Hot off the presses! Mar 25 LANCET

The Mar 25 issue of the LANCET is now up on Pubget (About LANCET): 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:

• Physicians as guardians of genetic knowledge
  - LANCET 377(9770):967 (2011)
  
• Japan: health after the earthquake
  - LANCET 377(9770):968 (2011)
  
• The end of the one-child policy in China?
  - LANCET 377(9770):968 (2011)
  
• Shared innovations in measurement and evaluation
  - LANCET 377(9770):969-970 (2011)
  
• Treating faecal incontinence with bulking-agent injections
  - LANCET 377(9770):971-972 (2011)
  
• Traumatic spinal cord injuries
  - LANCET 377(9770):972-974 (2011)
  
• Lessons from normal heart and respiratory rates in children
  - LANCET 377(9770):974-975 (2011)
  
• India: access to affordable drugs and the right to health
  - LANCET 377(9770):976-977 (2011)
  
• Cardiovascular safety and diabetes drug development
  - LANCET 377(9770):977-979 (2011)
  
• Offline: Run for the shadows in these golden years
  - LANCET 377(9770):980 (2011)
  
• Obama rescinds "overly broad" Bush-era conscience rule
  - LANCET 377(9770):981 (2011)
  
• Libyan exodus creates refugee and health worker crisis
  - LANCET 377(9770):982-983 (2011)
  
• Romania plans changes to clinical trials system
  - LANCET 377(9770):984 (2011)
  
• Reliving past glories
  - LANCET 377(9770):985 (2011)
  
• The challenges of scaling up
  - LANCET 377(9770):986 (2011)
  
• Joseph Murray: innovative surgeon and pioneer of transplantation
  - LANCET 377(9770):987 (2011)
  
• The crusade against out-relief: a nudge from history
  - LANCET 377(9770):988-989 (2011)
  
• Bernard Nathanson
  - LANCET 377(9770):990 (2011)
  
• Malaria-attributed death rates in India
  - LANCET 377(9770):991 (2011)
  
• Malaria-attributed death rates in India
  - LANCET 377(9770):991-992 (2011)
  
• Malaria-attributed death rates in India
  - LANCET 377(9770):992-993 (2011)
  
• Malaria-attributed death rates in India
  - LANCET 377(9770):993 (2011)
  
• Malaria-attributed death rates in India
  - LANCET 377(9770):993-994 (2011)
  
• Malaria-attributed death rates in India – Authors' reply
  - LANCET 377(9770):994-995 (2011)
  
• Doctors talk climate change—students take action
  - LANCET 377(9770):995 (2011)
  
• Health benefits of policies to mitigate climate change
  - LANCET 377(9770):995-996 (2011)
  
• Health benefits of policies to mitigate climate change
  - LANCET 377(9770):996 (2011)
  
• The role of business in public health
  - LANCET 377(9770):996 (2011)
  
• Department of Error
  - LANCET 377(9770):996 (2011)
  
• Efficacy of dextranomer in stabilised hyaluronic acid for treatment of faecal incontinence: a randomised, sham-controlled trial
  - LANCET 377(9770):997-1003 (2011)
  Background Injection of a bulking agent in the anal canal is an increasingly used treatment for faecal incontinence, but efficacy has not been shown in a controlled trial. We aimed to assess the efficacy of injection of dextranomer in stabilised hyaluronic acid (NASHA Dx) for treatment of faecal incontinence. Methods In this randomised, double-blind, sham-controlled trial, patients aged 18–75 years from centres in USA and Europe were randomly assigned (2:1) to receive either transanal submucosal injections of NASHA Dx or sham injections. Randomisation was stratified by sex and region in blocks of six, and managed with a computer generated, real-time, web-based system. Patients and investigators were masked to assignment for 6 months when the effect on severity of faecal incontinence and quality of life was assessed with a 2-week diary and clinical assessments. The primary endpoint was response to treatment based on the number of incontinence episodes. A response to treatment was defined as a reduction in number of episodes by 50% or more. Patients in the active treatment group are still being followed up. This trial was registered with ClinicalTrials.gov, number NCT00605826. Findings 278 patients were screened for inclusion, of whom 206 were randomised assigned to receive NASHA Dx (n=136) or sham treatment (n=70). 71 patients who received NASHA Dx (52%) had a 50% or more reduction in the number of incontinence episode, compared with 22 patients who received sham treatment (31%; odds ratio 2·36, 95% CI 1·24–4·47, p=0·0089). We recorded 128 treatment-related adverse events, of which two were serious (1 rectal abscess and 1 prostatic abscess). Interpretation Anal injection of NASHA Dx is an effective treatment for faecal incontinence. A refinement of selection criteria for patients, optimum injected dose, ideal site of injection, and long-term results might further increase the acceptance of this minimally invasive treatment. Funding Q-Med AB.
• A clinical prediction rule for ambulation outcomes after traumatic spinal cord injury: a longitudinal cohort study
  - LANCET 377(9770):1004-1010 (2011)
  Background Traumatic spinal cord injury is a serious disorder in which early prediction of ambulation is important to counsel patients and to plan rehabilitation. We developed a reliable, validated prediction rule to assess a patient's chances of walking independently after such injury. Methods We undertook a longitudinal cohort study of adult patients with traumatic spinal cord injury, with early (within the first 15 days after injury) and late (1-year follow-up) clinical examinations, who were admitted to one of 19 European centres between July, 2001, and June, 2008. A clinical prediction rule based on age and neurological variables was derived from the international standards for neurological classification of spinal cord injury with a multivariate logistic regression model. Primary outcome measure 1 year after injury was independent indoor walking based on the Spinal Cord Independence Measure. Model performances were quantified with respect to discrimination (area under receiver-operating-characteristics curve [AUC]). Temporal validation was done in a second group of patients from July, 2008, to December, 2009. Findings Of 1442 patients with spinal cord injury, 492 had available outcome measures. A combination of age (<65 vs ≥65 years), motor scores of the quadriceps femoris (L3), gastrocsoleus (S1) muscles, and light touch sensation of dermatomes L3 and S1 showed excellent discrimination in distinguishing independent walkers from dependent walkers and non-walkers (AUC 0·956, 95% CI 0·936–0·976, p<0·0001). Temporal validation in 99 patients confirmed excellent discriminating ability of the prediction rule (AUC 0·967, 0·939–0·995, p<0·0001). Interpretation Our prediction rule, including age and four neurological tests, can give an early prognosis of an individual's ability to walk after traumatic spinal cord injury, which can be used to set rehabilitation goals and might improve the ability to stratify patients in interventional trials. Funding Internationale Stiftung für Forschung in Paraplegie.
• Normal ranges of heart rate and respiratory rate in children from birth to 18 years of age: a systematic review of observational studies
  - LANCET 377(9770):1011-1018 (2011)
  Background Although heart rate and respiratory rate in children are measured routinely in acute settings, current reference ranges are not based on evidence. We aimed to derive new centile charts for these vital signs and to compare these centiles with existing international ranges. Methods We searched Medline, Embase, CINAHL, and reference lists for studies that reported heart rate or respiratory rate of healthy children between birth and 18 years of age. We used non-parametric kernel regression to create centile charts for heart rate and respiratory rate in relation to age. We compared existing reference ranges with those derived from our centile charts. Findings We identified 69 studies with heart rate data for 143 346 children and respiratory rate data for 3881 children. Our centile charts show decline in respiratory rate from birth to early adolescence, with the steepest fall apparent in infants under 2 years of age; decreasing from a median of 44 breaths per min at birth to 26 breaths per min at 2 years. Heart rate shows a small peak at age 1 month. Median heart rate increases from 127 beats per min at birth to a maximum of 145 beats per min at about 1 month, before decreasing to 113 beats per min by 2 years of age. Comparison of our centile charts with existing published reference ranges for heart rate and respiratory rate show striking disagreement, with limits from published ranges frequently exceeding the 99th and 1st centiles, or crossing the median. Interpretation Our evidence-based centile charts for children from birth to 18 years should help clinicians to update clinical and resuscitation guidelines. Funding National Institute for Health Research, Engineering and Physical Sciences Research Council.
• Alzheimer's disease
  - LANCET 377(9770):1019-1031 (2011)
  An estimated 24 million people worldwide have dementia, the majority of whom are thought to have Alzheimer's disease. Thus, Alzheimer's disease represents a major public health concern and has been identified as a research priority. Although there are licensed treatments that can alleviate symptoms of Alzheimer's disease, there is a pressing need to improve our understanding of pathogenesis to enable development of disease-modifying treatments. Methods for improving diagnosis are also moving forward, but a better consensus is needed for development of a panel of biological and neuroimaging biomarkers that support clinical diagnosis. There is now strong evidence of potential risk and protective factors for Alzheimer's disease, dementia, and cognitive decline, but further work is needed to understand these better and to establish whether interventions can substantially lower these risks. In this Seminar, we provide an overview of recent evidence regarding the epidemiolog! y, pathogenesis, diagnosis, and treatment of Alzheimer's disease, and discuss potential ways to reduce the risk of developing the disease.
• Aerosol drug delivery: developments in device design and clinical use
  - LANCET 377(9770):1032-1045 (2011)
  Aerosolised drugs are prescribed for use in a range of inhaler devices and systems. Delivering drugs by inhalation requires a formulation that can be successfully aerosolised and a delivery system that produces a useful aerosol of the drug; the particles or droplets need to be of sufficient size and mass to be carried to the distal lung or deposited on proximal airways to give rise to a therapeutic effect. Patients and caregivers must use and maintain these aerosol drug delivery devices correctly. In recent years, several technical innovations have led to aerosol drug delivery devices with efficient drug delivery and with novel features that take into account factors such as dose tracking, portability, materials of manufacture, breath actuation, the interface with the patient, combination therapies, and systemic delivery. These changes have improved performance in all four categories of devices: metered dose inhalers, spacers and holding chambers, dry powder inhalers, ! and nebulisers. Additionally, several therapies usually given by injection are now prescribed as aerosols for use in a range of drug delivery devices. In this Review, we discuss recent developments in the design and clinical use of aerosol devices over the past 10–15 years with an emphasis on the treatment of respiratory disorders.
• Silk road occlusion
  - LANCET 377(9770):1046 (2011)