Hot off the presses! Jul 01 Lancet

The Jul 01 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:

• Managing pain effectively
  - Lancet 377(9784):2151 (2011)
  
• Osteoporosis—striking the right balance
  - Lancet 377(9784):2152 (2011)
  
• "Respect your elders"
  - Lancet 377(9784):2152 (2011)
  
• SHARP: a stab in the right direction in chronic kidney disease
  - Lancet 377(9784):2153-2154 (2011)
  
• Antithrombotics and stent type for primary PCI
  - Lancet 377(9784):2154-2156 (2011)
  
• Extreme health inequalities: mortality in homeless people
  - Lancet 377(9784):2156-2157 (2011)
  
• Nudge smudge: UK Government misrepresents "nudge"
  - Lancet 377(9784):2158-2159 (2011)
  
• Universal health coverage: friend or foe of health equity?
  - Lancet 377(9784):2160-2161 (2011)
  
• The growing movement for universal health coverage
  - Lancet 377(9784):2161-2163 (2011)
  
• Offline: Looking forward to some surprises
  - Lancet 377(9784):2164 (2011)
  
• GAVI funding meeting exceeds expectations
  - Lancet 377(9784):2165-2166 (2011)
  
• South Sudan faces grim health and humanitarian situation
  - Lancet 377(9784):2167-2168 (2011)
  
• On the edge of forever
  - Lancet 377(9784):2169 (2011)
  
• The lives of stories, or the body of words
  - Lancet 377(9784):2170 (2011)
  
• Lul Riek: helping to improve public health in South Sudan
  - Lancet 377(9784):2171 (2011)
  
• "Why are the mentally ill still bearing arms?"
  - Lancet 377(9784):2172-2173 (2011)
  
• David Judson Sencer
  - Lancet 377(9784):2174 (2011)
  
• Triggers of myocardial infarction
  - Lancet 377(9784):2175 (2011)
  
• Triggers of myocardial infarction
  - Lancet 377(9784):2175 (2011)
  
• Triggers of myocardial infarction – Authors' reply
  - Lancet 377(9784):2175-2176 (2011)
  
• Wireless pulmonary artery haemodynamic monitoring
  - Lancet 377(9784):2176 (2011)
  
• Wireless pulmonary artery haemodynamic monitoring
  - Lancet 377(9784):2176-2177 (2011)
  
• Wireless pulmonary artery haemodynamic monitoring – Authors' reply
  - Lancet 377(9784):2177 (2011)
  
• Safety and efficacy of zoledronic acid in multiple myeloma
  - Lancet 377(9784):2177-2178 (2011)
  
• Safety and efficacy of zoledronic acid in multiple myeloma
  - Lancet 377(9784):2178 (2011)
  
• Decline in neonatal mortality in large poor populations
  - Lancet 377(9784):2178-2179 (2011)
  
• Decline in neonatal mortality in large poor populations – Authors' reply
  - Lancet 377(9784):2179 (2011)
  
• Rising liver death rate: food for thought
  - Lancet 377(9784):2179-2180 (2011)
  
• ECDC and the Escherichia coli outbreak in Germany
  - Lancet 377(9784):2180 (2011)
  
• Department of Error
  - Lancet 377(9784):2180 (2011)
  
• The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial
  - Lancet 377(9784):2181-2192 (2011)
  Background Lowering LDL cholesterol with statin regimens reduces the risk of myocardial infarction, ischaemic stroke, and the need for coronary revascularisation in people without kidney disease, but its effects in people with moderate-to-severe kidney disease are uncertain. The SHARP trial aimed to assess the efficacy and safety of the combination of simvastatin plus ezetimibe in such patients. Methods This randomised double-blind trial included 9270 patients with chronic kidney disease (3023 on dialysis and 6247 not) with no known history of myocardial infarction or coronary revascularisation. Patients were randomly assigned to simvastatin 20 mg plus ezetimibe 10 mg daily versus matching placebo. The key prespecified outcome was first major atherosclerotic event (non-fatal myocardial infarction or coronary death, non-haemorrhagic stroke, or any arterial revascularisation procedure). All analyses were by intention to treat. This trial is registered at ClinicalTrials.gov, NCT00125593, and ISRCTN54137607. Findings 4650 patients were assigned to receive simvastatin plus ezetimibe and 4620 to placebo. Allocation to simvastatin plus ezetimibe yielded an average LDL cholesterol difference of 0·85 mmol/L (SE 0·02; with about two-thirds compliance) during a median follow-up of 4·9 years and produced a 17% proportional reduction in major atherosclerotic events (526 [11·3%] simvastatin plus ezetimibe vs 619 [13·4%] placebo; rate ratio [RR] 0·83, 95% CI 0·74–0·94; log-rank p=0·0021). Non-significantly fewer patients allocated to simvastatin plus ezetimibe had a non-fatal myocardial infarction or died from coronary heart disease (213 [4·6%] vs 230 [5·0%]; RR 0·92, 95% CI 0·76–1·11; p=0·37) and there were significant reductions in non-haemorrhagic stroke (131 [2·8%] vs 174 [3·8%]; RR 0·75, 95% CI 0·60–0·94; p=0·01) and arterial revascularisation procedures (284 [6·1%] vs 352 [7·6%]; RR 0·79, 95% CI 0·68–0·93; p=0·0036). After weighting for subgroup-specific red! uctions in LDL cholesterol, there was no good evidence that the proportional effects on major atherosclerotic events differed from the summary rate ratio in any subgroup examined, and, in particular, they were similar in patients on dialysis and those who were not. The excess risk of myopathy was only two per 10 000 patients per year of treatment with this combination (9 [0·2%] vs 5 [0·1%]). There was no evidence of excess risks of hepatitis (21 [0·5%] vs 18 [0·4%]), gallstones (106 [2·3%] vs 106 [2·3%]), or cancer (438 [9·4%] vs 439 [9·5%], p=0·89) and there was no significant excess of death from any non-vascular cause (668 [14·4%] vs 612 [13·2%], p=0·13). Interpretation Reduction of LDL cholesterol with simvastatin 20 mg plus ezetimibe 10 mg daily safely reduced the incidence of major atherosclerotic events in a wide range of patients with advanced chronic kidney disease. Funding Merck/Schering-Plough Pharmaceuticals; Australian National Health and Medical Research Council; British Heart Foundation; UK Medical Research Council.
• Heparin plus a glycoprotein IIb/IIIa inhibitor versus bivalirudin monotherapy and paclitaxel-eluting stents versus bare-metal stents in acute myocardial infarction (HORIZONS-AMI): final 3-year results from a multicentre, randomised controlled trial
  - Lancet 377(9784):2193-2204 (2011)
  Background Primary results of the HORIZONS-AMI trial have been previously reported. In this final report, we aimed to assess 3-year outcomes. Methods HORIZONS-AMI was a prospective, open-label, randomised trial undertaken at 123 institutions in 11 countries. Patients aged 18 years or older were eligible for enrolment if they had ST-segment elevation myocardial infarction (STEMI), presented within 12 h after onset of symptoms, and were undergoing primary percutaneous coronary intervention. By use of a computerised interactive voice response system, we randomly allocated patients 1:1 to receive bivalirudin or heparin plus a glycoprotein IIb/IIIa inhibitor (GPI; pharmacological randomisation; stratified by previous and expected drug use and study site) and, if eligible, randomly allocated 3:1 to receive a paclitaxel-eluting stent or a bare metal stent (stent randomisation; stratified by pharmacological group assignment, diabetes mellitus status, lesion length, and study site). We produced Kaplan-Meier estimates of major adverse cardiovascular events at 3 years by intention to treat. This study is registered with ClinicalTria! ls.gov, number NCT00433966. Findings Compared with 1802 patients allocated to receive heparin plus a GPI, 1800 patients allocated to bivalirudin monotherapy had lower rates of all-cause mortality (5·9% vs 7·7%, difference −1·9% [−3·5 to −0·2], HR 0·75 [0·58–0·97]; p=0·03), cardiac mortality (2·9% vs 5·1%, −2·2% [−3·5 to −0·9], 0·56 [0·40–0·80]; p=0·001), reinfarction (6·2% vs 8·2%, −1·9% [−3·7 to −0·2], 0·76 [0·59–0·99]; p=0·04), and major bleeding not related to bypass graft surgery (6·9% vs 10·5%, −3·6% [−5·5 to −1·7], 0·64 [0·51–0·80]; p=0·0001) at 3 years, with no significant differences in ischaemia-driven target vessel revascularisation, stent thrombosis, or composite adverse events. Compared with 749 patients who received a bare-metal stent, 2257 patients who received a paclitaxel-eluting stent had lower rates of ischaemia-driven target lesion revascularisation (9·4% vs 15·1%, −5·7% [−8·6 to −2·7], 0·60 [0·48–0·76]; p<0·! 0001) after 3 years, with no significant differences in the rates of death, reinfarction, stroke or stent thrombosis. Stent thrombosis was high (≥4·5%) in both groups. Interpretation The effectiveness and safety of bivalirudin monotherapy and paclitaxel-eluting stenting are sustained at 3 years for patients with STEMI undergoing primary percutaneous coronary intervention. Funding Boston Scientific and The Medicines Company.
• Psychiatric disorders and mortality among people in homeless shelters in Denmark: a nationwide register-based cohort study
  - Lancet 377(9784):2205-2214 (2011)
  Background The increased mortality of homeless people compared with non-homeless people might be linked to psychiatric disorders. However, homeless people are, because of their insufficient accommodation, difficult to sample and monitor, which has limited previous studies. We aimed to assess registered psychiatric disorders, mortality, and predictors of mortality in the homeless shelter population in Denmark. Methods We did a nationwide, prospective, register-based cohort study of homeless people aged 16 years and older who were registered in the Danish Homeless Register between Jan 1, 1999, and Dec 31, 2009. We calculated the proportion of registered psychiatric disorders, overall and cause-specific standardised mortality ratio (SMR), and life expectancy. Hazard ratios (HRs) were used to assess predictors of death. Findings 32 711 homeless people (23 040 men and 9671 women) were included in the study population. 14 381 men (62·4%) and 5632 women (58·2%) had registered psychiatric disorders, and 11 286 men (49·0%) and 3564 women (36·9%) had a substance abuse diagnosis. During the study period, 3839 men (16·7%) and 951 women (9·8%) died. The overall SMR for men was 5·6 (95% CI 5·4–5·8) and for women was 6·7 (6·2–7·1), and external causes accounted for 1161 (27·9%) of 4161 deaths for which information on the cause was available. Remaining life expectancy at age 15–24 years was 21·6 years (95% CI 21·2–22·1) and 17·4 years (16·4–18·5) lower for homeless men and women, respectively, than the general population. Registered substance abuse disorder was associated with the highest mortality risk compared with no psychiatric contact registered (adjusted HR 1·4, 95% CI 1·3–1·5 for men; 1·7, 1·4–2·1 for women). Interpretation Health problems are extensive in the homeless shelter population and there is an urgent need for more sustained efforts to reduce the high morbidity and mortality, especially from external causes. Register data is an important resource to supplement existing knowledge on homeless people with more valid and detailed information. Funding The Danish Council for Independent Research.
• Treatment of acute postoperative pain
  - Lancet 377(9784):2215-2225 (2011)
  Although postoperative pain remains incompletely controlled in some settings, increased understanding of its mechanisms and the development of several therapeutic approaches have substantially improved pain control in past years. Advances in our understanding of the process of nociception have led to insight into gene-based pain therapy, the development of acute opioid-induced hyperalgesia, and persistent postsurgical pain. Use of specific analgesic techniques such as regional analgesia could improve patient outcomes. We also examine the development of new analgesic agents and treatment modalities and regimens for acute postoperative pain.
• Treatment of chronic non-cancer pain
  - Lancet 377(9784):2226-2235 (2011)
  Chronic pain is a pervasive problem that affects the patient, their significant others, and society in many ways. The past decade has seen advances in our understanding of the mechanisms underlying pain and in the availability of technically advanced diagnostic procedures; however, the most notable therapeutic changes have not been the development of novel evidenced-based methods, but rather changing trends in applications and practices within the available clinical armamentarium. We provide a general overview of empirical evidence for the most commonly used interventions in the management of chronic non-cancer pain, including pharmacological, interventional, physical, psychological, rehabilitative, and alternative modalities. Overall, currently available treatments provide modest improvements in pain and minimum improvements in physical and emotional functioning. The quality of evidence is mediocre and has not improved substantially during the past decade. There is a ! crucial need for assessment of combination treatments, identification of indicators of treatment response, and assessment of the benefit of matching of treatments to patient characteristics.
• Treatment of cancer pain
  - Lancet 377(9784):2236-2247 (2011)
  In patients with active cancer, the management of chronic pain is an essential element in a comprehensive strategy for palliative care. This strategy emphasises multidimensional assessment and the coordinated use of treatments that together mitigate suffering and provide support to the patient and family. This review describes this framework, an approach to pain assessment, and widely accepted techniques to optimise the safety and effectiveness of opioid drugs and other treatments. The advances of recent decades suggest a future that includes increased evidence-based targeting of specific analgesic interventions within an individualised plan of care that is appropriate throughout the course of illness.
• Bilateral hip pain
  - Lancet 377(9784):2248 (2011)