Systematic comparison of household income, consumption, and assets to measure health inequalities in low- and middle-income countries.

There has been no systematic comparison of how the three most common measures to quantify household SES-income, consumption, and asset indices-could impact the magnitude of health inequalities. Microdata from 22 Living Standards Measurement Study surveys were compiled and concentration indices, relative indices of inequality, and slope indices of inequality were calculated for underweight, stunting, and child deaths using income, consumption, asset indices, and hybrid predicted income. Meta-analyses of survey year subgroups (pre-1995, 1995-2004, and post-2004), outcomes (child deaths, stunting, and underweight), and World Bank country-income status (low, low-middle, and upper-middle) were then conducted. Asset indices and the related hybrid income proxy result in the largest magnitudes of health inequalities for all 12 overall outcomes, as well as most country-income and survey year subgroupings. There is no clear trend of health inequality magnitudes changing over time, but magnitudes of health inequality may increase as country-income levels increase. There is no significant difference between relative and absolute inequality measures, but the hybrid predicted income measure behaves more similarly to asset indices than the household income it is supposed to model. Health inequality magnitudes may be affected by the choice of household SES measure and should be studied in further detail.

Beyond MPOWER: a systematic review of population-level factors that affect European tobacco smoking rates.

BACKGROUND: Population-level factors within and beyond the scope of the World Health Organization's (WHO) MPOWER policy package have significant impacts on smoking rates. However, no synthesis of the existing evidence exists. This systematic review identifies population-level factors that influence cigarette smoking rates in European countries. METHODS: We searched the ProQuest database collection for original, peer-reviewed quantitative evaluations that investigated the effects of population-level exposures on smoking rates in European countries. Of the 3122 studies screened, 62 were ultimately included in the review. A standardized data extraction form was used to identify key characteristics of each study including publication year, years evaluated, countries studied, population characteristics, study design, data sources, analytic methods, exposure studied, relevant covariates and effects on tobacco smoking outcomes. RESULTS: One hundred and fifty-five population-level exposures were extracted from the 62 studies included in the review, 99 of which were related to WHO MPOWER measures. An additional 56 exposures fell into eight policy realms: economic crises, education policy, macro-economic factors, non-MPOWER tobacco regulations, population welfare, public policy, sales to minors and unemployment rates. About one-half of the MPOWER exposures affected smoking rates (55/99) and did so in an overwhelmingly positive way (55/55). Over three-quarters of the non-MPOWER exposures were associated with statistically significant changes in smoking outcomes (43/56), with about two-thirds of these exposures leading to a decrease in smoking (29/43). CONCLUSIONS: Population-level factors that fall outside of the WHO's MPOWER measures are an understudied research area. The impacts of these factors on tobacco control should be considered by policymakers.

Quasi-experimental evaluation of national border closures on COVID-19 transmission.

With over 200 pandemic threats emerging every year, the efficacy of closing national borders to control the transmission of disease in the first months of a pandemic remains a critically important question. Previous studies offer conflicting evidence for the potential effects of these closures on COVID-19 transmission and no study has yet empirically evaluated the global impact of border closures using quasi-experimental methods and real-world data. We triangulate results from interrupted time-series analysis, meta-regression, coarsened exact matching, and an extensive series of robustness checks to evaluate the effect of 166 countries' national border closures on the global transmission of COVID-19. Total border closures banning non-essential travel from all countries and (to a lesser extent) targeted border closures banning travel from specific countries had some effect on temporarily slowing COVID-19 transmission in those countries that implemented them. In contrast to these country-level impacts, the global sum of targeted border closures implemented by February 5, 2020 was not sufficient to slow global COVID-19 transmission, but the sum of total border closures implemented by March 19, 2020 did achieve this effect. Country-level results were highly heterogeneous, with early implementation and border closures so broadly targeted that they resemble total border closures improving the likelihood of slowing the pandemic's spread. Governments that can make productive use of extra preparation time and cannot feasibly implement less restrictive alternatives might consider enacting border closures. However, given their moderate and uncertain impacts and their significant harms, border closures are unlikely to be the best policy response for most countries and should only be deployed in rare circumstances and with great caution. All countries would benefit from global mechanisms to coordinate national decisions on border closures during pandemics.

Vorinostat Improves Myotonic Dystrophy Type 1 Splicing Abnormalities in DM1 Muscle Cell Lines and Skeletal Muscle from a DM1 Mouse Model.

Myotonic dystrophy type 1 (DM1), the most common form of adult muscular dystrophy, is caused by an abnormal expansion of CTG repeats in the 3' untranslated region of the dystrophia myotonica protein kinase (DMPK) gene. The expanded repeats of the DMPK mRNA form hairpin structures in vitro, which cause misregulation and/or sequestration of proteins including the splicing regulator muscleblind-like 1 (MBNL1). In turn, misregulation and sequestration of such proteins result in the aberrant alternative splicing of diverse mRNAs and underlie, at least in part, DM1 pathogenesis. It has been previously shown that disaggregating RNA foci repletes free MBNL1, rescues DM1 spliceopathy, and alleviates associated symptoms such as myotonia. Using an FDA-approved drug library, we have screened for a reduction of CUG foci in patient muscle cells and identified the HDAC inhibitor, vorinostat, as an inhibitor of foci formation; SERCA1 (sarcoplasmic/endoplasmic reticulum Ca2+-ATPase) spliceopathy was also improved by vorinostat treatment. Vorinostat treatment in a mouse model of DM1 (human skeletal actin-long repeat; HSALR) improved several spliceopathies, reduced muscle central nucleation, and restored chloride channel levels at the sarcolemma. Our in vitro and in vivo evidence showing amelioration of several DM1 disease markers marks vorinostat as a promising novel DM1 therapy.

Classifying European cigarette consumption trajectories from 1970 to 2015.

OBJECTIVES: To systematically code and classify longitudinal cigarette consumption trajectories in European countries since 1970. DESIGN: Blinded duplicate qualitative coding of periods of year-over-year relative increase, plateau, and decrease of national per capita cigarette consumption and categorisation of historical cigarette consumption trajectories based on longitudinal patterns emerging from the data. SETTING: 41 countries or former countries in the European region for which data are available between 1970 and 2015. RESULTS: Regional trends in longitudinal consumption patterns identify stable or decreasing consumption throughout Northern, Western and Southern European countries, while Eastern and Southeastern European countries experienced much greater instability. The 11 emergent classes of historical cigarette consumption trajectories were also regionally clustered, including a distinctive inverted U or sine wave pattern repeatedly emerging from former Soviet and Southeastern European countries. CONCLUSIONS: The open-access data produced by this study can be used to conduct comparative international evaluations of tobacco control policies by separating impacts likely attributable to gradual long-term trends from those more likely attributable to acute short-term events. The complex, regionally clustered historical trajectories of cigarette consumption in Europe suggest that the enduring normative frame of a gently sloping downward curve in cigarette consumption can offer a false sense of security among policymakers and can distract from plausible causal mechanisms among researchers. These multilevel and multisectoral causal mechanisms point to the need for a greater understanding of the political economy of regional and global determinants of cigarette consumption.

International treaties have mostly failed to produce their intended effects.

There are over 250,000 international treaties that aim to foster global cooperation. But are treaties actually helpful for addressing global challenges? This systematic field-wide evidence synthesis of 224 primary studies and meta-analysis of the higher-quality 82 studies finds treaties have mostly failed to produce their intended effects. The only exceptions are treaties governing international trade and finance, which consistently produced intended effects. We also found evidence that impactful treaties achieve their effects through socialization and normative processes rather than longer-term legal processes and that enforcement mechanisms are the only modifiable treaty design choice with the potential to improve the effectiveness of treaties governing environmental, human rights, humanitarian, maritime, and security policy domains. This evidence synthesis raises doubts about the value of international treaties that neither regulate trade or finance nor contain enforcement mechanisms.

Principles and methods of global legal epidemiology.

Although the theory and methods of legal epidemiology-the scientific study and deployment of law as a factor in the cause, distribution, and prevention of disease and injury in a population-have been well developed in the context of domestic law, the challenges posed by shifting the frame of analysis to the global legal space have not yet been fully explored. While legal epidemiology rests on the foundational principles that law acts as an intervention, that law can be an object of scientific study and that law has impacts that should be evaluated, its application to the global level requires the recognition that international laws, policies and norms can cause effects independently from their legal implementation within countries. The global legal space blurs distinctions between 'hard' and 'soft' law, often operating through pathways of global agenda setting, legal language, political pressures, social mobilisation and trade pressures to have direct impacts on people, places and products. Despite these complexities, international law has been overwhelmingly studied as operating solely through national policy change, with only one global quasi-experimental evaluation of an international law's impact on health published to date. To promote greater adoption of global legal epidemiology, we expand on an existing typology of public health law studies with examples of policymaking, mapping, implementation, intervention and mechanism studies. Global legal epidemiology holds great promise as a way to produce rigorous and impactful research on the international laws, policies and norms that shape our collective health, equity and well-being.

Informality, Social Citizenship, and Wellbeing among Migrant Workers in Costa Rica in the Context of COVID-19.

Costa Rica is home to 557,000 migrants, whose disproportionate exposure to precarious, dangerous, and informal work has resulted in persistent inequities in health and wellbeing in the midst of the COVID-19 pandemic. We used a novel multimodal grounded approach synthesizing documentary film, experiential education, and academic research to explore socioecological wellbeing among Nicaraguan migrant workers in Costa Rica. Participants pointed to the COVID-19 pandemic as exacerbating the underlying conditions of vulnerability, such as precarity and informality, dangerous working conditions, social and systemic discrimination, and additional burdens faced by women. However, the narrative that emerged most consistently in shaping migrants' experience of marginalization were challenges in obtaining documentation-both in the form of legal residency and health insurance coverage. Our results demonstrate that, in spite of Costa Rica's acclaimed social welfare policies, migrant workers continue to face exclusion due to administrative, social, and financial barriers. These findings paint a rich picture of how multiple intersections of precarious, informal, and dangerous working conditions; social and systemic discrimination; gendered occupational challenges; and access to legal residency and health insurance coverage combine to prevent the full achievement of a shared minimum standard of social and economic security for migrant workers in Costa Rica.

Adopting a Global AMR Target within the Pandemic Instrument Will Act as a Catalyst for Action.

Ensuring that life-saving antimicrobials remain available as effective treatment options in the face of rapidly rising levels of antimicrobial resistance will require a massive and coordinated global effort. Setting a collective direction for progress is the first step towards aligning global efforts on AMR. This process would be greatly accelerated by adopting a unifying global target - a well-defined global target that unites all countries and sectors. The proposed pandemic instrument - with its focus on prevention, preparedness and response - represents an ideal opportunity to develop and adopt a unifying global target that catalyzes global action on AMR. We propose three key characteristics of a unifying global target for AMR that - if embedded within the pandemic preparedness instrument - could rally public support, funding, and political commitment commensurate with the scale of the AMR challenge.

Is the lack of smartphone data skewing wealth indices in low-income settings?

BACKGROUND: Smartphones have rapidly become an important marker of wealth in low- and middle-income countries, but international household surveys do not regularly gather data on smartphone ownership and these data are rarely used to calculate wealth indices. METHODS: We developed a cross-sectional survey module delivered to 3028 households in rural northwest Burkina Faso to measure the effects of this absence. Wealth indices were calculated using both principal components analysis (PCA) and polychoric PCA for a base model using only ownership of any cell phone, and a full model using data on smartphone ownership, the number of cell phones, and the purchase of mobile data. Four outcomes (household expenditure, education level, and prevalence of frailty and diabetes) were used to evaluate changes in the composition of wealth index quintiles using ordinary least squares and logistic regressions and Wald tests. RESULTS: Households that own smartphones have higher monthly expenditures and own a greater quantity and quality of household assets. Expenditure and education levels are significantly higher at the fifth (richest) socioeconomic status (SES) quintile of full model wealth indices as compared to base models. Similarly, diabetes prevalence is significantly higher at the fifth SES quintile using PCA wealth index full models, but this is not observed for frailty prevalence, which is more prevalent among lower SES households. These effects are not present when using polychoric PCA, suggesting that this method provides additional robustness to missing asset data to measure underlying latent SES by proxy. CONCLUSIONS: The lack of smartphone data can skew PCA-based wealth index performance in a low-income context for the top of the socioeconomic spectrum. While some PCA variants may be robust to the omission of smartphone ownership, eliciting smartphone ownership data in household surveys is likely to substantially improve the validity and utility of wealth estimates.

MMP inhibitors attenuate doxorubicin cardiotoxicity by preventing intracellular and extracellular matrix remodelling.

AIMS: Heart failure is a major complication in cancer treatment due to the cardiotoxic effects of anticancer drugs, especially from the anthracyclines such as doxorubicin (DXR). DXR enhances oxidative stress and stimulates matrix metalloproteinase-2 (MMP-2) in cardiomyocytes. We investigated whether MMP inhibitors protect against DXR cardiotoxicity given the role of MMP-2 in proteolyzing sarcomeric proteins in the heart and remodelling the extracellular matrix. METHODS AND RESULTS: Eight-week-old male C57BL/6J mice were treated with DXR weekly with or without MMP inhibitors doxycycline or ONO-4817 by daily oral gavage for 4 weeks. Echocardiography was used to determine cardiac function and left ventricular remodelling before and after treatment. MMP inhibitors ameliorated DXR-induced systolic and diastolic dysfunction by reducing the loss in left ventricular ejection fraction, fractional shortening, and E'/A'. MMP inhibitors attenuated adverse left ventricular remodelling, reduced cardiomyocyte dropout, and prevented myocardial fibrosis. DXR increased myocardial MMP-2 activity in part also by upregulating N-terminal truncated MMP-2. Immunogold transmission electron microscopy showed that DXR elevated MMP-2 levels within the sarcomere and mitochondria which were associated with myofilament lysis, mitochondrial degeneration, and T-tubule distention. DXR-induced myofilament lysis was associated with increased titin proteolysis in the heart which was prevented by ONO-4817. DXR also increased the level and activity of MMP-2 in human embryonic stem cell-derived cardiomyocytes, which was reduced by ONO-4817. CONCLUSIONS: MMP-2 activation is an early event in DXR cardiotoxicity and contributes to myofilament lysis by proteolyzing cardiac titin. Two orally available MMP inhibitors ameliorated DXR cardiotoxicity by attenuating intracellular and extracellular matrix remodelling, suggesting their use may be a potential prophylactic strategy to prevent heart injury during chemotherapy.

Health technology assessment and judicial deference to priority-setting decisions in healthcare: Quasi-experimental analysis of right-to-health litigation in Brazil.

The constitutional right to health in Brazil has entitled patients to litigate against the government-funded national health system (SUS), claiming access to various health treatments including those excluded from the health system's benefits package. Courts have tended to rely on a single medical prescription to judge these cases in favor of individual patients and against the health system. The large volume of cases has had a substantial financial impact on the government's health budget and has created unfairness in accessing healthcare. To change courts' behavior, a new health technology assessment (HTA) body - CONITEC - was created in 2011. Its creation was accompanied by an administrative procedure that made decisions about the health system's benefits package more transparent, accountable, participative and evidence-informed. It was expected that this HTA system would bring more legitimacy to the government's priority-setting decisions and promote deference from the courts. This study tests whether Brazil's new HTA system succeeded in encouraging judicial deference by analyzing a stratified random sample of 13,263 court decisions for whether the existence of a CONITEC report resulted in less frequent court orders to provide treatment for individual litigants. The results show that the creation of CONITEC did not change courts' behavior; courts still decide in favor of patients in most cases. Indeed, even when there was a CONITEC report recommending against government funding for a particular healthcare treatment, the vast majority of the relatively few patients who were unsuccessful in obtaining a health benefit at their first court hearing later obtained a favorable decision after appealing to a higher court. This finding was confirmed through an interrupted time-series analysis that did not find an impact of having a CONITEC report on courts' willingness to override a government priority-setting decision. In fact, CONITEC was rarely cited in court decisions, even when litigants mentioned the existence of a CONITEC report.

Geographic Targeting and Normative Frames: Revisiting the Equity of Conditional Cash Transfer Program Distribution in Bolivia, Colombia, Ecuador, and Peru.

BACKGROUND: Four Andean countries of Bolivia, Colombia, Ecuador, and Peru introduced national health-focused conditional cash transfer (CCT) programs in the 2000s. This study probes whether policymakers in these countries targeted CCT programs to subregions with the highest prevalence of ill-health or those with the lowest socioeconomic status (SES) to evaluate the equity of geographic targeting and means-testing, as well as the potential role of normative frames, bounded rationality, and clientelism as explanatory mechanisms for inequities in social spending. METHODS: The distribution of vaccination coverage, underweight, stunting, and child deaths is established both within and between subnational regions and SES quintiles from 1998 to 2012 using every available nationally representative household survey. The equity of CCT program targeting and strength of association with subregional SES and health outcomes are measured using generalized entropy index decomposition and meta-regression. Finally, simple predictive models for CCT targeting are created using lagged subregional SES, health outcomes, and concentration indices. RESULTS: Bolivia and Peru both effectively targeted at-risk subregions, but subregions in Peru with no CCT program coverage result in higher mistargeting rates for the country as a whole. Only Bolivia failed to attain CCT coverage concentration indices that are at least as large as the health inequalities they are targeting. Despite this insufficient progressivity, Bolivia has the most efficient subregional targeting, while the lowest rates of mistargeting for child deaths are found in Colombia and Ecuador. Finally, the simple predictive model performs as well or better than observed CCT coverage distribution for every country, year, and outcome. CONCLUSIONS: Both Peru and Ecuador have targeted programs to their poorest populations effectively, demonstrating that this is possible with both universal and geographic targeting. No clear evidence of clientelism was found, while the dominant normative frame underlying CCT program targeting decisions appears to be the relative SES of subregions, rather than absolute SES, prevalence of health outcomes, or health inequalities. To reduce the inequitable impacts of bounded rationality, policymakers can use simple predictive models to target CCT coverage effectively and without leaving behind the most vulnerable populations that happen to live in more affluent subregions.

F-actin flashes on phagosomes mechanically deform contents for efficient digestion in macrophages.

The mechanism and role of transient F-actin recruitment, or F-actin 'flashes', on phagosomes remains enigmatic. Here we provide a comprehensive characterization of F-actin flashing dynamics on phagosomes, including receptor and signaling involvement. F-actin flashes predominate during the integrin-driven complement receptor (CR)-mediated phagocytosis. F-actin flashes begin shortly after internalization and persist on phagosomes for approximately 3 minutes before disassembling and reassembling several times within the first hour. Strikingly, the appearance of F-actin flashes on phagosomes coincides with morphological deformation, lysis and occasional fission of internalized red blood cells. The cadence of flashes depends on particle stiffness, and the F-actin networks on phagosomes are enriched in mechanosensitive components including focal adhesion proteins, RhoA and actomyosin. Inhibiting Arp2/3 and myosin IIA activity significantly reduces the frequency at which phagosome cargo becomes deformed during transient F-actin accumulation. At later time points, post-F-actin flashing, enhanced degradation of phagosome contents is observed, compared with non-flashing phagosomes. Taken together, these data suggest that actomyosin-driven phagosome contractions serve to disrupt malleable particles physically, a process akin to mastication, to enhance later enzymatic digestion.

The socio-economic distribution of exposure to Ebola: Survey evidence from Liberia and Sierra Leone.

Socio-economic factors are widely believed to have been an important driver of the transmission of Ebola Virus Disease (EVD) during the West African outbreak of 2014-16, however, studies that have investigated the relationship between socio-economic status (SES) and EVD have found inconsistent results. Using nationally representative household survey data on whether respondents knew a close friend or family member with Ebola, we explore the SES determinants of EVD exposure along individual, household, and community lines in Liberia and Sierra Leone. While we find no overall association between household wealth and EVD exposure, we find that pooled data mask important differences observed within countries with higher wealth households more likely to have been exposed to EVD in Sierra Leone and the opposite relationship in Liberia. Finally, we also generally find a positive association between education and EVD exposure both at the individual and the community levels in the full sample. There is an urgent need to better understand these relationships to examine both why the outbreak spread and to help prepare for future outbreaks.

Junctophilin-2 is a target of matrix metalloproteinase-2 in myocardial ischemia-reperfusion injury.

Junctophilin-2 is a structural membrane protein that tethers T-tubules to the sarcoplasmic reticulum to allow for coordinated calcium-induced calcium release in cardiomyocytes. Defective excitation-contraction coupling in myocardial ischemia-reperfusion (IR) injury is associated with junctophilin-2 proteolysis. However, it remains unclear whether preventing junctophilin-2 proteolysis improves the recovery of cardiac contractile dysfunction in IR injury. Matrix metalloproteinase-2 (MMP-2) is a zinc and calcium-dependent protease that is activated by oxidative stress in myocardial IR injury and cleaves both intracellular and extracellular substrates. To determine whether junctophilin-2 is targeted by MMP-2, isolated rat hearts were perfused in working mode aerobically or subjected to IR injury with the selective MMP inhibitor ARP-100. IR injury impaired the recovery of cardiac contractile function which was associated with increased degradation of junctophilin-2 and damaged cardiac dyads. In IR hearts, ARP-100 improved the recovery of cardiac contractile function, attenuated junctophilin-2 proteolysis, and prevented ultrastructural damage to the dyad. MMP-2 was co-localized with junctophilin-2 in aerobic and IR hearts by immunoprecipitation and immunohistochemistry. In situ zymography showed that MMP activity was localized to the Z-disc and sarcomere in aerobic hearts and accumulated at sites where the striated JPH-2 staining was disrupted in IR hearts. In vitro proteolysis assays determined that junctophilin-2 is susceptible to proteolysis by MMP-2 and in silico analysis predicted multiple MMP-2 cleavage sites between the membrane occupation and recognition nexus repeats and within the divergent region of junctophilin-2. Degradation of junctophilin-2 by MMP-2 is an early consequence of myocardial IR injury which may initiate a cascade of sequelae leading to impaired contractile function.

Impact of the WHO Framework Convention on Tobacco Control on global cigarette consumption: quasi-experimental evaluations using interrupted time series analysis and in-sample forecast event modelling.

OBJECTIVE: To evaluate the impact of the WHO Framework Convention on Tobacco Control (FCTC) on global cigarette consumption. DESIGN: Two quasi-experimental impact evaluations, using interrupted time series analysis (ITS) and in-sample forecast event modelling. SETTING AND POPULATION: 71 countries for which verified national estimates of cigarette consumption from 1970 to 2015 were available, representing over 95% of the world's cigarette consumption and 85% of the world's population. MAIN OUTCOME MEASURES: The FCTC is an international treaty adopted in 2003 that aims to reduce harmful tobacco consumption and is legally binding on the 181 countries that have ratified it. Main outcomes were annual national estimates of cigarette consumption per adult from 71 countries since 1970, allowing global, regional, and country comparisons of consumption levels and trends before and after 2003, with counterfactual control groups modelled using pre-intervention linear time trends (for ITS) and in-sample forecasts (for event modelling). RESULTS: No significant change was found in the rate at which global cigarette consumption had been decreasing after the FCTC's adoption in 2003, using either ITS or event modelling. Results were robust after realigning data to the year FCTC negotiations commenced (1999), or to the year when the FCTC first became legally binding in each country. By contrast to global consumption, high income and European countries showed a decrease in annual consumption by over 1000 cigarettes per adult after 2003, whereas low and middle income and Asian countries showed an increased annual consumption by over 500 cigarettes per adult when compared with a counterfactual event model. CONCLUSIONS: This study finds no evidence to indicate that global progress in reducing cigarette consumption has been accelerated by the FCTC treaty mechanism. This null finding, combined with regional differences, should caution against complacency in the global tobacco control community, motivate greater implementation of proven tobacco control policies, encourage assertive responses to tobacco industry activities, and inform the design of more effective health treaties.

Cigarette consumption estimates for 71 countries from 1970 to 2015: systematic collection of comparable data to facilitate quasi-experimental evaluations of national and global tobacco control interventions.

OBJECTIVES: To collect, appraise, select, and report the best available national estimates of cigarette consumption since 1970. DESIGN: Systematic collection of comparable data. SETTING AND POPULATION: 71 of 214 countries for which searches for national cigarette consumption data were conducted, representing over 95% of global cigarette consumption and 85% of the world's population. MAIN OUTCOME MEASURES: Validated cigarette consumption data covering 1970-2015 were identified for 71 countries. Data quality appraisal was conducted by two research team members in duplicate, with greatest weight given to official government sources. All data were standardised into units of cigarettes consumed per year in each country, a detailed accounting of data quality and sourcing was prepared, and all collected data and metadata were made freely available in an open access dataset. RESULTS: Cigarette consumption fell in most countries over the past three decades but trends in country specific consumption were highly variable. For example, China consumed 2.5 million metric tonnes (MMT) of cigarettes in 2013, more than Russia (0.36 MMT), the United States (0.28 MMT), Indonesia (0.28 MMT), Japan (0.20 MMT), and the next 35 highest consuming countries combined. The US and Japan achieved reductions of more than 0.1 MMT from a decade earlier, whereas Russian consumption plateaued, and Chinese and Indonesian consumption increased by 0.75 MMT and 0.1 MMT, respectively. These data generally concord with modelled country level data from the Institute for Health Metrics and Evaluation and have the additional advantage of not smoothing year-over-year discontinuities that are necessary for robust quasi-experimental impact evaluations. CONCLUSIONS: Before this study, publicly available data on cigarette consumption have been limited; they have been inappropriate for quasi-experimental impact evaluations (modelled data), held privately by companies (proprietary data), or widely dispersed across many national statistical agencies and research organisations (disaggregated data). This new dataset confirms that cigarette consumption has decreased in most countries over the past three decades, but that secular country specific consumption trends are highly variable. The findings underscore the need for more robust processes in data reporting, ideally built into international legal instruments or other mandated processes. To monitor the impact of the WHO Framework Convention on Tobacco Control and other tobacco control interventions, data on national tobacco production, trade, and sales should be routinely collected and openly reported.

Systematic review and updated meta-analysis of the use of drug-coated balloon angioplasty versus plain old balloon angioplasty for femoropopliteal arterial disease.

OBJECTIVE: An endovascular-first approach is usually recommended in femoropopliteal occlusive disease. However, despite high technical success, plain old balloon angioplasty (POBA) is burdened with high restenosis rates. To reduce this phenomenon, local delivery of drugs has been proposed by way of drug-coated balloons (DCBs). Our goal was to review the evidence for the use of DCBs in the management of femoropopliteal disease and to determine whether it is associated with improved outcomes compared with POBA. METHODS: Electronic searches of PubMed (MEDLINE), Embase, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and proceedings of international conferences were performed to identify randomized controlled trials (RCTs) and observational registries evaluating the use of DCBs for femoropopliteal arterial occlusive disease. RESULTS: This meta-analysis included 13 RCTs, 6 global registries, and 3 global registries focusing on long lesions. They all used paclitaxel in the DCB arm. There was heterogeneity between trials, and the frequency of stent deployment and duration of dual antiplatelet therapy differed. At 2 years, there were significantly better outcomes for DCBs in terms of target lesion revascularization (odds ratio [OR], 0.29; 95% confidence interval [CI], 0.20-0.40), primary patency (OR, 0.38; 95% CI, 0.27-0.54), late lumen loss (mean diameter, -0.80 mm; 95% CI, -1.44 to -0.16), and Rutherford category (OR, 0.82; 95% CI, 0.57-1.19). There was no significant difference between DCBs and POBA in amputation or change in ankle-brachial index. A subgroup analysis revealed that male patients treated with DCBs performed significantly better than female patients and that diabetics, heavily calcified lesions, and popliteal lesions performed significantly worse than nondiabetics, noncalcified and mild to moderately calcified lesions, and exclusive superficial femoral artery lesions, respectively. Secondarily stented and nonpredilated lesions did not perform significantly worse, but standard-dose (3 µg/mm2) DCBs were significantly more effective than low-dose (2 µg/mm2) DCBs in reducing binary restenosis. In addition, in a low-dose DCB, the polyethylene glycol excipient performed significantly better than polysorbate and sorbitol, whereas binary restenosis was significantly less frequent with the urea excipient, associated with a standard-dose DCB, compared with the polysorbate and sorbitol excipient, associated with a low-dose DCB. CONCLUSIONS: DCB angioplasty is an effective treatment associated with high procedural success. In a meta-analysis of industry-sponsored trials, it consistently reduced late lumen loss, binary restenosis, and target lesion revascularization compared with POBA alone in the treatment of femoropopliteal disease. Further independent, non-industry-sponsored RCTs are necessary to better delineate the role of DCBs in the treatment of infrainguinal occlusive disease.