How the Health and Social Care Bill 2011 would end entitlement to comprehensive health care in England.

Lancet. 2012 Jan 25;

Authors: Pollock AM, Price D, Roderick P, Treuherz T, McCoy D, McKee M, Reynolds L

PMID: 22284434 [PubMed - as supplied by publisher]

The Research Works Act: a damaging threat to science.

Lancet. 2012 Jan 28;379(9813):288

Authors:

PMID: 22284642 [PubMed - in process]

Neurological diseases remain neglected and ignored.

Lancet. 2012 Jan 28;379(9813):287

Authors:

PMID: 22284641 [PubMed - in process]

Tobacco in the USA: smoke and mirrors.

Lancet. 2012 Jan 28;379(9813):288

Authors:

PMID: 22284643 [PubMed - in process]

Optimisation of mass chemotherapy to control soil-transmitted helminth infection.

Lancet. 2012 Jan 28;379(9813):289-90

Authors: Anderson R, Hollingsworth TD, Truscott J, Brooker S

PMID: 22284644 [PubMed - in process]

Ndola Prata: fighting for women’s reproductive health.

Lancet. 2012 Jan 28;379(9813):305

Authors: Shetty P

PMID: 22284647 [PubMed - in process]

Screening for congenital heart disease with newborn pulse oximetry.

Lancet. 2012 Jan 28;379(9813):309-10; author reply 311

Authors: Ostman-Smith I, Granelli AW

PMID: 22284648 [PubMed - in process]

Screening for congenital heart disease with newborn pulse oximetry.

Lancet. 2012 Jan 28;379(9813):310-1; author reply 311

Authors: Nirantharakumar K

PMID: 22284649 [PubMed - in process]

Screening for congenital heart disease with newborn pulse oximetry.

Lancet. 2012 Jan 28;379(9813):310; author reply 311

Authors: Macfarlane P, Talekar R

PMID: 22284650 [PubMed - in process]

Coronary artery calcium for guiding statin treatment.

Lancet. 2012 Jan 28;379(9813):311-2; author reply 312-3

Authors: Ridker PM

PMID: 22284651 [PubMed - in process]

Coronary artery calcium for guiding statin treatment.

Lancet. 2012 Jan 28;379(9813):312; author reply 312-3

Authors: Kengne AP, Echouffo-Tcheugui JB, Sobngwi E

PMID: 22284653 [PubMed - in process]

ADDITION-Europe and the case for diabetes screening.

Lancet. 2012 Jan 28;379(9813):313; author reply 313-4

Authors: Yudkin JS, Montori VM, Lipska KJ, Gale EA

PMID: 22284655 [PubMed - in process]

Cited or read?

Lancet. 2012 Jan 28;379(9813):314

Authors: Bellini C

PMID: 22284657 [PubMed - in process]

Acute dyspnoea–not always above the diaphragm.

Lancet. 2012 Jan 28;379(9813):384

Authors: Chalisey A, Shah S, Karim M

PMID: 22284658 [PubMed - in process]

New antithrombotic drugs for atrial fibrillation: caution is needed.

Lancet. 2012 Jan 28;379(9813):e24; author reply e24-5

Authors: Bell S, Nand J, Spriggs D

PMID: 22284660 [PubMed - in process]

IAMP tackles a void in medical education: leadership.

Lancet. 2012 Jan 28;379(9813):e25

Authors: Gee RE, Jarvinen T, Sultana TA, Destura R, Gjoneska B

PMID: 22284661 [PubMed - in process]

Community-based treatment of severe childhood pneumonia.

Lancet. 2012 Jan 26;

Authors: Black RE, El Arifeen S

PMID: 22285052 [PubMed - as supplied by publisher]

A practical molecular assay to predict survival in resected non-squamous, non-small-cell lung cancer: development and international validation studies.

Lancet. 2012 Jan 26;

Authors: Kratz JR, He J, Van Den Eeden SK, Zhu ZH, Gao W, Pham PT, Mulvihill MS, Ziaei F, Zhang H, Su B, Zhi X, Quesenberry CP, Habel LA, Deng Q, Wang Z, Zhou J, Li H, Huang MC, Yeh CC, Segal MR, Ray MR, Jones KD, Raz DJ, Xu Z, Jahan TM, Berryman D, He B, Mann MJ, Jablons DM

Abstract

BACKGROUND: The frequent recurrence of early-stage non-small-cell lung cancer (NSCLC) is generally attributable to metastatic disease undetected at complete resection. Management of such patients depends on prognostic staging to identify the individuals most likely to have occult disease. We aimed to develop and validate a practical, reliable assay that improves risk stratification compared with conventional staging. METHODS: A 14-gene expression assay that uses quantitative PCR, runs on formalin-fixed paraffin-embedded tissue samples, and differentiates patients with heterogeneous statistical prognoses was developed in a cohort of 361 patients with non-squamous NSCLC resected at the University of California, San Francisco. The assay was then independently validated by the Kaiser Permanente Division of Research in a masked cohort of 433 patients with stage I non-squamous NSCLC resected at Kaiser Permanente Northern California hospitals, and on a cohort of 1006 patients with stage I-III non-squamous NSCLC resected in several leading Chinese cancer centres that are part of the China Clinical Trials Consortium (CCTC). FINDINGS: Kaplan-Meier analysis of the Kaiser validation cohort showed 5 year overall survival of 71·4% (95% CI 60·5-80·0) in low-risk, 58·3% (48·9-66·6) in intermediate-risk, and 49·2% (42·2-55·8) in high-risk patients (p(trend)=0·0003). Similar analysis of the CCTC cohort indicated 5 year overall survivals of 74·1% (66·0-80·6) in low-risk, 57·4% (48·3-65·5) in intermediate-risk, and 44·6% (40·2-48·9) in high-risk patients (p(trend)<0·0001). Multivariate analysis in both cohorts indicated that no standard clinical risk factors could account for, or provide, the prognostic information derived from tumour gene expression. The assay improved prognostic accuracy beyond National Comprehensive Cancer Network criteria for stage I high-risk tumours (p<0·0001), and differentiated low-risk, intermediate-risk, and high-risk patients within all disease stages. INTERPRETATION: Our practical, quantitative-PCR-based assay reliably identified patients with early-stage non-squamous NSCLC at high risk for mortality after surgical resection. FUNDING: UCSF Thoracic Oncology Laboratory and Pinpoint Genomics.

PMID: 22285053 [PubMed - as supplied by publisher]

Device regulation in the European Union: response from MHRA.

Lancet. 2012 Jan 26;

Authors: Woods K

PMID: 22285054 [PubMed - as supplied by publisher]

Effectiveness of community case management of severe pneumonia with oral amoxicillin in children aged 2-59 months in Matiari district, rural Pakistan: a cluster-randomised controlled trial.

Lancet. 2012 Jan 26;

Authors: Soofi S, Ahmed S, Fox MP, Macleod WB, Thea DM, Qazi SA, Bhutta ZA

Abstract

BACKGROUND: Pneumonia is a leading global cause of morbidity and mortality in children younger than 5 years. In Pakistan, the proportion of deaths due to pneumonia is higher in rural areas than it is in urban areas, with a substantial proportion of individuals dying at home because referral for care is problematic in such areas. We aimed to establish whether community case identification and management of severe pneumonia by oral antibiotics delivered through community health workers has the potential to reduce the number of infants dying at home. METHODS: We did a cluster-randomised controlled trial in Matiari district of rural Sindh, Pakistan. Public-sector lady health workers (LHWs) undertook community case management of WHO-defined severe pneumonia. The children in intervention clusters with suspected pneumonia were screened by LHWs and those diagnosed with severe pneumonia were prescribed oral amoxicillin syrup (90 mg/kg per day in two doses) for 5 days at home. Children in control clusters were given one dose of oral co-trimoxazole and were referred to their nearest health facility for admission and intravenous antibiotics, as per government policy. In both groups, follow-up visits at home were done at days 2, 3, 6, and 14 by LHW. The primary outcome was treatment failure by day 6 after enrolment. We matched and randomly allocated 18 clusters (union councils, the smallest administrative unit of the district) to either intervention and control using a computer-generated randomisation scheme. Analyses were done per-protocol. This trial is registered with ClinicalTrials.gov, number NCT01192789. FINDINGS: 2341 children in intervention clusters and 2069 children in control clusters participated in the study, enrolled between Feb 13, 2008, and March 15, 2010. We recorded 187 (8%) treatment failures by day 6 in the intervention group and 273 (13%) in the control group. After adjusting for clustering, the risk difference for treatment failure was -5·2% (95% CI -13·7% to 3·3%). We recorded three deaths, two by day 6 and one between days 7 and 14. We recorded no serious adverse events. INTERPRETATION: Public sector LHWs in Pakistan were able to satisfactorily diagnose and treat severe pneumonia at home in rural Pakistan. This strategy might effectively reach children with pneumonia in settings where referral is difficult, and it could be a key component of community detection and management strategies for childhood pneumonia. FUNDING: US Agency for International Development through grants to John Snow Incorporation and Boston University, USA.

PMID: 22285055 [PubMed - as supplied by publisher]

Homozygous familial hypercholesterolaemia.

Lancet. 2012 Jan 26;

Authors: Macchiaiolo M, Gagliardi MG, Toscano A, Guccione P, Bartuli A

PMID: 22285056 [PubMed - as supplied by publisher]

BRCA patent dispute may head to US Supreme Court.

Lancet. 2012 Jan 28;379(9813):300

Authors: Devi S

PMID: 22292161 [PubMed - in process]

CDC planning trial for mysterious nodding syndrome.

Lancet. 2012 Jan 28;379(9813):299

Authors: Donnelly J

PMID: 22292160 [PubMed - in process]

Anticoagulant loses its lustre.

Lancet. 2012 Jan 28;379(9813):301

Authors: Mullard A

PMID: 22292162 [PubMed - in process]

Shakespeare under water.

Lancet. 2012 Jan 28;379(9813):306-7

Authors: Boyce N

PMID: 22292164 [PubMed - in process]

Greece’s financial crisis dries up drug supply.

Lancet. 2012 Jan 28;379(9813):302

Authors: Karamanoli E

PMID: 22292163 [PubMed - in process]

What (if anything) to do about low-risk prostate cancer.

Lancet. 2012 Jan 23;

Authors: Parker C

PMID: 22277569 [PubMed - as supplied by publisher]

Dutasteride in localised prostate cancer management: the REDEEM randomised, double-blind, placebo-controlled trial.

Lancet. 2012 Jan 23;

Authors: Fleshner NE, Lucia MS, Egerdie B, Aaron L, Eure G, Nandy I, Black L, Rittmaster RS

Abstract

BACKGROUND: We aimed to investigate the safety and efficacy of dutasteride, a 5α-reductase inhibitor, on prostate cancer progression in men with low-risk disease who chose to be followed up with active surveillance. METHODS: In our 3 year, randomised, double-blind, placebo-controlled study, undertaken at 65 academic medical centres or outpatient clinics in North America, we enrolled men aged 48-82 years who had low-volume, Gleason score 5-6 prostate cancer and had chosen to be followed up with active surveillance. We randomly allocated participants in a one-to-one ratio, stratified by site and in block sizes of four, to receive once-daily dutasteride 0·5 mg or matching placebo. Participants were followed up for 3 years, with 12-core prostate biopsy samples obtained after 18 months and 3 years. The primary endpoint was time to prostate cancer progression, defined as the number of days between the start of study treatment and the earlier of either pathological progression (in patients with ≥1 biopsy assessment after baseline) or therapeutic progression (start of medical therapy). This trial is registered with ClinicalTrials.gov, number NCT00363311. FINDINGS: Between Aug 10, 2006, and March 26, 2007, we randomly allocated 302 participants, of whom 289 (96%) had at least one biopsy procedure after baseline and were included in the primary analysis. By 3 years, 54 (38%) of 144 men in the dutasteride group and 70 (48%) of 145 controls had prostate cancer progression (pathological or therapeutic; hazard ratio 0·62, 95% CI 0·43-0·89; p=0·009). Incidence of adverse events was much the same between treatment groups. 35 (24%) men in the dutasteride group and 23 (15%) controls had sexual adverse events or breast enlargement or tenderness. Eight (5%) men in the dutasteride group and seven (5%) controls had cardiovascular adverse events, but there were no prostate cancer-related deaths or instances of metastatic disease. INTERPRETATION: Dutasteride could provide a beneficial adjunct to active surveillance for men with low-risk prostate cancer. FUNDING: GlaxoSmithKline.

PMID: 22277570 [PubMed - as supplied by publisher]

Human embryonic stem cells: early hints on safety and efficacy.

Lancet. 2012 Jan 24;

Authors: Atala A

PMID: 22281387 [PubMed - as supplied by publisher]

Embryonic stem cell trials for macular degeneration: a preliminary report.

Lancet. 2012 Jan 24;

Authors: Schwartz SD, Hubschman JP, Heilwell G, Franco-Cardenas V, Pan CK, Ostrick RM, Mickunas E, Gay R, Klimanskaya I, Lanza R

Abstract

BACKGROUND: It has been 13 years since the discovery of human embryonic stem cells (hESCs). Our report provides the first description of hESC-derived cells transplanted into human patients. METHODS: We started two prospective clinical studies to establish the safety and tolerability of subretinal transplantation of hESC-derived retinal pigment epithelium (RPE) in patients with Stargardt’s macular dystrophy and dry age-related macular degeneration-the leading cause of blindness in the developed world. Preoperative and postoperative ophthalmic examinations included visual acuity, fluorescein angiography, optical coherence tomography, and visual field testing. These studies are registered with ClinicalTrials.gov, numbers NCT01345006 and NCT01344993. FINDINGS: Controlled hESC differentiation resulted in greater than 99% pure RPE. The cells displayed typical RPE behaviour and integrated into the host RPE layer forming mature quiescent monolayers after transplantation in animals. The stage of differentiation substantially affected attachment and survival of the cells in vitro after clinical formulation. Lightly pigmented cells attached and spread in a substantially greater proportion (>90%) than more darkly pigmented cells after culture. After surgery, structural evidence confirmed cells had attached and continued to persist during our study. We did not identify signs of hyperproliferation, abnormal growth, or immune mediated transplant rejection in either patient during the first 4 months. Although there is little agreement between investigators on visual endpoints in patients with low vision, it is encouraging that during the observation period neither patient lost vision. Best corrected visual acuity improved from hand motions to 20/800 (and improved from 0 to 5 letters on the Early Treatment Diabetic Retinopathy Study [ETDRS] visual acuity chart) in the study eye of the patient with Stargardt’s macular dystrophy, and vision also seemed to improve in the patient with dry age-related macular degeneration (from 21 ETDRS letters to 28). INTERPRETATION: The hESC-derived RPE cells showed no signs of hyperproliferation, tumorigenicity, ectopic tissue formation, or apparent rejection after 4 months. The future therapeutic goal will be to treat patients earlier in the disease processes, potentially increasing the likelihood of photoreceptor and central visual rescue. FUNDING: Advanced Cell Technology.

PMID: 22281388 [PubMed - as supplied by publisher]

India reports cases of totally drug-resistant tuberculosis.

Lancet. 2012 Jan 21;379(9812):205

Authors: Loewenberg S

PMID: 22272391 [PubMed - in process]

Germany’s hospital doctors prepare to strike en masse.

Lancet. 2012 Jan 21;379(9812):206

Authors: Holt E

PMID: 22272392 [PubMed - in process]

Blunting the legacy of alcohol abuse in Western Australia.

Lancet. 2012 Jan 21;379(9812):207-8

Authors: Kirby T

PMID: 22272393 [PubMed - in process]

Victorian visions of child development.

Lancet. 2012 Jan 21;379(9812):212-3

Authors: Shuttleworth S

PMID: 22272394 [PubMed - in process]

Subclinical thyroid disease.

Lancet. 2012 Jan 20;

Authors: Cooper DS, Biondi B

Abstract

Subclinical thyroid diseases-subclinical hyperthyroidism and subclinical hypothyroidism-are common clinical entities that encompass mild degrees of thyroid dysfunction. The clinical significance of mild thyroid overactivity and underactivity is uncertain, which has led to controversy over the appropriateness of diagnostic testing and possible treatment. In this Seminar, we discuss the definition, epidemiology, differential diagnoses, risks of progression to overt thyroid disease, potential effects on various health outcomes, and management of subclinical hyperthyroidism and subclinical hypothyroidism. Treatment recommendations are based on the degree to which thyroid-stimulating hormone concentrations have deviated from normal and underlying comorbidities. Large-scale randomised trials are urgently needed to inform how to best care for individuals with subclinical thyroid disease.

PMID: 22273398 [PubMed - as supplied by publisher]

Abortion: what is the problem?

Lancet. 2012 Jan 18;

Authors: Winikoff B, Sheldon WR

PMID: 22264434 [PubMed - as supplied by publisher]

Induced abortion: incidence and trends worldwide from 1995 to 2008.

Lancet. 2012 Jan 18;

Authors: Sedgh G, Singh S, Shah IH, Ahman E, Henshaw SK, Bankole A

Abstract

BACKGROUND: Data of abortion incidence and trends are needed to monitor progress toward improvement of maternal health and access to family planning. To date, estimates of safe and unsafe abortion worldwide have only been made for 1995 and 2003. METHODS: We used the standard WHO definition of unsafe abortions. Safe abortion estimates were based largely on official statistics and nationally representative surveys. Unsafe abortion estimates were based primarily on information from published studies, hospital records, and surveys of women. We used additional sources and systematic approaches to make corrections and projections as needed where data were misreported, incomplete, or from earlier years. We assessed trends in abortion incidence using rates developed for 1995, 2003, and 2008 with the same methodology. We used linear regression models to explore the association of the legal status of abortion with the abortion rate across subregions of the world in 2008. FINDINGS: The global abortion rate was stable between 2003 and 2008, with rates of 29 and 28 abortions per 1000 women aged 15-44 years, respectively, following a period of decline from 35 abortions per 1000 women in 1995. The average annual percent change in the rate was nearly 2·4% between 1995 and 2003 and 0·3% between 2003 and 2008. Worldwide, 49% of abortions were unsafe in 2008, compared to 44% in 1995. About one in five pregnancies ended in abortion in 2008. The abortion rate was lower in subregions where more women live under liberal abortion laws (p<0·05). INTERPRETATION: The substantial decline in the abortion rate observed earlier has stalled, and the proportion of all abortions that are unsafe has increased. Restrictive abortion laws are not associated with lower abortion rates. Measures to reduce the incidence of unintended pregnancy and unsafe abortion, including investments in family planning services and safe abortion care, are crucial steps toward achieving the Millennium Development Goals. FUNDING: UK Department for International Development, Dutch Ministry of Foreign Affairs, and John D and Catherine T MacArthur Foundation.

PMID: 22264435 [PubMed - as supplied by publisher]

Global health in 2012: development to sustainability.

Lancet. 2012 Jan 21;379(9812):193

Authors:

PMID: 22265616 [PubMed - in process]

Public health in England: from nudge to nag.

Lancet. 2012 Jan 21;379(9812):194

Authors:

PMID: 22265617 [PubMed - in process]

Global surgery–the final frontier?

Lancet. 2012 Jan 21;379(9812):194

Authors:

PMID: 22265618 [PubMed - in process]

Knowledge as a key resource for health challenges.

Lancet. 2012 Jan 21;379(9812):195-6

Authors: Antes G, Clarke M

PMID: 22265619 [PubMed - in process]

Hazel Dockrell: ambassador for international health research.

Lancet. 2012 Jan 21;379(9812):211

Authors: Morris K

PMID: 22265620 [PubMed - in process]

Novel melatonin-based treatments for major depression.

Lancet. 2012 Jan 21;379(9812):215-6; author reply 217-9

Authors: Howland RH

PMID: 22265621 [PubMed - in process]

Novel melatonin-based treatments for major depression.

Lancet. 2012 Jan 21;379(9812):215; author reply 217-9

Authors: Barbui C, Cipriani A

PMID: 22265622 [PubMed - in process]

Novel melatonin-based treatments for major depression.

Lancet. 2012 Jan 21;379(9812):216-7; author reply 217-9

Authors: Jureidini J, Raven M

PMID: 22265623 [PubMed - in process]

Novel melatonin-based treatments for major depression.

Lancet. 2012 Jan 21;379(9812):216; author reply 217-9

Authors: Carroll BJ

PMID: 22265624 [PubMed - in process]

Novel melatonin-based treatments for major depression.

Lancet. 2012 Jan 21;379(9812):216; author reply 217-9

Authors: Lloret-Linares C, Bergmann JF, Mouly S

PMID: 22265625 [PubMed - in process]

Novel melatonin-based treatments for major depression.

Lancet. 2012 Jan 21;379(9812):217; author reply 217-9

Authors: Serfaty M, Raven PW

PMID: 22265626 [PubMed - in process]

Haemopoietic stem-cell transplantation for systemic sclerosis.

Lancet. 2012 Jan 21;379(9812):219; author reply 219-20

Authors: Sullivan KM, Wigley FM, Denton CP, van Laar JM, Furst DE

PMID: 22265628 [PubMed - in process]

Stay the course–is it justified?

Lancet. 2012 Jan 21;379(9812):220

Authors: Sepehry AA, Lee PE, Hsiung GY, Jacova C

PMID: 22265630 [PubMed - in process]

Is it all cerebral toxoplasmosis?

Lancet. 2012 Jan 21;379(9812):286

Authors: Mentzer A, Perry M, Fitzgerald N, Barrington S, Siddiqui A, Kulasegaram R

PMID: 22265631 [PubMed - in process]

Child mental health care in Brazil: barriers and achievements.

Lancet. 2012 Jan 21;379(9812):e16-7

Authors: Fatori D, Evans-Lacko S, Bordin IA, de Paula C

PMID: 22265632 [PubMed - in process]

Ways out of the crisis behind Bribegate for Chinese doctors.

Lancet. 2012 Jan 21;379(9812):e16

Authors: Zhang H, Wu J

PMID: 22265633 [PubMed - in process]

Ways out of the crisis behind Bribegate for Chinese doctors.

Lancet. 2012 Jan 21;379(9812):e16

Authors: Li H, Zhang H

PMID: 22265634 [PubMed - in process]

Non-communicable disease priority actions and social inclusion.

Lancet. 2012 Jan 21;379(9812):e17-8

Authors: Mannan H, Amin M, MacLachlan M,

PMID: 22265635 [PubMed - in process]

Lithium toxicity profile: a systematic review and meta-analysis.

Lancet. 2012 Jan 19;

Authors: McKnight RF, Adida M, Budge K, Stockton S, Goodwin GM, Geddes JR

Abstract

BACKGROUND: Lithium is a widely used and effective treatment for mood disorders. There has been concern about its safety but no adequate synthesis of the evidence for adverse effects. We aimed to undertake a clinically informative, systematic toxicity profile of lithium. METHODS: We undertook a systematic review and meta-analysis of randomised controlled trials and observational studies. We searched electronic databases, specialist journals, reference lists, textbooks, and conference abstracts. We used a hierarchy of evidence which considered randomised controlled trials, cohort studies, case-control studies, and case reports that included patients with mood disorders given lithium. Outcome measures were renal, thyroid, and parathyroid function; weight change; skin disorders; hair disorders; and teratogenicity. FINDINGS: We screened 5988 abstracts for eligibility and included 385 studies in the analysis. On average, glomerular filtration rate was reduced by -6·22 mL/min (95% CI -14·65 to 2·20, p=0·148) and urinary concentrating ability by 15% of normal maximum (weighted mean difference -158·43 mOsm/kg, 95% CI -229·78 to -87·07, p<0·0001). Lithium might increase risk of renal failure, but the absolute risk was small (18 of 3369 [0·5%] patients received renal replacement therapy). The prevalence of clinical hypothyroidism was increased in patients taking lithium compared with those given placebo (odds ratio [OR] 5·78, 95% CI 2·00-16·67; p=0·001), and thyroid stimulating hormone was increased on average by 4·00 iU/mL (95% CI 3·90-4·10, p<0·0001). Lithium treatment was associated with increased blood calcium (+0·09 mmol/L, 95% CI 0·02-0·17, p=0·009), and parathyroid hormone (+7·32 pg/mL, 3·42-11·23, p<0·0001). Patients receiving lithium gained more weight than did those receiving placebo (OR 1·89, 1·27-2·82, p=0·002), but not those receiving olanzapine (0·32, 0·21-0·49, p<0·0001). We recorded no significant increased risk of congenital malformations, alopecia, or skin disorders. INTERPRETATION: Lithium is associated with increased risk of reduced urinary concentrating ability, hypothyroidism, hyperparathyroidism, and weight gain. There is little evidence for a clinically significant reduction in renal function in most patients, and the risk of end-stage renal failure is low. The risk of congenital malformations is uncertain; the balance of risks should be considered before lithium is withdrawn during pregnancy. Because of the consistent finding of a high prevalence of hyperparathyroidism, calcium concentrations should be checked before and during treatment. FUNDING: National Institute for Health Research Programme Grant for Applied Research.

PMID: 22265699 [PubMed - as supplied by publisher]

Chronic insomnia.

Lancet. 2012 Jan 19;

Authors: Morin CM, Benca R

Abstract

Insomnia is a prevalent complaint in clinical practice that can present independently or comorbidly with another medical or psychiatric disorder. In either case, it might need treatment of its own. Of the different therapeutic options available, benzodiazepine-receptor agonists (BzRAs) and cognitive-behavioural therapy (CBT) are supported by the best empirical evidence. BzRAs are readily available and effective in the short-term management of insomnia, but evidence of long-term efficacy is scarce and most hypnotic drugs are associated with potential adverse effects. CBT is an effective alternative for chronic insomnia. Although more time consuming than drug management, CBT produces sleep improvements that are sustained over time, and this therapy is accepted by patients. Although CBT is not readily available in most clinical settings, access and delivery can be made easier through use of innovative methods such as telephone consultations, group therapy, and self-help approaches. Combined CBT and drug treatment can optimise outcomes, although evidence to guide clinical practice on the best way to integrate these approaches is scarce.

PMID: 22265700 [PubMed - as supplied by publisher]

Is the safety of lithium no longer in the balance?

Lancet. 2012 Jan 19;

Authors: Malhi GS, Berk M

PMID: 22265701 [PubMed - as supplied by publisher]

Offline: The scandal of device regulation in the UK.

Lancet. 2012 Jan 17;

Authors: Horton R

PMID: 22260986 [PubMed - as supplied by publisher]

Prevention of serogroup B meningococcal disease.

Lancet. 2012 Jan 17;

Authors: Stephens DS

PMID: 22260987 [PubMed - as supplied by publisher]

Immunogenicity and tolerability of a multicomponent meningococcal serogroup B (4CMenB) vaccine in healthy adolescents in Chile: a phase 2b/3 randomised, observer-blind, placebo-controlled study.

Lancet. 2012 Jan 17;

Authors: Santolaya ME, O’Ryan ML, Valenzuela MT, Prado V, Vergara R, Muñoz A, Toneatto D, Graña G, Wang H, Clemens R, Dull PM,

Abstract

BACKGROUND: Effective glycoconjugate vaccines against Neisseria meningitidis serogroups A, C, W-135, and Y have been developed, but serogroup B remains a major cause of severe invasive disease in infants and adolescents worldwide. We assessed immunogenicity and tolerability of a four-component vaccine (4CMenB) in adolescents. METHODS: We did a randomised, observer-blind, placebo-controlled, study at 12 sites in Santiago and Valparaíso, Chile. Adolescents aged 11-17 years received one, two, or three doses of 4CMenB at 1 month, 2 month, or 6 month intervals. Immunogenicity was assessed as serum bactericidal activity using human complement (hSBA) against three reference strains for individual vaccine antigens, and assessed by ELISA against the fourth strain. Local and systemic reactions were recorded 7 days after each vaccination, and adverse events were monitored throughout the study. Participants were initially randomised to five groups (3:3:3:3:1) during the primary phase to receive either one dose, two doses 1 or 2 months apart, or three doses of 4CMenB, or three doses of placebo, with an additional three groups generated for the booster phase. All subjects received at least one dose of 4CMenB. Geometric mean titres, proportions of participants with serum bactericidal antibody titres of 4 or more, and Clopper-Pearson 95% CIs were calculated. The study is registered with ClinicalTrials.gov, number NCT00661713. FINDINGS: Overall, 1631 adolescents (mean age 13·8 [SD 1·9] years) received at least one dose of 4CMenB. After two or three doses, 99-100% of recipients had hSBA titres of 4 or more against test strains, compared with 92-97% after one dose (p<0·0145) and 29-50% after placebo. At 6 months 91-100% of participants still had titres of 4 or more for each strain after two or three doses, but only 73-76% after one dose; seroresponse rates reached 99-100% for each strain after second or third doses at 6 months. Local and systemic reaction rates were similar after each 4CMenB injection and did not increase with subsequent doses, but remained higher than placebo. No vaccine-related serious adverse events were reported and no significant safety signals were identified. INTERPRETATION: On the basis of immunogenicity responses this study provides evidence for an adolescent 4CMenB vaccine schedule of two doses, 1-6 months apart, to provide protection against meningococcal B infection. The extent of this protection against meningococcus B variants circulating worldwide will be determined by national surveys. FUNDING: Novartis Vaccines and Diagnostics.

PMID: 22260988 [PubMed - as supplied by publisher]

Dual inhibition of HER2 in breast cancer treatment.

Lancet. 2012 Jan 16;

Authors: Gnant M, Steger GG

PMID: 22257672 [PubMed - as supplied by publisher]

Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial.

Lancet. 2012 Jan 16;

Authors: Baselga J, Bradbury I, Eidtmann H, Di Cosimo S, de Azambuja E, Aura C, Gómez H, Dinh P, Fauria K, Van Dooren V, Aktan G, Goldhirsch A, Chang TW, Horváth Z, Coccia-Portugal M, Domont J, Tseng LM, Kunz G, Sohn JH, Semiglazov V, Lerzo G, Palacova M, Probachai V, Pusztai L, Untch M, Gelber RD, Piccart-Gebhart M,

Abstract

BACKGROUND: The anti-HER2 monoclonal antibody trastuzumab and the tyrosine kinase inhibitor lapatinib have complementary mechanisms of action and synergistic antitumour activity in models of HER2-overexpressing breast cancer. We argue that the two anti-HER2 agents given together would be better than single-agent therapy. METHODS: In this parallel groups, randomised, open-label, phase 3 study undertaken between Jan 5, 2008, and May 27, 2010, women from 23 countries with HER2-positive primary breast cancer with tumours greater than 2 cm in diameter were randomly assigned to oral lapatinib (1500 mg), intravenous trastuzumab (loading dose 4 mg/m(2), subsequent doses 2 mg/kg), or lapatinib (1000 mg) plus trastuzumab. Treatment allocation was by stratified, permuted blocks randomisation, with four stratification factors. Anti-HER2 therapy alone was given for the first 6 weeks; weekly paclitaxel (80 mg/m(2)) was then added to the regimen for a further 12 weeks, before definitive surgery was undertaken. After surgery, patients received adjuvant chemotherapy followed by the same targeted therapy as in the neoadjuvant phase to 52 weeks. The primary endpoint was the rate of pathological complete response (pCR), analysed by intention to treat. This trial is registered with ClinicalTrials.gov, NCT00553358. FINDINGS: 154 patients received lapatinib, 149 trastuzumab, and 152 the combination. pCR rate was significantly higher in the group given lapatinib and trastuzumab (78 of 152 patients [51·3%; 95% CI 43·1-59·5]) than in the group given trastuzumab alone (44 of 149 patients [29·5%; 22·4-37·5]; difference 21·1%, 9·1-34·2, p=0·0001). We recorded no significant difference in pCR between the lapatinib (38 of 154 patients [24·7%, 18·1-32·3]) and the trastuzumab (difference -4·8%, -17·6 to 8·2, p=0·34) groups. No major cardiac dysfunctions occurred. Frequency of grade 3 diarrhoea was higher with lapatinib (36 patients [23·4%]) and lapatinib plus trastuzumab (32 [21·1%]) than with trastuzumab (three [2·0%]). Similarly, grade 3 liver-enzyme alterations were more frequent with lapatinib (27 [17·5%]) and lapatinib plus trastuzumab (15 [9·9%]) than with trastuzumab (11 [7·4%]). INTERPRETATION: Dual inhibition of HER2 might be a valid approach to treatment of HER2-positive breast cancer in the neoadjuvant setting. FUNDING: GlaxoSmithKline.

PMID: 22257673 [PubMed - as supplied by publisher]

Eye can see a nest of worms!

Lancet. 2012 Jan 12;

Authors: Lin H, Liang X

PMID: 22244656 [PubMed - as supplied by publisher]

Republican presidential candidates united on health care.

Lancet. 2012 Jan 14;379(9811):107

Authors: Bristol N

PMID: 22256349 [PubMed - in process]

Grassroots project shines hope on Nairobi slum life.

Lancet. 2012 Jan 14;379(9811):108-9

Authors: Loewenberg S

PMID: 22256350 [PubMed - in process]

Pro-anorexia websites pose public health challenge.

Lancet. 2012 Jan 14;379(9811):110

Authors: Christodoulou M

PMID: 22256351 [PubMed - in process]

The short life of a race drug.

Lancet. 2012 Jan 14;379(9811):114-5

Authors: Krimsky S

PMID: 22256352 [PubMed - in process]

Effect of population-based screening on breast cancer mortality.

Lancet. 2012 Jan 10;

Authors: Gøtzsche PC, Jørgensen KJ

PMID: 22240405 [PubMed - as supplied by publisher]

Oral azithromycin for treatment of yaws.

Lancet. 2012 Jan 10;

Authors: Mabey D

PMID: 22240406 [PubMed - as supplied by publisher]

Single-dose azithromycin versus benzathine benzylpenicillin for treatment of yaws in children in Papua New Guinea: an open-label, non-inferiority, randomised trial.

Lancet. 2012 Jan 10;

Authors: Mitjà O, Hays R, Ipai A, Penias M, Paru R, Fagaho D, de Lazzari E, Bassat Q

Abstract

BACKGROUND: Yaws-an endemic treponematosis and, as such, a neglected tropical disease-is re-emerging in children in rural, tropical areas. Oral azithromycin is effective for syphilis. We assessed the efficacy of azithromycin compared with intramuscular long-acting penicillin to treat patients with yaws. METHODS: We did an open-label, non-inferiority, randomised trial at Lihir Medical Centre, Papua New Guinea, between Sept 1, 2010, and Feb 1, 2011. Children aged 6 months to 15 years with a serologically confirmed diagnosis of yaws were randomly allocated, by a computer-generated randomisation sequence, to receive either one 30 mg/kg oral dose of azithromycin or an intramuscular injection of 50 000 units per kg benzathine benzylpenicillin. Investigators were masked to group assignment. The primary endpoint was treatment efficacy, with cure rate defined serologically as a decrease in rapid plasma reagin titre of at least two dilutions by 6 months after treatment, and, in participants with primary ulcers, also by epithelialisation of lesions within 2 weeks. Non-inferiority was shown if the upper limit of the two-sided 95% CI for the difference in rates was lower than 10%. The primary analysis was per protocol. This trial is registered with ClinicalTrials.gov, number NCT01382004. FINDINGS: We allocated 124 patients to the azithromycin group and 126 to the benzathine benzylpenicillin group. In the per-protocol analysis, after 6 months of follow-up, 106 (96%) of 110 patients in the azithromycin group were cured, compared with 105 (93%) of 113 in the benzathine benzylpenicillin group (treatment difference -3·4%; 95% CI -9·3 to 2·4), thus meeting prespecified criteria for non-inferiority. The number of drug-related adverse events (all mild or moderate) was similar in both treatment groups (ten [8%] in the azithromycin group vs eight [7%] in the benzathine benzylpenicillin group). INTERPRETATION: A single oral dose of azithromycin is non-inferior to benzathine benzylpenicillin and avoids the need for injection equipment and medically trained personnel. A change to the simpler azithromycin treatment regimen could enable yaws elimination through mass drug administration programmes. FUNDING: International SOS and Newcrest Mining.

PMID: 22240407 [PubMed - as supplied by publisher]

Elimination of cholera transmission in Haiti and the Dominican Republic.

Lancet. 2012 Jan 10;

Authors: Periago MR, Frieden TR, Tappero JW, De Cock KM, Aasen B, Andrus JK

PMID: 22240408 [PubMed - as supplied by publisher]

Clinical features of paediatric pulmonary hypertension: a registry study.

Lancet. 2012 Jan 10;

Authors: Berger RM, Beghetti M, Humpl T, Raskob GE, Ivy DD, Jing ZC, Bonnet D, Schulze-Neick I, Barst RJ

Abstract

BACKGROUND: Paediatric pulmonary hypertension, is an important cause of morbidity and mortality, and is insufficiently characterised in children. The Tracking Outcomes and Practice in Pediatric Pulmonary Hypertension (TOPP) registry is a global, prospective study designed to provide information about demographics, treatment, and outcomes in paediatric pulmonary hypertension. METHODS: Consecutive patients aged 18 years or younger at diagnosis with pulmonary hypertension and increased pulmonary vascular resistance were enrolled in TOPP at 31 centres in 19 countries from Jan 31, 2008, to Feb 15, 2010. Patient and disease characteristics, including age at diagnosis and at enrolment, sex, ethnicity, presenting symptoms, pulmonary hypertension classification, comorbid disorders, medical and family history, haemodynamic indices, and functional class were recorded. Follow-up was decided by the patients’ physicians according to the individual’s health-care needs. FINDINGS: 362 of 456 consecutive patients had confirmed pulmonary hypertension (defined as mean pulmonary artery pressure ≥25 mm Hg, pulmonary capillary wedge pressure ≤12 mm Hg, and pulmonary vascular resistance index ≥3 WU/m(-2)). 317 (88%) patients had pulmonary arterial hypertension (PAH), which was idiopathic [IPAH] or familial [FPAH] in 182 (57%), and associated with other disorders in 135 (43%), of which 115 (85%) cases were associated with congenital heart disease. 42 patients (12%) had pulmonary hypertension associated with respiratory disease or hypoxaemia, with bronchopulmonary dysplasia most frequent. Finally, only three patients had either chronic thromboembolic pulmonary hypertension or miscellaneous causes of pulmonary hypertension. Chromosomal anomalies, mainly trisomy 21, were reported in 47 (13%) of patients with confirmed disease. Median age at diagnosis was 7 years (IQR 3-12); 59% (268 of 456) were female. Although dyspnoea and fatigue were the most frequent symptoms, syncope occurred in 31% (57 of 182) of patients with IPAH or FPAH and in 18% (eight of 45) of those with repaired congenital heart disease; no children with unrepaired congenital systemic-to-pulmonary shunts had syncope. Despite severe pulmonary hypertension, functional class was I or II in 230 of 362 (64%) patients, which is consistent with preserved right-heart function. INTERPRETATION: TOPP identifies important clinical features specific to the care of paediatric pulmonary hypertension, which draw attention to the need for paediatric data rather than extrapolation from adult studies. FUNDING: Actelion Pharmaceuticals.

PMID: 22240409 [PubMed - as supplied by publisher]

Pulmonary hypertension in early life.

Lancet. 2012 Jan 10;

Authors: Mallory GB

PMID: 22240410 [PubMed - as supplied by publisher]

Memantine for dementia in adults older than 40 years with Down’s syndrome (MEADOWS): a randomised, double-blind, placebo-controlled trial.

Lancet. 2012 Jan 9;

Authors: Hanney M, Prasher V, Williams N, Jones EL, Aarsland D, Corbett A, Lawrence D, Yu LM, Tyrer S, Francis PT, Johnson T, Bullock R, Ballard C,

Abstract

BACKGROUND: Prevalence of Alzheimer’s disease in people with Down’s syndrome is very high, and many such individuals who are older than 40 years have pathological changes characteristic of Alzheimer’s disease. Evidence to support treatment with Alzheimer’s drugs is inadequate, although memantine is beneficial in transgenic mice. We aimed to assess safety and efficacy of memantine on cognition and function in individuals with Down’s syndrome. METHODS: In our prospective randomised double-blind trial, we enrolled adults (>40 years) with karyotypic or clinically diagnosed Down’s syndrome, with and without dementia, at four learning disability centres in the UK and Norway. We randomly allocated participants (1:1) to receive memantine or placebo for 52 weeks by use of a computer-generated sequence and a minimisation algorithm to ensure balanced allocation for five prognostic factors (sex, dementia, age group, total Down’s syndrome attention, memory, and executive function scales [DAMES] score, and centre). The primary outcome was change in cognition and function, measured with DAMES scores and the adaptive behaviour scale (ABS) parts I and II. We analysed differences in DAMES and ABS scores between groups with analyses of covariance or quantile regression in all patients who completed the 52 week assessment and had available follow-up data. This study is registered, number ISRCTN47562898. FINDINGS: We randomly allocated 88 patients to receive memantine (72 [82%] had DAMES data and 75 [85%] had ABS data at 52 weeks) and 85 to receive placebo (74 [87%] and 73 [86%]). Both groups declined in cognition and function but rates did not differ between groups for any outcomes. After adjustment for baseline score, there were non-significant differences between groups of -4·1 (95% CI -13·1 to 4·8) in DAMES scores, -8·5 (-20·1 to 3·1) in ABS I scores, and 2·0 (-7·2 to 11·3) in ABS II scores, all in favour of controls. 10 (11%) of 88 participants in the memantine group and six (7%) of 85 controls had serious adverse events (p=0·33). Five participants in the memantine group and four controls died from serious adverse events (p=0·77). INTERPRETATION: There is a striking absence of evidence about pharmacological treatment of cognitive impairment and dementia in people older than 40 years with Down’s syndrome. Despite promising indications, memantine is not an effective treatment. Therapies that are effective for Alzheimer’s disease are not necessarily effective in this group of patients. FUNDING: Lundbeck.

PMID: 22236802 [PubMed - as supplied by publisher]

Improving Alzheimer’s disease outcomes in Down’s syndrome.

Lancet. 2012 Jan 9;

Authors: Livingston G, Strydom A

PMID: 22236803 [PubMed - as supplied by publisher]

Translational research and experimental medicine in 2012.

Lancet. 2012 Jan 7;379(9810):1

Authors:

PMID: 22225654 [PubMed - in process]

North Korea–who will help?

Lancet. 2012 Jan 7;379(9810):2

Authors:

PMID: 22225655 [PubMed - in process]

Addiction–a global problem with no global solution.

Lancet. 2012 Jan 7;379(9810):2

Authors:

PMID: 22225656 [PubMed - in process]

Louisa Degenhardt: hooked on addiction research.

Lancet. 2012 Jan 7;379(9810):21

Authors: Kirby T

PMID: 22225658 [PubMed - in process]

An open letter to Michael Ball, Chief Executive of Hospira Pharmaceuticals.

Lancet. 2012 Jan 7;379(9810):25; discussion 25

Authors: Nicholl DJ

PMID: 22225659 [PubMed - in process]

The new decade of vaccines.

Lancet. 2012 Jan 7;379(9810):25-6; author reply 27

Authors: Aaby P, Martins C, Benn CS, Whittle H

PMID: 22225660 [PubMed - in process]

The new decade of vaccines.

Lancet. 2012 Jan 7;379(9810):26; author reply 27

Authors: Shann F

PMID: 22225662 [PubMed - in process]

Global burden of disease in young people aged 10-24 years.

Lancet. 2012 Jan 7;379(9810):27-8; author reply 28

Authors: Harhay MO, King CH

PMID: 22225664 [PubMed - in process]

The new decade of vaccines.

Lancet. 2012 Jan 7;379(9810):27

Authors: Hachey K

PMID: 22225665 [PubMed - in process]

Misleading information concerning the University of Helsinki.

Lancet. 2012 Jan 7;379(9810):29

Authors: Niiniluoto I

PMID: 22225667 [PubMed - in process]

The NHS IT project: more than just a bad dream.

Lancet. 2012 Jan 7;379(9810):29-30

Authors: Robertson A, Cornford T, Barber N, Avery T, Sheikh A,

PMID: 22225668 [PubMed - in process]

Global burden of disease in young people aged 10-24 years.

Lancet. 2012 Jan 7;379(9810):29

Authors: Benyamina A, Blecha L, Reynaud M

PMID: 22225669 [PubMed - in process]

The unobtainable placebo: control of independent clinical research by industry?

Lancet. 2012 Jan 7;379(9810):30

Authors: Christensen M, Knop FK

PMID: 22225670 [PubMed - in process]

Extent of illicit drug use and dependence, and their contribution to the global burden of disease.

Lancet. 2012 Jan 7;379(9810):55-70

Authors: Degenhardt L, Hall W

Abstract

This paper summarises data for the prevalence, correlates, and probable adverse health consequences of problem use of amphetamines, cannabis, cocaine, and opioids. We discuss findings from systematic reviews of the prevalence of illicit drug use and dependence, remission from dependence, and mortality in illicit drug users, and evidence for acute and chronic effects of illicit drug use. We outline the regional and global distribution of use and estimated health burden from illicit drugs. These distributions are likely to be underestimates because they have not included all adverse outcomes of drug use and exclude those of cannabis–the mostly widely used illicit drug. In high-income countries, illicit drug use contributes less to the burden of disease than does tobacco but a substantial proportion of that due to alcohol. The major adverse health effects of cannabis use are dependence and probably psychotic disorders and other mental disorders. The health-related harms of cannabis use differ from those of amphetamine, cocaine, and opioid use, in that cannabis contributes little to mortality. Intelligent policy responses to drug problems need better data for the prevalence of different types of illicit drug use and the harms that their use causes globally. This need is especially urgent in high-income countries with substantial rates of illicit drug use and in low-income and middle-income countries close to illicit drug production areas.

PMID: 22225671 [PubMed - in process]

Drug policy and the public good: evidence for effective interventions.

Lancet. 2012 Jan 7;379(9810):71-83

Authors: Strang J, Babor T, Caulkins J, Fischer B, Foxcroft D, Humphreys K

Abstract

Debates about which policy initiatives can prevent or reduce the damage that illicit drugs cause to the public good are rarely informed by scientific evidence. Fortunately, evidence-based interventions are increasingly being identified that are capable of making drugs less available, reducing violence in drug markets, lessening misuse of legal pharmaceuticals, preventing drug use initiation in young people, and reducing drug use and its consequences in established drug users. We review relevant evidence and outline the likely effects of fuller implementation of existing interventions. The reasoning behind the final decisions for action might be of a non-scientific nature, focused more on what the public and policy-makers deem of value. Nevertheless, important opportunities exist for science to inform these deliberations and guide the selection of policies that maximise the public good.

PMID: 22225672 [PubMed - in process]

How well do international drug conventions protect public health?

Lancet. 2012 Jan 7;379(9810):84-91

Authors: Room R, Reuter P

Abstract

The Single Convention on Narcotic Drugs in 1961 aimed to eliminate the illicit production and non-medical use of cannabis, cocaine, and opioids, an aim later extended to many pharmaceutical drugs. Over the past 50 years international drug treaties have neither prevented the globalisation of the illicit production and non-medical use of these drugs, nor, outside of developed countries, made these drugs adequately available for medical use. The system has also arguably worsened the human health and wellbeing of drug users by increasing the number of drug users imprisoned, discouraging effective countermeasures to the spread of HIV by injecting drug users, and creating an environment conducive to the violation of drug users’ human rights. The international system has belatedly accepted measures to reduce the harm from injecting drug use, but national attempts to reduce penalties for drug use while complying with the treaties have often increased the number of drug users involved with the criminal justice system. The international treaties have also constrained national policy experimentation because they require nation states to criminalise drug use. The adoption of national policies that are more aligned with the risks of different drugs and the effectiveness of controls will require the amendment of existing treaties, the formulation of new treaties, or withdrawal of states from existing treaties and re-accession with reservations.

PMID: 22225673 [PubMed - in process]

Standard-dose and high-dose daily antiviral therapy for short episodes of genital HSV-2 reactivation: three randomised, open-label, cross-over trials.

Lancet. 2012 Jan 4;

Authors: Johnston C, Saracino M, Kuntz S, Magaret A, Selke S, Huang ML, Schiffer JT, Koelle DM, Corey L, Wald A

Abstract

BACKGROUND: Skin and mucosal herpes simplex virus type 2 (HSV-2) shedding predominantly occurs in short subclinical episodes. We assessed whether standard-dose or high-dose antiviral therapy reduces the frequency of such shedding. METHODS: HSV-2-seropositive, HIV-seronegative people were enrolled at the University of Washington Virology Research Clinic (WA, USA). We did three separate but complementary open-label cross-over studies comparing no medication with aciclovir 400 mg twice daily (standard-dose aciclovir), valaciclovir 500 mg daily (standard-dose valaciclovir) with aciclovir 800 mg three times daily (high-dose aciclovir), and standard-dose valaciclovir with valaciclovir 1 g three times daily (high-dose valaciclovir). The allocation sequence was generated by a random number generator. Study drugs were supplied in identical, numbered, sealed boxes. Study periods lasted 4-7 weeks, separated by 1 week wash-out. Participants collected genital swabs four times daily for quantitative HSV DNA PCR. Clinical data were masked from laboratory personnel. The primary endpoint was within-person comparison of shedding rate in each study group. Analysis was per protocol. The trials are registered at ClinicalTrials.gov (NCT00362297, NCT00723229, NCT01346475). RESULTS: Of 113 participants randomised, 90 were eligible for analysis of the primary endpoint. Participants collected 23 605 swabs; 1272 (5·4%) were HSV-positive. The frequency of HSV shedding was significantly higher in the no medication group (n=384, 18·1% of swabs) than in the standard-dose aciclovir group (25, 1·2%; incidence rate ratio [IRR] 0·05, 95% CI 0·03-0·08). High-dose aciclovir was associated with less shedding than standard-dose valaciclovir (198 [4·2%] vs 209 [4·5%]; IRR 0·79, 95% CI 0·63-1·00). Shedding was less frequent in the high-dose valaciclovir group than in the standard-dose valaciclovir group (164 [3·3%] vs 292 [5·8%]; 0·54, 0·44-0·66). The number of episodes per person-year did not differ significantly for standard-dose valaciclovir (22·6) versus high-dose aciclovir (20·2; p=0·54), and standard-dose valaciclovir (14·9) versus high-dose valaciclovir (16·5; p=0·34), but did for no medication (28·7) and standard-dose aciclovir (10·0; p=0·001). Median episode duration was longer for no medication than for standard-dose aciclovir (13 h vs 7 h; p=0·01) and for standard-dose valaciclovir than for high-dose valaciclovir (10 h vs 7 h; p=0·03), but did not differ significantly between standard-dose valaciclovir and high-dose aciclovir (8 h vs 8 h; p=0·23). Likewise, maximum log(10) copies of HSV detected per mL was higher for no medication than for standard dose aciclovir (3·3 vs 2·9; p=0·02), and for standard-dose valaciclovir than for high-dose valaciclovir (2·5 vs 3·0; p=0·001), but no significant difference was recorded for standard-dose valaciclovir versus high-dose aciclovir (2·7 vs 2·8; p=0·66). 80% of episodes were subclinical in all study groups. Except for a higher frequency of headaches with high-dose valaciclovir (n=13, 30%) than with other regimens, all regimens were well tolerated. INTERPRETATION: Short bursts of subclinical genital HSV reactivation are frequent, even during high-dose antiherpes therapy, and probably account for continued transmission of HSV during suppressive antiviral therapy. More potent antiviral therapy is needed to eliminate HSV transmission. FUNDING: NIH. Valaciclovir was provided for trial 3 for free by GlaxoSmithKline.

PMID: 22225814 [PubMed - as supplied by publisher]

Group B streptococcal disease in infants.

Lancet. 2012 Jan 4;

Authors: Cotton MF, Rabie H

PMID: 22226045 [PubMed - as supplied by publisher]

Herpes simplex virus: a new era?

Lancet. 2012 Jan 4;

Authors: Van de Perre P, Nagot N

PMID: 22226046 [PubMed - as supplied by publisher]

Group B streptococcal disease in infants aged younger than 3 months: systematic review and meta-analysis.

Lancet. 2012 Jan 4;

Authors: Edmond KM, Kortsalioudaki C, Scott S, Schrag SJ, Zaidi AK, Cousens S, Heath PT

Abstract

BACKGROUND: Despite widespread use of intrapartum antibiotic prophylaxis, group B streptococcus remains a leading cause of morbidity and mortality in infants in Europe, the Americas, and Australia. However, estimates of disease burden in many countries outside of these regions is not available. We aimed to examine the current global burden of invasive disease and the serotype distribution of group B streptococcus isolates. METHODS: We searched Medline, Embase, and Wholis databases for studies on invasive early-onset (day 0-6) and late-onset (day 7-89) group B streptococcal disease. Eligible studies were those that described incidence, deaths, or serotypes. We also reviewed reference lists and contacted experts to seek unpublished data and data missed by our search. Random effects meta-analysis was used to pool data. FINDINGS: 74 studies met the inclusion criteria; 56 studies reported incidence, 29 case fatality, and 19 serotype distribution. An additional search for studies that reported serotype distribution from Jan 1, 1980, yielded a total of 38 articles. Only five low-income countries were represented in the review and contributed 5% weight to the meta-analysis. 47 (69%) studies reported use of any intrapartum antibiotic prophylaxis. Substantial heterogeneity existed between studies. Mean incidence of group B streptococcus in infants aged 0-89 days was 0·53 per 1000 livebirths (95% CI 0·44-0·62) and the mean case fatality ratio was 9·6% (95% CI 7·5-11·8). Incidence of early-onset group B streptococcus (0·43 per 1000 livebirths [95% CI 0·37-0·49]) and case fatality (12·1%, [6·2-18·3]) were two-times higher than late-onset disease. Serotype III (48·9%) was the most frequently identified serotype in all regions with available data followed by serotypes Ia (22·9%), Ib (7·0%), II (6·2%), and V (9·1%). Studies that reported use of any intrapartum antibiotic prophylaxis were associated with lower incidence of early-onset group B streptococcus (0·23 per 1000 livebirths [95% CI 0·13-0·59]) than studies in which patients did not use prophylaxis (0·75 per 1000 livebirths [0·58-0·89]). INTERPRETATION: More high-quality studies are needed to accurately estimate the global burden of group B streptococcus, especially in low-income countries. A conjugate vaccine incorporating five serotypes (Ia, Ib, II, III, V) could prevent most global group B streptococcal disease. FUNDING: Child Epidemiology Reference Group (CHERG), WHO.

PMID: 22226047 [PubMed - as supplied by publisher]

Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial.

Lancet. 2012 Jan 6;

Authors: Bang YJ, Kim YW, Yang HK, Chung HC, Park YK, Lee KH, Lee KW, Kim YH, Noh SI, Cho JY, Mok YJ, Kim YH, Ji J, Yeh TS, Button P, Sirzén F, Noh SH,

Abstract

BACKGROUND: D2 gastrectomy is recommended in US and European guidelines, and is preferred in east Asia, for patients with resectable gastric cancer. Adjuvant chemotherapy improves patient outcomes after surgery, but the benefits after a D2 resection have not been extensively investigated in large-scale trials. We investigated the effect on disease-free survival of adjuvant chemotherapy with capecitabine plus oxaliplatin after D2 gastrectomy compared with D2 gastrectomy only in patients with stage II-IIIB gastric cancer. METHODS: The capecitabine and oxaliplatin adjuvant study in stomach cancer (CLASSIC) study was an open-label, parallel-group, phase 3, randomised controlled trial undertaken in 37 centres in South Korea, China, and Taiwan. Patients with stage II-IIIB gastric cancer who had had curative D2 gastrectomy were randomly assigned to receive adjuvant chemotherapy of eight 3-week cycles of oral capecitabine (1000 mg/m(2) twice daily on days 1 to 14 of each cycle) plus intravenous oxaliplatin (130 mg/m(2) on day 1 of each cycle) for 6 months or surgery only. Block randomisation was done by a central interactive computerised system, stratified by country and disease stage. Patients, and investigators giving interventions, assessing outcomes, and analysing data were not masked. The primary endpoint was 3 year disease-free survival, analysed by intention to treat. This study reports a prespecified interim efficacy analysis, after which the trial was stopped after a recommendation by the data monitoring committee. The trial is registered at ClinicalTrials.gov (NCT00411229). FINDINGS: 1035 patients were randomised (520 to receive chemotherapy and surgery, 515 surgery only). Median follow-up was 34·2 months (25·4-41·7) in the chemotherapy and surgery group and 34·3 months (25·6-41·9) in the surgery only group. 3 year disease-free survival was 74% (95% CI 69-79) in the chemotherapy and surgery group and 59% (53-64) in the surgery only group (hazard ratio 0·56, 95% CI 0·44-0·72; p<0·0001). Grade 3 or 4 adverse events were reported in 279 of 496 patients (56%) in the chemotherapy and surgery group and in 30 of 478 patients (6%) in the surgery only group. The most common adverse events in the intervention group were nausea (n=326), neutropenia (n=300), and decreased appetite (n=294). INTERPRETATION: Adjuvant capecitabine plus oxaliplatin treatment after curative D2 gastrectomy should be considered as a treatment option for patients with operable gastric cancer. FUNDING: F Hoffmann-La Roche and Sanofi-Aventis.

PMID: 22226517 [PubMed - as supplied by publisher]

Adjuvant therapy for gastric cancer after D2 gastrectomy.

Lancet. 2012 Jan 6;

Authors: Nishida T

PMID: 22226518 [PubMed - as supplied by publisher]

Endocardial fibroelastosis of the heart.

Lancet. 2011 Dec 29;

Authors: Steger CM, Antretter H, Moser PL

PMID: 22217671 [PubMed - as supplied by publisher]

Recurrent aspiration and upper lobe cavitation.

Lancet. 2011 Dec 21;

Authors: Czapran A, Doherty M, Haddon A, Labib M

PMID: 22196831 [PubMed - as supplied by publisher]