Hot off the presses! Feb 25 LANCET

The Feb 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:

• No mental health without physical health
  - LANCET 377(9766):611 (2011)
  
• The parlous state of research in paediatric oncology
  - LANCET 377(9766):612 (2011)
  
• A shot in the arm for MDG 4 in Africa
  - LANCET 377(9766):612 (2011)
  
• From GWAS to clinical utility in Parkinson's disease
  - LANCET 377(9766):613-614 (2011)
  
• New insights into the treatment of persistent asthma
  - LANCET 377(9766):614-616 (2011)
  
• Telemonitoring of fluid status in heart failure: CHAMPION
  - LANCET 377(9766):616-618 (2011)
  
• Gender equity and universal health coverage in India
  - LANCET 377(9766):618-619 (2011)
  
• Challenges in infection in ASEAN
  - LANCET 377(9766):619-621 (2011)
  
• The Havasu 'Baaja tribe and informed consent
  - LANCET 377(9766):621-622 (2011)
  
• The Lancet's paper of the year 2010
  - LANCET 377(9766):623 (2011)
  
• Offline: The breeze of freedom
  - LANCET 377(9766):624 (2011)
  
• US nurse practitioners push for more responsibilities
  - LANCET 377(9766):625-626 (2011)
  
• Health care for urban poor falls through the gap
  - LANCET 377(9766):627-628 (2011)
  
• Luminescent images from Marie Curie's life
  - LANCET 377(9766):629 (2011)
  
• Synergistic art
  - LANCET 377(9766):630 (2011)
  
• When the taps run dry
  - LANCET 377(9766):631 (2011)
  
• Bindheshwar Pathak
  - LANCET 377(9766):631 (2011)
  
• Medicine without pretence
  - LANCET 377(9766):632-633 (2011)
  
• Niilo Hallman
  - LANCET 377(9766):634 (2011)
  
• Paricalcitol for reduction of albuminuria in diabetes
  - LANCET 377(9766):635 (2011)
  
• Paricalcitol for reduction of albuminuria in diabetes
  - LANCET 377(9766):635 (2011)
  
• Paricalcitol for reduction of albuminuria in diabetes
  - LANCET 377(9766):635-636 (2011)
  
• Paricalcitol for reduction of albuminuria in diabetes
  - LANCET 377(9766):636 (2011)
  
• Paricalcitol for reduction of albuminuria in diabetes – Authors' reply
  - LANCET 377(9766):636-637 (2011)
  
• Genetic substudy of the PLATO trial
  - LANCET 377(9766):637 (2011)
  
• Genetic substudy of the PLATO trial – Authors' reply
  - LANCET 377(9766):637-638 (2011)
  
• Feasibility of malaria elimination
  - LANCET 377(9766):638 (2011)
  
• Feasibility of malaria elimination – Author's reply
  - LANCET 377(9766):638 (2011)
  
• Doctor stabbed to death two days after warning in The Lancet
  - LANCET 377(9766):639 (2011)
  
• The fight is far from over
  - LANCET 377(9766):639 (2011)
  
• Long-term care of AIDS and non-communicable diseases
  - LANCET 377(9766):639-640 (2011)
  
• Respect and care for the older person
  - LANCET 377(9766):640 (2011)
  
• Department of Error
  - LANCET 377(9766):640 (2011)
  
• Department of Error
  - LANCET 377(9766):640 (2011)
  
• Imputation of sequence variants for identification of genetic risks for Parkinson's disease: a meta-analysis of genome-wide association studies
  - LANCET 377(9766):641-649 (2011)
  Background Genome-wide association studies (GWAS) for Parkinson's disease have linked two loci (MAPT and SNCA) to risk of Parkinson's disease. We aimed to identify novel risk loci for Parkinson's disease. Methods We did a meta-analysis of datasets from five Parkinson's disease GWAS from the USA and Europe to identify loci associated with Parkinson's disease (discovery phase). We then did replication analyses of significantly associated loci in an independent sample series. Estimates of population-attributable risk were calculated from estimates from the discovery and replication phases combined, and risk-profile estimates for loci identified in the discovery phase were calculated. Findings The discovery phase consisted of 5333 case and 12 019 control samples, with genotyped and imputed data at 7 689 524 SNPs. The replication phase consisted of 7053 case and 9007 control samples. We identified 11 loci that surpassed the threshold for genome-wide significance (p<5×10−8). Six were previously identified loci (MAPT, SNCA, HLA-DRB5, BST1, GAK and LRRK2) and five were newly identified loci (ACMSD, STK39, MCCC1/LAMP3, SYT11, and CCDC62/HIP1R). The combined population-attributable risk was 60·3% (95% CI 43·7–69·3). In the risk-profile analysis, the odds ratio in the highest quintile of disease risk was 2·51 (95% CI 2·23–2·83) compared with 1·00 in the lowest quintile of disease risk. Interpretation These data provide an insight into the genetics of Parkinson's disease and the molecular cause of the disease and could provide future targets for therapies. Funding Wellcome Trust, National Institute on Aging, and US Department of Defense.
• Use of beclomethasone dipropionate as rescue treatment for children with mild persistent asthma (TREXA): a randomised, double-blind, placebo-controlled trial
  - LANCET 377(9766):650-657 (2011)
  Background Daily inhaled corticosteroids are an effective treatment for mild persistent asthma, but some children have exacerbations even with good day-to-day control, and many discontinue treatment after becoming asymptomatic. We assessed the effectiveness of an inhaled corticosteroid (beclomethasone dipropionate) used as rescue treatment. Methods In this 44-week, randomised, double-blind, placebo-controlled trial we enrolled children and adolescents with mild persistent asthma aged 5–18 years from five clinical centres in the USA. A computer-generated randomisation sequence, stratified by clinical centre and age group, was used to randomly assign participants to one of four treatment groups: twice daily beclomethasone with beclomethasone plus albuterol as rescue (combined group); twice daily beclomethasone with placebo plus albuterol as rescue (daily beclomethasone group); twice daily placebo with beclomethasone plus albuterol as rescue (rescue beclomethasone group); and twice daily placebo with placebo plus albuterol as rescue (placebo group). Twice daily beclomethasone treatment was one puff of beclomethasone (40 μg per puff) or placebo given in the morning and evening. Rescue beclomethasone treatment was two puffs of beclomethasone or placebo for each two puffs of albuterol (180 μg) needed for symptom relief. ! The primary outcome was time to first exacerbation that required oral corticosteroids. A secondary outcome measured linear growth. Analysis was by intention to treat. This study is registered with clinicaltrials.gov, number NCT00394329. Results 843 children and adolescents were enrolled into this trial, of whom 288 were assigned to one of four treatment groups; combined (n=71), daily beclomethasone (n=72), rescue beclomethasone (n=71), and placebo (n=74)—555 individuals were excluded during the run-in, according to predefined criteria. Compared with the placebo group (49%, 95% CI 37–61), the frequency of exacerbations was lower in the daily (28%, 18–40, p=0·03), combined (31%, 21–43, p=0·07), and rescue (35%, 24–47, p=0·07) groups. Frequency of treatment failure was 23% (95% CI 14–43) in the placebo group, compared with 5·6% (1·6–14) in the combined (p=0·012), 2·8% (0–10) in the daily (p=0·009), and 8·5% (2–15) in the rescue (p=0·024) groups. Compared with the placebo group, linear growth was 1·1 cm (SD 0·3) less in the combined and daily arms (p<0·0001), but not the rescue group (p=0·26). Only two individuals had severe adverse events; one in the daily beclomethasone group had viral! meningitis and one in the combined group had bronchitis. Interpretation Children with mild persistent asthma should not be treated with rescue albuterol alone and the most effective treatment to prevent exacerbations is daily inhaled corticosteroids. Inhaled corticosteroids as rescue medication with albuterol might be an effective step-down strategy for children with well controlled, mild asthma because it is more effective at reducing exacerbations than is use of rescue albuterol alone. Use of daily inhaled corticosteroid treatment and related side-effects such as growth impairment can therefore be avoided. Funding National Heart, Lung and Blood Institute.
• Wireless pulmonary artery haemodynamic monitoring in chronic heart failure: a randomised controlled trial
  - LANCET 377(9766):658-666 (2011)
  Background Results of previous studies support the hypothesis that implantable haemodynamic monitoring systems might reduce rates of hospitalisation in patients with heart failure. We undertook a single-blind trial to assess this approach. Methods Patients with New York Heart Association (NYHA) class III heart failure, irrespective of the left ventricular ejection fraction, and a previous hospital admission for heart failure were enrolled in 64 centres in the USA. They were randomly assigned by use of a centralised electronic system to management with a wireless implantable haemodynamic monitoring (W-IHM) system (treatment group) or to a control group for at least 6 months. Only patients were masked to their assignment group. In the treatment group, clinicians used daily measurement of pulmonary artery pressures in addition to standard of care versus standard of care alone in the control group. The primary efficacy endpoint was the rate of heart-failure-related hospitalisations at 6 months. The safety endpoints assessed at 6 months were freedom from device-related or system-related complications (DSRC) and freedom from pressure-sensor failures. All analyses were by intention to treat. This trial is registered with Cli! nicalTrials.gov, number NCT00531661. Findings In 6 months, 83 heart-failure-related hospitalisations were reported in the treatment group (n=270) compared with 120 in the control group (n=280; rate 0·31 vs 0·44, hazard ratio [HR] 0·70, 95% CI 0·60–0·84, p<0·0001). During the entire follow-up (mean 15 months [SD 7]), the treatment group had a 39% reduction in heart-failure-related hospitalisation compared with the control group (153 vs 253, HR 0·64, 95% CI 0·55–0·75; p<0·0001). Eight patients had DSRC and overall freedom from DSRC was 98·6% (97·3–99·4) compared with a prespecified performance criterion of 80% (p<0·0001); and overall freedom from pressure-sensor failures was 100% (99·3–100·0). Interpretation Our results are consistent with, and extend, previous findings by definitively showing a significant and large reduction in hospitalisation for patients with NYHA class III heart failure who were managed with a wireless implantable haemodynamic monitoring system. The addition of information about pulmonary artery pressure to clinical signs and symptoms allows for improved heart failure management. Funding CardioMEMS.
• Corkscrew oesophagus on virtual endoscopy
  - LANCET 377(9766):667 (2011)
  
• Financing health care for all: challenges and opportunities
  - LANCET 377(9766):668-679 (2011)
  India's health financing system is a cause of and an exacerbating factor in the challenges of health inequity, inadequate availability and reach, unequal access, and poor-quality and costly health-care services. Low per person spending on health and insufficient public expenditure result in one of the highest proportions of private out-of-pocket expenses in the world. Citizens receive low value for money in the public and the private sectors. Financial protection against medical expenditures is far from universal with only 10% of the population having medical insurance. The Government of India has made a commitment to increase public spending on health from less than 1% to 3% of the gross domestic product during the next few years. Increased public funding combined with flexibility of financial transfers from centre to state can greatly improve the performance of state-operated public systems. Enhanced public spending can be used to introduce universal medical insuranc! e that can help to substantially reduce the burden of private out-of-pocket expenditures on health. Increased public spending can also contribute to quality assurance in the public and private sectors through effective regulation and oversight. In addition to an increase in public expenditures on health, the Government of India will, however, need to introduce specific methods to contain costs, improve the efficiency of spending, increase accountability, and monitor the effect of expenditures on health.
• The rise of chronic non-communicable diseases in southeast Asia: time for action
  - LANCET 377(9766):680-689 (2011)
  Southeast Asia faces an epidemic of chronic non-communicable diseases, now responsible for 60% of deaths in the region. The problem stems from environmental factors that promote tobacco use, unhealthy diet, and inadequate physical activity. Disadvantaged populations are the hardest hit, with death rates inversely proportional to a country's gross national income. Families shoulder the financial burden, but entire economies suffer as well. Although attempts to control non-communicable diseases are increasing, more needs to be done. Health-care systems need to be redesigned to deliver chronic care that is founded on existing primary health-care facilities, but supported by good referral systems. Surveillance of key modifiable risk factors is needed to monitor the magnitude of the problem and to study the effects of interventions. All branches of government and all sectors of society have to get involved in establishing environments that are conducive to healthy living. T! he Association of Southeast Asian Nations is in a unique position to make a united stand against chronic non-communicable diseases in the region. Inaction will affect millions of lives—often, the lives of those who have the least.
• Blocking out the real diagnosis
  - LANCET 377(9766):690 (2011)