Hot off the presses! Aug 05 Lancet

The Aug 05 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:

• Improvement of care for young disabled people in Australia
  - Lancet 378(9789):373 (2011)
  
• Public health in Wales: a nation comes of age
  - Lancet 378(9789):374 (2011)
  
• Science journalism: a delicate balancing act
  - Lancet 378(9789):374 (2011)
  
• Antidepressant treatment in Alzheimer's disease
  - Lancet 378(9789):375-376 (2011)
  
• New hope for immune intervention therapy in type 1 diabetes
  - Lancet 378(9789):376-378 (2011)
  
• Scaling up breastfeeding in developing countries
  - Lancet 378(9789):378-380 (2011)
  
• Salt reduction lowers cardiovascular risk: meta-analysis of outcome trials
  - Lancet 378(9789):380-382 (2011)
  
• Will the Decade of Vaccines mean business as usual?
  - Lancet 378(9789):382-385 (2011)
  
• Public–private collaboration in vaccine research
  - Lancet 378(9789):385-386 (2011)
  
• Hope for young disabled Australians in elderly care homes
  - Lancet 378(9789):387-388 (2011)
  
• USA focuses on Ebola vaccine but research gaps remain
  - Lancet 378(9789):389 (2011)
  
• Risky business: children at work
  - Lancet 378(9789):390 (2011)
  
• Portraits of pain
  - Lancet 378(9789):391 (2011)
  
• Samuel Shem
  - Lancet 378(9789):392 (2011)
  
• A bug's life
  - Lancet 378(9789):392 (2011)
  
• Mohammed Keshtgar—a pioneering surgical oncologist
  - Lancet 378(9789):393 (2011)
  
• The cultural evolution of natural birth
  - Lancet 378(9789):394-395 (2011)
  
• David French
  - Lancet 378(9789):396 (2011)
  
• Rapid diagnostic protocol for patients with chest pain
  - Lancet 378(9789):397 (2011)
  
• Rapid diagnostic protocol for patients with chest pain
  - Lancet 378(9789):397 (2011)
  
• Rapid diagnostic protocol for patients with chest pain
  - Lancet 378(9789):398 (2011)
  
• Rapid diagnostic protocol for patients with chest pain
  - Lancet 378(9789):398 (2011)
  
• Rapid diagnostic protocol for patients with chest pain – Authors' reply
  - Lancet 378(9789):398-399 (2011)
  
• Febrile convulsions after seasonal influenza immunisation in UK
  - Lancet 378(9789):399-400 (2011)
  
• Febrile convulsions after seasonal influenza immunisation in UK – Authors' reply
  - Lancet 378(9789):400 (2011)
  
• Free health care in Sierra Leone: a mite too optimistic?
  - Lancet 378(9789):400-401 (2011)
  
• Free health care in Sierra Leone: a mite too optimistic? – Author's reply
  - Lancet 378(9789):401 (2011)
  
• Sharing research data to improve public health: a perspective from the global south
  - Lancet 378(9789):401-402 (2011)
  
• Fifty years of evolution of the term Down's syndrome
  - Lancet 378(9789):402 (2011)
  
• Department of Error
  - Lancet 378(9789):402 (2011)
  
• Department of Error
  - Lancet 378(9789):402 (2011)
  
• Sertraline or mirtazapine for depression in dementia (HTA-SADD): a randomised, multicentre, double-blind, placebo-controlled trial
  - Lancet 378(9789):403-411 (2011)
  Background Depression is common in dementia but the evidence base for appropriate drug treatment is sparse and equivocal. We aimed to assess efficacy and safety of two of the most commonly prescribed drugs, sertraline and mirtazapine, compared with placebo. Methods We undertook the parallel-group, double-blind, placebo-controlled, Health Technology Assessment Study of the Use of Antidepressants for Depression in Dementia (HTA-SADD) trial in participants from old-age psychiatry services in nine centres in England. Participants were eligible if they had probable or possible Alzheimer's disease, depression (lasting ≥4 weeks), and a Cornell scale for depression in dementia (CSDD) score of 8 or more. Participants were ineligible if they were clinically critical (eg, suicide risk), contraindicated to study drugs, on antidepressants, in another trial, or had no carer. The clinical trials unit at King's College London (UK) randomly allocated participants with a computer-generated block randomisation sequence, stratified by centre, with varying block sizes, in a 1:1:1 ratio to receive sertraline (target dose 150 mg per day), mirtazapine (45 mg), or placebo (control group), all with standard care. The primary outcome was reduction in depressio! n (CSDD score) at 13 weeks (outcomes to 39 weeks were also assessed), assessed with a mixed linear-regression model adjusted for baseline CSDD, time, and treatment centre. This study is registered, number ISRCTN88882979 and EudraCT 2006-000105-38. Findings Decreases in depression scores at 13 weeks did not differ between 111 controls and 107 participants allocated to receive sertraline (mean difference 1·17, 95% CI −0·23 to 2·58; p=0·10) or mirtazapine (0·01, −1·37 to 1·38; p=0·99), or between participants in the mirtazapine and sertraline groups (1·16, −0·25 to 2·57; p=0·11); these findings persisted to 39 weeks. Fewer controls had adverse reactions (29 of 111 [26%]) than did participants in the sertraline group (46 of 107, 43%; p=0·010) or mirtazapine group (44 of 108, 41%; p=0·031), and fewer serious adverse events rated as severe (p=0·003). Five patients in every group died by week 39. Interpretation Because of the absence of benefit compared with placebo and increased risk of adverse events, the present practice of use of these antidepressants, with usual care, for first-line treatment of depression in Alzheimer's disease should be reconsidered. Funding UK National Institute of Health Research HTA Programme.
• Co-stimulation modulation with abatacept in patients with recent-onset type 1 diabetes: a randomised, double-blind, placebo-controlled trial
  - Lancet 378(9789):412-419 (2011)
  Background The immunopathogenesis of type 1 diabetes mellitus is associated with T-cell autoimmunity. To be fully active, immune T cells need a co-stimulatory signal in addition to the main antigen-driven signal. Abatacept modulates co-stimulation and prevents full T-cell activation. We evaluated the effect of abatacept in recent-onset type 1 diabetes. Methods In this multicentre, double-blind, randomised controlled trial, patients aged 6–45 years recently diagnosed with type 1 diabetes were randomly assigned (2:1) to receive abatacept (10 mg/kg, maximum 1000 mg per dose) or placebo infusions intravenously on days 1, 14, 28, and monthly for a total of 27 infusions over 2 years. Computer-generated permuted block randomisation was used, with a block size of 3 and stratified by participating site. Neither patients nor research personnel were aware of treatment assignments. The primary outcome was baseline-adjusted geometric mean 2-h area-under-the-curve (AUC) serum C-peptide concentration after a mixed-meal tolerance test at 2 years' follow-up. Analysis was by intention to treat for all patients for whom data were available. This trial is registered at ClinicalTrials.gov, NCT00505375. Findings 112 patients were assigned to treatment groups (77 abatacept, 35 placebo). Adjusted C-peptide AUC was 59% (95% CI 6·1–112) higher at 2 years with abatacept (n=73, 0·378 nmol/L) than with placebo (n=30, 0·238 nmol/L; p=0·0029). The difference between groups was present throughout the trial, with an estimated 9·6 months' delay (95% CI 3·47–15·6) in C-peptide reduction with abatacept. There were few infusion-related adverse events (36 reactions occurred in 17 [22%] patients on abatacept and 11 reactions in six [17%] on placebo). There was no increase in infections (32 [42%] patients on abatacept vs 15 [43%] on placebo) or neutropenia (seven [9%] vs five [14%]). Interpretation Co-stimulation modulation with abatacept slowed reduction in β-cell function over 2 years. The beneficial effect suggests that T-cell activation still occurs around the time of clinical diagnosis of type 1 diabetes. Yet, despite continued administration of abatacept over 24 months, the decrease in β-cell function with abatacept was parallel to that with placebo after 6 months of treatment, causing us to speculate that T-cell activation lessens with time. Further observation will establish whether the beneficial effect continues after cessation of abatacept infusions. Funding US National Institutes of Health.
• Exclusive breastfeeding promotion by peer counsellors in sub-Saharan Africa (PROMISE-EBF): a cluster-randomised trial
  - Lancet 378(9789):420-427 (2011)
  Background Exclusive breastfeeding (EBF) is reported to be a life-saving intervention in low-income settings. The effect of breastfeeding counselling by peer counsellors was assessed in Africa. Methods 24 communities in Burkina Faso, 24 in Uganda, and 34 in South Africa were assigned in a 1:1 ratio, by use of a computer-generated randomisation sequence, to the control or intervention clusters. In the intervention group, we scheduled one antenatal breastfeeding peer counselling visit and four post-delivery visits by trained peers. The data gathering team were masked to the intervention allocation. The primary outcomes were prevalance of EBF and diarrhoea reported by mothers for infants aged 12 weeks and 24 weeks. Country-specific prevalence ratios were adjusted for cluster effects and sites. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00397150. Findings 2579 mother–infant pairs were assigned to the intervention or control clusters in Burkina Faso (n=392 and n=402, respectively), Uganda (n=396 and n=369, respectively), and South Africa (n=535 and 485, respectively). The EBF prevalences based on 24-h recall at 12 weeks in the intervention and control clusters were 310 (79%) of 392 and 139 (35%) of 402, respectively, in Burkina Faso (prevalence ratio 2·29, 95% CI 1·33–3·92); 323 (82%) of 396 and 161 (44%) of 369, respectively, in Uganda (1·89, 1·70–2·11); and 56 (10%) of 535 and 30 (6%) of 485, respectively, in South Africa (1·72, 1·12–2·63). The EBF prevalences based on 7-day recall in the intervention and control clusters were 300 (77%) and 94 (23%), respectively, in Burkina Faso (3·27, 2·13–5·03); 305 (77%) and 125 (34%), respectively, in Uganda (2·30, 2·00–2·65); and 41 (8%) and 19 (4%), respectively, in South Africa (1·98, 1·30–3·02). At 24 weeks, the prevalences based on 24-h recall were 2! 86 (73%) in the intervention cluster and 88 (22%) in the control cluster in Burkina Faso (3·33, 1·74–6·38); 232 (59%) and 57 (15%), respectively, in Uganda (3·83, 2·97–4·95); and 12 (2%) and two (<1%), respectively, in South Africa (5·70, 1·33–24·26). The prevalences based on 7-day recall were 279 (71%) in the intervention cluster and 38 (9%) in the control cluster in Burkina Faso (7·53, 4·42–12·82); 203 (51%) and 41 (11%), respectively, in Uganda (4·66, 3·35–6·49); and ten (2%) and one (<1%), respectively, in South Africa (9·83, 1·40–69·14). Diarrhoea prevalence at age 12 weeks in the intervention and control clusters was 20 (5%) and 36 (9%), respectively, in Burkina Faso (0·57, 0·27–1·22); 39 (10%) and 32 (9%), respectively, in Uganda (1·13, 0·81–1·59); and 45 (8%) and 33 (7%), respectively, in South Africa (1·16, 0·78–1·75). The prevalence at age 24 weeks in the intervention and control clusters was 26 (7%) and 32 (8%), respec! tively, in Burkina Faso (0·83, 0·45–1·54); 52 (13%) and 5! 9 (16%), respectively, in Uganda (0·82, 0·58–1·15); and 54 (10%) and 33 (7%), respectively, in South Africa (1·31, 0·89–1·93). Interpretation Low-intensity individual breastfeeding peer counselling is achievable and, although it does not affect the diarrhoea prevalence, can be used to effectively increase EBF prevalence in many sub-Saharan African settings. Funding European Union Sixth Framework International Cooperation–Developing Countries, Research Council of Norway, Swedish International Development Cooperation Agency, Norwegian Programme for Development, Research and Education, South African National Research Foundation, and Rockefeller Brothers Foundation.
• Vaccine production, distribution, access, and uptake
  - Lancet 378(9789):428-438 (2011)
  For human vaccines to be available on a global scale, complex production methods, meticulous quality control, and reliable distribution channels are needed to ensure that the products are potent and effective at the point of use. The technologies used to manufacture different types of vaccines can strongly affect vaccine cost, ease of industrial scale-up, stability, and, ultimately, worldwide availability. The complexity of manufacturing is compounded by the need for different formulations in different countries and age-groups. Reliable vaccine production in appropriate quantities and at affordable prices is the cornerstone of developing global vaccination policies. However, to ensure optimum access and uptake, strong partnerships are needed between private manufacturers, regulatory authorities, and national and international public health services. For vaccines whose supply is insufficient to meet demand, prioritisation of target groups can increase the effect of thes! e vaccines. In this report, we draw from our experience of vaccine development and focus on influenza vaccines as an example to consider production, distribution, access, and other factors that affect vaccine uptake and population-level effectiveness.
• The future of immunisation policy, implementation, and financing
  - Lancet 378(9789):439-448 (2011)
  Vaccines have already saved many lives and they have the potential to save many more as increasingly elaborate technologies deliver new and effective vaccines against both infectious diseases—for which there are currently no effective licensed vaccines—such as malaria, tuberculosis, and HIV and non-infectious diseases such as hypertension and diabetes. However, these new vaccines are likely to be more complex and expensive than those that have been used so effectively in the past, and they could have a multifaceted effect on the disease that they are designed to prevent, as has already been seen with pneumococcal conjugate vaccines. Deciding which new vaccines a country should invest in requires not only sound advice from international organisations such as WHO but also a well informed national immunisation advisory committee with access to appropriate data for local disease burden. Introduction of vaccines might need modification of immunisation schedules and deli! very procedures. Novel methods are needed to finance the increasing number of new vaccines that have the potential to save lives in countries that are too poor to afford them. Here, we discuss some options.
• UN High-Level Meeting on Non-Communicable Diseases: addressing four questions
  - Lancet 378(9789):449-455 (2011)
  Non-communicable diseases (NCDs), principally heart disease, stroke, cancer, diabetes, and chronic respiratory diseases, are a global crisis and require a global response. Despite the threat to human development, and the availability of affordable, cost-effective, and feasible interventions, most countries, development agencies, and foundations neglect the crisis. The UN High-Level Meeting (UN HLM) on NCDs in September, 2011, is an opportunity to stimulate a coordinated global response to NCDs that is commensurate with their health and economic burdens. To achieve the promise of the UN HLM, several questions must be addressed. In this report, we present the realities of the situation by answering four questions: is there really a global crisis of NCDs; how is NCD a development issue; are affordable and cost-effective interventions available; and do we really need high-level leadership and accountability? Action against NCDs will support other global health and developm! ent priorities. A successful outcome of the UN HLM depends on the heads of states and governments attending the meeting, and endorsing and implementing the commitments to action. Long-term success requires inspired and committed national and international leadership.
• An acutely confused young woman
  - Lancet 378(9789):456 (2011)