Hot off the presses! May 20 Lance

The May 20 issue of the Lance is now up on Pubget (About Lance): if you're at a subscribing institution, just click the link in the latest link at the home page. (Note you'll only be able to get all the PDFs in the issue if your institution subscribes to Pubget.)

Latest Articles Include:

• Stroke care—a work in progress
  - Lance 377(9778):1625 (2011)
  
• Fighting fake drugs: the role of WHO and pharma
  - Lance 377(9778):1626 (2011)
  
• Salt and cardiovascular disease mortality
  - Lance 377(9778):1626 (2011)
  
• Endovascular coils for cerebral aneurysm: HELPS has arrived
  - Lance 377(9778):1627-1628 (2011)
  
• Hydroxycarbamide for sickle-cell anaemia in infancy
  - Lance 377(9778):1628-1630 (2011)
  
• The cost of dengue control
  - Lance 377(9778):1630-1631 (2011)
  
• Lancet UK Policy Matters: better evidence for better health
  - Lance 377(9778):1631-1633 (2011)
  
• Science as a public enterprise: the case for open data
  - Lance 377(9778):1633-1635 (2011)
  
• Addressing the complexity of disparities in stillbirths
  - Lance 377(9778):1635-1636 (2011)
  
• Counting stillbirths: women's health and reproductive rights
  - Lance 377(9778):1636-1637 (2011)
  
• Offline: Ten commandments, G8 corruption, and OBL
  - Lance 377(9778):1638 (2011)
  
• Collaboration works to improve stroke outcomes in Ghana
  - Lance 377(9778):1639-1640 (2011)
  
• The rise of open-source electronic health records
  - Lance 377(9778):1641-1642 (2011)
  
• Clot-busting for stroke
  - Lance 377(9778):1643-1644 (2011)
  
• Life at the kerb
  - Lance 377(9778):1644 (2011)
  
• Peter Rothwell: a dedicated flouter of fashion
  - Lance 377(9778):1645 (2011)
  
• Listening to narratives from the Tuskegee syphilis study
  - Lance 377(9778):1646-1647 (2011)
  
• Kjell Bjartveit
  - Lance 377(9778):1648 (2011)
  
• Aspirin in the prevention of cancer
  - Lance 377(9778):1649 (2011)
  
• Aspirin in the prevention of cancer
  - Lance 377(9778):1649-1650 (2011)
  
• Aspirin in the prevention of cancer
  - Lance 377(9778):1650 (2011)
  
• Aspirin in the prevention of cancer
  - Lance 377(9778):1650-1651 (2011)
  
• Aspirin in the prevention of cancer
  - Lance 377(9778):1651 (2011)
  
• Aspirin in the prevention of cancer – Author's reply
  - Lance 377(9778):1651-1652 (2011)
  
• Earthquake in Japan
  - Lance 377(9778):1652 (2011)
  
• Earthquake in Japan
  - Lance 377(9778):1652 (2011)
  
• Earthquake in Japan
  - Lance 377(9778):1652-1653 (2011)
  
• Earthquake in Japan
  - Lance 377(9778):1653 (2011)
  
• Earthquake in Japan
  - Lance 377(9778):1653-1654 (2011)
  
• Sharing information on adverse events
  - Lance 377(9778):1654 (2011)
  
• Department of Error
  - Lance 377(9778):1654 (2011)
  
• Hydrogel-coated coils versus bare platinum coils for the endovascular treatment of intracranial aneurysms (HELPS): a randomised controlled trial
  - Lance 377(9778):1655-1662 (2011)
  Background Coated coils for endovascular treatment of cerebral aneurysm were developed to reduce recurrence and retreatment rates, and have been in clinical use for 8–9 years without robust evidence to determine their efficacy. We assessed the efficacy and safety of hydrogel-coated coils. Methods This randomised trial was undertaken in 24 centres in seven countries. Patients aged 18–75 years with a previously untreated ruptured or unruptured cerebral aneurysm of 2–25 mm in maximum diameter were randomly allocated (1:1) to aneurysm coiling with either hydrogel-coated coils or standard bare platinum coils (control). Randomisation was done with a computer-generated sequence, stratified by aneurysm size, shape, and dome-to-neck ratio; intention to use assist device; and by region. Participants and those assessing outcomes were masked to allocation. Analysis was by modified intention to treat (excluding missing data). Primary outcome was a composite of angiographic and clinical outcomes at 18-month follow-up. We also did prespecified subgroup analyses of characteristics likely to be relevant to angiographic outcome. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN30531382. Findings 249 patients were allocated to the hydrogel coil group and 250 to the control group. In 44 of 467 patients for whom an 18-month composite primary outcome was unavailable, 6-month angiographic results were used. 70 (28%) patients in the hydrogel group and 90 (36%) control patients had an adverse composite primary outcome, giving an absolute reduction in the proportion of adverse composite primary outcomes with hydrogel of 7·0% (95% CI −1·6 to 15·5), odds ratio (OR) 0·73 (0·49–1·1, p=0·13). In a prespecified subgroup analysis in recently ruptured aneurysms, there were more adverse composite primary outcomes in the control group than in the hydrogel group—OR 2·08 (1·24–3·46, p=0·014). There were 8·6% fewer major angiographic recurrences in patients allocated to hydrogel coils—OR 0·7 (0·4–1·0, p=0·049). There were five cases of unexplained hydrocephalus in not-recently-ruptured aneurysms in the hydrogel coil group and one case in the control group. Interpretation Whether use of hydrogel coils reduces late aneurysm rupture or improves long-term clinical outcome is not clear, but our results indicate that their use lowers major recurrence. Funding MicroVention Inc.
• Hydroxycarbamide in very young children with sickle-cell anaemia: a multicentre, randomised, controlled trial (BABY HUG)
  - Lance 377(9778):1663-1672 (2011)
  Background Sickle-cell anaemia is associated with substantial morbidity from acute complications and organ dysfunction beginning in the first year of life. Hydroxycarbamide substantially reduces episodes of pain and acute chest syndrome, admissions to hospital, and transfusions in adults with sickle-cell anaemia. We assessed the effect of hydroxycarbamide therapy on organ dysfunction and clinical complications, and examined laboratory findings and toxic effects. Methods This randomised trial was undertaken in 13 centres in the USA between October, 2003, and September, 2009. Eligible participants had haemoglobin SS (HbSS) or haemoglobin Sβ0thalassaemia, were aged 9–18 months at randomisation, and were not selected for clinical severity. Participants received liquid hydroxycarbamide, 20 mg/kg per day, or placebo for 2 years. Randomisation assignments were generated by the medical coordinating centre by a pre-decided schedule. Identical appearing and tasting formulations were used for hydroxycarbamide and placebo. Patients, caregivers, and coordinating centre staff were masked to treatment allocation. Primary study endpoints were splenic function (qualitative uptake on 99Tc spleen scan) and renal function (glomerular filtration rate by 99mTc-DTPA clearance). Additional assessments included blood counts, fetal haemoglobin concentration, chemistry profiles, spleen function biomarkers, urine osmolality, neurodevelopment, transcranial Doppler u! ltrasonography, growth, and mutagenicity. Study visits occurred every 2–4 weeks. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00006400. Findings 96 patients received hydroxycarbamide and 97 placebo, of whom 83 patients in the hydroxycarbamide group and 84 in the placebo group completed the study. Significant differences were not seen between groups for the primary endpoints (19 of 70 patients with decreased spleen function at exit in the hydroxycarbamide group vs 28 of 74 patients in the placebo group, p=0·21; and a difference in the mean increase in DTPA glomerular filtration rate in the hydroxycarbamide group versus the placebo group of 2 mL/min per 1·73 m2, p=0·84). Hydroxycarbamide significantly decreased pain (177 events in 62 patients vs 375 events in 75 patients in the placebo group, p=0·002) and dactylitis (24 events in 14 patients vs 123 events in 42 patients in the placebo group, p<0·0001), with some evidence for decreased acute chest syndrome, hospitalisation rates, and transfusion. Hydroxyurea increased haemoglobin and fetal haemoglobin, and decreased white blood-cell count. Toxicity was limited to m! ild-to-moderate neutropenia. Interpretation On the basis of the safety and efficacy data from this trial, hydroxycarbamide can now be considered for all very young children with sickle-cell anaemia. Funding The US National Heart, Lung, and Blood Institute; and the National Institute of Child Health and Human Development.
• Dengue vector control strategies in an urban setting: an economic modelling assessment
  - Lance 377(9778):1673-1680 (2011)
  Background An estimated 2·5 billion people are at risk of dengue. Incidence of dengue is especially high in resource-constrained countries, where control relies mainly on insecticides targeted at larval or adult mosquitoes. We did epidemiological and economic assessments of different vector control strategies. Methods We developed a dynamic model of dengue transmission that assesses the evolution of insecticide resistance and immunity in the human population, thus allowing for long-term evolutionary and immunological effects of decreased dengue transmission. We measured the dengue health burden in terms of disability-adjusted life-years (DALYs) lost. We did a cost-effectiveness analysis of 43 insecticide-based vector control strategies, including strategies targeted at adult and larval stages, at varying efficacies (high-efficacy [90% mortality], medium-efficacy [60% mortality], and low-efficacy [30% mortality]) and yearly application frequencies (one to six applications). To assess the effect of parameter uncertainty on the results, we did a probabilistic sensitivity analysis and a threshold analysis. Findings All interventions caused the emergence of insecticide resistance, which, with the loss of herd immunity, will increase the magnitude of future dengue epidemics. In our model, one or more applications of high-efficacy larval control reduced dengue burden for up to 2 years, whereas three or more applications of adult vector control reduced dengue burden for up to 4 years. The incremental cost-effectiveness ratios of the strategies for two high-efficacy adult vector control applications per year was US$615 per DALY saved and for six high-efficacy adult vector control applications per year was $1267 per DALY saved. Sensitivity analysis showed that if the cost of adult control was more than 8·2 times the cost of larval control then all strategies based on adult control became dominated. Interpretation Six high-efficacy adult vector control applications per year has a cost-effectiveness ratio that will probably meet WHO's standard for a cost-effective or very cost-effective intervention. Year-round larval control can be counterproductive, exacerbating epidemics in later years because of evolution of insecticide resistance and loss of herd immunity. We suggest the reassessment of vector control policies that are based on larval control only. Funding The Fulbright Programme, CAPES (Brazilian federal agency for post-graduate education), the Miriam Burnett trust, and the Notsew Orm Sands Foundation.
• Medical treatment in acute and long-term secondary prevention after transient ischaemic attack and ischaemic stroke
  - Lance 377(9778):1681-1692 (2011)
  Stroke is a major cause of death and disability worldwide. Without improvements in prevention, the burden will increase during the next 20 years because of the ageing population, especially in developing countries. Major advances have occurred in secondary prevention during the past three decades, which demonstrate the broader potential to prevent stroke. We review the main medical treatments that should be considered for most patients with transient ischaemic attack or ischaemic stroke in the acute phase and the long term, and draw attention to recent developments.
• Stroke rehabilitation
  - Lance 377(9778):1693-1702 (2011)
  Stroke is a common, serious, and disabling global health-care problem, and rehabilitation is a major part of patient care. There is evidence to support rehabilitation in well coordinated multidisciplinary stroke units or through provision of early supported provision of discharge teams. Potentially beneficial treatment options for motor recovery of the arm include constraint-induced movement therapy and robotics. Promising interventions that could be beneficial to improve aspects of gait include fitness training, high-intensity therapy, and repetitive-task training. Repetitive-task training might also improve transfer functions. Occupational therapy can improve activities of daily living; however, information about the clinical effect of various strategies of cognitive rehabilitation and strategies for aphasia and dysarthria is scarce. Several large trials of rehabilitation practice and of novel therapies (eg, stem-cell therapy, repetitive transcranial magnetic stimula! tion, virtual reality, robotic therapies, and drug augmentation) are underway to inform future practice.
• Stillbirths: the way forward in high-income countries
  - Lance 377(9778):1703-1717 (2011)
  Stillbirth rates in high-income countries declined dramatically from about 1940, but this decline has slowed or stalled over recent times. The present variation in stillbirth rates across and within high-income countries indicates that further reduction in stillbirth is possible. Large disparities (linked to disadvantage such as poverty) in stillbirth rates need to be addressed by providing more educational opportunities and improving living conditions for women. Placental pathologies and infection associated with preterm birth are linked to a substantial proportion of stillbirths. The proportion of unexplained stillbirths associated with under investigation continues to impede efforts in stillbirth prevention. Overweight, obesity, and smoking are important modifiable risk factors for stillbirth, and advanced maternal age is also an increasingly prevalent risk factor. Intensified efforts are needed to ameliorate the effects of these factors on stillbirth rates. Cultura! lly appropriate preconception care and quality antenatal care that is accessible to all women has the potential to reduce stillbirth rates in high-income countries. Implementation of national perinatal mortality audit programmes aimed at improving the quality of care could substantially reduce stillbirths. Better data on numbers and causes of stillbirth are needed, and international consensus on definition and classification related to stillbirth is a priority. All parents should be offered a thorough investigation including a high-quality autopsy and placental histopathology. Parent organisations are powerful change agents and could have an important role in raising awareness to prevent stillbirth. Future research must focus on screening and interventions to reduce antepartum stillbirth as a result of placental dysfunction. Identification of ways to reduce maternal overweight and obesity is a high priority for high-income countries.
• Coughing into the darkness
  - Lance 377(9778):1718 (2011)