Latest Articles Include:
- Strengthening research capacity in Africa
- Lancet 374(9683):1 (2009)
- UK falling behind on cancer care
- Lancet 374(9683):2 (2009)
- Where are we now with Indigenous health?
- Lancet 374(9683):2 (2009)
- Rivaroxaban in acute coronary syndromes: too soon to know?
Gurm HS Eagle K - Lancet 374(9683):3-4 (2009)
- GLP-1 receptor agonists for type 2 diabetes
De Block CE Van Gaal LF - Lancet 374(9683):4-6 (2009)
- Long-term outcome of placental-site trophoblastic tumours
Kohorn EI - Lancet 374(9683):6-7 (2009)
- NECT trial: more than a small victory over sleeping sickness
Opigo J Woodrow C - Lancet 374(9683):7-9 (2009)
- G8 Summit 2009: what approach will Italy take to health?
Missoni E Tediosi F Pacileo G Borgonovi E - Lancet 374(9683):9-10 (2009)
- Venice statement: global health initiatives and health systems
- Lancet 374(9683):10-12 (2009)
- End to whaling ban?
Maumi G - Lancet 374(9683):12 (2009)
- Pakistan's refugees face uncertain future
- Lancet 374(9683):13-14 (2009)
- Loss of land could threaten health of Sámi people
- Lancet 374(9683):15-16 (2009)
- Jails, justice, and public health
- Lancet 374(9683):17-18 (2009)
- Healthy spaces
- Lancet 374(9683):18 (2009)
- Marlene Kong: one of Australia's few Indigenous doctors
Shetty P - Lancet 374(9683):19 (2009)
- Writing values
- Lancet 374(9683):20-21 (2009)
- Turkan Saylan
- Lancet 374(9683):22 (2009)
- Crisis in the Swat Valley of Pakistan: need for international action
Bile KM Hafeez A - Lancet 374(9683):23 (2009)
- Crisis in the Swat Valley of Pakistan: need for international action
Chotani RA - Lancet 374(9683):23-24 (2009)
- Rosuvastatin, C-reactive protein, LDL cholesterol, and the JUPITER trial
de Tena JG - Lancet 374(9683):24 (2009)
- Rosuvastatin, C-reactive protein, LDL cholesterol, and the JUPITER trial
Feeman WE - Lancet 374(9683):24 (2009)
- Rosuvastatin, C-reactive protein, LDL cholesterol, and the JUPITER trial
Danchin N - Lancet 374(9683):24-25 (2009)
- Rosuvastatin, C-reactive protein, LDL cholesterol, and the JUPITER trial
Rosenstein R Parra D - Lancet 374(9683):25 (2009)
- Rosuvastatin, C-reactive protein, LDL cholesterol, and the JUPITER trial
Sniderman AD - Lancet 374(9683):25 (2009)
- Rosuvastatin, C-reactive protein, LDL cholesterol, and the JUPITER trial
Bloom JM - Lancet 374(9683):25-26 (2009)
- Rosuvastatin, C-reactive protein, LDL cholesterol, and the JUPITER trial
Segura J Ruilope LM - Lancet 374(9683):26 (2009)
- Rosuvastatin, C-reactive protein, LDL cholesterol, and the JUPITER trial – Authors' reply
- Lancet 374(9683):26-27 (2009)
- Buried data and the UK Healthcare Commission's legacy
Sherlaw-Johnson C - Lancet 374(9683):27 (2009)
- Prepared for a 'flu pandemic? I don't think so…
Baker S - Lancet 374(9683):27-28 (2009)
- Dietary fibre: refining a definition
Harris SS Pijls L - Lancet 374(9683):28 (2009)
- Department of Error
- Lancet 374(9683):28 (2009)
- Department of Error
- Lancet 374(9683):28 (2009)
- Rivaroxaban versus placebo in patients with acute coronary syndromes (ATLAS ACS-TIMI 46): a randomised, double-blind, phase II trial
Mega JL Braunwald E Mohanavelu S Burton P Poulter R Misselwitz F Hricak V Barnathan ES Bordes P Witkowski A Markov V Oppenheimer L Gibson CM ATLAS ACS-TIMI 46 study group - Lancet 374(9683):29-38 (2009)
Background Rivaroxaban is an oral direct factor Xa inhibitor that has been effective in prevention of venous thromboembolism in patients undergoing elective orthopaedic surgery. However, its use after acute coronary syndromes has not been investigated. In this setting, we assessed the safety and efficacy of rivaroxaban and aimed to select the most favourable dose and dosing regimen. Methods In this double-blind, dose-escalation, phase II study, undertaken at 297 sites in 27 countries, 3491 patients stabilised after an acute coronary syndrome were stratified on the basis of investigator decision to use aspirin only (stratum 1, n=761) or aspirin plus a thienopyridine (stratum 2, n=2730). Participants were randomised within each strata and dose tier with a block randomisation method at 1:1:1 to receive either placebo or rivaroxaban (at doses 5–20 mg) given once daily or the same total daily dose given twice daily. The primary safety endpoint was clinically significant bleeding (TIMI major, TIMI minor, or requiring medical attention); the primary efficacy endpoint was death, myocardial infarction, stroke, or severe recurrent ischaemia requiring revascularisation during 6 months. Safety analyses included all participants who received at least one dose of study drug; efficacy analyses were by intention to treat. This study is registered with ClinicalTrials.gov, num! ber NCT00402597. Findings Three patients in stratum 1 and 26 in stratum 2 never received the study drug. The risk of clinically significant bleeding with rivaroxaban versus placebo increased in a dose-dependent manner (hazard ratios [HRs] 2·21 [95% CI 1·25–3·91] for 5 mg, 3·35 [2·31–4·87] for 10 mg, 3·60 [2·32–5·58] for 15 mg, and 5·06 [3·45–7·42] for 20 mg doses; p<0·0001). Rates of the primary efficacy endpoint were 5·6% (126/2331) for rivaroxaban versus 7·0% (79/1160) for placebo (HR 0·79 [0·60–1·05], p=0·10). Rivaroxaban reduced the main secondary efficacy endpoint of death, myocardial infarction, or stroke compared with placebo (87/2331 [3·9%] vs 62/1160 [5·5%]; HR 0·69, [95% CI 0·50–0·96], p=0·0270). The most common adverse event in both groups was chest pain (248/2309 [10·7%] vs 118/1153 [10·2%]). Interpretation The use of an oral factor Xa inhibitor in patients stabilised after an acute coronary syndrome increases bleeding in a dose-dependent manner and might reduce major ischaemic outcomes. On the basis of these observations, a phase III study of low-dose rivaroxaban as adjunctive therapy in these patients is underway. Funding Johnson & Johnson Pharmaceutical Research & Development and Bayer Healthcare AG. - Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week randomised, parallel-group, multinational, open-label trial (LEAD-6)
Buse JB Rosenstock J Sesti G Schmidt WE Montanya E Brett JH Zychma M Blonde L LEAD-6 Study Group - Lancet 374(9683):39-47 (2009)
Background Unlike most antihyperglycaemic drugs, glucagon-like peptide-1 (GLP-1) receptor agonists have a glucose-dependent action and promote weight loss. We compared the efficacy and safety of liraglutide, a human GLP-1 analogue, with exenatide, an exendin-based GLP-1 receptor agonist. Methods Adults with inadequately controlled type 2 diabetes on maximally tolerated doses of metformin, sulphonylurea, or both, were stratified by previous oral antidiabetic therapy and randomly assigned to receive additional liraglutide 1·8 mg once a day (n=233) or exenatide 10 μg twice a day (n=231) in a 26-week open-label, parallel-group, multinational (15 countries) study. The primary outcome was change in glycosylated haemoglobin (HbA1c). Efficacy analyses were by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00518882. Findings Mean baseline HbA1c for the study population was 8·2%. Liraglutide reduced mean HbA1c significantly more than did exenatide (−1·12% [SE 0·08] vs −0·79% [0·08]; estimated treatment difference −0·33; 95% CI −0·47 to −0·18; p<0·0001) and more patients achieved a HbA1c value of less than 7% (54% vs 43%, respectively; odds ratio 2·02; 95% CI 1·31 to 3·11; p=0·0015). Liraglutide reduced mean fasting plasma glucose more than did exenatide (−1·61 mmol/L [SE 0·20] vs −0·60 mmol/L [0·20]; estimated treatment difference −1·01 mmol/L; 95% CI −1·37 to −0·65; p<0·0001) but postprandial glucose control was less effective after breakfast and dinner. Both drugs promoted similar weight losses (liraglutide −3·24 kg vs exenatide −2·87 kg). Both drugs were well tolerated, but nausea was less persistent (estimated treatment rate ratio 0·448, p<0·0001) and minor hypoglycaemia less frequent with liraglutide than with exenatide (1·93 vs 2·60 events ! per patient per year; rate ratio 0·55; 95% CI 0·34 to 0·88; p=0·0131; 25·5% vs 33·6% had minor hypoglycaemia). Two patients taking both exenatide and a sulphonylurea had a major hypoglycaemic episode. Interpretation Liraglutide once a day provided significantly greater improvements in glycaemic control than did exenatide twice a day, and was generally better tolerated. The results suggest that liraglutide might be a treatment option for type 2 diabetes, especially when weight loss and risk of hypoglycaemia are major considerations. Funding Novo Nordisk A/S. - Prognostic markers and long-term outcome of placental-site trophoblastic tumours: a retrospective observational study
Schmid P Nagai Y Agarwal R Hancock B Savage PM Sebire NJ Lindsay I Wells M Fisher RA Short D Newlands ES Wischnewsky MB Seckl MJ - Lancet 374(9683):48-55 (2009)
Background Placental-site trophoblastic tumours are a rare form of gestational trophoblastic disease and consequently information about optimum management or prognostic factors is restricted. We aimed to assess the long-term outcome of stage-adapted management by surgery, chemotherapy, or both for patients with the disorder. Methods 35 550 women were registered with gestational trophoblastic disease in the UK (1976–2006), of whom 62 were diagnosed with placental-site trophoblastic tumours and included, retrospectively, in the study. Patients were treated by surgery, chemotherapy, or both. We estimated the probabilities of overall survival and survival without recurrence of disease 5 and 10 years after the date of first treatment, and calculated the association of these endpoints with prognostic factors, including time since antecedent pregnancy, serum concentration of β-human chorionic gonadotropin, and stage of disease, with both univariate and multivariate analyses. Findings Probabilities of overall and recurrence-free survival 10 years after first treatment were 70% (95% CI 54–82) and 73% (54–85), respectively. Patients with stage I disease had a 10-year probability of overall survival of 90% (77–100) and did not benefit from postoperative chemotherapy. By contrast, patients with stage II, III, and IV disease required combined treatment with surgery and chemotherapy; probability of overall survival at 10 years was 52% (3–100) for patients with stage II disease and 49% (26–72) for stage III or IV disease. Outcome for patients who had recurrent or refractory disease was poor: only four (22%) patients achieved long-term survival beyond 60 months. Multivariate analysis showed that the only significant independent predictor of overall and recurrence-free survival was time since antecedent pregnancy. A cutoff point of 48 months since antecedent pregnancy could differentiate between patients' probability of survival (<48 months) or death (�! �48 months) with 93% specificity and 100% sensitivity, and with a positive predictive value of 100% and a negative predictive value of 98%. Interpretation Stage-adapted management with surgery for stage I disease, and combined surgery and chemotherapy for stage II, III, and IV disease could improve the effectiveness of treatment for placental-site trophoblastic tumours. Use of 48 months since antecedent pregnancy as a prognostic indicator of survival could help select patients for risk-adapted treatment. Funding National Commissioning Group. - Nifurtimox-eflornithine combination therapy for second-stage African Trypanosoma brucei gambiense trypanosomiasis: a multicentre, randomised, phase III, non-inferiority trial
Priotto G Kasparian S Mutombo W Ngouama D Ghorashian S Arnold U Ghabri S Baudin E Buard V Kazadi-Kyanza S Ilunga M Mutangala W Pohlig G Schmid C Karunakara U Torreele E Kande V - Lancet 374(9683):56-64 (2009)
Background Human African trypanosomiasis (HAT; sleeping sickness) caused by Trypanosoma brucei gambiense is a fatal disease. Current treatment options for patients with second-stage disease are toxic, ineffective, or impractical. We assessed the efficacy and safety of nifurtimox-eflornithine combination therapy (NECT) for second-stage disease compared with the standard eflornithine regimen. Methods A multicentre, randomised, open-label, active control, phase III, non-inferiority trial was done at four HAT treatment centres in the Republic of the Congo and the Democratic Republic of the Congo. Patients aged 15 years or older with confirmed second-stage T b gambiense infection were randomly assigned by computer-generated randomisation sequence to receive intravenous eflornithine (400 mg/kg per day, every 6 h; n=144) for 14 days or intravenous eflornithine (400 mg/kg per day, every 12 h) for 7 days with oral nifurtimox (15 mg/kg per day, every 8 h) for 10 days (NECT; n=143). The primary endpoint was cure (defined as absence of trypanosomes in body fluids and a leucocyte count ≤20 cells per μL) 18 months after treatment. Efficacy analyses were done in the intention-to-treat (ITT), modified ITT, and per-protocol (PP) populations. The non-inferiority margin for the difference in cure rates was defined as 10%. This study is registered with ClinicalTrials.gov, number NCT001! 46627. Findings One patient from the eflornithine group absconded after receiving the first dose, without any type of assessment done, and was excluded from all analyses. In the ITT population, 131 (91·6%) of 143 patients assigned to eflornithine and 138 (96·5%) of 143 patients assigned to NECT were cured at 18 months (difference −4·9%, one-sided 95% CI −0·3; p<0·0001). In the PP population, 122 (91·7%) of 133 patients in the eflornithine group and 129 (97·7%) of 132 in the NECT group were cured at 18 months (difference −6·0%, one-sided 95% CI −1·5; p<0·0001). Drug-related adverse events were frequent in both groups; 41 (28·7%) patients in the eflornithine group and 20 (14·0%) in the NECT group had major (grade 3 or 4) reactions, which resulted in temporary treatment interruption in nine and one patients, respectively. The most common major adverse events were fever (n=18), seizures (n=6), and infections (n=5) in the eflornithine group, and fever (n=7), seizures (n=6), a! nd confusion (n=2) in the NECT group. There were four deaths, which were regarded as related to study drug (eflornithine, n=3; NECT, n=1). Interpretation The efficacy of NECT is non-inferior to that of eflornithine monotherapy. Since this combination treatment also presents safety advantages, is easier to administer (ie, infusion every 12 h for 7 days vs every 6 h for 14 days), and potentially protective against the emergence of resistant parasites, it is suitable for first-line use in HAT control programmes. Funding Médecins Sans Frontières (Dutch section), Médecins Sans Frontières International, and the Drugs for Neglected Diseases Initiative. - Indigenous health part 1: determinants and disease patterns
Gracey M King M - Lancet 374(9683):65-75 (2009)
The world's almost 400 million Indigenous people have low standards of health. This poor health is associated with poverty, malnutrition, overcrowding, poor hygiene, environmental contamination, and prevalent infections. Inadequate clinical care and health promotion, and poor disease prevention services aggravate this situation. Some Indigenous groups, as they move from traditional to transitional and modern lifestyles, are rapidly acquiring lifestyle diseases, such as obesity, cardiovascular disease, and type 2 diabetes, and physical, social, and mental disorders linked to misuse of alcohol and of other drugs. Correction of these inequities needs increased awareness, political commitment, and recognition rather than governmental denial and neglect of these serious and complex problems. Indigenous people should be encouraged, trained, and enabled to become increasingly involved in overcoming these challenges. - Indigenous health part 2: the underlying causes of the health gap
King M Smith A Gracey M - Lancet 374(9683):76-85 (2009)
In this Review we delve into the underlying causes of health disparities between Indigenous and non-Indigenous people and provide an Indigenous perspective to understanding these inequalities. We are able to present only a snapshot of the many research publications about Indigenous health. Our aim is to provide clinicians with a framework to better understand such matters. Applying this lens, placed in context for each patient, will promote more culturally appropriate ways to interact with, to assess, and to treat Indigenous peoples. The topics covered include Indigenous notions of health and identity; mental health and addictions; urbanisation and environmental stresses; whole health and healing; and reconciliation. - Avoidable waste in the production and reporting of research evidence
Chalmers I Glasziou P - Lancet 374(9683):86-89 (2009)
- Neuroleptic malignant syndrome versus malignant disease: idiosyncratic or synchronous?
Shintani F Izumi M Fujimura N - Lancet 374(9683):90 (2009)
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