Impact of contractures on daily functioning in adolescents with spinal muscular atrophy: a qualitative study.

PURPOSE: Exploring the impact of contractures in adolescents and young adults (AYA) with spinal muscular atrophy (SMA) on daily functioning and participation and the impact of received contracture management. METHODS: We included 14, non-ambulant AYA with SMA types 2/3 (10 females and 4 males), aged 16-30 years. Interviews focused on two topics: perceived impact of contractures on daily functioning and of previous contracture management. We used inductive thematic analysis for interview analysis. RESULTS: In general, participants experienced muscle weakness to be more of a hindrance than contractures; they had adapted to their contractures over time. Participants considered contracture treatment useful when goals were meaningful and realistic. Participants mentioned that their perspective on contracture management would change in light of a promise of improved motor function due to disease-modifying treatment. CONCLUSION: Despite the relatively low impact of contractures in comparison to the loss of muscle strength, non-ambulant AYA with SMA should be informed on the potential impact of contractures and benefits and potential adverse effects of their management. This information can support the shared decision-making process. While respecting individual choices, allows for incorporating interventions into daily life and the promotion of daily functioning and participation when children with SMA are growing up.

The variability of the perceived impact of contractures in non-ambulant adolescents and young adults with spinal muscular atrophy (SMA) underscores the need for individualized assessment and contracture management based on discussions about challenges, benefits and burden.In the treatment plan for contracture management in SMA it is important to take into account: 1) that adolescents often experienced physiotherapy as additional comfort, with less feeling of stiffness, and 2) that most perceived orthosis and standers as unnecessary and burdensome as contracture management.Clinicians should consider postural management in an early stage given the improved prognosis on motor development of children with SMA.Clinicians should monitor and revisit treatment goals, benefits and adverse effects on a regular basis as part of the shared goal-setting and decision-making in contracture management for children with SMA.

Evaluation of the nation-wide implementation of ALS home monitoring & coaching: an e-health innovation for personalized care for patients with motor neuron disease.

BACKGROUND: To improve the care for patients with motor neuron disease an e-health innovation for continuous monitoring of disease progression and patients' well-being (ALS H&C) was implemented in 10 multidisciplinary rehabilitation settings. The first aim was to evaluate the implementation of ALS H&C by assessing several implementation outcomes, technology acceptance and usability of the innovation according to the end users. The secondary aim was to explore differences in these outcomes between the teams with sustainable and unsustainable implementation. METHODS: The chosen implementation strategy was a combination of the implementation process model by Grol & Wensing and a participatory action research approach. In three meetings with multidisciplinary project groups the innovation was introduced, the expected barriers/facilitators identified, and action plans to resolve each barrier developed. After a 3-month pilot phase, patients and their healthcare providers were asked to complete an online evaluation survey to assess implementation outcomes, based on Proctor's evaluation framework (i.e., acceptability, feasibility, fidelity, sustainability). Telemedicine technology acceptance was assessed according the technology acceptance model of Chau, and user experiences with the System Usability Scale (SUS). Implementation outcomes of teams with sustainable implementation (continuation after completion of the pilot phase) and unsustainable implementation (discontinuation after the pilot phase) were compared. RESULTS: The implementation outcomes from the patients' perspective (N = 71) were positive; they found ALS H&C to be an acceptable and feasible care concept. Patients' technology acceptance was high, with positive attitudes towards ALS H&C, and positive views on perceived technology control, usefulness, and ease of use. Patients rated their satisfaction with the (web) app on a scale from 1 (not satisfied at all) to 10 (very satisfied) with a 7.0 (median; IQR 1.0). Healthcare providers (N = 76) also found ALS H&C acceptable and appropriate as well, but were less positive about the feasibility and usability of ALS H&C (mean SUS 58.8 [SD 11.3]). ALS H&C has largely been implemented as intended and the implementation was sustainable in 7 teams. Teams who discontinued ALS H&C after the pilot phase (N = 2) had more fidelity issues. CONCLUSIONS: A participatory action research approach supported by theoretical approaches used in implementation science led to a sustainable implementation of ALS H&C in 7 of the participating teams. To improve implementation success, additional implementation strategies to increase feasibility, usability and fidelity are necessary. TRIAL REGISTRATION: Trial NL8542 registered at Netherlands Trial Register (trialregister.nl) on 15th April 2020.

Implementation and evaluation of an e-health innovation for personalized care for patients with amyotrophic lateral sclerosis (ALS): protocol for a participatory action research study.

BACKGROUND: In the absence of a cure for amyotrophic lateral sclerosis (ALS), a progressive neurodegenerative disease, treatment consists of symptomatic management by a multidisciplinary healthcare team and is mainly aimed at optimizing patients' quality of life. Because the course of the disease is often erratic and varies between patients, it is imperative for patients with ALS to be closely monitored. E-health innovations that can monitor disease progression remotely have great potential to tailor the care to the needs of individual patients with ALS. Therefore, the e-health innovation "ALS Home-monitoring and Coaching" was developed employing a user-centered design process and implemented at the University Medical Center Utrecht, the Netherlands in 2017. Because ALS Home-monitoring and Coaching was shown to be feasible and well received by patients and healthcare professionals at University Medical Centre Utrecht, we aim to implement this e-health innovation nationwide, starting with 10 ALS care teams in different rehabilitation settings spread across the Netherlands. METHODS: This research focuses on the implementation process and the user experiences with ALS Home-monitoring and Coaching of both patients and healthcare professionals. We will use a participatory action research approach, with the stakeholders involved in all stages of the implementation process. The implementation process model of Grol and Wensing was used to structure and support planning, execution and evaluation of the implementation strategy. The expected barriers and facilitators will be explored and identified in focus group settings using the Theoretical Domains Framework. After that, each team will develop their own action plan with strategies for how to resolve each barrier. The teams will include 5-10 ALS patients with whom they will test their implementation plan and provide care with ALS Home-monitoring and Coaching for approximately 3 months. Afterwards, the implementation and the user experiences will be evaluated with digital surveys based on the evaluation framework of Proctor (e.g., acceptability, adoption, appropriateness). DISCUSSION: Using implementation theories, this study will provide inside in factors influencing implementation outcomes and strategies that can be used to overcome barriers. This will enhance our understanding of how to successfully implement e-health innovations in multidisciplinary care in rehabilitation settings. TRIAL REGISTRATION: Trial NL8542 registered at Netherlands Trial Register (trialregister.nl) on 15th April 2020.

Drug-induced sleep endoscopy: the effect of different passive maneuvers on the distribution of collapse patterns of the upper airway in obstructive sleep apnea patients.

PURPOSE: To evaluate the effect of different passive maneuvers (lateral head rotation and jaw thrust) during drug-induced sleep endoscopy (DISE) on distribution of collapse patterns at the level of velum, oropharynx, tongue base, and epiglottis (VOTE). METHODS: Retrospective, single-center cohort study. Patients diagnosed with OSA who underwent DISE between August 2016 and February 2017 were included. During DISE procedure lateral head rotation, jaw thrust and a combination of both were applied and scored by VOTE obstruction level. Also, the effect of these maneuvers was analyzed for complete concentric collapse (CCC) versus complete non-concentric collapse (CNCC) subgroups. RESULTS: Two hundred patients were included (161 male (80.5%), mean age 50.1 ± 11.7 years, median AHI 19.2 (11.7, 31.0) events/h). For lateral head rotation, significant improvement in upper airway collapse at all levels was observed, with exception of the level of the oropharynx, where an increase in obstruction was seen. Jaw thrust resulted in a significant decrease of collapse on all four VOTE levels. The CCC group responded similarly to the CNCC group when only one maneuver was applied, but the CCC group showed less improvement when both maneuvers were combined. CONCLUSIONS: This study gives new insights into the changes in distribution of collapse patterns when passive maneuvers are applied during DISE. Jaw thrust and lateral head rotation gave improvement of obstruction mostly in line with previous research. The CNCC and CCC groups responded similarly to application of a single maneuver, but there was a significant difference found when both maneuvers were combined.

Subjective effects of the sleep position trainer on snoring outcomes in position-dependent non-apneic snorers.

PURPOSE: To evaluate the effect of a new-generation positional device, the sleep position trainer (SPT), in non-apneic position-dependent snorers. METHODS: Non-apneic position-dependent snorers with an apnea-hypopnea index (AHI) < 5 events/h were included between February 2015 and September 2016. After inclusion, study subjects used the SPT at home for 6 weeks. The Snore Outcome Survey (SOS) was filled out by the subjects at baseline and after 6 weeks, and at the same time, the Spouse/Bed Partner Survey (SBPS) was filled out by their bed partners. RESULTS: A total of 36 participants were included and 30 completed the study. SOS score improved significantly after 6 weeks from 35.0 ± 13.5 to 55.3 ± 18.6, p < 0.001. SBPS score also improved significantly after 6 weeks from 24.7 ± 16.0 versus 54.5 ± 25.2, p < 0.001. The severity of snoring assessed with a numeric visual analogue scale (VAS) by the bed partner decreased significantly from a median of 8.0 with an interquartile range (IQR) of [7.0-8.5] to 7.0 [3.8-8.0] after 6 weeks (p = 0.004). CONCLUSIONS: Results of this study indicate that positional therapy with the SPT improved several snoring-related outcome measures in non-apneic position-dependent snorers. The results of this non-controlled study demonstrate that this SPT could be considered as an alternative therapeutic option to improve sleep-related health status of snorers and their bed partners.

Towards a prediction model for drug-induced sleep endoscopy as selection tool for oral appliance treatment and positional therapy in obstructive sleep apnea.

PURPOSE: To evaluate the effect of different passive maneuvers on upper airway patency during drug-induced sleep endoscopy (DISE) compared to recent literature on treatment outcomes of positional therapy (PT), oral appliance therapy (OAT), and combined treatment in obstructive sleep apnea (OSA) patients. METHODS: A retrospective, single-center cohort study including a consecutive series of 200 OSA patients. All patients underwent DISE with and without manually performed jaw thrust and lateral head rotation by using the VOTE classification. The effect of these maneuvers were analyzed by using the sum VOTE score comparing non-positional (NPP) and positional OSA patients (PP). RESULTS: Two hundred patients were included (80.5% male) with a mean age of 50.1 ± 11.7 years, a BMI of 27.0 ± 3.1 kg/m2, and a median AHI of 19.2 events per hour. Forty-four percent of the patients were NPP; of the remaining 56%, 34% was diagnosed with supine isolated and 66% with supine predominant POSA. Manually performed jaw thrust showed a reduction of sum VOTE score of 66.7% in all subgroups. The effect of lateral head rotation was a reduction of 33.3% in NPP and supine predominant PP and 50% in supine isolated PP. Combining these maneuvers a reduction of more than 75% was seen in all patients. CONCLUSIONS: The present model leaves room for improvement. The effect of manually performed jaw thrust is greater and the effect of lateral head rotation alone is less than what was expected compared to recent literature on treatment outcome of OAT, PT, and combined treatment.

Feedback learning and behavior problems after pediatric traumatic brain injury.

BACKGROUND: Feedback learning is essential for behavioral development. We investigated feedback learning in relation to behavior problems after pediatric traumatic brain injury (TBI). METHOD: Children aged 6-13 years diagnosed with TBI (n = 112; 1.7 years post-injury) were compared with children with traumatic control (TC) injury (n = 52). TBI severity was defined as mild TBI without risk factors for complicated TBI (mildRF- TBI, n = 24), mild TBI with ⩾1 risk factor for complicated TBI (mildRF+ TBI, n = 51) and moderate/severe TBI (n = 37). The Probabilistic Learning Test was used to measure feedback learning, assessing the effects of inconsistent feedback on learning and generalization of learning from the learning context to novel contexts. The relation between feedback learning and behavioral functioning rated by parents and teachers was explored. RESULTS: No evidence was found for an effect of TBI on learning from inconsistent feedback, while the moderate/severe TBI group showed impaired generalization of learning from the learning context to novel contexts (p = 0.03, d = -0.51). Furthermore, the mildRF+ TBI and moderate/severe TBI groups had higher parent and teacher ratings of internalizing problems (p's ⩽ 0.04, d's ⩾ 0.47) than the TC group, while the moderate/severe TBI group also had higher parent ratings of externalizing problems (p = 0.006, d = 0.58). Importantly, poorer generalization of learning predicted higher parent ratings of externalizing problems in children with TBI (p = 0.03, ß = -0.21) and had diagnostic utility for the identification of children with TBI and clinically significant externalizing behavior problems (area under the curve = 0.77, p = 0.001). CONCLUSIONS: Moderate/severe pediatric TBI has a negative impact on generalization of learning, which may contribute to post-injury externalizing problems.

Elevated plasma inflammatory mediators in post-polio syndrome: No association with long-term functional decline.

A key feature of post-polio syndrome (PPS) is progressive loss of muscle strength. In other chronic diseases systemic inflammation has been linked to muscle wasting. In this study plasma TNF-α, IL-6, IL-8, and leptin levels were significantly increased in PPS-patients compared to healthy controls. There was however no association between these raised systemic levels of inflammatory mediators and long-term decline in quadriceps strength or other clinical parameters. In conclusion, there is evidence for systemic inflammation in PPS, yet the relationship with clinical deterioration remains tenuous.

Change in physical mobility over 10 years in post-polio syndrome.

Post-polio syndrome is characterised by progressive muscle weakness and other symptoms which can limit physical mobility. We assessed the rate of decline in mobility over 10 years in relation to strength decline; and investigated potential predictors for the rate of decline of walking capacity, a measure of mobility, in 48 patients with post-polio syndrome and proven quadriceps dysfunction at baseline. Average walking capacity and self-reported physical mobility declined over 10 years, by 6 and 14%, respectively. Concomitantly people lost an average of 15% of isometric quadriceps strength. Significantly more people used walking aids offering greater support at follow-up. Notably, there was much individual variation, with 18% of participants losing a substantial amount of walking capacity (27% decline) and concomitant self-reported physical mobility (38% decline). Loss of quadriceps strength only explained a small proportion of the variance of the decline in walking capacity (R = 11%) and the rate of decline could not be predicted from baseline values for strength, walking capacity, self-reported physical mobility or basic demographics. The individual variability, yet lack of predictive factors, underscores the need for personally tailored care based on actual functional decline in patients with post-polio syndrome.

Loss of motor unit size and quadriceps strength over 10 years in post-polio syndrome.

OBJECTIVE: To investigate whether strength decline in post-polio syndrome (PPS) results from excessive distal axonal degeneration of enlarged motor units. METHODS: We assessed changes over 10 years in isometric quadriceps strength, mean motor unit action potential (MUAP) size, root mean squared (RMS) amplitude, and level of interference (LOI) in 47 patients with PPS and 12 healthy controls, using high density surface EMG. At baseline, all patients had symptomatic quadriceps dysfunction, evidenced by transmission defects on single-fibre EMG. RESULTS: MU size and strength declined significantly by 20% and 15%, respectively in patients with PPS. Those with the largest initial MU sizes exhibited the greatest losses of mean MU size (27%) and proportional decreases in quadriceps strength (23%). Initial strength, change in LOI and change in RMS amplitude together explained 35% of the variability in strength changes in patients. MU size of controls did not change, although they lost 29% strength. CONCLUSIONS: MU size and strength declined concomitantly in a homogeneous cohort of patients with PPS and quadriceps dysfunction. SIGNIFICANCE: This long term follow-up study provides evidence that size diminution of enlarged MUs combined with a reduced number of active MUs contributes to the gradual strength decline in PPS.

Interobserver agreement on MRI evaluation of patients with cervical radiculopathy.

AIM: To evaluate the interobserver agreement on magnetic resonance imaging (MRI) evaluation of herniated discs, spondylotic neuroforaminal stenosis, and root compression in patients with recent onset cervical radiculopathy and in addition, to assess the added value of disclosure of clinical information to interobserver agreement. MATERIALS AND METHODS: The MRI images of 82 patients with less than 1 month of symptoms and signs of cervical radiculopathy were evaluated independently by two neuroradiologists who were unaware of clinical findings. MRI analysis was repeated after disclosure of clinical information. Interobserver agreement was calculated using kappa statistics. RESULTS: The kappa score for evaluation of herniated discs and of spondylotic foramen stenosis was 0.59 and 0.63, respectively. A kappa score of 0.67 was found for the presence of root compression. After disclosure of clinical information kappa scores increased slightly: from 0.59 to 0.62 for the detection of herniated discs, from 0.63 to 0.66 for spondylotic foramen stenosis, and from 0.67 to 0.76 for root compression. CONCLUSION: Interobserver reliability of MRI evaluation in patients with cervical radiculopathy was substantial for root compression, with or without clinical information. Agreement on the cause of the compression, i.e., herniated disc or spondylotic foraminal stenosis, was lower.

Degenerative cervical radiculopathy: diagnosis and conservative treatment. A review.

Degenerative cervical radiculopathy: clinical diagnosis and conservative treatment. A review. To provide a state-of-the-art assessment of diagnosis and non-surgical treatment of degenerative cervical radiculopathy a literature search for studies on epidemiology, diagnosis including electrophysiological examination and imaging studies, and different types of conservative treatment was undertaken. The most common causes of cervical root compression are spondylarthrosis and disc herniation. Diagnosis is made mainly on clinical grounds, although there are no well-defined criteria. Provocative tests like the foraminal compression test are widely used but not properly evaluated. The clinical diagnosis of degenerative cervical radiculopathy can be confirmed by magnetic resonance imaging. The role of electromyography is mainly to rule out other conditions. Cervical radiculopathy is initially treated conservatively, although no treatment modality has been evaluated in a randomized controlled trial. Degenerative cervical radiculopathy: diagnosis and conservative treatment. A review.

Motor axon loss is associated with hand dysfunction in Charcot-Marie-Tooth disease 1a.

BACKGROUND: Charcot Marie Tooth type 1a (CMT1a) is a primarily demyelinating neuropathy, characterized by slowly progressive muscle weakness, atrophy, and sensory loss, and is most pronounced in both feet and hands. There is increasing evidence that muscle weakness is determined by motor axonal dysfunction. OBJECTIVE: To investigate in patients with CMT1a whether motor axon loss, as estimated with motor unit number estimation (MUNE) and compound muscle action potential (CMAP), is related to hand function and manual dexterity. METHODS: Hand function, manual dexterity, and axon loss were studied in 48 patients with proven CMT1a. Using high-density surface EMG on the thenar muscles, MUNE was determined and CMAPs were measured. RESULTS: Pinch strength, clawing of the fingers, and manual dexterity correlated significantly with MUNE and CMAP (amplitude and area), while sensory impairments did not. Grip strength correlated significantly with CMAP amplitude but did not become significant with MUNE and CMAP area. Neurophysiologic variables were particularly associated with fine motor function of the hand. CONCLUSIONS: Motor axon loss is likely to be the major cause of hand dysfunction and impaired manual dexterity in Charcot Marie Tooth type 1a (CMT1a). In a clinical setting, the evaluation of the hands of patients with CMT1a should thus be mainly directed toward the evaluation of fine motor functions.

The reproducibility of the Canadian Occupational Performance Measure.

OBJECTIVE: To assess the reproducibility (reliability and inter-rater agreement) of the client-centred Canadian Occupational Performance Measure (COPM). DESIGN: The COPM was administered twice, with a mean interval of seven days (SD 1.6, range 4-14), by two different occupational therapists. Data analysis was based on intraclass correlation coefficients, the Bland and Altman method and Cohen's weighted kappas. SETTING: Occupational therapy departments of two university medical centres. SUBJECTS: Consecutive clients, with various diagnoses, newly referred to the outpatient clinic of two occupational therapy departments, were included. They were all over 18 years of age and perceived limitations in more than one activity of daily life. Complete data on 95 clients were obtained: 31 men and 64 women. RESULTS: Sixty-six per cent of the activities prioritized at the first assessment were also prioritized at the second assessment. The intraclass correlation coefficients were 0.67 (95% confidence interval (CI) 0.54-0.78) for the mean performance score and 0.69 (95% CI 0.56-0.79) for the mean satisfaction score. The limits of agreement were -2.5 to 2.4 for the mean performance score and -2.3 to 2.7 for the mean satisfaction score. For the separate prioritized problems, the weighted kappas ranged from 0.37 to 0.49. CONCLUSIONS: Inter-rater agreement of the prioritized problems was moderate. The reproducibility of the mean performance and satisfaction scores was moderate, but it was poor for the scores of the separate problems. Therefore, the mean scores should be used for individual assessment.

Pyridostigmine in postpolio syndrome: no decline in fatigue and limited functional improvement.

OBJECTIVES: To investigate the effect of pyridostigmine on fatigue, physical performance, and muscle function in subjects with postpoliomyelitis syndrome. METHODS: 67 subjects with increased fatigue and new weakness in one quadriceps muscle showing neuromuscular transmission defects, were included in a randomised, double blind, placebo controlled trial of 60 mg pyridostigmine four times a day for 14 weeks. Primary outcome was fatigue (on the "energy" category of the Nottingham health profile). Secondary outcomes included two minute walking distance and quadriceps strength and jitter. Motor unit size of the quadriceps was studied as a potential effect modifier. The primary data analysis compared the changes from baseline in the outcomes in the last week of treatment between groups. RESULTS: 31 subjects treated with pyridostigmine and 31 subjects treated with placebo completed the trial. No significant effect of pyridostigmine was found on fatigue. The walking distance improved more in the pyridostigmine group than in the placebo group (by 7.2 m (6.0%); p<0.01). Subgroup analysis showed that a significant improvement in walking performance was only found in subjects with normal sized motor units. Quadriceps strength improved more in the pyridostigmine group than in the placebo group (by 6.7 Nm (7.2%); p = 0.15). No effect of pyridostigmine was found on jitter. CONCLUSIONS: Pyridostigmine in the prescribed dose did not reduce fatigue in subjects with postpoliomyelitis syndrome. However, it may have a limited beneficial effect on physical performance, especially in subjects with neuromuscular transmission defects in normal sized motor units.

Tuberculin skin test reactions by time of reading among Dutch travellers.

SETTING: Five travel and TB control clinics in The Netherlands. OBJECTIVE: To assess the variation of skin test reactions between different days of reading. DESIGN: Cohort study of non-BCG-vaccinated travellers. Mantoux skin test data were analysed for associations between time interval between administration and reading and reaction size. RESULTS: There were no significant differences in reaction size to 1 TU PPD between readings at day 3 or 4, either for pre-travel (n = 1004) or post-travel (n = 577) tests, before (P = 0.990 and 0.210, respectively) or after exclusion of 0 mm reactions (P = 0.330 and 0.474). Time intervals were not different for reaction sizes of 0, 1-9 or > or = 10 mm (P = 0.826 and 0.306). There were also no significant associations for simultaneous tests with a sensitin of Mycobacterium scrofulaceum. CONCLUSIONS: Tuberculin skin tests can be read on day 3 or 4, without compromising their validity.

Perceived health in a population based sample of victims of the 1956 polio epidemic in the Netherlands.

OBJECTIVE: To investigate perceived health and its relation to residual paresis from polio, late onset neuromuscular symptoms following poliomyelitis (LSP), and sex, in a population based sample of polio survivors. METHODS: 350 subjects traced from the notification records of the Dutch 1956 polio epidemic received a mailed questionnaire on residual polio paresis and new neuromuscular symptoms. Perceived health was measured using the Nottingham health profile. Respondents with new muscle weakness and new neuromuscular symptoms were considered as cases with LSP. RESULTS: Health problems were perceived by 151 of the 260 respondents. Respondents with residual paresis had significantly more health problems than clinically recovered respondents for the Nottingham health profile category of physical mobility. The perceived health of respondents with LSP (45.5%) was significantly worse than that of respondents without LSP for all the health profile categories. Among the respondents with LSP, health status did not differ between those with residual paresis and those who had recovered, except for physical mobility. Female respondents with LSP reported worse health status than male respondents with regard to physical mobility and social isolation. CONCLUSIONS: In this population based sample, health problems were frequently reported. They were mainly related to late onset neuromuscular symptoms following poliomyelitis, which were perceived by a substantial proportion of all polio survivors-not only subjects with polio residuals but also individuals who (subjectively) had recovered from polio.

Neurobehavioral and developmental profile of very low birthweight preterm infants in early infancy.

AIM: To describe the neurobehavioral and developmental profile of very low birthweight (VLBW) preterm infants in early infancy. METHODS: Twenty VLBW infants and 10 term control infants were assessed at term, 3 and 6 mo of age. Neurobehavioral assessments included the Neonatal Behavioral Assessment Scale (NBAS) at term; the Infant Behavioral Assessment at term, 3 and 6 mo of age and the Behavioral Rating Scale of the Bayley Scales of Infant Development-II (BSID-II) at 3 and 6 mo of age. Development was evaluated with the Bayley Motor and Mental Scale at 3 and 6 mo. RESULTS: At term age VLBW infants differed from term infants on all the clusters and supplementary items of the NBAS. VLBW infants also showed more stress and less approach behavior at term and 6 mo of age and more problems with self-regulation in all subsystems at 6 mo of age. Moreover, VLBW infants performed lower on the Bayley Motor, Mental and Behavioral Rating Scale: 12 VLBW infants scored questionable or non-optimal on the Psychomotor Development Index and 18 questionable or non-optimal on the Behavioral Rating Scale. These results support the need for neurobehavioral intervention of VLBW infants in the first 6 mo of life. CONCLUSION: Almost all VLBW infants showed non-optimal motor quality behavior at 6 mo and encountered far more problems with self-regulation compared with term infants.

Coadministration of antigen and particles optimally stimulates the immune response in an intranasal administration model in mice.

Some particulate matter is known to affect human health, yet the mechanism(s) by which it acts is largely unknown. One of the factors that may play a role in the immune- stimulating activity of particles is binding of allergen to particles. This may turn the particles into allergen carriers, resulting in antigen deposition within the altered inflammatory microenvironment created by the particles. We compared the efficacy of simultaneous versus separate administration of antigen and particles during sensitization in an intranasal exposure model in BALB/c mice. Sensitization consisted of three separate doses (10 microg) of TNP-OVA at Days 1, 2, and 3. Two hundred micrograms of carbon black particles (CBP) were administered either 1 day before sensitization (Day 0), 1 day after sensitization (Day 4), or during sensitization. The latter was performed either at Day 1 (200 microg) or at Days 1, 2, and 3 (67 microg/day). At Day 10 a challenge with 10 microg of TNP-OVA was performed, and at Day 15 the immune response was assessed. The total number of cells as well as antibody-forming cells (AFC) in lymph nodes draining the lung (peribronchial lymph nodes [PBLN]) were determined, and immunoglobulin levels in blood were assessed. Cell numbers of PBLN increased significantly in all particle-treated groups compared to controls. The number of TNP-specific IgG1-forming cells in the groups receiving particles during sensitization was significantly higher than control level. Only groups receiving particles during or before sensitization displayed significantly higher IgG1 levels than controls, in contrast to the group receiving particles after sensitization. Only in animals receiving three doses of 67 microg during sensitization did TNP-specific IgE increase significantly compared to controls. IgG2a did not show significant differences compared to controls, indicating that the response is predominantly Th2 mediated. These data indicate that coadministration of particles at all time points of antigen dosing is the most effective way to stimulate an immune response in our model compared to separate particle and antigen dosing. Also, administration shortly before antigen administration was effective in stimulating an immune response, suggesting that time-dependent processes are involved in immune-stimulating activity of particles, supporting the important role of the altered inflammatory microenvironment created by the particles.