Hot off the presses! Apr 25 Lancet

The Apr 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:

• Medical emergency in Sri Lanka
  - Lancet 373(9673):1399 (2009)
  
• How ethical are for-profit institutional review boards?
  - Lancet 373(9673):1400 (2009)
  
• Resistance to the Affordable Medicines Facility for malaria?
  - Lancet 373(9673):1400 (2009)
  
• Advancing care for acute heart failure—no time to relax
  - Lancet 373(9673):1401-1402 (2009)
  
• Emergence of clinical vascular tissue engineering
  - Lancet 373(9673):1402-1404 (2009)
  
• Seguro Popular in Mexico: is premature evaluation healthy?
  - Lancet 373(9673):1404-1405 (2009)
  
• Ideas and ideals: ethical basis of health reform in Mexico
  - Lancet 373(9673):1406-1408 (2009)
  
• Whole-body CT in multiple trauma
  - Lancet 373(9673):1408-1409 (2009)
  
• Malaria: 2 years in the fast lane
  - Lancet 373(9673):1409-1411 (2009)
  
• A vaccine against malaria: a substantial step forward
  - Lancet 373(9673):1411-1412 (2009)
  
• Italy urged to give end-of-life bill more time for debate
  - Lancet 373(9673):1413 (2009)
  
• Novartis under fire for accepting new reward for old drug
  - Lancet 373(9673):1414 (2009)
  
• Outlook hazy for smoking rates in the USA
  - Lancet 373(9673):1415 (2009)
  
• North Korea halts foreign food-aid programme
  - Lancet 373(9673):1416 (2009)
  
• Women in medicine—whatever next?
  - Lancet 373(9673):1417-1418 (2009)
  
• Tales from Tapologo
  - Lancet 373(9673):1418 (2009)
  
• Bob Snow: championing malaria in Africa
  - Lancet 373(9673):1419 (2009)
  
• Human papillomavirus, abstinence, and the other risks
  - Lancet 373(9673):1420-1421 (2009)
  
• Charles Lieber
  - Lancet 373(9673):1422 (2009)
  
• Glycaemic control in paediatric critical care
  - Lancet 373(9673):1423 (2009)
  
• Glycaemic control in paediatric critical care
  - Lancet 373(9673):1423 (2009)
  
• Glycaemic control in paediatric critical care
  - Lancet 373(9673):1423-1424 (2009)
  
• Glycaemic control in paediatric critical care – Authors' reply
  - Lancet 373(9673):1424 (2009)
  
• Ethical criteria for allocating health-care resources
  - Lancet 373(9673):1424-1425 (2009)
  
• Ethical criteria for allocating health-care resources
  - Lancet 373(9673):1425 (2009)
  
• Ethical criteria for allocating health-care resources – Authors' reply
  - Lancet 373(9673):1425-1426 (2009)
  
• PTC124 for cystic fibrosis
  - Lancet 373(9673):1426 (2009)
  
• PTC124 for cystic fibrosis – Authors' reply
  - Lancet 373(9673):1426-1427 (2009)
  
• Humanitarian crisis in Vanni, Sri Lanka
  - Lancet 373(9673):1427 (2009)
  
• Assessment of childhood immunisation coverage
  - Lancet 373(9673):1427-1428 (2009)
  
• Assessment of childhood immunisation coverage
  - Lancet 373(9673):1428 (2009)
  
• Department of Error
  - Lancet 373(9673):1428 (2009)
  
• Relaxin for the treatment of patients with acute heart failure (Pre-RELAX-AHF): a multicentre, randomised, placebo-controlled, parallel-group, dose-finding phase IIb study
  - Lancet 373(9673):1429-1439 (2009)
  Background Most patients admitted for acute heart failure have normal or increase blood pressure. Relaxin is a natural human peptide that affects multiple vascular control pathways, suggesting potential mechanisms of benefit for such patients. We assessed the dose response of relaxin's effect on symptom relief, other clinical outcomes, and safety. Methods In a placebo-controlled, parallel-group, dose-ranging study, 234 patients with acute heart failure, dyspnoea, congestion on chest radiograph, and increased brain natriuretic peptide (BNP) or N-terminal prohormone of BNP, mild-to-moderate renal insufficiency, and systolic blood pressure greater than 125 mm Hg were recruited from 54 sites in eight countries and enrolled within 16 h of presentation. Patients were randomly assigned, in a double-blind manner via a telephone-based interactive voice response system, to standard care plus 48-h intravenous infusion of placebo (n=62) or relaxin 10 μg/kg (n=40), 30 μg/kg (n=43), 100 μg/kg (n=39), or 250 μg/kg (n=50) per day. Several clinical endpoints were explored to assess whether intravenous relaxin should be pursued in larger studies of acute heart failure, to identify an optimum dose, and to help to assess endpoint selection and power calculations. Analysis was by modified intention to treat. This study is registered with Clin! icalTrials.gov, number NCT00520806. Findings In the modified intention-to-treat population, 61 patients were assessed in the placebo group, 40 in the relaxin 10 μg/kg per day group, 42 in the relaxin 30 μg/kg per day group, 37 in the relaxin 100 μg/kg per day group, and 49 in the relaxin 250 μg/kg per day group. Dyspnoea improved with relaxin 30 μg/kg compared with placebo, as assessed by Likert scale (17 of 42 patients [40%] moderately or markedly improved at 6 h, 12 h, and 24 h vs 14 of 61 [23%]; p=0·044) and visual analogue scale through day 14 (8214 mm×h [SD 8712] vs 4622 mm×h [9003]; p=0·053). Length of stay was 10·2 days (SD 6·1) for relaxin-treated patients versus 12·0 days (7·3) for those given placebo, and days alive out of hospital were 47·9 (10·1) versus 44·2 (14·2). Cardiovascular death or readmission due to heart or renal failure at day 60 was reduced with relaxin (2·6% [95% CI 0·4–16·8] vs 17·2% [9·6–29·6]; p=0·053). The number of serious adverse events was similar between grou! ps. Interpretation When given to patients with acute heart failure and normal-to-increased blood pressure, relaxin was associated with favourable relief of dyspnoea and other clinical outcomes, with acceptable safety. Funding Corthera (USA).
• Effectiveness of haemodialysis access with an autologous tissue-engineered vascular graft: a multicentre cohort study
  - Lancet 373(9673):1440-1446 (2009)
  Background Application of a tissue-engineered vascular graft for small-diameter vascular reconstruction has been a long awaited and much anticipated advance for vascular surgery. We report results after a minimum of 6 months of follow-up for the first ten patients implanted with a completely biological and autologous tissue-engineered vascular graft. Methods Ten patients with end-stage renal disease who had been receiving haemodialysis through an access graft that had a high probability of failure, and had had at least one previous access failure, were enrolled from centres in Argentina and Poland between September, 2004, and April, 2007. Completely autologous tissue-engineered vascular grafts were grown in culture supplemented with bovine serum, implanted as arteriovenous shunts, and assessed for both mechanical stability during the safety phase (0–3 months) and effectiveness after haemodialysis was started. Findings Three grafts failed within the safety phase, which is consistent with failure rates expected for this high-risk patient population. One patient was withdrawn from the study because of severe gastrointestinal bleeding shortly before implantation, and another died of unrelated causes during the safety period with a patent graft. The remaining five patients had grafts functioning for haemodialysis 6–20 months after implantation, and a total of 68 patient-months of patency. In these five patients, only one intervention (surgical correction) was needed to maintain secondary patency. Overall, primary patency was maintained in seven (78%) of the remaining nine patients 1 month after implantation and five (60%) of the remaining eight patients 6 months after implantation. Interpretation Our proportion of primary patency in this high-risk cohort approaches Dialysis Outcomes Quality Initiative objectives (76% of patients 3 months after implantation) for arteriovenous fistulas, averaged across all patient populations. Funding Cytograft Tissue Engineering.
• Public policy for the poor? A randomised assessment of the Mexican universal health insurance programme
  - Lancet 373(9673):1447-1454 (2009)
  Background We assessed aspects of Seguro Popular, a programme aimed to deliver health insurance, regular and preventive medical care, medicines, and health facilities to 50 million uninsured Mexicans. Methods We randomly assigned treatment within 74 matched pairs of health clusters—ie, health facility catchment areas—representing 118 569 households in seven Mexican states, and measured outcomes in a 2005 baseline survey (August, 2005, to September, 2005) and follow-up survey 10 months later (July, 2006, to August, 2006) in 50 pairs (n=32 515). The treatment consisted of encouragement to enrol in a health-insurance programme and upgraded medical facilities. Participant states also received funds to improve health facilities and to provide medications for services in treated clusters. We estimated intention to treat and complier average causal effects non-parametrically. Findings Intention-to-treat estimates indicated a 23% reduction from baseline in catastrophic expenditures (1·9% points; 95% CI 0·14–3·66). The effect in poor households was 3·0% points (0·46–5·54) and in experimental compliers was 6·5% points (1·65–11·28), 30% and 59% reductions, respectively. The intention-to-treat effect on health spending in poor households was 426 pesos (39–812), and the complier average causal effect was 915 pesos (147–1684). Contrary to expectations and previous observational research, we found no effects on medication spending, health outcomes, or utilisation. Interpretation Programme resources reached the poor. However, the programme did not show some other effects, possibly due to the short duration of treatment (10 months). Although Seguro Popular seems to be successful at this early stage, further experiments and follow-up studies, with longer assessment periods, are needed to ascertain the long-term effects of the programme. Funding Mexican Ministry of Health, the National Institute of Public Health of Mexico, and Harvard University Institute for Quantitative Social Science.
• Effect of whole-body CT during trauma resuscitation on survival: a retrospective, multicentre study
  - Lancet 373(9673):1455-1461 (2009)
  Background The number of trauma centres using whole-body CT for early assessment of primary trauma is increasing. There is no evidence to suggest that use of whole-body CT has any effect on the outcome of patients with major trauma. We therefore compared the probability of survival in patients with blunt trauma who had whole-body CT during resuscitation with those who had not. Methods In a retrospective, multicentre study, we used the data recorded in the trauma registry of the German Trauma Society to calculate the probability of survival according to the trauma and injury severity score (TRISS), revised injury severity classification (RISC) score, and standardised mortality ratio (SMR, ratio of recorded to expected mortality) for 4621 patients with blunt trauma given whole-body or non-whole-body CT. Findings 1494 (32%) of 4621 patients were given whole-body CT. Mean age was 42·6 years (SD 20·7), 3364 (73%) were men, and mean injury-severity score was 29·7 (13·0). SMR based on TRISS was 0·745 (95% CI 0·633–0·859) for patients given whole-body CT versus 1·023 (0·909–1·137) for those given non-whole-body CT (p<0·001). SMR based on the RISC score was 0·865 (0·774–0·956) for patients given whole-body CT versus 1·034 (0·959–1·109) for those given non-whole-body CT (p=0·017). The relative reduction in mortality based on TRISS was 25% (14–37) versus 13% (4–23) based on RISC score. Multivariate adjustment for hospital level, year of trauma, and potential centre effects confirmed that whole-body CT is an independent predictor for survival (p ≤ 0·002). The number needed to scan was 17 based on TRISS and 32 based on RISC calculation. Interpretation Integration of whole-body CT into early trauma care significantly increased the probability of survival in patients with polytrauma. Whole-body CT is recommended as a standard diagnostic method during the early resuscitation phase for patients with polytrauma. Funding None.
• Green urine
  - Lancet 373(9673):1462 (2009)
  
• Early breast cancer
  - Lancet 373(9673):1463-1479 (2009)
  Adoption of urbanised lifestyles together with changes in reproductive behaviour might partly underlie the continued rise in worldwide incidence of breast cancer. Widespread mammographic screening and effective systemic therapies have led to a stage shift at presentation and mortality reductions in the past two decades. Loco-regional control of the disease seems to affect long-term survival, and attention to surgical margins together with improved radiotherapy techniques could further contribute to mortality gains. Developments in oncoplastic surgery and partial-breast reconstruction have improved cosmetic outcomes after breast-conservation surgery. Optimum approaches for delivering chest-wall radiotherapy in the context of immediate breast reconstruction present special challenges. Accurate methods for intraoperative assessment of sentinel lymph nodes remain a clinical priority. Clinical trials are investigating combinatorial therapies that use novel agents targeting ! growth factor receptors, signal transduction pathways, and tumour angiogenesis. Gene-expression profiling offers the potential to provide accurate prognostic and predictive information, with selection of best possible therapy for individuals and avoidance of overtreatment and undertreatment of patients with conventional chemotherapy. Short-term presurgical studies in the neoadjuvant setting allow monitoring of proliferative indices, and changes in gene-expression patterns can be predictive of response to therapies and long-term outcome.
• Coeliac disease
  - Lancet 373(9673):1480-1493 (2009)
  Coeliac disease is a chronic inflammatory disorder of the small bowel induced in genetically susceptible people by the irritant gluten and possibly other environmental cofactors. The disorder is characterised by a diverse clinical heterogeneity that ranges from asymptomatic to severely symptomatic, and it manifests with frank malabsorption, an increased morbidity attributable to the frequent association with autoimmune disorders and increased mortality resulting from the emergence of T-cell clonal proliferations that predispose the patient to enteropathy-type T-cell lymphoma. Our understanding of the molecular basis for this disorder has improved and enabled the identification of targets for new therapies, although a strict gluten-free diet remains the mainstay of safe and effective treatment. In this Seminar we critically reassess the clinical and diagnostic aspects of this disease and new perspectives in its pathogenesis and treatment.
• Painless jaundice with serial multi-organ dysfunction
  - Lancet 373(9673):1494 (2009)