The landscape of current research on pediatric diffuse midline glioma: a quantitative analysis of shifts, leaders, and future avenues.

PURPOSE: Diffuse midline glioma (DMG) has seen a surge of research interest in recent years with the growth in knowledge of new avenues for potential treatments. However, no bibliometric review of the field has been conducted to visualize the current state of the field. Here, we use bibliometric mapping to visualize the knowledge structure, collaborations, and trends in the field. METHODS: A total of 1079 original and review articles from 1996 to 2023 on diffuse midline glioma were extracted from the Web of Science Core Collection on June 3, 2023. These files were analyzed with R and VOSviewer to construct bibliometric visualizations. RESULTS: Research interest in DMG has continued to grow, driven by publications of original research. Molecular characterization of DMG has been a key focus of recent literature, and terms relating to novel small molecules, mutations, immunotherapy, the blood-brain barrier, and liquid biopsy may be areas for future growth in the literature. Collaborating nations have generally been the North American and European nations, but other nations have begun to make their mark in the field. Leading and rising institutions and journals are described. CONCLUSION: Research in DMG may continue to focus on molecular characterization and new therapeutics based on this knowledge. Novel collaborations between rising nations and institutions in the field may aid in accelerating this research.

Profile of children with developmental disabilities attending a complex pain clinic of a children's hospital in Australia.

AIM: To document the profile and management of children with developmental disabilities (DD) attending an outpatient complex pain clinic at a Children's Hospital in Sydney, Australia. METHODS: Children with DD from 2011 to 2014 were identified from a clinic database, and pain relevant data was collected. RESULTS: A total of 107 (19.6%) of 544 children were identified with DD, and accounted for one-third of clinic attendances. The median age was 14 years (interquartile range: 11-16) and females were slightly over-represented (62, 57.9%). About one-third of children had cerebral palsy (CP) from a variety of prenatal, natal and post-neonatal causes. The lower limb was the most common site for pain in children with CP, while back pain was more frequent in children with other disabilities. Comorbid emotional disorders were significantly associated with the non-CP disabilities. Children who required more than four clinic attendances were more likely to have comorbid anxiety/depression and to be reviewed by multiple specialists. CONCLUSIONS: Long-term persistent pain in children with DD forms a significant cohort of children requiring tertiary level paediatric pain services. Multisystem comorbidities and emotional disorders predict greater service utilisation. Further research into the effectiveness of multidisciplinary pain teams and interventions in this cohort of children is required.

Hypophosphatemic rickets and craniosynostosis: a multicenter case series.

OBJECTIVE This study examines a series of patients with hypophosphatemic rickets and craniosynostosis to characterize the clinical course and associated craniofacial anomalies. METHODS A 20-year retrospective review identified patients with hypophosphatemic rickets and secondary craniosynostosis at 3 major craniofacial centers. Parameters examined included sex, age at diagnosis of head shape anomaly, affected sutures, etiology of rickets, presenting symptoms, number and type of surgical interventions, and associated diagnoses. A review of the literature was performed to optimize treatment recommendations. RESULTS Ten patients were identified (8 males, 2 females). Age at presentation ranged from 1 to 9 years. The most commonly affected suture was the sagittal (6/10 patients). Etiologies included antacid-induced rickets, autosomal dominant hypophosphatemic rickets, and X-linked hypophosphatemic (XLH) rickets. Nine patients had undergone at least 1 cranial vault remodeling (CVR) surgery. Three patients underwent subsequent surgeries in later years. Four patients underwent formal intracranial pressure (ICP) monitoring, 3 of which revealed elevated ICP. Three patients were diagnosed with a Chiari Type I malformation. CONCLUSIONS Secondary craniosynostosis develops postnatally due to metabolic or mechanical factors. The most common metabolic cause is hypophosphatemic rickets, which has a variety of etiologies. Head shape changes occur later and with a more heterogeneous presentation compared with that of primary craniosynostosis. CVR may be required to prevent or relieve elevated ICP and abnormalities of the cranial vault. Children with hypophosphatemic rickets who develop head shape abnormalities should be promptly referred to a craniofacial specialist.

Patient-controlled analgesia for children at home.

CONTEXT: Pain is a common and significant symptom experienced by children with advanced malignant disease. There is limited research on pain management of these children at home. OBJECTIVES: To describe and review the indications for using patient-controlled analgesia (PCA) in the form of a Computerized Ambulatory Drug Delivery device (CADD(®)) in the home setting. METHODS: A retrospective chart review was conducted in children discharged home with opioid infusions using a CADD. Charts from January 2008 to February 2012 were surveyed. RESULTS: Thirty-seven CADDs were dispensed during the study period, and of these, 33 were prescribed for patients with cancer-related pain. A third of the CADDs were commenced at home and almost all PCA CADDs were used for end-of-life care. Hydromorphone was the most commonly prescribed opioid. Patients remained at home and pain control was achieved by either increasing the opioid dose or switching the opioid and using adjuvant therapy. Sixteen patients were readmitted to hospital from home and three admissions were related to pain. The median duration on a PCA CADD at home was 33.7 days (range, 1-150 days), and the mean morphine equivalent dose was 2.13 mg/kg/day. CONCLUSION: PCA with a CADD can be used to manage pain in the home setting. Dose adjustments and opioid switches were performed with no adverse incidents.

Exploratory study of sleeping patterns in children admitted to hospital.

AIMS: Sleep is considered an important time of healing and restoration during illness. The primary aim of this study was to determine the prevalence of self-reported sleep disturbance in children admitted to a tertiary children's hospital with a variety of medical diagnoses. METHODS: Parents of children admitted to the hospital, aged between 1 and 18 years, were asked to complete a sleep diary during one night of their child's hospital stay. Children older than 12 years were asked to complete a diary independently. Descriptive statistics were used to summarise the data. RESULTS: Overall, 107 children were surveyed for one hospital inpatient night. The overall prevalence of poor sleep was 52.3%. The wide age range and variety of diagnosis limited further detailed analysis of specific causes of this problem. Poor sleep prior to admission was the strongest predictor of poor sleep in hospital suggesting that these children already had an underlying sleep problem. Unprompted awakenings were predominantly due to toileting (17.8%) or were spontaneous (17.8%). Factors specific to the hospital environment that woke children were nursing cares (25.2%), alarms (12.1%) and pain (12.1%). CONCLUSIONS: Children admitted to hospital have a higher prevalence of poor sleep compared with healthy children in the community. Children were woken frequently by both external noise and attention provided by hospital staff. Education of hospital staff about the importance of sleep for children and factors that affect children's sleep may reduce the negative impact of hospitalisation on children's sleep.

Penetrating injury to the superior sagittal sinus by a nail in a 4-year-old child: a case report.

Penetrating head injuries are rare in children, with most injuries being accidental as a result of unsupervised use of sharp objects by young children. We present the case of a 4-year-old boy brought to our emergency department with a nail embedded through a wooden board and into his skull. The nail was determined to be entering the superior sagittal sinus through radiographic imaging. Thus, surgical removal of the nail was determined to be necessary. Inspection revealed a likely through-and-through injury to the sinus, and therefore, because sinus reconstruction was not deemed possible, the sinus was occluded with suture ties both in front and behind the nail before nail removal. Postoperatively, the patient did well and remained neurologically intact. Investigation for possible nonaccidental trauma was conducted. Although most commonly accidental in nature, nonaccidental penetrating traumas have been reported in both pediatric and adult populations. This patient did well after occlusion of his superior sagittal sinus at the coronal suture after penetrating injury by a nail. Penetrating injury in the pediatric population is predominantly thought to be accidental, but a high index of suspicion should be maintained for possible nonaccidental etiology.

Clomiphene citrate for unexplained subfertility in women.

BACKGROUND: The effectiveness of clomiphene citrate has been demonstrated in the treatment of subfertility associated with infrequent or irregular ovulation. The physiologic effects and clinical benefits in ovulatory women with unexplained subfertility are less clear. The drug is associated with an increased risk of multiple pregnancy and a suggestion of potentially increased ovarian cancer risks. In light of these concerns, defining the effectiveness of clomiphene citrate for ovulatory women with unexplained subfertility is extremely important. OBJECTIVES: To determine the effectiveness of clomiphene citrate in improving pregnancy outcomes in women with unexplained subfertility, used in a dose range of 50 to 250 mg for up to 10 days. The primary outcome was live births. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group Specialised Register (June 2009), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, Issue 2), MEDLINE (1966 to June 2009), EMBASE (1980 to June 2009) and reference lists of articles. SELECTION CRITERIA: Only randomised controlled trials were included. Quasi-randomised designs were excluded. DATA COLLECTION AND ANALYSIS: Fourteen potentially relevant trials were identified of which seven were included in this review. All trials were assessed for risk of bias using standardised Menstrual Disorders and Subfertility Group methodology. MAIN RESULTS: Data relating to 1159 participants from seven trials were collated. There was no evidence that clomiphene citrate was more effective than no treatment or placebo for live birth (odds ratio (OR) 0.79, 95% CI 0.45 to 1.38; P = 0.41) or for clinical pregnancy per woman randomised both with intrauterine insemination (IUI) (OR 2.40, 95% CI 0.70 to 8.19; P = 0.16), without IUI (OR 1.03, 95% CI 0.64 to 1.66; P = 0.91) and without IUI but using human chorionic gonadotropin (hCG) (OR 1.66, 95% CI 0.56 to 4.80; P = 0.35). It should be noted that heterogeneity between studies ranged from 34% to 58% using the I(2) statistic. AUTHORS' CONCLUSIONS: There is no evidence of clinical benefit of clomiphene citrate for unexplained fertility. When making this treatment choice, potential side effects should be discussed. These include the increased risk of multiple pregnancy and the concern that use for more that 12 cycles has been associated with a three-fold increase in risk of ovarian cancer.

Breakthrough pain in children with cancer.

The aims of this prospective study were to determine the prevalence, characteristics, and impact of breakthrough pain in children with cancer. Twenty-seven pediatric inpatients with cancer (aged 7-18 years) who had severe pain requiring treatment with opioids and who received care in the Oncology Unit at the Children's Hospital at Westmead, Sydney, Australia participated in this study. The children responded to a structured interview (Breakthrough Pain Questionnaire for Children), designed to characterize breakthrough pain in children. Measures of pain, anxiety, and depressed mood were completed. Fifty-seven percent of the children experienced one or more episodes of breakthrough pain during the preceding 24 hours, each episode lasting seconds to minutes, occurring 3-4 times/d, and most commonly characterized as "sharp" and "shooting" by the children. Younger children (7-12 years) had a significantly higher risk of experiencing breakthrough pain compared to teenagers. No statistical difference could be shown between children with and without breakthrough pain in regard to anxiety and depression. The most effective treatment of an episode of breakthrough pain was a patient-controlled analgesia opioid bolus dose. Further studies of breakthrough pain in children and more effective treatment strategies in this age group are necessary.

Palliative care and paediatric respiratory medicine.

Progressive respiratory failure is a common modality of death in children with a terminal illness. The management of respiratory failure, and in particular symptoms of dyspnoea and musculoskeletal chest pain in children receiving palliative care, remains challenging. The emergence of palliative care paediatricians and the application of non-invasive ventilation to children with progressive respiratory failure are the two major advances in the care of children with respiratory complaints in the palliative care setting. This article outlines current approaches to palliative care in children with progressive respiratory symptoms.

Pain in children who have life-limiting conditions.

Children and adolescents who have life-limiting conditions are vulnerableto acute and chronic pain problems. Many compounding and complicatingfactors often need to be explored in this setting. Barriers to effective painmanagement include poor assessment and measurement of pain anda lack of specialist knowledge. Fears regarding the use of opioids and theirassociation with the end of life must be addressed openly and with clarity.Day-to-day management should include continual appraisal of pain issuesif quality of life is to be maximized. Pain is a complicated phenomenon. The impact of pain and the compli-cated dynamic of suffering in children and young people who have life-lim-iting conditions must not be underestimated. The clinician must be vigilantand take responsibility for all aspects of pain management in these patients.

Percutaneous treatment of pediatric aneurysmal bone cyst at C1: a minimally invasive alternative: a case report.

An 11-year-old girl presenting with neck pain was diagnosed as having an aneurysmal bone cyst involving the posterior arch of C1. Minimally invasive treatment was performed with percutaneous injections of calcitonin and methylprednisolone. Two injections separated in time by 2 months were performed with complete sclerosis and ossification of the cyst over a period of 6 months. Such percutaneous sclerosis offers an important primary therapeutic option or an adjunct to surgery of these otherwise vascular cystic masses and should be contemplated as the initial step in the treatment of these benign tumors, especially those in the spine where surgical treatment can involve complex resection and fixation procedures.

Opioid rotation in children with cancer.

The purpose of this retrospective study was to determine the therapeutic value of opioid rotation in a large pediatric oncology center. The details for opioid prescriptions, over the course of a year, were obtained from the medical records of children with cancer who had a rotation of opioid during their admission. Twenty-two children or 14% of children on opioid therapy underwent 30 opioid rotations. Mucositis was the cause of pain in 19 (70%) children, bone pain in 3 (11%) children, and postoperative, visceral, or neuropathic pain in the remainder. The opioid was rotated either for excessive side effects with adequate analgesia (70%), excessive side effects with inadequate analgesia (16.7%), or tolerance (6.7%). Five (23%) children required two rotations, 3 during the same admission. The favored rotations were morphine to fentanyl in 20 (67%) children and fentanyl to hydromorphone in 6 (20%). Adverse opioid effects were resolved in 90% of cases, all failures occurred when morphine was rotated to fentanyl. There was no significant loss of pain control or increase in mean morphine equivalent dose requirements. Opioid rotation had a positive impact on managing dose-limiting side effects of, or tolerance to, opioid therapy during cancer pain treatment in children. This was accomplished without loss of pain control or having to significantly increase the dose of opioid therapy.

The dying child: how is care different?

Of children needing palliative care, less than half have a malignancy. Most families will elect to care for their child at home if this is offered as a realistic option. The often protracted and unpredictable nature of the many illness trajectories encountered in paediatric palliative care requires an approach that integrates palliative care with curative care. Children bring added dimensions to the physical, psychosocial and ethical aspects of palliative care. Health professionals from both paediatric and palliative care sectors have skills and knowledge to bring to palliative care of the child.

The symptoms of dying children.

The purpose of this study was to examine the symptom prevalence, characteristics, and distress of children dying in hospital. Symptoms during the last week of life were obtained from the medical records. Symptoms and their characteristics during the last day of life were determined by nurse interview. Thirty children with an average age of 8.9 years were evaluated. The dominant disease process was cancer (n=18), most likely location of death intensive care (n=20), and major physiological disturbances at the time of death respiratory failure (n=9) and encephalopathy (n=9). The majority of children (90%) did not have a pre-existing Do Not Resuscitate (DNR) order and 58% of these children had this addressed for the first time in the last day of life. The mean (+/-SD) number of symptoms per patient in the last week of life was 11.1+/-5.6 and six symptoms occurred with a prevalence of 50% or more. The location of death had a significant (P<0.02) impact on the mean number of symptoms: ward (14.3+/-6.1) vs. intensive care (9.5+/-4.7). In general, symptoms in the last day of life were not associated with a high level of distress. In summary, the symptom burden of dying children is high. Symptoms were, at times, distressing but children were generally comfortable. The findings suggest the application of the palliative care paradigm and a more aggressive approach to symptom control to all areas of the hospital may prove beneficial to dying children.

Computational and experimental analysis reveals a novel Src family kinase in the C. elegans genome.

MOTIVATION: The complete genomes of a number of organisms have already been sequenced. However, the vast majority of annotated genes are derived by gene prediction methods. It is important to not only validate the predicted coding regions but also to identify genes that may have been missed by these programs. METHODS: We searched the entire C.elegans genomic sequence database maintained by the Sanger Center using human c-Src sequence in a TBLASN search. We have confirmed one of the predicted regions by isolation of a cDNA and carried out a phylogenetic analysis of Src kinase family members in the worm, fly and several vertebrate species. RESULTS: Our analysis identified a novel tyrosine kinase in the C.elegans genome that contains functional features typical of the Src family kinases that we have designated as Src-1. The open reading frame contains a conserved N-terminal myristoylation site and a tyrosine residue within the C-terminus that is crucial for regulating the activity of Src kinases. Our phylogenetic analysis of Src family members from C. elegans, Drosophila and other higher organisms revealed a relationship among Src kinases from C. elegans and Drosophila.

Palliative care and the child with cancer.

There is a growing awareness and a WHO directive that the palliative care paradigm should be incorporated into the care of all children with cancer, irrespective of geographic location. The barriers to pediatric palliative care identified by pediatric oncologists [3] are lack of formal courses in pediatric palliative care, a high reliance on trial-and-error learning, lack of strong role models, and lack of access to a pain and palliative care service. These barriers must be overcome.

The measurement of symptoms in young children with cancer: the validation of the Memorial Symptom Assessment Scale in children aged 7-12.

Few studies have attempted to describe the experience of symptoms in young children with cancer. This is due, in part, to the lack of validated symptom assessment scales for this patient population. The objective of this study was to evaluate the reliability and validity of a revised Memorial Symptom Assessment Scale (MSAS) in patients aged 7-12 as an instrument for the assessment of symptoms in young children with cancer. The MSAS (7-12) was administered to 149 children (inpatients and outpatients) who were undergoing treatment at either the Royal Marsden NHS Trust, London, United Kingdom or The Children's Hospital at Westmead, Sydney, Australia. Validity was evaluated by comparison with the medical record, parental report, and concurrent assessment on visual analogue scales for selected symptoms. The data provide evidence of the reliability and validity of MSAS (7-12) and demonstrate that children with cancer as young as 7 years can report clinically relevant and consistent information about their symptom experience. Young children with cancer experience multiple symptoms. Approximately one-third had experienced lethargy and/or pain and/or insomnia during the 48 hours prior to the completion of MSAS (7-12). The completion rate for MSAS (7-12) was high and the majority of children completed the instrument in a short period of time and with little difficulty. The instrument appears to be age appropriate and may be helpful to older children unable to independently complete MSAS (10-18). Systematic symptom assessment may be useful in future epidemiological studies of symptoms and in cancer chemotherapy drug trials.

Regional anesthesia for pain associated with terminal pediatric malignancy.

The objectives of this study were to identify the characteristics of children who required regional anesthesia for pain associated with terminal malignancy and to identify the safety, tolerability and effectiveness of regional anesthesia as an analgesic modality in terminal pediatric malignancy. A retrospective examination was made of the medical records of children who died of malignancy following treatment at the Dana-Farber Cancer Institute and Children's Hospital, Boston, Massachusetts and who required either epidural or subarachnoid infusions, or neurolytic blockade for pain management (June, 1986--April, 1994) during the terminal phase of their illness. Eleven patients were identified, with a duration of epidural or subarachnoid infusions ranging from 3 days to 7 weeks. Indications for this intervention included limiting side effects of opioids, neuropathic pain unresponsive to either rapid escalation of opioids or massive opioid infusions, analgesia for thoracocenteses for the drainage of malignant pleural effusions and instillation of intrapleural chemotherapy. Pain was localized to one area in ll patients. Analgesia was judged to be satisfactory in all cases after regional anesthesia was instituted and remained satisfactory in all cases throughout the treatment course. Complications associated with regional anesthesia included dural puncture headache and mild respiratory depression. Five patients were nursed at home with either epidural or subarachnoid infusions.

Massive opioid resistance in an infant with a localized metastasis to the midbrain periaqueductal gray.

We report the case of a 4-month-old infant with terminal malignancy who had systemic metastases and a localized metastasis to the dorsal midbrain periaqueductal gray (PAG). Extraordinary doses of opioids (dose equivalent of 2680 mg morphine sulfate/h, i.v.) were required to achieve adequate analgesia. The behavior of the infant, interpreted as being representative of a response to pain, may have been an aversive reaction due to the location of the lesion in the dorsal PAG. We propose that the lesion in the PAG impaired the responsiveness of this infant to the effect of opioids. This report is to alert clinicians to the possible role of the PAG in impaired opioid responsiveness in patients with terminal malignancy, as well as the possibility that pain-like signs (e.g., tachycardia, tachypnea, vocalization, facial grimacing) may indicate an aversive reaction rather than pain in non-verbal patients.