Ten-year follow-up in a case series of integrative botulinum toxin intervention in adolescents with chronic daily headache and associated muscle pain.

INTRODUCTION: A total of 83% of children report headache during a 6-month period. The estimated 1-year prevalence of chronic daily headache (CDH) in children is at least 1 to 2%. Muscle pain is associated with headache severity and chronicity. Muscle pain can be associated with active muscular trigger points, a functional concept still remaining a controversy. An integrated approach including bio-behavioral management is accepted as standard treatment but does not provide sufficient pain relief in all patients. OBJECTIVE: We report the individual clinical course of five adolescents with treatment-refractory CDH associated with focal muscle pain. We describe a concept of short-term integrative intervention including botulinum toxin (StiBo) in a personalized "follow the referred pain pattern" injection regimen with the focus on long-term follow-up. RESULTS: StiBo showed short-term efficacy on headache frequency and severity. In the long-term follow-up, CDH was not existent in any of the patients. CONCLUSION: The treatment may have enabled the patients to draw attention away from a repeated circle of muscle-triggered pain and withdrawal of daily activities toward self-driven activities, thereby potentially preventing the development of further chronification. To prove this hypothesis, a prospective, placebo-controlled study in young adolescents with CDH should be initiated including objective outcome parameters on muscular level.

Incidence and clinical features of hyperimmunoglobulinemia D and periodic fever syndrome (HIDS) and spectrum of mevalonate kinase (MVK) mutations in German children.

Autoinflammatory diseases (AIDs) are characterized by recurrent, self-limiting systemic inflammation. Disorders include hereditary recurrent fever (HRF) syndromes such as hyperimmunoglobulinemia D and periodic fever syndrome (HIDS). To determine the incidence of HIDS and report clinical and genetic characteristics together with the underlying MVK genotypes in German children, a prospective active surveillance was conducted in Germany during a period of 3 years. Monthly inquiries were sent to 370 children's hospitals by the German Paediatric Surveillance Unit (Clinic-ESPED, n1) and to two laboratories (Laboratory-ESPED, n2) performing genetic analyses. Inclusion criteria were a MVK mutation-positive patient ≤16 years of age with more than three self-limiting episodes of fever >38.5°C associated with increased inflammation markers. Clinical, epidemiological, and genetic data were assessed via questionnaires. Eight out of 16 patients were identified in Clinic-ESPED (n1) and 15 of 16 in Laboratory-ESPED (n2). Clinical and laboratory surveys overlapped in 7 of 16 cases. Incidence of HIDS was estimated to be 0.39 (95% CI: 0.22, 0.64) per 10(6) person-years. HIDS symptoms generally started in infancy with recurrent fever episodes lasting 3-12 (median, 4.5) days and recurring every 1-12 weeks. Fever was accompanied by abdominal pain, vomiting, diarrhea, cervical lymphadenopathy, and sometimes by headache, skin and joint symptoms. The patients carried 11 different MVK mutations mostly in compound heterozygosity (75%, 12 out of 16). The most frequent mutation was p.Val377Ile (81%, 13 out of 16). In Germany, the incidence of HIDS is very low with 0.39 per 10(6) person-years.

Concurrent TNFRSF1A R92Q and pyrin E230K mutations in a child with multiple sclerosis.

We report a 16-year-old female patient with a severe course of multiple sclerosis and concomitant symptoms suggestive of a hereditary autoinflammatory disease. Genetic analyses revealed that she inherited a TNFRSF1A R92Q mutation from her mother and a pyrin E230K mutation from her father. To our knowledge, this is the first report of a patient with severe childhood multiple sclerosis and mutations in two genes which predispose to hereditary autoinflammatory disorders. We speculate that these mutations contribute to early multiple sclerosis manifestation and enhance the inflammatory damage inflicted by the autoimmune response.

Analysis of cryopyrin-associated periodic syndromes (CAPS) in German children: epidemiological, clinical and genetic characteristics.

BACKGROUND: Cryopyrin-associated periodic syndromes (CAPS) are rare disorders belonging to the group of hereditary periodic fever (HPF)syndromes. These auto-inflammatory diseases(AID) are characterized by recurrent episodes of inflammation with attacks of fever variably associated with serosal, synovial and / or cutaneous inflammation, usually in a self-limiting manner, and with a mostly monogenic origin. The aims were to determine the incidence of CAPS and the spectrum of mutations in the NLRP3 (formerly= CIAS1) gene and to describe the clinical manifestations. PATIENTS AND METHODS: A prospective surveillance of children with CAPS was conducted in Germany during a time period of 3 years(2003-2006). Monthly inquiries were sent to 370 children's hospitals by the German Paediatric Surveillance Unit (Clinic-ESPED, n1) and to 2 laboratories (Laboratory-ESPED, n2). Inclusion criteria were children ≤ 16 years of age, disease-associated NLRP3 mutation, more than 3 self-limiting episodes of fever > 38.5 ° C, and increased inflammation markers. Clinical, epidemiological and genetic data were evaluated via questionnaires. FINDINGS: 6 out of 14 patients were identified in Clinic-ESPED (n1) and 13 / 14 in Laboratory-ESPED(n2). Clinical and laboratory surveys overlapped in 5 of 14 cases. The incidence of CAPS in German children was estimated to be 3.43 per 107 person-years. The patients carried 11 different NLRP3 mutations and were classified as MWS(n = 6), CINCA (n = 4), FCAS (n = 1) and undefined CAPS (n = 3). INTERPRETATION: The incidence of CAPS in Germany is very low and corresponds to 2-7 newly diagnosed patients ≤ 16 years per year.

Antiviral efficacy, tolerability and pharmacokinetics of efavirenz in an unselected cohort of HIV-infected children.

OBJECTIVES: To obtain data on the pharmacokinetics of efavirenz in children in clinical practice. METHODS: HIV-1-infected children received efavirenz capsules or tablets in accordance with manufacturer's dosing recommendations. Plasma was collected at regular visits and analysed by HPLC. The therapeutic range of efavirenz was defined as 1.0-4.0 mg/L. RESULTS: Thirty-three children were included. Median (range) age, body weight, dose and dose/kg were 8.2 (2.1-16.7) years, 24 (12-62) kg, 300 (200-800) mg and 13.3 (9.7-22.5) mg/kg, respectively. Median (range) efavirenz plasma concentration at first sampling was 2.8 (0.13-11.6) mg/L. Plasma concentrations were not dependent on age (P = 0.97) or dose/kg (P = 0.87). A total of 307 efavirenz plasma concentrations were determined. Forty-five samples (14.7%) contained >4.0 mg/L, and 27 samples (8.8%) contained <1.0 mg/L. Eight children (24%) reported persistent adverse events probably caused by efavirenz [concentration problems (5), sleep disorder (1), psychotic reaction (1) and seizure (1)]; six discontinued efavirenz for this reason. A non-significant trend existed towards a higher proportion of toxic efavirenz plasma concentrations (>4.0 mg/L) in subjects who reported efavirenz adverse events: 25.9% versus 12.8% (P = 0.23; t-test). Viral load was <50 copies/mL in all 27 subjects who continued efavirenz, despite occasional subtherapeutic efavirenz plasma concentrations in 12 children. The occasional subtherapeutic levels suggest that temporal non-adherence was present. CONCLUSIONS: Efavirenz as part of highly active antiretroviral therapy was highly effective in children able to tolerate the drug. Therapeutic drug monitoring (TDM) as part of toxicity management may prevent discontinuation in a subset of patients. Temporal non-adherence occurs frequently. TDM may allow initiation of adherence interventions before viral load becomes detectable.

Clinical and functional characterisation of a novel TNFRSF1A c.605T>A/V173D cleavage site mutation associated with tumour necrosis factor receptor-associated periodic fever syndrome (TRAPS), cardiovascular complications and excellent response to etanercept treatment.

OBJECTIVES: To study the clinical outcome, treatment response, T-cell subsets and functional consequences of a novel tumour necrosis factor (TNF) receptor type 1 (TNFRSF1A) mutation affecting the receptor cleavage site. METHODS: Patients with symptoms suggestive of tumour necrosis factor receptor-associated periodic syndrome (TRAPS) and 22 healthy controls (HC) were screened for mutations in the TNFRSF1A gene. Soluble TNFRSF1A and inflammatory cytokines were measured by ELISAs. TNFRSF1A shedding was examined by stimulation of peripheral blood mononuclear cells (PBMCs) with phorbol 12-myristate 13-acetate followed by flow cytometric analysis (FACS). Apoptosis of PBMCs was studied by stimulation with TNFalpha in the presence of cycloheximide and annexin V staining. T cell phenotypes were monitored by FACS. RESULTS: TNFRSF1A sequencing disclosed a novel V173D/p.Val202Asp substitution encoded by exon 6 in one family, the c.194-14G>A splice variant in another and the R92Q/p.Arg121Gln substitution in two families. Cardiovascular complications (lethal heart attack and peripheral arterial thrombosis) developed in two V173D patients. Subsequent etanercept treatment of the V173D carriers was highly effective over an 18-month follow-up period. Serum TNFRSF1A levels did not differ between TRAPS patients and HC, while TNFRSF1A cleavage from monocytes was significantly reduced in V173D and R92Q patients. TNFalpha-induced apoptosis of PBMCs and T-cell senescence were comparable between V173D patients and HC. CONCLUSIONS: The TNFRSF1A V173D cleavage site mutation may be associated with an increased risk for cardiovascular complications and shows a strong response to etanercept. T-cell senescence does not seem to have a pathogenetic role in affected patients.

Unrestricted weight bearing and intensive physiotherapy after uncemented total hip arthroplasty.

BACKGROUND AND AIMS: The effectiveness of partial weightbearing after hip surgery has been questioned as well as the need of intensive physiotherapy. MATERIAL AND METHODS: 36 patients (average age 54.4, 19 women) operated with uncemented hip arthroplasty were randomized either to unrestricted weightbearing (UWB) combined with intensive physiotherapy or to partial weightbearing (PWB) for 3 months combined with a short self-training program. The load during walking and the muscle strength (MS) in abduction was measured preoperative and subsequent up to 12 months. RESULTS: The average peak load on the operated leg at one week was 39.0 kg for the UWB and 25.8 for the PWB group (P = 0.009) while at three months 70.0 and 31.7 (P = 0.001) respectively. At 6 and 12 months there were no differences between the groups. The muscle strength increased in both groups up to six months but there were no differences between the groups. CONCLUSIONS: Even though patients applied more load than the recommended 15 kg most patients were able to comply with partial weightbearing fairly well. The effect of intensive physiotherapy on the muscle strength after hip arthroplasty is questionable.

Medications used by children with asthma living in the inner city.

OBJECTIVE: The purpose of the study was to examine medication use reported by families participating in an urban school-based community intervention program and to relate this use to other social and medical variables. DESIGN: The design of the study was a cross-sectional questionnaire survey. SETTING: Patients and their families recruited from elementary schools in a community setting were interviewed between December 1991 and January 1992. PARTICIPANTS: A total of 508 children with asthma were identified by school health records and teacher surveys. Their families confirmed the diagnosis and agreed to enter the study. Questionnaires were completed by 392 families. INTERVENTION: The 392 families participated in a controlled trial of asthma education after providing the data that are the basis of this report. RESULTS: More than half of the children took two or more medications for asthma. Thirty-one percent took theophylline alone or in combination with an adrenergic agent; 11% took some form of daily antiinflammatory medication, either cromolyn (8%) or inhaled steroids (3%). The pattern of medication use related to measures of severity and to regular visits to physicians or nurses. In general, however, children were undermedicated. A total of 78 children (20%) reported no medication or over-the-counter medication use, although 37% reported asthma severe enough to be associated with >/=20 days of school missed per month, and 37% had had an emergency room visit for asthma in the past 6 months. More than half of children >/=9 years old supervised their own medication. CONCLUSIONS: We concluded that undermedication is common in poor children with asthma living in urban areas. Antiinflammatory medications are used less commonly than in the general population, and theophylline is used more often. School children may be likely to supervise their own medication.

Nebulizer use in inner-city children with asthma: morbidity, medication use, and asthma management practices.

OBJECTIVE: To assess the frequency of nebulizer use, describe morbidity and patterns of medication administration, and examine the potential relationships between inhaled anti-inflammatory medication administration, asthma morbidity, and asthma management practices in children with asthma using a nebulizer compared with children with asthma not using a nebulizer. RESEARCH DESIGN: A cross-sectional, descriptive survey of previous events. SETTING: Elementary schools and participants' homes in Baltimore, Md, and Washington, DC. PARTICIPANTS: Six hundred eighty-six families of children aged 5 to 12 years with a diagnosis of at least mild, persistent asthma. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Asthma morbidity, health care utilization, pattern of asthma medication administration, nebulizer use, and asthma management data were collected by telephone survey administered to caregivers. Nebulizer use was defined as use at least 1 or more days per month during the last 6 months. Of 686 children identified, 231 (33%) reported current nebulizer use. Nebulizer users had significantly increased lifetime hospital admissions, hospitalizations, and emergency department visits in the last 6 months compared with nonnebulizer users. Inhaled corticosteroid administration was low for both groups (nonnebulizer users, 8%; nebulizer users, 15%). In the nebulizer users group, administration of inhaled anti-inflammatory medications was associated with increased asthma morbidity (increased hospitalizations, days and nights with symptoms, and oral steroid use). CONCLUSIONS: Nebulizer use by inner-city children with asthma is higher than anticipated but is not associated with reduced asthma morbidity. This group of high-risk children was undertreated with inhaled corticosteroids for long-term control of asthma despite reports of adequate monitoring by a primary care physician.

Role of rural school nurses in asthma management.

Environmental, socioeconomic, psychological and familial factors in rural communities predispose children to asthma. This is not only the case in the US but also in the UK, New Zealand and other Western countries. Asthma prevalence ranges from 2.2 to 15%. Because children spend at least 6 hours of their day in school, school health personnel must be attentive to, and skilled in managing the needs and issues faced by children with asthma while at school. Rural school nurses or their deputies need to advise children with asthma about avoiding aeroallergens from hay, smoke, dust, grain in silos and animal dander from cattle and sheep. In the case of children with asthma in rural areas, symptoms may be accepted as long as the child can go to school and play. Parents in rural areas may not believe in routine preventive care for asthma as part of public health practice. Rural nurses need to be aware of current asthma guidelines and apply the concepts to prevention. They need to be proactive and engage in primary, secondary and tertiary prevention. Rural school nurses can begin by using existing resources and adapting these resources for use in rural school environments. Worldwide asthma education is fundamental to asthma patient management.

Patient priorities and needs for diabetes care among urban African American adults.

PURPOSE: This study was conducted to determine diabetes care priorities and needs in a group of urban African American adults with type 2 diabetes mellitus. METHODS: One hundred nineteen African American adults with type 2 diabetes, aged 35 to 75, received behavioral/educational interventions from a nurse case manager, a community health worker, or both. Priorities and needs were assessed during 3 intervention visits. RESULTS: The most frequently reported priorities for diabetes care were glucose self-monitoring (61%), medication adherence (47%), and healthy eating (36%). The most frequently addressed diabetes needs were glucose self-monitoring and medication adherence. Most of the intervention visits (77%) addressed non-diabetes-related health issues such as cardiovascular disease (36%) and social issues such as family responsibilities (30%). CONCLUSIONS: Participants' self-reported priorities for diabetes care directly reflected the diabetes needs addressed. Needs beyond the focus of traditional diabetes care (social issues and insurance) are important to address in urban African Americans with type 2 diabetes. Interventions designed to address comprehensive health and social needs should be included in treatment and educational plans for this population.

Factors associated with medication self-administration in children with asthma.

This study investigated factors associated with early self-administration of inhaled asthma medications by minority children. Specifically, the study evaluated: (1) the reasons parents allow early administration of inhaled medications, (2) childhood activities associated with early medication administration, (3) parent's perception of the child's ability to use a metered-dose inhaler (MDI), (4) the child's actual ability to use an MDI, and (5) concordance/discordance between physician-parent reports and parent-child reports of asthma medications. Study results indicated that 93% of the children were taking inhaled asthma medications without adult supervision. Early self-administration of asthma medications was related to the parent's employment status and the performance of other childhood behaviors such as completion of homework independently and crossing the street alone. Only 7% of the children had effective MDI skills, but 60% of the parents rated their child's MDI skills as excellent. Twenty percent, 67%, and 50%, respectively, of the parents' reports of beta-agonists, daily inhaled steroids, and cromolyn were discordant with the physician's actual prescriptions. Sixty-two percent, 57%, and 79%, respectively, of the children's reports for inhaled beta-agonists, daily inhaled steroids, and cromolyn were discordant with their parents' reports. Implications for anticipatory guidance, future educational strategies, and supervision of MDI technique are provided.

Social factors associated with behavioral problems in children with asthma.

The objective of this study was to describe the proportion of children with a behavior problem and examine which independent variables are associated with the presence of a behavior problem in a group of 392 inner-city children with asthma. Data on child asthma symptoms, medication use, health-care utilization, and school absences were obtained from the parent during a structured telephone interview. Included in the interview was a measure of behavior problems and social support questions. Children classified with a high level of asthma symptoms were more than twice as likely to experience a behavior problem than children classified with a low level of asthma symptoms (P = 0.002). Use of theophylline medication was not correlated with behavior problems (P = 0.45). Significant variables were low level of social support and high or moderate level of asthma symptoms. We have identified a group of children at risk for behavior problems, specifically in families that lack adequate social and financial resources.

Use of community health workers with inner-city children who have asthma.

Use of community health workers (CHWs) to obtain health, social, and environmental information from African-American inner-city children with asthma was one component of a larger intervention study designed to reduce morbidity in African-American children with asthma. A subset of 140 school-aged children with asthma was recruited and enrolled in a program to receive home visits by CHWs for the purposes of obtaining medical information and teaching basic asthma education to the families. Data obtained by the CHWs revealed low inhaled steroid use, high beta 2 agonist use, frequent emergency-room visits, decreased primary-care visits, and increased allergen and irritant exposure. Appropriately recruited and trained CHWs are effective in obtaining useful medical information from inner-city families with children with asthma and providing basic asthma education in the home.

Asthma knowledge, roles, functions, and educational needs of school nurses.

In October 1997, 790 school nurses in Maryland and the District of Columbia were surveyed to determine their attitudes, knowledge, and beliefs about asthma. Results for 550 (70%) nurses indicated school nurses possess a generally appropriate level of knowledge concerning asthma, and most asthma myths have been replaced with knowledge. However, school nurses also have varied responsibilities that affect their ability to provide health education and support services to children with asthma at school. Little time is available for a proactive role. Concerns about the criteria and follow-up for delegating medication administration within the school setting were reported. A lack of communication existed with parents about the child's asthma. Open communication between school nurses and the family is recommended to establish a partnership and improve asthma management outcomes. In addition, school policies and procedures should be updated to meet the demands of children with asthma.

Controlling allergies by assessing risks in the home.

Nurses and other health care providers will encounter children with allergies and asthma in virtually all practice sites. The skills with which they are able to assist these children and their families will depend on their understanding of the precipitating allergens and the most economical, feasible, and effective ways to reduce exposure to them.

Genetics of asthma and allergies.

This article is a literature review focusing on the underlying concepts of human genetics related to asthma and allergies. Asthma is classified as a complex genetic disorder with genetic susceptibility and an appropriate environmental stimulus necessary for the expression of disease. Intermediate phenotypes of asthma, which are used to study the disease, include the total IgE levels, the specific immune response, and end organ response. Because gene products cause the inflammation in asthma and allergies, the molecular cell biology of these events is reviewed. Although no one gene is implicated in causing asthma, candidate genes involved in the multiple phenotypic expressions of asthma are described.

Allergen avoidance in the treatment of dust-mite allergy and asthma.

House-dust-mite allergen is one of the primary causes of asthma. In many instances, asthma is an immunoglobulin gamma E mediated atopy (i.e., allergen-specific hypersensitivity) that leads to non-specific bronchial hyper-reactivity and subsequent symptom manifestations. These symptoms may range from an annoying cough to full-blown respiratory failure. Allergen-avoidance measures should be a primary mode of treatment for atopic asthmatics. This article focuses on the dust-mite allergen and its relationship to asthma. It details specific avoidance measures that should be implemented by the majority of asthmatics. Studies are cited that support the aggressive use of these measures to decrease allergen exposure, and to subsequently prevent or significantly reduce asthma symptoms. When health care providers have a better understanding of avoidance measures and the rationale underlying their use, these measures are more likely to be valued and given greater emphasis in education and treatment plans. Renewed emphasis on an immunomodulatory approach to asthma treatment may help to reverse the rise in asthma morbidity and mortality rates.

Moving health care education into the community.

The A+ Asthma Club, an educational program developed for elementary school children in inner-city schools, is offered through a series of six sessions during school hours with an additional three booster sessions. This article describes how the program was designed, its theoretical basis, the curriculum and its staffing.