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  • Erratum:Measuring progress and projecting attainment on the basis of past trends of the health-related Sustainable Development Goals in 188 countries: an analysis from the Global Burden of Disease Study 2016 (The Lancet (2017) 390(10100) (1423–1459) (S014067361732336X)(10.1016/S0140-6736(17)32336-X))

    13 August 2018

    © 2017 Elsevier Ltd GBD 2016 SDG Collaborators. Measuring progress and projecting attainment on the basis of past trends of the health-related Sustainable Development Goals in 188 countries: an analysis from the Global Burden of Disease Study 2016. Lancet 2017; 390: 1423–59—In figure 8B of this Article (published Online First on Sept 12, 2017), the number of indicator targets has been changed from 1 to 9 for Turkmenistan, from 0 to 1 for Afghanistan, and from 1 to 2 for Yemen. Ettore Beghi, Neeraj Bhala, Hélène Carabin, Raimundas Lunevicius, Donald H Silberberg, and Caitlyn Steiner have been added to the list of GBD 2016 SDG Collaborators. Their affiliations, along with the affiliation of Soumya Swaminathan, have been added to the Affiliations section. These corrections have been made to the online version as of Sept 18, 2017, and the printed Article is correct.

  • Erratum: Measuring progress and projecting attainment on the basis of past trends of the health-related Sustainable Development Goals in 188 countries: an analysis from the Global Burden of Disease Study 2016 (The Lancet (2017) 390(10100) (1423–1459) (S014067361732336X) (10.1016/S0140-6736(17)32336-X))

    13 August 2018

    © 2017 Elsevier Ltd GBD 2016 SDG Collaborators. Measuring progress and projecting attainment on the basis of past trends of the health-related Sustainable Development Goals in 188 countries: an analysis from the Global Burden of Disease Study 2016. Lancet 2017; 390: 1423–59—The full-text version of this Article has been updated so that the list of authors is displayed in the correct order, in line with the pdf version, rather than in alphabetical order. This correction has been made to the online version as of Oct 12, 2017.

  • A descriptive study of randomized trials of treatments for childhood acute lymphoblastic leukaemia.

    2 July 2018

    This report presents a historical and descriptive account of randomized trials in childhood leukaemia since the earliest such studies in the 1960s. It focuses on trials that began before 1988, making use of the register of trials developed for a systematic review of treatments for acute lymphoblastic leukaemia in children. The number of randomized trials starting each year increased from one or two in the 1960s to an annual average of five or six in the 1980s. However trials remained relatively small, with more than half of all randomizations accruing less than 200 patients and only five having more than 1000. Most trials were published more than once.

  • Methods to increase response to postal and electronic questionnaires.

    2 July 2018

    BACKGROUND: Postal and electronic questionnaires are widely used for data collection in epidemiological studies but non-response reduces the effective sample size and can introduce bias. Finding ways to increase response to postal and electronic questionnaires would improve the quality of health research. OBJECTIVES: To identify effective strategies to increase response to postal and electronic questionnaires. SEARCH STRATEGY: We searched 14 electronic databases to February 2008 and manually searched the reference lists of relevant trials and reviews, and all issues of two journals. We contacted the authors of all trials or reviews to ask about unpublished trials. Where necessary, we also contacted authors to confirm methods of allocation used and to clarify results presented. We assessed the eligibility of each trial using pre-defined criteria. SELECTION CRITERIA: Randomised controlled trials of methods to increase response to postal or electronic questionnaires. DATA COLLECTION AND ANALYSIS: We extracted data on the trial participants, the intervention, the number randomised to intervention and comparison groups and allocation concealment. For each strategy, we estimated pooled odds ratios (OR) and 95% confidence intervals (CI) in a random-effects model. We assessed evidence for selection bias using Egger's weighted regression method and Begg's rank correlation test and funnel plot. We assessed heterogeneity among trial odds ratios using a Chi(2) test and the degree of inconsistency between trial results was quantified using the I(2) statistic. MAIN RESULTS: PostalWe found 481 eligible trials. The trials evaluated 110 different ways of increasing response to postal questionnaires. We found substantial heterogeneity among trial results in half of the strategies. The odds of response were at least doubled using monetary incentives (odds ratio 1.87; 95% CI 1.73 to 2.04; heterogeneity P < 0.00001, I(2) = 84%), recorded delivery (1.76; 95% CI 1.43 to 2.18; P = 0.0001, I(2) = 71%), a teaser on the envelope - e.g. a comment suggesting to participants that they may benefit if they open it (3.08; 95% CI 1.27 to 7.44) and a more interesting questionnaire topic (2.00; 95% CI 1.32 to 3.04; P = 0.06, I(2) = 80%). The odds of response were substantially higher with pre-notification (1.45; 95% CI 1.29 to 1.63; P < 0.00001, I(2) = 89%), follow-up contact (1.35; 95% CI 1.18 to 1.55; P < 0.00001, I(2) = 76%), unconditional incentives (1.61; 1.36 to 1.89; P < 0.00001, I(2) = 88%), shorter questionnaires (1.64; 95% CI 1.43 to 1.87; P < 0.00001, I(2) = 91%), providing a second copy of the questionnaire at follow up (1.46; 95% CI 1.13 to 1.90; P < 0.00001, I(2) = 82%), mentioning an obligation to respond (1.61; 95% CI 1.16 to 2.22; P = 0.98, I(2) = 0%) and university sponsorship (1.32; 95% CI 1.13 to 1.54; P < 0.00001, I(2) = 83%). The odds of response were also increased with non-monetary incentives (1.15; 95% CI 1.08 to 1.22; P < 0.00001, I(2) = 79%), personalised questionnaires (1.14; 95% CI 1.07 to 1.22; P < 0.00001, I(2) = 63%), use of hand-written addresses (1.25; 95% CI 1.08 to 1.45; P = 0.32, I(2) = 14%), use of stamped return envelopes as opposed to franked return envelopes (1.24; 95% CI 1.14 to 1.35; P < 0.00001, I(2) = 69%), an assurance of confidentiality (1.33; 95% CI 1.24 to 1.42) and first class outward mailing (1.11; 95% CI 1.02 to 1.21; P = 0.78, I(2) = 0%). The odds of response were reduced when the questionnaire included questions of a sensitive nature (0.94; 95% CI 0.88 to 1.00; P = 0.51, I(2) = 0%).ElectronicWe found 32 eligible trials. The trials evaluated 27 different ways of increasing response to electronic questionnaires. We found substantial heterogeneity among trial results in half of the strategies. The odds of response were increased by more than a half using non-monetary incentives (1.72; 95% CI 1.09 to 2.72; heterogeneity P < 0.00001, I(2) = 95%), shorter e-questionnaires (1.73; 1.40 to 2.13; P = 0.08, I(2) = 68%), including a statement that others had responded (1.52; 95% CI 1.36 to 1.70), and a more interesting topic (1.85; 95% CI 1.52 to 2.26). The odds of response increased by a third using a lottery with immediate notification of results (1.37; 95% CI 1.13 to 1.65), an offer of survey results (1.36; 95% CI 1.15 to 1.61), and using a white background (1.31; 95% CI 1.10 to 1.56). The odds of response were also increased with personalised e-questionnaires (1.24; 95% CI 1.17 to 1.32; P = 0.07, I(2) = 41%), using a simple header (1.23; 95% CI 1.03 to 1.48), using textual representation of response categories (1.19; 95% CI 1.05 to 1.36), and giving a deadline (1.18; 95% CI 1.03 to 1.34). The odds of response tripled when a picture was included in an e-mail (3.05; 95% CI 1.84 to 5.06; P = 0.27, I(2) = 19%). The odds of response were reduced when "Survey" was mentioned in the e-mail subject line (0.81; 95% CI 0.67 to 0.97; P = 0.33, I(2) = 0%), and when the e-mail included a male signature (0.55; 95% CI 0.38 to 0.80; P = 0.96, I(2) = 0%). AUTHORS' CONCLUSIONS: Health researchers using postal and electronic questionnaires can increase response using the strategies shown to be effective in this systematic review.

  • PLUTO trial protocol: percutaneous shunting for lower urinary tract obstruction randomised controlled trial.

    2 July 2018

    OBJECTIVES: The primary objective is to determine whether intrauterine vesicoamniotic shunting for fetal bladder outflow obstruction, compared with conservative, noninterventional care, improves prenatal and perinatal mortality and renal function. The secondary objectives are to determine if shunting for fetal bladder outflow obstruction improves perinatal morbidity, to determine if improvement in outcomes is related to prognostic assessment at diagnosis and, if possible, derive a prognostic risk index and to determine the safety and long-term efficacy of shunting. DESIGN: A multicentre randomised controlled trial (RCT). SETTING: Fetal medicine units. POPULATION: Pregnant women with singleton, male fetus with isolated lower urinary tract obstruction (LUTO). METHODS: Following ultrasound diagnosis of LUTO in a male fetus and exclusion of other structural and chromosomal anomalies, participation in the trial will be discussed with the mother and written information given. Consent for participation in the trial will be taken and the mother randomised via the internet to either insertion of a vesicoamniotic shunt or expectant management. During pregnancy, both groups will be followed with regular ultrasound scans looking at viability, renal measurements and amniotic fluid volume. Following delivery, babies will be followed up by paediatric nephrologists/urologists at 4-6 weeks, 12 months and 3 and 5 years to assess renal function via serum creatinine, renal ultrasound and need for dialysis/transplant. MAIN OUTCOME MEASURES: The main outcome measures will be perinatal mortality rates and renal function at 4-6 weeks and 12 months measured via serum creatinine, renal ultrasound and need for dialysis/transplant. FUNDING: Wellbeing of Women. ESTIMATED COMPLETION DATE: September 2010. TRIAL ALGORITHM: [flowchart: see text].

  • Multiple sclerosis risk sharing scheme: two year results of clinical cohort study with historical comparator.

    2 July 2018

    OBJECTIVE: To generate evidence on the longer term cost effectiveness of disease modifying treatments in patients with relapsing-remitting multiple sclerosis. DESIGN: Prospective cohort study with historical comparator. SETTING: Specialist multiple sclerosis clinics in 70 centres in the United Kingdom. PARTICIPANTS: Patients with relapsing-remitting multiple sclerosis who started treatment from May 2002 to April 2005 under the UK risk sharing scheme. INTERVENTIONS: Treatment with interferon beta or glatiramer acetate in accordance with guidelines of the UK Association of British Neurologists. MAIN OUTCOME MEASURES: Observed utility weighted progression in disability at two years' follow-up assessed on the expanded disability status scale (EDSS) compared with that expected by applying the progression rates in a comparator dataset, modified for patients receiving treatment by multiplying by the hazard ratio derived separately for each disease modifying treatment from the randomised trials. RESULTS: In the primary per protocol analysis, progression in disability was worse than that predicted and worse than that in the untreated comparator dataset ("deviation score" of 113%; excess in mean disability status scale 0.28). In sensitivity analyses, however, the deviation score varied from -72% (using raw baseline disability status scale scores, rather than applying a "no improvement" algorithm) to 156% (imputing missing data for year two from progression rates for year one). CONCLUSIONS: It is too early to reach any conclusion about the cost effectiveness of disease modifying treatments from this first interim analysis. Important methodological issues, including the need for additional comparator datasets, the potential bias from missing data, and the impact of the "no improvement" rule, will need to be addressed and long term follow-up of all patients is essential to secure meaningful results. Future analyses of the cohort are likely to be more informative, not least because they will be less sensitive to short term fluctuations in disability.

  • Immediate versus deferred zidovudine (AZT) in asymptomatic or mildly symptomatic HIV infected adults.

    3 July 2018

    BACKGROUND: Zidovudine (AZT) monotherapy was the first antiretroviral drug to be tested widely. Subsequent trials in asymptomatic or early symptomatic HIV infection indicated short-term delays in disease progression with AZT, but not improved survival. OBJECTIVES: To assess the effects of immediate versus deferred zidovudine (AZT) on HIV disease progression and survival. SEARCH STRATEGY: Investigators and pharmaceutical companies were contacted, and MEDLINE searches were supplemented by searching conference abstracts. SELECTION CRITERIA: Randomised controlled trials comparing immediate versus deferred AZT in participants without AIDS which prospectively collected deaths and new AIDS events. DATA COLLECTION AND ANALYSIS: Individual patient data with, wherever possible, follow-up obtained beyond that previously published was obtained and checked for internal consistency and consistency with any published reports; any apparent discrepancies were resolved with the trialists. Time to death and to disease progression (defined as a new AIDS-defining event or prior death) were analysed on an intention to treat basis, stratified to avoid direct comparisons between participants in different trials. MAIN RESULTS: Nine trials were included in the meta-analysis. During a median follow-up of 50 months, 1908 individuals developed disease progression, of whom 1351 died. In the deferred group, 61% started antiretroviral therapy (median time to therapy 28 months, which was AZT monotherapy in 94%). During the first year of follow-up immediate AZT halved the rate of disease progression (P<0.0001), increasing the probability of AIDS-free survival at one year from 96% to 98%, but this early benefit did not persist: after 6 years AIDS-free survival was 54% in both groups, and at no time was there any difference in overall survival, which at 6 years was 64% with immediate and 65% with deferred AZT (rate ratio [RR] 1.04, 95% confidence interval [CI] 0. 94 to 1.15). REVIEWER'S CONCLUSIONS: Although immediate use of AZT halved disease progression during the first year, this effect was not sustained, and there was no improvement in survival in the short or long term.

  • Genetic Association of Lipids and Lipid Drug Targets With Abdominal Aortic Aneurysm: A Meta-analysis.

    3 July 2018

    Importance: Risk factors for abdominal aortic aneurysm (AAA) are largely unknown, which has hampered the development of nonsurgical treatments to alter the natural history of disease. Objective: To investigate the association between lipid-associated single-nucleotide polymorphisms (SNPs) and AAA risk. Design, Setting, and Participants: Genetic risk scores, composed of lipid trait-associated SNPs, were constructed and tested for their association with AAA using conventional (inverse-variance weighted) mendelian randomization (MR) and data from international AAA genome-wide association studies. Sensitivity analyses to account for potential genetic pleiotropy included MR-Egger and weighted median MR, and multivariable MR method was used to test the independent association of lipids with AAA risk. The association between AAA and SNPs in loci that can act as proxies for drug targets was also assessed. Data collection took place between January 9, 2015, and January 4, 2016. Data analysis was conducted between January 4, 2015, and December 31, 2016. Exposures: Genetic elevation of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG). Main Outcomes and Measures: The association between genetic risk scores of lipid-associated SNPs and AAA risk, as well as the association between SNPs in lipid drug targets (HMGCR, CETP, and PCSK9) and AAA risk. Results: Up to 4914 cases and 48 002 controls were included in our analysis. A 1-SD genetic elevation of LDL-C was associated with increased AAA risk (odds ratio [OR], 1.66; 95% CI, 1.41-1.96; P = 1.1 × 10-9). For HDL-C, a 1-SD increase was associated with reduced AAA risk (OR, 0.67; 95% CI, 0.55-0.82; P = 8.3 × 10-5), whereas a 1-SD increase in triglycerides was associated with increased AAA risk (OR, 1.69; 95% CI, 1.38-2.07; P = 5.2 × 10-7). In multivariable MR analysis and both MR-Egger and weighted median MR methods, the association of each lipid fraction with AAA risk remained largely unchanged. The LDL-C-reducing allele of rs12916 in HMGCR was associated with AAA risk (OR, 0.93; 95% CI, 0.89-0.98; P = .009). The HDL-C-raising allele of rs3764261 in CETP was associated with lower AAA risk (OR, 0.89; 95% CI, 0.85-0.94; P = 3.7 × 10-7). Finally, the LDL-C-lowering allele of rs11206510 in PCSK9 was weakly associated with a lower AAA risk (OR, 0.94; 95% CI, 0.88-1.00; P = .04), but a second independent LDL-C-lowering variant in PCSK9 (rs2479409) was not associated with AAA risk (OR, 0.97; 95% CI, 0.92-1.02; P = .28). Conclusions and Relevance: The MR analyses in this study lend support to the hypothesis that lipids play an important role in the etiology of AAA. Analyses of individual genetic variants used as proxies for drug targets support LDL-C lowering as a potential effective treatment strategy for preventing and managing AAA.