Hot off the presses! Jan 13 The Lancet

The Jan 13 issue of the The Lancet is now up on Pubget (About The 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:

• January 7â€"13, 2012
  - The Lancet 379(9810):i (2012)
  
• Translational research and experimental medicine in 2012
  - The Lancet 379(9810):1 (2012)
  
• Addictionâ€"a global problem with no global solution
  - The Lancet 379(9810):2 (2012)
  
• North Koreaâ€"who will help?
  - The Lancet 379(9810):2 (2012)
  
• Catheter-directed thrombolysis for acute DVT
  - The Lancet 379(9810):3-4 (2012)
  
• Treatment of prostate cancer metastases: more than semantics
  - The Lancet 379(9810):4-6 (2012)
  
• The control of non-communicable diseases in rural Iran
  - The Lancet 379(9810):6-7 (2012)
  
• Contracts with patients in clinical practice
  - The Lancet 379(9810):7-9 (2012)
  
• Human security and universal health insurance
  - The Lancet 379(9810):9-10 (2012)
  
• The remaining smallpox stocks: the healthiest outcome
  - The Lancet 379(9810):10-12 (2012)
  
• Science and consensus for health policy making in Japan
  - The Lancet 379(9810):12-13 (2012)
  
• Offline: Rearranging the furniture
  - The Lancet 379(9810):14 (2012)
  
• Innovating for every woman and every child
  - The Lancet 379(9810):e1-e2 (2012)
  
• Commitment and action to boost health workforce
  - The Lancet 379(9810):e2-e4 (2012)
  
• Legalise assisted suicide, UK Commission urges
  - The Lancet 379(9810):15 (2012)
  
• Haiti prepares for cholera vaccination but concerns remain
  - The Lancet 379(9810):16 (2012)
  
• Prescription drug addiction: the treatment challenge
  - The Lancet 379(9810):17-18 (2012)
  
• Anatomy of an artist
  - The Lancet 379(9810):19 (2012)
  
• Creatively confronting addiction
  - The Lancet 379(9810):20 (2012)
  
• Louisa Degenhardt: hooked on addiction research
  - The Lancet 379(9810):21 (2012)
  
• The rise, fall, and revival of recovery in drug policy
  - The Lancet 379(9810):22-23 (2012)
  
• Paul Robert Epstein
  - The Lancet 379(9810):24 (2012)
  
• An open letter to Michael Ball, Chief Executive of Hospira Pharmaceuticals
  - The Lancet 379(9810):25 (2012)
  
• An open letter to Michael Ball, Chief Executive of Hospira Pharmaceuticals â€" Response from Hospira
  - The Lancet 379(9810):25 (2012)
  
• The new decade of vaccines
  - The Lancet 379(9810):25-26 (2012)
  
• The new decade of vaccines
  - The Lancet 379(9810):26 (2012)
  
• The new decade of vaccines â€" Authors' reply
  - The Lancet 379(9810):27 (2012)
  
• The new decade of vaccines â€" Authors' reply
  - The Lancet 379(9810):27 (2012)
  
• Global burden of disease in young people aged 10â€"24 years
  - The Lancet 379(9810):27-28 (2012)
  
• Global burden of disease in young people aged 10â€"24 years â€" Authors' reply
  - The Lancet 379(9810):28 (2012)
  
• Global burden of disease in young people aged 10â€"24 years â€" Authors' reply
  - The Lancet 379(9810):29 (2012)
  
• Misleading information concerning the University of Helsinki
  - The Lancet 379(9810):29 (2012)
  
• The NHS IT project: more than just a bad dream
  - The Lancet 379(9810):29-30 (2012)
  
• The unobtainable placebo: control of independent clinical research by industry?
  - The Lancet 379(9810):30 (2012)
  
• Department of Error
  - The Lancet 379(9810):30 (2012)
  
• Long-term outcome after additional catheter-directed thrombolysis versus standard treatment for acute iliofemoral deep vein thrombosis (the CaVenT study): a randomised controlled trial
  - The Lancet 379(9810):31-38 (2012)
  Background Conventional anticoagulant treatment for acute deep vein thrombosis (DVT) effectively prevents thrombus extension and recurrence, but does not dissolve the clot, and many patients develop post-thrombotic syndrome (PTS). We aimed to examine whether additional treatment with catheter-directed thrombolysis (CDT) using alteplase reduced development of PTS. Methods Participants in this open-label, randomised controlled trial were recruited from 20 hospitals in the Norwegian southeastern health region. Patients aged 18–75 years with a first-time iliofemoral DVT were included within 21 days from symptom onset. Patients were randomly assigned (1:1) by picking lowest number of sealed envelopes to conventional treatment alone or additional CDT. Randomisation was stratified for involvement of the pelvic veins with blocks of six. We assessed two co-primary outcomes: frequency of PTS as assessed by Villalta score at 24 months, and iliofemoral patency after 6 months. Analyses were by intention to treat. This trial is registered at ClinicalTrials.gov, NCT00251771. Findings 209 patients were randomly assigned to treatment groups (108 control, 101 CDT). At completion of 24 months' follow-up, data for clinical status were available for 189 patients (90%; 99 control, 90 CDT). At 24 months, 37 (41·1%, 95% CI 31·5–51·4) patients allocated additional CDT presented with PTS compared with 55 (55·6%, 95% CI 45·7–65·0) in the control group (p=0·047). The difference in PTS corresponds to an absolute risk reduction of 14·4% (95% CI 0·2–27·9), and the number needed to treat was 7 (95% CI 4–502). Iliofemoral patency after 6 months was reported in 58 patients (65·9%, 95% CI 55·5–75·0) on CDT versus 45 (47·4%, 37·6–57·3) on control (p=0·012). 20 bleeding complications related to CDT included three major and five clinically relevant bleeds. Interpretation Additional CDT should be considered in patients with a high proximal DVT and low risk of bleeding. Funding South-Eastern Norway Regional Health Authority; Research Council of Norway; University of Oslo; Oslo University Hospital.
• Denosumab and bone-metastasis-free survival in men with castration-resistant prostate cancer: results of a phase 3, randomised, placebo-controlled trial
  - The Lancet 379(9810):39-46 (2012)
  Background Bone metastases are a major cause of morbidity and mortality in men with prostate cancer. Preclinical studies suggest that osteoclast inhibition might prevent bone metastases. We assessed denosumab, a fully human anti-RANKL monoclonal antibody, for prevention of bone metastasis or death in non-metastatic castration-resistant prostate cancer. Methods In this phase 3, double-blind, randomised, placebo-controlled study, men with non-metastatic castration-resistant prostate cancer at high risk of bone metastasis (prostate-specific antigen [PSA] ≥8·0 μg/L or PSA doubling time ≤10·0 months, or both) were enrolled at 319 centres from 30 countries. Patients were randomly assigned (1:1) via an interactive voice response system to receive subcutaneous denosumab 120 mg or subcutaneous placebo every 4 weeks. Randomisation was stratified by PSA eligibility criteria and previous or ongoing chemotherapy for prostate cancer. Patients, investigators, and all people involved in study conduct were masked to treatment allocation. The primary endpoint was bone-metastasis-free survival, a composite endpoint determined by time to first occurrence of bone metastasis (symptomatic or asymptomatic) or death from any cause. Efficacy analysis was by intention to treat. The masked treatment phase of the trial has been completed. This trial ! was registered at ClinicalTrials.gov, number NCT00286091. Findings 1432 patients were randomly assigned to treatment groups (716 denosumab, 716 placebo). Denosumab significantly increased bone-metastasis-free survival by a median of 4·2 months compared with placebo (median 29·5 [95% CI 25·4–33·3] vs 25·2 [22·2–29·5] months; hazard ratio [HR] 0·85, 95% CI 0·73–0·98, p=0·028). Denosumab also significantly delayed time to first bone metastasis (33·2 [95% CI 29·5–38·0] vs 29·5 [22·4–33·1] months; HR 0·84, 95% CI 0·71–0·98, p=0·032). Overall survival did not differ between groups (denosumab, 43·9 [95% CI 40·1–not estimable] months vs placebo, 44·8 [40·1–not estimable] months; HR 1·01, 95% CI 0·85–1·20, p=0·91). Rates of adverse events and serious adverse events were similar in both groups, except for osteonecrosis of the jaw and hypocalcaemia. 33 (5%) patients on denosumab developed osteonecrosis of the jaw versus none on placebo. Hypocalcaemia occurred in 12 (2%) patients on denosumab and two (<1%)! on placebo. Interpretation This large randomised study shows that targeting of the bone microenvironment can delay bone metastasis in men with prostate cancer. Funding Amgen Inc.
• Effectiveness of diabetes and hypertension management by rural primary health-care workers (Behvarz workers) in Iran: a nationally representative observational study
  - The Lancet 379(9810):47-54 (2012)
  Background Non-communicable diseases and their risk factors are leading causes of disease burden in Iran and other middle-income countries. Little evidence exists for whether the primary health-care system can effectively manage non-communicable diseases and risk factors at the population level. Our aim was to examine the effectiveness of the Iranian rural primary health-care system (the Behvarz system) in the management of diabetes and hypertension, and to assess whether the effects depend on the number of health-care workers in the community. Methods We used individual-level data from the 2005 Non-Communicable Disease Surveillance Survey (NCDSS) for fasting plasma glucose (FPG) and systolic blood pressure (SBP), body-mass index, medication use, and sociodemographic variables. Data for Behvarz-worker and physician densities were from the 2006 Population and Housing Census and the 2005 Outpatient Care Centre Mapping Survey. We assessed the effectiveness of treatment on FPG and SBP, and associations between FPG or SBP and Behvarz-worker density with two statistical approaches: a mixed-effects regression analysis of the full NCDSS sample adjusting for individual-level and community-level covariates and an analysis that estimated average treatment effect on data balanced with propensity score matching. Results NCDSS had data for 65 619 individuals aged 25 years or older (11 686 of whom in rural areas); of these, 64 694 (11 521 in rural areas) had data for SBP and 50 202 (9337 in rural areas) had data for FPG. Nationally, 39·2% (95% CI 37·7 to 40·7) of individuals with diabetes and 35·7% (34·9 to 36·5) of those with hypertension received treatment, with higher treatment coverage in women than in men and in urban areas than in rural areas. Treatment lowered mean FPG by an estimated 1·34 mmol/L (0·58 to 2·10) in rural areas and 0·21 mmol/L (−0·15 to 0·56) in urban areas. Individuals in urban areas with hypertension who received treatment had 3·8 mm Hg (3·1 to 4·5) lower SBP than they would have had if they had not received treatment; the treatment effect was 2·5 mm Hg (1·1 to 3·9) lower FPG in rural areas. Each additional Behvarz worker per 1000 adults was associated with a 0·09 mmol/L (0·01 to 0·18) lower district-level avera! ge FPG (p=0·02); for SBP this effect was 0·53 mm Hg (−0·44 to 1·50; p=0·28). Our findings were not sensitive to the choice of statistical method. Interpretation Primary care systems with trained community health-care workers and well established guidelines can be effective in non-communicable disease prevention and management. Iran's primary care system should expand the number and scope of its primary health-care worker programmes to also address blood pressure and to improve performance in areas with few primary care personnel. Funding None.
• Extent of illicit drug use and dependence, and their contribution to the global burden of disease
  - The Lancet 379(9810):55-70 (2012)
  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.
• Drug policy and the public good: evidence for effective interventions
  - The Lancet 379(9810):71-83 (2012)
  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.
• How well do international drug conventions protect public health?
  - The Lancet 379(9810):84-91 (2012)
  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 i! nvolved 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.
• Recurrent aspiration and upper lobe cavitation
  - The Lancet 379(9810):92 (2012)