Therapy of osteoid osteomas -- always surgically?

Osteoidosteomas are common bone tumours in childhood. Frequently they occur in the long bones of the lower extremities, less frequent in the humeri, phalanxes or the axial skeleton. The tumour is benign and noninfiltrative. Metastases do not occur. Typical complaints are nightly pain attacks, which are relieved by nonsteroidal antiinflammatory drugs. On X-ray, the classic finding is a small radiolucent area surrounded by sclerotic bone in the cortex. Surgical excision is often recommended, providing the possibility for a histological diagnosis. Therapeutic alternatives are percutaneous coagulation of the nidus by alcohol or laser, thermo-coagulation or high-frequency radioablation. Spontaneous remissions are well documented. Therefore the decision to wait and see and to treat with antiinflammatory medication is a considerable therapeutic option. We present two patient with an ostoidosteoma in the proximal femur. One of them underwent an unsuccessful trial for surgical extirpation and histological examination but afterwards developed a severe hip contraction with scoliosis. In the case of the other patient a primary operation was abandoned. Pain was completely controlled upon treatment with nonsteroidal antiinflammatory drugs in both patients. The contractions also disappeared completely upon physiotherapy. Serial MRI showed a significant regression of the inflammatory reaction in one case and the disappearance of the tumour in the other one. In conclusion, pharmacomedical therapy can be recommended, if the diagnosis is doubtlessly and a close follow up is established. The risk of anaesthesia and surgical treatment should be weighted against the risk of nonsteroidal antiinflammatory drug treatment.     

β-Blocker Therapy Failures in Symptomatic Probands with Genotyped Long-QT Syndrome

-Blocker therapy is one of the principal therapies for congenital long-QT syndrome (LQTS). However, breakthrough cardiac events occur while being treated with -blockers. We sought to determine the frequency of and clinical correlates underlying -blocker therapy failures in genotyped, symptomatic LQTS probands. The medical records were analyzed only for genotyped LQTS probands who presented with a LQTS-attributable clinical event and were receiving -blocker therapy. The study cohort comprised 28 such patients: 18 KCNQ1/KVLQT1(LQT1), 7 KCNH2/HERG (LQT2), and 3 SCN5A (LQT3). The prescribed -blocker was atenolol (12), propranolol (10), metoprolol (4), and nadolol (2). -Blocker therapy failure was defined as breakthrough cardiac events including syncope, aborted cardiac arrest (ACA), appropriate implantable cardioverter-defibrillator (ICD) therapy, or sudden death occurring while on -blocker therapy. During a median follow-up of 46 months, 7/28 (25%) LQTS probands experienced a total of 15 breakthrough cardiac events. Their initial presentation was ACA (3), bradycardia during infancy (2), and syncope (2). The underlying genotype was KVLQT1 (6) and HERG (1). Two breakthroughs were attributed to noncompliance. Of the 13 breakthroughs occurring while compliant, 10 occurred with atenolol and 3 with propranolol (p = 0.03). In this study cohort, one-fourth of genotyped LQTS probands failed -blocker therapy. Treatment with atenolol, young age at diagnosis, initial presentation with ACA, KVLQT1 genotype, and noncompliance may be important factors underlying -blocker therapy failures.     

Does Context Matter? Mastery Motivation and Therapy Engagement of Children with Cerebral Palsy

Aims: To determine if mastery motivation at baseline predicts engagement in two goal-directed upper limb (UL) interventions for children with unilateral cerebral palsy (UCP). Methods: Participants were 44 children with UCP, mean age 7 years 10 months, Manual Ability Classification System level I (N = 23) or II (N = 21). Twenty-six children received intensive novel group-based intervention (Hybrid Constraint Induced Movement Therapy, hCIMT) and 18 received distributed individual occupational therapy (OT). Caregivers completed the Dimensions of Mastery Questionnaire (DMQ) parent-proxy report at baseline. Children's engagement was independently rated using the Pediatric Volitional Questionnaire (PVQ). Associations between children's mastery motivation and engagement were examined using linear regression. Results: Children who received hCIMT had lower DMQ persistence at baseline (p = .05) yet higher PVQ volitional (p = .04) and exploration (p = .001) scores. Among children who received hCIMT, greater object-oriented persistence was associated with task-directedness (β 0.25, p = .05), seeking challenges (β = 0.51, p = .02), exploration (β = 0.10, p = .03), and volitional scores (β = 0.23, p = .01). Conclusion: Despite having lower levels of persistence prior to engaging in UL interventions, children who received hCIMT demonstrated greater engagement in goal-directed tasks than children who received individual OT. Within hCIMT, children's motivational predisposition to persist with tasks manifested in their exploration and engagement in therapy.     

Cardiac Remodeling After Enzyme Replacement Therapy with Acid α-Glucosidase for Infants with Pompe Disease

Background  Infantile Pompe disease (glycogen storage disease type 2) is a fatal disorder caused by deficiency of acid α-glucosidase. This deficiency results in glycogen accumulation in the lysosomes of many tissues including cardiac muscle. The disease is characterized by profound hypotonia, poor growth, organomegaly, and cardiomegaly. Severe hypertrophic cardiomyopathy often is present in early infancy, and most patients die of cardiac or respiratory failure in the first year of life. This report describes the cardiac response of infants with Pompe disease to a phase 2 trial of enzyme replacement therapy (ERT). Methods  Eight patients with classical infantile Pompe disease were given intravenous recombinant human GAA (rhGAA) for 1 year. Cardiac monitoring included echocardiography, electrocardiograms (ECGs), chest radiographs, and clinical cardiac evaluation at 4, 8, 12, 24, 36, and 52 weeks. At 52 weeks, 6 patients were alive. Results  Most of the treated patients had rapid regression of ventricular hypertrophy in response to ERT, with near normalization of posterior wall thickness, ventricular mass, and ventricular size. Systolic ventricular function was preserved despite rapid changes in ventricular mass and size. Concomitantly, ECGs documented lengthening of the PR interval and decreased ventricular voltages, whereas chest radiographs documented a decreased cardiothoracic ratio. Symptoms of pulmonary congestion were diminished, and survival was improved. Conclusion  The cardiovascular system responds quickly and strikingly to ERT with rhGAA, suggesting rapid reversal of excessive glycogen storage in cardiac muscle cells. Changes in ventricular mass and function are maintained throughout 1 year of follow-up evaluation and associated with decreased morbidity and prolonged survival.     

Therapy of monosymptomatic nocturnal enuresis in childhood and adolescence: what is the evidence?

Nocturnal enuresis (bedwetting) is one of the most frequent urological symptoms in children, affecting about 20% of five year olds. It is a heterogeneous disorder with a whole variety of etiologic factors (genetic, endocrinological, neurobiological), particularly a dysfunction of the lower urinary tract. Despite the prevalence of enuresis many questions regarding the complex pathophysiological mechanisms remain unanswered. While nocturnal enuresis per se is clearly not a disease, psychosocial problems have been reported in up to 40% of affected children. Management strategies comprise behavioural and pharmacological approaches, either in isolation or combined. Although expectations were high, especially with pharmacological interventions, the results are usually disappointing with high recurrence rates. Extensive analyses of the available literature on the efficacy of enuresis treatment modalities reveal a poor quality of many trials with a whole range of methodological flaws. Therefore, further comparative studies of adequate methodological quality are needed.     

Cardiac Functions in Children With Growth Hormone Deficiency Before and During Growth Hormone�CReplacement Therapy

Childhood growth hormone deficiency (GHD) decreases left-ventricular (LV) mass, but impairment of cardiac function has never been documented. The objective of this study was to assess the cardiac effects of GHD and recombinant human growth hormone (rhGH) treatment using conventional echocardiography and tissue Doppler imaging. Complete two-dimensional, M-mode, pulse-wave Doppler echocardiography and pulse-wave tissue Doppler imaging were performed in 12 children (6 male and 6 female patients) with GHD at baseline and at 5.86 ± 1.61 months after rhGH therapy. Recombinant human growth hormone treatment was associated with a significant increase in LV mass index (63.8 ± 27.1 to 79.3 ± 30.3 g/m²; P < 0.01) and LV internal dimensions (21.4 ± 2.63 to 24.0 ± 4.13 mm in systole [P = 0.03] and 36.5 ± 3.90 to 39.5 ± 4.94 mm in diastole [P < 0.01]). There were statistical differences of parameters, such as deceleration time of early peak velocity of mitral, isovolumic relaxation time, and myocardial performance index (103 ± 15.4 to 139 ± 21.2 ms [P < 0.01], 55.5 ± 9.24 to 69.2 ± 3.74 ms [P < 0.01], and 37.8 ± 4.46 to 44.9 ± 5.44% [P < 0.01], respectively). Before and during rhGH therapy, there were no significant differences in fractional shortening of the left ventricle, peak mitral, and tricuspid wave velocities with ratios determined using conventional echocardiography and tissue Doppler imaging. In children, GHD affects heart morphology by inducing a decrease in cardiac size, but it does not modify cardiac function. Recombinant human growth hormone treatment increases cardiac mass, deceleration time of early peak velocity of the mitral valve, isovolumic relaxation time, and myocardial performance index, but it does not make a difference in other parameters of conventional echocardiography and tissue Doppler imaging.     

Can Destination Therapy be implemented in children with heart failure? A study of provider perceptions

DT is an established final therapeutic choice in adult patients with severe heart failure who do not meet criteria for cardiac transplantation. Patients are given VADs, without the prospect of care escalation to transplantation. VADs are now established therapy for children and are currently used as a bridge until transplantation can be performed or heart failure improves. For children who present in severe heart failure but do not meet transplantation criteria, the question has emerged whether DT can be offered. This qualitative study aimed to elicit the perspectives of early adopters of DT at one of the few institutions where DT has been provided for children. Responses were recorded and coded and themes extracted using grounded theory. Interviewees discussed: envisioning of the DT candidate; approach to evaluation for DT; contraindications to choosing DT; and concerns about choosing DT. Providers articulated two frameworks for conceptualizing DT: as a long bridge through resolution of problems that would initially contraindicate transplantation or, alternatively, as a true destination instead of transplantation. True destination, however, may not be the lasting concept for long‐term VAD use in children given improvement in prognosis for current medical contraindications and improving VAD technology.     

Paracetamol Therapy for Patent Ductus Arteriosus in Premature İnfants: A Chance Before Surgical Ligation

Patent ductus arteriosus (PDA) remains a common problem in premature infants. Treatment options include pharmacologic therapy and surgical ligation, but these are associated with potentially significant adverse effects. This report describes the effect of administering oral paracetamol to premature neonates with PDA. The study enrolled seven premature neonates followed up with the diagnosis of hemodynamically significant PDA (hsPDA) between February and December 2012 and treated with oral paracetamol. Patients with hsPDA were given at least two or more courses of ibuprofen treatment. If this therapy failed to promote ductal closure, the patients with clinical symptoms who had hsPDA defined by echocardiography were treated with oral paracetamol (15 mg/kg every 6 h). If these patients did not respond to paracetamol therapy, the PDA was closed by surgical ligation. The mean gestational age of the seven patients in this study was 26.1 weeks, and their mean birth weight was 936 g. Paracetamol treatment was started at 36.2 ± 11.6 days. The mean internal ductal diameter was 2.0 ± 0.2 mm, and the left atrium-to-aorta ratio was 1.5 ± 0.2. All the patients were administered oral paracetamol because of no response to ibuprofen treatment. The hsPDA was successfully closed with oral paracetamol in five (71.4 %) of the seven patients. The remaining two patients had surgical ligation performed, but one of them died. No side effects related to paracetamol were observed. Oral paracetamol may be used as an alternative drug for the management of hsPDA in premature neonates when ibuprofen treatment is unsuccessful and the only other therapeutic option is surgery.     

Recombinant Human IGF-1 (Insulin-Like Growth Factor) Therapy: Where Do We Stand Today?

Recombinant human (rh) IGF-1 has been available for therapy since the 1980s and has been commercially available for over 5 y, yet the role of rhIGF-1 in treating children with short stature remains ambiguous. This is consequent to the inherent difficulty in defining criteria for IGF-1 deficiency, and in determining the outcome of rhIGF-1 therapy in terms of growth rate and adult height. The rationale for its efficacy compared with rhGH (recombinant human growth hormone) for treatment of short stature is still widely debated. Additionally, adverse events such as increased intracranial pressure and hypoglycemia are of therapeutic concern. The goal of this article is to review published data that describes the impact of IGF-1 therapy in treatment of short stature and other growth disorders.     

Effect of Interferon-α Therapy in a Patient with Common Variable Immunodeficiency and Chronic Epstein-Barr Virus Infection

We report an 18-year-old boy with common variable immunodeficiency who presented with splenomegaly as well as left axillary and lateral cervical lymphadenopathy. Main laboratory investigations showed severe thrombocytopenia. Epstein-Barr virus (EBV) DNA was delected in the patient's throat-washing specimens and lymph node biopsy. Lymphocytes from the lymph node biopsy were also positive for EBV nuclear antigen. Serology for EBV and cytomegalovirus was negative. A therapeutic attempt with acyclovir did not influence the course of infection. Six months' treatment with human lymphoblastoid interferon-α (IFN alfa) brought about the normalization of clinical and hematologic conditions. Detection on throat-washing specimens carried out 1 year after therapy was negative. Our preliminary experience suggests that human lymphoblastoid IFN-α is a valid alternative in therapy of immunodeficient EB virus-infected patients.     

CDC Kerala 5: Developmental Therapy Clinic Experience – Use of Child Development Centre Grading for Motor Milestones

Objectives

To document the experiences of the intervention given to children who attended the developmental therapy clinic of Child Development Centre (CDC) Kerala, a specialized clinic for providing developmental intervention/therapy for babies less than two years with developmental delay/disability.

Methods

All the babies referred to this speciality clinic from developmental screening/evaluation clinics of CDC were registered in the clinic and re-evaluation was done using CDC grading for head holding, sitting, standing, Amiel Tison passive angles, and Trivandrum Developmental Screening Chart (TDSC) 0–2 y.

Results

Out of a total of 600 consecutive babies below 2 y with developmental delay/disability referred to developmental therapy clinic, on comparing the test results at enrollment and after 6 mo of intervention, a statistically significant reduction was observed (i) in the 2–4 mo age group with regard to abnormal TDSC (25.5 %), (ii) in the 4–8 mo age group with regard to abnormal head holding grade (87.1 %) and abnormal TDSC (19.4 %), (iii) in the 8–12 mo age group, with regard to abnormal sitting grade (71.7 %) and (iv) in the above 12 mo age group with regard to abnormal sitting grade (35.3 %) and abnormal standing grade (78.8 %).

Conclusions

The experience of organizing the developmental intervention/therapy clinic at CDC Kerala has shown that therapy services by developmental therapists in a centre and supportive therapy by mother at home is useful in improving the developmental status of children with developmental delay.