Ten years of the manufacturing classification system: a review of literature applications and an extension of the framework to continuous manufacture.

The MCS initiative was first introduced in 2013. Since then, two MCS papers have been published: the first proposing a structured approach to consider the impact of drug substance physical properties on manufacturability and the second outlining real world examples of MCS principles. By 2023, both publications had been extensively cited by over 240 publications. This article firstly reviews this citing work and considers how the MCS concepts have been received and are being applied. Secondly, we will extend the MCS framework to continuous manufacture. The review structure follows the flow of drug product development focussing first on optimisation of API properties. The exploitation of links between API particle properties and manufacturability using large datasets seems particularly promising. Subsequently, applications of the MCS for formulation design include a detailed look at the impact of percolation threshold, the role of excipients and how other classification systems can be of assistance. The final review section focusses on manufacturing process development, covering the impact of strain rate sensitivity and modelling applications. The second part of the paper focuses on continuous processing proposing a parallel MCS framework alongside the existing batch manufacturing guidance. Specifically, we propose that continuous direct compression can accommodate a wider range of API properties compared to its batch equivalent.

UK Food Standards Agency Workshop Report: an investigation of the relative contributions of diet and sunlight to vitamin D status.

The UK Food Standards Agency (FSA) convened an international group of scientific experts to review three Agency-funded projects commissioned to provide evidence for the relative contributions of two sources, dietary vitamin D intake and skin exposure to UVB rays from sunlight, to vitamin D status. This review and other emerging evidence are intended to inform any future risk assessment undertaken by the Scientific Advisory Committee on Nutrition. Evidence was presented from randomised controlled trials to quantify the amount of vitamin D required to maintain a serum 25-hydroxy vitamin D (25OHD) concentration >25 nmol/l, a threshold that is regarded internationally as defining the risk of rickets and osteomalacia. Longitudinal evidence was also provided on summer sunlight exposure required to maintain 25OHD levels above this threshold in people living in the British Isles (latitude 51 degrees-57 degrees N). Data obtained from multi-level modelling of these longitudinal datasets showed that UVB exposure (i.e. season) was the major contributor to changes in 25OHD levels; this was a consistent finding in two Caucasian groups in the north and south of the UK, but was less apparent in the one group of British women of South Asian origin living in the south of the UK. The FSA-funded research suggested that the typical daily intake of vitamin D from food contributed less than UVB exposure to average year-round 25OHD levels in both Caucasian and Asian women. The low vitamin D status of Asian women has been acknowledged for some time, but the limited seasonal variation in Asian women is a novel finding. The Workshop also considered the dilemma of balancing the risks of vitamin D deficiency (from lack of skin exposure to sunlight in summer) and skin cancer (from excessive exposure to sunlight with concomitant sunburn and erythema). Cancer Research UK advises that individuals should stay below their personal sunburn threshold to minimise their skin cancer risk. The evidence suggests that vitamin D can be produced in summer at the latitude of the UK, with minimal risk of erythema and cell damage, by exposing the skin to sunlight for a short period at midday, when the intensity of UVB is at its daily peak. The implications of the new data were discussed in the context of dietary reference values for vitamin D for the general population aged 4-64 years. Future research suggestions included further analysis of the three FSA-funded studies as well as new research.

UK food standards agency workshop report: diet and immune function.

The UK Food Standards Agency convened a workshop on 13 May 2009 to discuss recently completed research on diet and immune function. The objective of the workshop was to review this research and to establish priorities for future research. Several of the trials presented at the workshop showed some effect of nutritional interventions (e.g. vitamin D, Zn, Se) on immune parameters. One trial found that increased fruit and vegetable intake may improve the antibody response to pneumococcal vaccination in older people. The workshop highlighted the need to further clarify the potential public health relevance of observed nutrition-related changes in immune function, e.g. susceptibility to infections and infectious morbidity.

Nutrition and bone health projects funded by the UK Food Standards Agency: have they helped to inform public health policy?

The UK Food Standards Agency convened an international group of expert scientists to review the Agency-funded projects on diet and bone health in the context of developments in the field as a whole. The potential benefits of fruit and vegetables, vitamin K, early-life nutrition and vitamin D on bone health were presented and reviewed. The workshop reached two conclusions which have public health implications. First, that promoting a diet rich in fruit and vegetable intakes might be beneficial to bone health and would be very unlikely to produce adverse consequences on bone health. The mechanism(s) for any effect of fruit and vegetables remains unknown, but the results from these projects did not support the postulated acid-base balance hypothesis. Secondly, increased dietary consumption of vitamin K may contribute to bone health, possibly through its ability to increase the gamma-carboxylation status of bone proteins such as osteocalcin. A supplementation trial comparing vitamin K supplementation with Ca and vitamin D showed an additional effect of vitamin K against baseline levels of bone mineral density, but the benefit was only seen at one bone site. The major research gap identified was the need to investigate vitamin D status to define deficiency, insufficiency and depletion across age and ethnic groups in relation to bone health.

Folate and colo-rectal cancer risk.

The UK Food Standards Agency convened a group of expert scientists to review current research investigating folate and colo-rectal cancer risk. The workshop aimed to examine current research and establish research priorities. The timing of folate exposure with respect to carcinogenesis, as well as the dose and form of folate, were considered key issues for future research. Also, the need to study further the influence of genetically defined subgroups was highlighted for future research.

A description of the social-ecological framework used in the trial of activity for adolescent girls (TAAG).

Social-ecological (SE) models are becoming more widely used in health behavior research. Applying SE models to the design of interventions is challenging because models must be tailor-made for each behavior and population, other theories need to be integrated into multi-level frameworks, and empirical research to guide model development is limited. The purpose of the present paper is to describe a SE framework that guided the intervention and measurement plans for a specific study. The trial of activity for adolescent girls (TAAG) is a multi-center study of interventions to reduce the decline of physical activity in adolescent girls. The TAAG framework incorporates operant learning theory, social cognitive theory, organizational change theory and the diffusion of innovation model in a multi-level model. The explicit and practical model developed for TAAG has already benefited the study and may have elements that can generalize to other health promotion studies.

Formative research in school and community-based health programs and studies: "state of the art" and the TAAG approach.

Formative research uses qualitative and quantitative methods to provide information for researchers to plan intervention programs. Gaps in the formative research literature include how to define goals, implementation plans, and research questions; select methods; analyze data; and develop interventions. The National Heart, Lung, and Blood Institute funded the Trial of Activity for Adolescent Girls (TAAG), a randomized, multicenter field trial, to reduce the decline in physical activity in adolescent girls. The goals of the TAAG formative research are to (a) describe study communities and schools, (b) help design the trial's interventions, (c) develop effective recruitment and retention strategies, and (d) design evaluation instruments. To meet these goals, a variety of methods, including telephone interviews, surveys and checklists, semistructured interviews, and focus group discussions, are employed. The purpose, method of development, and analyses are explained for each method.

School-based health education programs can be maintained over time: results from the CATCH Institutionalization study.

BACKGROUND: Developing and evaluating interventions to influence students' opportunities for healthful choices has been a focus of school-based health promotion research; however, few studies have examined the sustainability of these programs and viability of continued organizational implementation. METHODS: The purpose of this study was to determine the maintenance of Child and Adolescent Trial for Cardiovascular Health (CATCH) school-level changes in former intervention (n = 56) and former comparison (n = 20) schools 5 years post-intervention. Twelve schools unexposed to CATCH were measured as controls. Macronutrient content of 5 days of school lunch menus, amount and type of physical education (PE) classes, and health instruction practices in the classroom were assessed. An institutionalization score for schools was developed, using program maintenance variables: % kcal from fat and saturated fat in school lunches, % PE class spent in vigorous and moderate-to-vigorous physical activity, and class time devoted to CATCH topics. RESULTS: Menus from 50% of former intervention cafeterias met the Eat Smart guidelines for fat, compared to 10% of former control cafeterias and 17% of unexposed school cafeterias (P < 0.005). There were no significant differences in implementation of CATCH PE goals between conditions. Although the total time spent teaching CATCH was low in former CATCH schools, the former intervention schools spent significantly more time teaching CATCH and taught more lessons as compared to former comparison schools. Former intervention schools had a higher mean institutionalization score than former comparison schools (P < 0.001). Training had the greatest impact on maintenance of CATCH. CONCLUSIONS: Results from this study suggest that changes in the school environment to support healthful behaviors can be maintained over time. Staff training is an important factor in achieving institutionalization of these programs.

Defining the state of knowledge with respect to food, nutrition, physical activity, and the prevention of cancer.

The 1997 World Cancer Research Fund and the American Institute for Cancer Research (WCRF/AICR) report, Food, Nutrition and the Prevention of Cancer: a global perspective, has become the most authoritative statement on the topic. WCRF International has begun the process of producing its second global report on food, nutrition, physical activity, and the prevention of cancer. The process is in three stages. The first begins with the development of a suitable methodology as advised by a task force of experts. The second stage will involve the systematic collection and display of the evidence by independent review teams. The final stage will be the assessment and judgment of that evidence by an independent panel of experts responsible for the content of the report, including its conclusions and recommendations. Two major differences between this report and previous reports on the prevention of chronic diseases are that a portfolio approach to the evidence is being used in which all types of study are weighed and the process of collecting and displaying the evidence is being clearly separated from assessment and judgment. This paper outlines the methodological procedures and their development that will be applied for the second WCRF International report.

Obesity in American-Indian children: prevalence, consequences, and prevention.

BACKGROUND: American Indians of all ages and both sexes have a high prevalence of obesity. The health risks associated with obesity are numerous and include Type 2 diabetes mellitus, hypertension, dyslipidemia, and respiratory problems. Obesity has become a major health problem in American Indians only in the past few generations and it is believed to be associated with the relative abundance of high-fat, high-calorie foods and the rapid change from active to sedentary lifestyles. METHODS: The authors reviewed selected literature on prevalence of obesity in American-Indian children, and health consequences of obesity. RESULTS: Obesity is now one of the most serious public health problems facing American-Indian children, and it has grave implications for the immediate and long-term health of American-Indian youth. Unless this pattern is reversed, American-Indian populations will be burdened by an increased incidence of chronic diseases. Intervention studies are urgently needed in American-Indian communities to develop and test effective strategies for obesity prevention and treatment. CONCLUSIONS: To be effective, educational and environmental interventions must be developed with full participation of the American-Indian communities.

Pathways curriculum and family interventions to promote healthful eating and physical activity in American Indian schoolchildren.

BACKGROUND: Pathways, a multisite school-based study aimed at promoting healthful eating and increasing physical activity, was a randomized field trial including 1704 American Indian third to fifth grade students from 41 schools (21 intervention, 20 controls) in seven American Indian communities. METHODS: The intervention schools received four integrated components: a classroom curriculum, food service, physical activity, and family modules. The curriculum and family components were based on Social Learning Theory, American Indian concepts, and results from formative research. Process evaluation data were collected from teachers (n=235), students (n=585), and families. Knowledge, Attitudes, and Behavior Questionnaire data were collected from 1150 students including both intervention and controls. RESULTS: There were significant increases in knowledge and cultural identity in children in intervention compared to control schools with a significant retention of knowledge over the 3 years, based on the results of repeating the third and fourth grade test items in the fifth grade. Family members participated in Family Events and take-home activities, with fewer participating each year. CONCLUSION: A culturally appropriate school intervention can promote positive changes in knowledge, cultural identity, and self-reported healthful eating and physical activity in American Indian children and environmental change in school food service.

Design, implementation, and quality control in the Pathways American-Indian multicenter trial.

BACKGROUND: Pathways was the first multicenter American-Indian school-based study to test the effectiveness of an obesity prevention program promoting healthy eating and physical activity. METHODS: Pathways employed a nested cohort design in which 41 schools were randomized to intervention or control conditions and students within these schools were followed as a cohort (1,704 third graders at baseline). The study's primary endpoint was percent body fat. Secondary endpoints were levels of fat in school lunches; time spent in physical activity; and knowledge, attitudes, and behaviors regarding diet and exercise. Quality control (QC) included design of data management systems which provided standardization and quality assurance of data collection and processing. Data QC procedures at study centers included manuals of operation, training and certification, and monitoring of performance. Process evaluation was conducted to monitor dose and fidelity of the interventions. Registration and tracking systems were used for students and schools. RESULTS: No difference in mean percent body fat at fifth grade was found between the intervention and control schools. Percent of calories from fat and saturated fat in school lunches was significantly reduced in the intervention schools as was total energy intake from 24-hour recalls. Significant increases in self-reported physical activity levels and knowledge of healthy behaviors were found for the intervention school students. CONCLUSIONS: The Pathways study results provide evidence demonstrating the role schools can play in public health promotion. Its study design and QC systems and procedures provide useful models for other similar school based multi- or single-site studies.

Changes in the nutrient content of school lunches: results from the Pathways study.

BACKGROUND: Pathways, a randomized trial, evaluated the effectiveness of a school-based multicomponent intervention to reduce fatness in American-Indian schoolchildren. The goal of the Pathways food service intervention component was to reduce the fat in school lunches to no more than 30% of energy from fat while maintaining recommended levels of calories and key nutrients. METHODS: The intervention was implemented by school food service staff in intervention schools over a 3-year period. Five consecutive days of school lunch menu items were collected from 20 control and 21 intervention schools at four time periods, and nutrient content was analyzed. RESULTS: There was a significantly greater mean reduction in percent energy from fat and saturated fat in the intervention schools compared to the control schools. Mean percentages of energy from fat decreased from 33.1% at baseline to 28.3% at the end of the study in intervention schools compared to 33.2% at baseline and 32.2% at follow-up in the control schools (P<0.003). There were no statistically significant differences for calories or nutrients between intervention and control schools. CONCLUSIONS: The Pathways school food lunch intervention documented the feasibility of successfully lowering the percent of energy from fat, as part of a coordinated obesity prevention program for American-Indian children.

The effects of the Pathways Obesity Prevention Program on physical activity in American Indian children.

BACKGROUND: Inadequate opportunities for physical activity at school and overall low levels of activity contribute to the high prevalence of overweight and obesity in American-Indian children. METHODS: A school-based physical activity intervention was implemented which emphasized increasing the frequency and quality of physical education (PE) classes and activity breaks. Changes in physical activity were assessed using the TriTrac-R3D accelerometer in a subsample of 580 of the students (34%) randomly selected from the Pathways study cohort. Baseline measures were completed with children in second grade. Follow-up measurements were obtained in the spring of the fifth grade. RESULTS: Intervention schools were more active (+6.3 to +27.2%) than control schools at three of the four sites, although the overall difference between intervention and control schools (approximately 10%) was not significant (P>0.05). Boys were more active than girls by 17 to 21% (P < or =.01) at both baseline and follow-up. CONCLUSIONS: Despite the trend for greater physical activity at three of four study sites, and an overall difference of approximately 10% between intervention and control schools, high variability in accelerometer AVM and the opportunity to measure physical activity on only 1 day resulted in a the failure to detect the difference as significant.

Pathways process evaluation results: a school-based prevention trial to promote healthful diet and physical activity in American Indian third, fourth, and fifth grade students.

BACKGROUND: Pathways was a large-scale, multisite, 3-year, study testing a school-based intervention designed to lower percent body fat in American Indian children. METHODS: At the 21 intervention schools process evaluation data were collected for training of school personnel; implementation of the classroom and physical activity curricula; implementation of the project's food service guidelines in the school cafeterias; adult participation in the family events; and, students' perceived exposure to the Pathways interventions. RESULTS: Students received about 93% of the classroom curriculum lessons. The minimum requirement of physical education being taught three times per week for at least 30 minutes duration was achieved by the fifth grade. The implementation of the food service behavioral guidelines increased from 51% in the third grade to 87% in the fifth grade. The family events had lower than anticipated adult participation. The participation rates were 45% during the third grade, and 41 and 63% during the fourth and fifth grades, respectively. There was a significant difference between intervention and control students' perceived exposure to Pathways type interventions. CONCLUSION: The Pathways interventions were successfully implemented with good reach, high extent, and fidelity.

School climate and implementation of the Pathways study.

BACKGROUND: Pathways was a multisite school-based study to prevent obesity in American Indian school children by encouraging healthy eating and physical activity. METHODS: Over the 3-year study, a total of 290 in-depth interviews were conducted with school administrators, food service managers, classroom teachers, and physical education instructors in all 21 intervention schools to examine support and barriers for Pathways. Analysis included qualitative assessment of key themes using NUD*IST and quantitative modeling of the impact of a school climate score on implementation of intervention components. RESULTS: Overall, teachers, food service managers, and physical education instructors were supportive of the Pathways interventions. School administration and lack of family participation were perceived barriers at some schools. Attitudes toward the program ranged from neutral to positive during the first year, with about two-thirds giving positive ratings, with greater variation in successive years. Overall, the mean score was 3.5 on a 5-point scale (1=very negative, 5=very positive). School climate score was positively associated with classroom curriculum and student exposure indices, but not with family attendance, food service, or physical activity implementation indices. The latter two indices were associated with site. CONCLUSIONS: An assessment of school climate through interviews is useful in understanding successes and failures in a school-based health intervention and can predict implementation success for some programs.

Pathways: a school-based, randomized controlled trial for the prevention of obesity in American Indian schoolchildren.

BACKGROUND: Childhood obesity is a major public health problem in the United States, particularly among American Indian communities. OBJECTIVE: The objective was to evaluate the effectiveness of a school-based, multicomponent intervention for reducing percentage body fat in American Indian schoolchildren. DESIGN: This study was a randomized, controlled, school-based trial involving 1704 children in 41 schools and was conducted over 3 consecutive years, from 3rd to 5th grades, in schools serving American Indian communities in Arizona, New Mexico, and South Dakota. The intervention had 4 components: 1) change in dietary intake, 2) increase in physical activity, 3) a classroom curriculum focused on healthy eating and lifestyle, and 4) a family-involvement program. The main outcome was percentage body fat; other outcomes included dietary intake, physical activity, and knowledge, attitudes, and behaviors. RESULTS: The intervention resulted in no significant reduction in percentage body fat. However, a significant reduction in the percentage of energy from fat was observed in the intervention schools. Total energy intake (by 24-h dietary recall) was significantly reduced in the intervention schools but energy intake (by direct observation) was not. Motion sensor data showed similar activity levels in both the intervention and control schools. Several components of knowledge, attitudes, and behaviors were also positively and significantly changed by the intervention. CONCLUSIONS: These results document the feasibility of implementing a multicomponent program for obesity prevention in elementary schools serving American Indian communities. The program produced significant positive changes in fat intake and in food- and health-related knowledge and behaviors. More intense or longer interventions may be needed to significantly reduce adiposity in this population.

Institutionalization of a school health promotion program: background and rationale of the CATCH-ON study.

Research is lacking on how to make effective programs available on a large scale and how to maintain levels of implementation. CATCH: A Study of Institutionalization (CATCH-ON) was designed to help us understand the conditions under which such programs are institutionalized after the trial has ended. The Child and Adolescent Trial for Cardiovascular Health (CATCH) was the largest field trial of school-based health promotion in the United States conducted in 96 schools in four geographic areas of the United States: California, Louisiana, Minnesota. and Texas. The intervention was multicomponent, targeting school policy and practices in nutrition, physical activity, health education, and smoking. This report provides background on the CATCH study design, the conceptual framework for research on institutionalization of the CATCH program, and an overview of the seven original reports that present results from the CATCH-ON study in this theme issue.

Long-term implementation of the CATCH physical education program.

To test the effectiveness of the Child and Adolescent Trial for Cardiovascular Health (CATCH) program, a randomized trial was conducted in 96 elementary schools in four regions of the United States. Results from the original trial indicated a significant positive effect on the delivery of physical education (PE). All 56 former intervention schools (FI), 20 randomly selected former control schools (FC), and 12 newly selected unexposed control schools (UC) were assessed 5 years postintervention. Results indicate a strong secular trend of increasing moderate to vigorous physical activity (MVPA) in PE classes among both FC and UC schools. The FI schools surpassed the Healthy People 2010 goal for MVPA during PE lesson time (i.e., 50%), whereas the FC and UC schools came close to it. Barriers to implementing CATCH PE included insufficient training and lower importance of PE compared to other academic areas and indicate the need for in-service training.