Hot off the presses! May 30 Lancet

The May 30 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:

• Urgent: a UK Commission on Child Protection
  - Lancet 373(9678):1819 (2009)
  
• The UK's appalling failure to tackle HIV
  - Lancet 373(9678):1820 (2009)
  
• Chagas disease: a neglected emergency
  - Lancet 373(9678):1820 (2009)
  
• Aspirin in primary prevention: sex and baseline risk matter
  - Lancet 373(9678):1821-1822 (2009)
  
• Scratching the surface of ignorance on MDR tuberculosis
  - Lancet 373(9678):1822-1824 (2009)
  
• Physical and occupational therapy during sedation stops
  - Lancet 373(9678):1824-1826 (2009)
  
• Child marriage in India: a tradition with alarming implications
  - Lancet 373(9678):1826-1827 (2009)
  
• Working with WHO: the UK's institutional strategy
  - Lancet 373(9678):1827-1829 (2009)
  
• Improving social policy and practice: knowledge matters
  - Lancet 373(9678):1829-1831 (2009)
  
• The paediatric analgesia wheel: are you ready to roll?
  - Lancet 373(9678):1831-1832 (2009)
  
• Gazan patients targeted for interrogation
  - Lancet 373(9678):1833 (2009)
  
• China clamps down on controversial therapies
  - Lancet 373(9678):1834-1835 (2009)
  
• West African meningitis outbreak strains vaccine supplies
  - Lancet 373(9678):1836 (2009)
  
• Bodies and obesity
  - Lancet 373(9678):1837-1838 (2009)
  
• Surgeons making smiles
  - Lancet 373(9678):1838 (2009)
  
• Christine Laine: embracing the challenges of medical journalism
  - Lancet 373(9678):1839 (2009)
  
• Dying and choosing
  - Lancet 373(9678):1840-1841 (2009)
  
• I Herbert Scheinberg
  - Lancet 373(9678):1842 (2009)
  
• Health in the occupied Palestinian territories
  - Lancet 373(9678):1843 (2009)
  
• Health in the occupied Palestinian territories
  - Lancet 373(9678):1843 (2009)
  
• Health in the occupied Palestinian territories
  - Lancet 373(9678):1843-1844 (2009)
  
• Health in the occupied Palestinian territories
  - Lancet 373(9678):1844 (2009)
  
• Health in the occupied Palestinian territories – Author's reply
  - Lancet 373(9678):1844-1845 (2009)
  
• Prasugrel STEMI subgroup analysis
  - Lancet 373(9678):1845-1846 (2009)
  
• Prasugrel STEMI subgroup analysis
  - Lancet 373(9678):1846 (2009)
  
• Prasugrel STEMI subgroup analysis
  - Lancet 373(9678):1846 (2009)
  
• Prasugrel STEMI subgroup analysis – Authors' reply
  - Lancet 373(9678):1846-1848 (2009)
  
• Threshold for starting antiretroviral therapy: should there be one?
  - Lancet 373(9678):1848 (2009)
  
• Department of Error
  - Lancet 373(9678):1848 (2009)
  
• Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials
  - Lancet 373(9678):1849-1860 (2009)
  Background Low-dose aspirin is of definite and substantial net benefit for many people who already have occlusive vascular disease. We have assessed the benefits and risks in primary prevention. Methods We undertook meta-analyses of serious vascular events (myocardial infarction, stroke, or vascular death) and major bleeds in six primary prevention trials (95 000 individuals at low average risk, 660 000 person-years, 3554 serious vascular events) and 16 secondary prevention trials (17 000 individuals at high average risk, 43 000 person-years, 3306 serious vascular events) that compared long-term aspirin versus control. We report intention-to-treat analyses of first events during the scheduled treatment period. Findings In the primary prevention trials, aspirin allocation yielded a 12% proportional reduction in serious vascular events (0·51% aspirin vs 0·57% control per year, p=0·0001), due mainly to a reduction of about a fifth in non-fatal myocardial infarction (0·18% vs 0·23% per year, p<0·0001). The net effect on stroke was not significant (0·20% vs 0·21% per year, p=0·4: haemorrhagic stroke 0·04% vs 0·03%, p=0·05; other stroke 0·16% vs 0·18% per year, p=0·08). Vascular mortality did not differ significantly (0·19% vs 0·19% per year, p=0·7). Aspirin allocation increased major gastrointestinal and extracranial bleeds (0·10% vs 0·07% per year, p<0·0001), and the main risk factors for coronary disease were also risk factors for bleeding. In the secondary prevention trials, aspirin allocation yielded a greater absolute reduction in serious vascular events (6·7% vs 8·2% per year, p<0.0001), with a non-significant increase in haemorrhagic stroke but reductions of about a fifth in total stroke (2·08% vs 2·54% per year, p=0·002) and in coronary events (4·3% vs 5·3% per year, p<0·0001). In both primary and secondary prevention trials, the proportional reductions in the aggregate of all serious vascular events seemed similar for men and women. Interpretation In primary prevention without previous disease, aspirin is of uncertain net value as the reduction in occlusive events needs to be weighed against any increase in major bleeds. Further trials are in progress. Funding UK Medical Research Council, British Heart Foundation, Cancer Research UK, and the European Community Biomed Programme.
• Epidemiology of antituberculosis drug resistance 2002–07: an updated analysis of the Global Project on Anti-Tuberculosis Drug Resistance Surveillance
  - Lancet 373(9678):1861-1873 (2009)
  Background The Global Project on Anti-Tuberculosis Drug Resistance has been gathering data since 1994. This study provides the latest data on the extent of drug resistance worldwide. Methods Data for drug susceptibility were gathered from 90 726 patients in 83 countries and territories between 2002 and 2007. Standardised collection of results enabled comparison both between and within countries. Where possible, data for HIV status and resistance to second-line drugs were also obtained. Laboratory data were quality assured by the Supranational Tuberculosis Reference Laboratory Network. Findings The median prevalence of resistance to any drug in new cases of tuberculosis was 11·1% (IQR 7·0–22·3). The prevalence of multidrug resistance in new tuberculosis cases ranged from 0% in eight countries to 7% in two provinces in China, 11·1% in Northern Mariana Islands (although reporting only two cases), and between 6·8% and 22·3% in nine countries of the former Soviet Union, including 19·4% in Moldova and 22·3% in Baku, Azerbaijan (median for countries surveyed 1·6%, IQR 0·6–3·9). Trend analysis showed that between 1994 and 2007, the prevalence of multidrug-resistant (MDR) tuberculosis in new cases increased substantially in South Korea and in Tomsk Oblast and Orel Oblast, Russia, but was stable in Estonia and Latvia. The prevalence of MDR tuberculosis in all tuberculosis cases decreased in Hong Kong and the USA. 37 countries and territories reported representative data on extensively drug-resistant (XDR) tuberculosis. Five countries, all from the former Sovie t Union, reported 25 cases or more of XDR tuberculosis each, with prevalence among MDR-tuberculosis cases ranging between 6·6% and 23·7%. Interpretation MDR tuberculosis remains a threat to tuberculosis control in provinces in China and countries of the former Soviet Union. Data on drug resistance are unavailable in many countries, especially in Africa, emphasising the need to develop easier methods for surveillance of resistance in tuberculosis. Funding Global Project: United States Agency for International Development and Eli Lilly and Company. Drug resistance surveys: national tuberculosis programmes, the Government of the Netherlands, the Global Fund to Fight AIDS, Tuberculosis and Malaria, Japan International Cooperation Agency, and Kreditanstalt für Wiederaufbau.
• Early physical and occupational therapy in mechanically ventilated, critically ill patients: a randomised controlled trial
  - Lancet 373(9678):1874-1882 (2009)
  Background Long-term complications of critical illness include intensive care unit (ICU)-acquired weakness and neuropsychiatric disease. Immobilisation secondary to sedation might potentiate these problems. We assessed the efficacy of combining daily interruption of sedation with physical and occupational therapy on functional outcomes in patients receiving mechanical ventilation in intensive care. Methods Sedated adults (≥18 years of age) in the ICU who had been on mechanical ventilation for less than 72 h, were expected to continue for at least 24 h, and who met criteria for baseline functional independence were eligible for enrolment in this randomised controlled trial at two university hospitals. We randomly assigned 104 patients by computer-generated, permuted block randomisation to early exercise and mobilisation (physical and occupational therapy) during periods of daily interruption of sedation (intervention; n=49) or to daily interruption of sedation with therapy as ordered by the primary care team (control; n=55). The primary endpoint—the number of patients returning to independent functional status at hospital discharge—was defined as the ability to perform six activities of daily living and the ability to walk independently. Therapists who undertook patient assessments were blinded to treatment assignment. Secondary endpoints included duration of delirium and ventilator-free days during the first 28 days of hospital stay. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00322010. Findings All 104 patients were included in the analysis. Return to independent functional status at hospital discharge occurred in 29 (59%) patients in the intervention group compared with 19 (35%) patients in the control group (p=0·02; odds ratio 2·7 [95% CI 1·2–6·1]). Patients in the intervention group had shorter duration of delirium (median 2·0 days, IQR 0·0–6·0 vs 4·0 days, 2·0–8·0; p=0·02), and more ventilator-free days (23·5 days, 7·4–25·6 vs 21·1 days, 0·0–23·8; p=0·05) during the 28-day follow-up period than did controls. There was one serious adverse event in 498 therapy sessions (desaturation less than 80%). Discontinuation of therapy as a result of patient instability occurred in 19 (4%) of all sessions, most commonly for perceived patient-ventilator asynchrony. Interpretation A strategy for whole-body rehabilitation—consisting of interruption of sedation and physical and occupational therapy in the earliest days of critical illness—was safe and well tolerated, and resulted in better functional outcomes at hospital discharge, a shorter duration of delirium, and more ventilator-free days compared with standard care. Funding None.
• Prevalence of child marriage and its effect on fertility and fertility-control outcomes of young women in India: a cross-sectional, observational study
  - Lancet 373(9678):1883-1889 (2009)
  Background Child marriage is a substantial barrier to social and economic development in India, and a primary concern for women's health. We assessed the prevalence of child marriage—ie, before 18 years of age—in young adult women in India, and the associations between child marriage and women's fertility and fertility-control outcomes. Methods Data from the National Family Health Survey-3 (2005–06) were limited to a sample of Indian women aged 20–24 years (n=22 807), of whom 14 813 had been or were presently married (ever-married). Prevalence of child marriage was estimated for the whole sample. We used regression models adjusted for demographics, and models adjusted for demographics and duration of marriage to estimate odds ratios (ORs) for the associations between child marriage and both fertility and fertility-control outcomes, in the ever-married subsample. Findings 44·5% of women aged 20–24 years were married before age 18 years, 22·6% were married before age 16 years, and 2·6% were married before age 13 years. Child marriage was significantly associated with no contraceptive use before first childbirth (adjusted OR 1·37 [95% CI 1·22–1·54]), high fertility (three or more births) (7·40 [6·45–8·50]), a repeat childbirth in less than 24 months (3·00 [2·74–3·29]), multiple unwanted pregnancies (2·36 [1·90–2·94]), pregnancy termination (1·48 [1·34–1·63]), and female sterilisation (6·68 [5·78–7·60]). The association between child marriage and high fertility, a repeat childbirth in less than 24 months, multiple unwanted pregnancies, pregnancy termination, and sterilisation all remained significant after controlling for duration of marriage. Interpretation Increased enforcement of existing policies is crucial for prevention of child marriage. Improved family-planning education, access, and support are urgently needed for women married as children, their husbands, and their families to reduce the high fertility and poor fertility-control outcomes of this practice. Funding US National Institutes of Health and Indian Council of Medical Research.
• A swallowed denture
  - Lancet 373(9678):1890 (2009)
  
• Cystic fibrosis
  - Lancet 373(9678):1891-1904 (2009)
  Cystic fibrosis is the most common lethal genetic disease in white populations. The outlook for patients with the disease has improved steadily over many years, largely as a result of earlier diagnosis, more aggressive therapy, and provision of care in specialised centres. Researchers now have a more complete understanding of the molecular–biological defect that underlies cystic fibrosis, which is leading to new approaches to treatment. One of these treatments, hypertonic saline, is already in use, whereas others are in advanced stages of development. We review clinical care for cystic fibrosis and discuss recent advances in the understanding of its pathogenesis, implementation of screening of neonates, and development of therapies aimed at treating the basic defect.
• Glucocorticoid resistance in inflammatory diseases
  - Lancet 373(9678):1905-1917 (2009)
  Glucocorticoid resistance or insensitivity is a major barrier to the treatment of several common inflammatory diseases—including chronic obstructive pulmonary disease and acute respiratory distress syndrome; it is also an issue for some patients with asthma, rheumatoid arthritis, and inflammatory bowel disease. Several molecular mechanisms of glucocorticoid resistance have now been identified, including activation of mitogen-activated protein (MAP) kinase pathways by certain cytokines, excessive activation of the transcription factor activator protein 1, reduced histone deacetylase-2 (HDAC2) expression, raised macrophage migration inhibitory factor, and increased P-glycoprotein-mediated drug efflux. Patients with glucocorticoid resistance can be treated with alternative broad-spectrum anti-inflammatory treatments, such as calcineurin inhibitors and other immunomodulators, or novel anti-inflammatory treatments, such as inhibitors of phosphodiesterase 4 or nuclear facto r κB, although these drugs are all likely to have major side-effects. An alternative treatment strategy is to reverse glucocorticoid resistance by blocking its underlying mechanisms. Some examples of this approach are inhibition of p38 MAP kinase, use of vitamin D to restore interleukin-10 response, activation of HDAC2 expression by use of theophylline, antioxidants, or phosphoinositide-3-kinase-δ inhibitors, and inhibition of macrophage migration inhibitory factor and P-glycoprotein.
• When chewing gum is more than just a bad habit
  - Lancet 373(9678):1918 (2009)