First-line Treatment For Children Research Articles

High-flow nasal cannulas versus standard oxygen therapy for moderate bronchiolitis: a quasi-experimental analysis.

In the last decades none of the medical therapies investigated have shown clear efficacy in the treatment of bronchiolitis, and literature agrees on a general de-implementation of pharmacological therapies, recognizing an effective role only to nutritional support and oxygen therapy. High-flow nasal cannulas (HFNC) has become increasingly popular in the last decade, despite its lack of clear efficacy. Recent randomized controlled trials (RCT) comparing standard oxygen therapy (SOT) and HFNC did not demonstrate significant benefit of HFNC. To acquire more clinical data on HFNC efficacy we performed a retrospective, quasi-experimental analysis of patients admitted for bronchiolitis in the epidemic seasons 2021-2022 and 2022-2023. To assess the efficacy of SOT and HFNC we used a pragmatic approach, a fuzzy regression discontinuity design, which is a quasi-experimental test. Unlike RCTs, this process is not a true randomization, but may be interpreted as quasi-randomization in an observational setting. HFNC did not reduce length of oxygen therapy (LOO) nor length of hospitalization (LOS) (respectively, p: 0.383 and p: 0.454). Treatment failure was not significantly different in the treatment groups (p: 0.354). It is crucial to perform additional RCTs with uniform protocols to determine the efficacy of HFNC more accurately in the treatment of bronchiolitis. HFNC does not reduce LOO, suggesting that early use of HFNC does not change the course of disease in moderate bronchiolitis. In view of the greater complexity and higher cost, HFNC should not be routinely used as first-line treatment in children with moderate respiratory distress and mild hypoxemia.

Patterns, Barriers, and Preferences of Treating Migraine Within the School Setting: A Survey Study of Students

Background/Objectives: Migraine affects 10% of adolescents and children. Typical school protocols in the USA require pharmacological medications to be administered by school nurses, often resulting in treatment delays or omissions when migraine attacks occur during school hours. The Remote Electrical Neuromodulation (REN) wearable is an FDA-cleared smartphone-controlled device delivering acute and preventive treatment of migraine attacks in patients aged 8 and above, allowing safe, effective, discreet, and independent usage. Methods: This retrospective study (NCT06180577) evaluates treatment patterns, barriers, and preferences among school-age students. REN users < 18 years old were invited to complete an online survey. Participants signed an assent form, and their parents/legal guardians signed an informed consent form. Results: 332 patients aged 7–17 (15.5 ± 2.1) participated (80.4% female). After being prescribed the REN wearable, the percentage of students who treated their headaches at school increased from 78.3% to 89.8%. Most participants (65.4%) treated with either REN standalone (38.0%) or in combination with medications (27.4%). Common barriers to treatment included the need to leave class for the nurse’s office (64.2%), concerns about standing out (42.2%), and one barrier unique to REN–permission needed to use a smartphone in class (22.9%). The most common reasons given for preferring REN treatment at school are the ability to avoid going to the nurse’s office (42.5%) and to treat discreetly (39.2%). Conclusions: This study underscores the challenges of managing migraine at school while suggesting the importance of the REN wearable as a discreet and independently used first-line treatment for children and adolescents.

Pharmacogenomic associations of cyclophosphamide pharmacokinetic candidate genes with 4hydroxycyclophosphamide formation in children with Cancer.

4-hydroxycyclophosphamide (4HCY) is the principal precursor to the cytotoxic metabolite of cyclophosphamide (CY), which is often used as first-line treatment of children with cancer. There is conflicting data regarding the relationship between CY efficacy, toxicity, and pharmacokinetics with the genes encoding proteins involved in 4HCY pharmacokinetics, specifically its formation and elimination. We evaluated germline pharmacogenetics in children with various malignancies receiving their first CY dose. Using linear regression, we analyzed the associations between two pharmacokinetic outcomes - how fast a child cleared CY (i.e., CY clearance) and the ratio of the 4HCY/CY exposure, specifically area under the plasma concentration-time curve (AUC), and 372 single nucleotide polymorphisms (SNP) in 14 drug-metabolizing transporters or enzymes involved in 4HCY formation or elimination. Age was associated with the ratio of 4HCY/CY AUC (P = 0.004); Chemotherapy regimen was associated with CY clearance (P = 0.003). No SNPs were associated with CY clearance or the ratio of 4HCY/CY AUC after controlling for a false discovery rate. Age and chemotherapy regimen, but not germline pharmacogenomics, were associated with CY clearance or the ratio of 4HCY/CY AUC. Other methods, such as metabolomics or lipidomics, should be explored.

Complications after Heller myotomy in children: a national multicenter study on the impact of prior endoscopic dilatation and identification of risk factors.

Although esophageal achalasia has been historically treated by Heller myotomy, endoscopic esophageal dilatations are nowadays often the first-line treatment in children. The aim was to assess whether performing an endoscopic dilatation before a Heller myotomy is associated with higher risks of esophageal perforation in children. A retrospective multicentric study was performed, including children that underwent a Heller myotomy (2000-2022, 10 centers). Two groups were compared based on the history of previous dilatation before myotomy. Outcomes esophageal perforation (intra-operative or secondary) and post-operative complications requiring surgery (Clavien-Dindo III). Statistics Comparisons using contingency tables or Kruskal-Wallis when appropriate. Statistical significance: p-value < 0.05. A Heller myotomy was performed in 77 children (median age: 11.8 years), with prior endoscopic dilatation in 53% (n = 41). A laparoscopic approach was used in 90%, with associated fundoplication in 95%. Esophageal perforation occurred in 19% of children (n = 15), including 12 patients with intra-operative mucosal tear and 3 with post-operative complications related to an unnoticed esophageal perforation. Previous endoscopic dilatation did not increase the risk of esophageal perforation (22% vs 17%, OR: 1.4, 95%CI: 0.43-4.69). Post-operative complications occurred in 8% (n = 6), with similar rates regardless of prior endoscopic dilatation. Intra-operative mucosal tear was the only risk factor for post-operative complications, increasing the risk of complications from 5 to 25% (OR: 6.89, 95%CI: 1.38-31.87). Prior endoscopic dilatations did not increase the risk of esophageal perforation or postoperative complications of Heller myotomy in this cohort of children with achalasia. Mucosal tear was identified as a risk factor for post-operative complications.

Open reduction versus close treatment in management of children mandibular fracture: A systematic review

Mandibular fractures in children are the most common facial bone injury, which is 39% of all fractures. Adequate treatment of mandible fractures was still debated to restore the best physiological and aesthetic outcome. This systematic review aims to compare open reduction and closed treatment outcomes in children with mandibular fractures based on evidence from the current study. Four electronic databases were used: PubMed, ScienceDirect, Directory of Open Access Journals (DOAJ), and Google Scholar. Studies included were randomized and non-randomized clinical studies written in English and published in the last 10 years (2014). Children patients under 18 years of age, of any sex, with any mandible fracture treated with any functional appliance. Data was collected using a standard form agreed upon by two independent reviewers. The risk of bias and quality were assessed using the Newcastle-Ottawa Quality Assessment Scale (NOS). Ten studies were selected for this systematic review, including 554 patients. Half of studies chosen had a high risk of bias, 4 were deemed to have a moderate risk of bias, and one had a low risk of bias. Comparing ORIF and close treatment, we get the incidence of complications versus cases respectively, 9/182 versus 5/372. The data collected, although there is still a lot of bias in this review. We support close treatment as the first line treatment for children’s mandible fractures because the minimal number of possible complications.

Eltrombopag and high-dose dexamethasone as first-line treatment in children with newly diagnosed primary immune thrombocytopenia

Eltrombopag and high-dose dexamethasone as first-line treatment in children with newly diagnosed primary immune thrombocytopenia

Can low-dose intravenous immunoglobulin be an alternative to high-dose intravenous immunoglobulin in the treatment of children with newly diagnosed immune thrombocytopenia: a systematic review and meta-analysis

Intravenous immunoglobulin (IVIg) is a first-line treatment for children with newly diagnosed immune thrombocytopenia (ITP). Higher doses of IVIg are associated with a more insupportable financial burden to pediatric patients’ families and may produce more adverse reactions. Whether low-dose IVIg (LD-IVIg) can replace high-dose IVIg (HD-IVIg) has yet to be established. We conducted a comprehensive literature search from the establishment of the database to May 1, 2023, and eventually included 22 RCTs and 3 cohort studies compared different dosages of IVIg. A total of 1989 patients were included, with 991 patients in the LD-IVIg group and 998 patients in the HD-IVIg group. Our results showed no significant differences between the two groups in the effective rate (LD-IVIg: 91% vs. HD-IVIg: 93%; RR: 0.99; 95%CI: 0.96–1.02) and the durable remission rate (LD-IVIg: 65% vs. HD-IVIg: 67%; RR: 0.97; 95%CI: 0.89–1.07). Similar results were also found in the time of platelet counts (PC) starting to rise (MD: 0.01, 95%CI: -0.06–0.09), rising to normal (MD: 0.16, 95%CI: -0.03–0.35), and achieving hemostasis (MD: 0.11, 95%CI: -0.02–0.23) between the two groups. Subgroup analysis showed the effective rate of 0.6 g/kg was equal to 1 g/kg subgroup (91%) but higher than 0.8 g/kg subgroup (82%), and a combination with glucocorticoid may contribute to effect enhancement (combined with glucocorticoid: 91% vs. IVIg alone: 86%) whether combined with dexamethasone (92%) or methylprednisolone (91%). Besides, the incidence rate of adverse reactions in the LD-IVIg group (3%) was significantly lower than the HD-IVIg group (6%) (RR: 0.61; 95%CI: 0.38–0.98). So low-dose IVIg (≤ 1 g/kg) is effective, safe, and economical, which can replace high-dose IVIg (2 g/kg) as an initial treatment. This systematic review was registered in PROSPERO (CRD42022384604).

Use of Andexanet Alfa for Factor Xa Inhibitor Reversal in US Verified Trauma Centers: A National Survey.

Direct oral factor Xa inhibitors are replacing vitamin K-dependent antagonists as anticoagulation treatment in many clinical scenarios. Trauma centers are noting an increase in patients presenting on these medications. The 2018 Food and Drug Administration approval of andexanet alfa provides an alternative anticoagulation reversal. Barriers may limit utilization of new medications including a lack of grade 1A evidence supporting the use of prothrombin complex concentrate (PCC) versus andexanet alfa and cost. To evaluate barriers of andexanet alfa utilization by trauma surgeons, a 15-question survey was conducted. There was a 9% completion rate (n = 89). The results revealed 23.5% would choose andexanet alfa as first-line treatment in children, and 25.8% as first-line treatment in adults. The majority of respondents, 64.7% and 67.4%, would use PCC preferentially in children and adults, respectively. Respondents indicated that cost burden was an overriding factor (76.3%); 42.4% cited lack of high-level efficacy data of andexanet alfa for reversal of factor Xa inhibitors. Additional double-blinded multi-institutional randomized controlled trials comparing 4F-PCC and andexanet alfa for factor Xa inhibitor reversal are needed to support efficacy especially with the increased cost associated.

Effectiveness of Low Dose D-Penicillamine Therapy in Neurologic Wilson Disease - A Prospective Observational Study

Background: Wilson disease is an inherited disorder of copper metabolism that mostly manifests as hepatic and neurologic symptoms. Chelation therapy specially penicillamine is given as first line treatment in children with symptomatic Neurologic Wilson disease. Objective: Objective of the study was to assess the safety &amp; the clinical outcome of treatment with low dose penicillamine in Neurologic Wilson disease. Methods: A longitudinal observational study was conducted at Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, a tertiary care Premier Postgraduate Medical Institution of Bangladesh. Thirty-nine (39) patients of Neurologic Wilson disease who fulfill the inclusion and exclusion criteria were evaluated at In-patient Department of Paediatric Neurology, during the period of January 2015 to December 2019. All study children were treated with low dose penicillamine (Cap Artamin 250 mg) rather with conventional dose penicillamine (Cap Artamin 500 mg or 20 mg/kg/day). Subsequent follow up examination was performed at 2 weeks, 1, 3 and 6 months. Follow up was done by global assessment scoring (GAS) and slit lamp examination to see the clinical improvement after treatment with low dose penicillamine therapy. Results: Total number of studied cases were 39. Mean age was 10.2 ± 3.1 year and male to female ratio was 2:1. Most of the patients (66.67%) were arrived from rural area and 20.51% children had history of consanguineous mating parents. Common presenting features were progressive deterioration of school performance (89.74%), gait disturbance (92.31%), dysarthria (92.31%) and dystonia (82.06%) of our studied children. Ophthalmological manifestations like KF ring (100%) found in all patients. Neuroimaging showed bilateral basal ganglia involvement in (63.63%) children followed by hyperintense signal changes (18.18%) and ventricular dilatation in (18.18%) of cases. Majority of the children (74.36%) were improved with low penicillamine therapy clinically and KF ring disappeared in (5.12%) cases after drug therapy on follow up. Commonest side effects were worsening of neurological symptoms in (25.64%) and rash &amp; thrombocytopenia in (5.1%) cases after penicillamine therapy. Conclusion: About three-fourth children of studied Neurologic Wilson disease showed gradual improvement with low-dose penicillamine therapy. Moreover, one-fourth of cases experienced neurological deterioration, which was lower than previously used high dose penicillamine therapy. Therefore, low dose penicillamine may be beneficial as an initial therapy for Wilson disease with neurological manifestations.

Intravenous versus super-selected intra-arterial chemotherapy in children with advanced unilateral retinoblastoma: an open-label, multicentre, randomised trial.

Super-selected intra-arterial chemotherapy has increasingly been used as conservative management for retinoblastoma during the past decade. However, the absence of evidence from randomised controlled trials engendered controversy in the administration route of chemotherapy. We aimed to assess the efficacy and safety of intra-arterial chemotherapy compared with intravenous chemotherapy. This open-label, multicentre, randomised trial was done at six hospitals in China. Patients with new-onset unilateral group D or E retinoblastoma (poorly defined, large, or very large tumours, according to the International Intraocular Retinoblastoma Classification) without high-risk clinical factors were included. Patients were randomly assigned (1:1) to receive intra-arterial chemotherapy (injections of 0·5 mg/kg [or depending on age] melphalan with 20 mg carboplatin [first and third cycles] or with 1 mg topotecan [second and fourth cycles]) or intravenous chemotherapy (0·05 mg/kg [or 1·5 mg/m2] vincristine, 5 mg/kg [or 150 mg/m2] etoposide, and 18·6 mg/kg [or 560 mg/m2] carboplatin for six cycles). After intra-arterial chemotherapy, patients received a subcutaneous injection of 0·1 mL nadroparin calcium twice at a 12 h interval. Both intra-arterial and intravenous chemotherapy cycles were completed every 4 weeks. No masking was done, except of independent statisticians, who were masked to the allocation information. The primary outcome was 2-year progression-free globe salvage rate, defined as the time from randomisation to tumour progression or enucleation, whichever occurred first, and was analysed by intention to treat. We also recorded predefined safety outcomes (myelosuppression and ophthalmic arterial stenosis or occlusion) and severe adverse events likely to be related to study treatment. The study is registered with the Chinese Clinical Trial Registry, ChiCTR-IPR-15006469, and is complete. Between June 1, 2015, and June 1, 2018, 234 patients with newly diagnosed retinoblastoma were screened and 143 eligible patients (median age 23·6 months [IQR 14·0-31·9]) were enrolled and randomly assigned to the intra-arterial chemotherapy group (n=72) or the intravenous chemotherapy group (n=71). At a median follow-up of 35·8 months (IQR 28·4-43·0), the 2-year progression-free globe salvage rate was 53% (38 of 72 patients) in the intra-arterial chemotherapy group and 27% (19 of 71 patients) in the intravenous chemotherapy group (risk ratio 1·97, 95% CI 1·27-3·07, p=0·0020). Myelosuppression was less common in the intra-arterial chemotherapy group than in the intravenous chemotherapy group (37 [51%] of 72 patients vs 50 [70%] of 71 patients; 0·73, 95% CI 0·56-0·96, p=0·021) and less severe (ptrend=0·0070). In the intra-arterial chemotherapy group, two (3%) of 72 patients had ophthalmic artery occlusion and 13 (18%) patients had ophthalmic artery stenosis. Our findings show that intra-arterial chemotherapy could significantly improve the globe salvage rate in children with advanced unilateral retinoblastoma compared with intravenous chemotherapy, with mild systemic complications and no difference in overall survival rate. Intra-arterial chemotherapy could be an acceptable first-line treatment in children with advanced unilateral retinoblastoma. Scientific Research Program of the National Health and Family Planning Commission of China, the Clinical Research Plan of Shanghai Hospital Development Center, the National Natural Science Foundation of China, and the Science and Technology Commission of Shanghai Municipality.

Low-dose intravenous immunoglobulin for children with newly diagnosed immune thrombocytopenia: protocol of a systematic review and meta-analysis

IntroductionIntravenous immunoglobulin (IVIg) is a first-line treatment for children with newly diagnosed immune thrombocytopenia (ITP). However, the cost of IVIg is high. Higher doses of IVIg are associated with a...

Pediatric Intracranial Ependymoma - Recommendations for First-Line Treatment from the German HIT-MED study group

Biological subtypes of ependymoma (EPN) have been introduced by the recent WHO classification and appear to have great impact on the clinical course, but have not yet found their way into clinical risk stratification. Further, the overall unfavorable prognosis underlines the fact that current therapeutic strategies need further evaluation for improvement. To date, there is no international consensus regarding first-line treatment for children with intracranial EPN. Extent of resection is known to be the most important clinical risk factor, leading to the consensus that consequent evaluation for re-surgery of postoperative residual tumor needs to have highest priority. Furthermore, efficacy of local irradiation is unquestioned and recommended for patients aged>1 year. In contrast, efficacy of chemotherapy is still under discussion. The European trial SIOP Ependymoma II aims at evaluating efficacy of different chemotherapy elements, leading to the recommendation to include German patients. The BIOMECA study, as biological accompanying study, aims at identifying new prognostic parameters. These results might help to develop targeted therapies for unfavorable biological subtypes. For patient who are not qualified for inclusion into the interventional strata, the HIT-MED Guidance 5.2 provides specific recommendations. This article is meant as an overview of national guidelines regarding diagnostics and treatment as well as of treatment according to the SIOP Ependymoma II trial protocol.

The efficacy and the safety of eltrombopag in pediatric patients with severe aplastic anemia: a systematic review.

Acquired aplastic anemia (AAA) in pediatric patients is a rare disorder characterized by hypocellular bone marrow and pancytopenia. Eltrombopag, an oral thrombopoietin receptor agonist, provides a hematologic improvement in adults with severe aplastic anemia (SAA) refractory to immunosuppressive therapy (IST). The association of ELT and IST was approved by the US Food and Drug Administration (FDA) for adults and children ≥2 years of age as a first-line treatment for SAA. However, the effects of ELT on pediatric patients with SAA remain controversial and limited. We conducted a systematic review of the most recent literature from Pubmed, Web of Science, and Embase, published up to 20th December 2022, in order to evaluate the available evidence on the efficacy and safety of ELT added to IST for the treatment of SAA in the pediatric population. Eltrombopag added to the IST has shown a good safety profile, without manifestations of excessive toxic effects, although not all the results obtained from our studies support the addition of ELT to the IST in the first-line treatment of children with SAA. https://www.crd.york.ac.uk/prospero/, identifier: CRD42022325859.

Biliary drainage surgery before or after 3 months of life versus primary liver transplantation in children with biliary atresia: comparative cohort study.

Early biliary drainage surgery (BDS; Kasai) is associated with longer transplant-free survival in biliary atresia. However, evidence is lacking on whether an age limit can be established at which liver transplantation should be performed as first-line treatment for children with a delayed diagnosis of biliary atresia. The aim of the current study was to compare the outcome of a large cohort of children with biliary atresia who underwent BDS after 90 days of life with those who underwent early BDS (before 90 days) and those who did not receive BDS and were directly referred for primary liver transplantation. All patients with biliary atresia treated at Bicêtre, Paris-Saclay University Hospital between 1995 and 2017 were analysed in this STROBE-compliant study. Three groups were defined: BDS before 90 days of life (early BDS); BDS after 90 days of life (late BDS); and patients without BDS who were referred for primary liver transplantation (no BDS). Patient characteristics, overall survival, and native liver survival were compared. Of 424 children with biliary atresia, 69 patients (16 per cent) were older than 90 days when they underwent BDS. Twenty-five patients had no BDS and were referred for primary liver transplantation (6 per cent). The main reason for not performing BDS was manifest portal hypertension (18/25). Two- and 5-year transplant-free survival were significantly higher in patients with late BDS compared with no BDS (53.5 versus 12.0 per cent respectively for 2-year data and 30.4 versus 4.0 per cent respectively for 5-year data, P < 0.001). Five- and 10-year overall survival did not differ between early BDS (92 and 91 per cent respectively), late BDS (88 and 83 per cent respectively) and no BDS (80 and 80 per cent respectively, P = 0.061). Age alone should not routinely be considered a contraindication to BDS in patients older than 90 days. Liver transplantation in infancy (less than 12 months) could be avoided in 88 per cent of cases with late diagnosis of biliary atresia and is delayed significantly even when BDS is performed after 3 months. Overall survival is at least equal to patients who are referred for primary liver transplantation.

Closed reduction and plaster immobilization: an alternative solution for patients with developmental dysplasia of the hip who failed Pavlik harness treatment.

The current study aims to investigate the clinical efficacy of closed reduction and cast immobilization for patients with developmental dysplasia of the hip (DDH) who failed Pavlik harness treatment. Patients with DDH who underwent cast immobilization under general anaesthesia after the failure of the Pavlik harness or Tübingen brace treatment between January 2015 and December 2020 were retrospectively recruited. General information, including Graf classification of initial diagnosis, initial treatment, age of cast immobilization, IHDI classification, AI index, avascular necrosis (AVN), and residual dysplasia, was collected. The incidence of AVN and late acetabular dysplasia (LACD) was also estimated. Moreover, factors related to AVN and LACD were investigated by multiple logistic regression analysis. Thirty-four patients (47 hips) were finally included in the current study. Of these patients, 31 hips (66.0%) were successfully treated with closed reduction and cast immobilization. Open reduction was successfully performed in 16 hips (34.0%). Till the latest follow-up, LACD and AVN were found in 13 (27.7%) and 10 (21.3%) hips, respectively. In the open reduction group, type III and IV of the IHDI classification and type IV of the Ultrasound Graf classification were significantly higher when compared with the closed reduction group. Multiple logistic regression showed that failure of closed reduction was related to the initial types of the Ultrasound Graf and IHDI classifications. Although the success rate of closed reduction after early harness failure in DDH is only 66%, we still advocate closed reduction as a first-line treatment for children who have failed sling treatment. Even if closed reduction fails, open reduction can still achieve acceptable results.

Efficacy of eltrombopag with immunosuppressive therapy forchildren with acquired aplastic anemia.

Eltrombopag (EPAG), an oral thrombopoietin receptor agonist (TPO-RA), has been proven to improve the hematologic response without increasing toxic effects as a first-line therapy combined with standard immunosuppressive treatment (IST) in adults with severe aplastic anemia (SAA). Nevertheless, the clinical evidence on the efficacy of EPAG in children with acquired aplastic anemia is limited and controversial. We performed a single-center, retrospective study to analyze the clinical outcomes of fifteen patients aged ≤18 years with newly diagnosed acquired SAA who received first-line IST and EPAG (EPAG group) compared with those of forty-five patients who received IST alone (IST group) by propensity score matching (PSM). There was no difference in the overall response (OR) rate between the EPAG group and IST group (53.3% vs. 46.7% at 3 months, P = 0.655; 66.7% vs. 57.8% at 6 months, P = 0.543), but the complete response (CR) rate was statistically significant (20.0% vs. 4.4% at 3 months, P = 0.094; 46.7% vs. 13.3% at 6 months, P = 0.012). The median time to achieve a hematological response in the EPAG and IST groups was 105 days and 184 days, respectively. No difference was observed in the event-free survival (EFS) or overall survival (OS) rates. Adding EPAG to standard IST as the first-line treatment for children with acquired SAA improved the rapidity of hematological response and the CR rate but did not improve the OR or EFS rates.

Blinatumomab As Toxicity Sparing First Line Treatment of Children and Young Persons with B-Precursor Acute Lymphoblastic Leukaemia (B-ALL)

Introduction Recent studies have demonstrated that Blinatumomab is more effective and less toxic than intensive chemotherapy in children and young persons (CYP) with relapsed B-ALL. Although Blinatumomab is standard of care in adults with persistent MRD during first line therapy based on the BLAST study, there is no published evidence in CYP of its efficacy and toxicity in this setting. We report our experience of Blinatumomab as a toxicity sparing alternative to chemotherapy in first line treatment of CYP with B-ALL. Patients and Methods We audited the outcome of patients treated according to a consensus UK guideline for first line treatment with Blinatumomab of CYP patients with B-ALL who were considered unfit for post-remission intensive chemotherapy or CR1 HSCT because of toxicity to previous chemotherapy or significant co-morbidities. Treating clinicians obtained consent for treatment with Blinatumomab as standard of care after counselling patients and carers about the risk and benefits of this approach. The guideline mandated discussion of all such patients at national tumour board meetings and data was captured through a referral proforma and follow-up questionnaire. It recommended replacing consolidation and/or interim maintenance phases with 2 cycles of blinatumomab as a single agent with a 1-2 week break between cycles. Patients who obtained an MRD response (defined as MRD <0.01%) received delayed intensification (DI) followed by maintenance, or maintenance therapy alone if they were unfit for DI. Patients who had persistent MRD >0.01% were categorised as Blinatumomab failures and received either further chemotherapy, HSCT or CART depending on performance status. Events were defined as death, relapse, or secondary cancer. Results Sixty patients were eligible for analysis, including 4 cases of Ph+ ALL and 8 with Down syndrome. Compared to the B-ALL cohort in a previous trial, UKALL 2003, there was a higher proportion of NCI high risk, cytogenetic high risk, end of induction MRD positive and Down Syndrome patients (Table 1). All patients were in morphological complete remission prior to receiving Blinatumomab. Blinatumomab was administered for toxicity (47/60 (78%), including G3/4 pancreatitis, typhlitis, severe infections often requiring intensive care or surgery, disseminated fungal infections, CNS haemorrhage or liver failure) or co-morbidities (Down syndrome, Li-Fraumeni syndrome (n=2), Schimke immune-osseous dysplasia and 7q11.21-23 duplication) or in one case to minimise transfusion requirements (Jehovah's witness.) In the remaining 13 cases, blinatumomab was either administered for end of consolidation MRD of ≥0.05% (n=10) in patients unfit for intensive chemotherapy/HSCT, or positive end of induction MRD in patients with HR cytogenetics (n=3). Blinatumomab replaced consolidation and interim maintenance therapy in 32/60 (53%) cases, and interim maintenance in the remaining 28/60 (47%) cases. Blinatumomab was well tolerated with 1 G3 neurotoxicity (seizure in a Down syndrome patient who had not received prophylactic anti-convulsants) and no grade 2-4 CRS. Of the 50/60 patients with positive MRD pre-Blinatumomab (median = 0.1%, range = 0.01%-8%), 48 (96%) had a reduction in level to <0.01% (45 after cycle 1, 3 after cycle 2), and 10 patients maintained MRD negativity before and after 2 cycles of Blinatumomab. In the two patients who did not respond (3%), 1 received CART followed by transplant for persistent MRD, the other is receiving intensive chemotherapy. Of the responders, 47 (80%) received DI and maintenance and 10 maintenance alone. With a median follow up of 16 months (range 2-44 months), 2 patients have relapsed (1 at 2 years, the other at 9 months) but remain alive. The 4 patients with Ph+ ALL and the 8 with Down syndrome are alive and in remission, with a median follow up of 12.5 months (range 7-22 months). Conclusion In this large case series, we found Blinatumomab is safe and highly active with promising short-term efficacy in a higher risk cohort of CYP patients with B-ALL in first remission. Our results support its use in place of intensive chemotherapy for patients with relative chemo-intolerance. Furthermore, if the efficacy is sustained on longer follow-up, the results argue for replacing parts of post-remission intensive chemotherapy with Blinatumomab to reduce attendant morbidity and mortality. SS and AV are joint senior authors, AH and AM joint first authorsFigure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Knowledge, Attitudes, and Practices on Rocky Mountain Spotted Fever among Physicians in a Highly Endemic Region-Mexicali, Mexico.

Rocky Mountain spotted fever (RMSF) is a potentially fatal tickborne disease caused by the bacterium, Rickettsia rickettsii and transmitted primarily by the brown dog tick (Rhipicephalus sanguineus) in the southwestern United States and Mexico. RMSF can be rapidly fatal if not treated early with doxycycline, making healthcare worker awareness and education critical to reduce morbidity and mortality. During 2008-2019, Mexicali experienced a RMSF epidemic with 779 confirmed cases, and an 11-year case-fatality rate of 18% (N = 140). A cross-sectional study was conducted with 290 physicians and physicians-in-training across 12 medical facilities in Mexicali. They were asked to complete a 23-item questionnaire to assess knowledge, attitudes, and practices for clinical, epidemiologic, and preventive aspects of RMSF. Half of participants were female, the largest age group was aged 25 to 44 (47%), and median time in practice was 6 years (interquartile rate: 1-21.5). Less than half (48%) surveyed were confident where diagnostic testing could be performed, and two-thirds did not regularly order serology (67%) or molecular diagnostic (66%) tests for RMSF when a patient presented with fever. Sixty-four percent knew doxycycline as first-line treatment of children < 8 years with suspected RMSF. When comparing healthcare workers with < 6 years of experience to those with ≥ 6 years, more experience was associated with greater confidence in where to have diagnostic testing performed (prevalence odds ratio [prevalence odds ratios [pOR]] = 2.3; P = 0.004), and frequency of ordering laboratory tests (serology, pOR = 3.3; P = 0.002; polymerase chain reaction, pOR = 3.9; P = 0.001). Continued education, including information on diagnostic testing is key to reducing morbidity and mortality from RMSF.

Receipt of evidence-based care for children and adolescents with anxiety in Australia.

Cognitive-behavioural therapy is recommended as the first-line treatment for children and adolescents with anxiety. Despite its efficacy, a recent United Kingdom study indicated that few children with anxiety disorders receive cognitive-behavioural therapy. The primary aim of this study was to examine the receipt of cognitive-behavioural therapy for children and adolescents with elevated anxiety symptoms in Australia. Second, this study also examined whether there was a difference in the type of treatment received based on socioeconomic status and geographical location. Using self-reported questionnaires, parents of children aged 4-18 years and children aged 12-18 years (N = 784; elevated anxiety symptom sample n = 169) were recruited from four samples: community (n = 164), school (n = 177), clinic (n = 16) and online panel provider (n = 427). Participants reported on the child's anxiety symptoms and the type of treatment (if any) the child received for their anxiety symptoms. Results indicated that 19.5% of children and adolescents with elevated anxiety symptoms received evidence-based treatment (e.g. cognitive-behavioural therapy). Of those families who did seek help for anxiety in Australia, the majority (66.3%) did not receive cognitive-behavioural therapy. In addition, neither socioeconomic status (which was based on the Australian Index of Community Socio-Educational Advantage [ICSEA]) nor location (metropolitan vs regional/remote) affected whether individuals received evidence-based care or non-evidence-based care. Overall, children and adolescents in this study seeking support for their anxiety symptoms were not receiving adequate evidence-based care, regardless of socioeconomic status and location. These findings indicate there is a need to increase the receipt of cognitive-behavioural therapy for children and adolescents with anxiety symptoms. The findings should tentatively be interpreted, given data were collected during the COVID-19 pandemic.

A study to evaluate the efficacy and safety of intradermal and intralesional Purified Protein Derivative (PPD) for treatment of common warts in children

: Viral warts are common dermatological diseases with wide range of treatment modalities. Utilization of various vaccines and skin test antigens has broadened the horizon of available immunotherapeutic agents for the treatment of warts. In this study, we compared efficacy and safety of intradermal and intralesional purified protein derivative (PPD) for treating common warts in children.Toevaluate efficacy and safety of intradermal and intralesional PPD in treatment of common warts in children.: 180 children (aged 5-15 years) with common warts were randomly divided to receive intradermal (n=90) PPD 10 TU/0.1 ml at middle third of right forearm or intralesional PPD (n=90) 0.1 ml in the largest wart once in 2-weeks till there is complete clearance or maximum of five injections whichever is earlier. Patients were followed at 4 week after last injection for assessment of response, adverse effects, and recurrence of common warts.: Complete, partial clearance and no response in 51.2%, 45.3% and 2.3% children was observed in intradermal group as compared to 54.2%, 42.5% and 1.1% response in intralesional group respectively. Recurrence of warts was observed in 1.2% and 2.2% children in intradermal and intralesional group respectively. Pain was the most common adverse effect in both groups followed by erythema lasting for 2-3 days not warranting for discontinuation of treatment in any patient.: Overall 96.5% and 96.7% patients in both intradermal and intralesional group responded to treatment respectively. We conclude that immunotherapy with PPD appears safe, effective, and acceptable treatment modality for common warts in children. Although intralesional group showed slightly higher efficacy for warts (0.2%), intradermal PPD has advantage of less pain, high patient satisfaction, less spillage of injection material onto surroundings and better compliance over intralesional group and hence can be considered as valuable first line treatment in children in resource poor developing countries.