Ravi Maheswaran

The health benefits of urban green spaces: a review of the evidence

BACKGROUND Urban development projects can be costly and have health impacts. An evidence-based approach to urban planning is therefore essential. However, the evidence for physical and non-physical health benefits of urban green space is unclear. METHODS A literature search of academic and grey literature was conducted for studies and reviews of the health effects of green space. Articles found were appraised for their relevance, critically reviewed and graded accordingly. Their findings were then thematically categorized. RESULTS There is weak evidence for the links between physical, mental health and well-being, and urban green space. Environmental factors such as the quality and accessibility of green space affects its use for physical activity. User determinants, such as age, gender, ethnicity and the perception of safety, are also important. However, many studies were limited by poor study design, failure to exclude confounding, bias or reverse causality and weak statistical associations. CONCLUSION Most studies reported findings that generally supported the view that green space have a beneficial health effect. Establishing a causal relationship is difficult, as the relationship is complex. Simplistic urban interventions may therefore fail to address the underlying determinants of urban health that are not remediable by landscape redesign.

Stroke Mortality Associated With Living Near Main Roads in England and Wales: A Geographical Study

Background and Purpose— Air pollution is associated with stroke, and road traffic is a major source of outdoor air pollution. Using proximity to roads as a proxy for exposure to road traffic pollution, we examined the hypothesis that living near main roads increases the risk of stroke mortality. Methods— We used a small-area ecological study design based on 113 465 census enumeration districts in England and Wales. Stroke mortality (International Classification of Disease, 9th revision, codes 430 through 438) in England and Wales from 1990 to 1992 for people ≥45 years of age was examined through the use of 1991 population denominators. Exposure was calculated as distance from each enumeration district population centroid to the nearest main road. We adjusted for age, sex, socioeconomic deprivation (using Carstairs index), regional variation, urbanization, and metropolitan area using Poisson regression. Results— The analysis was based on 189 966 stroke deaths and a population of 19 083 979. After adjustment for potential confounders, stroke mortality was 7% (95% confidence interval [CI], 4 to 9) higher in men living within 200 m of a main road compared with men living ≥1000 m away. The corresponding increase in risk for women was 4% (95% CI, 2 to 6) and the risk for men and women combined was 5% (95% CI, 4 to 7). These raised risks diminished with increasing distance from main roads. Conclusions— Living near main roads is associated with excess risk of mortality from stroke, and if causality were assumed, ≈990 stroke deaths per year would have been attributable to road traffic pollution.

Socioeconomic deprivation, travel distance, location of service, and uptake of breast cancer screening in North Derbyshire, UK

Background and aim: This study examined the association between socioeconomic deprivation, travel distance, urban-rural status, location and type of screening unit, and breast screening uptake. Screening was provided at 13 locations—1 fixed and 12 mobile (3 at non-health locations). Methods: The study examined data from 1998 to 2001 for 34 868 women aged 50–64 years, calculated road travel distance, used 1991 enumeration district level Townsend socioeconomic deprivation scores, and a ward level urban-rural classification. Results: Odds of attendance for screening decreased with increasing socioeconomic deprivation, with an adjusted odds ratio of 0.64 (95%CI 0.59 to 0.70) in the most deprived relative to the least deprived category. 87% of women lived within 8 km of their screening location. The odds ratio for a 10 km increase in distance was 0.87 (95%CI 0.79 to 0.95). The odds ratios were 1.18 (95%CI 1.08 to 1.28) for screening at a non-health relative to a health location, 1.00 (95%CI 0.94 to 1.07) for the fixed site relative to the mobile unit and 1.00 (95%CI 0.91 to 1.09) for mainly rural relative to mainly urban areas. Conclusions: Socioeconomic inequality in breast screening uptake seems to persist in an established service. There was a small decrease with increasing distance, no difference between fixed and mobile units, and no difference between urban and rural areas but uptake seemed to be higher at non-health sites. Further work is needed to identify effective methods of decreasing socioeconomic inequalities in uptake and to confirm if non-health locations are associated with higher screening uptake.

Outdoor Air Pollution and Stroke in Sheffield, United Kingdom: A Small-Area Level Geographical Study

Background and Purpose— Current evidence suggests that stroke mortality and hospital admissions should be higher in areas with elevated levels of outdoor air pollution because of the combined acute and chronic exposure effects of air pollution. We examined this hypothesis using a small-area level ecological correlation study. Methods— We used 1030 census enumeration districts as the unit of analysis and examined stroke deaths and hospital admissions from 1994 to 1998, with census denominator counts for people ≥45 years. Modeled air pollution data for particulate matter (PM10), nitrogen oxides (NOx), and carbon monoxide (CO) were interpolated to census enumeration districts. We adjusted for age, sex, socioeconomic deprivation, and smoking prevalence. Results— The analysis was based on 2979 deaths, 5122 admissions, and a population of 199 682. After adjustment for potential confounders, stroke mortality was 37% (95% CI, 19 to 57), 33% (95% CI, 14 to 56), and 26% (95% CI, 10 to 46) higher in the highest, relative to the lowest, NOx, PM10, and CO quintile categories, respectively. Corresponding increases in risk for admissions were 13% (95% CI, 1 to 27), 13% (95% CI, −1 to 29), and 11% (95% CI, −1 to 25). Conclusion— The results are consistent with an excess risk of stroke mortality and, to a lesser extent, hospital admissions in areas with high outdoor air pollution levels. If causality were assumed, 11% of stroke deaths would have been attributable to outdoor air pollution. Targeting policy interventions at high pollution areas may be a feasible option for stroke prevention.

Variation within Genes Encoding Interleukin-1 and the Interleukin-1 Receptor Antagonist Influence the Severity of Meningococcal Disease

Context Prognoses of patients with meningococcal disease vary widely. Patients with severe disease may have unusually high levels of proinflammatory cytokines, such as interleukin-1. The release of such cytokines may be genetically determined. Contribution This genotype study of 1106 British patients with meningococcal disease found that carrying the common allele of one of the interleukin-1 genes (IL1B) was associated with increased likelihood of survival. Among patients carrying this allele, those who also carried the rare allele of another interleukin-1 gene (IL1RN) had a decreased likelihood of survival. Implications Genotype at the interleukin-1 gene cluster influences likelihood of survival from meningococcal disease. The Editors In the sepsis syndrome, patients with severe manifestations exhibit maladaptive proinflammatory cytokine release with unusually high plasma concentrations of cytokines (1). Meningococcal disease is an example of gram-negative sepsis in which the prognosis varies widely among patients. The mortality rate of meningococcal disease ranges from 5% to 20%, depending on whether patients present with predominant features of meningitis or septicemia (2); in patients with purpura fulminans, the mortality rate can be as high as 50% (3). The host cytokine response in meningococcal disease is genetically determined (4); lipopolysaccharide-stimulated peripheral monocytes derived from first-degree relatives of patients who have died of meningococcal disease exhibit low tumor necrosis factor (TNF) and high interleukin (IL)-10 release compared with monocytes derived from first-degree relatives of survivors. Interleukin-1, together with TNF, is a central, early, and highly inflammatory mediator of the innate response to bacterial challenge (5). Unusually high levels of IL-1 and its endogenous antagonist IL-1 receptor antagonist (IL-1ra) can be detected in patients with meningococcal disease, particularly those with severe manifestations (6). The IL-1 gene cluster on chromosome 2q contains three related genes within a 430-kilobase region (IL1A, IL1B, and IL1RN), which encode IL-1, IL-1, and IL-1ra (Figure 1) (7, 8). A single nucleotide polymorphism (SNP) is present within IL1B 511 nucleotides upstream of the transcriptional start site (IL1B[511]), which is in 99.5% linkage disequilibrium with another at position (31). This SNP at (31) affects the transcription-initiation complex of IL1B (9, 10). Also, the IL1RN gene contains a variable-number tandem repeat (VNTR) (denoted as IL1RN*2), which is in linkage disequilibrium with several polymorphisms in IL1RN, including one at position +2018 within exon 2 (11, 12) (Glossary). In the general white population, the frequency of the rarer alleles of the SNPs is 33% at IL1B(511) and 28% at IL1RN(+2018) (9, 11). In a previous study that we conducted, a relatively small number of patients with meningococcal disease had genotyping at various loci across the IL-1 gene cluster (13). We showed that the genotype at IL1B(511) had some association with likelihood of death from meningococcal disease; IL1RN(+2018) possibly contributed to the effect. We now examine DNA derived from a separate and much larger group of patients with microbiologically confirmed meningococcal disease to retest the association with these two SNPs. Figure 1. The interleukin-1 ( IL-1 ) gene cluster. kb IL1A IL1B IL1RN IL1B IL1B IL1RN VNTR Methods Patients The Meningococcal Reference Unit (MRU) for England and Wales offers a service for polymerase chain reaction (PCR) detection of Neisseria meningitidis in blood and cerebrospinal fluid (CSF) samples from patients with suspected meningococcal disease in addition to culture confirmation of disease. From July 1998 to November 1999, we archived all whole blood samples from patients who were subsequently confirmed to have meningococcal disease, either by culture or by PCR detection of N. meningitidis in blood or CSF. Demographic and clinical information relating to the samples was obtained from the submitting clinical team and confirmed by the Consultant in Communicable Disease Control of the relevant District Health Authority. To estimate socioeconomic status of patients, each was assigned a Townsend deprivation score on the basis of his or her residential post code, if available. This score is derived from four variables measured in the 1991 United Kingdom National Census: proportion of economically active residents unemployed, households without a car, households not owner occupied, and households overcrowded (14). Each enumeration district typically comprises a neighborhood of 200 to 400 people. A Townsend deprivation score of high positive indicates low economic status, and a negative score indicates high economic status. After clinical information had been collated, we coded samples so that patients could no longer be identified. DNA from 839 northern English blood donors (age range, 18 to 65 years) was used as a noninfected control sample. Blood donors in the United Kingdom are unpaid volunteers. The Ethics Committees of the Public Health Laboratory Service for England and Wales and of the South Sheffield Health District reviewed the study. The final protocols approved by the committees were adhered to throughout the study. Laboratory Methods DNA was extracted from whole blood samples by standard methods. We probed for two SNPs: IL1B(511) and IL1RN(+2018) using a validated 5 nuclease assay (TaqMan probe) allelic discrimination test (Applied Biosystems, Foster City, California). Probes, primer sequences, and cycling conditions have been previously published (12). We indicate the frequent allele of each gene variant as 1 and the rarer allele as 2, as is standard nomenclature. Homozygosity is indicated as 1/1 or 2/2, and heterozygosity is indicated as 1/2. Carriage of one particular allele is indicated, for example, as 2+ for the rarer allele, meaning that patients were either 2/2 or 1/2; lack of carriage is denoted as 1 or 2. Statistical Analysis The chi-square test was used for preliminary analysis of carriage of a specific allele, unless otherwise stated. Logistic regression analysis was used to elucidate interactions between genotypes, age, infecting serogroup, and Townsend deprivation score. Stata software, version 6 (Stata Corp., College Station, Texas), was used for statistical analyses. Role of the Funding Source The funding source had no role in the design, conduct, or reporting of the study or in the decision to submit the manuscript for publication. Results Patients and Microbiological and Demographic Data During the study period, 4620 cases of meningococcal disease occurring throughout England and Wales were notified to the Office for National Statistics on the basis of clinical or laboratory diagnosis; 3502 cases were verified by the MRU by culture or PCR detection of N. meningitidis in blood or CSF (Figure 2). During the same period, 2807 whole blood samples were received by the MRU for PCR detection of N. meningitidis because of suspected meningococcal infection. Among this group, we identified 1106 patients with meningococcal disease confirmed by culture or PCR (39% confirmed by culture, 25% by PCR, and 36% by both culture and PCR). Of the DNA samples, 91 were from patients who died and 1015 were from patients who survived. The mean (SD) age of patients who died (22.2 2.5 years; median, 15 years [range, 0 to 82 years]) was significantly higher than that of patients who survived (12.2 0.5 years; median, 6 years [range, 0 to 84 years]) (P = 0.002; MannWhitney U test) (Table 1). Children between 4 and 11 years of age made up 18.2% of all cases but only 6.6% of all deaths. In contrast, 3.5% of cases were in adults between 60 and 84 years of age, but this group made up 12.1% of all deaths within this cohort. Figure 2. The Meningococcal Reference Unit confirms the identity of all Neisseria meningitidis isolates recovered from blood and cerebrospinal fluid at hospitals throughout England and Wales and also receives blood samples for polymerase chain reaction ( PCR N. meningitidis. N. meningitidis Table 1. Characteristics of Patients Who Survived and Those Who Died Postal codes were available for 729 patients who survived and 75 patients who died. These were used to calculate a Townsend deprivation score for each patient (Table 1), which revealed a wide range of patient socioeconomic status. Table 1 also shows the serogroups of N. meningitidis causing disease in this cohort. As expected for a sample collected in England and Wales during this period, most patients in whom a serogroup was identified were infected with serogroup B; most of the remaining patients were infected with serogroup C. Among patients who died, 52% were infected with serogroup C; in contrast, 33% of survivors were infected with this serogroup. Effect of Interleukin Genotype on Likelihood of Infection Table 2 shows the genotypes of patients with meningococcal disease who died and those who survived, as well as genotypes of blood donor controls. Most of the whole blood samples were successfully genotyped for both markers. Table 2. Genotype Distribution forIL1B(511) andIL1RN(+2018) Chi-square analysis indicated a significant overall relationship between the distributions of both IL1B(511) and IL1RN(+2018) among patients who survived, patients who died, and blood donor controls (Table 2). However, when the genotypes of all patients with meningococcal disease (patients who survived and died combined) were compared with the genotypes of blood donor controls, the representation of IL1B(511) (P = 0.11) and of IL1RN(+2018) (P = 0.15) did not differ. This suggested that these polymorphisms are equally represented in the general population and in patients with meningococcal disease and that they do not influence the likelihood of disease. In contrast, preliminary analysis suggested some effect at both markers on likelihood of death among patients with meningococcal disease. E

Is smoking tobacco an independent risk factor for HIV infection and progression to AIDS? A systemic review.

Objectives: To systematically review the evidence of the relation between smoking tobacco and HIV seroconversion and progression to AIDS. Methods: A systematic review was undertaken of studies to look at tobacco smoking as a risk factor for either HIV seroconversion or progression to AIDS. Results: Six studies were identified with HIV seroconversion as an outcome measure. Five of these indicated that smoking tobacco was an independent risk factor after adjusting for important confounders with adjusted odds ratios ranging from 1.6 to 3.5. 10 studies were identified using progression to AIDS as an end point of which nine found no relation with tobacco smoking. Conclusions: Tobacco smoking may be an independent risk factor for HIV infection although residual confounding is another possible explanation. Smoking did not appear to be related to progression to AIDS although this finding may not be true in developing countries or with the longer life expectancies seen with highly active antiretroviral therapy.

Socioeconomic deprivation, urban-rural location and alcohol-related mortality in England and Wales

BackgroundMany causes of death are directly attributable to the toxic effects of alcohol and deaths from these causes are increasing in the United Kingdom. The aim of this study was to investigate variation in alcohol-related mortality in relation to socioeconomic deprivation, urban-rural location and age within a national context.MethodsAn ecological study design was used with data from 8797 standard table wards in England and Wales. The methodology included using the Carstairs Index as a measure of socioeconomic deprivation at the small-area level and the national harmonised classification system for urban and rural areas in England and Wales. Alcohol-related mortality was defined using the National Statistics definition, devised for tracking national trends in alcohol-related deaths. Deaths from liver cirrhosis accounted for 85% of all deaths included in this definition. Deaths from 1999-2003 were examined and 2001 census ward population estimates were used as the denominators.ResultsThe analysis was based on 28,839 deaths. Alcohol-related mortality rates were higher in men and increased with increasing age, generally reaching peak levels in middle-aged adults. The 45-64 year age group contained a quarter of the total population but accounted for half of all alcohol-related deaths. There was a clear association between alcohol-related mortality and socioeconomic deprivation, with progressively higher rates in more deprived areas. The strength of the association varied with age. Greatest relative inequalities were seen amongst people aged 25-44 years, with relative risks of 4.73 (95% CI 4.00 to 5.59) and 4.24 (95% CI 3.50 to 5.13) for men and women respectively in the most relative to the least deprived quintiles. People living in urban areas experienced higher alcohol-related mortality relative to those living in rural areas, with differences remaining after adjustment for socioeconomic deprivation. Adjusted relative risks for urban relative to rural areas were 1.35 (95% CI 1.20 to 1.52) and 1.13 (95% CI 1.01 to 1.25) for men and women respectively.ConclusionsLarge inequalities in alcohol-related mortality exist between sub-groups of the population in England and Wales. These should be considered when designing public health policies to reduce alcohol-related harm.

Magnesium in drinking water supplies and mortality from acute myocardial infarction in north west England

OBJECTIVES To examine whether higher concentrations of magnesium in drinking water supplies are associated with lower mortality from acute myocardial infarction at a small area geographical level; to examine if the association is modified by age, sex, and socioeconomic deprivation. DESIGN Small area geographical study using 13 794 census enumeration districts. Water constituent concentrations (magnesium, calcium, fluoride, lead) measured at water supply zone and assigned to enumeration districts. SETTING 305 water supply zones in north west England. SUBJECTS Resident population of 1 124 623 men and 1 372 036 women (1991 census) aged 45 years or more. MAIN OUTCOME MEASURE Mortality from acute myocardial infarction, International Classification of Diseases, ninth revision (ICD-9) 410. Subsidiary analysis examined deaths from ischaemic heart disease, ICD 410–414. RESULTS There were 21 339 male and 17 883 female deaths from acute myocardial infarction in 1990–92. Drinking water magnesium concentrations in water zones ranged from 2 mg/l to 111 mg/l (mean (SD) 19 (20) mg/l, median 12 mg/l); 24% of variation in magnesium concentrations was within zone and 76% was between zone. The relative risk of mortality from acute myocardial infarction (standardised for age, sex, and Carstairs deprivation quintile) for a quadrupling of magnesium concentrations in drinking water (for example, 20 mg/l v5 mg/l) was 1.01 (95% confidence interval (CI) 0.99 to 1.03). When adjusted for north-south and east-west trends in mortality from acute myocardial infarction and for drinking water calcium, fluoride, and lead concentrations, this relative risk was 1.01 (95% CI 0.96 to 1.06). There was no evidence of a protective effect for acute myocardial infarction even among age, sex, and deprivation groups that were likely to be relatively magnesium deficient. For ischaemic heart disease mortality there was an apparent protective effect of magnesium and calcium (with calcium predominating in the joint model), but these were no longer significant when the geographical trends were incorporated. CONCLUSIONS No evidence was found of an association between magnesium concentrations in drinking water supplies and mortality from acute myocardial infarction. These results do not support the hypothesis that magnesium is the key water factor in relation to mortality from heart disease.

Developing a summary hospital mortality index: retrospective analysis in English hospitals over five years

Objectives To develop a transparent and reproducible measure for hospitals that can indicate when deaths in hospital or within 30 days of discharge are high relative to other hospitals, given the characteristics of the patients in that hospital, and to investigate those factors that have the greatest effect in changing the rank of a hospital, whether interactions exist between those factors, and the stability of the measure over time. Design Retrospective cross sectional study of admissions to English hospitals. Setting Hospital episode statistics for England from 1 April 2005 to 30 September 2010, with linked mortality data from the Office for National Statistics. Participants 36.5 million completed hospital admissions in 146 general and 72 specialist trusts. Main outcome measures Deaths within hospital or within 30 days of discharge from hospital. Results The predictors that were used in the final model comprised admission diagnosis, age, sex, type of admission, and comorbidity. The percentage of people admitted who died in hospital or within 30 days of discharge was 4.2% for males and 4.5% for females. Emergency admissions comprised 75% of all admissions and 5.5% died, in contrast to 0.8% who died after an elective admission. The percentage who died with a Charlson comorbidity score of 0 was 2% in contrast with 15% who died with a score greater than 5. Given these variables, the relative standardised mortality rates of the hospitals were not noticeably changed by adjusting for the area level deprivation and number of previous emergency visits to hospital. There was little evidence that including interaction terms changed the relative values by any great amount. Using these predictors the summary hospital mortality index (SHMI) was derived. For 2007/8 the model had a C statistic of 0.911 and accounted for 81% of the variability of between hospital mortality. A random effects funnel plot was used to identify outlying hospitals. The outliers from the SHMI over the period 2005-10 have previously been identified using other mortality indicators. Conclusion The SHMI is a relatively simple tool that can be used in conjunction with other information to identify hospitals that may need further investigation.

Socioeconomic deprivation, ethnicity, and stroke mortality in Greater London and south east England.

OBJECTIVE AND SETTING: To examine geographical variation in stroke mortality in Greater London compared with the surrounding South East Region of England. DESIGN: Cross sectional, ecological analysis based on electoral wards. SUBJECTS: Resident population aged 45 years or more. MAIN OUTCOME MEASURE: Age specific stroke mortality rates in five age bands, 1986-92. MAIN OUTCOME MEASURE: Age specific stroke mortality rates in five age bands, 1986-92. MAIN RESULTS: In the 45-54 years age band, stroke mortality rate ratios (95% confidence intervals) relative to the surrounding south east were 2.09 (1.81, 2.4) for Inner London and 1.31 (1.15, 1.5) for Outer London for men and 1.64 (1.4, 1.93) and 1.13 (0.98, 1.31) respectively for women. This gradient diminished and reversed with increasing age. In the 85+ age band, rate ratios were 0.82 (0.76, 0.89) for Inner London and 0.89 (0.84, 0.94) for Outer London for men and 0.8 (0.75, 0.85) and 0.88 (0.84, 0.92) respectively for women. Carstairs deprivation index and the percentages of Afro-Caribbean men and women and Irish born men were significantly and positively correlated with stroke mortality at the ward level. The Carstairs effect diminished with increasing age. Adjustment for these variables diminished or abolished the higher stroke mortality risks in London for younger people but had little effect on the lower risks for older Londoners. CONCLUSIONS: Higher rates of stroke mortality among middle aged adults in Greater London, compared with the surrounding South East Region, are associated with socioeconomic deprivation and ethnicity. These factors do not explain the relatively lower stroke mortality among older Londoners.