Whole document restricted until August 2010, see Access Instructions file below for details of how to access the print copy. / Abstract Background Asthma is a common problem in New Zealand, and is associated with significant morbidity and costs to children, their families, and wider society. Previously published New Zealand literature suggested that Māori and Pacific children were less likely than NZ European children to receive asthma medications and elements of asthma education, had poorer knowledge of asthma, and experienced greater morbidity and hospitalisations. However, none of the previous literature had been specifically designed to assess the nature of asthma care in the community, or to specifically answer whether there were ethnic disparities in care. A systematic review of studies published in the international literature that compared asthma management among different ethnic groups drawn from community-based samples was undertaken. The results of this review suggested that minority ethnic group children were less likely to receive elements of asthma medication use, asthma education and self-management (action) plans. Objectives The primary objectives of the study were to: • describe the use of medications, medication delivery systems, asthma education, and self-management plans in primary care for Māori, Pacific, and Other ethnic group children • ascertain whether there were any ethnic disparities in the use of medications, medication delivery systems, asthma education, and self-management plans in primary care after controlling for differences in socio-economic position and other potential confounders. Secondary objectives were to: • describe the asthma-related utilisation of GP, after hours medical care, emergency departments, and hospital admissions among Māori, Pacific, and Other ethnic group children with asthma • ascertain whether differences in medication use, the provision of asthma education, and the provision of self-management plans explained ethnic differences in health service utilisation. Methods A cross-sectional survey was conducted in Auckland, New Zealand. The caregivers of 647 children who were aged 2–14 years, had a diagnosis of asthma or experienced ‘wheeze or whistling in the chest’, and had experienced symptoms in the previous 12 months were identified using random residential address start points and door knocking. Ethnically stratified sampling ratios were used to ensure that approximately equal numbers of children of Māori, Pacific and Other ethnicity were enrolled into the study. A face-to-face interview was conducted with the caregivers of these children. Data was collected about: socio-demographic factors; asthma morbidity; asthma medications and delivery devices; exposure to, and experiences of, asthma education and asthma action plans; and asthma-related health services utilisation. Results In this study, the caregivers of 647 eligible children were invited to participate and 583 completed the interview, giving an overall completion rate of 90.1%. There were no ethnic differences in completion rates. The overall use of inhaled corticosteroid medications had increased since previous New Zealand research was published. Multivariable modelling that adjusted for potential confounders did not identify ethnic differences in the use of inhaled corticosteroids or oral steroids. Some findings about medication delivery mechanisms indicated that care was not consistent with guidelines. About 15% of participants reported they had not received asthma education from a primary care health professional. After adjusting for potential confounders there were no ethnic differences in the likelihood of having received asthma education from a health professional. Among those participants who had received education from a primary care health professional, significantly fewer Māori and Pacific caregivers reported receiving education about asthma triggers, pathophysiology and action plans. Lower proportions of Pacific (77.7%; 95% confidence interval (95%CI) 70.3, 85.1) and Māori (79.8%; 95% CI 73.6, 85.9) caregivers were given information about asthma triggers compared to Other caregivers (89.2%; 95% CI 84.9, 93.6; p=0.01). Fewer Māori (63.6%; 95% CI 55.7, 71.4) and Pacific (68.1%; 95% CI 60.1, 76.1) caregivers reported receiving information about pathophysiology (Other 75.9%; 95% CI 69.5, 82.3; p=0.05). Information about asthma action plans had been given to 22.7% (95% CI 15.5, 29.9) of Pacific and 32.9% (95% CI 25.3, 40.6) of Māori compared to Other participants (36.5%; 95% CI 28.6, 44.3; p=0.04). In addition, fewer Māori (64.2%; 95% CI 56.1, 72.3) and Pacific (68.5%; 95% CI 60.1, 77.0) reported that the information they received was clear and easy to understand (Other 77.9%; 95% CI 71.8, 84.1; p=0.03). About half of those who had received education from a health professional reported receiving further education and, after adjustment for potential confounders, Pacific caregivers were less likely to have been given further education (odds ratio 0.57; 95% confidence interval 0.33, 0.96). A minority of participants (35.3%) had heard about action plans and, after adjustment for potential confounders, Pacific caregivers were less likely to have heard about these plans (odds ratio 0.54; 95% confidence interval 0.33, 0.96). About 10% of the sample was considered to have a current action plan. The mean number of visits to a GP for acute and routine asthma care (excluding after-hours doctors and medical services) in the previous twelve months were significantly higher for Pacific (3.89; CI 3.28, 4.60) and Māori (3.56; CI 3.03, 4.16) children than Other ethnic group children (2.47; CI 2.11, 2.85; p<0.0001). Multivariable modelling of health service utilization outcomes (‘number of GP visits for acute and routine asthma care in the previous twelve months’, ‘high use of hospital emergency departments’, and ‘hospital admissions’) showed that adjustment for potential confounding and asthma management variables reduced, but did not fully explain, ethnic differences in these outcomes. Māori children experienced 22% more GP visits and Pacific children 28% more visits than Other children (p=0.05). Other variables that were significantly associated with a higher number of GP visits were: regular source of care they always used (regression coefficient (RC) 0.24; p<0.01); lower household income (RC 0.31; p=0.004) and having a current action plan (RC 0.38; p=0.006). Increasing age (RC -0.04; p=0.003), a lay source of asthma education (RC -0.41; p=0.001), and higher scores on asthma management scenario (RC -0.03; p=0.05) were all associated with a lower number of GP visits. Pacific (odds ratio (OR) 6.93; 95% CI 2.40, 19.98) and Māori (OR 2.60; 95% CI 0.87, 8.32) children were more likely to have used an emergency department for asthma care in the previous twelve months (p=0.0007). Other variables that had a significant effect on the use of EDs in the multivariable model were: not speaking English in the home (OR 3.72; 95% CI 1.52, 9.09; p=0.004), male sex (OR 2.43; 95% CI 1.15, 5.15; p=0.02), and having a current action plan (OR 7.85; 95% CI 3.49, 17.66; p<0.0001). Increasing age was associated with a reduced likelihood of using EDs (OR 0.90; 95% CI 0.81, 1.00; p=0.05). Hospitalisations were more likely in the Pacific (OR 8.94; 95% CI 2.25, 35.62) and Māori (OR 5.40; 95% CI 1.28, 23.06) ethnic groups (p=0.007). Four other variables had a significant effect on hospital admissions in the multivariable model. Participants who had a low income (OR 3.70; 95% CI 1.49, 9.18; p=0.005), and those who had a current action plan (OR 8.39; 95% CI 3.85, 18.30; p<0.0001) were more likely to have been admitted to hospital in the previous 12 months. Increasing age (OR 0.88; 95% CI 0.80, 0.98; p=0.02) and parental history of asthma (OR 0.39; 95% CI 0.18, 0.85; p=0.02) were associated with reduced likelihood of admission. Conclusions The study is a robust example of cross-sectional design and has high internal validity. The study population is representative of the population of children with asthma in the community. The three ethnic groups are also considered to be representative of those ethnic groups in the community. The study, therefore, has good representativeness and the findings of the study can be generalised to the wider population of children with asthma in the Auckland region. The results suggested that some aspects of pharmacological management were more consistent with guideline recommendations than in the past. However, given the higher burden of disease experienced by Māori and Pacific children, the lack of observed ethnic differences in the use of preventative medications may reflect under treatment relative to need. There are important ethnic differences in the provision of asthma education and action plans. Future approaches to improving care should focus on interventions to assist health professionals to implement guideline recommendations and to monitor ethnic disparities in their practice. Asthma education that is comprehensive, structured and delivered in ways that are effective for the people concerned is needed.

Whole document restricted until August 2010, see Access Instructions file below for details of how to access the print copy. / Abstract Background Asthma is a common problem in New Zealand, and is associated with significant morbidity and costs to children, their families, and wider society. Previously published New Zealand literature suggested that Māori and Pacific children were less likely than NZ European children to receive asthma medications and elements of asthma education, had poorer knowledge of asthma, and experienced greater morbidity and hospitalisations. However, none of the previous literature had been specifically designed to assess the nature of asthma care in the community, or to specifically answer whether there were ethnic disparities in care. A systematic review of studies published in the international literature that compared asthma management among different ethnic groups drawn from community-based samples was undertaken. The results of this review suggested that minority ethnic group children were less likely to receive elements of asthma medication use, asthma education and self-management (action) plans. Objectives The primary objectives of the study were to: • describe the use of medications, medication delivery systems, asthma education, and self-management plans in primary care for Māori, Pacific, and Other ethnic group children • ascertain whether there were any ethnic disparities in the use of medications, medication delivery systems, asthma education, and self-management plans in primary care after controlling for differences in socio-economic position and other potential confounders. Secondary objectives were to: • describe the asthma-related utilisation of GP, after hours medical care, emergency departments, and hospital admissions among Māori, Pacific, and Other ethnic group children with asthma • ascertain whether differences in medication use, the provision of asthma education, and the provision of self-management plans explained ethnic differences in health service utilisation. Methods A cross-sectional survey was conducted in Auckland, New Zealand. The caregivers of 647 children who were aged 2–14 years, had a diagnosis of asthma or experienced ‘wheeze or whistling in the chest’, and had experienced symptoms in the previous 12 months were identified using random residential address start points and door knocking. Ethnically stratified sampling ratios were used to ensure that approximately equal numbers of children of Māori, Pacific and Other ethnicity were enrolled into the study. A face-to-face interview was conducted with the caregivers of these children. Data was collected about: socio-demographic factors; asthma morbidity; asthma medications and delivery devices; exposure to, and experiences of, asthma education and asthma action plans; and asthma-related health services utilisation. Results In this study, the caregivers of 647 eligible children were invited to participate and 583 completed the interview, giving an overall completion rate of 90.1%. There were no ethnic differences in completion rates. The overall use of inhaled corticosteroid medications had increased since previous New Zealand research was published. Multivariable modelling that adjusted for potential confounders did not identify ethnic differences in the use of inhaled corticosteroids or oral steroids. Some findings about medication delivery mechanisms indicated that care was not consistent with guidelines. About 15% of participants reported they had not received asthma education from a primary care health professional. After adjusting for potential confounders there were no ethnic differences in the likelihood of having received asthma education from a health professional. Among those participants who had received education from a primary care health professional, significantly fewer Māori and Pacific caregivers reported receiving education about asthma triggers, pathophysiology and action plans. Lower proportions of Pacific (77.7%; 95% confidence interval (95%CI) 70.3, 85.1) and Māori (79.8%; 95% CI 73.6, 85.9) caregivers were given information about asthma triggers compared to Other caregivers (89.2%; 95% CI 84.9, 93.6; p=0.01). Fewer Māori (63.6%; 95% CI 55.7, 71.4) and Pacific (68.1%; 95% CI 60.1, 76.1) caregivers reported receiving information about pathophysiology (Other 75.9%; 95% CI 69.5, 82.3; p=0.05). Information about asthma action plans had been given to 22.7% (95% CI 15.5, 29.9) of Pacific and 32.9% (95% CI 25.3, 40.6) of Māori compared to Other participants (36.5%; 95% CI 28.6, 44.3; p=0.04). In addition, fewer Māori (64.2%; 95% CI 56.1, 72.3) and Pacific (68.5%; 95% CI 60.1, 77.0) reported that the information they received was clear and easy to understand (Other 77.9%; 95% CI 71.8, 84.1; p=0.03). About half of those who had received education from a health professional reported receiving further education and, after adjustment for potential confounders, Pacific caregivers were less likely to have been given further education (odds ratio 0.57; 95% confidence interval 0.33, 0.96). A minority of participants (35.3%) had heard about action plans and, after adjustment for potential confounders, Pacific caregivers were less likely to have heard about these plans (odds ratio 0.54; 95% confidence interval 0.33, 0.96). About 10% of the sample was considered to have a current action plan. The mean number of visits to a GP for acute and routine asthma care (excluding after-hours doctors and medical services) in the previous twelve months were significantly higher for Pacific (3.89; CI 3.28, 4.60) and Māori (3.56; CI 3.03, 4.16) children than Other ethnic group children (2.47; CI 2.11, 2.85; p<0.0001). Multivariable modelling of health service utilization outcomes (‘number of GP visits for acute and routine asthma care in the previous twelve months’, ‘high use of hospital emergency departments’, and ‘hospital admissions’) showed that adjustment for potential confounding and asthma management variables reduced, but did not fully explain, ethnic differences in these outcomes. Māori children experienced 22% more GP visits and Pacific children 28% more visits than Other children (p=0.05). Other variables that were significantly associated with a higher number of GP visits were: regular source of care they always used (regression coefficient (RC) 0.24; p<0.01); lower household income (RC 0.31; p=0.004) and having a current action plan (RC 0.38; p=0.006). Increasing age (RC -0.04; p=0.003), a lay source of asthma education (RC -0.41; p=0.001), and higher scores on asthma management scenario (RC -0.03; p=0.05) were all associated with a lower number of GP visits. Pacific (odds ratio (OR) 6.93; 95% CI 2.40, 19.98) and Māori (OR 2.60; 95% CI 0.87, 8.32) children were more likely to have used an emergency department for asthma care in the previous twelve months (p=0.0007). Other variables that had a significant effect on the use of EDs in the multivariable model were: not speaking English in the home (OR 3.72; 95% CI 1.52, 9.09; p=0.004), male sex (OR 2.43; 95% CI 1.15, 5.15; p=0.02), and having a current action plan (OR 7.85; 95% CI 3.49, 17.66; p<0.0001). Increasing age was associated with a reduced likelihood of using EDs (OR 0.90; 95% CI 0.81, 1.00; p=0.05). Hospitalisations were more likely in the Pacific (OR 8.94; 95% CI 2.25, 35.62) and Māori (OR 5.40; 95% CI 1.28, 23.06) ethnic groups (p=0.007). Four other variables had a significant effect on hospital admissions in the multivariable model. Participants who had a low income (OR 3.70; 95% CI 1.49, 9.18; p=0.005), and those who had a current action plan (OR 8.39; 95% CI 3.85, 18.30; p<0.0001) were more likely to have been admitted to hospital in the previous 12 months. Increasing age (OR 0.88; 95% CI 0.80, 0.98; p=0.02) and parental history of asthma (OR 0.39; 95% CI 0.18, 0.85; p=0.02) were associated with reduced likelihood of admission. Conclusions The study is a robust example of cross-sectional design and has high internal validity. The study population is representative of the population of children with asthma in the community. The three ethnic groups are also considered to be representative of those ethnic groups in the community. The study, therefore, has good representativeness and the findings of the study can be generalised to the wider population of children with asthma in the Auckland region. The results suggested that some aspects of pharmacological management were more consistent with guideline recommendations than in the past. However, given the higher burden of disease experienced by Māori and Pacific children, the lack of observed ethnic differences in the use of preventative medications may reflect under treatment relative to need. There are important ethnic differences in the provision of asthma education and action plans. Future approaches to improving care should focus on interventions to assist health professionals to implement guideline recommendations and to monitor ethnic disparities in their practice. Asthma education that is comprehensive, structured and delivered in ways that are effective for the people concerned is needed.

Whole document restricted until August 2010, see Access Instructions file below for details of how to access the print copy. / Abstract Background Asthma is a common problem in New Zealand, and is associated with significant morbidity and costs to children, their families, and wider society. Previously published New Zealand literature suggested that Māori and Pacific children were less likely than NZ European children to receive asthma medications and elements of asthma education, had poorer knowledge of asthma, and experienced greater morbidity and hospitalisations. However, none of the previous literature had been specifically designed to assess the nature of asthma care in the community, or to specifically answer whether there were ethnic disparities in care. A systematic review of studies published in the international literature that compared asthma management among different ethnic groups drawn from community-based samples was undertaken. The results of this review suggested that minority ethnic group children were less likely to receive elements of asthma medication use, asthma education and self-management (action) plans. Objectives The primary objectives of the study were to: • describe the use of medications, medication delivery systems, asthma education, and self-management plans in primary care for Māori, Pacific, and Other ethnic group children • ascertain whether there were any ethnic disparities in the use of medications, medication delivery systems, asthma education, and self-management plans in primary care after controlling for differences in socio-economic position and other potential confounders. Secondary objectives were to: • describe the asthma-related utilisation of GP, after hours medical care, emergency departments, and hospital admissions among Māori, Pacific, and Other ethnic group children with asthma • ascertain whether differences in medication use, the provision of asthma education, and the provision of self-management plans explained ethnic differences in health service utilisation. Methods A cross-sectional survey was conducted in Auckland, New Zealand. The caregivers of 647 children who were aged 2–14 years, had a diagnosis of asthma or experienced ‘wheeze or whistling in the chest’, and had experienced symptoms in the previous 12 months were identified using random residential address start points and door knocking. Ethnically stratified sampling ratios were used to ensure that approximately equal numbers of children of Māori, Pacific and Other ethnicity were enrolled into the study. A face-to-face interview was conducted with the caregivers of these children. Data was collected about: socio-demographic factors; asthma morbidity; asthma medications and delivery devices; exposure to, and experiences of, asthma education and asthma action plans; and asthma-related health services utilisation. Results In this study, the caregivers of 647 eligible children were invited to participate and 583 completed the interview, giving an overall completion rate of 90.1%. There were no ethnic differences in completion rates. The overall use of inhaled corticosteroid medications had increased since previous New Zealand research was published. Multivariable modelling that adjusted for potential confounders did not identify ethnic differences in the use of inhaled corticosteroids or oral steroids. Some findings about medication delivery mechanisms indicated that care was not consistent with guidelines. About 15% of participants reported they had not received asthma education from a primary care health professional. After adjusting for potential confounders there were no ethnic differences in the likelihood of having received asthma education from a health professional. Among those participants who had received education from a primary care health professional, significantly fewer Māori and Pacific caregivers reported receiving education about asthma triggers, pathophysiology and action plans. Lower proportions of Pacific (77.7%; 95% confidence interval (95%CI) 70.3, 85.1) and Māori (79.8%; 95% CI 73.6, 85.9) caregivers were given information about asthma triggers compared to Other caregivers (89.2%; 95% CI 84.9, 93.6; p=0.01). Fewer Māori (63.6%; 95% CI 55.7, 71.4) and Pacific (68.1%; 95% CI 60.1, 76.1) caregivers reported receiving information about pathophysiology (Other 75.9%; 95% CI 69.5, 82.3; p=0.05). Information about asthma action plans had been given to 22.7% (95% CI 15.5, 29.9) of Pacific and 32.9% (95% CI 25.3, 40.6) of Māori compared to Other participants (36.5%; 95% CI 28.6, 44.3; p=0.04). In addition, fewer Māori (64.2%; 95% CI 56.1, 72.3) and Pacific (68.5%; 95% CI 60.1, 77.0) reported that the information they received was clear and easy to understand (Other 77.9%; 95% CI 71.8, 84.1; p=0.03). About half of those who had received education from a health professional reported receiving further education and, after adjustment for potential confounders, Pacific caregivers were less likely to have been given further education (odds ratio 0.57; 95% confidence interval 0.33, 0.96). A minority of participants (35.3%) had heard about action plans and, after adjustment for potential confounders, Pacific caregivers were less likely to have heard about these plans (odds ratio 0.54; 95% confidence interval 0.33, 0.96). About 10% of the sample was considered to have a current action plan. The mean number of visits to a GP for acute and routine asthma care (excluding after-hours doctors and medical services) in the previous twelve months were significantly higher for Pacific (3.89; CI 3.28, 4.60) and Māori (3.56; CI 3.03, 4.16) children than Other ethnic group children (2.47; CI 2.11, 2.85; p<0.0001). Multivariable modelling of health service utilization outcomes (‘number of GP visits for acute and routine asthma care in the previous twelve months’, ‘high use of hospital emergency departments’, and ‘hospital admissions’) showed that adjustment for potential confounding and asthma management variables reduced, but did not fully explain, ethnic differences in these outcomes. Māori children experienced 22% more GP visits and Pacific children 28% more visits than Other children (p=0.05). Other variables that were significantly associated with a higher number of GP visits were: regular source of care they always used (regression coefficient (RC) 0.24; p<0.01); lower household income (RC 0.31; p=0.004) and having a current action plan (RC 0.38; p=0.006). Increasing age (RC -0.04; p=0.003), a lay source of asthma education (RC -0.41; p=0.001), and higher scores on asthma management scenario (RC -0.03; p=0.05) were all associated with a lower number of GP visits. Pacific (odds ratio (OR) 6.93; 95% CI 2.40, 19.98) and Māori (OR 2.60; 95% CI 0.87, 8.32) children were more likely to have used an emergency department for asthma care in the previous twelve months (p=0.0007). Other variables that had a significant effect on the use of EDs in the multivariable model were: not speaking English in the home (OR 3.72; 95% CI 1.52, 9.09; p=0.004), male sex (OR 2.43; 95% CI 1.15, 5.15; p=0.02), and having a current action plan (OR 7.85; 95% CI 3.49, 17.66; p<0.0001). Increasing age was associated with a reduced likelihood of using EDs (OR 0.90; 95% CI 0.81, 1.00; p=0.05). Hospitalisations were more likely in the Pacific (OR 8.94; 95% CI 2.25, 35.62) and Māori (OR 5.40; 95% CI 1.28, 23.06) ethnic groups (p=0.007). Four other variables had a significant effect on hospital admissions in the multivariable model. Participants who had a low income (OR 3.70; 95% CI 1.49, 9.18; p=0.005), and those who had a current action plan (OR 8.39; 95% CI 3.85, 18.30; p<0.0001) were more likely to have been admitted to hospital in the previous 12 months. Increasing age (OR 0.88; 95% CI 0.80, 0.98; p=0.02) and parental history of asthma (OR 0.39; 95% CI 0.18, 0.85; p=0.02) were associated with reduced likelihood of admission. Conclusions The study is a robust example of cross-sectional design and has high internal validity. The study population is representative of the population of children with asthma in the community. The three ethnic groups are also considered to be representative of those ethnic groups in the community. The study, therefore, has good representativeness and the findings of the study can be generalised to the wider population of children with asthma in the Auckland region. The results suggested that some aspects of pharmacological management were more consistent with guideline recommendations than in the past. However, given the higher burden of disease experienced by Māori and Pacific children, the lack of observed ethnic differences in the use of preventative medications may reflect under treatment relative to need. There are important ethnic differences in the provision of asthma education and action plans. Future approaches to improving care should focus on interventions to assist health professionals to implement guideline recommendations and to monitor ethnic disparities in their practice. Asthma education that is comprehensive, structured and delivered in ways that are effective for the people concerned is needed.

<div>Delayed fracture healing is a major health issue involved with aging. Therefore, strategies to improve the pace of repair and prevent non-union are needed in order to improve patient outcomes and lower healthcare costs. In order to accelerate bone fracture healing noninvasively, we sought to develop a drug delivery system that could safely and effectively be used to deliver therapeutics to the site of a bone fracture. We elected to pursue the promising strategy of using small-molecule drug conjugates that deliver therapeutics to bone in an attempt to increase the efficacy and safety of drugs for treating bone-related diseases.</div><div>This strategy also opened the door for new methods of administering drugs. Traditionally, administering bone anabolic agents to treat bone fractures has relied entirely on local surgical application. However, because it is so invasive, this method’s use and development has been limited. By conjugating bone anabolic agents to bone-homing molecules, bone fracture treatment can be performed through minimally invasive subcutaneous administration. The exposure of raw hydroxyapatite that occurs with a bone fracture allows these high-affinity molecules to chelate the calcium component of hydroxyapatite and localize primarily to the fracture site.</div><div>Many bone-homing molecules (such as bisphosphonates and tetracycline targeting) have been developed to treat osteoporosis. However, many of these molecules have toxicity associated with them. We have found that short oligopeptides of acidic amino acids can localize to bone fractures with high selectivity and with very low toxicity compared to bisphosphonates and tetracyclines.</div><div>We have also demonstrated that these molecules can be used to target peptides of all chemical classes: hydrophobic, neutral, cationic, anionic, short, and long. This ability is particularly useful because many bone anabolics are peptidic in nature. We have found that acidic oligopeptides have better persistence at the site of the fracture than bisphosphonate-targeted therapeutics. This method allows for a systemic administration of bone anabolics to treat bone fractures, which it achieves by accumulating the bone anabolic at the fracture site. It also opens the door for a new way of treating the prevalent afflictions of broken bones and the deaths associated with them.</div><div>We further developed this technology by using it to deliver anabolic peptides derived from growth factors, angiogenic agents, neuropeptides, and extracellular matrix fragments. We found several promising therapeutics that accelerated the healing of bone fractures by improving the mineralization of the callus and improving the overall strength. We optimized the performance of these molecules by improving their stability, targeting ligands, linkers, dose, and dosing frequency.</div><div>We also found that these therapeutics could be used to accelerate bone fracture repair even in the presence of severe comorbidities (such as diabetes and osteoporosis) that typically slow the repair process. We found that, unlike the currently approved therapeutic for fracture healing (BMP2), our therapeutics improved functionality and reduced pain in addition to strengthening the bone. These optimized targeted bone anabolics were not only effective at healing bone fractures but they also demonstrated that they could be used to speed up spinal fusion. Additionally, we demonstrated that acidic oligopeptides have potential to be used to treat other bone diseases with damaged bone.</div><div>With these targeted therapeutics, we no longer have to limit bone fracture healing to casts or invasive surgeries. Rather, we can apply these promising therapeutics that can be administered non-invasively to augment existing orthopedic practices. As these therapeutics move into clinical development, we anticipate that they will be able to reduce the immobilization time that is the source of so many of the deadly complications associated with bone fracture healing, particularly in the elderly.</div>