Medscape Medical News Major scientific advances over 35 years have already led to the best way to treat the disease. And new science is turning up clues that could eventually lead to a cure, he said.
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theheart.org on Medscape
Lancet. 2016 Aug 13;388(10045):654
Authors: Snyder A
PMID: 27551696 [PubMed - indexed for MEDLINE]
The Lancet in 19th-century America.
Lancet. 2016 Aug 13;388(10045):652-3
Authors: Halperin EC
PMID: 27551695 [PubMed - indexed for MEDLINE]
Lancet. 2016 Aug 13;388(10045):649
Authors: Barnett R
PMID: 27551694 [PubMed - indexed for MEDLINE]
Refugees need health cards, say German doctors.
Lancet. 2016 Aug 13;388(10045):646-8
Authors: Hyde R
PMID: 27533428 [PubMed - indexed for MEDLINE]
Health crisis intensifying in Nigeria's Borno State.
Lancet. 2016 Aug 13;388(10045):645
Authors: Burki T
PMID: 27533427 [PubMed - indexed for MEDLINE]
The last Summer Olympics? Climate change, health, and work outdoors.
Lancet. 2016 Aug 13;388(10045):642-4
Authors: Smith KR, Woodward A, Lemke B, Otto M, Chang CJ, Mance AA, Balmes J, Kjellstrom T
PMID: 27533426 [PubMed - indexed for MEDLINE]
NHS England: preparing for PrEP.
Lancet. 2016 Aug 13;388(10045):634
PMID: 27533425 [PubMed - indexed for MEDLINE]
Making room for mental health reform.
Lancet. 2016 Aug 13;388(10045):634
PMID: 27533424 [PubMed - indexed for MEDLINE]
Refugee and migrant crisis: the deficient global response.
Lancet. 2016 Aug 13;388(10045):633
PMID: 27533423 [PubMed - indexed for MEDLINE]
Safety and durability of effect of contralateral-eye administration of AAV2 gene therapy in patients with childhood-onset blindness caused by RPE65 mutations: a follow-on phase 1 trial.
Lancet. 2016 Aug 13;388(10045):661-72
Authors: Bennett J, Wellman J, Marshall KA, McCague S, Ashtari M, DiStefano-Pappas J, Elci OU, Chung DC, Sun J, Wright JF, Cross DR, Aravand P, Cyckowski LL, Bennicelli JL, Mingozzi F, Auricchio A, Pierce EA, Ruggiero J, Leroy BP, Simonelli F, High KA, Maguire AM
BACKGROUND: Safety and efficacy have been shown in a phase 1 dose-escalation study involving a unilateral subretinal injection of a recombinant adeno-associated virus (AAV) vector containing the RPE65 gene (AAV2-hRPE65v2) in individuals with inherited retinal dystrophy caused by RPE65 mutations. This finding, along with the bilateral nature of the disease and intended use in treatment, prompted us to determine the safety of administration of AAV2-hRPE65v2 to the contralateral eye in patients enrolled in the phase 1 study.
METHODS: In this follow-on phase 1 trial, one dose of AAV2-hRPE65v2 (1.5 × 10(11) vector genomes) in a total volume of 300 μL was subretinally injected into the contralateral, previously uninjected, eyes of 11 children and adults (aged 11-46 years at second administration) with inherited retinal dystrophy caused by RPE65 mutations, 1.71-4.58 years after the initial subretinal injection. We assessed safety, immune response, retinal and visual function, functional vision, and activation of the visual cortex from baseline until 3 year follow-up, with observations ongoing. This study is registered with ClinicalTrials.gov, number NCT01208389.
FINDINGS: No adverse events related to the AAV were reported, and those related to the procedure were mostly mild (dellen formation in three patients and cataracts in two). One patient developed bacterial endophthalmitis and was excluded from analyses. We noted improvements in efficacy outcomes in most patients without significant immunogenicity. Compared with baseline, pooled analysis of ten participants showed improvements in mean mobility and full-field light sensitivity in the injected eye by day 30 that persisted to year 3 (mobility p=0.0003, white light full-field sensitivity p<0.0001), but no significant change was seen in the previously injected eyes over the same time period (mobility p=0.7398, white light full-field sensitivity p=0.6709). Changes in visual acuity from baseline to year 3 were not significant in pooled analysis in the second eyes or the previously injected eyes (p>0.49 for all time-points compared with baseline).
INTERPRETATION: To our knowledge, AAV2-hRPE65v2 is the first successful gene therapy administered to the contralateral eye. The results highlight the use of several outcome measures and help to delineate the variables that contribute to maximal benefit from gene augmentation therapy in this disease.
FUNDING: Center for Cellular and Molecular Therapeutics at The Children's Hospital of Philadelphia, Spark Therapeutics, US National Institutes of Health, Foundation Fighting Blindness, Institute for Translational Medicine and Therapeutics, Research to Prevent Blindness, Center for Advanced Retinal and Ocular Therapeutics, Mackall Foundation Trust, F M Kirby Foundation, and The Research Foundation-Flanders.
PMID: 27375040 [PubMed - indexed for MEDLINE]
Immediate total-body CT scanning versus conventional imaging and selective CT scanning in patients with severe trauma (REACT-2): a randomised controlled trial.
Lancet. 2016 Aug 13;388(10045):673-83
Authors: Sierink JC, Treskes K, Edwards MJ, Beuker BJ, den Hartog D, Hohmann J, Dijkgraaf MG, Luitse JS, Beenen LF, Hollmann MW, Goslings JC, REACT-2 study group
BACKGROUND: Published work suggests a survival benefit for patients with trauma who undergo total-body CT scanning during the initial trauma assessment; however, level 1 evidence is absent. We aimed to assess the effect of total-body CT scanning compared with the standard work-up on in-hospital mortality in patients with trauma.
METHODS: We undertook an international, multicentre, randomised controlled trial at four hospitals in the Netherlands and one in Switzerland. Patients aged 18 years or older with trauma with compromised vital parameters, clinical suspicion of life-threatening injuries, or severe injury were randomly assigned (1:1) by ALEA randomisation to immediate total-body CT scanning or to a standard work-up with conventional imaging supplemented with selective CT scanning. Neither doctors nor patients were masked to treatment allocation. The primary endpoint was in-hospital mortality, analysed in the intention-to-treat population and in subgroups of patients with polytrauma and those with traumatic brain injury. The χ(2) test was used to assess differences in mortality. This trial is registered with ClinicalTrials.gov, number NCT01523626.
FINDINGS: Between April 22, 2011, and Jan 1, 2014, 5475 patients were assessed for eligibility, 1403 of whom were randomly assigned: 702 to immediate total-body CT scanning and 701 to the standard work-up. 541 patients in the immediate total-body CT scanning group and 542 in the standard work-up group were included in the primary analysis. In-hospital mortality did not differ between groups (total-body CT 86 [16%] of 541 vs standard work-up 85 [16%] of 542; p=0.92). In-hospital mortality also did not differ between groups in subgroup analyses in patients with polytrauma (total-body CT 81 [22%] of 362 vs standard work-up 82 [25%] of 331; p=0.46) and traumatic brain injury (68 [38%] of 178 vs 66 [44%] of 151; p=0.31). Three serious adverse events were reported in patients in the total-body CT group (1%), one in the standard work-up group (<1%), and one in a patient who was excluded after random allocation. All five patients died.
INTERPRETATION: Diagnosing patients with an immediate total-body CT scan does not reduce in-hospital mortality compared with the standard radiological work-up. Because of the increased radiation dose, future research should focus on the selection of patients who will benefit from immediate total-body CT.
FUNDING: ZonMw, the Netherlands Organisation for Health Research and Development.
PMID: 27371185 [PubMed - indexed for MEDLINE]
Economic downturns, universal health coverage, and cancer mortality in high-income and middle-income countries, 1990-2010: a longitudinal analysis.
Lancet. 2016 Aug 13;388(10045):684-95
Authors: Maruthappu M, Watkins J, Noor AM, Williams C, Ali R, Sullivan R, Zeltner T, Atun R
BACKGROUND: The global economic crisis has been associated with increased unemployment and reduced public-sector expenditure on health care (PEH). We estimated the effects of changes in unemployment and PEH on cancer mortality, and identified how universal health coverage (UHC) affected these relationships.
METHODS: For this longitudinal analysis, we obtained data from the World Bank and WHO (1990-2010). We aggregated mortality data for breast cancer in women, prostate cancer in men, and colorectal cancers in men and women, which are associated with survival rates that exceed 50%, into a treatable cancer class. We likewise aggregated data for lung and pancreatic cancers, which have 5 year survival rates of less than 10%, into an untreatable cancer class. We used multivariable regression analysis, controlling for country-specific demographics and infrastructure, with time-lag analyses and robustness checks to investigate the relationship between unemployment, PEH, and cancer mortality, with and without UHC. We used trend analysis to project mortality rates, on the basis of trends before the sharp unemployment rise that occurred in many countries from 2008 to 2010, and compared them with observed rates.
RESULTS: Data were available for 75 countries, representing 2.106 billion people, for the unemployment analysis and for 79 countries, representing 2.156 billion people, for the PEH analysis. Unemployment rises were significantly associated with an increase in all-cancer mortality and all specific cancers except lung cancer in women. By contrast, untreatable cancer mortality was not significantly linked with changes in unemployment. Lag analyses showed significant associations remained 5 years after unemployment increases for the treatable cancer class. Rerunning analyses, while accounting for UHC status, removed the significant associations. All-cancer, treatable cancer, and specific cancer mortalities significantly decreased as PEH increased. Time-series analysis provided an estimate of more than 40,000 excess deaths due to a subset of treatable cancers from 2008 to 2010, on the basis of 2000-07 trends. Most of these deaths were in non-UHC countries.
INTERPRETATION: Unemployment increases are associated with rises in cancer mortality; UHC seems to protect against this effect. PEH increases are associated with reduced cancer mortality. Access to health care could underlie these associations. We estimate that the 2008-10 economic crisis was associated with about 260,000 excess cancer-related deaths in the Organisation for Economic Co-operation and Development alone.
PMID: 27236345 [PubMed - indexed for MEDLINE]
Association between air pollution and coronary artery calcification within six metropolitan areas in the USA (the Multi-Ethnic Study of Atherosclerosis and Air Pollution): a longitudinal cohort study.
Lancet. 2016 Aug 13;388(10045):696-704
Authors: Kaufman JD, Adar SD, Barr RG, Budoff M, Burke GL, Curl CL, Daviglus ML, Diez Roux AV, Gassett AJ, Jacobs DR, Kronmal R, Larson TV, Navas-Acien A, Olives C, Sampson PD, Sheppard L, Siscovick DS, Stein JH, Szpiro AA, Watson KE
BACKGROUND: Long-term exposure to fine particulate matter less than 2.5 μm in diameter (PM2.5) and traffic-related air pollutant concentrations are associated with cardiovascular risk. The disease process underlying these associations remains uncertain. We aim to assess association between long-term exposure to ambient air pollution and progression of coronary artery calcium and common carotid artery intima-media thickness.
METHODS: In this prospective 10-year cohort study, we repeatedly measured coronary artery calcium by CT in 6795 participants aged 45-84 years enrolled in the Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air) in six metropolitan areas in the USA. Repeated scans were done for nearly all participants between 2002 and 2005, for a subset of participants between 2005 and 2007, and for half of all participants between 2010 and 2012. Common carotid artery intima-media thickness was measured by ultrasound in all participants at baseline and in 2010-12 for 3459 participants. Residence-specific spatio-temporal pollution concentration models, incorporating community-specific measurements, agency monitoring data, and geographical predictors, estimated concentrations of PM2.5 and nitrogen oxides (NOX) between 1999 and 2012. The primary aim was to examine the association between both progression of coronary artery calcium and mean carotid artery intima-media thickness and long-term exposure to ambient air pollutant concentrations (PM2.5, NOX, and black carbon) between examinations and within the six metropolitan areas, adjusting for baseline age, sex, ethnicity, socioeconomic characteristics, cardiovascular risk factors, site, and CT scanner technology.
FINDINGS: In this population, coronary calcium increased on average by 24 Agatston units per year (SD 58), and intima-media thickness by 12 μm per year (10), before adjusting for risk factors or air pollutant exposures. Participant-specific pollutant concentrations averaged over the years 2000-10 ranged from 9.2-22.6 μg PM2.5/m(3) and 7.2-139.2 parts per billion (ppb) NOX. For each 5 μg PM2.5/m(3) increase, coronary calcium progressed by 4.1 Agatston units per year (95% CI 1.4-6.8) and for each 40 ppb NOX coronary calcium progressed by 4.8 Agatston units per year (0.9-8.7). Pollutant exposures were not associated with intima-media thickness change. The estimate for the effect of a 5 μg/m(3) higher long-term exposure to PM2.5 in intima-media thickness was -0.9 μm per year (95% CI -3.0 to 1.3). For 40 ppb higher NOX, the estimate was 0.2 μm per year (-1.9 to 2.4).
INTERPRETATION: Increased concentrations of PM2.5 and traffic-related air pollution within metropolitan areas, in ranges commonly encountered worldwide, are associated with progression in coronary calcification, consistent with acceleration of atherosclerosis. This study supports the case for global efforts of pollution reduction in prevention of cardiovascular diseases.
FUNDING: US Environmental Protection Agency and US National Institutes of Health.
PMID: 27233746 [PubMed - indexed for MEDLINE]
Use of serological surveys to generate key insights into the changing global landscape of infectious disease.
Lancet. 2016 Aug 13;388(10045):728-30
Authors: Metcalf CJ, Farrar J, Cutts FT, Basta NE, Graham AL, Lessler J, Ferguson NM, Burke DS, Grenfell BT
PMID: 27059886 [PubMed - indexed for MEDLINE]
Lancet. 2016 Aug 13;388(10045):706-16
Authors: Powell LW, Seckington RC, Deugnier Y
Haemochromatosis is now known to be an iron-storage disease with genetic heterogeneity but with a final common metabolic pathway resulting in inappropriately low production of the hormone hepcidin. This leads to increase in intestinal absorption and deposition of excessive amounts of iron in parenchymal cells which in turn results in eventual tissue damage and organ failure. A clinical enigma has been the variable clinical expression with some patients presenting with hepatic cirrhosis at a young age and others almost asymptomatic for life. Research is unravelling this puzzle by identifying environmental factors-especially alcohol consumption-and associated modifying genes that modulate phenotypic expression. A high index of suspicion is required for early diagnosis but this can lead to presymptomatic therapy and a normal life expectancy. Venesection (phlebotomy) therapy remains the mainstay of therapy, but alternative therapies are the subject of current research.
PMID: 26975792 [PubMed - indexed for MEDLINE]
Lancet. 2016 Aug 13;388(10045):717-27
Authors: Willison HJ, Jacobs BC, van Doorn PA
Guillain-Barré syndrome is the most common and most severe acute paralytic neuropathy, with about 100,000 people developing the disorder every year worldwide. Under the umbrella term of Guillain-Barré syndrome are several recognisable variants with distinct clinical and pathological features. The severe, generalised manifestation of Guillain-Barré syndrome with respiratory failure affects 20-30% of cases. Treatment with intravenous immunoglobulin or plasma exchange is the optimal management approach, alongside supportive care. Understanding of the infectious triggers and immunological and pathological mechanisms has advanced substantially in the past 10 years, and is guiding clinical trials investigating new treatments. Investigators of large, worldwide, collaborative studies of the spectrum of Guillain-Barré syndrome are accruing data for clinical and biological databases to inform the development of outcome predictors and disease biomarkers. Such studies are transforming the clinical and scientific landscape of acute autoimmune neuropathies.
PMID: 26948435 [PubMed - indexed for MEDLINE]
Morgagni's hernia in a hypoxaemic adult.
Lancet. 2016 Aug 13;388(10045):705
Authors: Humble AG, Sample CB
PMID: 26831471 [PubMed - indexed for MEDLINE]
Our findings differ.
CMAJ. 2015 Oct 20;187(15):1162
Authors: Famularo G, Gasbarrone L, Minisola G
PMID: 26483040 [PubMed - indexed for MEDLINE]