 pandemic, community pharmacists have played an important role in the provision of patient care, including the delivery of COVID-19 vaccines. The additional workload and related demands arising from these extended services might affect worklife burnout. This qualitative study explored the experiences of Canadian community pharmacists in providing COVID-19 vaccines during the COVID-19 pandemic.Methods: Eighteen community pharmacists across 10 provinces were asked about vaccination processes and perceptions about their role in separate, virtual semistructured interviews. Interviews were transcribed verbatim and analyzed using a deductive approach using the Areas of Worklife Burnout framework, with pharmacists’ self-reported descriptions of their activities summarized using the Association of Faculties of Pharmacy of Canada’s (AFPC) professional competencies framework.Results: Participants identified aspects of their role that were rewarding and challenging. Some challenges included lack of control, increased workload, inadequate communication, unfair treatment and conflicting values. They described being able to meet challenges and demonstrating resiliency via adaptability, developing communities and valuing their contribution to ending the COVID-19 pandemic. Self-identified AFPC competencies contributing to their ability to manage their worklife included care-provider, professional, leader-manager, collaborator and scholar.Conclusion: Pharmacists accepted their additional responsibility of managing COVID-19 vaccines during the COVID-19 pandemic. However, they expressed some challenges with this role. To ensure sustainability of these services, prioritizing adequate resources, work processes and efficient communication with all relevant stakeholder groups, including public health, government and corporate leaders, is recommended for the future. Can Pharm J (Ott)2023;156(Suppl):xx-xx.

Introduction: Community pharmacists report that providing vaccinations can be challenging, particularly if the vaccine recipient is a child, because of heightened levels of fear. The objective of this study was to determine acceptability and feasibility of the CARD (Comfort Ask Relax Distract) system as a vaccination delivery framework for children receiving COVID-19 vaccinations in a community pharmacy setting. CARD incorporates evidence-based interventions that reduce fear and immunization stress-related responses in vaccine recipients and was demonstrated to be effective and feasible in other vaccination settings providing vaccinations to children and adults.Methods: This mixed-methods study involved 5 independent pharmacies (with 6 vaccinators) offering COVID-19 vaccinations to children between 5 and 11 years of age. Vaccinating staff and implementation leads from the pharmacy organization participated in a small-scale CARD implementation project (before-and-after design). Afterwards, they filled in quantitative surveys and provided qualitative feedback about their perceptions and experiences in focus group discussions. Qualitative data were analyzed deductively, using the Consolidated Framework for Implementation Research (CFIR).Results: The study was conducted between January 16 and March 20, 2022. Across both quantitative and qualitative measures, vaccinating staff reported positive attitudes about CARD and alignment with their professional roles. They reported that CARD reduced children’s fear and improved the vaccination experiences in children and parents and for themselves. Vaccinators reported increased confidence due to CARD. They reported compatibility of CARD interventions within their practice and that it was time neutral. They maintained use of some interventions after the study. They also provided suggestions and shared concerns about fidelity and future feasibility of continuing various components of the program.Conclusion: CARD was demonstrated to be acceptable and feasible by vaccinators performing vaccinations in children in community pharmacies.

Background: Children being cared for in hospital undergo multiple painful procedures daily. However, little is known about the frequency of these procedures and associated interventions to manage the pain. We undertook this study to determine, for children in Canadian hospitals, the frequency of painful procedures, the types of pain management interventions associated with painful procedures and the influence of the type of hospital unit on procedural pain management. Methods: We reviewed medical charts for infants and children up to 18 years of age who had been admitted to 32 inpatient units at eight Canadian pediatric hospitals between October 2007 and April 2008. We recorded all of the painful procedures performed and the pain management interventions that had been implemented in the 24-hour period preceding data collection. We performed descriptive and comparative (analysis of variance, %2) analyses. Results: Of the 3822 children included in the study, 2987 (78.2%) had undergone at least one painful procedure in the 24-hour period preceding data collection, for a total of 18 929 painful procedures (mean 6.3 per child who had any painful procedure). For 2334 (78.1%) of the 2987 children who had a painful procedure, a pain management intervention in the previous 24 hours was documented in the chart: 1980 (84.8%) had a pharmacologic intervention, 609 (26.1%) a physical intervention, 584 (25.0%) a psychologic intervention and 753 (32.3%) a combination of interventions. However, for only 844 (28.3%) of the 2987 children was one or more pain management interventions administered and documented specifically for a painful procedure. Pediatric intensive care units reported the highest proportion of painful procedures and analgesics administered. Interpretation: For less than one-third of painful procedures was there documentation of one or more specific pain management interventions. Strategies for implementing changes in pain management must be tailored to the type of hospital unit., Children who are being cared for in hospital undergo multiple painful procedures daily. (1-3) The association between pain and negative physiologic, emotional and psychologic consequences is well established. (4,5) In [...]

Injections for vaccinations, the most common source of iatrogenic pain in childhood, (1) are administered repeatedly to almost all Canadian children throughout infancy, childhood and adolescence. (2) The pain associated [...]

Abstract Background: Sucrose is widely used to manage procedural pain in term newborns despite a lack of evidence of its effectiveness for different procedures and infant populations. Our objectives were [...]

Abstract Background: Historically, children have been undertreated for their pain, and they continue to undergo painful cutaneous procedures without analgesics. A new topical anesthetic, liposomal lidocaine 4% cream (Maxilene, RGR [...]

Background: The benefits of aminoglycoside antibiotics, such as tobramycin, administered as a once-daily dose to manage febrile neutropenia, have been demonstrated in many patient populations. However, toxicity and safety data are lacking for pediatric stem cell transplant recipients, who are at especially high risk for aminoglycoside-related toxicity and infectious morbidity. In particular, the relative nephrotoxicity and efficacy of tobramycin administered as a single daily dose or as three daily doses among this patient population is not known. Methods: We conducted a randomized, double-blind controlled study of tobramycin dosing among children 18 years or younger who had fever and neutropenia while undergoing stem cell transplantation. From October 2000 through November 2002, 60 children were randomly assigned to receive intravenous tobramycin, as either a single daily dose (n = 29) or every 8 hours (n = 31), in combination with either piperacillin or ceftazidime (intravenous). Tobramycin doses were adjusted to achieve pharmacokinetic targets. The primary outcome was nephrotoxicity, as represented by the maximal percent increase in serum creatinine concentration throughout the episode of febrile neutropenia relative to the baseline serum creatinine concentration. Efficacy was a secondary outcome and was defined as survival of the episode without modification of the antibacterial regimen. All statistical tests were two-sided. Results: In a modified intent-to-treat analysis, the mean maximal percent increase in serum creatinine concentration was 32% (N = 26) in the once daily dose group and 51% (N = 28) in the every 8 hours dose group (difference = 19%, 95% confidence interval [CI] = 0% to 38%; P = .054). Among patients evaluable for efficacy, 12 (46%) of 26 patients in the once daily dose group and five (19%) of 27 patients in the every 8 hours dose group survived the episode of febrile neutropenia without requiring antibacterial treatment modification (difference = 27%, 95% CI = 4% to 52%; P = .03). There was one death in each group. Conclusions: In febrile neutropenic children undergoing stem cell transplantation, tobramycin may be less nephrotoxic and more efficacious when administered as a once daily dose than when administered every 8 hours.

ObjectiveAcetaminophen is the most common medication prescribed in children’s hospitals. The aim of the study was to estimate the frequency and risk factors for acetaminophen underdosing and overdosing in the paediatric intensive care unit (PICU).DesignRetrospective cohort of drug administrations in a large tertiary care PICU.PatientsAll PICU admissions, less than 18 years of age, admitted between 1 January 2008 and 1 January 2018, having received at least one dose of enteral acetaminophen.MethodsThe primary outcome was acetaminophen underdosing and overdosing, defined as doses exceeding the 10% upper and lower limits of the standard reference range (10–15 mg/kg) and 10% above daily maximum dose (75 mg/kg). A generalised estimating equation regression assessed patient risk factors for single underdosing, single overdosing and cumulative daily overdosing of acetaminophen.ResultsOf the 147 485 doses of enteral acetaminophen administered, 7814 (5.3%) were single underdoses (1 in every 19 doses) and 4640 (3.1%) were single overdoses (1 in every 32 doses). There were 6813 cumulative overdose days (1 in every 9 patient-days). Risk factors for both underdosing and overdosing included older age and cardiac admission, whereas risk factors for cumulative overdosing were young age and cardiac admission. Electronic prescribing increased the risk of underdosing and overdosing, but decreased cumulative acetaminophen overdosing (relative risk 0.51, p=0.001).ConclusionAcetaminophen underdosing and overdosing are common in the PICU and can be detected with pharmacoepidemiology. Electronic prescribing increased the risk of single underdosing and overdosing, although it reduced the risk of cumulative overdosing.

Metronidazole, a treatment for trichomoniasis, does not appear to cause fetal anomalies when used during the first trimester of pregnancy. Trichomoniasis is a common vaginal infection, and it is not uncommon for women using it to discover that they are pregnant. The medication can cross the placenta. The literature was surveyed and seven articles were found. Data from the seven studies were subjected to group analysis. Overall, 1336 women were exposed to metronidazole during the first trimester. No increase was found in the odds of fetal anomalies in this group.

COVID-19 vaccine acceptance exists on a continuum from a minority who strongly oppose vaccination, to the “moveable middle” heterogeneous group with varying uncertainty levels about acceptance or hesitancy, to the majority who state willingness to be vaccinated. Intention for vaccine acceptance varies over time. COVID-19 vaccination decisions are influenced by many factors including knowledge, attitudes, and beliefs; social networks; communication environment; COVID-19 community rate; cultural and religious influences; ease of access; and the organization of health and community services and policies.Reflecting vaccine acceptance complexity, the Royal Society of Canada Working Group on COVID-19 Vaccine Acceptance developed a framework with four major factor domains that influence vaccine acceptance (people, communities, health care workers; immunization knowledge; health care and public health systems including federal/provincial/territorial/indigenous factors)—each influencing the others and all influenced by education, infection control, extent of collaborations, and communications about COVID-19 immunization. The Working Group then developed 37 interrelated recommendations to support COVID vaccine acceptance nested under four categories of responsibility: 1. People and Communities, 2. Health Care Workers, 3. Health Care System and Local Public Health Units, and 4. Federal/Provincial/Territorial/Indigenous. To optimize outcomes, all must be engaged to ensure co-development and broad ownership.

A 14-year-old adolescent girl presented with severe abdominal pain, tenderness, and guarding in the right upper quadrant associated with nonbilious vomiting, scleral icterus, and fever. Laboratory tests were consistent with acute hepatitis A virus–related cholestatic hepatitis. A point-of-care ultrasound showed mild gallbladder wall thickening with increased color Doppler flow and pericholecystic fluid collection, in the absence of gallstones or biliary ducts dilatation, thus suggesting acute acalculous cholecystitis. Both the clinical symptoms and the point-of-care ultrasound findings completely resolved within 1 week after admission with conservative treatment.

Belt conveyors are widely used in the cement industry as they are the cheapest system for transporting bulk materials. However, their poor resistance to ripping, cutting or impact damage means that their working life may be drastically reduced. SIG SpA of Italy has designed the Siderflex belt system for long-distance conveying applications which contains an electronic sensor system embedded in the belt, allowing for easy and fast detection of breakage. The new belt has been used in a range of applications, including power stations, cement and iron works, and mines.

Patients with juvenile myelomonocytic leukemia due to germline CBLmutation (10% to 15%) may have a subacute course occasionally associated with autoimmune disorders, which may resemble RAS-associated autoimmune lymphoproliferative disorder. In both conditions, prognosis and standard treatment for autoimmune phenomena remain poorly understood. We report the case of a 7-year-old boy with juvenile myelomonocytic leukemia with severe steroid-dependent uveitis, who did not respond to several therapeutic attempts with immunosuppressant agents, including sirolimus, and was finally successfully treated with adalimumab. This case offers further insight into the management of autoimmune disorders in the context of predisposing genetic conditions.

Infants undergo painful procedures involving skin puncture as part of routine medical care. Pain from needle puncture procedures is suboptimally managed. Numerous nonpharmacologic interventions are available that may be used for these painful procedures, including swaddling/containment, pacifier/non-nutritive sucking, rocking/holding, breastfeeding and breastmilk, skin-to-skin care, sweet tasting solutions, music therapy, sensorial saturation, and parental presence. Adoption these interventions into routine clinical practice is feasible and should be a standard of care in quality health care for infants. This review summarizes the epidemiology of pain from common needle puncture procedures in infants, the effectiveness of nonpharmacologic interventions, implementation considerations, and unanswered questions.

The costimulatory molecule CD80 is an early marker for immune activation. It is upregulated on activated antigen-presenting cells. We aimed at developing a tracer for imaging CD80 by positron emission tomography (PET). Novel CD80 ligands were synthesized and tested by SPR for affinity to human CD80 (hCD80) and displacement of endogenous ligands. Several compounds bound with one-digit nanomolar affinity to hCD80 and displaced CTLA-4 and CD28 at nanomolar concentrations. A structure–affinity relationship study revealed relevant moieties for strong affinity to hCD80 and positions for further modifications. Lead compound MT107 (7f) was radiolabeled with carbon-11. In vitro, [11C]MT107 showed specific binding to hCD80-positive tissue and high plasma protein binding. In vivo, [11C]MT107 accumulated in liver, gall bladder, and intestines but only scarcely in hCD80-positive xenografts. The unfavorable in vivo performance may result from high plasma protein binding and extensive biliary excretion.

Thiamine metabolism dysfunction syndrome-4 (THMD4) includes episodic encephalopathy, often associated with a febrile illness, causing transient neurologic dysfunction and a slowly progressive axonal polyneuropathy. Until now only two mutations (G125S and S194P) have been reported in the SLC25A19gene as causative for this disease and a third mutation (G177A) as related to the Amish lethal microcephaly. In this work, we describe the clinical and molecular features of a patient carrying a novel mutation (c.576G>C; Q192H) on SLC25A19gene. Functional studies on this mutation were performed explaining the pathogenetic role of c.576G>C in affecting the translational efficiency and/or stability of hMTPPT protein instead of the mRNA expression. These findings support the pathogenetic role of Q192H (c.576G>C) mutation on SLC25A19gene. Moreover, despite in other patients the thiamine supplementation leaded to a substantial improvement of peripheral neuropathy, our patient did not show a clinical improvement.

Care in the paediatric intensive care unit (PICU) involves many clinical activities. The objectives of this study were to evaluate the feasibility of a novel observation method, the reliability of data abstraction, and to report the initial findings from application of this approach.

ABSTRACTObjectives: Recommendations regarding the need to use alcohol prior to vaccine injections are inconsistent and based on low-level evidence. The objective was to assess the effectiveness of alcohol in reducing local skin reactions and infection post-vaccination.Methods: Randomized controlled trial in a pediatric clinic. A research assistant cleansed the skin with alcohol at (swab group) or adjacent to (control group) the pre-defined injection site(s). Clinicians, parents and children were blinded to group allocation. Parents reported local skin reactions using paper diaries for 15 days post-vaccination (Day 0–14). Telephone interviews were conducted Day 1, 5, and 14. The Brighton Collaboration criteria were used to diagnose cellulitis and infectious abscess Day 5 and afterward.Results: 170 children participated (May-November 2017). Baseline characteristics did not differ (p > 0.05) between groups. Children received 1–4 separate injections. There were no differences between swab and control groups in the incidence of any local skin reactions (58% vs. 54%), and specifically, pain (45% vs. 40%), redness (26% vs. 21%), swelling (20% vs. 13%), warmth (19% vs. 27%), and spontaneous drainage of pus (0% in both groups) over the post-vaccination follow-up period. Day 5 data was available for 99% of participants from diaries and telephone surveys; there were no cases of cellulitis or infectious abscess.Conclusion: These findings are the first direct evidence for vaccine injections demonstrating that cleansing the skin with alcohol may not be needed. Our study is underpowered; however, to detect a difference in incidence of skin infection, future research is recommended.

Anti-tumor necrosis factor antibodies have led to a revolution in the treatment of inflammatory bowel diseases (IBD); however, a sizable proportion of patients does not respond to therapy. There is increasing evidence suggesting that treatment failure may be classified as mechanistic (pharmacodynamic), pharmacokinetic, or immune-mediated. Data regarding the contribution of these factors in children with IBD treated with infliximab (IFX) are still incomplete. The aim was to assess the causes of treatment failure in a prospective cohort of pediatric patients treated with IFX. This observational study considered 49 pediatric (median age 14.4) IBD patients (34 Crohn disease, 15 ulcerative colitis) treated with IFX. Serum samples were collected at 6, 14, 22 and 54 weeks, before IFX infusions. IFX and anti-infliximab antibodies (AIA) were measured using enzyme linked immunosorbent assays. Disease activity was determined by Pediatric Crohn's Disease Activity Index or Pediatric Ulcerative Colitis Activity Index. Clinical remission, defined as a clinical score <10, was obtained by 76.3% of patients at week 14 and by 73.9% at week 54. Median trough IFX concentration was higher at all time points in patients achieving sustained clinical remission. IFX levels during maintenance correlated also with C-reactive protein, albumin, and fecal calprotectin. After multivariate analysis, IFX concentration at week 14 >3.11 µg/mL emerged as the strongest predictor of sustained clinical remission. AIA concentrations were correlated inversely with IFX concentrations and directly with adverse reactions. Most cases of therapeutic failure were associated with low serum drug levels. IFX trough levels at the end of induction are associated with sustained long-term response.

The objective of this cohort study was to document experience with intranasal (IN) fentanyl analgesia for procedural pain management in neonates in a surgical neonatal intensive care unit. A consecutive sample of 23 neonates without intravenous access treated with IN fentanyl was included.

Background: Pain of circumcision is only partially relieved by single modalities, such as penile nerve block, lidocaine-prilocaine cream, and sucrose pacifiers. Objective: To assess the effectiveness of a combination of interventions on the pain response of infants undergoing circumcision. Methods: Cohort study. Group 1 included infants circumcised using the Mogen clamp and combined analgesics (lidocaine dorsal penile nerve block, lidocaine-prilocaine, acetaminophen, and sugar-coated gauze dipped in grape juice). Group 2 included infants circumcised using the Gomco clamp and lidocaine-prilocaine. Infants were videotaped during circumcision, and pain was assessed using facial activity scores and percentage of time spent crying. Results: There were 57 infants in group 1 and 29 infants in group 2. Birth characteristics did not differ between groups. Infants in group 1 were older than infants in group 2 (17 days vs 2 days) (P [is less than] .001). The mean duration of the procedure was 55 seconds and 577 seconds for infants in group 1 and 2, respectively (P [is less than] .001). Facial action scores and percentage of time spent crying were significantly lower during circumcision for infants in group 1 (P [is less than] .001). The percentage of time spent crying was 18% and 40% for infants in groups 1 and 2, respectively. No adverse effects were observed in infants in group 1; 1 infant in group 2 had a local skin infection. Conclusions: Infants circumcised with the Mogen clamp and combined analgesia have substantially less pain than those circumcised with the Gomco clamp and lidocaine-prilocaine cream. Because of the immense pain during circumcision, combined local anesthesia and analgesia using the Mogen clamp should be considered. Arch Pediatr Adolesc Med. 2000; 154:620-623

To assess the time in remission after discontinuing biologic therapy in patients with juvenile idiopathic arthritis (JIA). We enrolled 135 patients followed in 3 tertiary‐care centers. The primary outcome was to assess, once remission was achieved, the time in remission up to the first flare after discontinuing treatment. Mann‐Whitney U test, Wilcoxon's signed rank test for paired samples, chi‐square tests, and Fisher's exact test were used to compare data. Pearson's and Spearman's correlation tests were used to determine correlation coefficients for different variables. To identify predictors of outcome, Cox regression model and Kaplan‐Meier curves were constructed, each one at the mean of entered covariates. The majority of enrolled patients flared after stopping treatment with biologics (102 of 135, 75.6%) after a median followup time in remission off therapy of 6 months (range 3–109 months). A higher probability of maintaining remission after discontinuing treatment was present in systemic‐onset disease compared to the rest of the JIApatients (Mantel‐Cox χ2= 8.31, P< 0.004). In analysis limited to children with JIAwith polyarticular and oligoarticular disease, patients who received biologics >2 years after achieving remission had a higher probability of maintaining such remission off therapy (mean ± SD18.64 ± 3.3 months versus 11.51 ± 2.7 months [P< 0.009]; Mantel‐Cox χ2= 9.06, P< 0.002). No other clinical variable was significantly associated with a long‐lasting remission. Children with oligoarticular and polyarticular JIAwho stop treatment before 2 years from remission have a higher chance of relapsing after biologic withdrawal.

ABSTRACTObjectives: In 2012, Ontario pharmacists were granted immunization privileges to administer influenza vaccines to the public. This study explored the experiences and practices of pharmacist vaccinators and the impact of vaccination pain on their practice. Methods: Semi-structured interviews were conducted with 12 pharmacists in the Greater Toronto Area. Transcribed interview data were coded and analyzed via thematic analysis. Key Findings: Data analysis revealed 4 main themes: 1) expanded scope of practice as an enhancement and challenge to relationships; 2) professional satisfaction and workload demands; 3) knowledge and attitudes regarding pain and fear; 4) practices regarding pain and fear management. Pharmacists reported satisfaction in their new role, despite the associated increased workload. Pharmacists felt that vaccination pain was not a key consideration when administering vaccines and that pain management was generally not necessary. Fear was identified as more important than pain and vaccinating children was challenging and time intensive. Pharmacists' main focus was on injection techniques in managing pain. Conclusion: These findings suggest that pharmacists are accepting of their role as vaccinators but more research is needed to examine impact on workload and pharmacist knowledge and perceptions of injection-related pain and fear.

Objective.This study aimed to test fecal calprotectin (FC) as a screening tool to identify inflammatory bowel disease (IBD) among patients with juvenile idiopathic arthritis (JIA).Methods.FC level < 100 g/kg was considered normal. Patients with 2 consecutive FC dosage ≥ 100 g/kg underwent endoscopic evaluation.Results.There were 113 patients with JIA enrolled. FC was raised in 7 patients out of 113. All patients had IBD. In 3/7 patients, high FC levels were the only sign consistent with IBD.Conclusion.FC is a useful, economical, and noninvasive diagnostic tool to identify JIA patients with underlying IBD.

We were most dismayed to read of the use of a placebo in a study of analgesia and the success rate of cannulation when a topical anesthetic was used on [...]

Objective.To identify clinical predictors of relapse in childhood autoimmune chronic uveitis after stopping systemic treatment.Methods.A retrospective, multicenter, cohort study.Results.Ninety-four children in remission, receiving no treatments and with at least a 6-month followup, were enrolled. A higher probability of maintaining remission after discontinuing treatment was shown in idiopathic compared with juvenile idiopathic arthritis uveitis (Mantel-Cox chi-square = 23.21) if inactivity had been obtained within 6 months from starting systemic treatment (Mantel-Cox chi-square = 24.17) and by antitumor necrosis factor-α treatment (Mantel-Cox chi-square = 6.43).Conclusion.Type of disease, time, and type of systemic therapy to achieve inactivity predict different duration of uveitis remission after treatment withdrawal.

Wandering spleen is a rare condition, typically not only due to embryological defects of the splenic ligaments, but also secondary to trauma and splenomegaly. The most common presentation is acute abdomen with a mobile abdominal mass or recurrent abdominal pain. However, the spleen may be temporary in its normal position, and patients could be asymptomatic. A familiarity, if present, strengthens the diagnostic suspect.Abdominal ultrasonography and computed tomography are the examination of choice, and the management is surgical.

Introduction: Vapocoolants are aerosols applied to the skin or intact mucous membranes, and instantly create a cooling effect on the surface by immediate evaporation of the product. Our objective was to determine if a vapocoolant reduces pain compared to placebo in infants and young children undergoing routine immunization. Methods: Prospective, randomized, double blind, placebo controlled trial in a Pediatric community clinic in a large urban area in Canada. Of 66 families approached, 2 declined participation and 1 was excluded as he did not undergo vaccination. Thirty-one (49%) were recruited to the vapocoolant group and 32 to the control group. Either vapocoolant or a placebo were administered to the area of immunization using a cotton ball. Children were videotaped and their films were scored by a blinded observer. The primary outcome measures were the Modified Behavioural Pain Scale (MBPS) and Faces Pain ScaleRevised (FPS-R). We also measured parental perception of the treatment. Results: The median difference MBPS score (injection- baseline) did not differ between groups (p = 0.66). There was also no significant difference in the observer FPS-R scores or in parental assessments of the benefits of the study intervention between the 2 groups. The interobserver intraclass correlation on 39 children's videotapes was 0.93 (p < 0.001). Conclusion: Vapocoolant did not reduce pain during immunization in infants and young children when applied using a cotton ball. We suggest that future studies will further assess vapocoolants in the young age group in order to determine if direct application using a spray is beneficial to reduce pain from immunization. Keywords: vapocoolant, vaccination, pediatrics