Measuring vincristine-induced peripheral neuropathy in children with cancer: validation of the Dutch pediatric-modified Total Neuropathy Score.

PURPOSE: The aims were to evaluate the construct validity and reliability of the Dutch version of the pediatric-modified Total Neuropathy Score (ped-mTNS) for assessing vincristine-induced peripheral neuropathy (VIPN) in Dutch pediatric oncology patients aged 5-18 years. METHODS: Construct validity (primary aim) of the ped-mTNS was determined by testing hypotheses about expected correlation between scores of the ped-mTNS (range: 0-32) and the Common Terminology Criteria for Adverse Events (CTCAE) (range: 0-18) for patients and healthy controls and by comparing patients and controls regarding their total ped-mTNS scores and the proportion of children identified with VIPN. Inter-rater and intra-rater reliability and measurement error (secondary aims) were assessed in a subgroup of study participants. RESULTS: Among the 112 children (56 patients and 56 age- and gender-matched healthy controls) evaluated, correlation between CTCAE and ped-mTNS scores was as expected (moderate (r = 0.60)). Moreover, as expected, patients had significantly higher ped-mTNS scores and more frequent symptoms of VIPN compared with controls (both p < .001). Reliability as measured within the intra-rater group (n = 10) (intra-class correlation coefficient (ICCagreement) = 0.64, standard error of measurement (SEMagreement) = 2.92, and smallest detectable change (SDCagreement) = 8.1) and within the inter-rater subgroup (n = 10) (ICCagreement = 0.63, SEMagreement = 3.7, and SDCagreement = 10.26) indicates insufficient reliability. CONCLUSION: The Dutch version of the ped-mTNS appears to have good construct validity for assessing VIPN in a Dutch pediatric oncology population, whereas reliability appears to be insufficient and measurement error high. To improve standardization of VIPN assessment in children, future research aimed at evaluating and further optimizing the psychometric characteristics of the ped-mTNS is needed.

Development and content of the biopsychosocial primary care intervention 'Back on Track' for a subgroup of people with chronic low back pain.

Biopsychosocial interventions provided in multidisciplinary settings are promising for improving functional disability levels in patients with chronic low back pain (CLBP). These multidisciplinary biopsychosocial interventions mainly focus on cognitive-behavioural approaches that aim to change negative cognitions, emotions, behaviour, work and social factors. As some patients with CLBP treated in primary care settings also experience psychosocial factors that influence their level of disability, these patients may benefit from the provision of a biopsychosocial intervention in primary care. This paper will provide a detailed description of the development and content of the biopsychosocial primary care intervention 'Back on Track' for this specific subgroup of patients. The Back on Track intervention was developed based on available scientific evidence and clinical experience from multidisciplinary pain rehabilitation programmes, and its effectiveness is currently being tested. CLINICAL TRIAL REGISTRATION NUMBER: NCT02220543.

Development of clinical practice guidelines for supportive care in childhood cancer--prioritization of topics using a Delphi approach.

INTRODUCTION: Currently, very few guidelines for supportive care for children with cancer exist. In the Netherlands, nationwide guidelines are over 10 years old and mostly based on expert opinion. Consequently, there is growing support and need for clinical practice guidelines (CPGs), which ought to be developed with a well-defined methodology and include a systematic search of literature, evidence summaries, and a transparent description of the decision process for the final recommendations. Development of CPGs is time consuming; therefore, it is important to prioritize topics for which there is the greatest clinical demand. OBJECTIVES: This study aims to prioritize childhood cancer supportive care topics for development of CPGs. METHODS: A Delphi survey consisting of two rounds was conducted to prioritize relevant childhood cancer supportive care topics for the development of CPGs. A group of experts comprising 15 pediatric oncologists, 15 pediatric oncology nurses, and 15 general pediatricians involved in care for childhood cancer patients were invited to participate. All relevant supportive care topics in childhood cancer were rated. RESULTS: In both rounds, 36 panellists (82%) responded. Agreement between panellists was very good, with an intraclass correlation coefficient of 0.918 (95% confidence interval (CI) = 0.849-0.966, p < 0.001) in round 2. The ten topics with the highest score in the final round were infection, sepsis, febrile neutropenia, pain, nausea/vomiting, restrictions in daily life and activities, palliative care, procedural sedation, terminal care, and oral mucositis. CONCLUSION: We successfully used a Delphi survey to prioritize childhood cancer supportive care topics for the development of CPGs. This is a first step towards uniform and evidence-based Dutch guidelines in supportive care in childhood cancer. Even though performed nationally, we believe that this study can also be regarded as an example starting point for international development of CPGs in the field of supportive care in cancer or any other field for that matter.

Familial hemophagocytic lymphohistiocytosis in a pediatric patient diagnosed by brain magnetic resonance imaging.

Familial hemophagocytic lymphohistiocytosis (fHLH) is an autosomal recessive disorder characterized by proliferation and infiltration of several organs by activated lymphocytes and macrophages. Without allogeneic stem cell transplantation, fHLH is fatal. We describe a previously healthy 11-month-old boy with a rapidly progressive encephalopathy. An older brother died at 8 months following a subacute encephalopathy diagnosed as meningoencephalitis. The family history led to the suspicion of a metabolic disease, but metabolic studies were unrevealing. MRI showed multiple inhomogeneous signal abnormalities in the cortex and white matter, most prominent in the cerebral hemispheres and around the dentate nucleus. Gadolinium-enhanced T1-weighted images showed a multitude of enhancing foci, suggestive of perivascular enhancement. Based on MRI pattern with multiple lesions, perivascular enhancement and family history, fHLH was suspected. DNA analysis showed that the patient was compound-heterozygous for the c.445 G>A (p.Gly149Ser) mutation in exon 1 and the c.757 G>A (p.Glu253Lys) mutation in exon 2 of the perforin 1 gene. The patient was treated according to the international HLH-2004 protocol (dexamethasone, etoposide, cyclosporine, intrathecal methotrexate and prednisolone) followed by allogeneic cord blood transplantation. He showed a significant neurological and radiological improvement. The reported case demonstrates that MRI pattern recognition can lead to early diagnosis of fHLH, with subsequent adequate treatment.

Health-related quality of life after completion of successful treatment for childhood cancer.

BACKGROUND: Previous studies have assessed health-related quality of life (HRQOL) during several treatment stages in children with cancer, but there is limited knowledge about HRQOL shortly after completing therapy. This study determined HRQOL of children with cancer shortly after the end of successful treatment compared with normative values. PROCEDURE: Several age-specific HRQOL questionnaires were administered: the ITQOL (generic, proxy-report, 0-4 years), CHQ PF 50 (generic, proxy-report, 5-7 years), Kidscreen (generic, self-report, 8-18 years) and Disabkids (chronic generic, self-report, 8-18 years). RESULTS: Children with cancer (N = 191, mean age 9.25, SD 5.06, 47.1% female) participated. Physical well-being was affected for all ages. Compared to normative values 0- to 7-year-olds were rated significantly lower on the majority of the scales. In addition, 12- to 18-year-olds had significantly better HRQOL than the norm on social scales. Compared to chronically ill norms, 8- to 18-year-olds demonstrated no differences, except for 12- to 18-year-olds who experienced significantly more physical limitations. Additionally, we found that HRQOL of parents of 0- to 7-year-olds was poorer than the norm. CONCLUSION: HRQOL in children with cancer and their parents can be impaired compared with the norm. Therefore, HRQOL should be monitored in clinical practice to make paediatric oncologists aware of these problems. For young children, we recommend checking whether certain HRQOL problems can be explained by parental worries. For older children and adolescents, paediatric oncologists need to consider social desirability and the child's adaptive style.

Long-term renal function after hemopoietic stem cell transplantation in children.

Glomerular function of all long-term survivors who underwent hemopoietic stem cell transplantation (HSCT) from 1991 to 1998 (study I, n=121) was studied retrospectively. In addition, we prospectively analyzed glomerular and tubular function of all long-term surviving children who received an HSCT between 1998 and 2000 (study II, n=41). We found a lower prevalence of children with chronic renal failure (CRF) post-HSCT in our more recent cohort (study II: 10%) as compared to the older cohort (study I: 24%) 5.0 (0.7 s.d.) and 7.6 (2.4 s.d.) year's post-HSCT, respectively. Furthermore, it seems that renal function may stabilize after 1-year post-HSCT. None of the patients required dialysis or antihypertensive medication at long-term follow-up. The sole predictor of CRF in our study was high serum creatinine pre-HSCT (P=0.007), while acute renal failure within 3 months after HSCT (P=0.08) only showed a trend towards predicting CRF. We could not confirm a relation of conditioning with irradiation with CRF post-HSCT, as was shown in several other pediatric and adult studies. Proximal and distal tubular dysfunction only occurred in a minority of long-time survivors of HSCT (3-12 and 9-13%, respectively) and had no clinical consequences.

[Rubella epidemic in the Netherlands, 2004/'05: awareness of congenital rubella syndrome required]. / Rubella-epidemie in Nederland in 2004/'05: alertheid op congenitaal rubellasyndroom vereist.

Rubella is a public health problem due to the teratogenic effects associated with primary rubella infection during pregnancy (congenital rubella syndrome). Following universal rubella vaccination of infants in the Netherlands, the incidence of rubella has declined dramatically. However, since September 2004, an outbreak has occurred among unvaccinated individuals, most of whom declined vaccination based on religious beliefs. In the period 1 September 2004-22 March 2005, 166 cases of rubella were reported, including 12 pregnant women. Monitoring for signs that the epidemic has spread to other populations in the Netherlands is important because this might indicate the need for additional interventions. Awareness among health-care workers of the possible occurrence of congenital rubella syndrome should be raised. The clinical manifestations of congenital rubella syndrome are diverse, can be transient or permanent, and may not present until adolescence or adulthood. All cases of laboratory-confirmed rubella infection and congenital rubella syndrome should be reported to municipal health authorities. There is a possibility that this outbreak will spread abroad. The WHO aims to reduce the incidence of congenital rubella syndrome to < 1/100,000 live births. Health-care workers in the Netherlands should be extra alert to detect and notify rubella in a timely manner.

Immunity to poliomyelitis in The Netherlands.

Despite a vaccination coverage rate of 97%, several poliomyelitis outbreaks occurred in the Netherlands during the last three decades, all among sociogeographically clustered, unvaccinated persons. Therefore, to eradicate polio, insight into poliomyelitis immunity is particularly useful. In 1995-1996, the authors conducted a population-based study and determined neutralizing antibodies against poliovirus types 1, 2, and 3 in 9,274 sera from the general population and from religious groups rejecting vaccination. In the general population, the antibody prevalence (>/=1:8) was 96.6% (95% confidence interval (CI): 95.9, 97.2), 93.4% (95% CI: 92.3, 94.5), and 89.7% (95% CI: 88.3, 91.0) for poliovirus types 1, 2, and 3, respectively. Antibodies persisted for long periods in persons with natural immunity as well as in persons whose immunity was induced by inactivated polio vaccine. In Orthodox Reformed persons, the antibody prevalence of poliovirus types 1, 2, and 3 was 65.0% (95% CI: 57.2, 72.9), 59.0% (95% CI: 40.1, 77.9), and 68.7% (95% CI: 65.2, 72.2), respectively. The recent outbreaks clearly affected the seroprevalence profiles of Orthodox Reformed groups but not the general population. At present, there is an insufficient social and political basis for mandatory vaccination; therefore, global eradication of poliovirus seems to be the only way to protect these Orthodox Reformed persons against future poliomyelitis outbreaks.

[Gait analysis in cerebral palsy patients--correlations between disorders of muscle coordination and gait abnormalities]. / Ganganalyse beim Cerebralparetiker--Beziehungen zwischen Störungen der Muskelkoordination und Ganganomalien.

Electromyographic and gait investigations of 35 patients and 32 healthy persons were evaluated in order to get hints upon the origin of anomalous movements of the pelvis and the spine with following results: a. The amount of the spine motions of CP-patients is significantly greater than that of health persons. The motions of the pelvis of the patients also seems to be greater, but there is no significance. b. The average electromyographical activity of the hip abductors of CP-patients is not remarkably diminished, that of the hip adductors is not increased. We also found no signs of an atrophy of the hip adductors or a hypertrophy of the hip adductors. c. There is no correlation between the disturbances of coordination of the entire lower leg measured by electromyography and the amount of the pathologic motions. d. We found a distinct correlation between the disturbances especially of the hip ab- and adductors and the amount of the pathologic motions. This amount is the smaller, the worse is the coordination of these two groups of muscles. The topics a-c do not allow to find the origin of the Duchenne- and Trendelenburg limpings of CP-patients, topic d also gives explanation of this fact. In opposition we may suppose here that the bad timing of the coordination resp. the corresponding permanent electrical activity of the hip ab- and adductors has a stabilizing influence upon the pelvis and the spine. As the most probable origin of the increased Duchenne limping we not suppose the increased motions of the stance phase. Our following investigations will deal with this hypothesis.

[Investigation of gait of patients with idiopathic scoliosis and the influence of the Milwaukee brace on gait (author's transl)]. / Ganguntersuchung an Patienten mit idiopathischen Skoliosen und der Einfluss des Milwaukee-Korsetts auf das Gangbild.

We investigated 42 juvenile patients with idiopathic scoliosist, 37 of them were provided with a Milwaukee brace and treated physically. The electromyographic activity of the musculi erectores trunci and the musculi glutaei medii were recorded during walking and standing on one leg. Simultaneously the motions of the trunc and the pelvis in the frontal plane were registered and calculated. Results without the brace: During walking the activity of the erectors trunci predominates on the convex side of the curvature of the spine. This applies as to the functional curve. The M. glutaeus medius shows an increased activity on the contralateral side of the overhang of the trunc. The priodical shifts of the trunc to the right and to the left during walking decrease with increasing activity of the M. glutaeus medius. In this way, we show the stabilizing influence of this muscle upon the statics of the spine. This should be especially considered with regard to the physical treatment of the patients. Results with the brace put on: There is only little influence of the brace upon the electrical activity of the musculi erectores trunci: we could not detect any activating ore inactivating effect of the brace. The amplitude of the periodical shifts of the trunc and the perlvis during walking is reduced by the brace. At the same time we found a greater activity of the musculi glutaei medii than with the brace taken off. We suppose that the reduced shifts of the trunc and the pelvis involved by the brace force a greater activity of the glutaeus medius.

[Electromyographic study of movements in infants with cerebral palsy (author's transl)]. / Elektromyographische Studie des Bewegungsverhaltens bei Säuglingen mit zerebraler Bewegungsstörung

In 43 infants between 3 and 16 months old electromyographic studies were performed by recording movement patterns. Surface electrodes were fixed to the legs, recording the activities of adductors, small gluteal muscles, M. rectus and hamstrings. The impulses were fed into the computer. Synergistic and antagonistic muscles were compared by correlation analysis. Certain movement patterns were provoked by turning the infants from supine to the sides, pulling up to sitting, tilting sideways, vertical hanging and standing. Synergistic and antagonistic muscle groups were compared by correlation anaysis. Significant differences in motor behavior were shown to exist between spastic and healthy infants: The spastic infants showed widely spread synchronous innervations. Besides, comparison of mean activity values exposed a significant preponderance of mean activity values exposed a significant preponderance of adductor activity to gluteal activity in spastic infants. - In qualitative analysis by a rating system diagnostic differentiation of individual cases was possible. This proved of special value in infants with postural asymmetries or abnormal musculatur tone.