Hot off the presses! Sep 12 Lancet

The Sep 12 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:

• Tomorrow's Doctors: an improvement if evaluated
  - Lancet 374(9693):851 (2009)
  
• Execution of prisoners with mental illnesses in Japan
  - Lancet 374(9693):852 (2009)
  
• Who should lead WHO EURO?
  - Lancet 374(9693):852 (2009)
  
• Young people: not as healthy as they seem
  - Lancet 374(9693):853-854 (2009)
  
• The deadly toll of S pneumoniae and H influenzae type b
  - Lancet 374(9693):854-856 (2009)
  
• Bone-marrow transplantation in non-malignant disease
  - Lancet 374(9693):856-858 (2009)
  
• The economic situation in South Africa and health inequities
  - Lancet 374(9693):858-859 (2009)
  
• Beyond HAART: scientists and activists need to work together
  - Lancet 374(9693):860-861 (2009)
  
• Consent for biobank tissue in somatic-cell nuclear transfer
  - Lancet 374(9693):861-863 (2009)
  
• Antenatal education programmes: do they work?
  - Lancet 374(9693):863-864 (2009)
  
• Five candidates compete for regional director of WHO EURO
  - Lancet 374(9693):865-867 (2009)
  
• Lead poisoning cases spark riots in China
  - Lancet 374(9693):868 (2009)
  
• A cinematic celebration of Charles Darwin
  - Lancet 374(9693):869-870 (2009)
  
• Eye-opening anecdotes
  - Lancet 374(9693):870 (2009)
  
• Quarraisha Abdool Karim: investigating HIV/AIDS in South Africa
  - Lancet 374(9693):871 (2009)
  
• The Death of Ivan Ilyich and pain relief at the end of life
  - Lancet 374(9693):872-873 (2009)
  
• Yury Verlinsky
  - Lancet 374(9693):874 (2009)
  
• The SERPING1 gene and age-related macular degeneration
  - Lancet 374(9693):875-876 (2009)
  
• The SERPING1 gene and age-related macular degeneration – Authors' reply
  - Lancet 374(9693):876-877 (2009)
  
• Aspirin in the primary prevention of vascular disease
  - Lancet 374(9693):877 (2009)
  
• Aspirin in the primary prevention of vascular disease
  - Lancet 374(9693):877-878 (2009)
  
• Aspirin in the primary prevention of vascular disease
  - Lancet 374(9693):878 (2009)
  
• Aspirin in the primary prevention of vascular disease
  - Lancet 374(9693):878-879 (2009)
  
• Aspirin in the primary prevention of vascular disease – ATT secretariat's reply
  - Lancet 374(9693):879 (2009)
  
• An academia–industry partnership
  - Lancet 374(9693):880 (2009)
  
• An academia–industry partnership
  - Lancet 374(9693):880 (2009)
  
• Department of Error
  - Lancet 374(9693):880 (2009)
  
• Department of Error
  - Lancet 374(9693):880 (2009)
  
• Global patterns of mortality in young people: a systematic analysis of population health data
  - Lancet 374(9693):881-892 (2009)
  Background Pronounced changes in patterns of health take place in adolescence and young adulthood, but the effects on mortality patterns worldwide have not been reported. We analysed worldwide rates and patterns of mortality between early adolescence and young adulthood. Methods We obtained data from the 2004 Global Burden of Disease Study, and used all-cause mortality estimates developed for the 2006 World Health Report, with adjustments for revisions in death from HIV/AIDS and from war and natural disasters. Data for cause of death were derived from national vital registration when available; for other countries we used sample registration data, verbal autopsy, and disease surveillance data to model causes of death. Worldwide rates and patterns of mortality were investigated by WHO region, income status, and cause in age-groups of 10–14 years, 15–19 years, and 20–24 years. Findings 2·6 million deaths occurred in people aged 10–24 years in 2004. 2·56 million (97%) of these deaths were in low-income and middle-income countries, and almost two thirds (1·67 million) were in sub-Saharan Africa and southeast Asia. Pronounced rises in mortality rates were recorded from early adolescence (10–14 years) to young adulthood (20–24 years), but reasons varied by region and sex. Maternal conditions were a leading cause of female deaths at 15%. HIV/AIDS and tuberculosis contributed to 11% of deaths. Traffic accidents were the largest cause and accounted for 14% of male and 5% of female deaths. Other prominent causes included violence (12% of male deaths) and suicide (6% of all deaths). Interpretation Present global priorities for adolescent health policy, which focus on HIV/AIDS and maternal mortality, are an important but insufficient response to prevent mortality in an age-group in which more than two in five deaths are due to intentional and unintentional injuries. Funding WHO and National Health and Medical Research Council.
• Burden of disease caused by Streptococcus pneumoniae in children younger than 5 years: global estimates
  - Lancet 374(9693):893-902 (2009)
  Background Streptococcus pneumoniae is a leading cause of bacterial pneumonia, meningitis, and sepsis in children worldwide. However, many countries lack national estimates of disease burden. Effective interventions are available, including pneumococcal conjugate vaccine and case management. To support local and global policy decisions on pneumococcal disease prevention and treatment, we estimated country-specific incidence of serious cases and deaths in children younger than 5 years. Methods We measured the burden of pneumococcal pneumonia by applying the proportion of pneumonia cases caused by S pneumoniae derived from efficacy estimates from vaccine trials to WHO country-specific estimates of all-cause pneumonia cases and deaths. We also estimated burden of meningitis and non-pneumonia, non-meningitis invasive disease using disease incidence and case-fatality data from a systematic literature review. When high-quality data were available from a country, these were used for national estimates. Otherwise, estimates were based on data from neighbouring countries with similar child mortality. Estimates were adjusted for HIV prevalence and access to care and, when applicable, use of vaccine against Haemophilus influenzae type b. Findings In 2000, about 14·5 million episodes of serious pneumococcal disease (uncertainty range 11·1–18·0 million) were estimated to occur. Pneumococcal disease caused about 826 000 deaths (582 000–926 000) in children aged 1–59 months, of which 91 000 (63 000–102 000) were in HIV-positive and 735 000 (519 000–825 000) in HIV-negative children. Of the deaths in HIV-negative children, over 61% (449 000 [316 000–501 000]) occurred in ten African and Asian countries. Interpretation S pneumoniae causes around 11% (8–12%) of all deaths in children aged 1–59 months (excluding pneumococcal deaths in HIV-positive children). Achievement of the UN Millennium Development Goal 4 for child mortality reduction can be accelerated by prevention and treatment of pneumococcal disease, especially in regions of the world with the greatest burden. Funding GAVI Alliance and the Vaccine Fund.
• Burden of disease caused by Haemophilus influenzae type b in children younger than 5 years: global estimates
  - Lancet 374(9693):903-911 (2009)
  Background Haemophilus influenzae type b (Hib) is a leading cause of childhood bacterial meningitis, pneumonia, and other serious infections. Hib disease can be almost completely eliminated through routine vaccination. We assessed the global burden of disease to help national policy makers and international donors set priorities. Methods We did a comprehensive literature search of studies of Hib disease incidence, case-fatality ratios, age distribution, syndrome distribution, and effect of Hib vaccine. We used vaccine trial data to estimate the proportion of pneumonia cases and pneumonia deaths caused by Hib. We applied these proportions to WHO country-specific estimates of pneumonia cases and deaths to estimate Hib pneumonia burden. We used data from surveillance studies to develop estimates of incidence and mortality of Hib meningitis and serious non-pneumonia, non-meningitis disease. If available, high-quality data were used for national estimates of Hib meningitis and non-pneumonia, non-meningitis disease burden. Otherwise, estimates were based on data from other countries matched as closely as possible for geographic region and child mortality. Estimates were adjusted for HIV prevalence and access to care. Disease burden was estimated for the year 2000 in children younger than 5 years. Findings We calculated that Hib caused about 8·13 million serious illnesses worldwide in 2000 (uncertainty range 7·33–13·2 million). We estimated that Hib caused 371 000 deaths (247 000–527 000) in children aged 1–59 months, of which 8100 (5600–10 000) were in HIV-positive and 363 000 (242 000–517 000) in HIV-negative children. Interpretation Global burden of Hib disease is substantial and almost entirely vaccine preventable. Expanded use of Hib vaccine could reduce childhood pneumonia and meningitis, and decrease child mortality. Funding Gavi Alliance and the Vaccine Fund.
• Haemopoietic stem-cell transplantation with antibody-based minimal-intensity conditioning: a phase 1/2 study
  - Lancet 374(9693):912-920 (2009)
  Background Stem-cell transplantation can cure primary immunodeficiencies. However, in patients with pre-existing organ toxicity, patients younger than 1 year, and those with DNA or telomere repair disorders, chemotherapy-based conditioning is poorly tolerated and results in major morbidity and mortality. We tested a novel antibody-based minimal-intensity conditioning (MIC) regimen to assess whether this approach allowed curative donor stem-cell engraftment without non-haemopoietic toxicity. Methods 16 high-risk patients underwent stem-cell transplantation for primary immunodeficiencies with an MIC regimen consisting of two rat anti-CD45 monoclonal antibodies YTH24.5 and YTH 54.12 for myelosuppression, and alemtuzumab (anti-CD52) and fludarabine, and low dose cyclophosphamide for immunosuppression. Donors were matched siblings (n=5), and matched (9) and mismatched (2) unrelated donors. Findings Antibody-based conditioning was well tolerated, with only two cases of grade 3 and no grade 4 toxicity. Rates of clinically significant acute (n=6, 36%) and chronic graft-versus-host disease (GVHD) (n=5, 31%) were acceptable. 15 of 16 patients (94%) engrafted, of whom 11 (69%) achieved full or high-level mixed chimerism in both lymphoid and myeloid lineages, and three achieved engraftment in the T-lymphoid lineage only. One patient needed retransplantation. At a median of 40 months post-transplant, 13 of 16 patients (81%) in this high-risk cohort were alive and cured from their underlying disease. Interpretation Monoclonal antibody-based conditioning seems well tolerated and can achieve curative engraftment even in patients with severe organ toxicity or DNA repair defects, or both. This novel approach represents a shift from the paradigm that intensive chemotherapy or radiotherapy, or both, is needed for donor stem-cell engraftment. This antibody-based conditioning regimen may reduce toxicity and late effects and enable SCT in virtually any primary immunodeficiency patient with a matched donor. Funding None.
• HIV infection and tuberculosis in South Africa: an urgent need to escalate the public health response
  - Lancet 374(9693):921-933 (2009)
  One of the greatest challenges facing post-apartheid South Africa is the control of the concomitant HIV and tuberculosis epidemics. HIV continues to spread relentlessly, and tuberculosis has been declared a national emergency. In 2007, South Africa, with 0·7% of the world's population, had 17% of the global burden of HIV infection, and one of the world's worst tuberculosis epidemics, compounded by rising drug resistance and HIV co-infection. Until recently, the South African Government's response to these diseases has been marked by denial, lack of political will, and poor implementation of policies and programmes. Nonetheless, there have been notable achievements in disease management, including substantial improvements in access to condoms, expansion of tuberculosis control efforts, and scale-up of free antiretroviral therapy (ART). Care for acutely ill AIDS patients and long-term provision of ART are two issues that dominate medical practice and the health-care sys! tem. Decisive action is needed to implement evidence-based priorities for the control of the HIV and tuberculosis epidemics. By use of the framework of the Strategic Plans for South Africa for tuberculosis and HIV/AIDS, we provide prioritised four-step approaches for tuberculosis control, HIV prevention, and HIV treatment. Strong leadership, political will, social mobilisation, adequate human and financial resources, and sustainable development of health-care services are needed for successful implementation of these approaches.
• The burden of non-communicable diseases in South Africa
  - Lancet 374(9693):934-947 (2009)
  15 years after its first democratic election, South Africa is in the midst of a profound health transition that is characterised by a quadruple burden of communicable, non-communicable, perinatal and maternal, and injury-related disorders. Non-communicable diseases are emerging in both rural and urban areas, most prominently in poor people living in urban settings, and are resulting in increasing pressure on acute and chronic health-care services. Major factors include demographic change leading to a rise in the proportion of people older than 60 years, despite the negative effect of HIV/AIDS on life expectancy. The burden of these diseases will probably increase as the roll-out of antiretroviral therapy takes effect and reduces mortality from HIV/AIDS. The scale of the challenge posed by the combined and growing burden of HIV/AIDS and non-communicable diseases demands an extraordinary response that South Africa is well able to provide. Concerted action is needed to st! rengthen the district-based primary health-care system, to integrate the care of chronic diseases and management of risk factors, to develop a national surveillance system, and to apply interventions of proven cost-effectiveness in the primary and secondary prevention of such diseases within populations and health services. We urge the launching of a national initiative to establish sites of service excellence in urban and rural settings throughout South Africa to trial, assess, and implement integrated care interventions for chronic infectious and non-communicable diseases.
• Poor reception?
  - Lancet 374(9693):948 (2009)