What does team science look like across the CTSA consortium? A qualitative analysis of the Great CTSA Team Science Contest submissions.

INTRODUCTION: The Great CTSA Team Science Contest (GTSC) was developed to discover how Clinical and Translational Science Award (CTSA) hubs promote and support team science [1]. The purpose of this study was a secondary qualitative analysis of the GTSC submissions to better understand the diversity of team science initiatives across the CTSA consortium. METHODS: Secondary qualitative analysis of the GTSC data addressed the following research questions, which defined the top-level coding: (1) What CTSA component sponsored it? (2) Who was the team doing the work? (3) Who were the intended beneficiaries? (4) What was the intended outcome? (5) What strategies did they use? (6) What translational science (TS) stage was addressed? (7) How do they align with the NCATS team science strategic goals? (8) How do the CTSA's team science efforts align with the National Academies Research Council (NRC) recommendations for enhancing the effectiveness of team science? RESULTS: The GTSC received 170 submissions from 45 unique CTSA hubs. Qualitative analysis revealed a great variety of team science strategies for virtually all team science stakeholders. In addition to strategies to promote team science, results show successful examples that focus on outcomes and illustrate ways of measuring success. CONCLUSIONS: The GTSC shows that the CTSA consortium is involved in an extremely diverse array of team science activities, which align well with both the NRC recommendations for enhancing the effectiveness of team science and the NCATS strategic goals for team science. Future research should evaluate the efficacy of team science strategies.

Treating High-Caries Risk Occlusal Surfaces in First Permanent Molars through Sealants and Supervised Toothbrushing: A 3-Year Cost-Effective Analysis.

We conducted a 3-year cost-effectiveness analysis on the cavitated dentine carious lesion preventive capabilities of composite resin (CR) (reference group) and atraumatic restorative treatment (ART) high-viscosity glass-ionomer cement (HVGIC) sealants compared to supervised toothbrushing (STB) in high-risk first permanent molars. School children aged 6-7 years in 6 schools (2 per group) received CR and ART/HVGIC sealants or STB daily for 180 days each school year. Data were collected prospectively and cost estimates were made for sample data and a projection of 1,000 sealants/STB high-risk permanent molars. Although STB had the best outcome, its high implementation cost (95% of cost for supervisors visiting schools 180 days/school year) affected the results. ART/HVGIC was cost-effective compared to CR for the sample data (savings of USD 37 per cavitated dentine carious lesion prevented), while CR was cost-effective compared to ART/HVGIC for the projection (savings of USD 17 per cavitated dentine carious lesion prevented), and both were cost-saving compared to STB. Two STB scenarios were tested in sensitivity analyses with variations in caries incidence and number of supervision days; results showed STB had lower costs and higher savings per cavitated dentine carious lesion prevented than CR and ART/HVGIC. A major assumption is that both scenarios have the same high effectiveness rate experienced by STB under study conditions; however, they point to the value of further research on the benefits of adopting STB as a long-term venture in a general population of school children.

Cost-effectiveness, in a randomized trial, of glass-ionomer-based and resin sealant materials after 4 yr.

This study, conducted from a government program perspective, compared the incremental cost-effectiveness of oral health interventions, in particular their delivery to underserved populations in whom dental sealants constitute an important, high-yielding complement to toothbrushing in dental-caries prevention. The study data concern the relative cost-effectiveness of three sealant materials in four approaches to prevent cavitated dentine carious lesions in permanent molars in a community intervention trial among school-age children in Wuhan, China. The four approaches were high-viscosity glass-ionomer cement without heat application (HVGIC); high-viscosity glass-ionomer cement with heat application [light-emitting diode (LED) thermocured HVGIC]; glass-carbomer; and composite resin. The costs studied were: cost of sealing permanent molars; adverse event costs for restoring cavitated dentine carious lesions developing within 4 yr in study data; and projections of 1,000 sealants per group. Preventing one more cavitated dentine carious lesion cost US$105 for the study data when comparing HVGIC (n = 405) with composite resin (n = 396) and US$59 per 1,000 sealants in the projections; LED thermocured HVGIC compared with composite resin cost US$115 for one more cavitated lesion and US$52 per 1,000 sealants, respectively. Although more expensive than composite resin, LED thermocured HVGIC was identified as the most cost-effective among the sealant materials studied. Ease of application, minimal technical and infrastructure requirements, and cost-effectiveness make glass-ionomers a practicable option for governments making decisions under economic constraints.

Methods and preliminary findings of a cost-effectiveness study of glass-ionomer-based and composite resin sealant materials after 2 yr.

The cost-effectiveness of glass-carbomer, conventional high-viscosity glass-ionomer cement (HVGIC) [without or with heat (light-emitting diode (LED) thermocuring) application], and composite resin sealants were compared after 2 yr in function. Estimated net costs per sealant were obtained from data on personnel time (measured with activity sampling), transportation, materials, instruments and equipment, and restoration costs for replacing failed sealants from a community trial involving 7- to 9-yr-old Chinese children. Cost data were standardized to reflect the placement of 1,000 sealants per group. Outcomes were the differences in the number of dentine caries lesions that developed between groups. The average sealant application time ranged from 5.40 min (for composite resin) to 8.09 min (for LED thermocured HVGIC), and the average cost per sealant for 1,000 performed per group (simulation sample) ranged from $US3.73 (for composite resin) to $US7.50 (for glass-carbomer). The incremental cost-effectiveness of LED thermocured HVGIC to prevent one additional caries lesion per 1,000 sealants performed was $US1,106 compared with composite resin. Sensitivity analyses showed that differences in the cost of materials across groups had minimal impact on the overall cost. Cost and effectiveness data enhance policymakers' ability to address issues of availability, access, and compliance associated with poor oral-health outcomes, particularly when large numbers of children are excluded from care, in economies where oral health services are still developing.

Modeling the impact and costs of semiannual mass drug administration for accelerated elimination of lymphatic filariasis.

The Global Program to Eliminate Lymphatic Filariasis (LF) has a target date of 2020. This program is progressing well in many countries. However, progress has been slow in some countries, and others have not yet started their mass drug administration (MDA) programs. Acceleration is needed. We studied how increasing MDA frequency from once to twice per year would affect program duration and costs by using computer simulation modeling and cost projections. We used the LYMFASIM simulation model to estimate how many annual or semiannual MDA rounds would be required to eliminate LF for Indian and West African scenarios with varied pre-control endemicity and coverage levels. Results were used to estimate total program costs assuming a target population of 100,000 eligibles, a 3% discount rate, and not counting the costs of donated drugs. A sensitivity analysis was done to investigate the robustness of these results with varied assumptions for key parameters. Model predictions suggested that semiannual MDA will require the same number of MDA rounds to achieve LF elimination as annual MDA in most scenarios. Thus semiannual MDA programs should achieve this goal in half of the time required for annual programs. Due to efficiency gains, total program costs for semiannual MDA programs are projected to be lower than those for annual MDA programs in most scenarios. A sensitivity analysis showed that this conclusion is robust. Semiannual MDA is likely to shorten the time and lower the cost required for LF elimination in countries where it can be implemented. This strategy may improve prospects for global elimination of LF by the target year 2020.

Costs of integrated mass drug administration for neglected tropical diseases in Haiti.

We conducted a cost analysis of Haiti's Ministry of Public Health and Population neglected tropical disease program, Projet des Maladies Tropicales Negligées and collected data for 9 of 55 communes participating in the May 2008-April 2009 mass drug administration (MDA). The Projet des Maladies Tropicales Negligées Program partnered with IMA World Health and Hôpital Ste. Croix to implement MDA for treatment of lymphatic filariasis and soil-transmitted helminthiasis by using once a year treatment with albendazole and diethylcarbamazine in a population of approximately 8 million persons. Methods included analyzing partner financial records and conducting retrospective surveys of personnel. In the nine communes, 633,261 persons were treated at a cost of U.S. $0.64 per person, which included the cost of donated drugs, and at a cost of U.S. $0.42 per person treated, when excluding donated drug costs. The MDA for lymphatic filariasis in Haiti began in 2000, with the treatment of 105,750 persons at a cost per person of U.S. $2.23. The decrease in cost per person treated is the result of cumulative implementation experience and economies of scale.

Global affordability of fluoride toothpaste.

OBJECTIVE: Dental caries remains the most common disease worldwide and the use of fluoride toothpaste is a most effective preventive public health measure to prevent it. Changes in diets following globalization contribute to the development of dental caries in emerging economies. The aim of this paper is to compare the cost and relative affordability of fluoride toothpaste in high-, middle- and low-income countries. The hypothesis is that fluoride toothpaste is not equally affordable in high-, middle- and low-income countries. METHODS: Data on consumer prices of fluoride toothpastes were obtained from a self-completion questionnaire from 48 countries. The cost of fluoride toothpaste in high-, middle- and low-income countries was compared and related to annual household expenditure as well as to days of work needed to purchase the average annual usage of toothpaste per head. RESULTS: The general trend seems to be that the proportion of household expenditure required to purchase the annual dosage of toothpaste increases as the country's per capita household expenditure decreases. While in the UK for the poorest 30% of the population only 0.037 days of household expenditure is needed to purchase the annual average dosage (182.5 g) of the lowest cost toothpaste, 10.75 days are needed in Kenya. The proportion of annual household expenditure ranged from 0.02% in the UK to 4% in Zambia to buy the annual average amount of lowest cost toothpaste per head. CONCLUSION: Significant inequalities in the affordability of this essential preventive care product indicate the necessity for action to make it more affordable. Various measures to improve affordability based on experiences from essential pharmaceuticals are proposed.

Opioid use in palliative care of children and young people with cancer.

OBJECTIVE: Identify opioids prescribed, preferred routes, and doses among children with incurable cancer. STUDY DESIGN: Prospective survey with monthly questionnaires regarding patients 0 to 19 years old from oncology centers. Data were collected by professionals on each patient for 6 months or until death, and analyzed from patients who died. Impact of tumor was analyzed with Kruskal-Wallis and Mann-Whitney tests. Major opioid dosages are expressed as oral morphine equivalents. RESULTS: Of 185 children recruited, 164 (88 boys, 76 girls) died. Mean palliative care duration was 67 days. One hundred forty-seven (89.6%) received major opioids. Morphine, diamorphine, and fentanyl were prescribed in 75%, 57.9%, and 11.6%, respectively. Seventy-three (44.5%) received >1 major opioid. Median monthly maximum doses prescribed rose from 2.1 mg/kg/24 h (study entry) to 4.4 mg/kg/24 h (death) (P < .001); overall variable (0.09-1500 mg/kg/24 h, median 3.7 mg/kg/24 h). Opioids were given by the oral (117/164, 71.3%), intravenous (68/164, 41.5%), subcutaneous (40, 28%), rectal (20, 12.2%), and transdermal (18, 11%) routes. There was a shift to intravenous use as death approached. Numbers within each tumor group were too small to show significance. Children with solid tumors outside the central nervous system were likely to receive more opioids, be given multiple different opioids, and receive opioids in the last month. CONCLUSIONS: The study shows the United Kingdom practice of opioid use and provides comparator data for practice in children's palliative medicine.

National mass drug administration costs for lymphatic filariasis elimination.

BACKGROUND: Because lymphatic filariasis (LF) elimination efforts are hampered by a dearth of economic information about the cost of mass drug administration (MDA) programs (using either albendazole with diethylcarbamazine [DEC] or albendazole with ivermectin), a multicenter study was undertaken to determine the costs of MDA programs to interrupt transmission of infection with LF. Such results are particularly important because LF programs have the necessary diagnostic and treatment tools to eliminate the disease as a public health problem globally, and already by 2006, the Global Programme to Eliminate LF had initiated treatment programs covering over 400 million of the 1.3 billion people at risk. METHODOLOGY/PRINCIPAL FINDINGS: To obtain annual costs to carry out the MDA strategy, researchers from seven countries developed and followed a common cost analysis protocol designed to estimate 1) the total annual cost of the LF program, 2) the average cost per person treated, and 3) the relative contributions of the endemic countries and the external partners. Costs per person treated ranged from $0.06 to $2.23. Principal reasons for the variation were 1) the age (newness) of the MDA program, 2) the use of volunteers, and 3) the size of the population treated. Substantial contributions by governments were documented - generally 60%-90% of program operation costs, excluding costs of donated medications. CONCLUSIONS/SIGNIFICANCE: MDA for LF elimination is comparatively inexpensive in relation to most other public health programs. Governments and communities make the predominant financial contributions to actual MDA implementation, not counting the cost of the drugs themselves. The results highlight the impact of the use of volunteers on program costs and provide specific cost data for 7 different countries that can be used as a basis both for modifying current programs and for developing new ones.

Understanding parents' approaches to care and treatment of children with cancer when standard therapy has failed.

PURPOSE: To examine US and United Kingdom (UK) parents' approaches to care and treatment when standard therapy has failed and consider implications for clinical practice. METHODS: We conducted a prospective, ethnographic study of parents, patients, and staff, including participant-observation; open-ended, semistructured interviews; and review of medical records at a US and UK pediatric oncology center. Thirty-four children (n = 17 US, 17 UK), whose disease had recurred with less than 30% chance of cure, were enrolled between March 2001 and June 2002 and followed until death (n = 11 US, 14 UK) or close of study in December 2005 (n = 6 US, 3 UK). RESULTS: There were no major differences between parents' approaches in the US and UK despite differences in health care systems, institutions, and parents' religion or ethnicity. All parents continued to have or request meetings with the oncologist and investigative procedures. No parent initiated discontinuation of cancer- or symptom-directed interventions. In 28 of 34 cases (13 US, 15 UK), parents continued to pursue cancer-directed therapies; in 16 of 28 cases (seven US, nine UK), parents initiated inquires beyond what was offered. CONCLUSION: Understanding parents' behavior requires attention to the reason and emotion they bring to decision making and their children's care, their unique responsibilities as parents, and what they learn throughout the illness. Parents do not see cancer-directed therapy and symptom-directed care as mutually exclusive, alternative approaches. Parents will not be constrained by what the oncologist offers. Physicians and parents discuss and negotiate care and treatment throughout the illness. Our findings suggest developing integrative care models incorporating cancer-directed, symptom-directed, and supportive care throughout the illness; they are most consistent with parents' approaches and advances in pediatric oncology.

Development of the paediatric pain profile: role of video analysis and saliva cortisol in validating a tool to assess pain in children with severe neurological disability.

The Paediatric Pain Profile (PPP) is a 20-item behavior-rating scale designed to assess pain in children with severe to profound neurological impairment. Three raters independently used the PPP to rate behavior of 29 children (mean age 9.6, SD 5.8) filmed during everyday morning activities. The validation process included assessment of interrater reliability and exploration of the relationship of PPP scores with saliva cortisol concentration. There was substantial agreement between raters. The PPP showed strong association with global pain assessments and differentiated between preselected high- and low-pain groups. PPP score showed moderate correlation with saliva cortisol concentration, but a single child explained the strength of the relationship and overall, saliva cortisol concentrations appeared low. The data provide additional evidence that the PPP is a reliable and valid instrument for pain assessment in neurologically impaired children. Cortisol levels are not a useful criterion for pain in this population and further study of cortisol response to stress/pain in children with severe neurological impairments is needed.

Symptoms in children/young people with progressive malignant disease: United Kingdom Children's Cancer Study Group/Paediatric Oncology Nurses Forum survey.

AIM: The purpose of this study was to survey symptoms in children/young people with progressive cancer and identify which are the most important and which are the most difficult to treat effectively. PATIENTS AND METHODS: This was a questionnaire survey of 22 United Kingdom Children's Cancer Study Group centers. Data were collected by clinical nurse specialists in pediatric oncology regarding children/young people between 0 and 20 years of age, using 2 questionnaires. The first collected demographic details and the second data about the occurrence and perceived impact of symptoms. RESULTS: There were 185 children/young people from 20 centers registered in the study, aged 4 months to 19 years (mean: 8.7 years), who received palliative care for a median of 34 days (range: 0-354 days). Data were analyzed for 164 children/young people who died during the study. Between referral to palliative care and death, there were significant increases in the number of symptoms reported and children/young people experiencing pain (70.6% vs 91.5%). Symptoms included some that often go unrecognized in children/young people, for example, anorexia, weight loss, and weakness. The nature of the underlying malignancy significantly influenced the prevalence of some symptoms. There were significant differences between the symptoms associated with central nervous system tumors and other groups. Pain other than headache occurred more commonly in children with solid tumors (98.4%) than in others (87%). Neurologic symptoms, including headache, were universal among those with central nervous system tumors. CONCLUSION: This study documents the frequency of symptoms and contrasts the experiences of children/young people with different groups of malignant disease. With access to skilled symptom control, pain can be effectively treated in most children/young people. Some other symptoms often remain intractable. The study highlights the need for further research to establish the effectiveness of therapeutic interventions for symptom control and their impact on the quality of life for children/young people dying from cancer.

Defining the cost of the Egyptian lymphatic filariasis elimination programme.

BACKGROUND: Lymphatic filariasis (LF) is targeted for global elimination. LF elimination programmes in different countries, including Egypt, are supported financially by national and international agencies. The national programme in Egypt is based on mass drug administration (MDA) of an annual dose of a combination of 2 drugs (DEC and albendazole) to all endemic villages. This study aimed primarily to estimate the Total and Government costs of two rounds of MDA conducted in Egypt in 2000 and 2001, the average cost per person treated, and the cost share of the different programme partners. METHODS: The Total costs reflect the overall annual costs of the MDA programme, and we defined Government costs as those expenditures made by the Egyptian government to develop, implement and sustain the MDA programmes. We used a generic protocol developed in coordination with the Emory Lymphatic Filariasis Support Center. Our study was concerned with all costs to the government, donors and other implementing parties. Cost data were retrospectively gathered from local, regional and national Ministry of Health and Population records. The total estimates for each governorate were based on data from a representative district for the governorate; these were combined with national programme data for a national estimate. RESULTS: The overall Total and Government costs for treating approximately 1,795,553 individuals living in all endemic villages in the year 2000 were USD 3,181,000 and USD 2,412,000, respectively. In 2001, the number of persons treated increased (29%) and the Total costs were USD 3,109,000 while Government costs were USD 2,331,000. In 2000, the average Total and Government costs per treated subject were USD 1.77 and USD 1.34, respectively, however, these costs decreased to USD 1.34 and USD 1.00, respectively in 2001. The coverage rate was 86.0% in 2000 and it increased to 88.0% in 2001. CONCLUSION: The Egyptian government provided 75.8% of all resources, as reflected in the Total cost estimates, and international agencies contributed the rest. Such data highlight both the commitment of the Egyptian government and the significance of the contributions of international bodies toward the LF elimination programme.

Clinical validation of the paediatric pain profile.

The Paediatric Pain Profile (PPP) is a 20-item behaviour rating scale designed to assess pain in children with severe neurological disability. We assessed the validity and reliability of the scale in 140 children (76 females, mean age 9 years 11 months, SD 4 years 7 months; range 1 to 18 years), unable to communicate through speech or augmentative communication. Parents used the PPP to rate retrospectively their child's behaviour when 'at their best' and when in pain. To assess interrater reliability, two raters concurrently observed and individually rated each child's behaviour. To assess construct validity and responsiveness of the scale, behaviour of 41 children was rated before and for four hours after administration of an 'as required' analgesic. Behaviour of 30 children was rated before surgery and for five days after. Children had significantly higher scores when reported to have pain than 'at their best' and scores increased in line with global evaluations of pain. Internal consistency ranged from 0.75 to 0.89 (Cronbach's alpha) and interrater reliability from 0.74 to 0.89 (intraclass correlation). Sensitivity (1.00) and specificity (0.91) were optimized at a cut-off of 14/60. PPP score was significantly greater before administration of the analgesic than after (paired-sample t-tests, p<0.001). Though there was no significant difference in mean pre- and postoperative scores, highest PPP score occurred in the first 24 hours after surgery in 14 (47%) children. Results suggest that the PPP is reliable and valid and has potential for use both clinically and in intervention research.

Not knowing--the problem of pain in children with severe neurological impairment.

This study uses a grounded theory approach to explore the diagnostic and clinical decision-making processes used by parents and healthcare professionals in relation to pain in children with severe to profound neurological impairment. Three forms of knowledge are required for optimal pain assessment and management (1) knowing the child, (2) familiarity with children with the same or similar conditions and (3) knowing the science. Pain relief can be compromised by systems of care that fragment rather than integrate care. A model which integrates knowledge of child, population and science is proposed together with an intersubjective attitude to assessing pain.