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Objective To describe current approaches in treatment of opioid use disorder (OUD) within Canadian psychosocial outpatient, day, and residential addiction treatment programs, with an emphasis on the use of opioid agonist therapy (OAT). Method An online census survey was conducted in English and French of Canadian psychosocial addiction treatment programs ( N = 214). Results Programs estimated that 25% of their clients have OUD. A slight majority of programs provide some type of specialized services to clients with OUD (58%), most frequently providing or facilitating access to OAT but also specialized counselling, case management, education, and harm reduction services. Most programs reported that they admitted clients on OAT (88%) and only a minority expected or encouraged clients to taper (14%) or discontinue (6%). Programs focusing on client abstinence as the treatment goal were more likely to expect or encourage tapering or discontinuation than programs that focus on helping clients achieve personal consumption goals. Of programs that did not currently facilitate OAT, 44% indicated that they would provide OAT, but lacked the necessary accreditation, physician support, or other resources. No philosophical objections to OAT were noted. OAT initiation was provided by 30% of programs, 23% referred to another service within their organization, and 29% referred to a service outside their organization. The remaining 18% did not facilitate OAT initiation at all, ranging from 0% in Quebec to 23% in the Prairies. Overdose response kits were provided by 86% of programs. The majority not providing kits indicated willingness if policy support and resources were provided (67%). Conclusions Overall, the results demonstrate that psychosocial programs provide some specialized services for OUD but desire further support specifically to provide OAT, including training, knowledge, and the expertise of individuals qualified to prescribe and dispense OAT. Many psychosocial treatment programs expressed a need for staff and resources for this purpose.

Disorganized morphogenesis of arteries, veins, capillaries, and lymphatic vessels results in vascular malformations. Most individuals with isolated vascular malformations have postzygotic (mosaic), activating pathogenic variants in a handful of oncogenes within the PI3K–RAS–MAPK pathway (Padia et al., Laryngoscope Investig Otolaryngol 4: 170–173 [2019]). Activating pathogenic variants in the gene PIK3CA, which encodes for the catalytic subunit of phosphatidylinositol 3-kinase, are present in both lymphatic and venous malformations as well as arteriovenous malformations in other complex disorders such as CLOVES syndrome (congenital, lipomatous, overgrowth, vascular malformations, epidermal anevi, scoliosis) (Luks et al., Pediatr Dev Pathol 16: 51 [2013]; Luks et al., J Pediatr 166: 1048–1054.e1–5 [2015]; Al-Olabi et al., J Clin Invest 128: 1496–1508 [2018]). These vascular malformations are part of the PIK3CA-related overgrowth spectrum, a spectrum of entities that have regionalized disordered growth due to the presence of tissue-restricted postzygotic PIK3CA pathogenic variants (Keppler-Noreuil et al., Am J Med Genet A 167A: 287–295 [2015]). Cerebrofacial vascular metameric syndrome (CVMS; also described as cerebrofacial arteriovenous metameric syndrome, Bonnet–Dechaume–Blanc syndrome, and Wyburn–Mason syndrome) is the association of retinal, facial, and cerebral vascular malformations (Bhattacharya et al., Interv Neuroradiol 7: 5–17 [2001]; Krings et al., Neuroimaging Clin N Am 17: 245–258 [2007]). The segmental distribution, the presence of tissue overgrowth, and the absence of familial recurrence are all consistent with CVMS being caused by a postzygotic mutation, which has been hypothesized by previous authors (Brinjiki et al., Am J Neuroradiol 39: 2103–2107 [2018]). However, the genetic cause of CVMS has not yet been described. Here, we present three individuals with CVMS and mosaic activating pathogenic variants within the gene PIK3CA. We propose that CVMS be recognized as part of the PIK3CA-related overgrowth spectrum, providing justification for future trials using pharmacologic PIK3CA inhibitors (e.g., alpelisib) for these difficult-to-treat patients.

Kaposiform lymphangiomatosis (KLA) is a complex lymphatic anomaly involving most commonly the mediastinum, lung, skin and bones with few effective treatments. In recent years, RAS-MAPK pathway mutations were shown to underlie the pathogenesis of several complex lymphatic anomalies. Specifically, an activating NRAS mutation (p.Q61R) was found in the majority of KLA patients. Recent reports demonstrated promising results of treatment with the MEK inhibitor, Trametinib, in patients with complex lymphatic anomalies harboring gain of function mutations in ARAF and SOS1, as well as loss of function mutation in the CBL gene, a negative regulator of the RAS-MAPK pathway. We present a 9-year-old child with a severe case of KLA harboring the typical NRAS (p.Q61R) mutation detected by plasma-derived cell free DNA, responsive to trametinib therapy.The NRAS somatic mutation was detected from plasma cfDNA using droplet digital PCR. Concurrent in-vitro studies of trametinib activity on mutant NRAS affected lymphatic endothelial cells were performed using a three-dimensional spheroid sprouting assay.Trametinib treatment lead to resolution of lifelong thrombocytopenia, improvement of pulmonary function tests and wellbeing, as well as weaning from prolonged systemic steroid treatment. Concurrent studies of mutant NRAS-expressing cells showed enhanced lymphangiogenic capacity along with over activation of the RAS-MAPK and PI3K-AKT-mTOR pathways, both reversed by trametinib.Trametinib treatment can substantially change the prognosis of patients with RAS pathway associated lymphatic anomalies.This is the first description of successful trametinib treatment of a patient with KLA harboring the most characteristic NRAS p.Q61R mutation. Treatment can significantly change the prognosis of patients with RAS pathway-associated lymphatic anomalies. We devised an in vitro model of KLA enabling a reproducible method for the continued study of disease pathogenesis. Mutated NRAS p.Q61R cells demonstrated increased lymphangiogenic capacity.

e18694 Background: PIK3CA mutations seen in cancer also drive other disease, exciting interest in repurposing oncology therapies for non-oncology indications. ALP is a PI3Kα inhibitor approved for HR+, HER2– ABC with fulvestrant. Clinical benefit of ALP in PROS, a group of rare phenotypically varied disorders driven by mutations in PIK3CA, was found in 19 pts (Venot, 2018). EPIK-P1 (NCT04285723) collected real-world data (RWD) to confirm ALP’s efficacy and safety in PROS. In the primary analysis of the primary endpoint, 12/32 pts (37.5%; 95% CI, 21.1-56.3%) with complete cases responded (≥20% reduction in the sum of target lesion volume from index/treatment [tx] start). Adverse events (AEs) and tx-related AEs were experienced by 82.5% (n = 47) and 38.6% (n = 22) of pts, respectively. The most common tx-related AE was hyperglycemia (n = 7, 12.3%). No deaths were reported (Canaud, ESMO 2021 LBA23). Methods: EPIK-P1 retrospectively abstracted data from the medical charts of pts aged ≥2 y with PROS experiencing severe/life-threatening conditions receiving ALP under compassionate use. Secondary endpoints evaluated safety and clinical benefit. Results: 57 pts were enrolled and followed for a median of 18.1 mo. No pt in the primary analysis (complete cases, n = 32) had progressive disease (PD) at wk 24; 1 pt discontinued ALP prior to wk 24 and considered a nonresponder. Of the 12 responders, median duration of response (time from first documented response to first documented PD or death due to any cause) was not estimable. Median time to censoring (date of last adequate lesion assessment) was 63.3 wk (̃14.6 mo; range, 1 d-186.7 wk); 2 pts had no further imaging assessments, 10 pts did not experience an event and tx was ongoing at data cutoff. Time to censoring was > 6 mo in 7 pts and > 12 mo in 6 pts. 11/20 nonresponders (55.0%) had target lesion volume reduction ranging from 0.7 to 19.6%. No pt required rescue surgery between index and wk 24. At index all pts reported ≥1 PROS-related symptom (eg, fatigue, pain). At wk 24, 82.5% (n = 47) reported symptom improvement regardless of primary analysis response status (responders, 10/12, 83.3%; nonresponders, 16/20, 80.0%). Median daily dose was 50 mg for pediatrics and 250 mg for adults. Dose reductions or interruptions were experienced by 15.8% of pts (n = 9); AEs led to dose reductions and interruptions in 3.5% (n = 2) and 10.5% (n = 6) of pts, respectively. 52 pts (91.2%) remained on tx at data cutoff; among 5 pts (8.8%) who discontinued, pt decision was the leading cause. Conclusions: RWD from EPIK-P1 demonstrate alpelisib as well tolerated, providing clinical benefit to pts with PROS regardless of response status in the primary analysis of the primary endpoint. Continued RWD collection complements planned prospective, randomized, placebo-controlled studies, facilitating access to alpelisib as an emerging pharmacologic option for PROS. Clinical trial information: NCT04285723.

e18707 Background: PROS is a group of rare disorders driven by activating mutations in PIK3CA. Overactivation of the PI3K pathway, which regulates growth and proliferation, results in asymmetric malformations/overgrowths. Localized interventions are often not curative and no medical therapy for PROS is approved; however, mTOR inhibitors (ie sirolimus) are used off-label with modest success. Using a patient (pt)-focused approach, we seek to better understand the current path to diagnosis (dx), course of disease, interventions, and pt outcomes to optimize future therapies. Methods: Pts treated in the US are being actively recruited via interactions with pt advocacy groups, pt communities, social media, and allstripes.com. Following research and HIPAA authorization from each pt/guardian, AllStripes’ proprietary real-world evidence (RWE) platform collects pt medical records into a master medical record from which study data are abstracted. All activities are covered under AllStripes’ IRB-approved protocol. To enroll in the PROS cohort, pts must have a confirmed PROS dx via PIK3CA genetic testing. Data completeness and nomenclature are dependent on physician documentation. Results: To date 14 pts (7 female, 7 male) have enrolled; median age at enrollment was 10.5 y (range, 1-38). Of the 14 pts, 71.4% of pts (n = 10) had congenital onset. PIK3CA genetic testing was primarily (n = 12, 85.7%) completed as a part of a multigene panel. The most frequent specialties involved in dx were medical genetics (n = 4, 28.6%) and pediatric heme-oncology (n = 3, 21.4%). Clinical presentation commonly included vascular malformations (n = 8, 57.1%). Most pts were diagnosed with CLOVES (n = 12, 85.7%). Seven pts (50.0%) had documented lesions at dx, median of 2 (range, 1-13) lesions per pt, increasing after dx to 3 (range, 1-14). All pts reported PROS-related complications; 50.0% (n = 7) required hospitalization/ER visit. Musculoskeletal, neurological, and gastrointestinal related complications were each reported by ≥50% of pts. All pts required ≥1 surgery; ≥50% of pts had diagnostic, debulking, vascular, or other procedures. Median number of surgeries per pt was 7 (range, 1-28), corresponding to a median of 0.76 surgeries per pt per year. Eight pts (57.1%) received PROS related medications: 6 (42.9%) received alpelisib, 5 (35.7%) received sirolimus. Conclusions: While each pt is unique, similarities in the path to dx (eg, specialties involved) and disease history (eg, clinical presentation, symptoms experienced) exist. RWE abstracted from medical records rapidly provides data in an otherwise limited field, helping to address key questions. Preliminary results highlight the burden of PROS and the reliance on repetitive surgical interventions for management, suggesting there remains a high unmet medical need for effective therapeutic strategies.

Este ensaio explora as interfaces estéticas e clínicas na performance Trêsformance (2017) de Arlindo Oliveira, colega e ex-companheiro de manicômio de Arthur Bispo do Rosário, e artista do Ateliê Gaia – um estúdio coletivo para artistas e ex-internos do antigo asilo na Colônia Juliano Moreira no subúrbio norte do Rio de Janeiro – administrado pelo Museu Bispo do Rosário Arte Contemporânea, e debruça-se sobre um conceito de curadoria ao avesso tateando outras institucionalidades e práticas dobradiças do entre.AbstractThis essay explores the intersections of clinical and aesthetic practices in the performance Trêsformance (2017) by Arlindo Oliveira, colleague and former asylum companion of Arthur Bispo do Rosário and member of Ateliê Gaia - a collective studio for artists and interns of the former asylum in Colony Juliano Moreira in the outskirts of Rio de Janeiro – managed by the Museu Bispo do Rosário Arte Contemporânea and reflects on a concept of an inside/out curatorship that seeks to nurture such intersections and “in-betweens” and the kind of institutionality that might support them.

Objective Conduct a systematic review of pediatric randomized controlled trials (RCTs) published in high-impact journals to assess the reporting of primary outcomes and the psychometric properties of their measures. Study Design and Setting Systematic review with screening and simultaneous data extraction conducted by two independent reviewers. Electronic searches of six general medicine and four pediatric journals were conducted in MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases. RCTs of a single phase/step in a single publication, published in English between 2000 and 2010 with participants less than 21 years of age were included. Results A random sample of 20% ( n = 445) of 2,229 initial references was screened and 206 (46%) met inclusion criteria. Half (48.5%) of included studies reported a singular primary outcome, 27% did not identify any primary outcome, and 24% identified multiple primary outcomes (range 2–20). Twenty-one trials used an instrument to measure their primary outcome, but only 7 (33%) reported its psychometric properties. Conclusion Pediatric trials published in top medical journals have inadequate reporting of their primary outcomes and the psychometric properties of their outcome measures. Whether the issue is one of poor reporting and/or poor validation will be further investigated.

Mapped the sources and types of evidence available on psychosocial interventions in the treatment of opioid use disorder (OUD), with and without pharmacotherapies.Six electronic databases were searched for research published until July 1, 2019. Included studies were coded on publication characteristics, evidence sources, treatment settings and modalities, study populations and patient characteristics, intervention(s) offered to patients, research questions addressed in experimental studies, and outcomes investigated.We identified 305 empirical studies of 54,607 patients. Most studies (64 %; n = 194) compared psychosocial interventions to alternative treatment(s) (183 RCTs and 11 quasi-experiments) while 28 % (n = 86) used observational designs, and 8% (n = 25) used qualitative methods. Trials infrequently investigated effects of stand-alone psychosocial interventions without pharmacotherapies (20% of all RCTs). Regardless of research question or study design, program retention and illicit drug use were the most common outcomes investigated (81% of all studies and RCTs), typically among longstanding male heroin users attending specialty outpatient addiction services. Studies rarely examined (a) OUD treatment in general health care or prescription OUD (each6 % of all studies and RCTs), (b) effects of social assistance (employment, education, social support) and harm reduction (each6 % of studies;7 % of RCTs), and (c) health-related quality of life and satisfaction with care (each10 % and15 % of all studies and RCTs, respectively).Scant evidence is available on the putative rehabilitative effects of psychosocial interventions, either as stand-alone treatments or in an adjunct role to pharmacotherapies.

Purpose: Video gaming is popular worldwide, and its benefits and risks have come to the attention of health care providers across disciplines. Blink rate, blink amplitude, and tear film stability are compromised during dynamic, prolonged use of digital devices, which can result in symptoms of discomfort with contact lens wear. In addition to lens material and design, the choice of lens care cleaning and disinfecting solution can affect wearer satisfaction. The purpose of this evaluation was to compare real world experiences with a hyaluronan-containing contact lens multipurpose solution (MPS) among subjects classified as video gamers and non-gamers. Methods: This study was a prospective, single arm, open label survey of contact lens wearers who used a computer, smartphone, or tablet for a minimum of three hours daily. Contact lens-wearing gamers (subjects who reported that they play electronic games while wearing contact lenses 2-hours or more daily) and non-gamers were provided Biotrue MPS to use for at least seven-days while wearing a fresh pair of their respective habitual contact lenses. Subjects rated performance attributes via an online survey using a 6-point Likert scale. Results: At baseline, gamers were younger than non-gamers, more likely male, spent more time using digital devices daily, and were more likely to report they suffer from eyestrain, sensitive eyes, and red eyes. Both groups rated all queried lens-wearing performance attributes positively; gamers gave higher mean ratings than did non-gamers to 23 of 24 queried attributes, including all four pertaining to long durations of digital device use. After adjusting for both age and gender, significant differences favoring gamers were noted for all 24 attributes. Conclusions: Contact lens wearing gamers and non-gamers rated Biotrue MPS highly based upon various performance attributes. Biotrue MPS remains a good choice for general lens wear, as well as during tear film-challenging video game play.

BACKGROUND The use of complementary and alternative medicine is high among children and youth with chronic illnesses, including patients with cardiac conditions. Our goal was to assess the prevalence and patterns of such use among patients presenting to academic pediatric cardiology clinics in Canada. METHODS A survey instrument was developed to inquire about current or previous use of complementary and alternative medicine products and practices, including indications, beliefs, sources of information and whether this use was discussed with physicians. Between February and July 2007, the survey was administered to patients (or their parents/guardians) presenting to 2 hospital-based cardiology clinics: the Stollery Children's Hospital in Edmonton, Alberta, and the Children's Hospital of Eastern Ontario in Ottawa, Ontario. RESULTS At the Stollery Children's Hospital, 64.1% of the 145 respondents had used complementary and alternative medicine compared with 35.5% of the 31 respondents at the Children's Hospital of Eastern Ontario (p = 0.003). Overall, the most common products in current use were multivitamins (70.6%), vitamin C (22.1%), calcium (13.2%), unspecified "cold remedies" (11.8%) and fish oil or omega-3 fatty acids (11.8%). The most common practices in current use were massage (37.5%), faith healing (25.0%), chiropractic (20.0%), aromatherapy (15.0%) and Aboriginal healing (7.5%). Many patients (44.9%) used complementary and alternative medicine products at the same time as conventional prescription drugs. Concurrent use was discussed with physicians or pharmacists by 64.3% and 31.3% of respondents, respectively. INTERPRETATION Use of complementary and alternative medicine products and practices was high among patients seen in the pediatric cardiology clinics in our study. Most respondents believed that the use of these products and practices was helpful; few reported harms and many did not discuss this use with their physicians, increasing the potential for interactions with prescribed medications.

The aim of the present study was to assess the prevalence and patterns of complementary and alternative medicine (CAM) use among pediatric patients with gastrointestinal (GI) disorders at academic clinics in Canada.The survey was carried out at 2 hospital-based gastroenterology clinics: the Stollery Children's Hospital in Edmonton and the Children's Hospital of Eastern Ontario (CHEO) in Ottawa.CAM use at the Stollery was 83% compared with 36% at CHEO (P 0.001). The most common reason for not using CAM was lack of knowledge about it. Most respondents felt comfortable discussing CAM in their clinic and wanted more information on CAM. The most common CAM products being taken were multivitamins (91%), calcium (35%), vitamin C (32%), probiotics (14%), and fish oil/omega-3 fatty acids (13%). The most common CAM practices being used were massage (43%), chiropractic (27%), faith healing (25%), and relaxation (18%). Most respondents believed that CAM was helpful, and most of the 23 reported adverse effects were minor. Seven were reported as moderate, and 3 were reported as severe. Many (42%) patients used CAM at the same time as prescription medicines, and of these patients, concurrent use was discussed with their physician (76%) or pharmacist (52%).CAM use is high among pediatric patients with GI disorders and is much greater among those in Edmonton than in Ottawa. Most respondents reported their CAM use as helpful, with little or no associated harm. Many patients fail to disclose their concurrent use of CAM and conventional medicines to their doctors, increasing the likelihood of interactions.

1. Jaden Wright, MD* 2. Denise Adams, PhD* 3. Sunita Vohra, MD, MSc* 1. *University of Alberta, Edmonton, Alberta, Canada. Although potentially important for a patient’s well-being, many medical procedures, including routine immunizations, are painful. Insufficient pain control during procedures can produce long-term negative effects, especially in the very young. (1) Pharmacotherapy is used commonly to treat pediatric pain; however, because of concerns about adverse effects, (2,3,4) many health care professionals and patients are interested in using nonpharmacologic options as well as or in place of medications. One potential option is the use of music or music therapy during a painful procedure. The formal definition of music therapy is “the skillful use of music and musical elements by an accredited music therapist to promote, maintain, and restore mental, physical, emotional, and spiritual health.” (5) Pediatric research has investigated the effects of both music therapy, in which a music therapist administers the intervention (active music therapy), and simply playing prerecorded music for the participant (passive music therapy). This review summarizes the evidence from randomized controlled trials (RCTs) of the use of music to reduce procedural pain in pediatric patients. Because pain is closely related to anxiety and distress, these measures are included when provided. We will look first at older children and then at neonates subject to procedural pain. The use of music for alleviating pain and anxiety in children (excluding neonates younger than 1 month) was summarized in a 2008 systematic review of 19 RCTs (5 trials of active and 14 trials of passive music therapy) that included a total of 1513 participants, ages 8 months to 20 years, who were undergoing procedures, including oral surgery, venipuncture, elective surgery, intramuscular injections, magnetic resonance imaging, general anesthesia, colposcopy, bone …

On the basis of review of the published literature,limitations in current data do not support the use ofa gluten-free and casein-free diet (gfcf-d) asa primary autism spectrum disorder (ASD) treatment.(13)(25)(26)(36) On the basis of clinical opinion, given the popularity of parents seeking a gfcf-d for their children with ASD, clinicians should acknowledge family’s concerns and provide appropriate information about a gfcf-d toguide them and prevent possible harm.

Background. Use of complementary and alternative medicine (CAM) by children with cancer is high; however, pediatric best cases are rare.Objectives. To investigate whether best cases exist in pediatric oncology using a three-phase approach and to compare our methods with other such programs.Methods. In phase I, Children’s Oncology Group (COG) oncologists were approached via email and asked to recall patients who were (i) under 18 when diagnosed with cancer, (ii) diagnosed between 1990 and 2006, (iii) had unexpectedly positive clinical outcome, and (iv) reported using CAM during or after cancer treatment. Phase II involved partnering with CAM research networks; patients who were self-identified as best cases were asked to submit reports completed in conjunction with their oncologists. Phase III extended this partnership to 200 CAM associations and training organizations.Results. In phase I, ten cases from three COG sites were submitted, and most involved use of traditional Chinese medicine to improve quality of life. Phases II and III did not yield further cases.Conclusion. Identification of best cases has been suggested as an important step in guiding CAM research. The CARE Best Case Series Program had limited success in identifying pediatric cases despite the three approaches we used.

Background Heterogeneity has been noted in the selection and reporting of disease-specific, pediatric outcomes in randomized controlled trials (RCTs). The consequence is invalid results or difficulty comparing results across trials. The primary objective of this systematic review was to assess primary outcome and outcome measure selection and reporting, in pediatric eosinophilic esophagitis (EoE) treatment trials. As secondary objectives, we compared trial disease definition to established concensus guidelines, and the efficacy of current EoE treatments. Methods We searched MEDLINE, EMBASE, The Cochrane Library, Cochrane Central Register of Controlled Trials (CENTRAL), and CINAHL since 2001. We also searched clinical trial registries (portal.nihr.ac.uk; clinicaltrials.gov; isrctn.com; and anzctr.org.au) and references of included studies. We included RCTs of EoE treatment in patients 0–18 years. Two authors independently assessed articles. Results Eleven studies met inclusion criteria. All identified primary outcomes, however, of 9 unique primary outcomes, only 2 were used in more than one study. In total, 25 unique primary and secondary outcome measures were employed for pediatric EoE treatment trials. Measurement properties and rationale for their selection was rarely provided. Uptake of consensus-based diagnostic criteria was 25 % in trials initiated after 2011. Due to the small number and heterogeneity of studies obtained, no meta-analysis of treatment efficacy could be undertaken. This SR was limited to exclusively pediatric RCTs. Conclusions The results of this study confirm the need for a standardized set of core outcomes that are universally reported in pediatric EoE trials. Consistent disease definition and standardized outcome reporting will facilitate meta-analyses across similar trials and inform future clinical decision-making. Systematic review registration number CRD42013003798

Cerebral palsy (CP) has been defined as a disorder affecting body movement, motor skills and postural control. It is caused by damage to the developing fetal or infant brain during pregnancy, at birth or during the first 3–5 years of life. Patients with CP often seek out CAM treatments, such as acupuncture. The objective of this study was to examine the evidence for the safety and effectiveness of acupuncture for CP. Four databases (Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, EMBASE and MEDLINE) were searched for RCTs and systematic reviews (SRs) of acupuncture and CP. Titles and abstracts were screened; articles meeting the selection criteria were retrieved in full. Studies were included if they were SRs or RCTs and evaluated the effectiveness of an acupoint stimulation technique in children with CP. Only English and Chinese language papers were included. The search identified seven studies; six RCTs and one quasi-RCT that included acupuncture in at least one group. Three of the RCTs compared different types of acupuncture, while four compared acupuncture to another active intervention, including osteopathy, massage, music and play. The evidence of safety and effectiveness for acupuncture and cerebral palsy is difficult to interpret due to poor reporting. When the effectiveness of a treatment is unknown, data about its safety are paramount. With regards to paediatric needle acupuncture, there is reasonable evidence to suggest that it is safe in trained hands. However, the safety of acupoint injection is unknown, particularly when foreign proteins are being injected.

Aim: Systematic reviews (SRs) are an important tool for the synthesis of research and are used to guide both research and clinical practice. Previous research suggests that changes to standard SR methodology may be warranted. The objectives of this study were to determine the value of adding Chinese-language databases to conventional systematic review (SR) search strategies, and ii) to determine the importance of methodological validation of TCM RCTs in the conduct of SRs of two health conditions, chronic fatigue syndrome (CFS) and EBV-infectious mononucleosis (mono). Methods: Ten English-language and two Chinese-language databases were searched from inception to 2008. After initial screening potentially relevant publications were retrieved and assessed based on predetermined inclusion criteria. Method of randomization was verified using author interviews. Results: Mono Search - While English-language database searches did not yield any potentially relevant references, Chinese-language database searches identified 14 studies labelled as RCTs. Author interview determined that 10 were clinical summaries and one a controlled clinical trial. Authors for three publications were unavailable. CFS Search - English-language and Chinese-language database searches identified 8 and 28 potentially relevant references, respectively, for a total of 36, however, none met all inclusion criteria. Conclusions: Utilization of Chinese-language databases greatly increased the number of potentially relevant references for each search. Unfortunately, due to methodological flaws, this additional information did not generate any usable information. Medical research in China continues to be active, including the conduct of RCTs, however, improvements in trial design and conduct in medical research in China are essential in order for this material to be useful in guiding research and practice.

Some cruciferous plants may serve as preventive treatments for several medical conditions; our objective was to systematically investigate their safety in humans. Four electronic databases were searched, and, of 10,831 references identified, 50 were included. Data were extracted by two independent reviewers, whereafter the association between interventions and adverse events was assessed. Adverse events in 53 subjects were identified through clinical trials; of these, altered drug metabolism was rated as certainly/likely caused by cruciferous plants. Adverse events in 1247 subjects were identified through observational studies, of which none received high causality ratings. Adverse events in 35 subjects were identified through case reports, of which allergies and warfarin resistance were rated as certainly/likely caused by cruciferous plants. We conclude that cruciferous plants are safe in humans, with the exception of allergies. Individuals treated with warfarin should consult their physician. Further investigation of uses of cruciferous plants in preventative medicine is warranted.

CONTEXT: Acupuncture is increasingly used in children; however, the safety of pediatric acupuncture has yet to be reported from systematic review. OBJECTIVE: To identify adverse events (AEs) associated with needle acupuncture in children. METHODS: Eighteen databases were searched, from inception to September 2010, irrespective of language. Inclusion criteria were that the study (1) was original peer-reviewed research, (2) included children from birth to 17 years, inclusively, (3) involved needle acupuncture, and (4) included assessment of AEs in a child. Safety data were extracted from all included studies. RESULTS: Of 9537 references identified, 450 were assessed for inclusion. Twenty-eight reports were included, and searches of reference lists identified 9 additional reports (total: 37). A total of 279 AEs were identified, 146 from randomized controlled trials, 95 from cohort studies, and 38 from case reports/series. Of the AEs, 25 were serious (12 cases of thumb deformity, 5 infections, and 1 case each of cardiac rupture, pneumothorax, nerve impairment, subarachnoid hemorrhage, intestinal obstruction, hemoptysis, reversible coma, and overnight hospitalization), 1 was moderate (infection), and 253 were mild. The mild AEs included pain, bruising, bleeding, and worsening of symptoms. We calculated a mild AE incidence per patient of 168 in 1422 patients (11.8% [95% confidence interval: 10.1–13.5]). CONCLUSIONS: Of the AEs associated with pediatric needle acupuncture, a majority of them were mild in severity. Many of the serious AEs might have been caused by substandard practice. Our results support those from adult studies, which have found that acupuncture is safe when performed by appropriately trained practitioners.

Aims: To assess the long-term outcome of patients who underwent radioactive stent (RS) implantation. Methods and results: The RS study population consisted of 133 consecutive patients who underwent RS implantation between November 1997 and July 2000. They were matched using the propensity score method with 266 patients who underwent bare metal stenting (BMS) in the same span. Long-term survival status and information on MACE (death, non-fatal myocardial infarction or any re-intervention) was retrospectively obtained. Eight-year cumulative survival (90.2% vs. 87.4%, p=0.57) was similar between the RS and BMS group respectively, while 8-year cumulative MACE-free survival was significantly lower in RS patients (42.1% vs. 64.3%, p

Michael Kenneth Weaver (“Mike”) trained in anaesthesia at the Northern School of Anaesthesia, followed by a period of post-CCT specialist training in paediatric anaesthesia in Pittsburgh, USA. He was appointed consultant at the Queen Elizabeth Hospital in Gateshead in 1996. As college tutor and clinical director, he developed a modern department that remains one of the most popular training …

We examined perceived skin cancer risk and its relationship to sunscreen use among a large ( N = 1932) random sample of African American adults for the first time. Skin cancer risk perceptions were low (Mean = 16.11 on a 1—100 scale). Sun-sensitive skin type and a prior cancer diagnosis were associated with higher perceived skin cancer risk, but demographic factors were not. Unlike findings for Whites, perceived skin cancer risk was not associated with sunscreen use among African Americans. Directions for future research, and suggestions for increasing sunscreen use among African Americans are provided.

1. Denise Adams, BSc* 2. Sunita Vohra, MD, MSc* 1. *Complementary and Alternative Research and Education (CARE) Program, Department of Pediatrics, Faculty of Medicine, University of Alberta, Edmonton, Alberta, Canada. On behalf of the American Academy of Pediatrics Section on Complementary and Integrative Medicine Nocturnal enuresis (NE) is characterized by the involuntary discharge of urine at night in those 5 years of age or older. Primary NE (PNE) is diagnosed in an individual who has never achieved nighttime dryness; in secondary NE (SNE), incontinence follows a dry period of at least 6 months. In either, the enuresis must not be due exclusively to a medical condition or diuretic therapy. Prevalence is estimated at 5% to 10% among 5-year-olds, 3% to 5% among 10-year-olds, and 1% among those 15 years of age and older. Between 5% and 10% of cases resolve annually without treatment. (1) The causes of PNE and SNE remain unclear, although physical, neurologic, and psychological factors; genetics; sleep structure; and other medical conditions have been implicated. (2) Treatment for NE includes pharmacologic and nonpharmacologic options, and many families are interested in complementary and integrative approaches. This review assesses the efficacy and safety of acupuncture/acupressure, hypnosis, and biofeedback in treating NE. Originally developed as a health-care tool in China thousands of years ago, the stimulation of specific points on the body (called acupoints) may be carried out by a variety of techniques, including insertion of thin needles (acupuncture), surface pressure (acupressure), electricity (electro-acupuncture), and laser (laser acupuncture). The effect of acupuncture on PNE was assessed through two recent systematic reviews. (3)(4) The Cochrane review summarized the results of three randomized controlled trials (RCTs). (5)(6)(7) In the first study, 111 patients ages 5 to 15 years were assigned randomly to two different forms of acupuncture. (5) In the treatment group, a needle was embedded under the skin and left in place; in the control group, a needle was placed on the skin surface for 30 minutes each day. The number of treatment courses (of 6 days …

In preparation for a clinical trial on the efficacy of Echinacea products with a pediatric population, a rational method for selection of test products was developed, based on phytochemical and bioassay evaluation. Ten currently available commercial products of Echinacea angustifolia (EA) or Echinacea purpurea (EP) were selected, and 3 bottles of each of 2 different lots were purchased for each product. Investigators were blinded to product identity before phytochemical analysis. Lot-to-lot variation was small, but product variation due to species and formulation was large. Products derived from ethanol extracts had low polysaccharide content and high levels of alkamides (EA), echinacoside (EA), cynarin (EA), cichoric acid (EP), and caftaric acid (EP). These products possessed high antiviral activities that differed between EA and EP products, but limited immune activation properties. In contrast, products derived without ethanol extraction had higher polysaccharide levels, but low levels of other components. These aqueous compounds showed immunostimulant activity as measured in a mouse macrophage model and a somewhat different antiviral profile. The choice of Echinacea product for clinical trial must therefore consider the impact of immune enhancement, the specific viral infection targeted, and the potential to reduce symptoms via antiinflammatory activity. Product selection may also depend on whether the intent of the trial is prophylaxis or treatment.

Purpose: To report the results of the first pharmacokinetic study in pediatric patients of O6-benzylguanine (O6BG), which irreversibly inactivates the DNA repair protein alkylguanine-alkyltransferase, thus enhancing the cytotoxicity of nitrosoureas. Experimental Design: As part of a Pediatric Oncology Group Phase I study, 120 mg/m2 of O6BG was administered i.v. over 1 h, before 1,3-bis(2-chloroethyl)-1-nitrosourea administration in children with recurrent or refractory brain tumors. Serial blood samples for plasma pharmacokinetic studies were obtained. Concentrations of O6BG and its active metabolite O6-benzyl-8-oxoguanine (8-oxo-O6BG) were measured by high-performance liquid chromatography. A pharmacokinetic model and additional first-order elimination rate constants for each compound were developed. Results: O6BG concentration versus time data were evaluated for 25 patients. The peak concentration of O6BG (mean ± SD) was 11 ± 4 μm, and the peak concentration of its active metabolite, 8-oxo-O6BG, was 35 ± 10 μm. O6BG was rapidly eliminated with a half-life of 85 ± 140 min, area under the curve of 795 ± 320 μm · min and clearance of 760 ± 400 ml/min/m2. The area under the curve of 8-oxo-O6BG when extrapolated to infinity was 22,700 ± 11,800 μm · min. The clearance and terminal half-life of 8-oxo-O6BG were 30 ± 15 ml/min/m2 and 360 ± 220 min, respectively. Conclusions: There is rapid elimination of O6BG after i.v. administration over 1 h. In contrast, the terminal half-life for the active metabolite, 8-oxo-O6BG, is 4-fold longer. The pharmacokinetic parameters for O6BG and 8-oxo-O6BG are similar to those reported previously in adults.

Background The Core Outcome Measures in Effectiveness Trials (COMET) initiative aims to facilitate the development and application of ‘core outcome sets’ (COS). A COS is an agreed minimum set of outcomes that should be measured and reported in all clinical trials of a specific disease or trial population. The overall aim of the Core Outcome Measurement Instrument Selection (COMIS) project is to develop a guideline on how to select outcome measurement instruments for outcomes included in a COS. As part of this project, we describe our current efforts to achieve a consensus on the methods for selecting outcome measurement instruments for outcomes to be included in a COS. Methods/Design A Delphi study is being performed by a panel of international experts representing diverse stakeholders with the intention that this will result in a guideline for outcome measurement instrument selection. Informed by a literature review, a Delphi questionnaire was developed to identify potentially relevant tasks on instrument selection. The Delphi study takes place in a series of rounds. In the first round, panelists were asked to rate the importance of different tasks in the selection of outcome measurement instruments. They were encouraged to justify their choices and to add other relevant tasks. Consensus was reached if at least 70% of the panelists considered a task ‘highly recommended’ or ‘desirable’ and if no opposing arguments were provided. These tasks will be included in the guideline. Tasks that at least 50% of the panelists considered ‘not relevant’ will be excluded from the guideline. Tasks that were indeterminate will be taken to the second round. All responses of the first round are currently being aggregated and will be fed back to panelists in the second round. A third round will only be performed if the results of the second round require it. Discussion Since the Delphi method allows a large group of international experts to participate, we consider it to be the preferred consensus-based method for our study. Based upon this consultation process, a guideline will be developed on instrument selection for outcomes to be included in a COS.

Humanism and professionalism are virtues intrinsic to the practice of medicine, for which we lack a standard, evidence-based approach for teaching and evaluation. Pediatric hematology-oncology (PHO) fellowship training brings new and significant stressors, making it an attractive setting for innovation in humanism and professionalism training.We electronically surveyed a national sample of PHO fellows to identify fellows' educational needs in humanism and professionalism. Next, we developed a case-based, faculty-facilitated discussion curriculum to teach this content within pilot fellowship programs. We assessed whether fellowships would decide to offer the curriculum, feasibility of administering the curriculum, and satisfaction of fellow and faculty participants.Surveys were completed by 187 fellows (35%). A minority (29%) reported that their training program offers a formal curriculum in humanism and/or professionalism. A majority desires more formal teaching on balancing clinical practice and research (85%), coping with death/dying (85%), bereavement (78%), balancing work and personal life (75%), navigating challenging relationships with patients (74%), and depression/burn out (71%). These six topics were condensed into four case-based modules, which proved feasible to deliver at all pilot sites. Ten fellowship programs agreed to administer the novel curriculum. The majority (90%) of responding fellows and faculty reported the sessions touched on issues important for training, stimulated reflective communication, and were valuable.Pediatric hematology-oncology fellows identify numerous gaps in their training related to humanism and professionalism. This curriculum offers an opportunity to systematically address these educational needs and can serve as a model for wider implementation. Pediatr Blood Cancer 2015;62:335-340. © 2014 Wiley Periodicals, Inc.

Kaposiform lymphangiomatosis (KLA) is a rare proliferation of abnormal lymphatic vessels often complicated by pleural/pericardial effusions and a consumptive coagulopathy that may lead to life threatening hemorrhage. Establishing the diagnosis is challenging due to the clinical heterogeneity and variable findings in laboratory values, radiographic features, and pathologic characteristics. We report three patients who had slowly progressive symptoms and presented with pleural or pericardial effusions, evidence of a consumptive coagulopathy and anemia. Despite being a rare and challenging diagnosis, KLA should be considered in patients presenting with non-specific indolent symptoms, pleural or pericardial effusions and laboratory evidence of a consumptive coagulopathy.

We describe a child initially diagnosed with multi-focal infantile hemangioma (cutaneous, hepatic, pulmonary), a benign vascular lesion, which underwent malignant transformation to angiosarcoma. The use of anti-angiogenic agents, such as bevacizumab, an anti-vascular endothelial growth factor (VEGF) antibody, has been reported in adults with angiosarcoma. Treatment with chemotherapy (gemcitabine and docetaxel) and bevacizumab resulted in disease response with progression free survival of 12 months. This report describes the response to chemotherapy and bevacizumab in a child with angiosarcoma and highlights the potential for malignant transformation of benign vascular lesions and the need for careful monitoring.

The Children's Oncology Group (COG) study ANBL00P2 showed that expectant observation of patients younger than six months of age with perinatal neuroblastoma presenting as a small adrenal mass yields excellent overall survival and spares surgical resection to the majority of patients. We report a 5-year-old female who was initially diagnosed with a perinatal neuroblastoma. The patient was observed on COG study ANBL00P2. By nine months of age she had no ultrasonographic or biochemical evidence of disease. She presented four years later with abdominal pain and was found to have high-risk stage 4 MYCN amplified neuroblastoma.

Two types of polymorphic DNA markers suitable for genome analyses, population genetic and ecological studies on lodgepole pine (Pinus contorta var. latifolia) have been developed. We detected 52 decameric oligonucleotides, within a set of 200, that could be used to amplify the pine DNA. From these, 4 that allowed unambiguous amplification of 10 random polymorphic (RAPD) loci, have been chosen for use in this species. Five polymorphic microsatellite loci were found following the screening of a genomic library and all contained the AGn motif. Such loci were present at a frequency of 1 in every 345 kb pairs of genomic DNA. Three loci were comprised of a simple dinucleotide repeat, one locus was of the form TAn -G A m and one was ATn -A G m. The number of alleles at the 5 microsatellite loci ranged from 3 to 8 in a sample of 6 trees from the eastern foothills of the Rocky Mountains in Alberta and the alleles at all loci exhibited Mendelian segregation. Resume : Deux types de marqueurs moleculaires polymorphes adaptes aux analyses genomiques, aux etudes en genetique des population et en ecologie ont ete developpes chez le pin lodgepole (Pinus contorta var. latifolia). Parmi 200 amorces decanucleotidiques, 52 permettaient d'amplifier l'ADN du pin. De celles-ci, quatre ont permis l'amplification non-ambigue de 10 loci RAPD et ont ete utilisees chez cette espece. Cinq microsatellites polymorphes ont ete identifies suite au criblage d'une banque genomique et tous contenaient le motif (AG) n. De tels loci etaient presents a tous les 345 kilobases en moyenne chez l'ADN genomique. Trois de ces loci comptaient de simples repetitions du motif dinucleotidique alors qu'un locus presentait un motif TA n -G A m et un dernier un motif ATn - AGm. Le nombre d'alleles pour les cinq microsatellites variait de trois a huit parmi un echantillon de six arbres provenant des collines situees au pied des Montagnes Rocheuses en Alberta et les alleles de ces marqueurs segregait de facon mendelienne.

Respiratory tract infectious diseases are a group of the most common, widespread diseases, from common cold and influenza to tuberculosis and pneumonia; some of them may cause serious and even life-threatening health problems. Most cases of upper respiratory tract infectious diseases include common cold and influenza, which are mainly caused by various virus infections, and tuberculosis, pneumonia, and other low respiratory tract infectious diseases caused by different bacterial infections. Releasing the symptoms and preventing complicated bacterial infection are a rule of treating virus infected upper respiratory tract infectious diseases. Traditionally, herbal medicines are used to treat and prevent the respiratory tract infectious diseases such as common cold and influenza worldwide. For example, more than two hundred patent products of traditional Chinese medicines have been approved into market for treatment and prevention of the common cold as well as influenza. In the past decades, some herbal medicines are developed as injections for clinical use for treating respiratory tract infections, such as Caihu injection, Shuanghuanglian injection, Yuxincao injection, and Qinkailing injection. Some of these medicines are believed to effectively release the symptoms; some are believed to strengthen the immune function of patient and therefore result in the virus and bacteria being eliminated; some are believed to kill the microorganisms directly. A fact is that although a lot of herbal medicines are widely used clinically, most evidence supporting their use came from poorly reported published clinical studies or studies with questionable methodology, as Drs. Q. Yang, H. Zhang, C. Zou, and L. Wu, concluded in their systematic reviews. Call for high quality evidence is a mission of this special issue. Fortunately, Dr. J. Chang and her colleagues contributed high quality evidence about a patent Chinese medicine Shi-Cha capsule for common cold by a well-designed, well-conducted, and well-reported randomized controlled trial. In this multicenter study, they have done very well on the ethicas issues including protocol aproval by ethical committee, properly informed consent and registered their protocol in a public clinical trial registry—Chinese Clinical Trial Registry; and high quality methodological issues, including the randomization method and allocation procedure, the recruitment of patients, the data management, the analysis method of results, all of these were described in detail and very clearly according to CONSORT statement. This transparency makes readers confident to trust the result of the study and we believe such evidence should be graded as high quality. if the reporting referes to CONSORT for TCM to provide more information of the principle of using Shi-Cha capsule for with “wind-cold type common cold” will makes readers better understanding on the rational of this medicine. Another advantage of this trial is that placebo control was used for comparison with Shi-Cha capsule. Usually, use of a medicine in which “the effect is accepted by public recognition” as the control is one of rules of the new medicine development clinical trial in China. The shortcoming of this rule is that it caused difficulty to assess the effects for a lot of traditional Chinese medicines because of the lack of evidence of effect of the controls. For the self-limited disease, a placebo control should be encouraged to be used in the treatment study. We believe that this study and its report could be a good example of high quality study and good reporting. Another valuable thing we have seen is that Dr. C. Zou and his colleagues, physicians of traditional Chinese medicine, are using evidence-based medicine (EBM) method to critically appraise the evidence and using the results to guide their clinical practice successfully. This absolutely is a revolutionary event in the field while most traditional medical clinicians may not know EBM exactly. We hope more and more clinicians in the field can use EBM method to guide their practices and make the health care service better and better. Studies came from France, Japan, South Africa, and Taiwan provide from in vitro and animal study suggesting that some herbal medicines may have antimicrobial activity or can strengthen the immune function. It is expected that these lines of evidence will result in more confidence to support the clinical use of complementary and alternative medicines. Taixiang Wu Zhao-Xiang Bian Minawaer Abudu Denise Adams Seong-Gyu Ko

Objectives Little is known about polytobacco use among African-American adults. This study is the first to explore this among a random, statewide, community sample of African-American adults. Setting Community-based sampling obtained a random, household-probability sample of African-American adults from California, surveyed door to door in randomly selected census tracts statewide. Participants Participants were a statewide, random-household sample of N=2118 African-American adults from California who completed a survey on past 30-day smoking of cigarettes, blunts, bidis, kreteks, cigarillos, marijuana and cigars. Results Almost half (49.3%) of the African-American cigarette-smokers and 14.9% of the cigarette non-smokers had smoked at least one non-cigarette product in the past 30 days. Smokers had a substantial prevalence of smoking cigarillos (28.7%) and blunts (27.7%). Logistic regressions revealed that the odds of smoking most of the non-cigarette products were higher for cigarette smokers and men, inversely related to age, and unrelated to socioeconomic status. However, smoking of blunts, bidis and kreteks was not predicted by cigarette smoking. Conclusions Smoking of cigarillos (eg, Phillies , Black & Mild ) and blunts may be prevalent among African-American cigarette-smokers and non-smokers alike, but such products are not examined in most population-level smoking research. Smoking of these products should be included in surveillance studies, in cancer prevention programmes and in healthcare provider-assessment of smoking, and addressed in smoking cessation programmes as well.

Background.The use of complementary and alternative medicine (CAM) is high among children and youths with chronic illnesses, including cancer. The objective of this study was to assess prevalence and patterns of CAM use among pediatric oncology outpatients in two academic clinics in Canada.Procedure.A survey was developed to ask patients (or their parents/guardians) presenting to oncology clinics at the Stollery Children’s Hospital in Edmonton and the Children’s Hospital of Eastern Ontario (CHEO) in Ottawa about current or previous use of CAM products and practices.Results.Of the 137 families approached, 129 completed the survey. Overall CAM use was 60.5% and was not significantly different between the two hospitals. The most commonly reported reason for not using CAM was lack of knowledge about it. The most common CAM products ever used were multivitamins (86.5%), vitamin C (43.2%), cold remedies (28.4%), teething remedies (27.5%), and calcium (23.0%). The most common CAM practices ever used were faith healing (51.0%), massage (46.8%), chiropractic (27.7%), and relaxation (25.5%). Many patients (40.8%) used CAM products at the same time as prescription drugs.Conclusion.CAM use was high among patients at two academic pediatric oncology clinics. Although most respondents felt that their CAM use was helpful, many were not discussing it with their physicians.

Systematic reviews (SRs) are an important tool for the synthesis of research and are used to guide both research and clinical practice. Previous research suggests that changes to standard SR methodology may be warranted. The objectives of this study were to determine the value of adding Chinese-language databases to conventional systematic review (SR) search strategies, and ii) to determine the importance of methodological validation of TCM RCTs in the conduct of SRs of two health conditions, chronic fatigue syndrome (CFS) and EBV-infectious mononucleosis (mono).Ten English-language and two Chinese-language databases were searched from inception to 2008. After initial screening potentially relevant publications were retrieved and assessed based on predetermined inclusion criteria. Method of randomization was verified using author interviews.Mono Search - While English-language database searches did not yield any potentially relevant references, Chinese-language database searches identified 14 studies labelled as RCTs. Author interview determined that 10 were clinical summaries and one a controlled clinical trial. Authors for three publications were unavailable. CFS Search - English-language and Chinese-language database searches identified 8 and 28 potentially relevant references, respectively, for a total of 36, however, none met all inclusion criteria.Utilization of Chinese-language databases greatly increased the number of potentially relevant references for each search. Unfortunately, due to methodological flaws, this additional information did not generate any usable information. Medical research in China continues to be active, including the conduct of RCTs, however, improvements in trial design and conduct in medical research in China are essential in order for this material to be useful in guiding research and practice.