Timeline of diagnosed pain causes in children with severe neurological impairment.

Objective: Pain's causes in children with severe cognitive impairment may be challenging to diagnose. This study aimed to investigate if there is a relationship between pain causes and the age of children. Methods: We conducted a multicenter retrospective study in three Italian Pediatric Units. Eligible subjects were patients from 1 to 18 years with severe neurological impairment. We collected data regarding diagnoses, pain causes and medical or surgical procedures. The timing of pain episodes was categorized into age-related periods: infants and toddlers (0-24 months), preschool children (3-5 years), schoolchildren (6-12 years), and adolescents (13-17 years). Results: Eighty children with severe neurological impairment were enrolled. The mean age was 11 years (±5.8). Gastroenterological pain was most common in the first years of life (p = 0.004), while orthopaedic and tooth pain was the most typical in schoolchildren and adolescents (p = 0.001 and p = 0.02). Concerning surgical procedures, PEG placement and gastric fundoplication were significantly more common in the first 5 years of age (p = 0.03), and heart surgery was typical of infants (p = 0.04). Orthopaedic surgery was more commonly reported in older children and adolescents (p < 0.001). Conclusions: Some causes of pain are more frequent in children with severe neurological impairment in defined age-related periods. Specific age-related pain frequencies may help physicians in the diagnostic approach.

Dexmedetomidine at Home for Intractable Dystonia and Insomnia in Children With Special Needs: A Case Series.

BACKGROUND: We know that syndromic conditions and severe chronic diseases can be associated with symptoms that may interfere with sleep, significantly impacting the life quality of children and caregivers. Drugs commonly used in treating insomnia, such as melatonin, benzodiazepines, niaprazine, and antihistamines, are often either ineffective or associated with adverse effects, requiring new therapeutic perspectives. Dexmedetomidine is a selective alpha-2 agonist with hypnotic and anxiolytic effects, which, by stimulating alpha-2 adrenergic receptors in the locus coeruleus, induces sleep comparable to stages 2-3 of the non-REM phase without substantially affecting the respiratory drive during sedation. Its use has already been extensively described in pediatric intensive care or procedural sedation literature. In 2018, the Italian Medicines Agency (Agenzia Italiana Del Farmaco AIFA) authorized the off-label use of dexmedetomidine outside of intensive care in Children undergoing palliative treatment to control distressing symptoms related to pathology and refractory sleep disorders, and the literature reported cases of children who received dexmedetomidine at home. OBJECTIVE: Our study aims to describe the home use of dexmedetomidine in children with insomnia or intractable dystonic states. MEASURES: We conducted a retrospective analysis through a questionnaire addressed to 12 Italian pediatric palliative care centers regarding the home use of dexmedetomidine in sleep disorders and intractable dystonic states. INTERVENTION: We collected a case series of 9 children treated with dexmedetomidine at home, 8 via intranasal and 1 via intravenous route. All children received the first drug administration in the hospital or hospice during a dedicated admission, under close monitoring of vital signs parameters for 72 hours (3 days, range 2-7 days). After discharge, the potential side effects of the drug were explained to the patient's families, and, once informed consent was obtained, the home administration of dexmedetomidine continued, with follow-up by the palliative care team. At home, dexmedetomidine was administered for 3000 days (minimum 1 month, maximum 36 months). The first patient was treated for 1095 days, from 2019 to 2021 (discontinued due to underlying condition-related death). OUTCOMES: All patients observed a persistent benefit from the treatment on symptoms, and none of them discontinued dexmedetomidine administration due to drug-related adverse effects or perceived lack of therapeutic efficacy. CONCLUSIONS: Therefore, its use at home may represent a promising therapeutic approach for intractable sleep disorders or dystonic states in pediatric palliative care children. Further studies are needed to confirm our results.

Fifteen-minute consultation: The prepubescent gender-diverse child: how to answer parents' questions.

Parents and caregivers may seek help with different questions or concerns on how to handle the diverse gender expressions of their children. Sometimes the issue may be evident while seeking medical advice for other concerns. Because of the many uncertainties around this topic, clinicians need to know what to say and what can be done to provide the best possible care for gender-diverse children.

Pediatricians' awareness of galenic drugs for children with special needs: a regional survey.

The prevalence of children with medical complexity is increasing, therefore drug formulations must be updated in accordance with their needs. Furthermore, a different drug formulation may be also needed for patients who require a very low dosage which is not easily reachable with those of the industrial products or for those following a ketogenic diet. Galenic (or compounded) drugs have been recently pointed out as effective in treating children. Nonetheless, their knowledge among healthcare providers is limited. We investigated how much did pediatricians know about galenic compounds by a short questionnaire administered to family and hospital pediatricians and pediatric residents in Friuli Venezia Giulia, Italy. We collected answers from 65 family pediatricians (57,5%), 39 hospital pediatricians (36,1%), and 47 pediatric residents (41,2%). Overall, both family and hospital pediatricians substantially know what is a galenic compound and the indications to its use. Of note, most of pediatricians ignore which is the legislation that allows the galenic compounds' preparation and use, and which is the correct procedure to prescribe them. Moreover, half of the hospital pediatricians and one-third of the family ones erroneously stated that galenic formulations cost more or like the industrial products, and around the 15% of both categories affirmed that galenic compounds are less safe than the commercial product. In conclusion, the use of galenic drug may significantly improve children's and caregivers' quality of life. We believe that all pediatricians should be updated on this quite new and interesting topic.

Impact of compounded drugs on the caregivers' burden of home therapy management in pediatric palliative care: A descriptive study.

BACKGROUND: Children with medical complexity need complex assistance, that considerably affects caregivers' quality of life. They often need multiple medications, with a consequent relevant risk of errors or poor compliance. Galenic (or compounded) drugs are blended in the pharmacy's laboratory worldwide according to different rules and tailoring the patient's needs. While their use may sometimes simplify these therapies, little is known about parents' attitude about this issue. AIM: This study aimed at investigating the complexity of the daily therapy management and exploring the parents' opinions about galenic compounds. DESIGN: Parents were interviewed by using a structured questionnaire. SETTING: Children followed by the Pediatric Palliative Care Network in Friuli Venezia Giulia, Italy, were included from November 2021 to April 2022. Those diagnosed with malignancies were excluded, since therapies are mainly administered through a central venous catheter. RESULTS: Thirty-four parents were interviewed. Fourteen patients took drugs orally, one via nasogastric tube (NGT), 18 via gastrostomy, and one orally + NGT. The mean number of drugs taken every day was six (2-14), in mean 10 (3-18) administrations, that overall required a mean of 44 (8-180) minutes to be delivered. Twenty-eight parents used galenic compounds, and 24 reported relevant advantages, because of a ready-to-use and safe formulation. CONCLUSIONS: The therapy management of children with medical complexity relies on parents. Galenic compounds may improve both patients' and caregivers' quality of life, either in terms of shorter time of administration or smaller risk of errors. Therefore, their use should be encouraged worldwide, according to the different reference rules.

The ongoing impact of Covid-19 pandemic on children with medical complexity: the experience of an Italian pediatric palliative care network.

BACKGROUND: Italy was the first European country to experience a massive outbreak of Sars-coV-2 in March 2020. Severe measures were introduced to face the pandemic, significantly impacting all healthcare services, including pediatric palliative care (PPC) networks. We investigated how the Covid-19 pandemic modified the provision of PPC services in Friuli Venezia Giulia, Italy. Both the acute and long-term impacts on the families were addressed. METHODS: We administered a retrospective three-sections online questionnaire to the eligible families assisted by our regional PPC network. Inclusion criteria were: child needing specialistic PPC, adequate knowledge of the Italian language, being in charge of the PPC regional network of Friuli Venezia Giulia from February 1, 2020. The three sections examined the same issues in different periods: the pre-covid period (until February 29, 2020), the lockdown period (March 1, 2020, to April 30, 2020), and the post-lockdown period (May 2021). RESULTS: Twelve patients were included. During the lockdown period, 54.6% of children had to stop physiotherapy sessions, while, among those who continued, 80.0% experienced a reduction in the sessions' frequency. In the post-lockdown period, 45.5% of children did not have physiotherapy as often as before the pandemic onset. Overall, the access to medical visits during the lockdown and after its end was significantly reduced (p = 0.01). The level of support perceived by the families descended from grade 3 (intermediate) in the pre-covid period to 2 (low) during the lockdown (p < 0.05) and returned to grade 3 in the post-lockdown period. CONCLUSION: The COVID-19 pandemic and the related restrictions impacted the families and caused a transitory contraction of the perceived support. The most significant change was reduced access to medical visits and physiotherapy, which lasted over a year after the start of the pandemic.

International Standards for Pediatric Palliative Care: From IMPaCCT to GO-PPaCS.

CONTEXT: Since the publication of the IMPaCCT project in 2007, much effort has been made to develop new approaches to pediatric palliative care (PPC). Fifteen years later, it is time to redefine the standards in PPC. OBJECTIVES: An international group of experts in PPC has revised the standards in PPC through the GO-PPaCS project (Global Overview - PPC Standards). The goal was to update the PPC standards considering the specificity of different settings, resources, and emerging challenges. The present document is intended to reach all people directly or indirectly involved in PPC. METHODS: A literature review in MEDLINE was conducted to expand on the fundamental points and current standards on PPC and to cover an international setting. The literature search (updated on the 15th of April 2021) was carried out using different combinations of keywords and focusing on papers published in English over the past 5 years (2016-2020), but older articles were considered when relevant. The consensus on the fundamental points, standards of care and paper contents was reached by open discussion. RESULTS: Fundamental points were defined regarding the definition of PPC, eligibility criteria and the magnitude of the need for PPC, while standards were redefined for the following six areas: 1) clinical, developmental, psychological, social, ethical and spiritual needs; 2) end-of-life care; 3) care models and settings of care; 4) PPC in humanitarian emergencies; 5) care tools; and 6) education and training for healthcare providers. CONCLUSION: The present document, developed with the contribution of an international group of experts from different countries, experiences and models of care, provides fundamental points and standards for a wider implementation of PPC worldwide.

Safety and Feasibility of Home Transfusions in Pediatric Palliative Care: A Preliminary Report.

BACKGROUND: While hematological symptoms are considered difficult to manage in a Pediatric Palliative Care setting, home may still represent a safe and convenient place for transfusions in patients with advanced malignancy or chronic conditions. This research focuses on the safety and feasibility of a home transfusion program. METHODS: This is a case series of patients between 0 and 18 years diagnosed with advanced malignancy or incurable chronic conditions and eligible to Pediatric Palliative Care who received home platelet or packed red cell transfusions. For all patients, we recorded adverse events such as acute hemolytic reactions, allergic reactions, or any emergency condition requiring hospital admission, equipment failure, blood product transport or storage errors, errors in patient identification, and personnel safety issues. We explored parental satisfaction with a Likert-type questionnaire and short open questions. RESULTS: We reviewed 101 transfusion procedures for six patients in Pediatric Palliative Care performed by the Regional Pediatric Palliative Care network between 2014 and 2020. We did not report any adverse effects. Families reported satisfaction and a sense of safety and positively evaluated the opportunity of having transfusion at home to minimize the disruption in everyday life. The cost analysis resulted in a consistent saving for the Regional Health System. CONCLUSION: This study supports the safety and feasibility of home transfusion in Pediatric Palliative Care.

Safety and family satisfaction of a home-delivered chemotherapy program for children with cancer.

BACKGROUND: Home chemotherapy programs for children with cancer are safe and feasible, and their impact on the quality of life has been reported in different countries. A home chemotherapy program was implemented between 2011 and 2019 in an Italian region. This pilot study investigates its safety and feasibility, along with parental satisfaction. METHODS: Patients between 0 and 18 years diagnosed with malignancy were included. Deceased patients and patients whose families moved abroad or interrupted contact with the service were excluded. Adverse events comprised immediate deterioration of the patient's condition, equipment failure, errors in drug storage, dose or patient identification and personnel safety issues. Parental satisfaction was explored through an email survey of 32 Likert-type and short open questions. RESULTS: Thirty-five patients received 419 doses of intravenous chemotherapy at home (cytarabine, vincristine, vinblastine). No adverse events were reported. Twenty-three families out of 25 eligible completed the survey. Most reported being "very satisfied" with the possibility of maintaining a work/domestic routine and reducing time and financial burden of hospital access. Most were "very satisfied" with the opportunity for their child of being less troubled by the treatment. Besides, most reported being "very satisfied" with the chance for healthy siblings of maintaining their routine and coping with their brother/sister's disease. Most perceived the program as safe. All families recommended extending the program to all children in the region. CONCLUSIONS: This first Italian study supports home chemotherapy as safe and effective, positively influencing the quality of life for children and their families.

An estimation of the number of children requiring pediatric palliative care in Italy.

BACKGROUND: Pediatric palliative care (PPC) addresses the physical and psychological needs of children suffering from life-limiting diseases. To define prevention and educational plans and to properly allocate resources, a precise estimation of the PPC burden is required. OBJECTIVES: To estimate the current number of children requiring PPC in Italy, useful to assist policy-makers and healthcare bodies in the organization and allocation of PPC resources. METHODS: Literature data, The Global Atlas of Palliative Care at the End of Life and Italian national databases have been consulted. RESULTS: According to our estimation, at present, a total of 20,540-32,864 children in Italy require PPC (34-54 children/100,000 inhabitants) of whom 18 children/100,000 inhabitants require specialized PPC. CONCLUSIONS: The present work is a fundamental tool to be used by the institutions, the local networks of PPC and the health programmers when formulating organizational models and care plans consistent with the actual need for PPC.

Home Use of Intranasal Dexmedetomidine in a Child With An Intractable Sleep Disorder.

Sleep disturbance is a crucial issue in pediatric palliative care, with a dramatic impact on the quality of life of children and families. Dexmedetomidine (DEX) is a selective α-2 agonist, with anxiolytic, hypnotic, and analgesic properties, that could play a role in the management of refractory sleep disturbances. We describe the use of intranasal DEX as a sleep inductor in a 10-year-old female with dystrophic epidermolysis bullosa and a severe sleep disorder. After treatment with melatonin, benzodiazepines, and niaprazine had failed, she was admitted to the hospital where 3 mcg/kg/day of intranasal DEX was administered before bedtime. She received 0.7 mL of the IV formulation at a concentration of 100 mcg/mL with half the dose given in each nostril via a Mucosal Atomization Device. During this time, she was also monitored for potential side effects (e.g., bradycardia, blood pressure derangements). After 2 weeks of hospitalization, she was discharged with ready-to-use doses of DEX for home treatment. The child's heart rate and blood oxygen saturation were monitored at home. There was a definite improvement in sleep quality and duration, daytime alertness, pain control, and quality of life. No side effects were reported and the drug retained its effect over time (the patient is currently taking the drug). Intranasal DEX could be a safe and effective strategy to manage refractory sleep disturbances in children in pediatric palliative care.

A consensus conference report on defining the eligibility criteria for pediatric palliative care in Italy.

BACKGROUND: The definition of the eligibility criteria of newborn, infant, child, or adolescent patients for palliative care (PC) is complicated by the fact that these patients generally present with very specific case histories that make it inadvisable to directly adopt existing PC protocols devised for adult patients. Thus, the goal of this paper is to define a standard set of criteria for establishing pediatric palliative care (PPC) eligibility. METHODS: The method adopted was that of the consensus conference. According to the guidelines issued by the Higher Institute of Health, the Board of the Italian Society for Palliative Care (i.e. steering committee) appointed a multidisciplinary group of eight health care professionals (i.e. doctors, nurses and psychologists) who worked from May 2014 to February 2016 to reach a consensus over PPC eligibility. This panel of relevant experts redacted a report summarizing all available scientific information concerning PPC, which was then submitted to the attention of a multidisciplinary jury composed of specialists and non-specialists of the field. The document thus produced was subsequently reviewed by an extended team of experts. RESULTS: The consensus conference drafted a final document determining the guidelines for PPC eligibility of newborns, infants, children, and adolescents suffering from either oncological or non-oncological diseases. CONCLUSIONS: This report provides health care providers with practical guidelines on how to define the eligibility of pediatric patients for PPC. Given the current situation in Italy, these guidelines will be instrumental in assisting the implementation of adequate generalist and specialist PPC services as well as in helping policymakers draft and implement national legislation pertaining to PPC.

Off-label drugs use in pediatric palliative care.

BACKGROUND: Paediatric palliative care (PPC) aim to ensure the control of symptoms and the best possible quality of life for patients whose underlying disease, characterized by an unstoppable evolution and negative prognosis, no longer responds to specific treatments. The scientific evidence in this context are very deficient and, in order to obtain welfare objectives consistent with the situation, in the overwhelming majority of cases the prescription of drugs is off-label for indication of use and/or for age and/or for way of administration and/or formulation. The Agenzia Italiana del Farmaco - AIFA and the Italian Society of Palliative Care (Società Italiana di Cure Palliative - SICP), under a dedicated working group, wrote a document that collects the scientific evidence available to support the off-label use of medicines more frequently used in PPC. The goal is to certify the consolidated off-label use of these drugs and propose their use under the Law 648/96, in the absence of data from its pivotal clinical trials. Aim of the commentary is to report the conditions for this important work and to present the 10 drugs, usually used off-label in PPC and in pain therapy, now included in Law 648/96. CONCLUSION: This work is deemed essential to resolve, at least in part, the lack of availability of medicines researched and approved.

Barriers to the development of pediatric palliative care in Italy.

INTRODUCTION: In recent years the emergence of new types of patient, clinical situations, technological frontiers and "health" objectives have changed considerably the needs of ill children, this also concerns pediatric palliative care (PPC). In Italy, despite the introduction of legislation (Law 38/2010) stipulating the right of children and families to access appropriate services for pain control and pediatric palliative care, the availability of these services is still limited. AIM: The aim of this study is to highlight, through a review of the existing data and published literature, the critical issues that obstacle the planning and development of PPC services in Italy. RESULTS: Four main areas identified were: socio-cultural setting; types of patients and nature of diseases requiring PPC; training for PPC providers; regulatory and political issues. CONCLUSIONS: This type of analysis can provide the rational for advancing proposals and developing supportive, corrective and implementation strategies.

Lessons learned from the H1N1 pandemic: the need to improve systematic vaccination in Sickle Cell Disease children. A multi center survey in Italy.

During the recent H1N1 pandemic, children with Sickle Cell Disease (SCD) experienced more hospitalizations and more complications than the general pediatric population. We performed a retrospective multicenter survey at 9 Pediatric Haematology-Oncology Units across Italy. H1N1 admission rate was 5.2%, with all admissions occurring before vaccine availability. Length Of Stay (LOS) was 6.06 days (7.85 for Acute Chest Syndrome), longer than in other countries. Vaccination coverage was not homogeneous, ranging from 0 to 99%; several family-related and health-system related barriers in accessing vaccinations were identified that should be ameliorated to improve coverage in this high risk group of children.

Expression of CD58 in normal, regenerating and leukemic bone marrow B cells: implications for the detection of minimal residual disease in acute lymphocytic leukemia.

BACKGROUND AND OBJECTIVES: CD58, a member of the Ig superfamily, is expressed by hematopoietic and non- hematopoietic cells. It has been demonstrated to be over-expressed in precursor-B acute lymphoblastic leukemia (ALL) blasts when compared to in their normal counterparts, suggesting its potential use in the detection of minimal residual disease (MRD) by flow cytometry (FC). To assess the reliability and accuracy of CD58 for this purpose, we studied its expression in a large series of normal and ALL bone marrow (BM) samples using quantitative FC. DESIGN AND METHODS: We studied 180 precursor-B ALL BM samples at diagnosis (8 pro-B, 164 early-B, 8 mature-B ALL) and 123 follow-up BM samples (n=54 at day +15 and n=69 at day +78), as well as 51 normal BM samples and 7 regenerating BM samples from patients with T-ALL at week 12. We used four-color quantitative FC, focusing analysis on CD58 expression. In follow-up samples from day +78, the MRD level was simultaneously evaluated by real time quantitative polymerase chain reaction (RQ-PCR) amplification of antigen receptor genes. RESULTS: CD58 expression was significantly higher in ALL blasts than in normal B lymphocytes, while no significant differences between regenerating and normal B lymphocytes were observed. CD58 was expressed in 99.4% of the precursor-B ALL cases and 93.5% of these showed over-expression compared to normal. No significant modulation of CD58 expression during remission induction therapy was noted. Finally, 66 (95.6%) of 69 BM samples simultaneously analyzed using both FC and RQ-PCR at day +78 showed concordant results regarding MRD. INTERPRETATION AND CONCLUSIONS: Our results confirm and further evidence the role of CD58 in the diagnosis and monitoring of precursor-B ALL. In particular, we demonstrated its stability and accuracy in MRD detection at clinically relevant time points. These findings indicate that CD58 is a powerful tool for MRD detection in precursor-B ALL.