Assessing discrepancies in estimates of road traffic deaths in Brazil.

INTRODUCTION: The First UN Decade of Action for Road Safety (2011-2020) ended with most low/middle-income countries (LMICs) failing to reduce road traffic deaths. In contrast, Brazil reported a strong decline starting in 2012. However, comparisons with global health statistical estimates suggest that official statistics from Brazil under-report traffic deaths and overestimate declines. Therefore, we sought to assess the quality of official reporting in Brazil and explain discrepancies. METHODS: We obtained national death registration data and classified deaths to road traffic deaths and partially specified causes that could include traffic deaths. We adjusted data for completeness and reattributed partially specified causes proportionately over specified causes. We compared our estimates with reported statistics and estimates from the Global Burden of Disease (GBD)-2019 study and other sources. RESULTS: We estimate that road traffic deaths in 2019 exceeded the official figure by 31%, similar to traffic insurance claims (27.5%) but less than GBD-2019 estimates (46%). We estimate that traffic deaths have declined by 25% since 2012, close to the decline estimated by official statistics (27%) but much more than estimated by GBD-2019 (10%). We show that GBD-2019 underestimates the extent of recent improvements because GBD models do not track the trends evident in the underlying data. CONCLUSION: Brazil has made remarkable progress in reducing road traffic deaths in the last decade. A high-level evaluation of what has worked in Brazil could provide important guidance to other LMICs.

Addressing discrepancies in estimates of road traffic deaths and injuries in Ethiopia.

BACKGROUND: There are large discrepancies between official statistics of traffic injuries in African countries and estimates from the Global Burden of Disease (GBD) study and WHO's Global Status Reports on Road Safety (GSRRS). We sought to assess the magnitude of the discrepancy in Ethiopia, its implications and how it can be addressed. METHODS: We systematically searched for nationally representative epidemiological data sources for road traffic injuries and vehicle ownership in Ethiopia and compared estimates with those from GBD and GSRRS. FINDINGS: GBD and GSRRS estimates vary substantially across revisions and across projects. GSRRS-2018 estimates of deaths (27 326 in 2016) are more than three times GBD-2019 estimates (8718), and these estimates have non-overlapping uncertainty ranges. GSRRS estimates align well with the 2016 Demographic and Health Survey (DHS-2016; 27 838 deaths, 95th CI: 15 938 to 39 738). Official statistics are much lower (5118 deaths in 2018) than all estimates. GBD-2019 estimates of serious non-fatal injuries are consistent with DHS-2016 estimates (106 050 injuries, 95th CI: 81 728 to 130 372) and older estimates from the 2003 World Health Survey. Data from five surveys confirm that vehicle ownership levels in Ethiopia are much lower than in other countries in the region. INTERPRETATION: Inclusion of data from national health surveys in GBD and GSRRS can help reduce discrepancies in estimates of deaths and support their use in highlighting under-reporting in official statistics and advocating for better prioritisation of road safety in the national policy agenda. GBD methods for estimating serious non-fatal injuries should be strengthened to allow monitoring progress towards Sustainable Development Goal target 3.6.

Estimates of road traffic deaths in Tanzania.

INTRODUCTION: There is considerable uncertainty in estimates of traffic deaths in many sub-Saharan African countries, with the Global Burden of Disease (GBD) and the Global Status Report on Road Safety (GSRRS) reporting widely differing estimates. As a case study, we reviewed and compared estimates for Tanzania. METHODS: We estimated the incidence of traffic deaths and vehicle ownership in Tanzania from nationally representative surveys. We compared findings with GBD and GSRRS estimates. RESULTS: Traffic death estimates based on the 2012 census (9382 deaths; 95% CI: 7565 to 11 199) and the 2011-2014 Sample Vital Registration with Verbal Autopsy (8778; 95% CI: 7631 to 9925) were consistent with each other and were about halfway between GBD (5 608; 95% UI: 4506 to 7014) and WHO (16 252; 95% CI: 13 130 to 19 374) estimates and more than twice official statistics (3885 deaths in 2013). Surveys and vehicle registrations data show that motorcycles have increased rapidly since 2007 and now comprise 66% of vehicles. However, these trends are not reflected in GBD estimates of motorcycles in the country, likely resulting in an underestimation of motorcyclist deaths. CONCLUSION: Reducing discrepancies between GBD and GSRRS estimates and demonstrating consistency with local epidemiological data will increase the legitimacy of such estimates among national stakeholders. GBD, which is the only project that models the road-user distribution of traffic deaths in all countries, likely severely underestimates motorcycle deaths in countries where there has been a recent increase in motorcycles. Addressing police under-reporting and strengthening surveillance capacity in Tanzania will allow a better understanding of the road safety problem and better targeting of interventions.

Comparing estimates of road traffic deaths and non-fatal road traffic injuries in Cambodia.

INTRODUCTION: Timely, accurate and detailed information about traffic injuries are essential for managing national road safety programmes. However, there is considerable under-reporting in official statistics of many low and middle-income countries (LMICs) and large discrepancies between estimates from the Global Burden of Disease (GBD) study and WHO's Global Health Estimates (GHE). We compared all sources of epidemiological information on traffic injuries in Cambodia to guide efforts to improve traffic injury statistics. METHODS: We estimated the incidence of traffic deaths and injuries and household ownership of motor vehicles in Cambodia from nationally representative surveys and censuses. We compared findings with GDB and GHE estimates. RESULTS: We identified seven sources for estimating traffic deaths and three for non-fatal injuries that are not included as data sources in GBD and GHE models. These sources and models suggest a fairly consistent estimate of approximately 3100 deaths annually, about 50% higher than official statistics, likely because most hospital deaths are not recorded. Surveys strongly suggest that the vehicle fleet is dominated by motorcycles, which is not consistent with GBD estimates that suggest similar numbers of motorcyclist and vehicle occupant deaths. Estimates of non-fatal injuries from health surveys were about 7.5 times official statistics and 1.5 times GBD estimates. CONCLUSION: Including local epidemiological data sources from LMICs can help reduce uncertainty in estimates from global statistical models and build trust in estimates among local stakeholders. Such analysis should be used as a benchmark to assess and strengthen the completeness of reporting of the national surveillance system.

Availability of population-level data sources for tracking the incidence of deaths and injuries from road traffic crashes in low-income and middle-income countries.

INTRODUCTION: Tracking progress towards Sustainable Development Goal (SDG) 3·6 of reducing traffic deaths and serious injuries poses a measurement challenge in most low-income and middle-income countries (LMICs) due to large discrepancies between reported official statistics and estimates from global health measurement studies. We assess the extent to which national population censuses and health surveys can fill the information gaps. METHODS: We reviewed questionnaires for nationally representative surveys and censuses conducted since 2000 in LMICs. We identified sources that provide estimates of household ownership of vehicles, incidence of traffic deaths and non-fatal injuries, and prevalence of disability. RESULTS: We identified 802 data sources from 132 LMICs. Sub-Saharan African countries accounted for 43% of all measurements. The number of measurements since 2000 was high, with 97% of the current global LMIC population having at least one measurement for vehicle ownership, 77% for deaths, 90% for non-fatal injuries and 50% for disability due to traffic injuries. Recent data (since 2010) on traffic injuries were available from far fewer countries (deaths: 21 countries; non-fatal injuries: 62 and disability: 12). However, there were many more countries with recent data on less-specific questions about unintentional or all injuries (deaths: 41 countries, non-fatal: 87, disability: 32). CONCLUSION: Traffic injuries are substantially underreported in official statistics of most LMICs. National surveys and censuses provide a viable alternative information source, but despite a large increase in their use to monitor SDGs, traffic injury measurements have not increased. We show that relatively small modifications and additions to questions in forthcoming surveys can provide countries with a way to benchmark their existing surveillance systems and result in a substantial increase in data for tracking road traffic injuries globally.

Pharmacist Intentions to Prescribe Hormonal Contraception Following New Legislative Authority in California.

OBJECTIVE:: Following a California law expanding pharmacists' scope of practice to include directly providing self-administered hormonal contraception to patients pursuant to a statewide protocol, this study aimed to assess California pharmacists' intentions to provide this new service prior to the protocol development and implementation. DESIGN:: Descriptive, nonexperimental, cross-sectional study. SETTING:: California between August and September 2014. PARTICIPANTS:: California pharmacists working in community pharmacies. INTERVENTION:: Invitations to participate in the online survey were sent to 1774 pharmacists. MAIN OUTCOME MEASURES:: Main outcomes included pharmacists' current practices, intentions to prescribe hormonal contraception, comfort performing various activities, knowledge about contraceptive methods, training needs, and barriers to prescribing. RESULTS:: A total of 257 responses (14.5% response rate) were received. Of those, 121 respondents met inclusion criteria and were included in the analysis. About half of the respondents (49.6%) reported working in a community chain pharmacy, 46.3% in an independent pharmacy, and 4.1% in other community pharmacy settings. The majority (72.7%) of pharmacists reported that they would likely provide this new service. Respondents reported being comfortable educating patients on short-acting (94.2%) and long-acting reversible contraception (81.7%), as well as identifying drug interactions with hormonal contraception (96.7%). Respondents indicated time constraints (74.4%), lack of reimbursement (63.6%), and liability concerns (62.0%) as barriers to prescribing hormonal contraception. CONCLUSIONS:: California pharmacists expressed strong intentions and comfort in prescribing hormonal contraception. Pharmacists' additional training needs and barriers should be addressed for successful implementation. This new service has great potential to increase access to contraception, potentially fostering increased use and adherence.

Mixed-methods investigation of women's experiences with second-trimester abortion care in the Midwest and Northeast United States.

OBJECTIVE(S): We studied women's experiences seeking and receiving second-trimester abortion care in two geographically and legislatively different settings to inform ways to improve abortion care access and services. STUDY DESIGN: We conducted in-depth interviews with women who obtained second-trimester abortion care. Themes from the interviews were then used to inform a self-administered survey, which was completed by 108 women who received second-trimester abortion care in the Northeast and Midwest. We calculated descriptive statistics and used chi-squared and t-tests to compare responses. RESULTS: We interviewed eight women and surveyed 108 women. Most interviewees and 65.2% of survey respondents reported difficulties accessing care. Although most interview and survey respondents had insurance, a slight majority reported difficulty funding care. All interviewees and 57.9% of survey respondents reported positive experiences with providers, with many interviewees and 62.0% of survey respondents saying their abortion care was better than their usual health care. Most interviewees and 75.8% of survey respondents reported pain as low to moderate, and the majority of participants reported it was the same or less than expected. Knowledge about abortion restrictions was low. Most interviewees and 68.4% survey respondents disagreed with restrictions on insurance coverage of abortion. Common recommendations to improve experiences were to ensure travel and financial support and to decrease wait times at clinics. There were few regional differences among outcomes. CONCLUSION(S): Women seeking second-trimester abortion in these locations reported positive abortion experiences. However, they had to overcome significant obstacles to obtain care. IMPLICATIONS: This is the first study to systematically research women's second-trimester care experiences in two different regions of the United States. Regardless of location, women experienced barriers due to policies that impose gestational age restrictions, limit provider availability (consequently increasing wait times), and increase costs. Policy change to reduce these barriers is critical to improve access to and experiences with second trimester abortion care.

Contraceptive Use among Women in Accra, Ghana: 2003 and 2008.

Despite a relatively low fertility rate, maternal mortality in Ghana still remains high. According to the Ghana Demographic and Health Surveys, about 22% of Ghanaian women of reproductive age currently use contraception. We analyzed contraceptive use among a representative sample of women in Accra, Ghana, to better understand contraceptive use patterns. We used data from two cross-sectional surveys of a representative cohort of women in Accra. In 2003, 28.9% of sexually active women used a contraceptive method. In 2008, 31.5% of sexually active women used a contraceptive method. Additionally, we observed high rates of discontinuation-from 64.1% among those using longer-acting methods to 82.1% among those using traditional methods-between years. Further research on women's contraceptive decision-making is needed to explain these patterns and to ensure that family planning interventions meet the needs of women in Ghana.

Estimation of indices of health service readiness with a principal component analysis of the Tanzania Service Provision Assessment Survey.

BACKGROUND: Service Provision Assessment (SPA) surveys have been conducted to gauge primary health care and family planning clinical readiness throughout East and South Asia as well as sub-Saharan Africa. Intended to provide useful descriptive information on health system functioning to supplement the Demographic and Health Survey data, each SPA produces a plethora of discrete indicators that are so numerous as to be impossible to analyze in conjunction with population and health survey data or to rate the relative readiness of individual health facilities. Moreover, sequential SPA surveys have yet to be analyzed in ways that provide systematic evidence that service readiness is improving or deteriorating over time. METHODS: This paper presents an illustrative analysis of the 2006 Tanzania SPA with the goal of demonstrating a practical solution to SPA data utilization challenges using a subset of variables selected to represent the six building blocks of health system strength identified by the World Health Organization (WHO) with a focus on system readiness to provide service. Principal Components Analytical (PCA) models extract indices representing common variance of readiness indicators. Possible uses of results include the application of PCA loadings to checklist data, either for the comparison of current circumstances in a locality with a national standard, for the ranking of the relative strength of operation of clinics, or for the estimation of trends in clinic service quality improvement or deterioration over time. RESULTS: Among hospitals and health centers in Tanzania, indices representing two components explain 32% of the common variance of 141 SPA indicators. For dispensaries, a single principal component explains 26% of the common variance of 86 SPA indicators. For hospitals/HCs, the principal component is characterized by preventive measures and indicators of basic primary health care capabilities. For dispensaries, the principal component is characterized by very basic newborn care as well as preparedness for delivery. CONCLUSIONS: PCA of complex facility survey data generates composite scale coefficients that can be used to reduce indicators to indices for application in comparative analyses of clinical readiness, or for multi-level analysis of the impact of clinical capability on health outcomes or on survival.

Childhood Illness Prevalence and Health Seeking Behavior Patterns in Rural Tanzania.

INTRODUCTION: This paper identifies factors influencing differences in the prevalence of diarrhea, fever and acute respiratory infection (ARI), and health seeking behavior among caregivers of children under age five in rural Tanzania. METHODS: Using cross-sectional survey data collected in Kilombero, Ulanga, and Rufiji districts, the analysis included 1,643 caregivers who lived with 2,077 children under five years old. Logistic multivariate and multinomial regressions were used to analyze factors related to disease prevalence and to health seeking behavior. RESULTS: One quarter of the children had experienced fever in the past two weeks, 12.0 % had diarrhea and 6.7 % experienced ARI. Children two years of age and older were less likely to experience morbidity than children under one year [ORfever = 0.77, 95 % CI 0.61-0.96; ORdiarrhea = 0.26, 95 % CI 0.18-0.37; ORARI = 0.60 95 % CI 0.41-0.89]. Children aged two and older were more likely than children under one to receive no care or to receive care at home, rather than to receive care at a facility [RRRdiarrhea = 3.47, 95 % CI 1.19-10.17 for "No care"]. Children living with an educated caregiver were less likely to receive no care or home care rather than care at a facility as compared to those who lived with an uneducated caregiver [RRRdiarrhea = 0.28, 95 % CI 1.10-0.79 for "No care"]. Children living in the wealthiest households were less likely to receive no care or home care for fever as compared to those who lived poorest households. Children living more than 1 km from health facility were more likely to receive no care or to receive home care for diarrhea rather than care at a facility as compared to those living less than 1 km from a facility [RRRdiarrhea = 3.50, 95 % CI 1.13-10.82 for "No care"]. Finally, caregivers who lived with more than one child under age five were more likely to provide no care or home care rather than to seek treatment at a facility as compared to those living with only one child under five. CONCLUSIONS: Our results suggest that child age, caregiver education attainment, and household wealth and location may be associated with childhood illness and care seeking behavior patterns. Interventions should be explored that target children and caregivers according to these factors, thereby better addressing barriers and optimizing health outcomes especially for children at risk of dying before the age of five.

Health Care Coverage Decision Making in Low- and Middle-Income Countries: Experiences from 25 Coverage Schemes.

Lessons learned by countries that have successfully implemented coverage schemes for health services may be valuable for other countries, especially low- and middle-income countries (LMICs), which likewise are seeking to provide/expand coverage. The research team surveyed experts in population health management from LMICs for information on characteristics of health care coverage schemes and factors that influenced decision-making processes. The level of coverage provided by the different schemes varied. Nearly all the health care coverage schemes involved various representatives and stakeholders in their decision-making processes. Maternal and child health, cardiovascular diseases, cancer, and HIV were among the highest priorities guiding coverage development decisions. Evidence used to inform coverage decisions included medical literature, regional and global epidemiology, and coverage policies of other coverage schemes. Funding was the most commonly reported reason for restricting coverage. This exploratory study provides an overview of health care coverage schemes from participating LMICs and contributes to the scarce evidence base on coverage decision making. Sharing knowledge and experiences among LMICs can support efforts to establish systems for accessible, affordable, and equitable health care.

Effect of increased potassium intake on cardiovascular risk factors and disease: systematic review and meta-analyses.

OBJECTIVE: To conduct a systematic review of the literature and meta-analyses to fill the gaps in knowledge on potassium intake and health. DATA SOURCES: Cochrane Central Register of Controlled Trials, Medline, Embase, WHO International Clinical Trials Registry Platform, Latin American and Caribbean Health Science Literature Database, and the reference lists of previous reviews. STUDY SELECTION: Randomised controlled trials and cohort studies reporting the effects of potassium intake on blood pressure, renal function, blood lipids, catecholamine concentrations, all cause mortality, cardiovascular disease, stroke, and coronary heart disease were included. DATA EXTRACTION AND SYNTHESIS: Potential studies were independently screened in duplicate, and their characteristics and outcomes were extracted. When possible, meta-analysis was done to estimate the effects (mean difference or risk ratio with 95% confidence interval) of higher potassium intake by using the inverse variance method and a random effect model. RESULTS: 22 randomised controlled trials (including 1606 participants) reporting blood pressure, blood lipids, catecholamine concentrations, and renal function and 11 cohort studies (127,038 participants) reporting all cause mortality, cardiovascular disease, stroke, or coronary heart disease in adults were included in the meta-analyses. Increased potassium intake reduced systolic blood pressure by 3.49 (95% confidence interval 1.82 to 5.15) mm Hg and diastolic blood pressure by 1.96 (0.86 to 3.06) mm Hg in adults, an effect seen in people with hypertension but not in those without hypertension. Systolic blood pressure was reduced by 7.16 (1.91 to 12.41) mm Hg when the higher potassium intake was 90-120 mmol/day, without any dose response. Increased potassium intake had no significant adverse effect on renal function, blood lipids, or catecholamine concentrations in adults. An inverse statistically significant association was seen between potassium intake and risk of incident stroke (risk ratio 0.76, 0.66 to 0.89). Associations between potassium intake and incident cardiovascular disease (risk ratio 0.88, 0.70 to 1.11) or coronary heart disease (0.96, 0.78 to 1.19) were not statistically significant. In children, three controlled trials and one cohort study suggested that increased potassium intake reduced systolic blood pressure by a non-significant 0.28 (-0.49 to 1.05) mm Hg. CONCLUSIONS: High quality evidence shows that increased potassium intake reduces blood pressure in people with hypertension and has no adverse effect on blood lipid concentrations, catecholamine concentrations, or renal function in adults. Higher potassium intake was associated with a 24% lower risk of stroke (moderate quality evidence). These results suggest that increased potassium intake is potentially beneficial to most people without impaired renal handling of potassium for the prevention and control of elevated blood pressure and stroke.

Cost-effectiveness of gene-expression profiling for tumor-site origin.

OBJECTIVES: Gene-expression profiling (GEP) reliably supplements traditional clinicopathological information on the tissue of origin (TOO) in metastatic or poorly differentiated cancer. A cost-effectiveness analysis of GEP TOO testing versus usual care was conducted from a US third-party payer perspective. METHODS: Data on recommendation changes for chemotherapy, surgery, radiation therapy, blood tests, imaging investigations, and hospice care were obtained from a retrospective, observational study of patients whose physicians received GEP TOO test results. The effects of chemotherapy recommendation changes on survival were based on the results of trials cited in National Comprehensive Cancer Network and UpToDate guidelines. Drug and administration costs were based on average doses reported in National Comprehensive Cancer Network guidelines. Other unit costs came from Centers for Medicare & Medicaid Services fee schedules. Quality-of-life weights were obtained from literature. Bootstrap analysis estimated sample variability; probabilistic sensitivity analysis addressed parameter uncertainty. RESULTS: Chemotherapy regimen recommendations consistent with guidelines for final tumor-site diagnoses increased significantly from 42% to 65% (net difference 23%; P<0.001). Projected overall survival increased from 15.9 to 19.5 months (mean difference 3.6 months; two-sided 95% confidence interval [CI] 3.2-3.9). The average increase in quality-adjusted life-months was 2.7 months (95% CI 1.5-4.3), and average third-party payer costs per patient increased by $10,360 (95% CI $2,982-$19,192). The cost per quality-adjusted life-year gained was $46,858 (95% CI $13,351-$104,269). CONCLUSIONS: GEP TOO testing significantly altered clinical practice patterns and is projected to increase overall survival, quality-adjusted life-years, and costs, resulting in an expected cost per quality-adjusted life-year of less than $50,000.

National, regional, and global trends in adult overweight and obesity prevalences.

BACKGROUND: Overweight and obesity prevalence are commonly used for public and policy communication of the extent of the obesity epidemic, yet comparable estimates of trends in overweight and obesity prevalence by country are not available. METHODS: We estimated trends between 1980 and 2008 in overweight and obesity prevalence and their uncertainty for adults 20 years of age and older in 199 countries and territories. Data were from a previous study, which used a Bayesian hierarchical model to estimate mean body mass index (BMI) based on published and unpublished health examination surveys and epidemiologic studies. Here, we used the estimated mean BMIs in a regression model to predict overweight and obesity prevalence by age, country, year, and sex. The uncertainty of the estimates included both those of the Bayesian hierarchical model and the uncertainty due to cross-walking from mean BMI to overweight and obesity prevalence. RESULTS: The global age-standardized prevalence of obesity nearly doubled from 6.4% (95% uncertainty interval 5.7-7.2%) in 1980 to 12.0% (11.5-12.5%) in 2008. Half of this rise occurred in the 20 years between 1980 and 2000, and half occurred in the 8 years between 2000 and 2008. The age-standardized prevalence of overweight increased from 24.6% (22.7-26.7%) to 34.4% (33.2-35.5%) during the same 28-year period. In 2008, female obesity prevalence ranged from 1.4% (0.7-2.2%) in Bangladesh and 1.5% (0.9-2.4%) in Madagascar to 70.4% (61.9-78.9%) in Tonga and 74.8% (66.7-82.1%) in Nauru. Male obesity was below 1% in Bangladesh, Democratic Republic of the Congo, and Ethiopia, and was highest in Cook Islands (60.1%, 52.6-67.6%) and Nauru (67.9%, 60.5-75.0%). CONCLUSIONS: Globally, the prevalence of overweight and obesity has increased since 1980, and the increase has accelerated. Although obesity increased in most countries, levels and trends varied substantially. These data on trends in overweight and obesity may be used to set targets for obesity prevalence as requested at the United Nations high-level meeting on Prevention and Control of NCDs.

Clinical validity/utility, change in practice patterns, and economic implications of risk stratifiers to predict outcomes for early-stage breast cancer: a systematic review.

BACKGROUND: At least 14 stratifiers exist to assess recurrence risk, chemotherapy response, and overall survival (OS) in women with early-stage breast cancer (ESBC). These stratifiers have not been compared using a recently developed rigorous framework. We performed a systematic review of the literature on clinical validity/utility, change in clinical practice, and economic implications of ESBC stratifiers. METHODS: A systematic literature search was performed using PubMed, Cumulative Index to Nursing and Allied Health Literature, the Cochrane Database of Systematic Reviews, and bibliographies of relevant studies. Data were extracted by two investigators and graded using a previously published framework. The Level-of-Evidence determination for each study was summarized, and the studies that provide evidence on change in clinical practice and economic implications are reported. RESULTS: Fifty-six articles published original evidence addressing the 21-gene recurrence score (n = 31), 70-gene signature (n = 14), Adjuvant! Online (n = 12), 5-antibody immunohistochemistry panel (n = 3), 5-gene expression index (n = 1), and 14-gene signature (n = 1). The 21-gene recurrence score satisfied Level I evidence (the highest level of evidence among five levels) for estimating distant recurrence risk (DRR), OS, and response to adjuvant chemotherapy, and Level II for estimating local recurrence risk. The 5-antibody immunohistochemistry panel and 70-gene signature satisfied Level II evidence for estimating DRR and OS. Adjuvant! Online satisfied Level II evidence for estimating DRR, OS, and chemotherapy response. The 5-gene expression index satisfied Level III evidence for predicting DRR. The 14-gene signature satisfied Level III evidence for predicting DRR and OS. Ten studies reported changes in clinical practice patterns; seven studies reported economic implications. CONCLUSION: The available evidence on the ability of stratifiers to predict risks of recurrence and response to chemotherapy in ESBC is growing. Level-of-Evidence determinations using the newer framework provide a solid scientific foundation for clinical recommendations.

Clinical utility of gene-expression profiling for tumor-site origin in patients with metastatic or poorly differentiated cancer: impact on diagnosis, treatment, and survival.

PURPOSE: The primary tissue-site origin in over 4% of cancers remains uncertain despite thorough clinicopathological evaluation. This study assessed the effect of a Food and Drug Administration-cleared 2,000- gene-expression-profiling (GEP) test on primary tissue-site working diagnoses and management for metastatic and poorly differentiated cancers. METHODS: Clinical information was collected from physicians ordering the GEP test for patients with difficult to diagnose cancers. Endpoints included diagnostic procedures, physicians' working diagnoses and treatment recommendations before and after GEP result availability, and physician reports of the test's usefulness for clinical decision making. Patient date of death was obtained, with a minimum of one year follow-up from date of biopsy. RESULTS: Sixty-five physicians participated in the study (n=107 patients). Before GEP, patients underwent 3.2 investigations on average (e.g., radiology, endoscopy). Ten immunohistochemistry tests were used per biopsy (SD 5.2). After GEP testing, physicians changed the primary working diagnosis for 50% of patients (95% CI: 43%,58%) and management for 65% of patients (95% CI: 58%,73%). With GEP results, the recommendation for guideline-consistent chemotherapy increased from 42% to 65% of patients, and the recommendation for non-guideline-consistent regimens declined from 28% to 13%. At last follow-up, 69 patients had died, and median survival was 14.0 months (95% CI: 10.2,18.6). Thirty-three percent of patients were alive at 2 years. CONCLUSION: In patients with difficult-to-diagnose cancers, GEP changed the working diagnosis and management for the majority of patients. Patients for whom the GEP test was ordered had longer median survival than that historically reported for patients enrolled in treatment trials for cancer of unknown primary.

Cost-effectiveness of adding rituximab to fludarabine and cyclophosphamide for the treatment of previously untreated chronic lymphocytic leukemia.

A recent phase III trial demonstrated improved progression-free survival (PFS) and overall survival (OS) associated with adding rituximab to fludarabine and cyclophosphamide (R-FC) compared to FC in treatment of previously untreated chronic lymphocytic leukemia (CLL). A cost-effectiveness analysis of R-FC over FC was performed from a US third-party payer perspective over a lifetime horizon in the base case. One-way, two-way and probabilistic sensitivity analyses were conducted to assess the robustness of the results. A secondary analysis was performed by also considering a societal perspective. R-FC was associated with an incremental 1.15 quality-adjusted life-years (QALYs) compared to FC and resulted in an incremental cost-effectiveness ratio of $23 530 per QALY in the base case and $31 513 per QALY considering a societal perspective. Results were most sensitive to time horizon, discount rate and unit drug cost for rituximab. Within the limitations of modeling long-term outcomes, R-FC is cost-effective for previously untreated CLL.

National, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9·1 million participants.

BACKGROUND: Excess bodyweight is a major public health concern. However, few worldwide comparative analyses of long-term trends of body-mass index (BMI) have been done, and none have used recent national health examination surveys. We estimated worldwide trends in population mean BMI. METHODS: We estimated trends and their uncertainties of mean BMI for adults 20 years and older in 199 countries and territories. We obtained data from published and unpublished health examination surveys and epidemiological studies (960 country-years and 9·1 million participants). For each sex, we used a Bayesian hierarchical model to estimate mean BMI by age, country, and year, accounting for whether a study was nationally representative. FINDINGS: Between 1980 and 2008, mean BMI worldwide increased by 0·4 kg/m(2) per decade (95% uncertainty interval 0·2-0·6, posterior probability of being a true increase >0·999) for men and 0·5 kg/m(2) per decade (0·3-0·7, posterior probability >0·999) for women. National BMI change for women ranged from non-significant decreases in 19 countries to increases of more than 2·0 kg/m(2) per decade (posterior probabilities >0·99) in nine countries in Oceania. Male BMI increased in all but eight countries, by more than 2 kg/m(2) per decade in Nauru and Cook Islands (posterior probabilities >0·999). Male and female BMIs in 2008 were highest in some Oceania countries, reaching 33·9 kg/m(2) (32·8-35·0) for men and 35·0 kg/m(2) (33·6-36·3) for women in Nauru. Female BMI was lowest in Bangladesh (20·5 kg/m(2), 19·8-21·3) and male BMI in Democratic Republic of the Congo 19·9 kg/m(2) (18·2-21·5), with BMI less than 21·5 kg/m(2) for both sexes in a few countries in sub-Saharan Africa, and east, south, and southeast Asia. The USA had the highest BMI of high-income countries. In 2008, an estimated 1·46 billion adults (1·41-1·51 billion) worldwide had BMI of 25 kg/m(2) or greater, of these 205 million men (193-217 million) and 297 million women (280-315 million) were obese. INTERPRETATION: Globally, mean BMI has increased since 1980. The trends since 1980, and mean population BMI in 2008, varied substantially between nations. Interventions and policies that can curb or reverse the increase, and mitigate the health effects of high BMI by targeting its metabolic mediators, are needed in most countries. FUNDING: Bill & Melinda Gates Foundation and WHO.