The risk of developing major depression among individuals with subthreshold depression: a systematic review and meta-analysis of longitudinal cohort studies.

BACKGROUND: Studies have consistently shown that subthreshold depression is associated with an increased risk of developing major depression. However, no study has yet calculated a pooled estimate that quantifies the magnitude of this risk across multiple studies. METHODS: We conducted a systematic review to identify longitudinal cohort studies containing data on the association between subthreshold depression and future major depression. A baseline meta-analysis was conducted using the inverse variance heterogeneity method to calculate the incidence rate ratio (IRR) of major depression among people with subthreshold depression relative to non-depressed controls. Subgroup analyses were conducted to investigate whether IRR estimates differed between studies categorised by age group or sample type. Sensitivity analyses were also conducted to test the robustness of baseline results to several sources of study heterogeneity, such as the case definition for subthreshold depression. RESULTS: Data from 16 studies (n = 67 318) revealed that people with subthreshold depression had an increased risk of developing major depression (IRR = 1.95, 95% confidence interval 1.28-2.97). Subgroup analyses estimated similar IRRs for different age groups (youth, adults and the elderly) and sample types (community-based and primary care). Sensitivity analyses demonstrated that baseline results were robust to different sources of study heterogeneity. CONCLUSION: The results of this study support the scaling up of effective indicated prevention interventions for people with subthreshold depression, regardless of age group or setting.

The population cost-effectiveness of delivering universal and indicated school-based interventions to prevent the onset of major depression among youth in Australia.

AIMS: School-based psychological interventions encompass: universal interventions targeting youth in the general population; and indicated interventions targeting youth with subthreshold depression. This study aimed to: (1) examine the population cost-effectiveness of delivering universal and indicated prevention interventions to youth in the population aged 11-17 years via primary and secondary schools in Australia; and (2) compare the comparative cost-effectiveness of delivering these interventions using face-to-face and internet-based delivery mechanisms. METHODS: We reviewed literature on the prevention of depression to identify all interventions targeting youth that would be suitable for implementation in Australia and had evidence of efficacy to support analysis. From this, we found evidence of effectiveness for the following intervention types: universal prevention involving group-based psychological interventions delivered to all participating school students; and indicated prevention involving group-based psychological interventions delivered to students with subthreshold depression. We constructed a Markov model to assess the cost-effectiveness of delivering universal and indicated interventions in the population relative to a 'no intervention' comparator over a 10-year time horizon. A disease model was used to simulate epidemiological transitions between three health states (i.e., healthy, diseased and dead). Intervention effect sizes were based on meta-analyses of randomised control trial data identified in the aforementioned review; while health benefits were measured as Disability-adjusted Life Years (DALYs) averted attributable to reductions in depression incidence. Net costs of delivering interventions were calculated using relevant Australian data. Uncertainty and sensitivity analyses were conducted to test model assumptions. Incremental cost-effectiveness ratios (ICERs) were measured in 2013 Australian dollars per DALY averted; with costs and benefits discounted at 3%. RESULTS: Universal and indicated psychological interventions delivered through face-to-face modalities had ICERs below a threshold of $50 000 per DALY averted. That is, $7350 per DALY averted (95% uncertainty interval (UI): dominates - 23 070) for universal prevention, and $19 550 per DALY averted (95% UI: 3081-56 713) for indicated prevention. Baseline ICERs were generally robust to changes in model assumptions. We conducted a sensitivity analysis which found that internet-delivered prevention interventions were highly cost-effective when assuming intervention effect sizes of 100 and 50% relative to effect sizes observed for face-to-face delivered interventions. These results should, however, be interpreted with caution due to the paucity of data. CONCLUSIONS: School-based psychological interventions appear to be cost-effective. However, realising efficiency gains in the population is ultimately dependent on ensuring successful system-level implementation.

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.

Estimating remission from untreated major depression: a systematic review and meta-analysis.

BACKGROUND: Few studies have examined spontaneous remission from major depression. This study investigated the proportion of prevalent cases of untreated major depression that will remit without treatment in a year, and whether remission rates vary by disorder severity. METHOD: Wait-list controlled trials and observational cohort studies published up to 2010 with data describing remission from untreated depression at ≤ 2-year follow-up were identified. Remission was defined as rescinded diagnoses or below threshold scores on standardized symptom measures. Nineteen studies were included in a regression model predicting the probability of 12-month remission from untreated depression, using logit transformed remission proportion as the dependent variable. Covariates included age, gender, study type and diagnostic measure. RESULTS: Wait-listed compared to primary-care samples, studies with longer follow-up duration and older adult compared to adult samples were associated with lower probability of remission. Child and adolescent samples were associated with higher probability of remission. Based on adult samples recruited from primary-care settings, the model estimated that 23% of prevalent cases of untreated depression will remit within 3 months, 32% within 6 months and 53% within 12 months. CONCLUSIONS: It is undesirable to expect 100% treatment coverage for depression, given many will remit before access to services is feasible. Data were drawn from consenting wait-list and primary-care samples, which potentially over-represented mild-to-moderate cases of depression. Considering reported rates of spontaneous remission, a short untreated period seems defensible for this subpopulation, where judged appropriate by the clinician. Conclusions may not apply to individuals with more severe depression.

Systematic review and meta-analysis of the effect of North American working hours restrictions on mortality and morbidity in surgical patients.

BACKGROUND: Short duty hours, imposed by the Accreditation Council of Graduate Medical Education (ACGME) regulations, have been claimed to be associated with loss of continuity of care among surgical patients, leading to a potentially increased risk of adverse surgical outcomes. This systematic review and meta-analysis assessed the strength of associations between duty hour restrictions and morbidity and mortality of various surgical procedures. METHODS: MEDLINE, Embase, BIOSIS Previews(®), the Education Resources Information Center and the Cochrane Central Register of Controlled Trials (January 2000 to September 2009) were searched, and reports screened to identify comparative studies of mortality and morbidity before and after the introduction of ACGME regulation periods. Random-effects (RE) and quality-effects (QE) meta-analyses were performed to determine the risk of morbidity or death associated with long duty hours compared with shorter duty hours. Results are presented as odds ratio (OR) with 95 per cent confidence interval. RESULTS: A total of 19 data sets (10 articles), including 730,648 subjects in the mortality studies and 64,346 in the morbidity studies, were analysed. Long duty hours were associated with a non-significantly increased risk of death compared with shorter duty hours (OR 1·28, 0·94 to 1·73). There was no difference in morbidity between the two groups (OR 1·03, 0·67 to 1·57). Mortality associations were generally stronger for general surgery, more recent studies and higher-quality studies. Heterogeneity was evident among the studies included. CONCLUSION: The reduction in working hours has not affected patient care negatively in terms of demonstrable differences in morbidity and mortality. However, it cannot be distinguished whether this effect is actually due to a non-detrimental effect of the reduction in working hours or whether any such detriment is offset by continually improving patient care and increased surgical supervision.

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.

Lifestyle changes and reduction of colon cancer incidence in Europe: A scenario study of physical activity promotion and weight reduction.

BACKGROUND: Across Europe, there are over 300,000 new cases of colorectal cancer annually. Major risk factors include excess body weight (usually expressed by a high body mass index, BMI) and physical inactivity (PA). In this study we modelled the potential long-term effects on colon cancer incidence of changes in prevalence of excess body weight and physical inactivity in seven European countries across Europe with adequate data. METHODS: We addressed the impact of interventions aimed at preventing weight gain and increasing physical activity on colon cancer incidence using the Prevent model as refined in the FP-6 Eurocadet project. Relative risk (RR) estimates were derived from meta-analyses; sex- and country-specific prevalences of BMI and PA were determined from survey data. Models were made for Czech Republic, Denmark, France, Latvia, the Netherlands, Spain and the United Kingdom. RESULTS: In a hypothetical scenario in which a whole population had obtained an ideal weight distribution in the year 2009, up to 11 new cases per 100,000 person-years would be avoided by 2040. The population attributable fractions (PAF) for excess weight were much higher for males (between 13.5% and 18.2%) than for females (2.3-4.6%). In contrast, using the optimum scenario where everybody in Europe would adhere to the recommended guideline of at least 30 min of moderate PA 5d per week, the PAFs for PA in various countries were substantially greater in women (4.4-21.2%) than in men (3.2-11.6%). Sensitivity analyses were performed assuming underreporting of BMI by using self-reports (difference of 5 and 0.8 percent-points in males and females, respectively), using different risk estimates (between 5.8 and 11.5 percent-points difference for BMI for men and women, respectively, and up to 11.6 percent-points difference for PA for women). INTERPRETATION: Changes in lifestyle can indeed result in large health benefits, including for colon cancer. Two interesting patterns emerged: for colon cancer, achieving optimum BMI levels in the population appears to offer the greatest health benefits in population attributable fractions in males, while increased physical activity might offer the greatest fraction of avoidable cancers in females. These observations suggest a sex-specific strategy to colon cancer prevention.

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.

Population prevalence of depression and mean Beck Depression Inventory score.

BACKGROUND: For some phenomena the mean of population distributions predicts the proportion of people exceeding a threshold value. AIMS: To investigate whether in depression, too, the population mean predicts the number of individuals at the extreme end of the distribution. METHOD: We used data from the European Outcome in Depression International Network (ODIN) study from populations in Finland, Norway and the UK to create models that predicted the prevalence of depression based on the mean Beck Depression Inventory (BDI) score. The models were tested on data from Ireland and Spain. RESULTS: Mean BDI score correlated well with the prevalence of depression determined by clinical interviews. A model based on the beta distribution best fitted the BDI distribution. Both models predicted the depression prevalence in Ireland and Spain fairly well. CONCLUSIONS: The mean of a continuous population distribution of mood predicts the prevalence of depression. Characteristics of both individuals and populations determine depression rates.

Predicting the future prevalence of cigarette smoking in Australia: how low can we go and by when?

BACKGROUND: In Australia, smoking prevalence has declined in men since the 1950s and in women since the 1980s. Future smoking prevalence in Australia is predicted from estimates of previous and current age-specific and sex-specific cessation rates and smoking uptake in young people derived from national survey data on the prevalence of smoking between 1980 and 2007. METHODS: A dynamic forecasting model was used to estimate future smoking prevalence in the Australian population based on a continuation of these current trends in smoking uptake and cessation. RESULTS: The results suggest that Australia's smoking prevalence will continue to fall while current rates of initiation and cessation are maintained. But a continuation of current smoking cessation and initiation patterns will see around 14% of adults still smoking in 2020. CONCLUSIONS: Smoking cessation rates will need to double for Australian smoking prevalence to reach a policy target of 10% by 2020.

Quantitative health impact assessment: current practice and future directions.

STUDY OBJECTIVE: To assess what methods are used in quantitative health impact assessment (HIA), and to identify areas for future research and development. DESIGN: HIA reports were assessed for (1) methods used to quantify effects of policy on determinants of health (exposure impact assessment) and (2) methods used to quantify health outcomes resulting from changes in exposure to determinants (outcome assessment). MAIN RESULTS: Of 98 prospective HIA studies, 17 reported quantitative estimates of change in exposure to determinants, and 16 gave quantified health outcomes. Eleven (categories of) determinants were quantified up to the level of health outcomes. Methods for exposure impact assessment were: estimation on the basis of routine data and measurements, and various kinds of modelling of traffic related and environmental factors, supplemented with experts' estimates and author's assumptions. Some studies used estimates from other documents pertaining to the policy. For the calculation of health outcomes, variants of epidemiological and toxicological risk assessment were used, in some cases in mathematical models. CONCLUSIONS: Quantification is comparatively rare in HIA. Methods are available in the areas of environmental health and, to a lesser extent, traffic accidents, infectious diseases, and behavioural factors. The methods are diverse and their reliability and validity are uncertain. Research and development in the following areas could benefit quantitative HIA: methods to quantify the effect of socioeconomic and behavioural determinants; user friendly simulation models; the use of summary measures of public health, expert opinion and scenario building; and empirical research into validity and reliability.

Stochastic league tables: communicating cost-effectiveness results to decision-makers.

The presentation of the results of uncertainty analysis in cost-effectiveness analysis (CEA) in the literature has been relatively academic with little attention paid to the question of how decision-makers should interpret the information particularly when confidence intervals overlap. This question is especially relevant to sectorial CEA providing information on the costs and effects of a wide range of interventions. This paper introduces stochastic league tables to inform decision-makers about the probability that a specific intervention would be included in the optimal mix of interventions for various levels of resource availability, taking into account the uncertainty surrounding costs and effectiveness. This information helps decision-makers decide on the relative attractiveness of different intervention mixes, and also on the implications for trading gains in efficiency for gains in other goals such as reducing health inequalities and increasing health system responsiveness.

An indirect estimate of the incidence of non-insulin-dependent diabetes mellitus.

Our goal was to estimate non-insulin-dependent diabetes mellitus incidence in the Netherlands in the absence of equivocal empirical data. Incidence can be expressed as a function of age, sex, prevalence, and mortality. We obtained prevalence data from a study that pooled existing prevalence estimates. We calculated diabetes-related mortality using relative risks on all-cause mortality. Sensitivity for the rate of excess mortality was determined using the 95% confidence intervals (95% CI) of the relative risks. The estimated incidence increases exponentially with age, with a doubling time of 10 years for men and 9 years for women. The rate increases from 8.1 per 10,000 (95% CI = 7.7-8.8) for men ages 40-44 years and 7.0 (95% CI = 6.8-8.0) for women to 79.7 per 10,000 (95% CI = 69.5-90.9) for men ages 75-79 years and 85.8 (95% CI = 80.6-91.0) for women. When empirical estimates of incidence are largely lacking, the methodology described offers a useful alternative, in particular for the assessment of potential intervention effects.

Burden of mortality and morbidity from dementia.

The purpose of this study was to estimate severity-specific mortality and to quantify the global health burden of dementia by assessing the time spent disabled with dementia and the life years lost due to dementia. We used mortality data from the Rotterdam study, a population-based prospective study in the 55+-year age range to calculate overall and severity-specific excess mortality for the demented. Lost life years were calculated by decomposing the (mixed) Dutch life table of 1990-1992 in two populations, the demented and the healthy, using prevalence and excess (all cause) mortality. Healthy life loss was calculated by a modified Sullivan technique, weighting for disease severity. Our results indicated that mortality was increased in the demented, in all age, sex, and severity groups. Mortality rate ratios were 2.1 (men) and 2.3 (women), with ranges of 1.7-3.4 (men) and 2.0-3.1 (women), depending on severity. Fifty-five-year-old men lose 1.2 life years due to morbidity and mortality and 0.7 life years due to mortality resulting from dementia. Women lose 3.1 and 1.9 life years, respectively. This population-based study provides evidence that mortality is increased in the demented at all stages, including minimal dementia. The quantified health impact on the general population is in the same order as that of lung cancer or stroke.

[Primary prevention remains expensive, notwithstanding the consensus on lowering serum cholesterol levels]. / Ook met de consensus over verlaging van de serumcholesterolconcentratie blijft primaire preventie duur.

Recently guidelines for cholesterol lowering therapy by means of 'statines' (HMG-CoA reductase inhibitors) were published by the National Organization of Quality Assurance in Hospitals. The part about primary prevention of cardiovascular disease is based on absolute risks for coronary heart disease as calculated by the Framingham Heart Study risk functions and on a cost-effectiveness analysis. However, the function predicts risk of disease such as silent infarction and angina pectoris. The incidence thus produced is higher than any observed clinical incidence. Absolute risk increases exponentially with age, but remaining life expectancy, and thus benefit, decreases. Therefore, decisions about treatment levels are based on arbitrary assumptions. The function is ultimately only used to advise treatment to the smoker, while the better choice is always to stop smoking. The effectiveness is overestimated by using a long time horizon of treatment of 25 years in the cost-effectiveness analysis. Primary prevention of coronary heart disease according to the new guidelines is still very expensive.

The burden of mortality of diabetes mellitus in The Netherlands.

Our objective was to estimate the excess mortality and the reduction in life expectancy related to diabetes mellitus. We developed a life table to describe the Dutch population in two states, diabetic and non-diabetic, using age- and sex-specific prevalence of diabetes mellitus and risks of dying for diabetic subjects. We compared the calculated excess deaths with registered deaths. The cause-of-death registration practice underestimates diabetes-related mortality. The method used in this study, combining mortality data with data from epidemiologic studies, provides an assessment of the impact of diabetes on the Dutch population.

The new old epidemic of coronary heart disease.

OBJECTIVES: This study quantified the consequences for prevalence of increased survival of coronary heart disease (CHD) in the Netherlands from 1980 to 1993. METHODS: A multistage life table fitted observed mortality and registration rates from the nationwide hospital register. The outcome was prevalence by age, sex, period, and disease state. RESULTS: The prevalence of CHD from 1980 to 1993 was 4.4% (men, aged 25 to 84 years) and 1.4% (women, aged 25 to 84 years). Between 1980-1983 and 1990-1993, the incidence changed little, but age-adjusted prevalence increased by 19% (men) and 59% (women). CONCLUSIONS: Sharply decreasing mortality but near-constant attack rates of CHD caused distinct increases in prevalence, particularly among the elderly.

Preventing fatal diseases increases healthcare costs: cause elimination life table approach.

OBJECTIVES: To examine whether elimination of fatal diseases will increase healthcare costs. DESIGN: Mortality data from vital statistics combined with healthcare spending in a cause elimination life table. Costs were allocated to specific diseases through the various healthcare registers. SETTING AND SUBJECTS: The population of the Netherlands, 1988. MAIN OUTCOME MEASURES: Healthcare costs of a synthetic life table cohort, expressed as life time expected costs. RESULTS: The life time expected healthcare costs for 1988 in the Netherlands were 56,600 Pounds for men and 80,900 Pounds for women. Elimination of fatal diseases--such as coronary heart disease, cancer, or chronic obstructive lung disease--increases healthcare costs. Major savings will be achieved only by elimination of non-fatal disease--such as musculoskeletal diseases and mental disorders. CONCLUSION: The aim of prevention is to spare people from avoidable misery and death not to save money on the healthcare system. In countries with low mortality, elimination of fatal diseases by successful prevention increases healthcare spending because of the medical expenses during added life years.

The expiry date of man: a synthesis of evolutionary biology and public health.

In industrialised countries, mortality and morbidity are dominated by age related chronic degenerative diseases. The health and health care needs of future populations will be heavily determined by these conditions of old age. Two opposite scenarios of future morbidity exist: morbidity might decrease ("compress"), because life span is limited, and the incidence of disease is postponed. Or morbidity might increase ("expand"), because death is delayed more than disease incidence. Optimality theory in evolutionary biology explains senescence as a by product of an optimised life history. The theory clarifies how senescence is timed by the competing needs for reproduction and survival, and why this leads to a generalised deterioration of many functions at many levels. As death and disease are not independent, future morbidity will depend on duration and severity of the process of senescence, partly determined by health care, palliating the disease severity but increasing the disease duration by postponing death. Even if morbidity might be compressed, health care needs will surely expand.

Coping with multiple morbidity in a life table.

PIP: "We present the proportional multi-state life table method, that makes the inclusion of multiple diseases better manageable and allows for comorbidity implicitly, without the need to define additional states. We implement the method for heart disease and stroke [among Dutch males in 1988], and look at the effect of hypothetical but not unrealistic changes in incidence and survival on disease prevalence and comorbidity. Finally we discuss limitations and extensions of the method." (EXCERPT)^ieng