Hot off the presses! Aug 06 LANCET

The Aug 06 issue of the LANCET is now up on Pubget (About LANCET): if you're at a subscribing institution, just click the link in the latest link at the home page. (Note you'll only be able to get all the PDFs in the issue if your institution subscribes to Pubget.)

Latest Articles Include:

• Home birth—proceed with caution
  - LANCET 376(9738):303 (2010)
  
• The science and practice of HIV prevention
  - LANCET 376(9738):304 (2010)
  
• Delays in UK stroke prevention
  - LANCET 376(9738):304 (2010)
  
• Dissociating HDL cholesterol from cardiovascular risk
  Hausenloy DJ Opie L Yellon DM - LANCET 376(9738):305-306 (2010)
  
• Untreated HIV: harmful even at high CD4 cell counts
  Bassett IV Sax PE - LANCET 376(9738):306-308 (2010)
  
• NO for preterm infants at risk of bronchopulmonary dysplasia
  Sosenko IR Bancalari E - LANCET 376(9738):308-310 (2010)
  
• Vienna Declaration: a call for evidence-based drug policies
  Wood E Werb D Kazatchkine M Kerr T Hankins C Gorna R Nutt D Des Jarlais D Barré-Sinoussi F Montaner J - LANCET 376(9738):310-312 (2010)
  
• HIV and women who use drugs: double neglect, double risk
  El-Bassel N Terlikbaeva A Pinkham S - LANCET 376(9738):312-314 (2010)
  
• The double-helix derailed: the story of the BRCA patent
  - LANCET 376(9738):314-315 (2010)
  
• Offline: The following day, no one died
  - LANCET 376(9738):316 (2010)
  
• The future of the International AIDS Society
  - LANCET 376(9738):317 (2010)
  
• North Korea's health system in disarray
  - LANCET 376(9738):318 (2010)
  
• Norway rethinks law on use of electronic patients' records
  - LANCET 376(9738):319 (2010)
  
• Antiretroviral vaginal gel shows promise against HIV
  - LANCET 376(9738):320 (2010)
  
• Abortion: the view from both sides of the street
  - LANCET 376(9738):321 (2010)
  
• Understanding the misfit
  - LANCET 376(9738):322 (2010)
  
• Jean William Pape: GHESKIO founder and Gates Award winner
  - LANCET 376(9738):323 (2010)
  
• The Validus Medicus and a new gold standard
  - LANCET 376(9738):324-325 (2010)
  
• David Hazell Clark
  - LANCET 376(9738):326 (2010)
  
• Carotid artery stenting versus endarterectomy for carotid stenosis
  - LANCET 376(9738):327 (2010)
  
• Carotid artery stenting versus endarterectomy for carotid stenosis
  - LANCET 376(9738):327 (2010)
  
• Carotid artery stenting versus endarterectomy for carotid stenosis – Authors' reply
  - LANCET 376(9738):327-328 (2010)
  
• Human papillomavirus vaccine coverage
  - LANCET 376(9738):328-329 (2010)
  
• Human papillomavirus vaccine coverage
  - LANCET 376(9738):329-330 (2010)
  
• Human papillomavirus vaccine coverage – Author's reply
  - LANCET 376(9738):330 (2010)
  
• Colorectal cancer
  - LANCET 376(9738):330 (2010)
  
• Colorectal cancer
  - LANCET 376(9738):331 (2010)
  
• Colorectal cancer – Authors' reply
  - LANCET 376(9738):331-332 (2010)
  
• Clinical Trials Directive: better regulation required now
  - LANCET 376(9738):332 (2010)
  
• Department of Error
  - LANCET 376(9738):332 (2010)
  
• Department of Error
  - LANCET 376(9738):332 (2010)
  
• HDL cholesterol and residual risk of first cardiovascular events after treatment with potent statin therapy: an analysis from the JUPITER trial
  Ridker PM Genest J Boekholdt SM Libby P Gotto AM Nordestgaard BG Mora S Macfadyen JG Glynn RJ Kastelein JJ for the JUPITER Trial Study Group - LANCET 376(9738):333-339 (2010)
  Background HDL-cholesterol concentrations are inversely associated with occurrence of cardiovascular events. We addressed, using the JUPITER trial cohort, whether this association remains when LDL-cholesterol concentrations are reduced to the very low ranges with high-dose statin treatment. Methods Participants in the randomised placebo-controlled JUPITER trial were adults without diabetes or previous cardiovascular disease, and had baseline concentrations of LDL cholesterol of less than 3·37 mmol/L and high-sensitivity C-reactive protein of 2 mg/L or more. Participants were randomly allocated by a computer-generated sequence to receive rosuvastatin 20 mg per day or placebo, with participants and adjudicators masked to treatment assignment. In the present analysis, we divided the participants into quartiles of HDL-cholesterol or apolipoprotein A1 and sought evidence of association between these quartiles and the JUPITER primary endpoint of first non-fatal myocardial infarction or stroke, hospitalisation for unstable angina, arterial revascularisation, or cardiovascular death. This trial is registered with ClinicalTrials.gov, number NCT00239681. Findings For 17 802 patients in the JUPITER trial, rosuvastatin 20 mg per day reduced the incidence of the primary endpoint by 44% (p<0·0001). In 8901 (50%) patients given placebo (who had a median on-treatment LDL-cholesterol concentration of 2·80 mmol/L [IQR 2·43–3·24]), HDL-cholesterol concentrations were inversely related to vascular risk both at baseline (top quartile vs bottom quartile hazard ratio [HR] 0·54, 95% CI 0·35–0·83, p=0·0039) and on-treatment (0·55, 0·35–0·87, p=0·0047). By contrast, among the 8900 (50%) patients given rosuvastatin 20 mg (who had a median on-treatment LDL-cholesterol concentration of 1·42 mmol/L [IQR 1·14–1·86]), no significant relationships were noted between quartiles of HDL-cholesterol concentration and vascular risk either at baseline (1·12, 0·62–2·03, p=0·82) or on-treatment (1·03, 0·57–1·87, p=0·97). Our analyses for apolipoprotein A1 showed an equivalent strong relation to frequency of primary outcomes in the! placebo group but little association in the rosuvastatin group. Interpretation Although measurement of HDL-cholesterol concentration is useful as part of initial cardiovascular risk assessment, HDL-cholesterol concentrations are not predictive of residual vascular risk among patients treated with potent statin therapy who attain very low concentrations of LDL cholesterol. Funding AstraZeneca.
• Death rates in HIV-positive antiretroviral-naive patients with CD4 count greater than 350 cells per μL in Europe and North America: a pooled cohort observational study
  Study Group on Death Rates at High CD4 Count in Antiretroviral Naive Patients - LANCET 376(9738):340-345 (2010)
  Background Whether people living with HIV who have not received antiretroviral therapy (ART) and have high CD4 cell counts have higher mortality than the general population is unknown. We aimed to examine this by analysis of pooled data from industrialised countries. Methods We merged data on demographics, CD4 cell counts, viral-load measurements, hepatitis C co-infection status, smoking status, date of death, and whether death was AIDS-related or not from 23 European and North American cohorts. We calculated standardised mortality ratios (SMRs) standardised by age, sex, and year, stratifying by risk group. Data were included for patients aged 20–59 years who had at least one CD4 count greater than 350 cells per μL while ART naive. All pre-ART CD4 counts greater than 350 cells per μL from January, 1990, to December, 2004, were included. We investigated mortality for four risk groups—men who have sex with men, heterosexual people, injecting drug users, and those at other or unknown risk. The association between CD4 cell count and death rate was investigated by use of Poisson regression methods. Findings Data were analysed for 40 830 patients contributing 80 682 person-years of follow-up. Of 419 deaths, 401 were used in the SMR analysis: 100 men who have sex with men (SMR 1·30, 95% CI 1·06–1·58); 68 heterosexual people (2·94, 2·28–3·73); 203 injecting drug users (9·37, 8·13–10·75); and 30 in the other or unknown risk category (4·57, 3·09–6·53). Compared with CD4 counts of 350–499 cells per μL, death rate was lower in patients with counts of 500–699 cells per μL (adjusted rate ratio 0·77, 95% CI 0·61–0·95) and counts of 700 cells per μL (0·66, 0·52–0·85). Interpretation In HIV-infected ART-naive patients with high CD4 cell counts, death rates were raised compared with the general population. In men who have sex with men this was modest, suggesting that a substantial proportion of the increased risk in other groups is due to confounding by other factors. Even though the increased risk is small, new studies of potential benefits of ART in this group are merited. Funding European Commission, FP6. European AIDS Treatment Network (NEAT). Project number LSHP-CT-2006-037570.
• Inhaled nitric oxide for prevention of bronchopulmonary dysplasia in premature babies (EUNO): a randomised controlled trial
  Mercier JC Hummler H Durrmeyer X Sanchez-Luna M Carnielli V Field D Greenough A Van Overmeire B Jonsson B Hallman M Baldassarre J for the EUNO Study Group - LANCET 376(9738):346-354 (2010)
  Background In animal models, inhaled nitric oxide improved gas exchange and lung structural development, but its use in premature infants at risk of developing bronchopulmonary dysplasia remains controversial. We therefore tested the hypothesis that inhaled nitric oxide at a low concentration, started early and maintained for an extended period in babies with mild respiratory failure, might reduce the incidence of bronchopulmonary dysplasia. Methods 800 preterm infants with a gestational age at birth of between 24 weeks and 28 weeks plus 6 days (inclusive), weighing at least 500 g, requiring surfactant or continuous positive airway pressure for respiratory distress syndrome within 24 h of birth were randomly assigned in a one-to-one ratio to inhaled nitric oxide (5 parts per million) or placebo gas (nitrogen gas) for a minimum of 7 days and a maximum of 21 days in a double-blind study done at 36 centres in nine countries in the European Union. Care providers and investigators were masked to the computer-generated treatment assignment. The primary outcome was survival without development of bronchopulmonary dysplasia at postmenstrual age 36 weeks. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00551642. Findings 399 infants were assigned to inhaled nitric oxide, and 401 to placebo. 395 and 400, respectively, were analysed. Treatment with inhaled nitric oxide and placebo did not result in significant differences in survival of infants without development of bronchopulmonary dysplasia (258 [65%] of 395 vs 262 [66%] of 400, respectively; relative risk 1·05, 95% CI 0·78–1·43); in survival at 36 weeks' postmenstrual age (343 [86%) of 399 vs 359 [90%] of 401, respectively; 0·74, 0·48–1·15); and in development of bronchopulmonary dysplasia (81 [24%] of 339 vs 96 [27%] of 358, respectively; 0·83, 0·58–1·17). Interpretation Early use of low-dose inhaled nitric oxide in very premature babies did not improve survival without bronchopulmonary dysplasia or brain injury, suggesting that such a preventive treatment strategy is unsuccessful. Funding INO Therapeutics.
• Treatment and care for injecting drug users with HIV infection: a review of barriers and ways forward
  Wolfe D Carrieri MP Shepard D - LANCET 376(9738):355-366 (2010)
  We review evidence for effectiveness, cost-effectiveness, and coverage of antiretroviral therapy (ART) for injecting drug users (IDUs) infected with HIV, with particular attention to low-income and middle-income countries. In these countries, nearly half (47%) of all IDUs infected with HIV are in five nations—China, Vietnam, Russia, Ukraine, and Malaysia. In all five countries, IDU access to ART is disproportionately low, and systemic and structural obstacles restrict treatment access. IDUs are 67% of cumulative HIV cases in these countries, but only 25% of those receiving ART. Integration of ART with opioid substitution and tuberculosis treatment, increased peer engagement in treatment delivery, and reform of harmful policies—including police use of drug-user registries, detention of drug users in centres offering no evidence-based treatment, and imprisonment for possession of drugs for personal use—are needed to improve ART coverage of IDUs.
• Treatment of medical, psychiatric, and substance-use comorbidities in people infected with HIV who use drugs
  Altice FL Kamarulzaman A Soriano VV Schechter M Friedland GH - LANCET 376(9738):367-387 (2010)
  HIV-infected drug users have increased age-matched morbidity and mortality compared with HIV-infected people who do not use drugs. Substance-use disorders negatively affect the health of HIV-infected drug users, who also have frequent medical and psychiatric comorbidities that complicate HIV treatment and prevention. Evidence-based treatments are available for the management of substance-use disorders, mental illness, HIV and other infectious complications such as viral hepatitis and tuberculosis, and many non-HIV-associated comorbidities. Tuberculosis co-infection in HIV-infected drug users, including disease caused by drug-resistant strains, is acquired and transmitted as a consequence of inadequate prescription of antiretroviral therapy, poor adherence, and repeated interfaces with congregate settings such as prisons. Medication-assisted therapies provide the strongest evidence for HIV treatment and prevention efforts, yet are often not available where they are need! ed most. Antiretroviral therapy, when prescribed and adherence is at an optimum, improves health-related outcomes for HIV infection and many of its comorbidities, including tuberculosis, viral hepatitis, and renal and cardiovascular disease. Simultaneous clinical management of multiple comorbidities in HIV-infected drug users might result in complex pharmacokinetic drug interactions that must be adequately addressed. Moreover, interventions to improve adherence to treatment, including integration of health services delivery, are needed. Multifaceted, interdisciplinary approaches are urgently needed to achieve parity in health outcomes in HIV-infected drug users.
• Pneumonia's link with the head and heart
  - LANCET 376(9738):388 (2010)