Qualitative interviews to improve patient-reported outcome measures in late-onset Pompe disease: the patient perspective.

BACKGROUND: Late-onset Pompe Disease (LOPD) is a rare, heterogeneous disease manifested by a range of symptoms varying in severity. Research establishing the frequency of these symptoms and their impact on patients' daily lives is limited. The objective of this study was to develop a conceptual model that captures the most relevant symptoms and functional limitations experienced by patients with LOPD, to inform the development of new patient-reported outcome (PRO) tools. METHODS: A preliminary conceptual model was constructed following a literature review and revised through interviews with expert clinicians to identify important and relevant concepts regarding symptoms and impacts of LOPD. This preliminary model informed the development of a qualitative patient interview guide, which was used to gather the patient perspective on symptoms and impacts relating to LOPD or its treatment (including symptom/impact frequency and levels of disturbance). Patient interviews aided further refinement of the conceptual model. The findings from the patient interviews were triangulated with the literature review and clinician interviews to identify the most relevant and significant effects of LOPD from the patient perspective. RESULTS: Muscle weakness, fatigue, pain, and breathing difficulties (especially while lying down) were the most common and highly disturbing symptoms experienced by patients. Limitations associated with mobility (e.g., difficulty rising from a sitting position, getting up after bending) and activities of daily living, (e.g., reduced ability to participate in social/family activities or work/study) were the most frequently reported impacts with the highest levels of disturbance on the patient's daily life. These identified symptoms and impacts were included in the new conceptual model of disease. CONCLUSIONS: This qualitative patient interview study, also informed by a literature review and clinician interviews, identified the most frequent and relevant symptoms and the functional impact of LOPD on patients. The study interviews also captured the patient-preferred language to describe symptoms and impacts of LOPD. The results from this study can be used to develop future PRO instruments that are tailored to the specific symptoms and impacts experienced by patients with LOPD.

Examination of mental health status and aggravation level among mothers of children with isolated oral clefts.

OBJECTIVE: To examine self-reported mental health status and aggravation level in mothers of children with isolated oral clefts. METHODS: Population-based sample of children (aged 4 to 9 years) with isolated oral clefts was enumerated from births from 1998 through 2003 in Arkansas, Iowa, and New York State. Mothers of 294 children completed the Mental Health Inventory 5-item questionnaire and Aggravation in Parenting Scale. The Mental Health Inventory and Aggravation in Parenting Scale scores, stratified by poor (Mental Health Inventory ≤ 67) and better (Mental Health Inventory > 67) mental health status or high (Aggravation in Parenting Scale ≤ 11), moderate (Aggravation in Parenting Scale = 12 to 15) and low (Aggravation in Parenting Scale = 16) aggravation, were compared by selected maternal and child characteristics. Mean scores for each instrument and proportion of mothers with poor mental health or high aggravation were compared with those reported in the National Survey of American Families. RESULTS: Mean scores for each instrument and proportion of mothers with poor mental health or high aggravation differed little from published data. Mothers with poor mental health tended to be less educated, to have lower household incomes, and to rate their health and their child's health lower than those in better mental health. Mothers with high aggravation tended to have lower household incomes, to have more children, and to rate their health and their child's health lower than those with moderate or low aggravation. CONCLUSIONS: Mothers of affected children were not more likely to experience poor mental health or high aggravation compared with published data; however, sociodemographic characteristics were associated with maternal psychosocial adaptation. Brief screeners for mental health and parenting administered during routine appointments may facilitate identifying at-risk caregivers.

Separation anxiety in children ages 4 through 9 with oral clefts.

Background : Psychosocial research on children with oral clefts (OCs), i.e., clefts of the lip, palate, or lip and palate, has suggested that these children may have higher rates of anxiety in general, but overall results have been equivocal. In this study we estimated the prevalence of separation anxiety disorder (SAD) in a population-based sample of children with OCs and identified associated risk factors. Methods : Parents of 279 children with OCs, identified through three state birth defect registries, responded to a postal survey that included the Separation Anxiety subscale of the Screen for Child Anxiety-Related Emotional Disorders (SCARED) and items regarding the child's OC and its sequelae, parent and child health, parent mental health, family structure, and socioeconomic status indicators. Associations with SA were evaluated using bivariate and multivariate statistics. Results : One quarter (24%) of the children screened positive for SAD, which was substantially higher than the U.S. child population estimates of 3% to 5%. OC-related impairments in speaking and eating more than doubled the risk of SAD, as did lower socioeconomic status and lower maternal health rating. Maternal mental health and marital status remained in the logistic model but were not significant. Conclusions : Children with OCs appear to be at increased risk for SAD as measured by the SCARED instrument. OC-related problems with speech and eating more than doubled the risk of SAD. The use of targeted screening tools may help refine our understanding of psychosocial adjustment in children with OCs.

Primary care physician experience with children with oral clefts in three states.

BACKGROUND: The experience of primary care physicians in Arkansas, Iowa, and New York treating children with oral clefts (OCs) was investigated, along with their knowledge and comfort caring for or referring these children. METHODS: A mail survey was conducted with all primary care physicians in Iowa and Arkansas, and a random sample of 4000 physicians in New York, selected from the American Medical Association (AMA) Master File. The final dataset consisted of 1435 usable surveys. Outcome measures were experience and comfort providing care to or referring children with OC. Differences between states were tested using Pearson or Kruskal-Wallis chi-square tests, or F-tests for differences in means. RESULTS: Two-thirds of respondents had provided care to a child with an OC since completing residency. Physicians were most comfortable providing routine care and much less comfortable providing counseling on cleft-related issues. Eighty percent had an organized cleft team to which they could refer. About two-thirds were very comfortable with the expertise available for surgical care, speech, and hearing; half were for dental care; only 40% were for behavioral or emotional counseling. Two-thirds were interested in continuing medical education (CME) on cleft care. CONCLUSIONS: Primary care physicians in all three states had little experience with children with OCs. This limited experience poses significant barriers to care. Increased experience during training and CME opportunities could improve knowledge and comfort with providing OC-related care. Increasing knowledge of referral options for team care and other cleft-related services could also help physicians when caring for children with OCs.

Prenatal diagnosis of orofacial clefts: association with maternal satisfaction, team care, and treatment outcomes.

OBJECTIVE: Prenatal diagnosis of an orofacial cleft is thought to allow mothers greater opportunity to become prepared for the special needs of an infant with a cleft and plan for the care of their child. Using a population-based sample, we determined which children were more likely to be diagnosed prenatally, and whether early diagnosis was associated with maternal satisfaction and treatment outcomes. DESIGN: Interviews were completed with 235 (49% of eligible) mothers of children ages 2 to 7 with orofacial clefts initially enrolled in the National Birth Defects Prevention Study from the Arkansas, Iowa, and New York sites. Maternal satisfaction with information, support, and treatment outcomes was compared between women who received a prenatal diagnosis and those who did not. RESULTS: Of 235 infants with clefts, 46 (19.6%) were identified prenatally. One third of mothers were somewhat or not satisfied with information provided by medical staff. Satisfaction did not vary by timing of the diagnosis. Infants diagnosed prenatally were no more likely to have received care provided by a recognized multidisciplinary cleft team (76%) than were infants diagnosed at birth (78%). Speech problems and facial appearance as rated by the mother did not vary by timing of the diagnosis. CONCLUSIONS: Timing of the cleft diagnosis did not alter maternal satisfaction with information, whether care was provided by a designated cleft team, or maternal perception of facial appearance or speech. Further research should determine whether prenatal diagnoses alter maternal anxiety or influence postnatal morbidity.

Interdisciplinary craniofacial teams compared with individual providers: is orofacial cleft care more comprehensive and do parents perceive better outcomes?

OBJECTIVE: The primary objective was to examine whether children with orofacial clefts received more comprehensive care and whether their parents perceived better outcomes if the care was delivered by interdisciplinary teams compared with individual providers. DESIGN: Data about services received and outcomes were collected from mothers of children with orofacial clefts. PARTICIPANTS: Mothers of children born between 1998 and 2003 with orofacial clefts from Arkansas, Iowa, and New York who participated in the National Birth Defects Prevention Study were eligible. MAIN OUTCOME MEASURE(S): Services and treatments received and maternal perception of cleft care, health status, aesthetics, and speech were evaluated by team care status. RESULTS: Of 253 children, 24% were not receiving team care. Of those with cleft lip and palate, 86% were enrolled in team care. Compared with children with team care, those without had fewer surgeries and were less likely to have seen a dentist, received a hearing test, or had a genetic consultation. Mothers of children lacking team care were twice as likely to give lower ratings for overall cleft care; maternal perceptions of global health, facial appearance, and speech did not differ by team care status. CONCLUSIONS: Recommended care tended to be received more often among those with team care. A larger, longitudinal study might answer questions about whether team care provides the best care and the role that type and severity of the condition and racial/ethnic differences play in the services received and outcomes experienced.

Demographic characteristics, care, and outcomes for children with oral clefts in three states using participants from the National Birth Defects Prevention Study.

OBJECTIVE: The primary objective of this study was to evaluate whether there were differences in the characteristics and outcomes of care for children with oral clefts (OCs) among population-based samples in three states. DESIGN: Data on the health status and on speech and esthetic outcomes were collected using structured telephone interviews conducted during 2005-2006 with mothers of children with OCs aged 2 to 7 in Arkansas, Iowa, and New York. PARTICIPANTS: Mothers of children born with nonsyndromic OCs on or after January 1, 1998, and on or before December 31, 2003, in Arkansas, Iowa, or New York. Subjects were identified through their participation in the ongoing National Birth Defects Prevention Study. MAIN OUTCOME MEASURES: Demographic characteristics, rating of cleft care, severity of condition, health status, esthetic outcomes, and speech problems were evaluated by state of residence. RESULTS: Children with OCs from Arkansas were from lower income families, and their parents were less likely to be married. Children with OCs from Arkansas were more likely to have special health care needs and to require mental health care. Few differences were found across states in type of cleft, severity of cleft, or outcomes of cleft care. CONCLUSIONS: Combining results from population-based samples across multiple studies increases the variability of sample characteristics. Including multiple states can be an efficient way to learn more about the outcomes of medical care for less common conditions such as oral cleft.

Immunization with a synthetic robustoxin derivative lacking disulphide bridges protects against a potentially lethal challenge with funnel-web spider (Atrax robustus) venom.

The venom of male Atrax robustus spiders is potentially lethal to primates. These spiders have been responsible for a number of human deaths. Robustoxin is the lethal toxin in the venom. It is a highly cross-linked polypeptide that has 42 amino acid residues and four disulphide bridges. If these bridges are broken, the resulting polypeptide is non-toxic. Robustoxin was chemically synthesized with all of its eight cysteine residues protected with acetamidomethyl groups in order to avoid formation of disulphide bridges. The resulting derivative was co-polymerized with keyhole limpet haemocyanin. Two Macaca fascicularis monkeys were immunized with this conjugate. The monkeys were challenged,under anaesthesia,with a potentially lethal dose of male A.robustus crude venom. Both monkeys showed some minor symptoms of intoxication but recovered fully with no adverse after-effects. Immunization with the same immunogen, in the absence of keyhole limpet haemocyanin, did not protect a third monkey. The N-terminal 23 amino acid peptide derived from the sequence of robustoxin was synthesized and conjugated with ovalbumin. A fourth monkey was immunized with this conjugate. However,it was not protected against challenge.The implications of these results for the preparation of synthetic peptide vaccines are discussed.

Maternal reports of satisfaction with care and outcomes for children with craniosynostosis.

Craniosynostosis is a congenital deformity caused by premature fusion of cranial suture(s). Surgical outcomes of craniosynostosis have been well documented; however, limited published data are available regarding access to care and social and psychological health outcomes for children with craniosynostosis. The authors conducted a population-based, multistate study of maternal perceptions of care and outcomes for children with craniosynostosis born from January 1998 through December 2003. Mothers of 147 children were contacted and asked to complete a structured telephone interview; 82 mothers (55.8%) participated. Overall, the mean ages of children and their mothers at the time of interview were 4.4 and 34.8 years, respectively. Mothers interviewed tended to be white and, at a minimum, high school graduates. Most mothers reported being satisfied with the craniosynostosis-related information and support provided by medical care providers, and access to primary and specialty care was most often rated as satisfactory. Mothers tended to report the physical health of their child to be good; however, delays in cognitive and emotional development, hearing loss, and speech problems were identified. In addition, statistically significant differences among mothers in each state were noted for reports of the quality of team care, primary care, learning interventions, and perceived need for additional surgeries. These results suggest some limitations in craniosynostosis-related care and provide guidance to medical and surgical care providers in making need-based improvements in craniosynostosis surgery and care. Future studies are recommended to replicate this evaluation in additional populations.

Evaluation of a disease-specific instrument for idiopathic clubfoot outcome.

UNLABELLED: In 2001, Roye et al. developed a disease-specific instrument (DSI) to measure outcomes of treatment for clubfoot. We assessed this instrument using a cohort of 62 patients, ages 5 through 12 years (mean, 8.6 years), with idiopathic clubfoot who were treated as infants by various methods. Treatment groups were defined by whether the patient received joint-invasive surgery (posterior or posteromedial release surgery) or joint-sparing treatment only (manipulation and casting with or without tendo-Achilles lengthening or anterior tibial tendon transfer). The DSI scales demonstrated internal consistency reliability of 0.74 to 0.85 using Cronbach's alpha. Higher (better) DSI scores were associated with "excellent" general health ratings and better health-related quality of life; lower DSI score were related to special healthcare needs. Patients treated using joint-sparing techniques only (eg, Ponseti technique) had higher DSI scores than those who had received joint-invasive surgery. DSI scores for patients who had received posterior or posterior medial release surgery were very similar to those reported by Roye et al. in New York for a comparable group of patients. Our findings suggest the DSI is sensitive to differences in treatment technique or underlying severity of disease. These data support the use of the Roye DSI as an outcome measure for idiopathic clubfoot in children. LEVEL OF EVIDENCE: Level III, diagnostic study. See the Guidelines for Authors for a complete description of levels of evidence.

Health-related quality of life among preadolescent children with oral clefts: the mother's perspective.

OBJECTIVE: The purpose of this study was to evaluate the factors that affect the health-related quality of life of preadolescent children with nonsyndromic oral clefts using the Pediatric Quality of Life Inventory instrument and to evaluate whether there were any differences related to the type of cleft or other factors. METHODS: Data for this study were derived from telephone interviews with the parents of a statewide population of children who were in the Iowa Registry for Congenital and Inherited Disorders, were aged 2 to 12 years, had nonsyndromic oral clefts, and were born in Iowa between January 1, 1990, and December 31, 2000. Twenty-minute interviews were conducted with mothers of 104 children in the spring and summer of 2003; respondents then completed and mailed back Pediatric Quality of Life Inventory surveys 2 to 3 weeks after the interviews (69% participation rate). RESULTS: After controlling for demographic characteristics, children with less severe speech problems had higher total Pediatric Quality of Life Inventory scores as well as higher physical and psychosocial health domain scores. Age and cleft type interacted, with younger children (aged 2-7 years) with a cleft lip or cleft lip and palate having higher health-related quality of life scores than children with an isolated cleft palate; however, this pattern was reversed for older children (aged 8-12 years). CONCLUSIONS: Speech and aesthetic concerns seem to have been important factors affecting the health-related quality of life for children with oral clefts. These factors seem to be more important as children get closer to adolescence (ages 8-12 years) when acceptance by peers becomes more critical.

Oral and parenteral immunization with synthetic retro-inverso peptides induce antibodies that cross-react with native peptides and parent antigens.

The objective of this study was to determine whether certain retro-inverso peptides have the potential to act as synthetic vaccines in mice, when immunized by injection or orally. Immunization of mice parenterally with conjugates of three such retro-inverso peptides and orally with the unconjugated peptides elicited generally high titres of anti-peptide antibodies. Antibodies against the same three peptides cross-reacted by binding strongly in ELISA to the native peptides and vice versa, regardless of the mode of immunization. Antibodies against a retro-inverso diphtheria peptide also reacted strongly with diphtheria toxin. Seven of 8 mice, immunized by injection of the conjugate of a retro-inverso derivative of robustoxin [a lethal spider (Atrax robustus) venom toxin] were protected from challenge involving injection with twice the minimum lethal dose of A. robustus venom containing the toxin.

Type of oral cleft and mothers' perceptions of care, health status, and outcomes for preadolescent children.

OBJECTIVE: To evaluate the outcomes of care for children by type of oral cleft. DESIGN: Data were collected through structured telephone interviews during 2003 in Iowa with mothers of 2- to 12-year-old children with oral clefts. Interviews with mothers of children with clubfoot and statewide data on Iowa children were used for comparison. PARTICIPANTS: Participants included mothers of children in Iowa born between 1990 and 2000 with nonsyndromic oral clefts. Children were identified by the statewide Iowa Registry for Congenital and Inherited Disorders. MAIN OUTCOME MEASURES: Rating of cleft care, severity of condition, health status, esthetic outcome, speech, and school performance were evaluated by type of oral cleft. RESULTS: Children with cleft lip and palate were most likely to have their clefts rated as very severe. Children with palatal involvement were reported to have a lower health status and were almost twice as likely to be identified as having a special health care need compared with either children with cleft lip or children statewide. Children with cleft lip had more esthetic concerns; children with palatal involvement had the most speech concerns. CONCLUSIONS: Although mothers generally believed their children had received high-quality care, ratings of the children's current health status and outcomes of care varied significantly by type of cleft (cleft lip, cleft palate, and cleft lip and palate). Differences observed in this population-based study support the proposition that cleft type should be considered when examining outcomes of care for children with oral clefts.

Cost of outpatient medical care for children and youth with special health care needs: investigating the impact of the medical home.

OBJECTIVE: Our goal was to evaluate the impact of having a medical home on the outpatient medical costs of children and youth with special health care needs. DESIGN: Data from 2 sources were matched at the individual level: (1) the 2002 Iowa Consumer Assessment of Health Plans Study survey of Medicaid enrollees and (2) Iowa Medicaid administrative claims, encounter, and enrollment files. PARTICIPANTS: The subjects were 1140 children aged 6 months to 12 years for whom both sources of data were available. MAIN OUTCOME MEASURE(S): Outcomes measures included medical homeness, as developed by a scale of items in the Consumer Assessment of Health Plans Study survey, and outpatient costs, as determined from Medicaid administrative data. RESULTS: From the regression models, we found that (1) for all Medicaid-enrolled children, outpatient costs were significantly higher for female children and children and youth with special health care needs, (2) for children and youth without special health care needs, costs were significantly higher for female children, those with a personal doctor or nurse, and those with more of a medical home, and (3) for children and youth with special health care needs, costs were significantly higher for those in a lower health state, for those in health maintenance organization 2, and for older children. CONCLUSIONS: Although the degree of medical homeness was not related to outpatient costs for children and youth with special health care needs, medical homeness may affect inpatient costs more than outpatient costs for children and youth with special health care needs and should be investigated further.

CAHPS in practice: the Iowa demonstration.

This article evaluates the usefulness of the Consumer Assessment of Health Plan Study (CAHPS) surveys and reports in a demonstration and evaluation with three health care purchasers in Iowa. The CAHPS survey detected significant differences between health plans in several domains of health care. Both paper- and Web-based consumer reports were developed and distributed to consumers and stakeholders. There was some agreement on the value of these reports, but areas for improvement were noted.