'This battle, between your gut feeling and your mind. Try to find the right balance': Parental experiences of children with spinal muscular atrophy during COVID-19 pandemic.

AIMS: Parents of children with spinal muscular atrophy (SMA) often struggle with the all-consuming nature of the demands of caring for a child with substantial physical needs. Our aim was to explore experiences, challenges and needs of parents of a child with SMA in a COVID-19 pandemic situation. METHOD: Nineteen parents of 21 children (15 months to 13 years of age) with SMA types 1-3 participated in semi-structured interviews in June to July 2020. The interviews were analysed using inductive thematic analysis. RESULTS: Parents mentioned the protection of the health and well-being of the child as the central perspective and driving force during the COVID-19 pandemic. Three subthemes were identified: (1) responsibility, (2) balancing vulnerability and resilience and (3) (in)security. Some parents focused on the positive aspects during the lockdown, such as continuation of nusinersen treatment and family life. Some parents described helpful and positive cognitions to cope with the situation. In general, parents described a need for information with regard to COVID-19 and their child with SMA and a need for discussing their dilemmas and insecurities with a healthcare professional. INTERPRETATION: Parents put the health and well-being of their children first during the pandemic. From this study, we learned that parents of children with SMA need information and value direct contact with a healthcare professional to share their dilemmas and insecurities. The dialogue can help to empower parents in the conflicts and decisions they have to make during a pandemic.

Investigation of inflammatory and allergic responses to common mold species: Results from in vitro experiments, from a mouse model of asthma, and from a group of asthmatic patients.

Most studies on molds focus on Alternaria alternata and Aspergillus fumigatus. Here, we report on inflammatory and allergenic properties of more typical indoor species Aspergillus versicolor, P. chrysogenum, C. cladosporioïdes, and C. sphaerospermum that were compared to A. alternata and A. fumigatus. In a mouse model, after intranasal instillation, A. alternaria, A. versicolor, and C. sphaerospermum induced the early recruitment of neutrophils and the strong expression of inflammatory markers in the bronchoalveolar lavages fluids. A. fumigatus also induced the early accumulation of neutrophils but with lower levels of inflammatory markers. Chronic treatment induced variable response according to species: P. chrysogenum and A. fumigatus appeared strong pro-allergenic inducers compared to A. alternata and C. sphaerospermum while A. versicolor and C. cladosporioides induced a mixed pro-allergenic/pro-inflammatory response. In mold-sensitized asthmatics, mold-specific Immunoglobulin E (IgE) were detected with an in-house dot-blot assay. A. fumigatus and A. alternata were the most frequent sensitizers. Altogether, P. chrysogenum, P. brevicompactum, C. sphaerospermum, and C. cladosporïoides were the "major sensitizer" (defined as the strongest response against a single mold species) for almost 30% of the asthmatics. These results show that, not only A. alternata and A. fumigatus, but also indoor species have strong inflammatory and allergic properties and a harmful potency.

Is chronic ventilatory support really effective in patients with amyotrophic lateral sclerosis?

Most patients with amyotrophic lateral sclerosis (ALS) develop respiratory insufficiency in the advanced stage of their disease. Non-invasive ventilation (NIV) is commonly regarded to be a treatment that is effective in reducing these complaints. To assess whether the effect of NIV on gas exchange and quality of life (QOL) is different in patients with ALS versus without ALS. A post hoc analysis was done with data from a previously published trial, in which all patients were instituted on NIV. Arterial blood gasses were assessed next to QOL by generic as well as disease-specific questionnaires. 77 patients started NIV: 30 with ALS and 47 without. Both groups showed significant improvements in blood gasses after 2 and 6 months. Compared to the non-ALS group, the ALS group had significantly worse scores after 6 months in MRF-28, SRI, HADS and SF-36 than the non-ALS group. This study shows that NIV improves gas exchange, both in patients with and without ALS. QOL improves markedly more in patients without ALS than in those with ALS, in whom only some domains improve. Our observation of little or no effect in ALS patients warrants a large study limited to ALS patients only.

Initiation of home mechanical ventilation at home: a randomised controlled trial of efficacy, feasibility and costs.

INTRODUCTION: Home mechanical ventilation (HMV) in the Netherlands is normally initiated in hospital, but this is expensive and often a burden for the patient. In this randomised controlled study we investigated whether initiation of HMV at home in patients with chronic respiratory failure is non-inferior to an in hospital based setting. METHODS: Seventy-seven patients were included, of which 38 patients started HMV at home. All patients were diagnosed with chronic respiratory failure due to a neuromuscular or thoracic cage disease. Primary outcome was the arterial carbon dioxide (PaCO2) while quality of life and costs were secondary outcomes. Telemonitoring was used in the home group to provide therapeutic information, for example; transcutaneous carbon dioxide, oxygen saturation and ventilator information, to the caregivers. Follow-up was six months. RESULTS: PaCO2, improved by 0.72 (SE ± 0.16) kPa in the hospital group and by 0.91 (±0.20) in the home group, both improvements being significant and the latter clearly not inferior. There were also significant improvements in quality of life in both groups, again not being inferior with home treatment. CONCLUSION: This study is the first to show that initiation of HMV at home in a selective group of patients with chronic respiratory failure is as effective for gas exchange and quality of life as hospital initiation. In addition we found that it is safe, technically feasible and that more than € 3000 per patient can be saved compared to our standard care.

Doxapram use for apnoea of prematurity in neonatal intensive care.

Apnoea of prematurity is treated with noninvasive respiratory therapy and methylxanthines. For therapy unresponsive apnoea doxapram is often prescibed in preterm neonates. The duration, dosage and route of administration of doxapram together with its efficacy was evaluated in two Dutch neonatal intensive care. Outcome concerning short-term safety and neonatal morbidity were evaluated. During 5 years, 122 of 1,501 admitted newborns <32 weeks of gestational age received doxapram. 64.8% of patients did not need intubation after doxapram. 25% of treated neonates were <27 weeks of gestation. A positive response to doxapram therapy on apnoea was associated with longer duration of doxapram usage (P < 0.001), lower mean doses (P < 0.003), and less days of intensive care (median 33 versus 42 days; P < 0.002). No patients died during doxapram therapy. Incidence of necrotizing enterocolitis, intraventricular hemorrhage, periventricular leukomalacia, retinopathy of prematurity, persistent ductus arteriosus, or worsening of pulmonary condition did not increase during doxapram therapy. Doxapram is frequently used for apnoea of prematurity, despite a lack of data on short-term efficacy and long-term safety. Until efficacy and safety are confirmed in prospective trials, doxapram should be used with caution.

Motor Development of Premature Infants Born between 32 and 34 Weeks.

Little is known about motor development in late preterm born infants. Our objective was to determine long-term outcome of motor skills of infants born between 32 and 34 weeks. All infants were assessed at corrected ages of 3 and 9 months, using the Alberta Infant Motor Scale. At corrected ages of 4 years, the Movement Assessment Battery for Children was done. Seventy infants were seen at 4 years of age (median of 3 assessments per infant). Abnormal assessment at 3 or 9 months of age resulted in normal outcome in almost 80% at 4 years. On the other hand, a normal outcome in the first year of life resulted in an abnormal outcome at 4 years in 10% of the infants. Our results suggest that long-term followup of these late preterm born infants is necessary, as the assessments in the first year do not predict the long-term outcome.

Propofol 6% as sedative in children under 2 years of age following major craniofacial surgery.

BACKGROUND: After alarming reports concerning deaths after sedation with propofol, infusion of this drug was contraindicated by the US Food and Drug Administration in children <18 yr receiving intensive care. We describe our experiences with propofol 6%, a new formula, during postoperative sedation in non-ventilated children following craniofacial surgery. METHODS: In a prospective cohort study, children admitted to the paediatric surgical intensive care unit following major craniofacial surgery were randomly allocated to sedation with propofol 6% or midazolam, if judged necessary on the basis of a COMFORT behaviour score. Exclusion criteria were respiratory infection, allergy for proteins, propofol or midazolam, hypertriglyceridaemia, familial hypercholesterolaemia or epilepsy. We assessed the safety of propofol 6% with triglycerides (TG) and creatine phosphokinase (CPK) levels, blood gases and physiological parameters. Efficacy was assessed using the COMFORT behaviour scale, Visual Analogue Scale and Bispectral Index monitor. RESULTS: Twenty-two children were treated with propofol 6%, 23 were treated with midazolam and 10 other children did not need sedation. The median age was 10 (IQR 3-17) months in all groups. Median duration of infusion was 11 (range 6-18) h for propofol 6% and 14 (range 5-17) h for midazolam. TG levels remained normal and no metabolic acidosis or adverse events were observed during propofol or midazolam infusion. Four patients had increased CPK levels. CONCLUSION: We did not encounter any problems using propofol 6% as a sedative in children with a median age of 10 (IQR 3-17) months, with dosages <4 mg kg(-1) h(-1) during a median period of 11 (range 6-18) h.

[Quantitative ultrasound bone measurements]. / Kvantitative UL-målinger til undersøgelse af knogler.

Quantitative ultrasound (QUS) bone measurement is a relatively new technique for the diagnosis of osteoporosis which is cheaper and easier to use than the more established method of bone densitometry (measurement of bone mineral density, BMD) by x-ray absorptiometry. The two QUS parameters currently measured are BUA (broadband ultrasound attenuation) and SOS (speed of sound). The reported age related changes for healthy women range from -0.27% to -1.62% per year for BUA and from -0.06% to -0.19% per year for SOS. Precision ranges from 1.0-3.8% (CV) for BUA and 0.19-0.30% (CV) for SOS. QUS is believed to reflect mainly BMD. However, studies indicate that QUS also reflects trabecular orientation and other determinants of bone strength independently of BMD. In both cross sectional and prospective studies, QUS seems to be as good a predictor of osteoporotic fractures as BMD.

Hip fracture discrimination by imaging ultrasound measurements of the calcaneus.

Quantitative ultrasound measurements of the os calcis have recently been upgraded with imaging facilities. This has made measurements of a specific region of interest possible and improved the reproducibility of the method, but the diagnostic ability of imaging ultrasound has not yet been investigated thoroughly. We measured broadband ultrasound attenuation (BUA) and speed of sound (SOS) using imaging ultrasound as well as forearm bone mineral density (BMDarm) using dual-energy X-ray absorptiometry in three age-matched groups of women: (1) 25 women who were admitted to hospital due to a hip fracture; (2) 23 women who were admitted to hospital due to a fall without any fracture; and (3) 26 normal women. Furthermore, BMD of the hip (BMDhip) was measured in a subgroup of the hip fracture patients and those who had fallen. All measurements were performed during the index hospitalization in order to avoid any influence from bone loss due to immobilization after the fracture. We found a -0.48 SD deviation from expected age-matched values in BUA among the hip fracture patients, whereas the patients who had fallen showed a +0.16 SD deviance. For SOS, the figures were -0.70 SD for the hip fracture group and -0.06 SD for the patients who had fallen. For BMD of the arm we found values of -0.65 SD and +0.08 SD, respectively, whereas the figures for BMD of the hip were -0.66 SD and +0.13 SD, respectively. All parameters were significantly lower in the hip fracture group compared with the patients who had fallen. None of the parameters in the patients who had fallen deviated significantly from expected normal age-matched values. Neither BMD of the arm or BMD of the hip separated hip fracture patients and patients who had fallen significantly better than ultrasound (BUA or SOS) did. We conclude that imaging ultrasound (BUA or SOS) separates age-matched groups of hip fracture and non-fracture patients as well as BMD measurements do.

Typing of bovine viral diarrhea viruses directly from blood of persistently infected cattle by multiplex PCR.

A nested multiplex PCR was developed for genotyping of bovine viral diarrhea viruses (BVDVs). The assay could detect as little as 3 50% tissue culture infective doses of BVDV per ml and typed 42 out of 42 cell culture isolates. BVDV was also successfully typed, with or without RNA extraction, from all 27 whole-blood samples examined from 22 carriers or probable carriers and 5 experimentally infected cattle.

A monoclonal antibody-based immunoperoxidase monolayer (micro-isolation) assay for detection of type 1 and type 2 bovine viral diarrhea viruses.

A monoclonal antibody (mAb)-based immunoperoxidase monolayer assay (IPMA) for detection of bovine viral diarrhea virus (BVDV) was developed and compared with an existing bovine polyclonal antibody (pAb)-based IPMA. A pool of 5 mAbs, 4 mAbs produced to a type 1 BVDV and 1 mAb produced to a type 2 BVDV, was utilized in the mAb-IPMA. The mAbs were chosen for inclusion in the pool because of their broad cross-reactivities with type 1 and/or type 2 BVDV, their apparent avidities for antigen, their reactivity to different BVDV proteins, and their lack of competition for binding sites or their binding to unusual BVDV isolates. The mAb-IPMA outperformed the pAb-IPMA in staining, ease of reading test results, and relative sensitivity with a panel of known BVDV positive and negative sera. The relative sensitivities of the mAb-IPMA and pAb-IPMA were 100% and 93.5%, respectively, for 62 positive samples including several that were known to contain type 2 BVDV. With retesting, the pAb-IPMA gave a similar level of sensitivity as that of the mAb-IPMA. Both tests gave a specificity of 100% for 40 negative serum samples obtained from a BVDV-free herd.

The role of quantitative ultrasound in the assessment of bone: a review.

Quantitative ultrasound (QUS) bone measurement is a promising, relatively new technique for the diagnosis of osteoporosis. Unlike to the more established method of bone densitometry [measurement of bone mineral density (BMD) e.g. using dual X-ray absorptiometry (DEXA)], QUS does not use ionizing radiation. It is cheaper, takes up less space and is easier to use than densitometry techniques. The two QUS parameters currently measured are broadband ultrasound attenuation (BUA) and speed of sound (SOS). The reported age-related changes for healthy women range from -0.27% to -1.62% per year for BUA and from -0.06% to -0.19% per year for SOS. Precision ranges from 1.0 to 3.8% (CV) for BUA and from 0.19 to 0.30% (CV) for SOS. The new method of imaging ultrasound has improved the precision of QUS measurements. QUS is significantly correlated with BMD. Studies with the latest equipment have shown r-values between 0.6 and 0.9 in site-specific measurements, and QUS is thus believed to reflect mainly BMD. However, other studies indicate that QUS measures something other than the actual mineral content of bone, namely bone quality, e.g. in vitro studies have shown that QUS reflects trabecular orientation independently of BMD. In both cross-sectional and prospective studies, QUS seems to be as good a predictor of osteoporotic fractures as BMD. In two large prospective studies, QUS also predicted fracture risk independently of BMD. QUS has just begun to be used systematically for monitoring the response to anti-osteoporotic treatments in prospective trials. In the studies performed, QUS has been found to be useful in the follow-up of patients. QUS is thus a promising new technique for bone assessment.

Comparative study of serological methods for the detection of antibodies to porcine reproductive and respiratory syndrome virus.

A comparison was made of serological diagnostic methods used for the detection of antibodies against porcine reproductive and respiratory syndrome (PRRS) virus. In the "phase I" PRRS test panel comparison, a panel of sera collected from 135 pigs of various ages, from North American herds with and without PRRS histories, were sent to 4 different laboratories and tested by an indirect immunofluorescent assay (IFA), an immunoperoxidase monolayer assay (IPMA) and an indirect enzyme-linked immunosorbent assay (iELISA). In the "phase II" PRRS test panel comparison, a panel of 382 sera collected from pigs of various ages, PRRS histories, and from various locations in North America and France, were divided into 2 panels (A & B) and sent to 3 Canadian laboratories and tested by the IFA and iELISA. In the phase I comparison, agreement between the IFA of laboratory 4 and the iELISA and IPMA of laboratory 3 was excellent (kappa values of 95% and 98%, respectively). This contrasted with the poor agreement between these laboratories and the IFA results of laboratories 1 and 2 in the phase I trial. In the phase II comparison, the results demonstrated good agreement between various tests both within and between laboratories. The overall performance of the iELISA was superior in the combination of sensitivity (96.1%) and specificity (100%) relative to the reference classification of the serum samples and repeatability (kappa value 98%). The iELISA is technically superior to IFA and IPMA, time efficient, cost effective and suitable for testing of a large number of samples over a short period of time. Thus, the iELISA may be a better alternative to IFA or IPMA for routine detection of PRRS viral antibodies in swine sera.

Rapid detection of bovine herpesvirus 1 in the semen of infected bulls by a nested polymerase chain reaction assay.

A nested polymerase chain reaction (PCR) assay was developed for the detection of bovine herpesvirus 1 (BHV-1) in bovine semen and compared with the virus isolation method. When extended semen, commonly used in the bovine artificial insemination industry, was inoculated with BHV-1, the PCR assay detected BHV-1 DNA in semen inoculated at 0.25-2.5 TCID50 per 0.5 mL. In contrast, the lower limit of detection for virus isolation was 250 TCID50 of BHV-1 inoculated in 0.5 mL of extended semen. These methods were also used to detect BHV-1 in the semen of four bulls which were experimentally infected with BHV-1. All infected bulls demonstrated balanitis at 3 d post-inoculation (DPI) and severe balanoposthitis at 4 DPI. BHV-1 was detected in raw semen by virus isolation and PCR at 2 DPI, before balanitis was evident. For virus isolation, the last day that BHV-1 was detected during primary infection was 7 DPI for two bulls and 9 and 11 DPI for the other two bulls. In contrast, PCR detected BHV-1 in the bulls' semen until 14 or 18 DPI. For individual animals, PCR detected BHV-1 during primary infection for at least 1-10 d longer than virus isolation. Reactivation of BHV-1 from latency without the presence of visible lesions was promoted twice by two series of 5 d dexamethasone injections. For the first series of dexamethasone treatments, a positive virus isolation result was obtained on the 5th d of treatment for only one bull. In contrast, two bulls demonstrated evidence of viral reactivation on this day by PCR. All bulls shed BHV-1 in semen on d 4 after dexamethasone treatment, as evidenced by positive virus isolation and PCR results. One bull was still PCR positive 13 d later. For the second series of dexamethasone treatments, a small amount of virus was isolated from semen collected on d 3 or 4 after treatment for two bulls but not from the other two bulls. In contrast, semen samples from all bulls were PCR positive for either or both of these 2 d. In total, from 80 semen samples, 45 were PCR positive and 26 were virus isolation positive. Thus, the PCR assay detected BHV-1 shedding in bulls earlier, more often, and for a longer duration, than did the virus isolation method.

[Skin cancers following organ transplantation: clinical and therapeutic approach]. / Cancers cutanés après transplantation d'organes: approche clinique et thérapeutique.

Three of the most frequent cancers occurring in transplant recipients affect the skin: Kaposi's sarcoma and spino- and baso-cellular carcinomas. The two latter neoplasms are often preceded by precancerous lesions such as keratosis, warts, porokeratosis and keratoacanthomas. We describe the clinical presentations of these lesions and detail the possible therapies in each case: local treatment, surgery, modulation of immunosuppression, and chemotherapy.