Epidemiology and management of fetal and neonatal alloimmune thrombocytopenia.

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a disease in pregnancy characterized by maternal alloantibodies directed against the human platelet antigen (HPA). These antibodies can cause intracranial hemorrhage (ICH) or other major bleeding resulting in lifelong handicaps or death. Optimal fetal care can be provided by timely identification of pregnancies at risk. However, this can only be done by routinely antenatal screening. Whether nationwide screening is cost-effective is still being debated. HPA-1a alloantibodies are estimated to be found in 1 in 400 pregnancies resulting in severe burden and fetal ICH in 1 in 10.000 pregnancies. Antenatal treatment is focused on the prevention of fetal ICH and consists of weekly maternal IVIg administration. In high-risk FNAIT treatment should be initiated at 12-18 weeks gestational age using high dosage and in standard-risk FNAIT at 20-28 weeks gestational age using a lower dosage. Postnatal prophylactic platelet transfusions are often given in case of severe thrombocytopenia to prevent bleedings. The optimal threshold and product for postnatal transfusion is not known and international consensus is lacking. In this review practical guidelines for antenatal and postnatal management are offered to clinicians that face the challenge of reducing the risk of bleeding in fetuses and infants affected by FNAIT.

Burden of neurodegenerative diseases in the Eastern Mediterranean Region, 1990-2016: findings from the Global Burden of Disease Study 2016.

BACKGROUND AND PURPOSE: The Eastern Mediterranean Region (EMR) is experiencing a demographic shift towards rapid aging at a time of political unrest. We aimed to estimate the burden of neurodegenerative disorders and its relationship with sociodemographic index in the EMR countries from 1990 to 2016. METHODS: Using data from the Global Burden of Disease Study 2016, we calculated country-specific trends for prevalence, mortality, disability-adjusted life-years (DALY), years of life lost and years lived with disability (YLD) for Alzheimer's disease/other dementias and Parkinson's disease in the EMR during 1990-2016. RESULTS: In the EMR, the age-standardized prevalence rate of Alzheimer's disease/other dementias and Parkinson's disease was estimated at 759.8/100 000 (95% uncertainty intervals, 642.9-899.9) and 87.1/100 000 (95% uncertainty intervals, 69.8-108.2) people in 2016, demonstrating 0.01% and 42.3% change from 1990, respectively. Neurodegenerative disorders contributed to 5.4% of total DALY and 4.6% of total YLD among the older EMR population (70 years of age or older in 2016). Age-standardized DALY due to Parkinson's disease were strongly correlated with the sociodemographic index level (r = 0.823, P < 0.001). The YLD:DALY ratio of neurodegenerative diseases declined during this period in the low-income but not the high-income EMR countries. CONCLUSIONS: Our findings demonstrated an increasing trend in the burden of dementias and Parkinson's disease in most EMR countries between 1990 and 2016. With aging of the EMR populations, countries should target the modifiable risk factors of neurodegenerative diseases to control their increasing burden.

Global, Regional, and National Prevalence, Incidence, and Disability-Adjusted Life Years for Oral Conditions for 195 Countries, 1990-2015: A Systematic Analysis for the Global Burden of Diseases, Injuries, and Risk Factors.

The Global Burden of Disease 2015 study aims to use all available data of sufficient quality to generate reliable and valid prevalence, incidence, and disability-adjusted life year (DALY) estimates of oral conditions for the period of 1990 to 2015. Since death as a direct result of oral diseases is rare, DALY estimates were based on years lived with disability, which are estimated only on those persons with unmet need for dental care. We used our data to assess progress toward the Federation Dental International, World Health Organization, and International Association for Dental Research's oral health goals of reducing the level of oral diseases and minimizing their impact by 2020. Oral health has not improved in the last 25 y, and oral conditions remained a major public health challenge all over the world in 2015. Due to demographic changes, including population growth and aging, the cumulative burden of oral conditions dramatically increased between 1990 and 2015. The number of people with untreated oral conditions rose from 2.5 billion in 1990 to 3.5 billion in 2015, with a 64% increase in DALYs due to oral conditions throughout the world. Clearly, oral diseases are highly prevalent in the globe, posing a very serious public health challenge to policy makers. Greater efforts and potentially different approaches are needed if the oral health goal of reducing the level of oral diseases and minimizing their impact is to be achieved by 2020. Despite some challenges with current measurement methodologies for oral diseases, measurable specific oral health goals should be developed to advance global public health.

Air pollution and ST-elevation myocardial infarction: A case-crossover study of the Belgian STEMI registry 2009-2013.

BACKGROUND: Previous studies have shown that air pollution particulate matter (PM) is associated with an increased risk for myocardial infarction. The effects of air pollution on the risk of ST-elevation myocardial infarction (STEMI), in particular the role of gaseous air pollutants such as NO2 and O3 and the susceptibility of specific populations, are still under debate. METHODS: All patients entered in the Belgian prospective STEMI registry between 2009 and 2013 were included. Based on a validated spatial interpolation model from the Belgian Environment Agency, a national index was used to address the background level of air pollution exposure of Belgian population. A time-stratified and temperature-matched case-crossover analysis of the risk of STEMI was performed. RESULTS: A total of 11,428 STEMI patients were included in the study. Each 10µg/m3 increase in PM10, PM2.5 and NO2 was associated with an increased odds ratio (ORs) of STEMI of 1.026 (CI 95%: 1.005-1.048), 1.028 (CI 95%: 1.003-1.054) and 1.051 (CI 95%: 1.018-1.084), respectively. No effect of O3 was found. STEMI was associated with PM10 exposure in patients ≥75y.o. (OR: 1.046, CI 95%: 1.002-1.092) and with NO2 in patients ≤54y.o. (OR: 1.071, CI 95%: 1.010-1.136). No effect of air pollution on cardiac arrest or in-hospital STEMI mortality was found. CONCLUSION: PM2.5 and NO2 exposures incrementally increase the risk of STEMI. The risk related to PM appears to be greater in the elderly, while younger patients appear to be more susceptible to NO2 exposure.

Post-traumatic stress disorder and major depression in conflict-affected populations: an epidemiological model and predictor analysis.

BACKGROUND: Despite significant research examining mental health in conflict-affected populations we do not yet have a comprehensive epidemiological model of how mental disorders are distributed, or which factors influence the epidemiology in these populations. We aim to derive prevalence estimates specific for region, age and sex of major depression, and PTSD in the general populations of areas exposed to conflict, whilst controlling for an extensive range of covariates. METHODS: A systematic review was conducted to identify epidemiological estimates of depression and PTSD in conflict-affected populations and potential predictors. We analyse data using Bayesian meta-regression techniques. RESULTS: We identified 83 studies and a list of 34 potential predictors. The age-standardised pooled prevalence of PTSD was 12.9% (95% UI 6.9-22.9), and major depression 7.6% (95% UI 5.1-10.9) - markedly lower than estimated in previous research but over two-times higher than the mean prevalence estimated by the Global Burden of Disease Study [3.7% (95% UI 3.0-4.5) and 3.5% (95% UI 2.9-4.2) for anxiety disorders and MDD, respectively]. The age-patterns reveal sharp prevalence inclines in the childhood years. A number of ecological variables demonstrated associations with prevalence of both disorders. Symptom scales were shown to significantly overestimate prevalence of both disorders. Finding suggests higher prevalence of both disorders in females. CONCLUSION: This study provides, for the first time, age-specific estimates of PTSD and depression prevalence adjusted for an extensive range of covariates and is a significant advancement on our current understanding of the epidemiology in conflict-affected populations.

Counting children with tuberculosis: why numbers matter.

In the last 5 years, childhood tuberculosis (TB) has received increasing attention from international organisations, national TB programmes and academics. For the first time, a number of different groups are developing techniques to estimate the burden of childhood TB. We review the challenges in diagnosing TB in children and the reasons why cases in children can go unreported. We discuss the importance of an accurate understanding of burden for identifying problems in programme delivery, targeting interventions, monitoring trends, setting targets, allocating resources appropriately and providing strong advocacy. We briefly review the estimates produced by new analytical methods, and outline the reasons for recent improvements in our understanding and potential future directions. We conclude that while innovation, collaboration and better data have improved our understanding of the childhood TB burden, it remains substantially incomplete.

The epidemiology and global burden of autism spectrum disorders.

BACKGROUND: Autism spectrum disorders (ASDs) are persistent disabling neurodevelopmental disorders clinically evident from early childhood. For the first time, the burden of ASDs has been estimated for the Global Burden of Disease Study 2010 (GBD 2010). The aims of this study were to develop global and regional prevalence models and estimate the global burden of disease of ASDs. METHOD: A systematic review was conducted for epidemiological data (prevalence, incidence, remission and mortality risk) of autistic disorder and other ASDs. Data were pooled using a Bayesian meta-regression approach while adjusting for between-study variance to derive prevalence models. Burden was calculated in terms of years lived with disability (YLDs) and disability-adjusted life-years (DALYs), which are reported here by world region for 1990 and 2010. RESULTS: In 2010 there were an estimated 52 million cases of ASDs, equating to a prevalence of 7.6 per 1000 or one in 132 persons. After accounting for methodological variations, there was no clear evidence of a change in prevalence for autistic disorder or other ASDs between 1990 and 2010. Worldwide, there was little regional variation in the prevalence of ASDs. Globally, autistic disorders accounted for more than 58 DALYs per 100 000 population and other ASDs accounted for 53 DALYs per 100 000. CONCLUSIONS: ASDs account for substantial health loss across the lifespan. Understanding the burden of ASDs is essential for effective policy making. An accurate epidemiological description of ASDs is needed to inform public health policy and to plan for education, housing and financial support services.

Surgically avertable burden of obstetric conditions in low- and middle-income regions: a modelled analysis.

OBJECTIVE: To quantify the burden of maternal and neonatal conditions in low- and middle-income countries (LMICs) that could be averted by full access to quality first-level obstetric surgical procedures. DESIGN: Burden of disease and epidemiological modelling. SETTING: LMICs from all global regions. POPULATION: The entire population in 2010. METHODS: We included five conditions in our analysis: maternal haemorrhage; obstructed labour; obstetric fistula; abortion(1) ; and neonatal encephalopathy. Demographic and epidemiological data were obtained from the Global Burden of Disease 2010 study. We split the disability-adjusted life years (DALYs) of these conditions into surgically 'avertable' and 'non-avertable' burdens. We applied the lowest age-specific fatality rates from all global regions to each LMIC region to estimate the avertable deaths, assuming that the differences of death rates between each region and the lowest rates reflect the gap in surgical care. MAIN OUTCOME MEASURES: Deaths and DALYs avertable. RESULTS: Of the estimated 56.6 million DALYs (i.e. 56.6 million years of healthy life lost) of the selected five conditions, 21.1 million DALYs (37%) are avertable by full coverage of quality obstetric surgery in LMICs. The avertable burden in absolute term is substantial given the size of burden of these conditions in LMICs. Neonatal encephalopathy constitutes the largest portion of avertable burden (16.2 million DALYs) among the five conditions, followed by abortion (2.1 million DALYs). CONCLUSIONS: Improving access to quality surgical care at first-level hospitals could reduce a tremendous burden of maternal and neonatal conditions in LMICs.

Excess mortality from mental, neurological and substance use disorders in the Global Burden of Disease Study 2010.

AIMS: Mortality-associated burden of disease estimates from the Global Burden of Disease 2010 (GBD 2010) may erroneously lead to the interpretation that premature death in people with mental, neurological and substance use disorders (MNSDs) is inconsequential when evidence shows that people with MNSDs experience a significant reduction in life expectancy. We explore differences between cause-specific and excess mortality of MNSDs estimated by GBD 2010. METHODS: GBD 2010 cause-specific death estimates were produced using the International Classification of Diseases death-coding system. Excess mortality (all-cause) was estimated using natural history models. Additional mortality attributed to MNSDs as underlying causes but not captured through GBD 2010 methodology is quantified in the comparative risk assessments. RESULTS: In GBD 2010, MNSDs were estimated to be directly responsible for 840 000 deaths compared with more than 13 million excess deaths using natural history models. CONCLUSIONS: Numbers of excess deaths and attributable deaths clearly demonstrate the high degree of mortality associated with these disorders. There is substantial evidence pointing to potential causal pathways for this premature mortality with evidence-based interventions available to address this mortality. The life expectancy gap between persons with MNSDs and the general population is high and should be a focus for health systems reform.

A heavy burden on young minds: the global burden of mental and substance use disorders in children and youth.

BACKGROUND: Mental and substance use disorders are common and often persistent, with many emerging in early life. Compared to adult mental and substance use disorders, the global burden attributable to these disorders in children and youth has received relatively little attention. METHOD: Data from the Global Burden of Disease Study 2010 was used to investigate the burden of mental and substance disorders in children and youth aged 0-24 years. Burden was estimated in terms of disability-adjusted life years (DALYs), derived from the sum of years lived with disability (YLDs) and years of life lost (YLLs). RESULTS: Globally, mental and substance use disorders are the leading cause of disability in children and youth, accounting for a quarter of all YLDs (54.2 million). In terms of DALYs, they ranked 6th with 55.5 million DALYs (5.7%) and rose to 5th when mortality burden of suicide was reattributed. While mental and substance use disorders were the leading cause of DALYs in high-income countries (HICs), they ranked 7th in low- and middle-income countries (LMICs) due to mortality attributable to infectious diseases. CONCLUSIONS: Mental and substance use disorders are significant contributors to disease burden in children and youth across the globe. As reproductive health and the management of infectious diseases improves in LMICs, the proportion of disease burden in children and youth attributable to mental and substance use disorders will increase, necessitating a realignment of health services in these countries.

The global burden attributable to low bone mineral density.

INTRODUCTION: The Global Burden of Disease Study 2010 estimated the worldwide health burden of 291 diseases and injuries and 67 risk factors by calculating disability-adjusted life years (DALYs). Osteoporosis was not considered as a disease, and bone mineral density (BMD) was analysed as a risk factor for fractures, which formed part of the health burden due to falls. OBJECTIVES: To calculate (1) the global distribution of BMD, (2) its population attributable fraction (PAF) for fractures and subsequently for falls, and (3) the number of DALYs due to BMD. METHODS: A systematic review was performed seeking population-based studies in which BMD was measured by dual-energy X-ray absorptiometry at the femoral neck in people aged 50 years and over. Age- and sex-specific mean ± SD BMD values (g/cm(2)) were extracted from eligible studies. Comparative risk assessment methodology was used to calculate PAFs of BMD for fractures. The theoretical minimum risk exposure distribution was estimated as the age- and sex-specific 90th centile from the Third National Health and Nutrition Examination Survey (NHANES III). Relative risks of fractures were obtained from a previous meta-analysis. Hospital data were used to calculate the fraction of the health burden of falls that was due to fractures. RESULTS: Global deaths and DALYs attributable to low BMD increased from 103 000 and 3 125 000 in 1990 to 188 000 and 5 216 000 in 2010, respectively. The percentage of low BMD in the total global burden almost doubled from 1990 (0.12%) to 2010 (0.21%). Around one-third of falls-related deaths were attributable to low BMD. CONCLUSIONS: Low BMD is responsible for a growing global health burden, only partially representative of the real burden of osteoporosis.

The global burden of occupationally related low back pain: estimates from the Global Burden of Disease 2010 study.

OBJECTIVES: The study was part of the Global Burden of Disease 2010 study and aimed to quantify the burden arising from low back pain (LBP) due to occupational exposure to ergonomic risk factors. METHODS: Exposure prevalence was based on occupation distribution; estimates of relative risk came from a meta-analysis of relevant published literature. The work-related burden was estimated as disability-adjusted life years (DALYs). Estimates were made for each of 21 world regions and 187 countries, separately for 1990 and 2010 using consistent methods. RESULTS: Worldwide, LBP arising from ergonomic exposures at work was estimated to cause 21.7 million DALYs in 2010. The overall population attributable fraction was 26%, varying considerably with age, sex and region. 62% of LBP DALYs were in males-the largest numbers were in persons aged 35-55 years. The highest relative risk (3.7) was in the agricultural sector. The largest number of DALYs occurred in East Asia and South Asia, but on a per capita basis the biggest burden was in Oceania. There was a 22% increase in overall LBP DALYs arising from occupational exposures between 1990 and 2010 due to population growth; rates dropped by 14% over the same period. CONCLUSIONS: LBP arising from ergonomic exposures at work is an important cause of disability. There is a need for improved information on exposure distributions and relative risks, particularly in developing countries.

The global burden of anxiety disorders in 2010.

BACKGROUND: Despite their high prevalence, the global burden of anxiety disorders has never been calculated comprehensively. The new Global Burden of Disease (GBD) study has estimated burden due to morbidity and mortality caused by any anxiety disorder. METHOD: Prevalence was estimated using Bayesian meta-regression informed by data identified in a systematic review. Years of life lived with disability (YLDs) were calculated by multiplying prevalent cases by an average disability weight based on severity proportions (mild, moderate and severe). Disability-adjusted life years (DALYs) were then calculated and age standardized using global standard population figures. Estimates were also made for additional suicide mortality attributable to anxiety disorders. Findings are presented for YLDs, DALYs and attributable burden due to suicide for 21 world regions in 1990 and 2010. RESULTS: Anxiety disorders were the sixth leading cause of disability, in terms of YLDs, in both high-income (HI) and low- and middle-income (LMI) countries. Globally, anxiety disorders accounted for 390 DALYs per 100,000 persons [95% uncertainty interval (UI) 191-371 DALYs per 100,000] in 2010, with no discernible change observed over time. Females accounted for about 65% of the DALYs caused by anxiety disorders, with the highest burden in both males and females experienced by those aged between 15 and 34 years. Although there was regional variation in prevalence, the overlap between uncertainty estimates means that substantive differences in burden between populations could not be identified. CONCLUSIONS: Anxiety disorders are chronic, disabling conditions that are distributed across the globe. Future estimates of burden could be further improved by obtaining more representative data on severity state proportions.

Leiomyomatosis peritonealis disseminata associated with ascites and endometriosis: a case report and review of the literature.

We present a case of leiomyomatosis peritonealis disseminata (LPD) and review the literature. LPD is a rare, benign disorder that is characterized by multiple subperitoneal or peritoneal nodules of varying sizes on the omentum and peritoneal surfaces, grossly resembling disseminated carcinoma. It should be differentiated from other peritoneal tumors. It is mostly asymptomatic and diagnosis is often incidental during surgery. One should be aware of the iatrogenic component of this entity. LPD is being documented with increasing frequency. We report the case of a 39-year-old woman with chronic abdominal pain and heavy dysmenorrhea due to endometriosis associated with LPD. She underwent an abdominal hysterectomy with bilateral salpingo-oophorectomy and omentectomy. LPD and endometriosis is a known association. LPD with ascites and endometriosis however has not yet been reported.

Global variation in the prevalence and incidence of major depressive disorder: a systematic review of the epidemiological literature.

BACKGROUND: Summarizing the epidemiology of major depressive disorder (MDD) at a global level is complicated by significant heterogeneity in the data. The aim of this study is to present a global summary of the prevalence and incidence of MDD, accounting for sources of bias, and dealing with heterogeneity. Findings are informing MDD burden quantification in the Global Burden of Disease (GBD) 2010 Study. METHOD: A systematic review of prevalence and incidence of MDD was undertaken. Electronic databases Medline, PsycINFO and EMBASE were searched. Community-representative studies adhering to suitable diagnostic nomenclature were included. A meta-regression was conducted to explore sources of heterogeneity in prevalence and guide the stratification of data in a meta-analysis. RESULTS: The literature search identified 116 prevalence and four incidence studies. Prevalence period, sex, year of study, depression subtype, survey instrument, age and region were significant determinants of prevalence, explaining 57.7% of the variability between studies. The global point prevalence of MDD, adjusting for methodological differences, was 4.7% (4.4-5.0%). The pooled annual incidence was 3.0% (2.4-3.8%), clearly at odds with the pooled prevalence estimates and the previously reported average duration of 30 weeks for an episode of MDD. CONCLUSIONS: Our findings provide a comprehensive and up-to-date profile of the prevalence of MDD globally. Region and study methodology influenced the prevalence of MDD. This needs to be considered in the GBD 2010 study and in investigations into the ecological determinants of MDD. Good-quality estimates from low-/middle-income countries were sparse. More accurate data on incidence are also required.

Global prevalence of anxiety disorders: a systematic review and meta-regression.

BACKGROUND: The literature describing the global prevalence of anxiety disorders is highly variable. A systematic review and meta-regression were undertaken to estimate the prevalence of anxiety disorders and to identify factors that may influence these estimates. The findings will inform the new Global Burden of Disease study. Method A systematic review identified prevalence studies of anxiety disorders published between 1980 and 2009. Electronic databases, reference lists, review articles and monographs were searched and experts then contacted to identify missing studies. Substantive and methodological factors associated with inter-study variability were identified through meta-regression analyses and the global prevalence of anxiety disorders was calculated adjusting for study methodology. RESULTS: The prevalence of anxiety disorders was obtained from 87 studies across 44 countries. Estimates of current prevalence ranged between 0.9% and 28.3% and past-year prevalence between 2.4% and 29.8%. Substantive factors including gender, age, culture, conflict and economic status, and urbanicity accounted for the greatest proportion of variability. Methodological factors in the final multivariate model (prevalence period, number of disorders and diagnostic instrument) explained an additional 13% of variance between studies. The global current prevalence of anxiety disorders adjusted for methodological differences was 7.3% (4.8-10.9%) and ranged from 5.3% (3.5-8.1%) in African cultures to 10.4% (7.0-15.5%) in Euro/Anglo cultures. CONCLUSIONS: Anxiety disorders are common and the substantive and methodological factors identified here explain much of the variability in prevalence estimates. Specific attention should be paid to cultural differences in responses to survey instruments for anxiety disorders.

Cost-effectiveness of diet and exercise interventions to reduce overweight and obesity.

OBJECTIVE: To analyze whether two dietary weight loss interventions--the dietary approaches to stop hypertension (DASH) program and a low-fat diet program--would be cost-effective in Australia, and to assess their potential to reduce the disease burden related to excess body weight. DESIGN: We constructed a multi-state life-table-based Markov model in which the distribution of body weight influences the incidence of stroke, ischemic heart disease, hypertensive heart disease, diabetes mellitus, osteoarthritis, post-menopausal breast cancer, colon cancer, endometrial cancer and kidney cancer. The target population was the overweight and obese adult population in Australia in 2003. We used a lifetime horizon for health effects and costs, and a health sector perspective for costs. We populated the model with data identified from Medline and Cochrane searches, Australian Bureau of Statistics published catalogues, Australian Institute of Health and Welfare, and Department of Health and Ageing. OUTCOME MEASURES: Disability adjusted life years (DALYs) averted, incremental cost-effectiveness ratios (ICERs) and proportions of disease burden avoided. ICERs under AUS$50,000 per DALY are considered cost-effective. RESULTS: The DASH and low-fat diet programs have ICERs of AUS$12,000 per DALY (95% uncertainty range: Cost-saving- 68,000) and AUS$13,000 per DALY (Cost-saving--130,000), respectively. Neither intervention reduced the body weight-related disease burden at population level by more than 0.1%. The sensitivity analysis showed that when participants' costs for time and travel are included, the ICERs increase to AUS$75,000 per DALY for DASH and AUS$49,000 per DALY for the low-fat diet. Modest weight loss during the interventions, post-intervention weight regain and low participation limit the health benefits. CONCLUSION: Diet and exercise interventions to reduce obesity are potentially cost-effective but have a negligible impact on the total body weight-related disease burden.

Assessing the cost-effectiveness of drug and lifestyle intervention following opportunistic screening for pre-diabetes in primary care.

AIMS/HYPOTHESIS: This study aims to evaluate the cost-effectiveness of a screening programme for pre-diabetes, which was followed up by treatment with pharmaceutical interventions (acarbose, metformin, orlistat) or lifestyle interventions (diet, exercise, diet and exercise) in order to prevent or slow the onset of diabetes in those at high risk. METHODS: To approximate the experience of individuals with pre-diabetes in the Australian population, we used a microsimulation approach, following patient progression through diabetes, cardiovascular disease and renal failure. The model compares costs and disability-adjusted life years lived in people identified through an opportunistic screening programme for each intervention compared with a 'do nothing' scenario, which is representative of current practice. It is assumed that the effect of a lifestyle change will decay by 10% per year, while the effect of a pharmaceutical intervention remains constant throughout use. RESULTS: The most cost-effective intervention options are diet and exercise combined, with a cost-effectiveness ratio of AUD 22,500 per disability-adjusted life year (DALY) averted, and metformin with a cost-effectiveness ratio of AUD 21,500 per DALY averted. The incremental addition of one intervention to the other is not cost-effective. CONCLUSIONS/INTERPRETATION: Screening for pre-diabetes followed by diet and exercise, or metformin treatment is cost-effective and should be considered for incorporation into current practice. The number of dietitians and exercise physiologists needed to deliver such lifestyle change interventions will need to be increased to appropriately support the intervention.

Phosphodiesterase (PDE) 7 in inflammatory cells from patients with asthma and COPD.

In inflammatory cells, the low K(m) cyclic adenosine monophosphate (cAMP)-specific phosphodiesterase (PDE) 4 subtype is predominant in terms of expression and function, although more recently it has been suggested that PDE 7 may also play a role in regulating inflammatory cell activity. In the present study, PDE 4 and PDE 7 subtype messenger ribonucleic acid (mRNA) transcripts in CD4 and CD8 lymphocytes from healthy (n=10) and asthmatic (n=10) subjects and polymorphonuclear neutrophils (PMNs) and CD8 lymphocytes obtained from healthy (n=10) and chronic obstructive pulmonary disease (COPD) (n=7) subjects were identified and quantified. PDE 4A, PDE 4B, PDE 4D and PDE 7A mRNA were present in similar quantities in both CD4 and CD8 lymphocytes obtained from healthy and asthmatic subjects and in CD8 lymphocytes obtained from healthy and COPD subjects. Expression of PDE 4C and PDE 7B mRNA was also observed, although transcript levels were low and variable between individuals. In addition, the effects of selective PDE 7 inhibition on both phytohaemagluttinin (PHA)-induced human peripheral blood mixed mononuclear cell (HPBMNC) proliferation and fMLP-induced neutrophil elastase (NE) release were studied. HPBMNC and human neutrophils, isolated from the venous blood of healthy volunteers (n=6) were treated with either a novel selective PDE 7 inhibitor PF 0332040 alone or in combination with rolipram. Proliferation of HPBMNC was stimulated by PHA (2microgml(-1)) and assessed by [(3)H]-thymidine incorporation, while fMLP-induced (100nM) NE release was determined using a chromogenic substrate. Both rolipram (0.003-10microM) and PF 0332040 (0.003-10microM) significantly inhibited PHA-stimulated proliferation of HPBMNC ((**)P<0.01). Co-administration of rolipram (0.3-10microM) and PF 0332040 (0.003-10microM) significantly increased the degree of inhibition observed, compared to when either drug was administered alone ((**)P<0.01). PF 0332040 (0.003-10microM) had no inhibitory effect on NE release from human peripheral blood neutrophils stimulated with fMLP (100nM), while rolipram (0.003-10microM) significantly inhibited neutrophil degranulation ((**)P<0.01). These findings suggest no evidence of altered PDE 4 or PDE 7 mRNA transcript levels in inflammatory cells isolated from the peripheral venous blood of mild asymptomatic asthmatic subjects or stable COPD subjects, however, inhibition of PDE 7 may influence mononuclear cell function.