Frequency-dependent tolerance to aircraft disturbance drastically alters predicted impact on shorebirds.

Anthropogenic disturbance of wildlife is increasing globally. Generalizing impacts of disturbance to novel situations is challenging, as the tolerance of animals to human activities varies with disturbance frequency (e.g. due to habituation). Few studies have quantified frequency-dependent tolerance, let alone determined how it affects predictions of disturbance impacts when these are extrapolated over large areas. In a comparative study across a gradient of air traffic intensities, we show that birds nearly always fled (80%) if aircraft were rare, while birds rarely responded (7%) if traffic was frequent. When extrapolating site-specific responses to an entire region, accounting for frequency-dependent tolerance dramatically alters the predicted costs of disturbance: the disturbance map homogenizes with fewer hotspots. Quantifying frequency-dependent tolerance has proven challenging, but we propose that (i) ignoring it causes extrapolations of disturbance impacts from single sites to be unreliable, and (ii) it can reconcile published idiosyncratic species- or source-specific disturbance responses.

Beyond "Safe and Effective": The urgent need for high-impact smoking cessation medications.

Smoking cessation medications (SCMs) are an evidence-based cornerstone of comprehensive tobacco control programs globally. However, the impact of SCMs on population smoking prevalence is controversial, with inconsistencies between randomized controlled trials (RCTs) and population-based observational studies. We estimated SCM impact on permanent cessation and population smoking prevalence by extrapolating efficacy estimates from meta-analyses of RCTs, using the standard population impact formula: efficacy*reach. We calculated the potential SCM impact under a range of assumptions for permanent cessation (20%,14%), behavioral support (yes/no), reach (40%-2%), and underlying smoking prevalence. Assuming behavioral support for all, depending on reach, 8%-0.3% of smokers are expected to quit permanently. Without behavioral support, permanent cessation is estimated to be 6.4%-0.2%. Assuming an underlying population smoking prevalence of 14%, (current U.S. prevalence), the maximum impact on population smoking prevalence is 1.12%. Impact on prevalence increases with increasing underlying country-specific levels of prevalence. With current U.S. levels of reach, behavioral support and smoking prevalence, we estimate that, based on a single course of treatment, 2.3% of smokers would quit permanently, contributing to a 0.3% decrease in population level smoking prevalence. Even under ideal conditions, the potential of current first-line SCMs to increase cessation in a substantial proportion of smokers, and reduce population smoking prevalence, is limited. In order to avert the predicted billion tobacco-caused deaths in this century, "safe and effective" medications are not sufficient: SCMs with high population impact are urgently needed. Policies to ensure the availability and accessibility of highly efficacious SCMs, with behavioral support, are crucial.

[Reduction of red and processed meats in the Spanish population: What is its impact on total and cardiovascular mortality?] / Reducción de carnes rojas y procesadas en la población española: ¿cuál es su impacto sobre la mortalidad cardiovascular?

OBJECTIVE: Quantify the impact of reducing the consumption of red/processed meats on cardiovascular mortality and all-cause mortality of the Spanish adult population based in 5 revisions published. PARTICIPANTS AND MAIN MEASUREMENTS: We defined exposure as consumption of ≥3 servings/week of red or processed meats and considered four possible scenarios of exposed population (30%-60%). Based on data from the Spanish National Statistics Institute, we calculated the weighted mortality between 40 and 80years. Using the relative risks (RR) and 95% confidence intervals (CI) published by the referred revisions (RR=0.88; IC95%: 0.84-0.93 for all-cause mortality and RR=0.92; IC95%: 0.90-0.93 for cardiovascular mortality), we calculated the expected mortality rate in both exposed and unexposed categories. By multiplying these rates by the number of exposed individuals, we estimated the attributable number of yearly deaths. RESULTS: If 60% of the population was exposed, with a 95%CI, the number of cardiovascular deaths that could be averted each year if population consumed <3 servings/week of red or processed meats was between 2.112 and 3.055. If was exposed that 30%, the difference in the yearly number of potentially averted deaths was between 1.079 and 1.577. CONCLUSIONS: Even under the most conservative assumption, the benefit, at the population level, of reducing red or processed meats consumption <3 servings/week on cardiovascular mortality is important. The conclusions of the recently published reviews contradicted their own results and contributed to a state of confusion that can create substantial harm for public health.

Designing precision medicine trials to yield a greater population impact.

Traditionally, a clinical trial is conducted comparing treatment to standard care for all patients. However, it could be inefficient given patients' heterogeneous responses to treatments, and rapid advances in the molecular understanding of diseases have made biomarker-based clinical trials increasingly popular. We propose a new targeted clinical trial design, termed as Max-Impact design, which selects the appropriate subpopulation for a clinical trial and aims to optimize population impact once the trial is completed. The proposed design not only gains insights on the patients who would be included in the trial but also considers the benefit to the excluded patients. We develop novel algorithms to construct enrollment rules for optimizing population impact, which are fairly general and can be applied to various types of outcomes. Simulation studies and a data example from the SWOG Cancer Research Network demonstrate the competitive performance of our proposed method compared to traditional untargeted and targeted designs.

Human papillomavirus (HPV) vaccination: from clinical studies to immunization programs.

Cervical cancer incidence and mortality have decreased in high-income countries, but low- and middle-income countries continue to bear a significant burden from the disease. Human papillomavirus (HPV) vaccines are a promising alternative for disease control; however, their introduction is slow in settings with greater need. We conducted a review of HPV vaccine efficacy and effectiveness reported in clinical trials and population-based studies. Efficacy of HPV vaccines is close to 100% when using a three-dose schedule in HPV-negative young women (<25 years old) for protection against persistent infection and HPV vaccine-type associated pre-cancerous lesions. Furthermore, sustained protection for up to 12 years of follow-up has been demonstrated; cross-protection against non-vaccine types is particularly observed for the bivalent vaccine, and preliminary data regarding impact on invasive cancer have emerged. Given its lower efficacy, catch-up vaccination beyond 19 years of age and proposals for vaccinating adult women deserve careful evaluation in accurately designed studies and economic analyses. Despite positive results regarding immunogenicity and post-hoc analysis for cervical intra-epithelial neoplasia in clinical trials, population-based data for prime and booster two-dose schedules are not available. Evaluation of vaccine safety from surveillance systems in immunization programs that have already distributed more than 270 million doses found no association of HPV vaccination with serious side effects. The introduction of HPV vaccination in national immunization programs remains the main challenge in tackling the burden of cervical cancer (up to 2018, only 89 countries have introduced vaccination worldwide, and most of these are high-income countries). Access models and technical capacity require further development to help low- and middle-income countries to increase the pace of vaccine delivery. Alternative approaches such as one-dose schedules and vaccination at younger ages may help reduce the programmatic and economic challenges to adolescent vaccination.

Comparing apples and pears: misleading conclusions about the population mental health impact of a parenting programme, a commentary on Marryat, Thompson and Wilson (2017).

BACKGROUND: The article by Marryat, Thompson and Wilson (2017) in BMC Pediatrics presents an evaluation of the implementation of the Triple P system as a public health intervention conducted by the Glasgow City Council and NHS Greater Glasgow and Clyde. DISCUSSION: Unfortunately, the conclusions drawn are questionable for multiple reasons. The lack of a controlled design precludes defensible conclusions about intervention effects free from routine threats to internal validity. There was a substantial mismatch between the intervention sample and the population sample assessed. The article's title and abstract leave readers with the mistaken impression that the children assessed for outcome were suitably representative of intervention families, when in fact many of the children in the intervention families were missing from the teacher-report outcome assessment (a single questionnaire), and many or most of the children in the teacher-report outcome assessment belonged to families who had never received the intervention. Although Triple P targets parent-child relations and child behavioural and emotional problems at home, Marryat et al. narrowly defined mental health impact as child difficulties in nursery or preschool, while not reporting data from practitioners and parents in the same evaluation that did not support the authors' conclusion. The paper was further diminished by a number of misleading statements and factual errors related for example to other research on Triple P. Studying the extent to which child mental health functioning at home can generalise to school settings is an important topic of inquiry in relation to parenting support interventions, but unfortunately the Marryat et al. article did not move this area forward.

Concordant and discordant familial cancer: Familial risks, proportions and population impact.

Relatives of cancer patients are at an increased risk of the same (concordant) cancer but whether they are at a risk for different (discordant) cancers is largely unknown - beyond well characterized hereditary cancer syndromes - but would be of major scientific and clinical interest. We therefore decided to resolve the issue by analyzing familial risks when family members were diagnosed with any discordant cancers. We compared the population impact of concordant to discordant familial cancer. The Swedish Family-Cancer Database (FCD) was used to calculate familial relative risks (RRs) for family members of cancer patients, for the 27 most common cancers. Population attributable fractions (PAFs) were estimated for concordant and discordant family histories. Discordant cancers in the family were detected as significant risk factors for the majority of cancers, although the corresponding RRs were modest compared to RRs for concordant cancers. Risks increased with the number of affected family members with the highest RRs for pancreatic (2.31), lung (1.69), kidney (1.98), nervous system (1.79) and thyroid cancers (3.28), when 5 or more family members were diagnosed with discordant cancers. For most cancers, the PAF for discordant family history exceeded that for concordant family history. Our findings suggest that there is an unspecific genetic predisposition to cancer with clinical consequences. We consider it unlikely that shared environmental risk factors could essentially contribute to the risks for diverse discordant cancers, which are likely driven by genetic predisposition. The identification of genes that moderately increase the risk for many cancers will be a challenge.

Population Impact and Effectiveness of Monovalent Rotavirus Vaccination in Urban Malawian Children 3 Years After Vaccine Introduction: Ecological and Case-Control Analyses.

BACKGROUND: Rotavirus vaccines have been introduced in many low-income African countries including Malawi in 2012. Despite early evidence of vaccine impact, determining persistence of protection beyond infancy, the utility of the vaccine against specific rotavirus genotypes, and effectiveness in vulnerable subgroups is important. METHODS: We compared rotavirus prevalence in diarrheal stool and hospitalization incidence before and following rotavirus vaccine introduction in Malawi. Using case-control analysis, we derived vaccine effectiveness (VE) in the second year of life and for human immunodeficiency virus (HIV)-exposed and stunted children. RESULTS: Rotavirus prevalence declined concurrent with increasing vaccine coverage, and in 2015 was 24% compared with prevaccine mean baseline in 1997-2011 of 32%. Since vaccine introduction, population rotavirus hospitalization incidence declined in infants by 54.2% (95% confidence interval [CI], 32.8-68.8), but did not fall in older children. Comparing 241 rotavirus cases with 692 test-negative controls, VE was 70.6% (95% CI, 33.6%-87.0%) and 31.7% (95% CI, -140.6% to 80.6%) in the first and second year of life, respectively, whereas mean age of rotavirus cases increased from 9.3 to 11.8 months. Despite higher VE against G1P[8] than against other genotypes, no resurgence of nonvaccine genotypes has occurred. VE did not differ significantly by nutritional status (78.1% [95% CI, 5.6%-94.9%] in 257 well-nourished and 27.8% [95% CI, -99.5% to 73.9%] in 205 stunted children;P= .12), or by HIV exposure (60.5% [95% CI, 13.3%-82.0%] in 745 HIV-unexposed and 42.2% [95% CI, -106.9% to 83.8%] in 174 exposed children;P= .91). CONCLUSIONS: Rotavirus vaccination in Malawi has resulted in reductions in disease burden in infants <12 months, but not in older children. Despite differences in genotype-specific VE, no genotype has emerged to suggest vaccine escape. VE was not demonstrably affected by HIV exposure or stunting.

A population model of the impact of a rodenticide containing strychnine on Great Basin Gophersnakes (Pituophis catenifer deserticola).

Strychnine is a neurotoxin and an active ingredient in some rodenticides which are placed in burrows to suppress pocket gopher (Thomomys talpoides) populations in range and crop land in western North America. The population level impact was modelled of the use of strychnine-based rodenticides on a non-target snake species, the Great Basin Gophersnake (Pituophis catenifer deserticola), which is a predator of pocket gopher and a Species at Risk in Canada. Using information on population density, demographics, and movement and habitat suitability for the Gophersnake living in an agricultural valley in BC, Canada, we estimated the impact of the poisoning of adult snakes on the long-term population size. To determine the area where Gophersnakes could be exposed to strychnine, we used vendor records of a rodenticide, and quantified the landcover areas of orchards and vineyards where the compound was most commonly applied. GIS analysis determined the areas of overlap between those agricultural lands and suitable habitats used by Gophersnakes. Stage-based population matrix models revealed that in a low density (0.1/ha) population scenario, a diet of one pocket gopher per year wherein 10 % of them carried enough strychnine to kill an adult snake could cause the loss of 2 females annually from the population and this would reduce the population by 35.3 % in 25 years. Under the same dietary exposure, up to 35 females could die per year in a high density (0.4/ha) population which would result in a loss of 50 % of adults in 25 years.

Healthy behaviours and 10-year incidence of diabetes: a population cohort study.

OBJECTIVE: To examine the association between meeting behavioural goals and diabetes incidence over 10 years in a large, representative Swedish population. METHODS: Population-based prospective cohort study of 32,120 individuals aged 35 to 55 years participating in a health promotion intervention in Västerbotten County, Sweden (1990 to 2013). Participants underwent an oral glucose tolerance test, clinical measures, and completed diet and activity questionnaires. Poisson regression quantified the association between achieving six behavioural goals at baseline - body mass index (BMI) <25 kg/m(2), moderate physical activity, non-smoker, fat intake <30% of energy, fibre intake ≥15 g/4184 kJ and alcohol intake ≤20 g/day - and diabetes incidence over 10 years. RESULTS: Median interquartile range (IQR) follow-up time was 9.9 (0.3) years; 2211 individuals (7%) developed diabetes. Only 4.4% of participants met all 6 goals (n=1245) and compared to these individuals, participants meeting 0/1 goals had a 3.74 times higher diabetes incidence (95% confidence interval (CI)=2.50 to 5.59), adjusting for sex, age, calendar period, education, family history of diabetes, history of myocardial infarction and long-term illness. If everyone achieved at least four behavioural goals, 14.1% (95% CI: 11.7 to 16.5%) of incident diabetes cases might be avoided. CONCLUSION: Interventions promoting the achievement of behavioural goals in the general population could significantly reduce diabetes incidence.

App Usage Factor: A Simple Metric to Compare the Population Impact of Mobile Medical Apps.

BACKGROUND: One factor when assessing the quality of mobile apps is quantifying the impact of a given app on a population. There is currently no metric which can be used to compare the population impact of a mobile app across different health care disciplines. OBJECTIVE: The objective of this study is to create a novel metric to characterize the impact of a mobile app on a population. METHODS: We developed the simple novel metric, app usage factor (AUF), defined as the logarithm of the product of the number of active users of a mobile app with the median number of daily uses of the app. The behavior of this metric was modeled using simulated modeling in Python, a general-purpose programming language. Three simulations were conducted to explore the temporal and numerical stability of our metric and a simulated app ecosystem model using a simulated dataset of 20,000 apps. RESULTS: Simulations confirmed the metric was stable between predicted usage limits and remained stable at extremes of these limits. Analysis of a simulated dataset of 20,000 apps calculated an average value for the app usage factor of 4.90 (SD 0.78). A temporal simulation showed that the metric remained stable over time and suitable limits for its use were identified. CONCLUSIONS: A key component when assessing app risk and potential harm is understanding the potential population impact of each mobile app. Our metric has many potential uses for a wide range of stakeholders in the app ecosystem, including users, regulators, developers, and health care professionals. Furthermore, this metric forms part of the overall estimate of risk and potential for harm or benefit posed by a mobile medical app. We identify the merits and limitations of this metric, as well as potential avenues for future validation and research.

COVID-19 Vaccination and Public Health: Addressing Global, Regional, and Within-Country Inequalities.

The COVID-19 pandemic, with over 775 million cases and 7 million deaths by May 2024, has drastically impacted global public health and exacerbated existing healthcare inequalities. The swift development and distribution of COVID-19 vaccines have been critical in combating the virus, yet disparities in access to and administration of the vaccine have highlighted deep-seated inequities at global, regional, and national levels. Wealthier nations have benefited from early access to vaccines, while low- and middle-income countries (LMICs) have faced persistent shortages. Initiatives such as COVAX aimed to address these disparities, but challenges persist. Socioeconomic factors, education, ethnic identity, and the healthcare infrastructure play crucial roles in vaccine equity. For example, lower-income individuals often face barriers such as poor access to healthcare, misinformation, and logistical challenges, particularly in rural areas. Addressing these inequities requires a multifaceted approach, integrating national policies with local strategies to enhance vaccines' accessibility, counter misinformation, and ensure equitable distribution. Collaborative efforts at all levels are essential to promote vaccine equity and effectively control the pandemic, ensuring that all populations have fair access to life-saving vaccines. This review explores these complex issues, offering insights into the barriers and facilitators of vaccine equity and providing recommendations to promote more equitable and effective vaccination programs. With a focus on the different levels at which vaccination policies are planned and implemented, the text provides guidelines to steer vaccination strategies, emphasizing the role of international cooperation and local policy frameworks as keys to achieving equitable vaccination coverage.

Disease Burden in Children With Spinal Muscular Atrophy: Results From a Large Cross-Sectional Study.

Background:To facilitate advances in spinal muscular atrophy therapeutic research, it is important to determine the impact and prevalence of symptoms experienced by children with spinal muscular atrophy. Methods: We conducted qualitative interviews with caregivers of children with spinal muscular atrophy. From these interviews, we generated a survey inquiring about 260 symptoms of importance grouped into 17 symptomatic themes. Results: Sixteen caregivers of children with spinal muscular atrophy aged from 4 months to 12 years participated in initial interviews, and 77 caregivers completed the survey. Higher symptom prevalence was associated with spinal muscular atrophy type, SMN2 copy number, and functional status. Hip, thigh, or knee weakness had the greatest reported impact on the lives of children with spinal muscular atrophy. Conclusions: This research provides one of the largest data sets regarding disease burden in children with spinal muscular atrophy. The most prevalent symptoms are not identical to those with the greatest impact. This unique insight into the most impactful symptoms will help focus therapeutic development in spinal muscular atrophy.

The Effect of COVID-19 Pandemic on Overall and Cause-Specific Mortality in Pavia, Northern Italy: Updated Estimates for the Year 2021.

Excess mortality estimates are considered relevant indicators of direct and indirect pandemic effects on the population. Scant data have been published on cause-specific excess mortality. Using individual-level administrative data covering the Pavia province of Italian northern Lombardy region, we provided all-cause and cause-specific raw (RMR) and age-standardized (ASMR) mortality rates in 2021 and 2015-2019, the rate ratio, and 95% confidence intervals, overall and by sex. We obtained the excess deaths in 2021 as the difference between the number of observed and expected deaths from all causes and the two leading causes of death (all neoplasms and circulatory system diseases) by fitting over-dispersed quasi-Poisson regression models, accounting for temporal, seasonal and demographic changes. The total ASMR in 2021 was 972.4/100,000 (6836 certified deaths), with the highest ASMRs for circulatory system diseases (272.6/100,000) and all neoplasms (270.3/100,000), followed by COVID-19 (94.8/100,000 and 662 deaths). Compared to the expected, we estimated a total of 6.2% excess deaths in 2021 (7.2% in males and 5.4% in females), with no excess deaths from all neoplasms and a 6.2% reduction from circulatory system diseases. COVID-19 continued to affect total mortality in 2021, albeit to a lesser extent than in 2020, consistently with national patterns.

Organizational perspectives on implementing complex health interventions: clinical genomics in Australia.

PURPOSE: Clinical genomics is a complex, innovative medical speciality requiring clinical and organizational engagement to fulfil the clinical reward promised to date. Focus thus far has been on gene discovery and clinicians' perspectives. The purpose of this study was to use implementation science theory to identify organizational barriers and enablers to implementation of clinical genomics along an organizations' implementation journey from Preadoption through to Adoption and Implementation. DESIGN/METHODOLOGY/APPROACH: We used a deductive qualitative approach study design drawing on implementation science theory - (1) Translation Science to Population Impact Framework, to inform semi structured interviews with organizational decision-makers collaborating with Australian and Melbourne Genomics, alongside and (2) Theoretical Domains Framework (TDF), to guide data analysis. FINDINGS: We identified evolving organizational barriers across the implementation journey from Preadoption to Implementation. Initially the organizational focus is on understanding the value of clinical genomics (TDF code: belief about consequences) and setting the scene (TDF code: goals) before organizational (TDF codes: knowledge and belief about consequences) and clinician (TDF codes: belief about capability and intentions) willingness to adopt is apparent. Once at the stage of Implementation, leadership and clarity in organizational priorities (TDF codes: intentions, professional identity and emotion) that include clinical genomics are essential prerequisites to implementing clinical genomics in practice. Intuitive enablers were identified (e.g. 'providing multiple opportunities for people to come on board) and mapped hypothetically to barriers. ORIGINALITY/VALUE: Attention to date has centred on the barriers facing clinicians when introducing clinical genomics into practice. This paper uses a combination of implementation science theories to begin to unravel the organizational perspectives of implementing this complex health intervention.

Potential Impact of the 2017 High Blood Pressure Guideline Beyond the United States: A Case Study of the People's Republic of China.

BACKGROUND: The 2017 American College of Cardiology (ACC)/American Heart Association (AHA) (US) Guideline for the Prevention, Detection, Evaluation and Management of High Blood Pressure in Adults expanded the definition of hypertension and now considers atherosclerotic cardiovascular disease (ASCVD) risk in determining treatment for people with hypertension. US guidelines are influential around the world and it is therefore justified to study their impact in other settings. Our study determined the impact of adopting the 2017 ACC/AHA guideline in China. METHODS: We analyzed the population impact of the 2017 ACC/AHA guideline using the 2011-2012 year of the China Health and Retirement Longitudinal Study (CHARLS), a nationally representative sample of Chinese adults 45-74 years of age (n = 11,822). Our analysis was unique because for the first time it used a population-appropriate equation to calculate ASCVD risk instead of the US Pooled Cohort Equation (the latter misrepresents risk in non-US populations). RESULTS: Adopting the 2017 ACC/AHA guideline in China would increase the prevalence of hypertension from 44.1% to 56.4% (12.3 percentage points) and increase the number of adults recommended for antihypertensive medication from 41.6% to 49.1% (7.5 percentage points) in the 45-74-year age range. According to Chinese (but not US) risk calculations, the 2017 ACC/AHA guideline more selectively assigns antihypertensive medication to patients at higher risk for ASCVD. CONCLUSIONS: The 2017 ACC/AHA guideline brings potential for risk reduction in China and selectively recommends medication for those who would benefit most. Realizing such benefits would ultimately depend on the acceptance, adherence, and feasibility of adopting this guideline.

Implementation science to reduce the prevalence and burden of MSK disorders following sport and exercise-related injury.

Although safety in sports and physical activity is an important prerequisite for continuing participation and maintenance of a healthy, physically active lifestyle, to date little effort has been placed upon moving evidence into preventive practice. Amongst researchers it is still often assumed that a program will disseminate itself after proven to be effective. Recently, however, there has been an increased recognition of the importance of theory-driven approaches to enhance implementation research. This manuscript aims to provide guidance for sports and physical activity injury researchers and practitioners to perform implementation research and practice. First, we will discuss the differences between research questions across the research spectrum and explain the 'drop' in effect when moving controlled evidence to a practical context. We will discuss two ways of increasing real-world effectiveness of preventive programs, i.e. through targeting the users' behaviour or through revising the intervention. Finally, we will present various implementation frameworks and tools that can guide the reader in their own efforts towards implementation practice and research.

The Potential Impact of the New York State Smokers' Quitline on Population-Level Smoking Rates in New York.

Receiving smoking cessation services from telephone quitlines significantly increases quit success compared with no intervention or other quitting methods. To affect population-level smoking, quitlines must provide a sufficient proportion of smokers with effective interventions. Nationally, quitlines reach around 1% of adult smokers annually. From 2011 through 2016, the average annual reach of the New York State Smokers' Quitline (NYSSQL) was 2.9%. We used data on the reach and cessation outcomes of NYSSQL to estimate its current impact on population-level smoking prevalence and to estimate how much reach would have to increase to achieve population-level smoking prevalence reductions. We estimate NYSSQL is associated with a 0.02 to 0.04 percentage point reduction in smoking prevalence in New York annually. If NYSSQL achieved the recommended annual reach of 8% (CDC Best Practices) and 16% (NAQC), state-level prevalence would decrease by an estimated 0.07-0.12 and 0.13-0.24 percentage points per year, respectively. To achieve those recommended levels of reach, NYSSQL would need to provide services to approximately 3.5 to 6.9 times more smokers annually. Given their reach, quitlines are limited in their ability to affect population-level smoking. Increasing quitline reach may not be feasible and would likely be cost-prohibitive. It may be necessary to re-think the role of quitlines in tobacco control efforts. In New York, the quitline is being integrated into larger efforts to promote cessation through health systems change.

Temporal trends in TB notification rates during ART scale-up in Cape Town: an ecological analysis.

INTRODUCTION: Although antiretroviral therapy (ART) reduces individual tuberculosis (TB) risk by two-thirds, the population-level impact remains uncertain. Cape Town reports high TB notification rates associated with endemic HIV. We examined population trends in TB notification rates during a 10-year period of expanding ART. METHODS: Annual Cape Town TB notifications were used as numerators and mid-year Cape Town populations as denominators. HIV-stratified population was calculated using overall HIV prevalence estimates from the Actuarial Society of South Africa AIDS and Demographic model. ART provision numbers from Western Cape government reports were used to calculate overall ART coverage. We calculated rates per 100,000 population over time, overall and stratified by HIV status. Rates per 100,000 total population were also calculated by ART use at treatment initiation. Absolute numbers of notifications were compared by age and sub-district. Changes over time were described related to ART provision in the city as a whole (ART coverage) and by sub-district (numbers on ART). RESULTS: From 2003 to 2013, Cape Town's population grew from 3.1 to 3.7 million inhabitants, and estimated HIV prevalence increased from 3.6 to 5.2%. ART coverage increased from 0 to 63% in 2013. TB notification rates declined by 16% (95% confidence interval (CI), 14-17%) from a 2008 peak (851/100,000) to a 2013 nadir (713/100,000). Decreases were higher among the HIV-positive (21% (95% CI, 19-23%)) than the HIV-negative (9% (95% CI, 7-11%)) population. The number of HIV-positive TB notifications decreased mainly among 0- to 4- and 20- to 34-year-olds. Total population rates on ART at TB treatment initiation increased over time but levelled off in 2013. Overall median CD4 counts increased from 146 cells/µl (interquartile range (IQR), 66, 264) to 178 cells/µl (IQR 75, 330; p<0.001). Sub-district antenatal HIV seroprevalence differed (10-33%) as did numbers on ART (9-29 thousand). Across sub-districts, infant HIV-positive TB decreased consistently whereas adult decreases varied. CONCLUSIONS: HIV-positive TB notification rates declined during a period of rapid scale-up of ART. Nevertheless, both HIV-positive and HIV-negative TB notification rates remained very high. Decreases among HIV positives were likely blunted by TB remaining a major entry to the ART programme and occurring after delayed ART initiation.