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1.
Int J Mol Sci ; 25(10)2024 May 16.
Article in English | MEDLINE | ID: mdl-38791454

ABSTRACT

Previous omics research in patients with complex congenital heart disease and single-ventricle circulation (irrespective of the stage of palliative repair) revealed alterations in cardiac and systemic metabolism, inter alia abnormalities in energy metabolism, and inflammation, oxidative stress or endothelial dysfunction. We employed an affinity-proteomics approach focused on cell surface markers, cytokines, and chemokines in the serum of 20 adult Fontan patients with a good functioning systemic left ventricle, and we 20 matched controls to reveal any specific processes on a cellular level. Analysis of 349 proteins revealed 4 altered protein levels related to chronic inflammation, with elevated levels of syndecan-1 and glycophorin-A, as well as decreased levels of leukemia inhibitory factor and nerve growth factor-ß in Fontan patients compared to controls. All in all, this means that Fontan circulation carries specific physiological and metabolic instabilities, including chronic inflammation, oxidative stress imbalance, and consequently, possible damage to cell structure and alterations in translational pathways. A combination of proteomics-based biomarkers and the traditional biomarkers (uric acid, γGT, and cholesterol) performed best in classification (patient vs. control). A metabolism- and signaling-based approach may be helpful for a better understanding of Fontan (patho-)physiology. Syndecan-1, glycophorin-A, leukemia inhibitory factor, and nerve growth factor-ß, especially in combination with uric acid, γGT, and cholesterol, might be interesting candidate parameters to complement traditional diagnostic imaging tools and the determination of traditional biomarkers, yielding a better understanding of the development of comorbidities in Fontan patients, and they may play a future role in the identification of targets to mitigate inflammation and comorbidities in Fontan patients.


Subject(s)
Biomarkers , Blood Proteins , Fontan Procedure , Inflammation , Proteomics , Humans , Adult , Male , Inflammation/metabolism , Female , Blood Proteins/metabolism , Fontan Procedure/adverse effects , Biomarkers/blood , Proteomics/methods , Heart Defects, Congenital/surgery , Heart Defects, Congenital/metabolism , Heart Defects, Congenital/blood , Heart Defects, Congenital/pathology , Fibrosis , Young Adult , Neovascularization, Pathologic/metabolism , Oxidative Stress , Angiogenesis
2.
Front Cardiovasc Med ; 9: 994068, 2022.
Article in English | MEDLINE | ID: mdl-36277761

ABSTRACT

Introduction: It is increasingly common to simultaneously determine a large number of metabolites in order to assess the metabolic state of, or clarify biochemical pathways in, an organism ("metabolomics"). This approach is increasingly used in the investigation of the development of heart failure. Recently, the first reports with respect to a metabolomic approach for the assessment of patients with complex congenital heart disease have been published. Classical statistical analysis of such data is challenging. Objective: This study aims to present an alternative to classical statistics with respect to identifying relevant metabolites in a classification task and numerically estimating their relative impact. Methods: Data from two metabolomic studies on 20 patients with complex congenital heart disease and Fontan circulation and 20 controls were reanalysed using random forest (RF) methodology. Results were compared to those of classical statistics. Results: RF analysis required no elaborate data pre-processing. The ranking of the variables with respect to classification impact (subject diseased, or not) was remarkably similar irrespective of the evaluation method used, leading to identical clinical interpretation. Conclusion: In metabolomic classification in adult patients with complex congenital heart disease, RF analysis as a one-step method delivers the most adequate results with minimum effort. RF may serve as an adjunct to traditional statistics also in this small but crucial-to-monitor patient group.

3.
Dev Med Child Neurol ; 56(12): 1187-1193, 2014 Dec.
Article in English | MEDLINE | ID: mdl-24962083

ABSTRACT

AIM: In childhood, severe psychomotor impairment (SPMI) is associated with profound sleep disturbances. With the help of newly developed and validated measures, we systematically assessed how much a child's sleep disturbance affects parental sleep and quality of life (QoL) in this specific patient group. METHOD: Parents and their children with SPMI were enrolled from three outpatient centers and one in-patient center in Germany. We administered a set of questionnaires to the parents that addressed their child's sleep quality, the sleep disturbance-related parental burden, and the impact on both parental sleep and QoL. Additional questionnaires were used to gather data describing our sample group to allow for comparison with published norms. RESULTS: Parents of 214 children, adolescents, and young adults with SPMI (114 males, 100 females; mean age 10y 5mo, SD 5y 6mo, range 0.1-25y) responded to the questionnaire set (response rate of 66%). We found severe impairment of parental health status and QoL. More than 50% of the parents suffered from a sleep disorder (e.g. prolonged sleep latency, shortened sleep duration). Sleep disturbances in children, adolescents, and young adults correlated strongly with parental sleep disturbances, parental impairment of physical and mental functioning, parental social functioning, and parental working ability. INTERPRETATION: Sleep-related difficulties have a significant sociomedical impact on the parents of children, adolescents, and young adults with complex neurological diseases. Typically, parents are severely affected in various aspects of daily living. There is a need for novel diagnostic and therapeutic approaches that match the complex sociomedical needs of these patients and their families.


Subject(s)
Parents/psychology , Psychomotor Disorders/psychology , Quality of Life/psychology , Sleep Wake Disorders/etiology , Adolescent , Adult , Caregivers/psychology , Child , Child, Preschool , Female , Health Status , Humans , Infant , Infant, Newborn , Male , Retrospective Studies , Sleep Wake Disorders/psychology , Surveys and Questionnaires , Young Adult
4.
Sleep Med ; 15(2): 219-27, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24360535

ABSTRACT

BACKGROUND: Children with severe psychomotor impairment (SPMI) often experience sleep disturbances that severely distress both the child and his or her parents. Validated questionnaires for the assessment of parents' distress related to their child's sleep disturbances are lacking. METHODS: We developed and validated a new questionnaire, the HOST (holistic assessment of sleep and daily troubles in parents of children with SPMI) to assess the effect of the sleep disturbances in children with SPMI on their parents. The questionnaire was developed based on published data and expert opinion, and it was refined via direct consultation with affected parents. Its psychometric characteristics were assessed in a sample of parents of 214 children with SPMI. It was retested using a random subsample of the participants. RESULTS: Explorative factor analysis revealed that the HOST was composed of four scales. Fit indices, item analysis, and convergent validity (coherence with preexisting instruments of sleep disturbances and health status) were adequate. Retest analysis (n=62) revealed high stability of the HOST questionnaire and adequate replication validity. CONCLUSION: Sleep-related difficulties significantly impact the sociomedical characteristics of the parents of children with complex neurologic diseases. Typically, parents are severely affected in various aspects of daily life (i.e., medical health, social life, professional life). The HOST proved to be a valid, reliable and economical assessment tool of sleep-related difficulties in parents and relatives of children with SPMI. The HOST is capable of identifying individuals and specific areas requiring intervention.


Subject(s)
Activities of Daily Living/psychology , Psychomotor Disorders/diagnosis , Sleep Wake Disorders/diagnosis , Adolescent , Adult , Caregivers/psychology , Child , Child, Preschool , Cross-Sectional Studies , Factor Analysis, Statistical , Female , Health Surveys , Humans , Infant , Infant, Newborn , Male , Parents/psychology , Psychometrics , Psychomotor Disorders/complications , Psychomotor Disorders/psychology , Sleep Wake Disorders/etiology , Sleep Wake Disorders/psychology , Surveys and Questionnaires , Young Adult
5.
Sleep Med ; 14(4): 339-51, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23453904

ABSTRACT

OBJECTIVE: Sleep disturbance and daytime restlessness are present in 50% to 80% of children with severe psychomotor impairment due to neurologic or other complex diseases. Although these issues severely impair the quality of life of the children and their families, they are not well addressed or managed by professionals. The lack of validated assessment tools prevents further research and the development of adequate therapies. Our aim is to develop and validate a sleep questionnaire for these children that could be used both for clinical management and systematic research. METHODS: The sleep questionnaire for children with severe psychomotor impairment (Schlaffragebogen für Kinder mit Neurologischen und Anderen Komplexen Erkrankungen, SNAKE) is based on expert opinion and consultation with parents. The psychometric quality of the questionnaire was assessed in a sample of 224 children with severe psychomotor impairment. RESULTS: Confirmative factor analysis showed that SNAKE comprises of five factors (based on ICSD-2). Fit indices, analysis of item characteristics and convergent validity (coherence with measures of sleep [i.e., sleep efficiency]) and correlation with selected subscales of the Sleep Disturbance Scale for Children (SDSC) were good. Re-test analysis (n=62) depicted high stability and good replication of validity. CONCLUSIONS: SNAKE is a reliable and valid tool for the diagnosis of sleep disturbances in children with severe psychomotor impairment. The SNAKE questionnaire is the first tool that addresses the specific relationship between sleep disturbance and severe disability in children.


Subject(s)
Mass Screening/methods , Mass Screening/standards , Psychomotor Disorders/physiopathology , Sleep Wake Disorders/diagnosis , Sleep Wake Disorders/physiopathology , Surveys and Questionnaires/standards , Adolescent , Adult , Child , Child, Preschool , Comorbidity , Female , Humans , Infant , Infant, Newborn , Male , Psychomotor Disorders/epidemiology , Reproducibility of Results , Severity of Illness Index , Sleep/physiology , Sleep Wake Disorders/epidemiology , Young Adult
6.
Sleep Med Rev ; 16(2): 117-27, 2012 Apr.
Article in English | MEDLINE | ID: mdl-21620745

ABSTRACT

INTRODUCTION: Although sleep disturbances in disabled children are of central clinical importance, there is little research on that topic. There are no data available on frequency, severity or aetiology of sleep disturbances and related symptoms in this specific patient group. OBJECTIVE: To review the current state of research and outline future research objectives. METHODS: We searched international scientific databases for relevant publications from 1980-2009. From all papers qualifying for further analysis we retrieved systematic information on sample characteristics, sleep assessment tools and their test quality criteria, and core findings. RESULTS: 61 publications including 4392 patients were categorized as "mixed" (reporting on heterogeneous diagnoses), or "specified" papers (specific diagnoses) based on international classification of diseases (ICD) 10 classification. To assess sleep disturbances, most authors relied on subjective instruments with poor psychometric quality. Mean prevalence of sleep disturbances was 67% (76%,"mixed" group; 65%, "specified" group). In children suffering severe global cerebral injury, the prevalence of sleep disturbances was even higher (>90%). The most frequent symptoms were insomnia and sleep-related respiratory disorders. Some of these symptoms were closely associated with specific medical syndromes. CONCLUSION: There is an urgent need for sleep disturbance assessment tools evaluated for the patient group of interest. By use of validated assessment tools, patient factors, which may be crucial in causing sleep disturbances, may be investigated and appropriate treatment strategies may be developed.


Subject(s)
Disabled Children , Sleep Wake Disorders/complications , Adolescent , Child , Disabled Children/psychology , Disabled Children/statistics & numerical data , Humans , Prevalence , Sleep Wake Disorders/diagnosis , Sleep Wake Disorders/epidemiology , Sleep Wake Disorders/etiology , Sleep Wake Disorders/therapy
7.
Paediatr Anaesth ; 21(3): 280-90, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21091589

ABSTRACT

OBJECTIVE: The transdermal therapeutic system (TTS) with buprenorphine is currently being used 'off-label' to treat chronic pediatric pain. We compiled available pharmacokinetic (PK), pharmacodynamic (PD), and clinical pediatric data on buprenorphine to rationalize treatment regimens. METHODS: We conducted a systematic biomedical literature review focusing on pediatric buprenorphine data. RESULTS: There are few relevant pediatric buprenorphine data, particularly in children suffering chronic pain. There are no pediatric PK and PD data for children with chronic pain given sublingual or TTS formulations. Children given single dose buprenorphine have increased drug clearance referenced to bodyweight with a possible paradoxical longer duration of action. Buprenorphine metabolism is independent of renal function, which is advantageous in renal insufficiency. The risk of respiratory depression after buprenorphine is difficult to quantify. A concentration-response relationship for respiratory effects has not been described and it is unknown whether children have a ceiling effect similar to that described in healthy adult volunteers. CONCLUSIONS: Buprenorphine is of interest in pediatric postoperative pain and cancer pain control because of its multiple administration routes, long duration of action, and metabolism largely independent of renal function. There is little reason to expect buprenorphine effects in children out of infancy are fundamentally different to those in adults. From the limited pediatric data available, it appears that buprenorphine has no higher adverse potential than the more commonly used opioids. There is an urgent need for focused PK, PD, and safety studies in children before use in children becomes more widespread.


Subject(s)
Administration, Cutaneous , Analgesics, Opioid/administration & dosage , Analgesics, Opioid/pharmacology , Analgesics, Opioid/therapeutic use , Buprenorphine/administration & dosage , Buprenorphine/pharmacology , Buprenorphine/therapeutic use , Adolescent , Adult , Analgesics, Opioid/adverse effects , Analgesics, Opioid/pharmacokinetics , Buprenorphine/adverse effects , Buprenorphine/pharmacokinetics , Child , Drug Delivery Systems , Drug Eruptions/pathology , Female , Humans , Male , Pain/drug therapy , Pain, Postoperative/drug therapy , Receptors, Opioid, mu/drug effects , Receptors, Opioid, mu/metabolism , Respiratory Insufficiency/chemically induced , Substance Withdrawal Syndrome/psychology , Young Adult
8.
Paediatr Drugs ; 11(2): 129-51, 2009.
Article in English | MEDLINE | ID: mdl-19301934

ABSTRACT

Pediatric palliative care (PPC) is provided to children experiencing life-limiting diseases (LLD) or life-threatening diseases (LTD). Sixty to 90% of children with LLD/LTD undergoing PPC receive opioids at the end of life. Analgesia is often insufficient. Reasons include a lack of knowledge concerning opioid prescribing and adjustment of opioid dose to changing requirements. The choice of first-line opioid is based on scientific evidence, pain pathophysiology, and available administration modes. Doses are calculated on a bodyweight basis up to a maximum absolute starting dose. Morphine remains the gold standard starting opioid in PPC. Long-term opioid choice and dose administration is determined by the pathology, analgesic effectiveness, and adverse effect profile. Slow-release oral morphine remains the dominant formulation for long-term use in PPC with hydromorphone slow-release preparations being the first rotation opioid when morphine shows severe adverse effects. The recently introduced fentanyl transdermal therapeutic system with a drug-release rate of 12.5 microg/hour matches the lower dose requirements of pediatric cancer pain control. Its use may be associated with less constipation compared with morphine use. Though oral transmucosal fentanyl citrate has reduced bioavailability (25%), it inherits potential for breakthrough pain management. However, the gold standard breakthrough opioid remains immediate-release morphine. Buprenorphine is of special clinical interest as a result of its different administration routes, long duration of action, and metabolism largely independent of renal function. Antihyperalgesic effects, induced through antagonism at the kappa-receptor, may contribute to its effectiveness in neuropathic pain. Methadone also has a long elimination half-life (19 [SD 14] hours) and NMDA receptor activity although dose administration is complicated by highly variable morphine equianalgesic equivalence (1 : 2.5-20). Opioid rotation to methadone requires special protocols that take this into account. Strategies to minimize adverse effects of long-term opioid treatment include dose reduction, symptomatic therapy, opioid rotation, and administration route change. Patient- or nurse-controlled analgesia devices are useful when pain is rapidly changing, or in terminal care where analgesic requirements may escalate. In this article, we present detailed pediatric pharmacokinetic and pharmacodynamic data for opioids, their indications and contraindications, as well as dose-administration regimens that include practical strategies for opioid switching and dose reduction. Additionally, we discuss the problem of hyperalgesia and the use of adjuvant drugs to support opioid therapy.


Subject(s)
Analgesics, Opioid , Pain/drug therapy , Palliative Care , Administration, Cutaneous , Administration, Oral , Analgesics, Opioid/administration & dosage , Analgesics, Opioid/therapeutic use , Buprenorphine/administration & dosage , Buprenorphine/therapeutic use , Child , Delayed-Action Preparations , Fentanyl/adverse effects , Fentanyl/therapeutic use , Humans , Hydromorphone/administration & dosage , Hydromorphone/therapeutic use , Methadone/administration & dosage , Methadone/therapeutic use , Morphine/administration & dosage , Morphine/therapeutic use , Narcotics/administration & dosage , Narcotics/therapeutic use
9.
Eur J Pain ; 12(7): 819-33, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18222100

ABSTRACT

INTRODUCTION: Little is known about the impact of translation of pain management clinical practice guidelines on pain control in paediatrics. In an effort to overcome this, a longitudinal, nation-wide, multi-centre paediatric quality improvement (QI) study was initiated by the German Society of Pediatric Haematology and Oncology (GPOH) entitled Schmerz-Therapie in der Onkologischen Paediatrie (STOP). OBJECTIVE: The project's primary major aims were to improve paediatric oncology pain control in Germany, and to evaluate the project's impact on the pain management quality. To achieve these aims, STOP encompassed six sequential phases to evaluate present practice, develop recommendations for practical pain control, actively engage participants in improvement strategies, and assess change. The purpose of this paper is to briefly describe STOP in its entirety, report on comparisons between active quality management (QM) departments that actively participated in the project and non-active QM departments regarding differences in pain control, patients' and parents' perspectives on pain control and health professionals' knowledge, and to discuss the impact of STOP as a whole. METHODS: Four hypotheses were examined: (1) changes in health care professionals' knowledge on pain in paediatric oncology and pain management after a three-year period (2) impact of active participation in the STOP-project; (3) differences in patients' and parents' perspective in active QM versus non-active QM departments; (4) impact of the STOP-project on the health care professionals' knowledge in active QM versus non-active QM departments. Data included surveys, interviews, and standardised pre-/post-intervention documentation of pain control. All German paediatric oncology departments were invited to participate. The prime means of intervention was education (printed material, passive participation; additional lectures and feed-back, active participation). Quality indicators were defined and compared with regards to the four hypotheses. RESULTS: Sixty-eight departments participated passively. Eight departments participated actively, enrolling 224 patients (median age, 9 years) and documenting a total of 2265 treatment days. In the areas addressed, all health professionals demonstrated increases in knowledge on pain and pain control after a three-year period. STOP objectively improved pain control in the actively participating departments. Painful modes of drug administration were used less frequently; the usage of mixed opioid agonists-antagonists was reduced; the physicians' knowledge of the treatment of neuropathic pain increased; pain ratings significantly decreased, and less episodes of strong pain were observed. There was a significant increase in the proportion of health-care professionals who post-interventionally judged that pain therapy had been initiated earlier and at exactly the right time. Neither patients nor parents felt, however, that there was any quality improvement. According to participants' self-assessment, STOP improved practical pain management in actively participating departments, while in passively participating departments the change to the better was negligible. CONCLUSION: STOP predominantly aimed at and succeeded in the improvement of structure, process and outcome quality. With regard to patients' and parents' opinions, the interview tools might have been unsuited to measure the quality of pain control, or STOP was insufficient to improve pain control to a magnitude significant to the patient.


Subject(s)
Neoplasms/physiopathology , Pain/prevention & control , Quality Assurance, Health Care/organization & administration , Adolescent , Adult , Analgesia/statistics & numerical data , Analgesics/therapeutic use , Child , Child, Preschool , Disease Management , Germany , Health Knowledge, Attitudes, Practice , Health Personnel/psychology , Hospital Departments , Humans , Infant , Medical Oncology , Outcome and Process Assessment, Health Care , Pain Management , Pain Measurement , Parents/psychology , Patient Satisfaction , Patients/psychology , Pediatrics , Program Evaluation , Quality Assurance, Health Care/methods , Societies, Medical
10.
J Pain ; 8(3): 187-207, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17350554

ABSTRACT

UNLABELLED: The recently introduced fentanyl transdermal therapeutic system (TTS) with a drug release rate of 12.5 microg/h matches the lower dosing requirements of cancer pain control in children. It is likely that fentanyl TTS will be used in pediatrics with increasing frequency. We compiled the published evidence on pediatric applications of this drug formulation to help physicians get the most benefit from its use. Within this systematic review, a total of 11 observational clinical or pharmacokinetic studies were identified. There are no pediatric randomized or controlled cohort studies. Pharmacokinetic studies poorly described time-concentration profiles after application. The time to reach steady-state serum drug concentrations seems to be longer, clearance (expressed as liters per kilogram per hour) higher, and elimination half-life shorter in children than in adults. There are no fundamental differences in effect or profile of adverse effects compared with adults. Fentanyl TTS may be associated with less constipation compared with morphine use. Frequently, pediatric patients need supplemental mechanical fixation of the fentanyl TTS by means of medical tape. Younger patients tend to have a higher fentanyl requirement when referenced to body weight. Both parents and medical professionals are satisfied with fentanyl TTS to a higher degree than with individual analgesic pretreatment regimens. Fentanyl TTS is a promising option for chronic pain control in children. An approximate conversion factor of 45 mg/day oral morphine to 12.5 microg/h fentanyl TTS is used for initial therapy dose estimation in children receiving long-term morphine therapy. This is conservatively low to avoid respiratory depression. Daily oral morphine equivalent dose should be at least 30 mg/d before fentanyl TTS therapy is started with 12.5 microg/h. Evidence for superiority of fentanyl TTS treatment above conventional opioid administration is both scarce and of low quality. PERSPECTIVE: The article gives a comprehensive overview of all pediatric data concerning the fentanyl TTS. Children may take longer to reach steady-state fentanyl serum concentrations than adults, and younger children may require higher doses referenced to body weight than older children or adults. Consequently, there is a need to provide sufficient medication in the phase of therapy initiation to prevent breakthrough pain. The 72-hour dosing schedule recommended by the manufacturers may not be applicable to children because of poor patch adhesiveness. The authors suggest to ensure firm fixation of the fentanyl TTS with additional medical tape if necessary and to change the fentanyl TTS after 48 hours. Transdermal fentanyl in children may exhibit fewer side effects when compared with other opioids, especially constipation. Randomized studies are urgently needed to definitively answer this question.


Subject(s)
Administration, Cutaneous , Fentanyl/administration & dosage , Narcotics/administration & dosage , Pain/drug therapy , Adolescent , Child , Drug Delivery Systems , Humans , Pediatrics
11.
Eur J Pain ; 10(7): 587-95, 2006 Oct.
Article in English | MEDLINE | ID: mdl-16243549

ABSTRACT

OBJECTIVE: To collect data on pain management in paediatric oncology with respect to the WHO ladder approach. SETTING, DESIGN, PATIENTS AND METHODS: Eight German tertiary care paediatric oncology centres prospectively documented all their in-patient pain treatment courses from June 1999 to December 2000. Pain was scored using a 1-6 faces scale. RESULTS: Two hundred and twenty four patients (median age, 9 years; range 0.2-32.1) were enrolled. Three hundred and thirty three pain episodes comprising a total of 2265 treatment days were documented. Pain was mostly therapy associated. The most frequently administered non-opioid analgesics were dipyrone and paracetamol. On WHO step 2, tramadol was almost the only opioid used. During tramadol monotherapy average daily pain scores were lower than with a combination of tramadol and non-opioid analgesics. On WHO step 3, morphine was at least part of the analgesic regimen on most treatment days. Strong opioids were combined with a non-opioid analgesic on 41% of the treatment days. The mean intravenous morphine equivalence dose was 0.034 mg/kg/h. During opioid and non-opioid combination therapy, adverse effects were more frequent, and average pain scored higher than on opioid monotherapy. CONCLUSIONS: WHO-guidelines were closely followed in Germany and seem to provide effective analgesia for children with cancer pain. In our patient group there is no evidence that a combination of an opioid with a non-opioid is more effective than opioid therapy alone in in-patient paediatric oncology pain treatment.


Subject(s)
Analgesia/methods , Analgesics/standards , Analgesics/therapeutic use , Neoplasms/complications , Pain/drug therapy , Pain/etiology , Acetaminophen/administration & dosage , Acetaminophen/adverse effects , Adolescent , Adult , Analgesia/standards , Analgesia/trends , Analgesics, Opioid/administration & dosage , Analgesics, Opioid/adverse effects , Antineoplastic Agents/adverse effects , Child , Child, Preschool , Dipyrone/administration & dosage , Dipyrone/adverse effects , Drug Therapy, Combination , Germany , Humans , Infant , Medical Oncology/methods , Medical Oncology/standards , Medical Oncology/trends , Neoplasms/drug therapy , Pain/nursing , Pain Measurement , Pediatric Nursing/methods , Pediatric Nursing/standards , Pediatric Nursing/trends , Pediatrics/methods , Pediatrics/standards , Pediatrics/trends , Prospective Studies , Quality Assurance, Health Care , Treatment Outcome , World Health Organization
12.
Eur J Pain ; 9(4): 395-406, 2005 Aug.
Article in English | MEDLINE | ID: mdl-15979020

ABSTRACT

There is a lack of valid epidemiological data on malignancy-associated pain in modern pediatric oncology. Pediatric oncology patients (self-assessment) and their parents from 28 hospitals were questioned using age-adapted, structured interviews and validated pain assessment tools. Pain intensity was measured by the NRS and Bieri faces scale. We conducted 363 interviews with patients and their parents, and 46 with the parents alone (if patients <2.5 years). Pain was reported at the time of the interview or within the last 24 h, 7 d, or 4 weeks in 15%, 28%, 50% and 58% of cases, respectively. The proportion of patients suffering severe to maximal pain (NRS>3; Bieri>2) increased significantly (p=0.001, chi2 test). The median pain intensity for the most severe pain episode within the last 4 weeks was 6.7 (NRS 0-10). Adverse effects of anti-tumor therapy were the most frequent cause of pain. Multivariate analyses depicted general physical condition either "severely reduced" (ASA status 3) (OR 4.0, 95% CI 1.1-14.7, p=0.037) or "moderately reduced" (ASA status 2) (OR 1.8, 95% CI 1.1-2.9, p=0.018), "in-patient status" (OR 1.8, 95% CI 1.2-2.9, p=0.010), and "co-morbidity present" (OR 3.5, 95% CI 1.1-10.7, p=0.030) as risk factors for severe to maximal pain. General anesthesia was the only factor significantly (OR 0.14, 95% CI 0.05-0.39, p<0.01) associated with a reduction in the proportion of patients suffering severe to maximal pain during bone marrow aspiration. Our data emphasize both the importance of in-house acute pain control and the need for general anesthesia during painful procedures in pediatric oncology.


Subject(s)
Antineoplastic Agents/adverse effects , Biopsy, Needle/adverse effects , Neoplasms/complications , Pain/epidemiology , Radiotherapy/adverse effects , Spinal Puncture/adverse effects , Adolescent , Analgesics/therapeutic use , Anesthesia, General/standards , Bone Marrow/surgery , Child , Child, Preschool , Female , Humans , Infant , Male , Multivariate Analysis , Neoplasms/therapy , Pain/etiology , Pain/psychology , Pain Measurement , Parent-Child Relations , Patient Satisfaction , Risk Factors , Spinal Puncture/psychology , Surveys and Questionnaires
13.
J Perinat Med ; 32(3): 288-92, 2004.
Article in English | MEDLINE | ID: mdl-15188807

ABSTRACT

BACKGROUND: Congenital biliary atresia is suspected to originate from prenatal biliary duct inflammation of unknown etiology. OBJECTIVE: Based on clinical grounds, we aimed to establish a hypothesis on the primary cause of inflammation, and to suggest a causal treatment modality. CASE REPORT: History. A 28 years old Turkish woman had lost her first child aged two years from congenital biliary atresia (parents second degree cousins). After a miscarriage, in her otherwise uneventful third pregnancy sonography at 34 wks revealed echogenic material in the fetal gallbladder. Nine days later the gallbladder was completely filled with sludge. Chemical inflammation was suspected, and birth was induced at 36+3 weeks in order to allow for surgical flushing of the bile duct. Neonatal clinical chemistry was insuspicious. There was no spontaneous resolution of the sludge within the first 24 hours of life. A trial of medical treatment with intermittent i.v. secretin (0.03 CU/kg/h) and i.v. coeruletid (60 ng/kg/h) was started. Within 24 hours, sludge had resolved. CONCLUSIONS: We hypothesize that dysmaturation may lead to insufficient induction/production/activity of intrinsic gut hormones resulting in prenatally impaired bile flow, or even inspissated bile. Familial occurrence suggests a genetic defect. Exogenous hormone therapy might be an appropriate treatment modality.


Subject(s)
Biliary Atresia/diagnosis , Ultrasonography, Prenatal , Adult , Biliary Atresia/diagnostic imaging , Biliary Atresia/embryology , Biliary Atresia/genetics , Biliary Atresia/therapy , Diagnosis, Differential , Female , Genetic Predisposition to Disease , Humans , Infant, Newborn , Male , Pregnancy
14.
Med Inform Internet Med ; 28(3): 209-19, 2003 Sep.
Article in English | MEDLINE | ID: mdl-14612308

ABSTRACT

UNLABELLED: PRISM is claimed to score disease severity which has attributed an impact on length of PICU stay (LOS). PRIMARY OBJECTIVE: To determine the impact of PRISM on LOS, and evaluate an Artificial Neural Network's (ANN) performance to estimate LOS from PRISM item patterns. RESEARCH DESIGN AND METHODS: Retrospectively we performed correlation and regression analyses on routinely scored PRISM data of all consecutive admissions to our level-III PICU from 1994 to 1999 (n > 2000) with individual LOS. In addition, an ANN was trained on the chronologically first 75% of those data (inputs, PRISM items + age + sex; output, LOS). The ANN's performance was tested on the remaining most recent 25% of the data sets. MAIN RESULTS: The Spearman and Pearson coefficients of correlation between PRISM and LOS were 0.2 (p < 0.001) and 0.08 (p = 0.0003), the latter being slightly higher when LOS was logarithmically transformed. Pearson's coefficient of correlation between ANN derived LOS estimate and actual LOS was 0.21 (p < 0.001) (LOS logarithmically transformed: 0.34; p < 0.001) in the independent validation sample. CONCLUSIONS: The ANN with its intrinsic ability to detect non-linear correlation, and to relate specific item patterns to LOS, outperformed linear statistics but was still disappointing in estimating individual LOS. It might be speculated that therapeutic intervention modulates the natural course of the disease thus counteracting both disease severity as initially scored by PRISM, and LOS. This being true, the inverse of the correlation between PRISM (or PRISM based LOS estimate) and LOS might be a candidate indicator of quality of care.


Subject(s)
Intensive Care Units, Pediatric/statistics & numerical data , Length of Stay/trends , Neural Networks, Computer , Severity of Illness Index , Cohort Studies , Health Services Research , Humans , Netherlands , Patient Readmission , Probability , Retrospective Studies
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