Food Environments Within and Outside of Schools Play a Critical Role in Curtailing the Rise in Obesity among School-Aged Children over Time.

BACKGROUND: Sound evidence for effective community-based strategies is needed to curtail upward trends in childhood obesity in the United States (US). OBJECTIVES: The aim of the study was to assess the association between school and community food environments and the prevalence of obesity over time. METHODS: Data were collected from K-12 schools in 4 low-income New Jersey cities in the US. School-level obesity prevalence, calculated from nurse-measured heights and weights at 4 time points, was used as the outcome variable. Data on the school food environment (SFE) measured the healthfulness of school lunch and competitive food offerings annually. The community food environment (CFE), i.e., the number of different types of food outlets within 400 m of schools, was also captured annually. The count and presence of food outlets likely to be frequented by students were calculated. Exposure to composite environment profiles both within schools and in communities around schools was assessed using latent class analysis. Data from 106 schools were analyzed using multilevel linear regression. RESULTS: The prevalence of obesity increased from 25% to 29% over the course of the study. Obesity rates were higher in schools that had nearby access to a greater number of limited-service restaurants and lower in schools with access to small grocery stores and upgraded convenience stores participating in initiatives to improve healthful offerings. Interaction analysis showed that schools that offered unhealthier, competitive foods experienced a faster increase in obesity rates over time. Examining composite food environment exposures, schools with unhealthy SFEs and high-density CFEs experienced a steeper time trend (ß = 0.018, P < 0.001) in obesity prevalence compared to schools exposed to healthy SFE and low-density CFEs. CONCLUSIONS: Food environments within and outside of schools are associated with differential obesity trajectories over time and can play an important role in curtailing the rising trends in childhood obesity.

The relationship between changes in neighborhood physical environment and changes in physical activity among children: a prospective cohort study.

BACKGROUND: Physical activity (PA) is associated with positive health outcomes over the entire life course. Many community-based interventions that promote PA focus on implementing incremental changes to existing facilities and infrastructure. The objective of this study was to determine if such upgrades were associated with increases in children's PA. METHODS: Two cohorts of 3- to 15-year-old children (n = 599) living in 4 low-income New Jersey cities were followed during 2- to 5-year periods from 2009 to 2017. Data on children's PA were collected at 2 time points (T1 and T2) from each cohort using telephone survey of parents; data on changes to existing PA facilities were collected yearly from 2009 to 2017 using Open Public Records Act requests, publicly available data sources, and interviews with key stakeholders. PA changes were categorized into six domains (PA facility, park, trail, complete street, sidewalk, or bike lane) and coded as new opportunity, renovated opportunity, or amenity. A scale variable capturing all street-related upgrades (complete street, sidewalk, and bike lane) was constructed. PA was measured as the number of days per week the child engaged in at least 60 min of PA. The association between change in PA between T1 and T2, ranging from - 7 to + 7, and changes to the PA environment was modeled using weighted linear regression controlling for PA at T1, child age, sex, race, as well as household and neighborhood demographic and socioeconomic characteristics. RESULTS: While most measures of the changes to the PA environment were not associated with change in PA between T1 and T2, the street-related upgrades were positively associated with the change in PA; specifically, for each additional standard deviation in street upgrades within a 1-mile radius of their homes, the change in PA was 0.42 (95% CI: 0.02, 0.82; p = 0.039) additional days. This corresponds to an 11% increase over the mean baseline value (3.8 days). CONCLUSIONS: The current study supports funding of projects aimed at improving streets and sidewalks in cities, as it was shown that incremental improvements to the PA environment near children's homes will likely result in increased PA among children.

Active commuting to school: A longitudinal analysis examining persistence of behavior over time in four New Jersey cities.

Evidence suggests that healthy behaviors initiated during childhood may continue over time. The objective of this study was to determine whether active commuting to/from school (ACS) at baseline predicted continued ACS at follow-up two to five years later. Two cohorts of households with 3-15 year-olds in four low-income New Jersey cities were randomly sampled and followed for two to five year periods between 2009 and 2017. Children who walked, bicycled, or skateboarded to/from school at least one day/week were classified as active commuters. Children with complete data at both time points were included in this analysis (n = 383). Multivariate logistic regression was used to examine the association between ACS at T1 and T2. Models adjusted for child age, sex, and race/ethnicity; parent's education and nativity status (native-born vs foreign-born); household poverty level; car availability; neighborhood level characteristics; and distance from home to school. Children who engaged in ACS at T1 had over seven times the odds of ACS at T2 compared to children who did not actively commute at T1 (p < 0.001), after adjusting for distance to school and other relevant covariates. Distance, regardless of active commuting status at T1 was inversely associated with active commuting at T2. Policies and interventions encouraging ACS, and those that decrease the distance between a child's home and school, may result in increased, habitual active commuting and physical activity behavior throughout childhood and possibly into adulthood.

Access to paediatric cardiac surgery in Colombia: a population-based study.

OBJECTIVES: Globally congenital heart disease mortality is declining, yet the proportion of infant deaths attributable to heart disease rises in Colombia and other middle-sociodemographic countries. We aimed to assess the accessibility of paediatric cardiac surgery (PCS) to children <18 years of age in 2016 in the South American country of Colombia. METHODS: In Bogotá, Colombia, a multi-national team used cross-sectional and retrospective cohort study designs to adapt and evaluate 4 health system indicators at the national level: first, the population with timely geographic access to an institution providing PCS; second, the number of paediatric cardiac surgeons; third, this specialized procedure volume and its national distribution; and fourth, the 30-day perioperative mortality rate after PCS in Colombia. RESULTS: Geospatial mapping approximates 64% (n = 9 894 356) of the under-18 Colombian population lives within 2-h drivetime of an institution providing PCS. Twenty-eight cardiovascular surgeons report performing PCS, 82% (n = 23) with formal training. In 2016, 1281 PCS procedures were registered, 90% of whom were performed in 6 of the country's 32 departments. National non-risk-adjusted all-cause 30-day perioperative mortality rate after PCS was 2.73% (n = 35). CONCLUSIONS: Colombia's paediatric population had variable access to cardiac surgery in 2016, largely dependent upon geography. While the country may have the capacity to provide timely, high-quality care to those who need it, our study enables future comparative analyses to measure the impact of health system interventions facilitating healthcare equity for the underserved populations across Colombia and the Latin American region.

Differential Associations Between Changes in Food Environment and Changes in BMI Among Adults Living in Urban, Low-Income Communities.

BACKGROUND: Food environments can contribute to excess weight gain among adults, but the evidence is mixed. OBJECTIVES: This longitudinal study investigated the associations between changes in the food environment and changes in BMI in adults and whether changes in the food environment differentially impact various subgroups. METHODS: At 2 time points, BMI was calculated using self-reported height and weight data from 517 adults (mean age, 41 years) living in 4 New Jersey cities. The counts of different types of food outlets within 0.4, 0.8, and 1.6 km of respondents' residences were collected at baseline and tracked until follow-up. A binary measure of social standing (social-advantage group, n = 219; social-disadvantage group, n = 298) was created through a latent class analysis using social, economic, and demographic variables. Multivariable linear regression modeled the associations between changes in BMI with measures of the food environment; additionally, interaction terms between the measures of food environment and social standing were examined. RESULTS: Overall, over 18 months, an increase in the number of small grocery stores within 0.4 km of a respondent's residence was associated with a decrease in BMI (ß = -1.0; 95% CI: -1.9, -0.1; P = 0.024), while an increase in the number of fast-food restaurants within 1.6 km was associated with an increase in BMI (ß = 0.1; 95% CI: 0.01, 0.2; P = 0.027). These overall findings, however, masked some group-specific associations. Interaction analyses suggested that associations between changes in the food environment and changes in BMI varied by social standing. For instance, the association between changes in fast-food restaurants and changes in BMI was only observed in the social-disadvantage group (ß = 0.1; 95% CI: 0.02, 0.2; P = 0.021). CONCLUSIONS: In a sample of adults living in New Jersey, changes in the food environment had differential effects on individuals' BMIs, based on their social standing.

A granular analysis of service delivery for surgical system strengthening: Application of the Lancet indicators for policy development in Colombia.

Background: The Lancet Commission on Global Surgery (LCoGS) surgical indicators have given the surgical community metrics for objectively characterizing the disparity in access to surgical healthcare. However, aggregate national statistics lack sufficient specificity to inform strengthening plans at the community level. We performed a second-stage analysis of Colombian surgical system service delivery to inform the development of resource- and context-sensitive interventions to inform a revision of the Decennial Public Health Plan for access inequity resolution. Methods: Data from the year 2016 to inform total operative volume (TOV) and 30-day non-risk adjusted peri-operative mortality (POMR) were collected from the Colombian national health information system. TOV and POMR were sub-characterized by demographics, urgency, service line, disease pathology and facility location. Findings: In 2016, aggregate national mortality was 0·87%, while mortality attributable to elective and emergency surgery was 0·73% and 1·30%, respectively. The elderly experienced a 5·6-fold higher mortality, with 4·2% undergoing an operation within 30 days of dying. Individuals undergoing hepatobiliary, thoracic, cardiac, and neurosurgical operations experienced the highest mortality rates while obstetrics, general surgery, orthopaedics, and urology performed the largest procedure volume. Finally, analysis of operation and service line specific POMR reveals opportunities for improvement. Interpretation: This granular second-stage analysis provides actionable data which is fundamental to the development of resource and context-sensitive interventions to address gaps and inequities in surgical system service delivery. Furthermore, this analysis validates the modeling underlying development of the LCoGS indicators. These data will inform the assessment of implementation priorities and revision of the Colombian Decennial Public Health Plan. Funding: None.

Evidence That Changes in Community Food Environments Lead to Changes in Children's Weight: Results from a Longitudinal Prospective Cohort Study.

BACKGROUND: Strategies to improve the community food environment have been recommended for addressing childhood obesity, but evidence substantiating their effectiveness is limited. OBJECTIVE: Our aim was to examine the impact of changes in availability of key features of the community food environment, such as supermarkets, small grocery stores, convenience stores, upgraded convenience stores, pharmacies, and limited service restaurants, on changes in children's body mass index z scores (zBMIs). DESIGN: We conducted a longitudinal cohort study. PARTICIPANTS/SETTING: Two cohorts of 3- to 15-year-old children living in 4 low-income New Jersey cities were followed during 2- to 5-year periods from 2009 through 2017. Data on weight status were collected at 2 time points (T1 and T2) from each cohort; data on food outlets in the 4 cities and within a 1-mile buffer around each city were collected multiple times between T1 and T2. MAIN OUTCOME MEASURES: We measured change in children's zBMIs between T1 and T2. STATISTICAL ANALYSIS: Changes in the food environment were conceptualized as exposure to changes in counts of food outlets across varying proximities (0.25 mile, 0.5 mile, and 1.0 mile) around a child's home, over different lengths of time a child was exposed to these changes before T2 (12 months, 18 months, and 24 months). Multivariate models examined patterns in relationships between changes in zBMI and changes in the food environment. RESULTS: Increased zBMIs were observed in children with greater exposure to convenience stores over time, with a consistent pattern of significant associations across varying proximities and lengths of exposure. For example, exposure to an additional convenience store over 24 months within 1 mile of a child's home resulted in 11.7% higher odds (P = 0.007) of a child being in a higher zBMI change category at T2. Lower zBMIs were observed in children with increased exposure to small grocery stores selling an array of healthy items, with exposure to an additional small grocery store within 1 mile over 24 months, resulting in 37.3% lower odds (P < 0.05) of being in a higher zBMI change category at T2. No consistent patterns were observed for changes in exposure to supermarkets, limited service restaurants, or pharmacies. CONCLUSIONS: Increased availability of small grocery stores near children's homes may improve children's weight status, whereas increased availability of convenience stores is likely to be detrimental.

Use of the six core surgical indicators from the Lancet Commission on Global Surgery in Colombia: a situational analysis.

BACKGROUND: Surgical, anaesthetic, and obstetric (SAO) health-care system strengthening is needed to address the emergency and essential surgical care that approximately 5 billion individuals lack globally. To our knowledge, a complete, non-modelled national situational analysis based on the Lancet Commission on Global Surgery surgical indicators has not been done. We aimed to undertake a complete situation analysis of SAO system preparedness, service delivery, and financial risk protection using the core surgical indicators proposed by the Commission in Colombia, an upper-middle-income country. METHODS: Data to inform the six core surgical system indicators were abstracted from the Colombian national health information system and the most recent national health survey done in 2007. Geographical access to a Bellwether hospital (defined as a hospital capable of providing essential and emergency surgery) within 2 h was assessed by determining 2 h drive time boundaries around Bellwether facilities and the population within and outside these boundaries. Physical 2 h access to a Bellwether was determined by the presence of a motor vehicle suitable for individual transportation. The Department Administrativo Nacional de Estadística population projection for 2016 and 2018 was used to calculate the SAO provider density. Total operative volume was calculated for 2016 and expressed nationally per 100 000 population. The total number of postoperative deaths that occurred within 30 days of a procedure was divided by the total operative volume to calculate the all-cause, non-risk-adjusted postoperative mortality. The proportion of the population subject to impoverishing costs was calculated by subtracting the baseline number of impoverished individuals from those who fell below the poverty line once out-of-pocket payments were accounted for. Individuals who incurred out-of-pocket payments that were more than 10% of their annual household income were considered to have experienced catastrophic expenditure. Using GIS mapping, SAO system preparedness, service delivery, and cost protection were also contextualised by socioeconomic status. FINDINGS: In 2016, at least 7·1 million people (15·1% of the population) in Colombia did not have geographical access to SAO services within a 2 h driving distance. SAO provider density falls short of the Commission's minimum target of 20 providers per 100 000 population, at an estimated density of 13·7 essential SAO health-care providers per 100 000 population in 2018. Lower socioeconomic status of a municipality, as indicated by proportion of people enrolled in the subsidised insurance regime, was associated with a smaller proportion of the population in the municipality being within 2 h of a Bellwether facility, and the most socioeconomically disadvantaged municipalities often had no SAO providers. Furthermore, Colombian providers appear to be working at or beyond capacity, doing 2690-3090 procedures per 100 000 population annually, but they have maintained a relatively low median postoperative mortality of 0·74% (IQR 0·48-0·84). Finally, out-of-pocket expenses for indirect health-care costs were a key barrier to accessing surgical care, prompting 3·1 million (6·4% of the population) individuals to become impoverished and 9·5 million (19·4% of the population) individuals to incur catastrophic expenditures in 2007. INTERPRETATION: We did a non-modelled, indicator-based situation analysis of the Colombian SAO system, finding that it has not yet met, but is working towards achieving, the targets set by the Lancet Commission on Global Surgery. The observed interdependence of these indicators and correlation with socioeconomic status are consistent with well recognised factors and outcomes of social, health, and health-care inequity. The internal consistency observed in Colombia's situation analysis validates the use of the indicators and has now informed development of an early national SAO plan in Colombia, to set a data-informed stage for implementation and evaluation of timely, safe, and affordable SAO health care, within the National Public Health Decennial Plan, which is due in 2022. FUNDING: Zoll Medical.

Community food environment moderates association between health care provider advice to lose weight and eating behaviors.

Patients who receive weight loss advice from a health care provider (HCP) are more likely to eat healthy. The food environment affects eating behaviors. This study explored how the community food environment may moderate the relationship between HCP advice to lose weight and eating behaviors. Data were obtained from a household telephone survey in 4 New Jersey cities from two cross-sectional panels (2009-10 and 2014). Analyses were limited to 1427 overweight and obese participants. Self-reports assessed frequency of consumption of fruits, vegetables, sugar sweetened beverages, and fast food. Community food data were purchased from InfoUSA and Nielsen and classified according to previously established protocol. Stratified gamma regression analysis determined the differences in the association between receiving weight loss advice and eating behaviors stratified by community food environment. Stratified analyses revealed that receiving advice to lose weight from a HCP was associated with lower reported consumption of total sugar-sweetened beverages, soda, and sweetened fruit drinks when participants lived near a small grocery store, or far from a supermarket, limited service restaurant, or convenience store. There were no associations between receiving weight loss advice and sugar sweetened beverage consumption when participants lived near supermarkets, limited service restaurants, or convenience stores. There were no associations with fruit, vegetable, salad or fast-food consumption, regardless of the community food environment. Food environment may play a critical role in moderating the association between HCP advice and eating behaviors. Interventions that enhance the community food environment may help convert HCP advice into improved eating behaviors.

Healthy Food Access in Low-Income High-Minority Communities: A Longitudinal Assessment-2009-2017.

Disparities in healthy food access are well documented in cross-sectional studies in communities across the United States. However, longitudinal studies examining changes in food environments within various neighborhood contexts are scarce. In a sample of 142 census tracts in four low-income, high-minority cities in New Jersey, United States, we examined the availability of different types of food stores by census tract characteristics over time (2009-2017). Outlets were classified as supermarkets, small grocery stores, convenience stores, and pharmacies using multiple sources of data and a rigorous protocol. Census tracts were categorized by median household income and race/ethnicity of the population each year. Significant declines were observed in convenience store prevalence in lower- and medium-income and majority black tracts (p for trend: 0.004, 0.031, and 0.006 respectively), while a slight increase was observed in the prevalence of supermarkets in medium-income tracts (p for trend: 0.059). The decline in prevalence of convenience stores in lower-income and minority neighborhoods is likely attributable to declining incomes in these already poor communities. Compared to non-Hispanic neighborhoods, Hispanic communities had a higher prevalence of small groceries and convenience stores. This higher prevalence of smaller stores, coupled with shopping practices of Hispanic consumers, suggests that efforts to upgrade smaller stores in Hispanic communities may be more sustainable.

Participation in the Supplemental Nutrition Assistance Program and Dietary Behaviors: Role of Community Food Environment.

BACKGROUND: The United States Department of Agriculture's Supplemental Nutrition Assistance Program (SNAP) is the country's largest nutrition assistance program for low-income populations. Although SNAP has been shown to reduce food insecurity, research findings on the diet quality of program participants are inconsistent. OBJECTIVE: This study evaluated whether the community food environment is a potential moderator of the association between SNAP participation and eating behaviors. DESIGN: This cross-sectional study used participant data from a telephone survey of 2,211 households in four cities in New Jersey. Data were collected from two cross-sectional panels from 2009 to 2010 and 2014. Food outlet data were purchased from commercial sources and classified as supermarkets, small grocery stores, convenience stores, or limited service restaurants. PARTICIPANTS/SETTING: Analysis is limited to 983 respondents (588 SNAP participants) with household incomes below 130% of the federal poverty level. MAIN OUTCOME MEASURES: Eating behaviors were assessed as frequency of consumption of fruit, vegetables, salad, and sugar-sweetened beverages. STATISTICAL ANALYSES PERFORMED: Interaction and stratified analyses using gamma regression determined the differences in the association between SNAP participation and eating behaviors by the presence or absence of food outlets adjusted for covariates. RESULTS: SNAP participation was associated with a higher frequency of consuming sugar-sweetened beverages (P<0.05) when respondents lived within » to ½ mile of a small grocery store, supermarket, and limited service restaurant. SNAP participants who did not live close to a convenience store reported a lower frequency of sugar-sweetened beverage consumption (P=0.01), and those living more than ½ mile away from a supermarket reported a lower frequency of fruit consumption (P=0.03). CONCLUSIONS: The findings from this study suggest that the community food environment may play a role in moderating the association between SNAP participation and eating behaviors. Although SNAP participation is associated with some unhealthy behaviors, this association may only hold true when respondents live in certain food environments.

Assessing and Mapping the Availability of the Female Condom in the Philadelphia Metropolitan Area.

This study assessed and mapped the availability of the female condom in relation to the male condom and HIV prevalence in the Philadelphia metropolitan area, which has a high density of HIV. One percent of the 1228 service providers contacted sold/provided the female condom and 77 % sold/provided the male condom. The lack of availability of the female condom suggests this product will have no public health impact on reducing HIV and that interventions that promote use of the female condom are not sustainable in this high-risk area. Our findings may help policy makers increase female condom availability in this area.

Medical Students and informed consent: A consensus statement prepared by the Faculties of Medical and Health Science of the Universities of Auckland and Otago, Chief Medical Officers of District Health Boards, New Zealand Medical Students' Association and the Medical Council of New Zealand.

To develop a national consensus statement to promote a pragmatic, appropriate and unified approach to seeking consent for medical student involvement in patient care. A modified Delphi technique was used to develop the consensus statement involving stakeholders. Feedback from consultation and each stakeholder helped to shape the final consensus statement. The consensus statement is a nationally-agreed statement concerning medical student involvement in patient care, which will be useful for medical students, health care professionals and patients.

Associations between food environment around schools and professionally measured weight status for middle and high school students.

BACKGROUND: Obesity rates among school-age children remain high. Access to energy-dense foods at home, in schools, in stores, and restaurants around homes and schools is of concern. Research on the relationship between food environment around schools and students' weight status is inconclusive. This study examines the association between weight status of middle and high school students and proximity to a comprehensive set of food outlets around schools. METHODS: Deidentified nurse-measured heights and weights data were obtained for 12,954 middle and high school students attending 33 public schools in four low-income communities in New Jersey. Geocoded locations of supermarkets, convenience stores, small grocery stores, and limited-service restaurants were obtained from commercial sources. Random-effect regression models with robust standard errors were developed to adjust for unequal variances across schools and clustering of students within schools. RESULTS: Proximity to small grocery stores that offered some healthy options (e.g., five fruits, five vegetables, and low-fat/skim milk) and supermarkets was associated with healthier student weight status. Having a small grocery store within 0.25 mile of school and an additional such store within that radius was associated with a lower BMI z-score (p<0.05). An additional supermarket within 0.25 mile of schools was associated with a lower probability of being overweight/obese (p<0.05). CONCLUSIONS: Improving access to healthy food outlets, such as small stores, that offer healthy food options and supermarkets around middle and high schools is a potential strategy for improving weight outcomes among students.

Neighborhood perceptions and active school commuting in low-income cities.

BACKGROUND: Few children accumulate the recommended ≥60 minutes of physical activity each day. Active travel to and from school (ATS) is a potential source of increased activity for children, accounting for 22% of total trips and time spent traveling by school-aged children. PURPOSE: This study identifies the association of parents' perceptions of the neighborhood, geospatial variables, and demographic characteristics with ATS among students in four low-income, densely populated urban communities with predominantly minority populations. METHODS: Data were collected in 2009-2010 from households with school-attending children in four low-income New Jersey cities. Multivariate logistic regression analyses (n=765) identified predictors of ATS. Analyses were conducted in 2012. RESULTS: In all, 54% of students actively commuted to school. Students whose parents perceived the neighborhood as very unpleasant for activity were less likely (OR=0.39) to actively commute, as were students living farther from school, with a 6% reduction in ATS for every 0.10 mile increase in distance to school. Perceptions of crime, traffic, and sidewalk conditions were not predictors of ATS. CONCLUSIONS: Parents' perceptions of the pleasantness of the neighborhood, independent of the effects of distance from school, may outweigh concerns about crime, traffic, or conditions of sidewalks in predicting active commuting to school in the low-income urban communities studied. Efforts such as cleaning up graffiti, taking care of abandoned buildings, and providing shade trees to improve neighborhood environments are likely to increase ATS, as are efforts that encourage locating schools closer to the populations they serve.

A closer examination of the relationship between children's weight status and the food and physical activity environment.

OBJECTIVES: Conflicting findings on associations between food and physical activity (PA) environments and children's weight status demand attention in order to inform effective interventions. We assess relationships between the food and PA environments in inner-city neighborhoods and children's weight status and address sources of conflicting results of prior research. METHODS: Weight status of children ages 3-18 was assessed using parent-measured heights and weights. Data were collected from 702 children living in four low-income cities in New Jersey between 2009 and 2010. Proximity of a child's residence to a variety of food and PA outlets was measured in multiple ways using geo-coded data. Multivariate analyses assessed the association between measures of proximity and weight status. RESULTS: Significant associations were observed between children's weight status and proximity to convenience stores in the 1/4 mile radius (OR = 1.9) and with presence of a large park in the 1/2 mile radius (OR = 0.41). No associations were observed for other types of food and PA outlets. CONCLUSIONS: Specific aspects of the food and PA environments are predictors of overweight and obese status among children, but the relationships and their detection are dependent upon aspects of the geospatial landscape of each community.

Trends in reporting Gleason score 1991 to 2001: changes in the pathologist's practice.

OBJECTIVE: The prostate specific antigen (PSA) era has been associated with a grade migration towards moderately-differentiated (Gleason 5-7) prostate cancer. We investigated whether changes in interpretation of the Gleason system could be a contributing factor by reviewing the Gleason scores for prostate cancer in our region. PATIENTS AND METHODS: Records of patients with prostate cancer assigned a Gleason score between 1991-2001 were retrospectively reviewed. We analysed trends in Gleason score, method of diagnosis and age at diagnosis. Following this, 50 cases from the dataset were randomly selected (stratified to contain half Gleason 2-4 reports) and reviewed in a blinded manner by an uropathologist and given a new Gleason score. RESULTS: 2737 patients were diagnosed and given a Gleason score; 1484 by prostate biopsy (PB) and 1172 by transurethral resection of prostate (TURP). 273 radical prostatectomy (RP) specimens were received, although the results of pre-operative biopsies were available in only 192 of these patients. Over time, there was an increase in the proportion of patients with Gleason 5-7, and a significant decrease in reporting of Gleason 2-4 cancer (r2 = 0.81, p < 0.0001). In 1991, 24% of cancers were Gleason 2-4; in 2001 this had decreased to 2.4%. TURP was associated with more Gleason 2-4 reports (23%) compared with PB (13.2%) and RP (9.2%). On blinded review, all Gleason 2-4 reports were upgraded to Gleason 5-7 cancer (p < 0.001). CONCLUSION: Over time, the proportion of Gleason 2-4 prostate cancer reported has significantly decreased. Our study suggests that a change in practice by the pathologist is a significant factor in this grade migration.

Nitric oxide donating nonsteroidal anti-inflammatory drugs induce apoptosis in human prostate cancer cell systems and human prostatic stroma via caspase-3.

PURPOSE: New nitric oxide (NO) donating nonsteroidal anti-inflammatory drugs (NSAIDs) have been synthesized to counteract the side effects of conventional NSAIDs. Mounting evidence suggests that NSAIDs may have a possible chemopreventative/therapeutic role in prostate cancer. NO is a powerful biological messenger with multiple cellular effects. We established the effects of 2 of these new drugs in prostate cell systems. MATERIALS AND METHODS: We studied the effects of NO-ibuprofen (NCX 2111) and NO-aspirin (NCX 4060) on hormone sensitive (LNCap) and insensitive (PC3) prostate cancer epithelial cell lines as well as primary cultures of prostatic stroma. Proliferation was measured using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazalium bromide) assay to examine proliferation. Subsequently flow cytometry, cell cycle analysis and TUNEL staining were used to look for apoptosis. Caspase-3 expression was also examined in treated cell types. RESULTS: NCX 2111 and NCX 4060 were found to be potent inhibitors of proliferation in a dose dependent fashion. The 2 drugs induced apoptosis, as seen by flow cytometry, cell cycle analysis and TUNEL staining, at doses between 10 and 100 microM. These NO-NSAIDs increased caspase-3 expression. NCX 4060 was more effective at lower concentrations (10 microM) but each compound was much more potent than conventional ibuprofen and aspirin at inducing apoptosis and inhibiting proliferation. CONCLUSIONS: NO-NSAIDs are potent antiproliferative pro-apoptotic compounds in prostate cell systems. This pro-apoptotic effect is mediated via caspase-3 and it is independent of the type of prostate cell used. These findings have ramifications for the use of these new drugs in prostate cancer chemoprevention or treatment.