The Global Fund: replenishment and redefinition in 2010.

Lancet. 2010 Mar 13;375(9718):865

Authors:

PMID: 20226967 [PubMed - in process]

A 10-year plan to reduce road-traffic accidents.

Lancet. 2010 Mar 13;375(9718):866

Authors:

PMID: 20226969 [PubMed - in process]

The price of foodborne illness in the USA.

Lancet. 2010 Mar 13;375(9718):866

Authors:

PMID: 20226968 [PubMed - in process]

Offline: The facts on the ground.

Lancet. 2010 Mar 13;375(9718):878

Authors: Horton R

PMID: 20226973 [PubMed - in process]

Surgery--call for papers.

Lancet. 2010 Mar 13;375(9718):877

Authors: Summerskill W

PMID: 20226972 [PubMed - in process]

Expression of concern--Probiotic prophylaxis in predicted severe acute pancreatitis: a randomised, double-blind, placebo-controlled trial.

Lancet. 2010 Mar 13;375(9718):875-6

Authors:

PMID: 20226971 [PubMed - in process]

Stroke and blood-pressure variation: new permutations on an old theme.

Lancet. 2010 Mar 13;375(9718):867-9

Authors: Carlberg B, Lindholm LH

PMID: 20226970 [PubMed - in process]

Magic is acceptable.

Lancet. 2010 Mar 13;375(9718):885

Authors: Laurance J

PMID: 20226975 [PubMed - in process]

Lord Nigel Crisp.

Lancet. 2010 Mar 13;375(9718):885

Authors: Bristol N

PMID: 20226974 [PubMed - in process]

Humanitarian disaster response.

Lancet. 2010 Mar 13;375(9718):891-2

Authors: Lee A

PMID: 20226980 [PubMed - in process]

VTACH trial.

Lancet. 2010 Mar 13;375(9718):890; author reply 890-1

Authors: Kida Y

PMID: 20226978 [PubMed - in process]

Variant or sporadic Creutzfeldt-Jakob disease?

Lancet. 2010 Mar 13;375(9718):889; author reply 889-90

Authors: Brandel JP, Galanaud D, Freeman L, Laplanche JL, Haik S

PMID: 20226976 [PubMed - in process]

Ethical standards in Cambodia: is silent witnessing sufficient?

Lancet. 2010 Mar 13;375(9718):892

Authors: Loff B, Overs C

PMID: 20226982 [PubMed - in process]

Humanitarian disaster response.

Lancet. 2010 Mar 13;375(9718):891

Authors: Shoham J, Watson F, McGrath M

PMID: 20226981 [PubMed - in process]

The Health Impact Fund.

Lancet. 2010 Mar 13;375(9718):893

Authors: Norris J

PMID: 20226985 [PubMed - in process]

The Health Impact Fund.

Lancet. 2010 Mar 13;375(9718):893

Authors: Light DW

PMID: 20226984 [PubMed - in process]

Donors' commitments to neglected tropical diseases: not all bad.

Lancet. 2010 Mar 13;375(9718):892-3

Authors: Sakisaka K, Nakamura J

PMID: 20226983 [PubMed - in process]

Health and human rights education: time to act.

Lancet. 2010 Mar 13;375(9718):894

Authors: Hall P

PMID: 20226987 [PubMed - in process]

Health and human rights education: time to act.

Lancet. 2010 Mar 13;375(9718):894

Authors: Backman G, Fitchett JR

PMID: 20226986 [PubMed - in process]

Effects of antihypertensive-drug class on interindividual variation in blood pressure and risk of stroke: a systematic review and meta-analysis.

Lancet. 2010 Mar 13;375(9718):906-15

Authors: Webb AJ, Fischer U, Mehta Z, Rothwell PM

INTRODUCTION: Unexplained differences between classes of antihypertensive drugs in their effectiveness in preventing stroke might be due to class effects on intraindividual variability in blood pressure. We did a systematic review to assess any such effects in randomised controlled trials. METHODS: Baseline and follow-up data for mean (SD) of systolic blood pressure (SBP) were extracted from trial reports. Effect of treatment on interindividual variance (SD2) in blood pressure (a surrogate for within-individual variability), expressed as the ratio of the variances (VR), was related to effects on clinical outcomes. Pooled estimates were derived by use of random-effects meta-analysis. FINDINGS: Mean (SD) SBP at follow-up was reported in 389 (28%) of 1372 eligible trials. There was substantial heterogeneity between trials in VR (p<1 x 10(-40)), 68% of which was attributable to allocated drug class. Compared with other drugs, interindividual variation in SBP was reduced by calcium-channel blockers (VR 0.81, 95% CI 0.76-0.86, p<0.0001) and non-loop diuretic drugs (0.87, 0.79-0.96, p=0.007), and increased by angiotensin-converting enzyme (ACE) inhibitors (1.08, 1.02-1.15, p=0.008), angiotensin-receptor blockers (1.16, 1.07-1.25, p=0.0002), and beta blockers (1.17, 1.07-1.28, p=0.0007). Compared with placebo only, interindividual variation in SBP was reduced the most by calcium-channel blockers (0.76, 0.67-0.85, p<0.0001). Effects were consistent in parallel group and crossover design trials, and in analyses of dose-response. Across all trials, effects of treatment on VR of SBP (r2=0.372, p=0.0006) and on mean SBP (r2=0.328, p=0.0015) accounted for effects on stroke risk (eg, odds ratio 0.79, 0.71-0.87, p<0.0001, for VR< or =0.80), and both remained significant in a combined model. INTERPRETATION: Drug-class effects on interindividual variation in blood pressure can account for differences in effects of antihypertensive drugs on risk of stroke independently of effects on mean SBP. FUNDING: None.

PMID: 20226989 [PubMed - in process]

Prognostic significance of visit-to-visit variability, maximum systolic blood pressure, and episodic hypertension.

Lancet. 2010 Mar 13;375(9718):895-905

Authors: Rothwell PM, Howard SC, Dolan E, O'Brien E, Dobson JE, Dahlöf B, Sever PS, Poulter NR

BACKGROUND: The mechanisms by which hypertension causes vascular events are unclear. Guidelines for diagnosis and treatment focus only on underlying mean blood pressure. We aimed to reliably establish the prognostic significance of visit-to-visit variability in blood pressure, maximum blood pressure reached, untreated episodic hypertension, and residual variability in treated patients. METHODS: We determined the risk of stroke in relation to visit-to-visit variability in blood pressure (expressed as standard deviation [SD] and parameters independent of mean blood pressure) and maximum blood pressure in patients with previous transient ischaemic attack (TIA; UK-TIA trial and three validation cohorts) and in patients with treated hypertension (Anglo-Scandinavian Cardiac Outcomes Trial Blood Pressure Lowering Arm [ASCOT-BPLA]). In ASCOT-BPLA, 24-h ambulatory blood-pressure monitoring (ABPM) was also studied. FINDINGS: In each TIA cohort, visit-to-visit variability in systolic blood pressure (SBP) was a strong predictor of subsequent stroke (eg, top-decile hazard ratio [HR] for SD SBP over seven visits in UK-TIA trial: 6.22, 95% CI 4.16-9.29, p<0.0001), independent of mean SBP, but dependent on precision of measurement (top-decile HR over ten visits: 12.08, 7.40-19.72, p<0.0001). Maximum SBP reached was also a strong predictor of stroke (HR for top-decile over seven visits: 15.01, 6.56-34.38, p<0.0001, after adjustment for mean SBP). In ASCOT-BPLA, residual visit-to-visit variability in SBP on treatment was also a strong predictor of stroke and coronary events (eg, top-decile HR for stroke: 3.25, 2.32-4.54, p<0.0001), independent of mean SBP in clinic or on ABPM. Variability on ABPM was a weaker predictor, but all measures of variability were most predictive in younger patients and at lower (<median) values of mean SBP in every cohort. INTERPRETATION: Visit-to-visit variability in SBP and maximum SBP are strong predictors of stroke, independent of mean SBP. Increased residual variability in SBP in patients with treated hypertension is associated with a high risk of vascular events. FUNDING: None.

PMID: 20226988 [PubMed - in process]

Limitations of the usual blood-pressure hypothesis and importance of variability, instability, and episodic hypertension.

Lancet. 2010 Mar 13;375(9718):938-48

Authors: Rothwell PM

Although hypertension is the most prevalent treatable vascular risk factor, how it causes end-organ damage and vascular events is poorly understood. Yet, a widespread belief exists that underlying usual blood pressure can alone account for all blood-pressure-related risk of vascular events and for the benefits of antihypertensive drugs, and this notion has come to underpin all major clinical guidelines on diagnosis and treatment of hypertension. Other potentially informative measures, such as variability in clinic blood pressure or maximum blood pressure reached, have been neglected, and effects of antihypertensive drugs on such measures are largely unknown. Clinical guidelines recommend that episodic hypertension is not treated, and the potential risks of residual variability in blood pressure in treated hypertensive patients have been ignored. This Review discusses shortcomings of the usual blood-pressure hypothesis, provides background to accompanying reports on the importance of blood-pressure variability in prediction of risk of vascular events and in accounting for benefits of antihypertensive drugs, and draws attention to clinical implications and directions for future research.

PMID: 20226991 [PubMed - in process]

Porphyrias.

Lancet. 2010 Mar 13;375(9718):924-37

Authors: Puy H, Gouya L, Deybach JC

Hereditary porphyrias are a group of eight metabolic disorders of the haem biosynthesis pathway that are characterised by acute neurovisceral symptoms, skin lesions, or both. Every porphyria is caused by abnormal function of a separate enzymatic step, resulting in a specific accumulation of haem precursors. Seven porphyrias are the result of a partial enzyme deficiency, and a gain of function mechanism has been characterised in a new porphyria. Acute porphyrias present with acute attacks, typically consisting of severe abdominal pain, nausea, constipation, confusion, and seizure, and can be life-threatening. Cutaneous porphyrias present with either acute painful photosensitivity or skin fragility and blisters. Rare recessive porphyrias usually manifest in early childhood with either severe cutaneous photosensitivity and chronic haemolysis or chronic neurological symptoms with or without photosensitivity. Porphyrias are still underdiagnosed, but when they are suspected, and dependent on clinical presentation, simple first-line tests can be used to establish the diagnosis in all symptomatic patients. Diagnosis is essential to enable specific treatments to be started as soon as possible. Screening of families to identify presymptomatic carriers is crucial to decrease risk of overt disease of acute porphyrias through counselling about avoidance of potential precipitants.

PMID: 20226990 [PubMed - in process]

Antisense technology to lower LDL cholesterol.

Lancet. 2010 Mar 12;

Authors: Neely RD, Bassendine MF

PMID: 20227757 [PubMed - as supplied by publisher]

Hiccups, nausea, and vomiting: water channels under attack!

Lancet. 2010 Mar 13;375(9718):954

Authors: Riphagen J, Modderman P, Verrips A

PMID: 20226992 [PubMed - in process]

Efficacy and safety of zotarolimus-eluting and sirolimus-eluting coronary stents in routine clinical care (SORT OUT III): a randomised controlled superiority trial.

Lancet. 2010 Mar 13;

Authors: Rasmussen K, Maeng M, Kaltoft A, Thayssen P, Kelbæk H, Tilsted HH, Abildgaard U, Christiansen EH, Engstrøm T, Krusell LR, Ravkilde J, Hansen PR, Hansen KN, Abildstrøm SZ, Aarøe J, Jensen JS, Kristensen SD, Bøtker HE, Madsen M, Johnsen SP, Jensen LO, Sørensen HT, Thuesen L, Lassen JF,

BACKGROUND: In low-risk patients, the zotarolimus-eluting stent has been shown to reduce rates of restenosis without increasing the risk of stent thrombosis. We compared the efficacy and safety of the zotarolimus-eluting stent versus the sirolimus-eluting stent in patients with coronary artery disease who were receiving routine clinical care with no direct follow-up. METHODS: We did a single-blind, all-comer superiority trial in adult patients with chronic stable coronary artery disease or acute coronary syndromes, and at least one target lesion. Patients were treated at one of five percutaneous coronary intervention centres between January, 2006, and August, 2007. Computer-generated block randomisation and a telephone allocation service were used to randomly assign patients to receive the zotarolimus-eluting or the sirolimus-eluting stent. Data for follow-up were obtained from national Danish administrative and health-care registries. The primary endpoint was a composite of major adverse cardiac events within 9 months: cardiac death, myocardial infarction, and target vessel revascularisation. Intention-to-treat analyses were done at 9-month and 18-month follow-up. This trial is registered with ClinicalTrials.gov, number NCT00660478. FINDINGS: 1162 patients (1619 lesions) were assigned to receive the zotarolimus-eluting stent, and 1170 patients (1611 lesions) to receive the sirolimus-eluting stent. 67 patients (72 lesions) had stent failure, and six patients were lost to follow-up. All randomly assigned patients were included in analyses at 9-month follow-up; 2200 patients (94%) had completed 18-month follow-up by the time of our assessment. At 9 months, the primary endpoint had occurred in a higher proportion of patients treated with the zotarolimus-eluting stent than in those treated with the sirolimus-eluting stent (72 [6%] vs 34 [3%]; HR 2.15, 95% CI 1.43-3.23; p=0.0002). At 18-month follow-up, this difference was sustained (113 [10%] vs 53 [5%]; 2.19, 1.58-3.04; p<0.0001). For patients receiving the zotarolimus-eluting stent and those receiving the sirolimus-eluting stent, all cause-mortality was similar at 9-month follow-up (25 [2%] vs 18 [2%]; 1.40, 0.76-2.56; p=0.28), but was significantly different at 18-month follow-up (51 [4%] vs 32 [3%]; 1.61, 1.03-2.50; p=0.035). INTERPRETATION: The sirolimus-eluting stent is superior to the zotarolimus-eluting stent for patients receiving routine clinical care. FUNDING: Cordis and Medtronic.

PMID: 20231034 [PubMed - as supplied by publisher]

Mipomersen, an apolipoprotein B synthesis inhibitor, for lowering of LDL cholesterol concentrations in patients with homozygous familial hypercholesterolaemia: a randomised, double-blind, placebo-controlled trial.

Lancet. 2010 Mar 12;

Authors: Raal FJ, Santos RD, Blom DJ, Marais AD, Charng MJ, Cromwell WC, Lachmann RH, Gaudet D, Tan JL, Chasan-Taber S, Tribble DL, Flaim JD, Crooke ST

BACKGROUND: Homozygous familial hypercholesterolaemia is a rare genetic disorder in which both LDL-receptor alleles are defective, resulting in very high concentrations of LDL cholesterol in plasma and premature coronary artery disease. This study investigated whether an antisense inhibitor of apolipoprotein B synthesis, mipomersen, is effective and safe as an adjunctive agent to lower LDL cholesterol concentrations in patients with this disease. METHODS: This randomised, double-blind, placebo-controlled, phase 3 study was undertaken in nine lipid clinics in seven countries. Patients aged 12 years and older with clinical diagnosis or genetic confirmation of homozygous familial hypercholesterolaemia, who were already receiving the maximum tolerated dose of a lipid-lowering drug, were randomly assigned to mipomersen 200 mg subcutaneously every week or placebo for 26 weeks. Randomisation was computer generated and stratified by weight (<50 kg vs >/=50 kg) in a centralised blocked randomisation, implemented with a computerised interactive voice response system. All clinical, medical, and pharmacy personnel, and patients were masked to treatment allocation. The primary endpoint was percentage change in LDL cholesterol concentration from baseline. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00607373. FINDINGS: 34 patients were assigned to mipomersen and 17 to placebo; data for all patients were analysed. 45 patients completed the 26-week treatment period (28 mipomersen, 17 placebo). Mean concentrations of LDL cholesterol at baseline were 11.4 mmol/L (SD 3.6) in the mipomersen group and 10.4 mmol/L (3.7) in the placebo group. The mean percentage change in LDL cholesterol concentration was significantly greater with mipomersen (-24.7%, 95% CI -31.6 to -17.7) than with placebo (-3.3%, -12.1 to 5.5; p=0.0003). The most common adverse events were injection-site reactions (26 [76%] patients in mipomersen group vs four [24%] in placebo group). Four (12%) patients in the mipomersen group but none in the placebo group had increases in concentrations of alanine aminotransferase of three times or more the upper limit of normal. INTERPRETATION: Inhibition of apolipoprotein B synthesis by mipomersen represents a novel, effective therapy to reduce LDL cholesterol concentrations in patients with homozygous familial hypercholesterolaemia who are already receiving lipid-lowering drugs, including high-dose statins. FUNDING: ISIS Pharmaceuticals and Genzyme Corporation.

PMID: 20227758 [PubMed - as supplied by publisher]

Sri Lanka struggles with mental health burden.

Lancet. 2010 Mar 13;375(9718):880-1

Authors: Siva N

PMID: 20232497 [PubMed - in process]

Sorting out drug-eluting stents.

Lancet. 2010 Mar 13;

Authors: Webster MW, Ormiston JA

PMID: 20231035 [PubMed - as supplied by publisher]

Mothers and infants to get free health care in Sierra Leone.

Lancet. 2010 Mar 13;375(9718):882

Authors: Wakabi W

PMID: 20232514 [PubMed - in process]

Obama attempts to push through health reform bill.

Lancet. 2010 Mar 13;375(9718):879

Authors: Bristol N

PMID: 20232513 [PubMed - in process]

Music, medicine, and embodiment.

Lancet. 2010 Mar 13;375(9718):886-7

Authors: Evans HM

PMID: 20232498 [PubMed - in process]

Infection-related stillbirths.

Lancet. 2010 Mar 9;

Authors: Goldenberg RL, McClure EM, Saleem S, Reddy UM

Infection is an important cause of stillbirths worldwide: in low-income and middle-income countries, 50% of stillbirths or more are probably caused by infection. By contrast, in high-income countries only 10-25% of stillbirths are caused by infection. Syphilis, where prevalent, causes most infectious stillbirths, and is the infection most amenable to screening and treatment. Ascending bacterial infection is a common cause of stillbirths, but prevention has proven elusive. Many viral infections cause stillbirths but aside from vaccination for common childhood diseases, we do not have a clear prevention strategy. Malaria, because of its high prevalence and extensive placental damage, accounts for large numbers of stillbirths. Intermittent malarial prophylaxis and insecticide-treated bednets should decrease stillbirths. Many infections borne by animals and vectors cause stillbirths, and these types of infections occur frequently in low-income countries. Research that better defines the relation between these infections and stillbirths, and develops strategies to reduce associated adverse outcomes, should play an important part in reduction of stillbirths in low-income countries.

PMID: 20223514 [PubMed - as supplied by publisher]

GAVI enters its second decade with massive funding gap.

Lancet. 2010 Mar 6;375(9717):791

Authors: Usher AD

PMID: 20217910 [PubMed - in process]

Reports focus on female genital mutilation in Iraqi Kurdistan.

Lancet. 2010 Mar 6;375(9717):794

Authors: Burki T

PMID: 20217912 [PubMed - in process]

US plans to boost number of medical schools.

Lancet. 2010 Mar 6;375(9717):792-3

Authors: Devi S

PMID: 20217911 [PubMed - in process]

Thinking in time: does health policy need history as evidence?

Lancet. 2010 Mar 6;375(9717):798-9

Authors: Berridge V

PMID: 20217913 [PubMed - in process]

Time for a responsible internet age.

Lancet. 2010 Mar 6;375(9717):778

Authors:

PMID: 20206756 [PubMed - in process]

International Women's Day 2010.

Lancet. 2010 Mar 6;375(9717):777

Authors:

PMID: 20206755 [PubMed - in process]

Apixaban to prevent venous thromboembolism after knee replacement.

Lancet. 2010 Mar 6;375(9717):779-80

Authors: Fareed J, Hull R

PMID: 20206758 [PubMed - in process]

Raising awareness of antiphospholipid antibody syndrome.

Lancet. 2010 Mar 6;375(9717):778

Authors:

PMID: 20206757 [PubMed - in process]

Offline: Those who think freely think well.

Lancet. 2010 Mar 6;375(9717):790

Authors: Horton R

PMID: 20206762 [PubMed - in process]

Peer review: what would we do without it?

Lancet. 2010 Mar 6;375(9717):789

Authors: Kleinert S

PMID: 20206761 [PubMed - in process]

Calling young researchers.

Lancet. 2010 Mar 6;375(9717):788-9

Authors: Samarasekera U, Jupp S

PMID: 20206760 [PubMed - in process]

Radiotherapy for endometrial cancer: a key piece in the jigsaw.

Lancet. 2010 Mar 6;375(9717):781-2

Authors: Kitchener H, Powell M

PMID: 20206759 [PubMed - in process]

Seasonal vaccine effectiveness against pandemic A/H1N1.

Lancet. 2010 Mar 6;375(9717):801-2; author reply 802-3

Authors: Janjua NZ, Skowronski DM, Hottes TS, De Serres G, Crowcroft NS, Rosella LC

PMID: 20206765 [PubMed - in process]

Agnes Moses: preventing maternal transmission of HIV in Malawi.

Lancet. 2010 Mar 6;375(9717):797

Authors: Shetty P

PMID: 20206763 [PubMed - in process]

Colombia's health reform: false debates, real imperatives.

Lancet. 2010 Mar 6;375(9717):803

Authors: Yamin AE

PMID: 20206768 [PubMed - in process]

White blood.

Lancet. 2010 Mar 6;375(9717):801; author reply 801

Authors: Lommerse K, Mwagomba B, van den Akker T

PMID: 20206766 [PubMed - in process]

Abortion in Australia: still to emerge from the 19th century.

Lancet. 2010 Mar 6;375(9717):804-5

Authors: de Costa CM, Russell DB, Carrette M

PMID: 20206770 [PubMed - in process]

Colombia's health reform: false debates, real imperatives.

Lancet. 2010 Mar 6;375(9717):803

Authors: Londoño E, Dario-Gómez R, de Vos P

PMID: 20206769 [PubMed - in process]

Snake bite: simple steps to prevention and reduction of morbidity.

Lancet. 2010 Mar 6;375(9717):805

Authors: Bawaskar HS, Bawaskar PH

PMID: 20206773 [PubMed - in process]

Health benefits of interventions to reduce greenhouse gases.

Lancet. 2010 Mar 6;375(9717):804; author reply 804

Authors: Ezzati M, Lin HH

PMID: 20206772 [PubMed - in process]

Apixaban versus enoxaparin for thromboprophylaxis after knee replacement (ADVANCE-2): a randomised double-blind trial.

Lancet. 2010 Mar 6;375(9717):807-15

Authors: Lassen MR, Raskob GE, Gallus A, Pineo G, Chen D, Hornick P,

BACKGROUND: Low-molecular-weight heparins such as enoxaparin are preferred for prevention of venous thromboembolism after major joint replacement. Apixaban, an orally active factor Xa inhibitor, might be as effective, have lower bleeding risk, and be easier to use than is enoxaparin. We assessed efficacy and safety of these drugs after elective total knee replacement. METHODS: In ADVANCE-2, a multicentre, randomised, double-blind phase 3 study, patients undergoing elective unilateral or bilateral total knee replacement were randomly allocated through an interactive central telephone system to receive oral apixaban 2.5 mg twice daily (n=1528) or subcutaneous enoxaparin 40 mg once daily (1529). The randomisation schedule was generated by the Bristol-Myers Squibb randomisation centre and stratified by study site and by unilateral or bilateral surgery with a block size of four. Investigators, patients, statisticians, adjudicators, and steering committee were masked to allocation. Apixaban was started 12-24 h after wound closure and enoxaparin 12 h before surgery; both drugs were continued for 10-14 days, when bilateral ascending venography was scheduled. Primary outcome was the composite of asymptomatic and symptomatic deep vein thrombosis, non-fatal pulmonary embolism, and all-cause death during treatment. The statistical plan required non-inferiority of apixaban before testing for superiority; analysis was by intention to treat for non-inferiority testing. The study is registered at ClinicalTrials.gov, number NCT00452530. FINDINGS: 1973 of 3057 patients allocated to treatment (1528 apixaban, 1529 enoxaparin) were eligible for primary efficacy analysis. The primary outcome was reported in 147 (15%) of 976 apixaban patients and 243 (24%) of 997 enoxaparin patients (relative risk 0.62 [95% CI 0.51-0.74]; p<0.0001; absolute risk reduction 9.3% [5.8-12.7]). Major or clinically relevant non-major bleeding occurred in 53 (4%) of 1501 patients receiving apixaban and 72 (5%) of 1508 treated with enoxaparin (p=0.09). INTERPRETATION: Apixaban 2.5 mg twice daily, starting on the morning after total knee replacement, offers a convenient and more effective orally administered alternative to 40 mg per day enoxaparin, without increased bleeding. FUNDING: Bristol-Myers Squibb; Pfizer.

PMID: 20206776 [PubMed - in process]

Governments should reduce prices before rationing care.

Lancet. 2010 Mar 6;375(9717):806

Authors: Ford N, Berman D

PMID: 20206775 [PubMed - in process]

The post-Darwinist concept of species: a place for Lamarck?

Lancet. 2010 Mar 6;375(9717):806

Authors: Landires I

PMID: 20206774 [PubMed - in process]

Bacterial septic arthritis in adults.

Lancet. 2010 Mar 6;375(9717):846-55

Authors: Mathews CJ, Weston VC, Jones A, Field M, Coakley G

Symptoms and signs of septic arthritis are an important medical emergency, with high morbidity and mortality. We review the changing epidemiology of septic arthritis of native joints in adults, encompassing the increasing frequency of the disorder and its evolving antibiotic resistance. We discuss various risk factors for development of septic arthritis and examine host factors (tumour necrosis factor alpha, interleukins 1 and 10) and bacterial proteins, toxins, and enzymes reported to be important determinants of pathogenesis in mouse models. Diagnosis of disease is largely clinical, guided by investigations and the opinion of skilled clinicians. We emphasise the need for timely medical and surgical intervention-most importantly, through diagnostic aspiration of relevant joints, choice of suitable antibiotic, and appropriate supportive measures. Management is growing in complexity with the advent of novel and antibiotic-resistant causative microorganisms and within the current climate of increased immunosuppression. Findings from animal models and patients are shedding light on disease pathogenesis and the possibility of novel adjunctive treatments, including systemic corticosteroids, cytokines and anticytokines, and bisphosphonates.

PMID: 20206778 [PubMed - in process]

Vaginal brachytherapy versus pelvic external beam radiotherapy for patients with endometrial cancer of high-intermediate risk (PORTEC-2): an open-label, non-inferiority, randomised trial.

Lancet. 2010 Mar 6;375(9717):816-23

Authors: Nout RA, Smit VT, Putter H, Jürgenliemk-Schulz IM, Jobsen JJ, Lutgens LC, van der Steen-Banasik EM, Mens JW, Slot A, Kroese MC, van Bunningen BN, Ansink AC, van Putten WL, Creutzberg CL,

BACKGROUND: After surgery for intermediate-risk endometrial carcinoma, the vagina is the most frequent site of recurrence. This study established whether vaginal brachytherapy (VBT) is as effective as pelvic external beam radiotherapy (EBRT) in prevention of vaginal recurrence, with fewer adverse effects and improved quality of life. METHODS: In this open-label, non-inferiority, randomised trial undertaken in 19 Dutch radiation oncology centres, 427 patients with stage I or IIA endometrial carcinoma with features of high-intermediate risk were randomly assigned by a computer-generated, biased coin minimisation procedure to pelvic EBRT (46 Gy in 23 fractions; n=214) or VBT (21 Gy high-dose rate in three fractions, or 30 Gy low-dose rate; n=213). All investigators were masked to the assignment of treatment group. The primary endpoint was vaginal recurrence. The predefined non-inferiority margin was an absolute difference of 6% in vaginal recurrence. Analysis was by intention to treat, with competing risk methods. The study is registered, number ISRCTN16228756. FINDINGS: At median follow-up of 45 months (range 18-78), three vaginal recurrences had been diagnosed after VBT and four after EBRT. Estimated 5-year rates of vaginal recurrence were 1.8% (95% CI 0.6-5.9) for VBT and 1.6% (0.5-4.9) for EBRT (hazard ratio [HR] 0.78, 95% CI 0.17-3.49; p=0.74). 5-year rates of locoregional relapse (vaginal or pelvic recurrence, or both) were 5.1% (2.8-9.6) for VBT and 2.1% (0.8-5.8) for EBRT (HR 2.08, 0.71-6.09; p=0.17). 1.5% (0.5-4.5) versus 0.5% (0.1-3.4) of patients presented with isolated pelvic recurrence (HR 3.10, 0.32-29.9; p=0.30), and rates of distant metastases were similar (8.3% [5.1-13.4] vs 5.7% [3.3-9.9]; HR 1.32, 0.63-2.74; p=0.46). We recorded no differences in overall (84.8% [95% CI 79.3-90.3] vs 79.6% [71.2-88.0]; HR 1.17, 0.69-1.98; p=0.57) or disease-free survival (82.7% [76.9-88.6] vs 78.1% [69.7-86.5]; HR 1.09, 0.66-1.78; p=0.74). Rates of acute grade 1-2 gastrointestinal toxicity were significantly lower in the VBT group than in the EBRT group at completion of radiotherapy (12.6% [27/215] vs 53.8% [112/208]). INTERPRETATION: VBT is effective in ensuring vaginal control, with fewer gastrointestinal toxic effects than with EBRT. VBT should be the adjuvant treatment of choice for patients with endometrial carcinoma of high-intermediate risk. FUNDING: Dutch Cancer Society.

PMID: 20206777 [PubMed - in process]

Community-associated meticillin-resistant Staphylococcus aureus.

Lancet. 2010 Mar 4;

Authors: Deleo FR, Otto M, Kreiswirth BN, Chambers HF

Meticillin-resistant Staphylococcus aureus (MRSA) is endemic in hospitals worldwide, and causes substantial morbidity and mortality. Health-care-associated MRSA infections arise in individuals with predisposing risk factors, such as surgery or presence of an indwelling medical device. By contrast, many community-associated MRSA (CA-MRSA) infections arise in otherwise healthy individuals who do not have such risk factors. Additionally, CA-MRSA infections are epidemic in some countries. These features suggest that CA-MRSA strains are more virulent and transmissible than are traditional hospital-associated MRSA strains. The restricted treatment options for CA-MRSA infections compound the effect of enhanced virulence and transmission. Although progress has been made towards understanding emergence of CA-MRSA, virulence, and treatment of infections, our knowledge remains incomplete. Here we review the most up-to-date knowledge and provide a perspective for the future prophylaxis or new treatments for CA-MRSA infections.

PMID: 20206987 [PubMed - as supplied by publisher]

Altered pain perception in schizophrenia.

Lancet. 2010 Mar 6;375(9717):864

Authors: Murakami H, Tamasawa N, Yamashita M, Takayasu S, Nigawara T, Matsui J, Suda T

PMID: 20206779 [PubMed - in process]

Effect of scaling up women's groups on birth outcomes in three rural districts in Bangladesh: a cluster-randomised controlled trial.

Lancet. 2010 Mar 5;

Authors: Azad K, Barnett S, Banerjee B, Shaha S, Khan K, Rego AR, Barua S, Flatman D, Pagel C, Prost A, Ellis M, Costello A

BACKGROUND: Two recent trials have shown that women's groups can reduce neonatal mortality in poor communities. We assessed the effectiveness of a scaled-up development programme with women's groups to address maternal and neonatal care in three rural districts of Bangladesh. METHODS: 18 clusters (with a mean population of 27 953 [SD 5953]) in three districts were randomly assigned to either intervention or control (nine clusters each) by use of stratified randomisation. For each district, cluster names were written on pieces of paper, which were folded and placed in a bottle. The first three cluster names drawn from the bottle were allocated to the intervention group and the remaining three to control. All clusters received health services strengthening and basic training of traditional birth attendants. In intervention clusters, a facilitator convened 18 groups every month to support participatory action and learning for women, and to develop and implement strategies to address maternal and neonatal health problems. Women were eligible to participate if they were aged 15-49 years, residing in the project area, and had given birth during the study period (Feb 1, 2005, to Dec 31, 2007). Neither study investigators nor participants were masked to treatment assignment. In a population of 229 195 people (intervention clusters only), 162 women's groups provided coverage of one group per 1414 population. The primary outcome was neonatal mortality rate (NMR). Analysis was by intention to treat. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN54792066. FINDINGS: We monitored outcomes for 36 113 births (intervention clusters, n=17 514; control clusters, n=18 599) in a population of 503 163 over 3 years. From 2005 to 2007, there were 570 neonatal deaths in the intervention clusters and 656 in the control clusters. Cluster-level mean NMR (adjusted for stratification and clustering) was 33.9 deaths per 1000 livebirths in the intervention clusters compared with 36.5 per 1000 in the control clusters (risk ratio 0.93, 95% CI 0.80-1.09). INTERPRETATION: For participatory women's groups to have a significant effect on neonatal mortality in rural Bangladesh, detailed attention to programme design and contextual factors, enhanced population coverage, and increased enrolment of newly pregnant women might be needed. FUNDING: Women and Children First, the UK Big Lottery Fund, Saving Newborn Lives, and the UK Department for International Development.

PMID: 20207412 [PubMed - as supplied by publisher]

Effect of a participatory intervention with women's groups on birth outcomes and maternal depression in Jharkhand and Orissa, India: a cluster-randomised controlled trial.

Lancet. 2010 Mar 5;

Authors: Tripathy P, Nair N, Barnett S, Mahapatra R, Borghi J, Rath S, Rath S, Gope R, Mahto D, Sinha R, Lakshminarayana R, Patel V, Pagel C, Prost A, Costello A

BACKGROUND: Community mobilisation through participatory women's groups might improve birth outcomes in poor rural communities. We therefore assessed this approach in a largely tribal and rural population in three districts in eastern India. METHODS: From 36 clusters in Jharkhand and Orissa, with an estimated population of 228 186, we assigned 18 clusters to intervention or control using stratified randomisation. Women were eligible to participate if they were aged 15-49 years, residing in the project area, and had given birth during the study. In intervention clusters, a facilitator convened 13 groups every month to support participatory action and learning for women, and facilitated the development and implementation of strategies to address maternal and newborn health problems. The primary outcomes were reductions in neonatal mortality rate (NMR) and maternal depression scores. Analysis was by intention to treat. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN21817853. FINDINGS: After baseline surveillance of 4692 births, we monitored outcomes for 19 030 births during 3 years (2005-08). NMRs per 1000 were 55.6, 37.1, and 36.3 during the first, second, and third years, respectively, in intervention clusters, and 53.4, 59.6, and 64.3, respectively, in control clusters. NMR was 32% lower in intervention clusters adjusted for clustering, stratification, and baseline differences (odds ratio 0.68, 95% CI 0.59-0.78) during the 3 years, and 45% lower in years 2 and 3 (0.55, 0.46-0.66). Although we did not note a significant effect on maternal depression overall, reduction in moderate depression was 57% in year 3 (0.43, 0.23-0.80). INTERPRETATION: This intervention could be used with or as a potential alternative to health-worker-led interventions, and presents new opportunities for policy makers to improve maternal and newborn health outcomes in poor populations. FUNDING: Health Foundation, UK Department for International Development, Wellcome Trust, and the Big Lottery Fund (UK).

PMID: 20207411 [PubMed - as supplied by publisher]

Bystander CPR for paediatric out-of-hospital cardiac arrest.

Lancet. 2010 Mar 2;

Authors: López-Herce J, Alvarez AC

PMID: 20202678 [PubMed - as supplied by publisher]

Conventional and chest-compression-only cardiopulmonary resuscitation by bystanders for children who have out-of-hospital cardiac arrests: a prospective, nationwide, population-based cohort study.

Lancet. 2010 Mar 2;

Authors: Kitamura T, Iwami T, Kawamura T, Nagao K, Tanaka H, Nadkarni VM, Berg RA, Hiraide A,

BACKGROUND: The American Heart Association recommends cardiopulmonary resuscitation (CPR) by bystanders with chest compression only for adults who have cardiac arrests, but not for children. We assessed the effect of CPR (conventional with rescue breathing or chest compression only) by bystanders on outcomes after out-of-hospital cardiac arrests in children. METHODS: In a nationwide, prospective, population-based, observational study, we enrolled 5170 children aged 17 years and younger who had an out-of-hospital cardiac arrest from Jan 1, 2005, to Dec 31, 2007. Data collected included age, cause, and presence and type of CPR by bystander. The primary endpoint was favourable neurological outcome 1 month after an out-of-hospital cardiac arrest, defined as Glasgow-Pittsburgh cerebral performance category 1 or 2. FINDINGS: 3675 (71%) children had arrests of non-cardiac causes and 1495 (29%) cardiac causes. 1551 (30%) received conventional CPR and 888 (17%) compression-only CPR. Data for type of CPR by bystander were not available for 12 children. Children who were given CPR by a bystander had a significantly higher rate of favourable neurological outcome than did those not given CPR (4.5% [110/2439] vs 1.9% [53/2719]; adjusted odds ratio [OR] 2.59, 95% CI 1.81-3.71). In children aged 1-17 years who had arrests of non-cardiac causes, favourable neurological outcome was more common after bystander CPR than no CPR (5.1% [51/1004] vs 1.5% [20/1293]; OR 4.17, 2.37-7.32). However, conventional CPR produced more favourable neurological outcome than did compression-only CPR (7.2% [45/624] vs 1.6% [six of 380]; OR 5.54, 2.52-16.99). In children aged 1-17 years who had arrests of cardiac causes, favourable neurological outcome was more common after bystander CPR than no CPR (9.5% [42/440] vs 4.1% [14/339]; OR 2.21, 1.08-4.54), and did not differ between conventional and compression-only CPR (9.9% [28/282] vs 8.9% [14/158]; OR 1.20, 0.55-2.66). In infants (aged <1 year), outcomes were uniformly poor (1.7% [36/2082] with favourable neurological outcome). INTERPRETATION: For children who have out-of-hospital cardiac arrests from non-cardiac causes, conventional CPR (with rescue breathing) by bystander is the preferable approach to resuscitation. For arrests of cardiac causes, either conventional or compression-only CPR is similarly effective. FUNDING: Fire and Disaster Management Agency and the Ministry of Education, Culture, Sports, Science and Technology (Japan).

PMID: 20202679 [PubMed - as supplied by publisher]

Reforms on the horizon for Australia's health system.

Lancet. 2010 Feb 27;375(9716):712-3

Authors: McLachlan G

PMID: 20201133 [PubMed - in process]

China boosts medical research.

Lancet. 2010 Feb 27;375(9716):711

Authors: Guo L

PMID: 20201132 [PubMed - in process]

Institute to investigate cancer hotspot in Czech Republic.

Lancet. 2010 Feb 27;375(9716):714

Authors: Holt E

PMID: 20201134 [PubMed - in process]

Atherosclerosis and diet in ancient Egypt.

Lancet. 2010 Feb 27;375(9716):718-9

Authors: David AR, Kershaw A, Heagerty A

PMID: 20201135 [PubMed - in process]

Health workers detained in the Philippines.

Lancet. 2010 Feb 20;375(9715):628

Authors: Cheng MH

PMID: 20198724 [PubMed - in process]

Health experts concerned over India's asbestos industry.

Lancet. 2010 Feb 20;375(9715):626-7

Authors: Burki T

PMID: 20198723 [PubMed - in process]

US region to model health service on Iranian system.

Lancet. 2010 Feb 20;375(9715):625

Authors: Bristol N

PMID: 20198722 [PubMed - in process]

Enrolling pregnant women in biomedical research.

Lancet. 2010 Feb 20;375(9715):632-3

Authors: Macklin R

PMID: 20198725 [PubMed - in process]

How would you spend pound1 million to tackle ageing?

Lancet. 2010 Feb 27;375(9716):698

Authors: The Lancet

PMID: 20189008 [PubMed - in process]

State of the heart in the USA.

Lancet. 2010 Feb 27;375(9716):697

Authors: The Lancet

PMID: 20189007 [PubMed - in process]

Survival effect of para-aortic lymphadenectomy in endometrial cancer (SEPAL study): a retrospective cohort analysis.

Lancet. 2010 Feb 24;

Authors: Todo Y, Kato H, Kaneuchi M, Watari H, Takeda M, Sakuragi N

BACKGROUND: In response to findings that pelvic lymphadenectomy does not have any therapeutic benefit for endometrial cancer, we aimed to establish whether complete, systematic lymphadenectomy, including the para-aortic lymph nodes, should be part of surgical therapy for patients at intermediate and high risk of recurrence. METHODS: We selected 671 patients with endometrial carcinoma who had been treated with complete, systematic pelvic lymphadenectomy (n=325 patients) or combined pelvic and para-aortic lymphadenectomy (n=346) at two tertiary centres in Japan (January, 1986-June, 2004). Patients at intermediate or high risk of recurrence were offered adjuvant radiotherapy or chemotherapy. The primary outcome measure was overall survival. FINDINGS: Overall survival was significantly longer in the pelvic and para-aortic lymphadenectomy group than in the pelvic lymphadenectomy group (HR 0.53, 95% CI 0.38-0.76; p=0.0005). This association was also recorded in 407 patients at intermediate or high risk (p=0.0009), but overall survival was not related to lymphadenectomy type in low-risk patients. Multivariate analysis of prognostic factors showed that in patients with intermediate or high risk of recurrence, pelvic and para-aortic lymphadenectomy reduced the risk of death compared with pelvic lymphadenectomy (0.44, 0.30-0.64; p<0.0001). Analysis of 328 patients with intermediate or high risk who were treated with adjuvant radiotherapy or chemotherapy showed that patient survival improved with pelvic and para-aortic lymphadenectomy (0.48, 0.29-0.83; p=0.0049) and with adjuvant chemotherapy (0.59, 0.37-1.00; p=0.0465) independently of one another. INTERPRETATION: Combined pelvic and para-aortic lymphadenectomy is recommended as treatment for patients with endometrial carcinoma of intermediate or high risk of recurrence. If a prospective randomised or comparative cohort study is planned to validate the therapeutic effect of lymphadenectomy, it should include both pelvic and para-aortic lymphadenectomy in patients of intermediate or high risk of recurrence. FUNDING: Japanese Foundation for Multidisciplinary Treatment of Cancer, and the Japan Society for the Promotion of Science.

PMID: 20188410 [PubMed - as supplied by publisher]

Lymphadenectomy in endometrial cancer: when, not if.

Lancet. 2010 Feb 24;

Authors: Dowdy SC, Mariani A

PMID: 20188409 [PubMed - as supplied by publisher]

Respiratory administration of measles vaccine.

Lancet. 2010 Feb 27;375(9716):706-8

Authors: Omer SB, Hiremath GS, Halsey NA

PMID: 20189011 [PubMed - in process]

Giving the ischaemic heart a shot in the arm.

Lancet. 2010 Feb 27;375(9716):699-700

Authors: Ovize M, Bonnefoy E

PMID: 20189010 [PubMed - in process]

Moving towards a world without cluster bombs.

Lancet. 2010 Feb 27;375(9716):698

Authors: The Lancet

PMID: 20189009 [PubMed - in process]

Low-level laser therapy for neck pain.

Lancet. 2010 Feb 27;375(9716):721-2

Authors: Shiri R, Viikari-Juntura E

PMID: 20189015 [PubMed - in process]

Terje Pedersen: a pioneer trialist in preventive cardiology.

Lancet. 2010 Feb 27;375(9716):717

Authors: Morris K

PMID: 20189014 [PubMed - in process]

Offline: History lessons.

Lancet. 2010 Feb 27;375(9716):710

Authors: Horton R

PMID: 20189013 [PubMed - in process]

Rare diseases and legislation in China.

Lancet. 2010 Feb 27;375(9716):708-9

Authors: Wang JB, Guo JJ, Yang L, Zhang YD, Sun ZQ, Zhang YJ

PMID: 20189012 [PubMed - in process]

Effectiveness of intensive autism programmes.

Lancet. 2010 Feb 27;375(9716):722-3

Authors: Dawson M, Gernsbacher MA

PMID: 20189018 [PubMed - in process]

Low-level laser therapy for neck pain - Authors' reply.

Lancet. 2010 Feb 27;375(9716):722

Authors: Chow R, Johnson M, Bjordal J, Lopes-Martins R

PMID: 20189017 [PubMed - in process]

Low-level laser therapy for neck pain.

Lancet. 2010 Feb 27;375(9716):721

Authors: Verhagen AP, Schellingerhout JM

PMID: 20189016 [PubMed - in process]

ADRB2 Arg16Gly polymorphism in the LARGE trial.

Lancet. 2010 Feb 27;375(9716):724-5

Authors: Manolopoulos KN, Karpe F

PMID: 20189021 [PubMed - in process]

Effectiveness of intensive autism programmes - Authors' reply.

Lancet. 2010 Feb 27;375(9716):723

Authors: Mandell DS, Levy SE, Schultz RT

PMID: 20189020 [PubMed - in process]

Nutt damage.

Lancet. 2010 Feb 27;375(9716):723-4

Authors: Bown WC

PMID: 20189019 [PubMed - in process]

ADRB2 Arg16Gly polymorphism in the LARGE trial - Authors' reply.

Lancet. 2010 Feb 27;375(9716):725

Authors: Wechsler ME, Israel E,

PMID: 20189024 [PubMed - as supplied by publisher]

Drug development for neglected diseases.

Lancet. 2010 Feb 27;375(9716):725-6

Authors: Alleyne G

PMID: 20189023 [PubMed - in process]

Nutt damage - Author's reply.

Lancet. 2010 Feb 27;375(9716):724

Authors: Nutt D

PMID: 20189022 [PubMed - in process]

Remote ischaemic conditioning before hospital admission, as a complement to angioplasty, and effect on myocardial salvage in patients with acute myocardial infarction: a randomised trial.

Lancet. 2010 Feb 27;375(9716):727-734

Authors: Bøtker HE, Kharbanda R, Schmidt MR, Bøttcher M, Kaltoft AK, Terkelsen CJ, Munk K, Andersen NH, Hansen TM, Trautner S, Lassen JF, Christiansen EH, Krusell LR, Kristensen SD, Thuesen L, Nielsen SS, Rehling M, Sørensen HT, Redington AN, Nielsen TT

BACKGROUND: Remote ischaemic preconditioning attenuates cardiac injury at elective surgery and angioplasty. We tested the hypothesis that remote ischaemic conditioning during evolving ST-elevation myocardial infarction, and done before primary percutaneous coronary intervention, increases myocardial salvage. METHODS: 333 consecutive adult patients with a suspected first acute myocardial infarction were randomly assigned in a 1:1 ratio by computerised block randomisation to receive primary percutaneous coronary intervention with (n=166 patients) versus without (n=167) remote conditioning (intermittent arm ischaemia through four cycles of 5-min inflation and 5-min deflation of a blood-pressure cuff). Allocation was concealed with opaque sealed envelopes. Patients received remote conditioning during transport to hospital, and primary percutaneous coronary intervention in hospital. The primary endpoint was myocardial salvage index at 30 days after primary percutaneous coronary intervention, measured by myocardial perfusion imaging as the proportion of the area at risk salvaged by treatment; analysis was per protocol. This study is registered with ClinicalTrials.gov, number NCT00435266. FINDINGS: 82 patients were excluded on arrival at hospital because they did not meet inclusion criteria, 32 were lost to follow-up, and 77 did not complete the follow-up with data for salvage index. Median salvage index was 0.75 (IQR 0.50-0.93, n=73) in the remote conditioning group versus 0.55 (0.35-0.88, n=69) in the control group, with median difference of 0.10 (95% CI 0.01-0.22; p=0.0333); mean salvage index was 0.69 (SD 0.27) versus 0.57 (0.26), with mean difference of 0.12 (95% CI 0.01-0.21; p=0.0333). Major adverse coronary events were death (n=3 per group), reinfarction (n=1 per group), and heart failure (n=3 per group). INTERPRETATION: Remote ischaemic conditioning before hospital admission increases myocardial salvage, and has a favourable safety profile. Our findings merit a larger trial to establish the effect of remote conditioning on clinical outcomes. FUNDING: Fondation Leducq.

PMID: 20189026 [PubMed - as supplied by publisher]

China's irrational medical pricing scheme.

Lancet. 2010 Feb 27;375(9716):726

Authors: Zhang H

PMID: 20189025 [PubMed - in process]

Systemic infection and delirium: when cytokines and acetylcholine collide.

Lancet. 2010 Feb 27;375(9716):773-775

Authors: van Gool WA, van de Beek D, Eikelenboom P

Systemic infection and drugs with anticholinergic effects are well-recognised and prevalent risk factors for delirium in elderly people. Experimental findings and neuropathological observations suggest that activation of microglia is pivotal for mediation of the behavioural effects of systemic infections. The microglial response is usually regulated tightly, but defensive features could turn neurotoxic once microglial cells escape from cholinergic inhibition. A self-propelling neuroinflammatory reaction might follow, and this cascade could account for the strong association between delirium and long-term cognitive impairment and even dementia. Here, we propose a hypothetical model, suggesting that poor outcome after delirium can be averted in vulnerable elderly people by use of readily available drugs. Agents that either restore cholinergic control of microglia or directly inhibit neuroinflammation warrant testing in clinical trials.

PMID: 20189029 [PubMed - as supplied by publisher]

Management of stable coronary artery disease.

Lancet. 2010 Feb 27;375(9716):763-772

Authors: Pfisterer ME, Zellweger MJ, Gersh BJ

Results of two randomised controlled trials for the management of mild-to-moderate chronic stable coronary artery disease (Clinical Outcomes Utilizing Revascularization and Aggressive drug Evaluation [COURAGE] and Bypass Angioplasty Revascularization Investigation type-2 Diabetes [BARI-2D]) have stimulated a vigorous debate about whether an initial strategy of revascularisation or a conservative approach with drugs is most effective. The conclusions of these two trials were clear: for some patients randomly assigned after angiography to revascularisation or pharmacological therapy, rates of death and myocardial infarction did not differ between the two strategies. What remains unresolved is how to generalise these data to patients without angiography, the role of stress testing, and the preferred approach to patients with relevant ischaemia on stress testing. This Review draws attention to the controversial issues in both management approaches, analyses the strengths and limitations of recent trials, and proposes a treatment algorithm that is applicable to daily clinical practice. Findings suggest that the severity of anginal symptoms and the extent of ischaemia in stress testing could help to identify patients who are at increased risk and who might benefit from an early invasive strategy. On the basis of the data and considerations presented, a strategy of initial optimum pharmacological therapy or direct invasive management can be tailored to an individual's circumstances and preferences.

PMID: 20189028 [PubMed - as supplied by publisher]

Dilated cardiomyopathy.

Lancet. 2010 Feb 27;375(9716):752-762

Authors: Jefferies JL, Towbin JA

Dilated cardiomyopathy is characterised by left ventricular dilation that is associated with systolic dysfunction. Diastolic dysfunction and impaired right ventricular function can develop. Affected individuals are at risk of left or right ventricular failure, or both. Heart failure symptoms can be exercise-induced or persistent at rest. Many patients are asymptomatic. Chronically treated patients sometimes present acutely with decompensated heart failure. Other life-threatening risks are ventricular arrhythmias and atrioventricular block, syncope, and sudden death. Genetic inheritance arises in 30-48% of patients, and inflammatory disorders such as myocarditis or toxic effects from medications, alcohol, or illicit drugs also result in dilated cardiomyopathy. Genes that cause dilated cardiomyopathy generally encode cytoskeletal and sarcomeric (contractile apparatus) proteins, although disturbance of calcium homeostasis also seems to be important. In children, disrupted mitochondrial function and metabolic abnormalities have a causal role. Treatments focus on improvement of cardiac efficiency and reduction of mechanical stress. Arrhythmia therapy and prevention of sudden death continue to be mainstays of treatment. Despite progress over the past 10 years, outcomes need to be improved.

PMID: 20189027 [PubMed - as supplied by publisher]

Group cognitive behavioural treatment for low-back pain in primary care: a randomised controlled trial and cost-effectiveness analysis.

Lancet. 2010 Feb 25;

Authors: Lamb SE, Hansen Z, Lall R, Castelnuovo E, Withers EJ, Nichols V, Potter R, Underwood MR,

BACKGROUND: Low-back pain is a common and costly problem. We estimated the effectiveness of a group cognitive behavioural intervention in addition to best practice advice in people with low-back pain in primary care. METHODS: In this pragmatic, multicentre, randomised controlled trial with parallel cost-effectiveness analysis undertaken in England, 701 adults with troublesome subacute or chronic low-back pain were recruited from 56 general practices and received an active management advisory consultation. Participants were randomly assigned by computer-generated block randomisation to receive an additional assessment and up to six sessions of a group cognitive behavioural intervention (n=468) or no further intervention (control; n=233). Primary outcomes were the change from baseline in Roland Morris disability questionnaire and modified Von Korff scores at 12 months. Assessment of outcomes was blinded and followed the intention-to-treat principle, including all randomised participants who provided follow-up data. This study is registered, number ISRCTN54717854. FINDINGS: 399 (85%) participants in the cognitive behavioural intervention group and 199 (85%) participants in the control group were included in the primary analysis at 12 months. The most frequent reason for participant withdrawal was unwillingness to complete questionnaires. At 12 months, mean change from baseline in the Roland Morris questionnaire score was 1.1 points (95% CI 0.39-1.72) in the control group and 2.4 points (1.89-2.84) in the cognitive behavioural intervention group (difference between groups 1.3 points, 0.56-2.06; p=0.0008). The modified Von Korff disability score changed by 5.4% (1.99-8.90) and 13.8% (11.39-16.28), respectively (difference between groups 8.4%, 4.47-12.32; p<0.0001). The modified Von Korff pain score changed by 6.4% (3.14-9.66) and 13.4% (10.77-15.96), respectively (difference between groups 7.0%, 3.12-10.81; p<0.0001). The additional quality-adjusted life-year (QALY) gained from cognitive behavioural intervention was 0.099; the incremental cost per QALY was pound1786, and the probability of cost-effectiveness was greater than 90% at a threshold of pound3000 per QALY. There were no serious adverse events attributable to either treatment. INTERPRETATION: Over 1 year, the cognitive behavioural intervention had a sustained effect on troublesome subacute and chronic low-back pain at a low cost to the health-care provider. FUNDING: National Institute for Health Research Health Technology Assessment Programme.

PMID: 20189241 [PubMed - as supplied by publisher]

CBT for low-back pain in primary care.

Lancet. 2010 Feb 25;

Authors: Manchikanti L

PMID: 20189240 [PubMed - as supplied by publisher]

Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomised controlled trial.

Lancet. 2010 Feb 25;

Authors:

BACKGROUND: Stents are an alternative treatment to carotid endarterectomy for symptomatic carotid stenosis, but previous trials have not established equivalent safety and efficacy. We compared the safety of carotid artery stenting with that of carotid endarterectomy. METHODS: The International Carotid Stenting Study (ICSS) is a multicentre, international, randomised controlled trial with blinded adjudication of outcomes. Patients with recently symptomatic carotid artery stenosis were randomly assigned in a 1:1 ratio to receive carotid artery stenting or carotid endarterectomy. Randomisation was by telephone call or fax to a central computerised service and was stratified by centre with minimisation for sex, age, contralateral occlusion, and side of the randomised artery. Patients and investigators were not masked to treatment assignment. Patients were followed up by independent clinicians not directly involved in delivering the randomised treatment. The primary outcome measure of the trial is the 3-year rate of fatal or disabling stroke in any territory, which has not been analysed yet. The main outcome measure for the interim safety analysis was the 120-day rate of stroke, death, or procedural myocardial infarction. Analysis was by intention to treat (ITT). This study is registered, number ISRCTN25337470. FINDINGS: The trial enrolled 1713 patients (stenting group, n=855; endarterectomy group, n=858). Two patients in the stenting group and one in the endarterectomy group withdrew immediately after randomisation, and were not included in the ITT analysis. Between randomisation and 120 days, there were 34 (Kaplan-Meier estimate 4.0%) events of disabling stroke or death in the stenting group compared with 27 (3.2%) events in the endarterectomy group (hazard ratio [HR] 1.28, 95% CI 0.77-2.11). The incidence of stroke, death, or procedural myocardial infarction was 8.5% in the stenting group compared with 5.2% in the endarterectomy group (72 vs 44 events; HR 1.69, 1.16-2.45, p=0.006). Risks of any stroke (65 vs 35 events; HR 1.92, 1.27-2.89) and all-cause death (19 vs seven events; HR 2.76, 1.16-6.56) were higher in the stenting group than in the endarterectomy group. Three procedural myocardial infarctions were recorded in the stenting group, all of which were fatal, compared with four, all non-fatal, in the endarterectomy group. There was one event of cranial nerve palsy in the stenting group compared with 45 in the endarterectomy group. There were also fewer haematomas of any severity in the stenting group than in the endarterectomy group (31 vs 50 events; p=0.0197). INTERPRETATION: Completion of long-term follow-up is needed to establish the efficacy of carotid artery stenting compared with endarterectomy. In the meantime, carotid endarterectomy should remain the treatment of choice for patients suitable for surgery. FUNDING: Medical Research Council, the Stroke Association, Sanofi-Synthélabo, European Union.

PMID: 20189239 [PubMed - as supplied by publisher]