Hot off the presses! Nov 18 Lancet

The Nov 18 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:

• November 12â€"18, 2011
  - Lancet 378(9804):i (2011)
  
• Non-medical use of painkillers in the USA
  - Lancet 378(9804):1677 (2011)
  
• Improving rates of surgery for lung cancer
  - Lancet 378(9804):1678 (2011)
  
• Moving toward precision medicine
  - Lancet 378(9804):1678 (2011)
  
• Improvement of care in acute stroke units
  - Lancet 378(9804):1679-1680 (2011)
  
• Radiotherapy and survival in breast cancer
  - Lancet 378(9804):1680-1682 (2011)
  
• Targeting of household air pollution: interpretation of RESPIRE
  - Lancet 378(9804):1682-1684 (2011)
  
• Reporting quality of life in clinical trials: a CONSORT extension
  - Lancet 378(9804):1684-1685 (2011)
  
• What the African fluid-bolus trial means
  - Lancet 378(9804):1685-1687 (2011)
  
• Offline: A 10-minute rule bill
  - Lancet 378(9804):1688 (2011)
  
• New Zealand's bold strategy for reducing health disparities
  - Lancet 378(9804):1689-1690 (2011)
  
• The Lancet Technology: November, 2011
  - Lancet 378(9804):1691 (2011)
  
• Bayes rules: the legacy of Thomas Bayes
  - Lancet 378(9804):1692 (2011)
  
• William Seeley: brain explorer
  - Lancet 378(9804):1693 (2011)
  
• Winstone Mwenda Zulu
  - Lancet 378(9804):1694 (2011)
  
• Outpatient treatment for pulmonary embolism
  - Lancet 378(9804):1695 (2011)
  
• Outpatient treatment for pulmonary embolism
  - Lancet 378(9804):1695 (2011)
  
• Outpatient treatment for pulmonary embolism â€" Authors' reply
  - Lancet 378(9804):1695-1696 (2011)
  
• Use of research evidence in practice
  - Lancet 378(9804):1696 (2011)
  
• Use of research evidence in practice
  - Lancet 378(9804):1696 (2011)
  
• Use of research evidence in practice
  - Lancet 378(9804):1696-1697 (2011)
  
• Use of research evidence in practice â€" Author's reply
  - Lancet 378(9804):1697 (2011)
  
• Political will ushers in a new era for tobacco control in Israel
  - Lancet 378(9804):1697-1698 (2011)
  
• Value-based pricing: time for a NICEr way of measuring health?
  - Lancet 378(9804):1698 (2011)
  
• Conflicts of interest and the UN high-level meeting on non-communicable diseases
  - Lancet 378(9804):e6 (2011)
  
• The remaining smallpox stocks: the wrong debate?
  - Lancet 378(9804):e7 (2011)
  
• The remaining smallpox stocks: the wrong debate? â€" Authors' reply
  - Lancet 378(9804):e7 (2011)
  
• Implementation of evidence-based treatment protocols to manage fever, hyperglycaemia, and swallowing dysfunction in acute stroke (QASC): a cluster randomised controlled trial
  - Lancet 378(9804):1699-1706 (2011)
  Background We assessed patient outcomes 90 days after hospital admission for stroke following a multidisciplinary intervention targeting evidence-based management of fever, hyperglycaemia, and swallowing dysfunction in acute stroke units (ASUs). Methods In the Quality in Acute Stroke Care (QASC) study, a single-blind cluster randomised controlled trial, we randomised ASUs (clusters) in New South Wales, Australia, with immediate access to CT and on-site high dependency units, to intervention or control group. Patients were eligible if they spoke English, were aged 18 years or older, had had an ischaemic stroke or intracerebral haemorrhage, and presented within 48 h of onset of symptoms. Intervention ASUs received treatment protocols to manage fever, hyperglycaemia, and swallowing dysfunction with multidisciplinary team building workshops to address implementation barriers. Control ASUs received only an abridged version of existing guidelines. We recruited pre-intervention and post-intervention patient cohorts to compare 90-day death or dependency (modified Rankin scale [mRS] ≥2), functional dependency (Barthel index), and SF-36 physical and mental component summary scores. Research assistants, the statistician, and patient! s were masked to trial groups. All analyses were done by intention to treat. This trial is registered at the Australia New Zealand Clinical Trial Registry (ANZCTR), number ACTRN12608000563369. Findings 19 ASUs were randomly assigned to intervention (n=10) or control (n=9). Of 6564 assessed for eligibility, 1696 patients' data were obtained (687 pre-intervention; 1009 post-intervention). Results showed that, irrespective of stroke severity, intervention ASU patients were significantly less likely to be dead or dependent (mRS ≥2) at 90 days than control ASU patients (236 [42%] of 558 patients in the intervention group vs 259 [58%] of 449 in the control group, p=0·002; number needed to treat 6·4; adjusted absolute difference 15·7% [95% CI 5·8–25·4]). They also had a better SF-36 mean physical component summary score (45·6 [SD 10·2] in the intervention group vs 42·5 [10·5] in the control group, p=0·002; adjusted absolute difference 3·4 [95% CI 1·2–5·5]) but no improvement was recorded in mortality (21 [4%] of 558 in intervention group and 24 [5%] of 451 in the control group, p=0·36), SF-36 mean mental component summary score (49·5 [10·9] in the interventi! on group vs 49·4 [10·6] in the control group, p=0·69) or functional dependency (Barthel Index ≥60: 487 [92%] of 532 patients vs 380 [90%] of 423 patients; p=0·44). Interpretation Implementation of multidisciplinary supported evidence-based protocols initiated by nurses for the management of fever, hyperglycaemia, and swallowing dysfunction delivers better patient outcomes after discharge from stroke units. Our findings show the possibility to augment stroke unit care. Funding National Health & Medical Research Council ID 353803, St Vincent's Clinic Foundation, the Curran Foundation, Australian Diabetes Society-Servier, the College of Nursing, and Australian Catholic University.
• Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10 801 women in 17 randomised trials
  - Lancet 378(9804):1707-1716 (2011)
  Background After breast-conserving surgery, radiotherapy reduces recurrence and breast cancer death, but it may do so more for some groups of women than for others. We describe the absolute magnitude of these reductions according to various prognostic and other patient characteristics, and relate the absolute reduction in 15-year risk of breast cancer death to the absolute reduction in 10-year recurrence risk. Methods We undertook a meta-analysis of individual patient data for 10 801 women in 17 randomised trials of radiotherapy versus no radiotherapy after breast-conserving surgery, 8337 of whom had pathologically confirmed node-negative (pN0) or node-positive (pN+) disease. Findings Overall, radiotherapy reduced the 10-year risk of any (ie, locoregional or distant) first recurrence from 35·0% to 19·3% (absolute reduction 15·7%, 95% CI 13·7–17·7, 2p<0·00001) and reduced the 15-year risk of breast cancer death from 25·2% to 21·4% (absolute reduction 3·8%, 1·6–6·0, 2p=0·00005). In women with pN0 disease (n=7287), radiotherapy reduced these risks from 31·0% to 15·6% (absolute recurrence reduction 15·4%, 13·2–17·6, 2p<0·00001) and from 20·5% to 17·2% (absolute mortality reduction 3·3%, 0·8–5·8, 2p=0·005), respectively. In these women with pN0 disease, the absolute recurrence reduction varied according to age, grade, oestrogen-receptor status, tamoxifen use, and extent of surgery, and these characteristics were used to predict large (≥20%), intermediate (10–19%), or lower (<10%) absolute reductions in the 10-year recurrence risk. Absolute reductions in 15-year risk of breast cancer death in these three prediction categories! were 7·8% (95% CI 3·1–12·5), 1·1% (–2·0 to 4·2), and 0·1% (–7·5 to 7·7) respectively (trend in absolute mortality reduction 2p=0·03). In the few women with pN+ disease (n=1050), radiotherapy reduced the 10-year recurrence risk from 63·7% to 42·5% (absolute reduction 21·2%, 95% CI 14·5–27·9, 2p<0·00001) and the 15-year risk of breast cancer death from 51·3% to 42·8% (absolute reduction 8·5%, 1·8–15·2, 2p=0·01). Overall, about one breast cancer death was avoided by year 15 for every four recurrences avoided by year 10, and the mortality reduction did not differ significantly from this overall relationship in any of the three prediction categories for pN0 disease or for pN+ disease. Interpretation After breast-conserving surgery, radiotherapy to the conserved breast halves the rate at which the disease recurs and reduces the breast cancer death rate by about a sixth. These proportional benefits vary little between different groups of women. By contrast, the absolute benefits from radiotherapy vary substantially according to the characteristics of the patient and they can be predicted at the time when treatment decisions need to be made. Funding Cancer Research UK, British Heart Foundation, and UK Medical Research Council.
• Effect of reduction in household air pollution on childhood pneumonia in Guatemala (RESPIRE): a randomised controlled trial
  - Lancet 378(9804):1717-1726 (2011)
  Background Pneumonia causes more child deaths than does any other disease. Observational studies have indicated that smoke from household solid fuel is a significant risk factor that affects about half the world's children. We investigated whether an intervention to lower indoor wood smoke emissions would reduce pneumonia in children. Methods We undertook a parallel randomised controlled trial in highland Guatemala, in a population using open indoor wood fires for cooking. We randomly assigned 534 households with a pregnant woman or young infant to receive a woodstove with chimney (n=269) or to remain as controls using open woodfires (n=265), by concealed permuted blocks of ten homes. Fieldworkers visited homes every week until children were aged 18 months to record the child's health status. Sick children with cough and fast breathing, or signs of severe illness were referred to study physicians, masked to intervention status, for clinical examination. The primary outcome was physician-diagnosed pneumonia, without use of a chest radiograph. Analysis was by intention to treat (ITT). Infant 48-h carbon monoxide measurements were used for exposure-response analysis after adjustment for covariates. This trial is registered, number ISRCTN29007941. Findings During 29 125 child-weeks of surveillance of 265 intervention and 253 control children, there were 124 physician-diagnosed pneumonia cases in intervention households and 139 in control households (rate ratio [RR] 0·84, 95% CI 0·63–1·13; p=0·257). After multiple imputation, there were 149 cases in intervention households and 180 in controls (0·78, 0·59–1·06, p=0·095; reduction 22%, 95% CI −6% to 41%). ITT analysis was undertaken for secondary outcomes: all and severe fieldworker-assessed pneumonia; severe (hypoxaemic) physician-diagnosed pneumonia; and radiologically confirmed, RSV-negative, and RSV-positive pneumonia, both total and severe. We recorded significant reductions in the intervention group for three severe outcomes—fieldworker-assessed, physician-diagnosed, and RSV-negative pneumonia—but not for others. We identified no adverse effects from the intervention. The chimney stove reduced exposure by 50% on average (from 2·2 to 1·1 ppm carbon m! onoxide), but exposure distributions for the two groups overlapped substantially. In exposure-response analysis, a 50% exposure reduction was significantly associated with physician-diagnosed pneumonia (RR 0·82, 0·70–0·98), the greater precision resulting from less exposure misclassification compared with use of stove type alone in ITT analysis. Interpretation In a population heavily exposed to wood smoke from cooking, a reduction in exposure achieved with chimney stoves did not significantly reduce physician-diagnosed pneumonia for children younger than 18 months. The significant reduction of a third in severe pneumonia, however, if confirmed, could have important implications for reduction of child mortality. The significant exposure-response associations contribute to causal inference and suggest that stove or fuel interventions producing lower average exposures than these chimney stoves might be needed to substantially reduce pneumonia in populations heavily exposed to biomass fuel air pollution. Funding US National Institute of Environmental Health Sciences and WHO.
• Non-small-cell lung cancer
  - Lancet 378(9804):1727-1740 (2011)
  In the decade since the last Lancet Seminar on lung cancer there have been advances in many aspects of the classification, diagnosis, and treatment of non-small-cell lung cancer (NSCLC). An international panel of experts has been brought together to focus on changes in the epidemiology and pathological classification of NSCLC, the role of CT screening and other techniques that could allow earlier diagnosis and more effective treatment of the disease, and the recently introduced seventh edition of the TNM classification and its relation to other prognostic factors such as biological markers. We also describe advances in treatment that have seen the introduction of a new generation of chemotherapy agents, a proven advantage to adjuvant chemotherapy after complete resection for specific stage groups, new techniques for the planning and administration of radiotherapy, and new surgical approaches to assess and reduce the risks of surgical treatment.
• Small-cell lung cancer
  - Lancet 378(9804):1741-1755 (2011)
  The incidence and mortality of small-cell lung cancer worldwide make this disease a notable health-care issue. Diagnosis relies on histology, with the use of immunohistochemical studies to confirm difficult cases. Typical patients are men older than 70 years who are current or past heavy smokers and who have pulmonary and cardiovascular comorbidities. Patients often present with rapid-onset symptoms due to local intrathoracic tumour growth, extrapulmonary distant spread, paraneoplastic syndromes, or a combination of these features. Staging aims ultimately to define disease as metastatic or non-metastatic. Combination chemotherapy, generally platinum-based plus etoposide or irinotecan, is the mainstay first-line treatment for metastatic small-cell lung cancer. For non-metastatic disease, evidence supports early concurrent thoracic radiotherapy. Prophylactic cranial irradiation should be considered for patients with or without metastases whose disease does not progress a! fter induction chemotherapy and radiotherapy. Despite high initial response rates, most patients eventually relapse. Except for topotecan, few treatment options then remain. Signalling pathways have been identified that might yield new drug targets.
• Fever of unknown origin
  - Lancet 378(9804):1756 (2011)