Hot off the presses! Jan 07 LANCET

The Jan 07 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:

• A new year in medicine
  - LANCET 377(9759):1 (2011)
  
• On synthetic biology
  - LANCET 377(9759):2 (2011)
  
• A breath of fresh indoor air
  - LANCET 377(9759):2 (2011)
  
• Will an aspirin a day help keep fatal cancer away?
  - LANCET 377(9759):3-4 (2011)
  
• Rituximab maintenance in follicular lymphoma: PRIMA
  - LANCET 377(9759):4-6 (2011)
  
• Wormy mothers, healthy babies: case closed or conundrum?
  - LANCET 377(9759):6-8 (2011)
  
• Pathogenic C difficile is here (and everywhere) to stay
  - LANCET 377(9759):8-9 (2011)
  
• The white plague returns to London—with a vengeance
  - LANCET 377(9759):10-11 (2011)
  
• Health and philanthropy—the tobacco connection
  - LANCET 377(9759):11-13 (2011)
  
• Offline: Revising our expectations
  - LANCET 377(9759):14 (2011)
  
• Myths and realities about drug addiction in Mexico
  - LANCET 377(9759):15-16 (2011)
  
• Pulse oximeters breathe life into surgery in poorer nations
  - LANCET 377(9759):17-18 (2011)
  
• Eyewitness accounts from surgeons in Gaza
  - LANCET 377(9759):19 (2011)
  
• Journey through the afterlife
  - LANCET 377(9759):20 (2011)
  
• Clare Gerada: Chair of UK's Royal College of General Practitioners
  - LANCET 377(9759):21 (2011)
  
• Of wandering doctors, cities, and humane hospitals
  - LANCET 377(9759):22-23 (2011)
  
• Frank John Fenner
  - LANCET 377(9759):24 (2011)
  
• Oral sucrose for procedural pain in infants
  - LANCET 377(9759):25 (2011)
  
• Oral sucrose for procedural pain in infants
  - LANCET 377(9759):25 (2011)
  
• Oral sucrose for procedural pain in infants
  - LANCET 377(9759):25-26 (2011)
  
• Oral sucrose for procedural pain in infants
  - LANCET 377(9759):26 (2011)
  
• Oral sucrose for procedural pain in infants
  - LANCET 377(9759):26-27 (2011)
  
• Oral sucrose for procedural pain in infants – Authors' reply
  - LANCET 377(9759):27-28 (2011)
  
• International response to Niger's hunger crisis
  - LANCET 377(9759):28 (2011)
  
• The Greek economic crisis: a primary health-care perspective
  - LANCET 377(9759):28-29 (2011)
  
• When will the sun shine on Cyprus's National Health Service?
  - LANCET 377(9759):29 (2011)
  
• Reporting on the modes of data collection
  - LANCET 377(9759):30 (2011)
  
• All important contributions to papers should be recognised
  - LANCET 377(9759):30 (2011)
  
• Department of Error
  - LANCET 377(9759):30 (2011)
  
• Department of Error
  - LANCET 377(9759):30 (2011)
  
• Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials
  - LANCET 377(9759):31-41 (2011)
  Background Treatment with daily aspirin for 5 years or longer reduces subsequent risk of colorectal cancer. Several lines of evidence suggest that aspirin might also reduce risk of other cancers, particularly of the gastrointestinal tract, but proof in man is lacking. We studied deaths due to cancer during and after randomised trials of daily aspirin versus control done originally for prevention of vascular events. Methods We used individual patient data from all randomised trials of daily aspirin versus no aspirin with mean duration of scheduled trial treatment of 4 years or longer to determine the effect of allocation to aspirin on risk of cancer death in relation to scheduled duration of trial treatment for gastrointestinal and non-gastrointestinal cancers. In three large UK trials, long-term post-trial follow-up of individual patients was obtained from death certificates and cancer registries. Results In eight eligible trials (25 570 patients, 674 cancer deaths), allocation to aspirin reduced death due to cancer (pooled odds ratio [OR] 0·79, 95% CI 0·68–0·92, p=0·003). On analysis of individual patient data, which were available from seven trials (23 535 patients, 657 cancer deaths), benefit was apparent only after 5 years' follow-up (all cancers, hazard ratio [HR] 0·66, 0·50–0·87; gastrointestinal cancers, 0·46, 0·27–0·77; both p=0·003). The 20-year risk of cancer death (1634 deaths in 12 659 patients in three trials) remained lower in the aspirin groups than in the control groups (all solid cancers, HR 0·80, 0·72–0·88, p<0·0001; gastrointestinal cancers, 0·65, 0·54–0·78, p<0·0001), and benefit increased (interaction p=0·01) with scheduled duration of trial treatment (≥7·5 years: all solid cancers, 0·69, 0·54–0·88, p=0·003; gastrointestinal cancers, 0·41, 0·26–0·66, p=0·0001). The latent period before an effect on deaths was a! bout 5 years for oesophageal, pancreatic, brain, and lung cancer, but was more delayed for stomach, colorectal, and prostate cancer. For lung and oesophageal cancer, benefit was confined to adenocarcinomas, and the overall effect on 20-year risk of cancer death was greatest for adenocarcinomas (HR 0·66, 0·56–0·77, p<0·0001). Benefit was unrelated to aspirin dose (75 mg upwards), sex, or smoking, but increased with age—the absolute reduction in 20-year risk of cancer death reaching 7·08% (2·42–11·74) at age 65 years and older. Interpretation Daily aspirin reduced deaths due to several common cancers during and after the trials. Benefit increased with duration of treatment and was consistent across the different study populations. These findings have implications for guidelines on use of aspirin and for understanding of carcinogenesis and its susceptibility to drug intervention. Funding None.
• Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomised controlled trial
  - LANCET 377(9759):42-51 (2011)
  Background Patients with follicular lymphoma can have long survival times, but disease progression typically occurs 3–5 years after initial treatment. We assessed the potential benefit of 2 years of rituximab maintenance after first-line treatment in patients with follicular lymphoma receiving a rituximab plus chemotherapy regimen. Methods The randomised, open-label PRIMA study was undertaken in 223 centres in 25 countries. 1217 patients with previously untreated follicular lymphoma needing systemic therapy received one of three non-randomised immunochemotherapy induction regimens used in routine practice. 1019 patients achieving a complete or partial response were then randomly assigned to receive 2 years of rituximab maintenance therapy (375 mg/m2 every 8 weeks) or observation. Treatment was assigned equally by centralised block randomisation, stratified by induction regimen, response, region, and centre. Neither the participants nor those giving the interventions, assessing outcomes, and analysing data were masked to group assignments. The primary endpoint was progression-free survival (PFS). Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00140582. Findings 505 patients were assigned to rituximab maintenance and 513 to observation (one patient died during randomisation). With a median follow-up of 36 months (IQR 30–42), PFS was 74·9% (95% CI 70·9–78·9) in the rituximab maintenance group (130 patients progressed) and 57·6% (53·2–62·0) in the observation group (218 progressed; hazard ratio [HR] 0·55, 95% CI 0·44–0·68, p<0·0001). 2 years after randomisation, 361 patients (71·5%) in the rituximab maintenance group were in complete or unconfirmed complete response versus 268 (52·2%) in the observation group (p=0·0001). Overall survival did not differ significantly between groups (HR 0·87, 95% CI 0·51–1·47). Grade 3 and 4 adverse events were recorded in 121 patients (24%) in the rituximab maintenance group and 84 (17%) in the observation group (risk ratio 1·46, 95% CI 1·14–1·87; p=0·0026). Infections (grades 2–4) were the most common adverse event, occurring in 197 (39%) and 123 (24%) patients, respe! ctively (risk ratio 1·62, 95% CI 1·35–1·96; p<0·0001). Interpretation 2 years of rituximab maintenance therapy after immunochemotherapy as first-line treatment for follicular lymphoma significantly improves PFS. Funding Groupe d'Etude des Lymphomes de l'Adulte (GELA) and F Hoffmann-La Roche.
• Effect of single-dose anthelmintic treatment during pregnancy on an infant's response to immunisation and on susceptibility to infectious diseases in infancy: a randomised, double-blind, placebo-controlled trial
  - LANCET 377(9759):52-62 (2011)
  Background Helminth infections affect the human immune response. We investigated whether prenatal exposure to and treatment of maternal helminth infections affects development of an infant's immune response to immunisations and unrelated infections. Methods In this randomised, double-blind, placebo-controlled trial, we enrolled 2507 women in the second or third trimester of pregnancy who were planning to deliver in Entebbe General Hospital, Entebbe, Uganda. With a computer-generated random number sequence in blocks of 100, we assigned patients to 440 mg albendazole and 40 mg/kg praziquantel (n=628), 440 mg albendazole and a praziquantel-matching placebo (n=625), 40 mg/kg praziquantel and an albendazole-matching placebo (n=626), or an albendazole-matching placebo and praziquantel-matching placebo (n=628). All participants and hospital staff were masked to allocation. Primary outcomes were immune response at age 1 year to BCG, tetanus, and measles immunisation; incidence of infectious diseases during infancy; and vertical HIV transmission. Analysis was by intention-to-treat. This trial is registered, number ISRCTN32849447. Findings Data were available at delivery for 2356 women, with 2345 livebirths; 2115 (90%) of liveborn infants remained in follow-up at 1 year of age. Neither albendazole nor praziquantel treatments affected infant response to BCG, tetanus, or measles immunisation. However, in infants of mothers with hookworm infection, albendazole treatment reduced interleukin-5 (geometric mean ratio 0·50, 95% CI 0·30–0·81, interaction p=0·02) and interleukin-13 (0·52, 0·34–0·82, 0·0005) response to tetanus toxoid. The rate per 100 person-years of malaria was 40·9 (95% CI 38·3–43·7), of diarrhoea was 134·1 (129·2–139·2), and of pneumonia was 22·3 (20·4–24·4). We noted no effect on infectious disease incidence for albendazole treatment (malaria [hazard ratio 0·95, 95% CI 0·79–1.14], diarrhoea [1·06, 0·96–1·16], pneumonia [1·11, 0·90–1·38]) or praziquantel treatment (malaria [1·00, 0·84–1·20], diarrhoea [1·07, 0·98–1·18], pneumonia [1·00, 0·80–1·2! 4]). In HIV-exposed infants, 39 (18%) were infected at 6 weeks; vertical transmission was not associated with albendazole (odds ratio 0·70, 95% CI 0·35–1·42) or praziquantel (0·60, 0·29–1·23) treatment. Interpretation These results do not accord with the recently advocated policy of routine antenatal anthelmintic treatment, and the value of such a policy may need to be reviewed. Funding Wellcome Trust.
• Clostridium difficile infection in Europe: a hospital-based survey
  - LANCET 377(9759):63-73 (2011)
  Background Little is known about the extent of Clostridium difficile infection in Europe. Our aim was to obtain a more complete overview of C difficile infection in Europe and build capacity for diagnosis and surveillance. Methods We set up a network of 106 laboratories in 34 European countries. In November, 2008, one to six hospitals per country, relative to population size, tested stool samples of patients with suspected C difficile infection or diarrhoea that developed 3 or more days after hospital admission. A case was defined when, subsequently, toxins were identified in stool samples. Detailed clinical data and stool isolates were collected for the first ten cases per hospital. After 3 months, clinical data were followed up. Findings The incidence of C difficile infection varied across hospitals (weighted mean 4·1 per 10 000 patient-days per hospital, range 0·0–36·3). Detailed information was obtained for 509 patients. For 389 of these patients, isolates were available for characterisation. 65 different PCR ribotypes were identified, of which 014/020 (61 patients [16%]), 001 (37 [9%]), and 078 (31 [8%]) were the most prevalent. The prevalence of PCR-ribotype 027 was 5%. Most patients had a previously identified risk profile of old age, comorbidity, and recent antibiotic use. At follow up, 101 (22%) of 455 patients had died, and C difficile infection played a part in 40 (40%) of deaths. After adjustment for potential confounders, an age of 65 years or older (adjusted odds ratio 3·26, 95% CI 1·08–9·78; p=0·026), and infection by PCR-ribotypes 018 (6·19, 1·28–29·81; p=0·023) and 056 (13·01; 1·14–148·26; p=0·039) were significantly associated with complicated disease outcome. Interpretation PCR ribotypes other than 027 are prevalent in European hospitals. The data emphasise the importance of multicountry surveillance to detect and control C difficile infection in Europe. Funding European Centre for Disease Prevention and Control.
• Borderline personality disorder
  - LANCET 377(9759):74-84 (2011)
  Recent research findings have contributed to an improved understanding and treatment of borderline personality disorder. This disorder is characterised by severe functional impairments, a high risk of suicide, a negative effect on the course of depressive disorders, extensive use of treatment, and high costs to society. The course of this disorder is less stable than expected for personality disorders. The causes are not yet clear, but genetic factors and adverse life events seem to interact to lead to the disorder. Neurobiological research suggests that abnormalities in the frontolimbic networks are associated with many of the symptoms. Data for the effectiveness of pharmacotherapy vary and evidence is not yet robust. Specific forms of psychotherapy seem to be beneficial for at least some of the problems frequently reported in patients with borderline personality disorder. At present, there is no evidence to suggest that one specific form of psychotherapy is more effe! ctive than another. Further research is needed on the diagnosis, neurobiology, and treatment of borderline personality disorder.
• Measuring impact in the Millennium Development Goal era and beyond: a new approach to large-scale effectiveness evaluations
  - LANCET 377(9759):85-95 (2011)
  Evaluation of large-scale programmes and initiatives aimed at improvement of health in countries of low and middle income needs a new approach. Traditional designs, which compare areas with and without a given programme, are no longer relevant at a time when many programmes are being scaled up in virtually every district in the world. We propose an evolution in evaluation design, a national platform approach that: uses the district as the unit of design and analysis; is based on continuous monitoring of different levels of indicators; gathers additional data before, during, and after the period to be assessed by multiple methods; uses several analytical techniques to deal with various data gaps and biases; and includes interim and summative evaluation analyses. This new approach will promote country ownership, transparency, and donor coordination while providing a rigorous comparison of the cost-effectiveness of different scale-up approaches.
• Killing two birds with one stone
  - LANCET 377(9759):96 (2011)