Hot off the presses! Jun 24 Lance

The Jun 24 issue of the Lance is now up on Pubget (About Lance): 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:

• A strategic revolution in HIV and global health
  - Lance 377(9783):2055 (2011)
  
• Health concerns of adolescents who are in a sexual minority
  - Lance 377(9783):2056 (2011)
  
• Russia's punitive drug laws
  - Lance 377(9783):2056 (2011)
  
• HPV vaccine effect: is the glass half full or half empty?
  - Lance 377(9783):2057-2058 (2011)
  
• The global burden of disease in 10–24-year-olds
  - Lance 377(9783):2058-2060 (2011)
  
• First-line treatment of advanced colorectal cancer
  - Lance 377(9783):2060-2062 (2011)
  
• Taxing tobacco profits to prevent the smoking epidemic
  - Lance 377(9783):2063-2064 (2011)
  
• China's primary health-care reform
  - Lance 377(9783):2064-2066 (2011)
  
• Health initiatives by Indigenous people in Australia
  - Lance 377(9783):2066-2067 (2011)
  
• Clinical Series and our clinical content
  - Lance 377(9783):2067 (2011)
  
• Offline: "The depth of the deception"?
  - Lance 377(9783):2068 (2011)
  
• Scalpel solidarity: surgery in Palestine
  - Lance 377(9783):2069-2070 (2011)
  
• Mental health care for US veterans heavily criticised
  - Lance 377(9783):2071-2072 (2011)
  
• Cast into the light
  - Lance 377(9783):2073-2074 (2011)
  
• A "difficult" patient's journey
  - Lance 377(9783):2074 (2011)
  
• Leonard Hayflick and the limits of ageing
  - Lance 377(9783):2075 (2011)
  
• Advance decisions, chronic mental illness, and everyday care
  - Lance 377(9783):2076-2077 (2011)
  
• Jürgen F J Kun
  - Lance 377(9783):2078 (2011)
  
• Open letter to Ulf Wiinberg, Chief Executive of Lundbeck Pharmaceuticals
  - Lance 377(9783):2079 (2011)
  
• Open letter to Ulf Wiinberg, Chief Executive of Lundbeck Pharmaceuticals – Response from Lundbeck
  - Lance 377(9783):2079 (2011)
  
• Belimumab for systemic lupus erythematosus
  - Lance 377(9783):2079-2080 (2011)
  
• Belimumab for systemic lupus erythematosus
  - Lance 377(9783):2080 (2011)
  
• Belimumab for systemic lupus erythematosus – Author's reply
  - Lance 377(9783):2080-2081 (2011)
  
• Milestones in treatment: the tipping point and the ResQ Trial
  - Lance 377(9783):2081-2082 (2011)
  
• Milestones in treatment: the tipping point and the ResQ Trial
  - Lance 377(9783):2082 (2011)
  
• Milestones in treatment: the tipping point and the ResQ Trial – Author's reply
  - Lance 377(9783):2082-2083 (2011)
  
• Social networking and health
  - Lance 377(9783):2083 (2011)
  
• Social networking and health
  - Lance 377(9783):2083 (2011)
  
• Facebook use leads to health-care reform in Taiwan
  - Lance 377(9783):2083-2084 (2011)
  
• Department of Error
  - Lance 377(9783):2084 (2011)
  
• Early effect of the HPV vaccination programme on cervical abnormalities in Victoria, Australia: an ecological study
  - Lance 377(9783):2085-2092 (2011)
  Background Australia introduced a human papillomavirus (HPV) vaccination programme with the quadrivalent HPV vaccine for all women aged 12–26 years between 2007 and 2009. We analysed trends in cervical abnormalities in women in Victoria, Australia, before and after introduction of the vaccination programme. Methods With data from the Victorian Cervical Cytology Registry between 2003 and 2009, we compared the incidence of histopathologically defined high-grade cervical abnormalities (HGAs, lesions coded as cervical intraepithelial neoplasia of grade 2 or worse or adenocarcinoma in situ; primary outcome) and low-grade cytological abnormalities (LGAs) in five age groups before (Jan 1, 2003, to March 31, 2007) and after (April 1, 2007, to Dec 31, 2009) the vaccination programme began. Binary comparisons between the two periods were done with Fisher's exact test. Poisson piecewise regression analysis was used to compare incident rate trends. Findings After the introduction of the vaccination programme, we recorded a decrease in the incidence of HGAs by 0·38% (95% CI 0·61–0·16) in girls younger than 18 years. This decrease was progressive and significantly different to the linear trend in incidence before introduction of the vaccination (incident rate ratio 1·14, 1·00–1·30, p=0·05). No similar temporal decline was recorded for LGAs or in older age groups. Interpretation This is the first report of a decrease in incidence of HGAs within 3 years after the implementation of a population-wide HPV vaccination programme. Linkage between vaccination and screening registers is needed to confirm that this ecological observation is attributable to vaccination and to monitor participation in screening among vaccinated women. Funding None.
• Global burden of disease in young people aged 10–24 years: a systematic analysis
  - Lance 377(9783):2093-2102 (2011)
  Background Young people aged 10–24 years represent 27% of the world's population. Although important health problems and risk factors for disease in later life emerge in these years, the contribution to the global burden of disease is unknown. We describe the global burden of disease arising in young people and the contribution of risk factors to that burden. Methods We used data from WHO's 2004 Global Burden of Disease study. Cause-specific disability-adjusted life-years (DALYs) for young people aged 10–24 years were estimated by WHO region on the basis of available data for incidence, prevalence, severity, and mortality. WHO member states were classified into low-income, middle-income, and high-income countries, and into WHO regions. We estimated DALYs attributable to specific global health risk factors using the comparative risk assessment method. DALYs were divided into years of life lost because of premature mortality (YLLs) and years lost because of disability (YLDs), and are presented for regions by sex and by 5-year age groups. Findings The total number of incident DALYs in those aged 10–24 years was about 236 million, representing 15·5% of total DALYs for all age groups. Africa had the highest rate of DALYs for this age group, which was 2·5 times greater than in high-income countries (208 vs 82 DALYs per 1000 population). Across regions, DALY rates were 12% higher in girls than in boys between 15 and 19 years (137 vs 153). Worldwide, the three main causes of YLDs for 10–24-year-olds were neuropsychiatric disorders (45%), unintentional injuries (12%), and infectious and parasitic diseases (10%). The main risk factors for incident DALYs in 10–24-year-olds were alcohol (7% of DALYs), unsafe sex (4%), iron deficiency (3%), lack of contraception (2%), and illicit drug use (2%). Interpretation The health of young people has been largely neglected in global public health because this age group is perceived as healthy. However, opportunities for prevention of disease and injury in this age group are not fully exploited. The findings from this study suggest that adolescent health would benefit from increased public health attention. Funding None.
• Addition of cetuximab to oxaliplatin-based first-line combination chemotherapy for treatment of advanced colorectal cancer: results of the randomised phase 3 MRC COIN trial
  - Lance 377(9783):2103-2114 (2011)
  Background In the Medical Research Council (MRC) COIN trial, the epidermal growth factor receptor (EGFR)-targeted antibody cetuximab was added to standard chemotherapy in first-line treatment of advanced colorectal cancer with the aim of assessing effect on overall survival. Methods In this randomised controlled trial, patients who were fit for but had not received previous chemotherapy for advanced colorectal cancer were randomly assigned to oxaliplatin and fluoropyrimidine chemotherapy (arm A), the same combination plus cetuximab (arm B), or intermittent chemotherapy (arm C). The choice of fluoropyrimidine therapy (capecitabine or infused fluouroracil plus leucovorin) was decided before randomisation. Randomisation was done centrally (via telephone) by the MRC Clinical Trials Unit using minimisation. Treatment allocation was not masked. The comparison of arms A and C is described in a companion paper. Here, we present the comparison of arm A and B, for which the primary outcome was overall survival in patients with KRAS wild-type tumours. Analysis was by intention to treat. Further analyses with respect to NRAS, BRAF, and EGFR status were done. The trial is registered, ISRCTN27286448. Findings 1630 patients were randomly assigned to treatment groups (815 to standard therapy and 815 to addition of cetuximab). Tumour samples from 1316 (81%) patients were used for somatic molecular analyses; 565 (43%) had KRAS mutations. In patients with KRAS wild-type tumours (arm A, n=367; arm B, n=362), overall survival did not differ between treatment groups (median survival 17·9 months [IQR 10·3–29·2] in the control group vs 17·0 months [9·4–30·1] in the cetuximab group; HR 1·04, 95% CI 0·87–1·23, p=0·67). Similarly, there was no effect on progression-free survival (8·6 months [IQR 5·0–12·5] in the control group vs 8·6 months [5·1–13·8] in the cetuximab group; HR 0·96, 0·82–1·12, p=0·60). Overall response rate increased from 57% (n=209) with chemotherapy alone to 64% (n=232) with addition of cetuximab (p=0·049). Grade 3 and higher skin and gastrointestinal toxic effects were increased with cetuximab (14 vs 114 and 67 vs 97 patients in the control! group vs the cetuximab group with KRAS wild-type tumours, respectively). Overall survival differs by somatic mutation status irrespective of treatment received: BRAF mutant, 8·8 months (IQR 4·5–27·4); KRAS mutant, 14·4 months (8·5–24·0); all wild-type, 20·1 months (11·5–31·7). Interpretation This trial has not confirmed a benefit of addition of cetuximab to oxaliplatin-based chemotherapy in first-line treatment of patients with advanced colorectal cancer. Cetuximab increases response rate, with no evidence of benefit in progression-free or overall survival in KRAS wild-type patients or even in patients selected by additional mutational analysis of their tumours. The use of cetuximab in combination with oxaliplatin and capecitabine in first-line chemotherapy in patients with widespread metastases cannot be recommended. Funding Cancer Research UK, Cancer Research Wales, UK Medical Research Council, Merck KGgA.
• Osteoarthritis: an update with relevance for clinical practice
  - Lance 377(9783):2115-2126 (2011)
  Osteoarthritis is thought to be the most prevalent chronic joint disease. The incidence of osteoarthritis is rising because of the ageing population and the epidemic of obesity. Pain and loss of function are the main clinical features that lead to treatment, including non-pharmacological, pharmacological, and surgical approaches. Clinicians recognise that the diagnosis of osteoarthritis is established late in the disease process, maybe too late to expect much help from disease-modifying drugs. Despite efforts over the past decades to develop markers of disease, still-imaging procedures and biochemical marker analyses need to be improved and possibly extended with more specific and sensitive methods to reliably describe disease processes, to diagnose the disease at an early stage, to classify patients according to their prognosis, and to follow the course of disease and treatment effectiveness. In the coming years, a better definition of osteoarthritis is expected by de! lineating different phenotypes of the disease. Treatment targeted more specifically at these phenotypes might lead to improved outcomes.
• Spondyloarthritis
  - Lance 377(9783):2127-2137 (2011)
  Spondyloarthritis is a group of several related but phenotypically distinct disorders: psoriatic arthritis, arthritis related to inflammatory bowel disease, reactive arthritis, a subgroup of juvenile idiopathic arthritis, and ankylosing spondylitis (the prototypic and best studied subtype). The past decade yielded major advances in the recognition of spondyloarthritis as an entity, the classification of the disease, and understanding of the genetic and pathophysiological mechanisms of disease-related inflammation and tissue damage. In parallel, new clinical and imaging outcomes have allowed the assessment of various therapeutic modalities. Blockers of tumour necrosis factor are a major therapeutic advance, but the exact roles of physiotherapy, and treatment with non-steroidal anti-inflammatory drugs and other biological treatments are unknown. The major challenges with direct relevance for clinical practice for the next decade are the development of techniques for earl! y diagnosis, therapeutic modulation of structural damage, and, ultimately, induction of long-term, drug-free remission.
• Juvenile idiopathic arthritis
  - Lance 377(9783):2138-2149 (2011)
  Juvenile idiopathic arthritis is a heterogeneous group of diseases characterised by arthritis of unknown origin with onset before age of 16 years. Pivotal studies in the past 5 years have led to substantial progress in various areas, ranging from disease classification to new treatments. Gene expression profiling studies have identified different immune mechanisms in distinct subtypes of the disease, and can help to redefine disease classification criteria. Moreover, immunological studies have shown that systemic juvenile idiopathic arthritis is an acquired autoinflammatory disease, and have led to successful studies of both interleukin-1 and interleukin-6 blockade. In other forms of the disease, synovial inflammation is the consequence of a disturbed balance between proinflammatory effector cells (such as T-helper-17 cells), and anti-inflammatory regulatory cells (such as FOXP3-positive regulatory T cells). Moreover, specific soluble biomarkers (S100 proteins) can gui! de individual treatment. Altogether these new developments in genetics, immunology, and imaging are instrumental to better define, classify, and treat patients with juvenile idiopathic arthritis.
• Return of the usual suspect
  - Lance 377(9783):2150 (2011)