Hot off the presses! Nov 25 The Lancet

The Nov 25 issue of the The Lancet is now up on Pubget (About The 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:

• November 19â€"25, 2011
  - The Lancet 378(9805):i (2011)
  
• Politics and patient care
  - The Lancet 378(9805):1757 (2011)
  
• Breast cancer: old and new debates
  - The Lancet 378(9805):1758 (2011)
  
• CRASH-2 goes viral
  - The Lancet 378(9805):1758 (2011)
  
• Multiple sclerosisâ€"quenching the flames of inflammation
  - The Lancet 378(9805):1759-1760 (2011)
  
• Tackling domestic violence: is increasing referral enough?
  - The Lancet 378(9805):1760-1762 (2011)
  
• Community management of severe pneumonia in children
  - The Lancet 378(9805):1762-1764 (2011)
  
• The Global Fund: getting the reforms right
  - The Lancet 378(9805):1764-1765 (2011)
  
• The European Respiratory Roadmap
  - The Lancet 378(9805):1765-1767 (2011)
  
• Offline: Nursing, but not as you know it
  - The Lancet 378(9805):1768 (2011)
  
• Drug withdrawal sends critical care specialists back to basics
  - The Lancet 378(9805):1769 (2011)
  
• Health 2020: WHO's missing link?
  - The Lancet 378(9805):1770 (2011)
  
• Saving Chile's angelitos
  - The Lancet 378(9805):1771-1772 (2011)
  
• Book Lost words
  - The Lancet 378(9805):1772 (2011)
  
• Moving pictures of Parkinson's disease
  - The Lancet 378(9805):1773-1774 (2011)
  
• Effect of population-based screening on breast cancer mortality
  - The Lancet 378(9805):1775-1776 (2011)
  
• Leadership and public health
  - The Lancet 378(9805):1776 (2011)
  
• Leadership and public health
  - The Lancet 378(9805):1776 (2011)
  
• Leadership and public health
  - The Lancet 378(9805):1776-1777 (2011)
  
• Hydroxycarbamide use in young children with sickle-cell anaemia
  - The Lancet 378(9805):1777 (2011)
  
• Hydroxycarbamide use in young children with sickle-cell anaemia
  - The Lancet 378(9805):1777 (2011)
  
• Need to realign patient-oriented and commercial and academic research
  - The Lancet 378(9805):1777-1778 (2011)
  
• The forgotten psychosocial dimension of the obesity epidemic
  - The Lancet 378(9805):e8 (2011)
  
• Non-communicable diseases and surgery at the UN? “Fugetaboutit!”
  - The Lancet 378(9805):e8 (2011)
  
• Department of Error
  - The Lancet 378(9805):1778 (2011)
  
• Department of Error
  - The Lancet 378(9805):1778 (2011)
  
• Department of Error
  - The Lancet 378(9805):1778 (2011)
  
• Department of Error
  - The Lancet 378(9805):1778 (2011)
  
• Department of Error
  - The Lancet 378(9805):1778 (2011)
  
• Ocrelizumab in relapsing-remitting multiple sclerosis: a phase 2, randomised, placebo-controlled, multicentre trial
  - The Lancet 378(9805):1779-1787 (2011)
  Background B lymphocytes are implicated in the pathogenesis of multiple sclerosis. We aimed to assess efficacy and safety of two dose regimens of the humanised anti-CD20 monoclonal antibody ocrelizumab in patients with relapsing-remitting multiple sclerosis. Methods We did a multicentre, randomised, parallel, double-blind, placebo-controlled study involving 79 centres in 20 countries. Patients aged 18–55 years with relapsing-remitting multiple sclerosis were randomly assigned (1:1:1:1) via an interactive voice response system to receive either placebo, low-dose (600 mg) or high-dose (2000 mg) ocrelizumab in two doses on days 1 and 15, or intramuscular interferon beta-1a (30 亮g) once a week. The randomisation list was not disclosed to the study centres, monitors, project statisticians or to the project team at Roche. All groups were double blinded to group assignment, except the interferon beta-1a group who were rater masked. At week 24, patients in the initial placebo, 600 mg ocrelizumab, and interferon beta-1a groups received ocrelizumab 600 mg; the 2000 mg group received 1000 mg. Our primary endpoint was the total number of gadolinium-enhancing lesions (GEL) and T1-weighted MRI at weeks 12, 16, 20, and 24. Analyses were done on an! intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT00676715. Findings 218 (99%) of the 220 randomised patients received at least one dose of ocrelizumab, 204 (93%) completed 24 weeks of the study and 196 (89%) completed 48 weeks. In the intention-to-treat population of 218 patients, at week 24, the number of gadolinium-enhancing lesions was 89% (95% CI 68–97; p<0·0001) lower in the 600 mg ocrelizumab group than in the placebo group, and 96% (89–99; p<0·0001) lower in the 2000 mg group. In exploratory analyses, both 600 mg and 2000 mg ocrelizumab groups were better than interferon beta-1a for GEL reduction. We noted serious adverse events in two of 54 (4%; 95% CI 3·0–4·4) patients in the placebo group, one of 55 (2%; 1·3–2·3) in the 600 mg ocrelizumab group, three of 55 (5%; 4·6–6·3) in the 2000 mg group, and two of 54 (4%; 3·0–4·4) in the interferon beta-1a group. Interpretation The similarly pronounced effects of B-cell depletion with both ocrelizumab doses on MRI and relapse-related outcomes support a role for B-cells in disease pathogenesis and warrant further assessment in large, long-term trials. Funding F Hoffmann-La Roche Ltd, Biogen Idec Inc.
• Identification and Referral to Improve Safety (IRIS) of women experiencing domestic violence with a primary care training and support programme: a cluster randomised controlled trial
  - The Lancet 378(9805):1788-1795 (2011)
  Background Most clinicians have no training about domestic violence, fail to identify patients experiencing abuse, and are uncertain about management after disclosure. We tested the effectiveness of a programme of training and support in primary health-care practices to increase identification of women experiencing domestic violence and their referral to specialist advocacy services. Methods In this cluster randomised controlled trial, we selected general practices in two urban primary care trusts, Hackney (London) and Bristol, UK. Practices in which investigators from this trial were employed or those who did not use electronic records were excluded. Practices were stratified by proportion of female doctors, postgraduate training status, number of patients registered, and percentage of practice population on low incomes. Within every primary care trust area, we randomised practices with a computer-minimisation programme with a random component to intervention or control groups. The intervention programme included practice-based training sessions, a prompt within the medical record to ask about abuse, and a referral pathway to a named domestic violence advocate, who also delivered the training and further consultancy. The primary outcome was recorded referral of patients to domestic violence advocacy services. The prespecified secondary outcome was recorded iden! tification of domestic violence in the electronic medical records of the general practice. Poisson regression analyses accounting for clustering were done for all practices receiving the intervention. Practice staff and research associates were not masked and patients were not aware they were part of a study. This study is registered at Current Controlled Trials, ISRCTN74012786. Findings We randomised 51 (61%) of 84 eligible general practices in Hackney and Bristol. Of these, 24 received a training and support programme, 24 did not receive the programme, and three dropped out before the trial started. 1 year after the second training session, the 24 intervention practices recorded 223 referrals of patients to advocacy and the 24 control practices recorded 12 referrals (adjusted intervention rate ratio 22·1 [95% CI 11·5–42·4]). Intervention practices recorded 641 disclosures of domestic violence and control practices recorded 236 (adjusted intervention rate ratio 3·1 [95% CI 2·2–4·3). No adverse events were recorded. Interpretation A training and support programme targeted at primary care clinicians and administrative staff improved referral to specialist domestic violence agencies and recorded identification of women experiencing domestic violence. Our findings reduce the uncertainty about the benefit of training and support interventions in primary care settings for domestic violence and show that screening of women patients for domestic violence is not a necessary condition for improved identification and referral to advocacy services. Funding Health Foundation.
• Community case management of severe pneumonia with oral amoxicillin in children aged 2â€"59 months in Haripur district, Pakistan: a cluster randomised trial
  - The Lancet 378(9805):1796-1803 (2011)
  Background First dose oral co-trimoxazole and referral are recommended for WHO-defined severe pneumonia. Difficulties with referral compliance are reported in many low-resource settings, resulting in low access to appropriate treatment. The objective in this study was to assess whether community case management by lady health workers (LHWs) with oral amoxicillin in children with severe pneumonia was equivalent to current standard of care. Methods In Haripur district, Pakistan, 28 clusters were randomly assigned with stratification in a 1:1 ratio to intervention and control clusters by use of a computer-generated randomisation sequence. Children were included in the study if they were aged 2–59 months with WHO-defined severe pneumonia and living in the study area. In the intervention clusters, community-based LHWs provided mothers with oral amoxicillin (80–90 mg/kg per day or 375 mg twice a day for infants aged 2–11 months and 625 mg twice a day for those aged 12–59 months) with specific guidance on its use. In control clusters, LHWs gave the first dose of oral co-trimoxazole (age 2–11 months, sulfamethoxazole 200 mg plus trimethoprim 40 mg; age 12 months to 5 years, sulfamethoxazole 300 mg plus trimethoprim 60 mg) and referred the children to a health facility for standard of care. Participants, carers, and assessors were not masked to treatment assignment. The primary outcome was treatment failure by day 6! . Analysis was per protocol with adjustment for clustering within groups by use of generalised estimating equations. This study is registered, number ISRCTN10618300. Findings We assigned 1995 children to treatment in 14 intervention clusters and 1477 in 14 control clusters, and we analysed 1857 and 1354 children, respectively. Cluster-adjusted treatment failure rates by day 6 were significantly reduced in the intervention clusters (165 [9%] vs 241 [18%], risk difference −8·9%, 95% CI −12·4 to −5·4). Further adjustment for baseline covariates made little difference (−7·3%, −10·1 to −4·5). Two deaths were reported in the control clusters and one in the intervention cluster. Most of the risk reduction was in the occurrence of fever and lower chest indrawing on day 3 (−6·7%, −10·0 to −3·3). Adverse events were diarrhoea (n=4) and skin rash (n=1) in the intervention clusters and diarrhoea (n=3) in the control clusters. Interpretation Community case management could result in a standardised treatment for children with severe pneumonia, reduce delay in treatment initiation, and reduce the costs for families and health-care systems. Funding United States Agency for International Development (USAID).
• MRI for breast cancer screening, diagnosis, and treatment
  - The Lancet 378(9805):1804-1811 (2011)
  MRI is used widely both for screening women who are at increased risk of breast cancer and for treatment selection. Prospective studies confirm that MRI screening of women with known or suspected genetic mutation results in a higher sensitivity for cancer detection than does mammography. However, survival data are not available. In women with breast cancer, MRI detects cancer not identified with other types of screening. In two randomised trials, this increased sensitivity did not translate into improved selection of surgical treatment or a reduction in the number of operations. Data for longer-term outcomes such as ipsilateral breast tumour recurrence rates and contralateral breast cancer incidence are scarce, but to date do not show clear benefit for MRI. MRI is better than other methods of assessing the response to neoadjuvant chemotherapy, and is helpful in identifying the primary tumour in patients who present with axillary adenopathy.
• Gene expression profiling in breast cancer: classification, prognostication, and prediction
  - The Lancet 378(9805):1812-1823 (2011)
  Microarray-based gene expression profiling has had a major effect on our understanding of breast cancer. Breast cancer is now perceived as a heterogeneous group of different diseases characterised by distinct molecular aberrations, rather than one disease with varying histological features and clinical behaviour. Gene expression profiling studies have shown that oestrogen-receptor (ER)-positive and ER-negative breast cancers are distinct diseases at the transcriptomic level, that additional molecular subtypes might exist within these groups, and that the prognosis of patients with ER-positive disease is largely determined by the expression of proliferation-related genes. On the basis of these principles, a molecular classification system and prognostic multigene classifiers based on microarrays or derivative technologies have been developed and are being tested in randomised clinical trials and incorporated into clinical practice. In this review, we focus on the concep! tual effect and potential clinical use of the molecular classification of breast cancer, and discuss prognostic and predictive multigene predictors.
• A strange case of waitress headache
  - The Lancet 378(9805):1824 (2011)