The Lancet

• [Articles] Effect of palliative oxygen versus room air in relief of breathlessness in patients with refractory dyspnoea: a double-blind, randomised controlled trial
  Palliative oxygen therapy is widely used for treatment of dyspnoea in individuals with life-limiting illness who are ineligible for long-term oxygen therapy. We assessed the effectiveness of oxygen compared with room air delivered by nasal cannula for relief of breathlessness in this population of patients.
  
  
• [Correspondence] Antitrypanosomal agents: treatment or threat? – Authors' reply
  Allergic dermatitis, the most common adverse effect of benznidazole, is self-limiting, usually of mild-to-moderate intensity, easily manageable with corticosteroids, and in most patients does not require interruption of therapy. Polyneuropathy (5–10% of patients) occurs late in the treatment course, is dose-dependent, can be avoided by decreasing the cumulative or daily dose of benznidazole (≤300 mg/day), and is always reversible. Serious side-effects, such as bone-marrow depression, are extremely rare (<0·1–0·5%). The possible mutagenic effects of benznidazole and nifurtimox have been described only in animals. Of thousands of patients treated in several countries for many decades, this effect has never been directly linked to either nifurtimox or benznidazole.
  
  
• [Editorial] Stigmatisation of problem-drug users
  William S Burroughs II, the American Beat Generation author, published Junkie: Confessions of an Unredeemed Drug Addict in 1953 about life dependent on heroin (some editions use Junky). Junk was a slang term for heroin, possibly from users being seen as the “junk of society”, an early use of a stigmatising phrase.
  
  
• [Editorial] Physician, know thyself
  “No religion, no politics”, reads the sign above the bar in one of north London's otherwise very accommodating public houses, and it is a rule that all the customers seem happy to abide by. In a culturally pluralist society, there are areas of shared public life in which the respect for personal autonomy that defines most democracies in the developed world precludes any intrusion by politics or religion, which are so often seen as wellsprings of division. Medicine in developed countries is a secular profession, and it is taken somewhat ironically as an article of faith that a doctor's religious beliefs will have no influence on his or her professional judgment.
  
  
• [Editorial] Perils of asthma research in vulnerable groups
  To coincide with the annual European Respiratory Society meeting, in Barcelona, on Sept 18–22, The Lancet today focuses on asthma and respiratory diseases. WHO estimates that asthma affects 300 million people worldwide, and vulnerable groups—particularly children and elderly people—can be especially difficult to treat. Two Reviews in this issue focus on these groups, for which asthma is associated with substantial morbidity and mortality, and is characterised by scarce data from research.
  
  
• [Correspondence] The Lancet–Palestinian Health Alliance
  The Lancet–Palestinian Health Alliance (July 3, p 7) provides unfortunate evidence that a political agenda inexorably debases medical science. There are many regions of the world with far more pressing public health problems than those experienced in Gaza, the West Bank, and the portions of Jerusalem occupied by Jordan between 1948 and 1967. But given this prominent effort by The Lancet, one would at least hope for reasonable science by investigators committed to objective evaluation of data.
  
  
• [Comment] Perioperative respiratory complications in children
  Respiratory events are a major risk for perioperative morbidity and cause 30% of perioperative cardiac arrests in children. In The Lancet today, Britta von Ungern-Sternberg and colleagues present a prospective cohort of more than 9000 children who had had general anaesthesia in a single children's hospital. The investigators evaluated specific details in the children's history (with the International Study Group for Asthma and Allergies in Childhood [ISAAC] questionnaire), demographic data, and anaesthetic management, and correlated these variables with occurrence of perioperative respiratory adverse events. Multivariate analysis showed that airway sensitivity, eczema, a family history of airway disorders, and anaesthetic management statistically contributed to the risk of such events. Although today's results are mostly consistent with previous studies, they do raise questions.
  
  
• [Review] Management of severe asthma in children
  Children who are referred to specialist care with asthma that does not respond to treatment (problematic severe asthma) are a heterogeneous group, with substantial morbidity. The evidence base for management is sparse, and is mostly based on data from studies in children with mild and moderate asthma and on extrapolation of data from studies in adults with severe asthma. In many children with severe asthma, the diagnosis is wrong or adherence to treatment is poor. The first step is a detailed diagnostic assessment to exclude an alternative diagnosis (“not asthma at all”), followed by a multidisciplinary approach to exclude comorbidities (“asthma plus”) and to assess whether the child has difficult asthma (improves when the basic management needs, such as adherence and inhaler technique, are corrected) or true, therapy-resistant asthma (still symptomatic even when the basic management needs are resolved). In particular, environmental causes of secondary steroid resistance should be identified. An individualised treatment plan should be devised depending on the clinical and pathophysiological characterisation. Licensed therapeutic approaches include high-dose inhaled steroids, the Symbicort maintenance and reliever (SMART) regimen (with budesonide and formoterol fumarate), and anti-IgE therapy. Unlicensed treatments include methotrexate, azathioprine, ciclosporin, and subcutaneous terbutaline infusions. Paediatric data are needed on cytokine-specific monoclonal antibody therapies and bronchial thermoplasty. However, despite the interest in innovative approaches, getting the basics right in children with apparently severe asthma will remain the foundation of management for the foreseeable future.
  
  
• [Comment] Refractory breathlessness: oxygen or room air?
  Breathlessness is a frightening and devastating symptom which affects patients with many diseases in advanced stages. The prevalence reaches 90% in cancer, 95% in chronic obstructive pulmonary disease (COPD), 88% in cardiac failure, and 80% in advanced-stage renal disease. Patients with various neurological conditions also become breathless. Oxygen therapy is often used to manage breathlessness. However, although there is accepted evidence for using oxygen in patients with COPD and hypoxaemia, palliative oxygen is often used in patients with advanced life-limiting illness, irrespective of the partial pressure of oxygen in arterial blood (PaO2). Three systematic reviews raised concerns about a lack of robust evidence with trials that were underpowered, inadequately controlled, or had unclear outcomes.
  
  
• [Correspondence] Community-associated meticillin-resistant Staphylococcus aureus
  We wish to comment on the Seminar by Frank DeLeo and colleagues on community-associated meticillin-resistant Staphylococcus aureus (MRSA).
  
  
• [Comment] A complement to kidney disease: CFHR5 nephropathy
  Isolated microscopic haematuria of glomerular origin in the context of normal renal function without proteinuria has traditionally been managed conservatively. Among the conditions that are included in this rubric, IgA nephropathy and thin-basement-membrane disease account for most cases. Although the precise worldwide prevalence of these two disorders is unknown, one is frequently the culprit in this setting. The clinical diagnosis of IgA nephropathy—the most common glomerulonephritis worldwide—is strongly supported when microscopic haematuria is accompanied by macroscopic haematuria after an upper respiratory tract infection. Without renal impairment, proteinuria, or hypertension, the need for renal biopsy to further characterise isolated microscopic haematuria is not recommended.
  
  
• [Correspondence] Cause-of-death data to support MDG 4 progress
  Cause-of-death data, as presented by Robert Black and colleagues (June 5, p 1969), will be important in guiding intervention priorities to reach Millennium Development Goal 4 (MDG 4; to reduce mortality in children younger than 5 years by two-thirds between 1990 and 2015). India accounts for 21% of global deaths in children younger than 5 years; 54% of these deaths occur in the neonatal period. Two further steps are needed, however, to improve performance of countries that are currently unlikely to meet MDG 4, such as India.
  
  
• [Comment] Call for withdrawal of LABA single-therapy inhaler in asthma
  Long-acting β agonists (LABAs) might increase the risk of asthma mortality when used by patients with unstable asthma without concomitant inhaled corticosteroids or scheduled medical review. This potential risk has contributed to the recommendations in asthma guidelines that LABAs should always be taken with the steroid. Inhaled corticosteroids and LABAs can be prescribed separately or as a combination inhaler. However, in many patients, the use of separate inhalers will inevitably result in periods of LABA monotherapy because of poor compliance with inhaled corticosteroids in standard clinical practice. Prescription databases reveal that patients might stop taking their steroid for variable periods, which will result in LABA monotherapy if they continue to take their LABA inhaler for symptomatic relief. Such periods of monotherapy can be avoided by prescribing a combination inhaler. Combination use applies to all patients with asthma, not just paediatric and adolescent patients, as suggested by the US Food and Drug Administration guidelines.
  
  
• [Department of Error] Department of Error
  Bhutta ZA, Chopra M, Axelson H, et al. Countdown to 2015 decade report (2000–10): taking stock of maternal, newborn, and child survival, Lancet 2010; 375: 2032–44—In this Review (June 5), the median coverages shown by several of the bars in figure 2 were incorrect. The corrected figure is shown below. These corrections have been made to the online version as of Sept 3, 2010.
  
  
• [Comment] The impact of asthma guidelines
  Asthma prevalence is increasing and the economic burden is substantial. Although cost-effective therapies are available, drug regimens are not always adhered to. The impact of asthma guidelines needs re-assessing, not only for patients' care but also for a broader framework, especially because the interface between big pharma and academic institutions is under increasing scrutiny. The initial iteration of the Canadian asthma guidelines were first published in the 1990s. The primary focus of the guidelines has been an emphasis on the role of inflammation and the primary efficacy of inhaled corticosteroids. Additionally, the Canadian guidelines have focused on the importance of asthma control rather than classifying asthma on the basis of the level of severity. The guidelines use a schematic continuum to overview management (). The guidelines have formed the basis of continuing professional development—which is mostly sponsored by drug companies—and for many programmes, which are developed by professional societies. Since the first Canadian asthma guidelines were developed in 1989, hospital admissions for asthma and asthma-related deaths (which now mainly occur in elderly people) have decreased substantially.
  
  
• [Clinical Picture] Jugular venous pressure: a cardinal sign
  A 40-year-old woman presented to our outpatient clinic for routine follow-up. 6 years earlier she had been diagnosed with a stenotic bicuspid aortic valve, which was treated with a 25 mm bioprosthesis implantation. She had no symptoms and her physical examination was unremarkable; however, her external jugular veins were moderately distended (). A chest radiograph showed right cardiac border enlargement (), and an aneurism of the ascending aorta was seen on transthoracic echocardiography. Chest CT showed a De-Bakey type I, Stanford A aortic aneurism dissection (). The maximum diameter was 7·3 cm, and the false lumen started 3 cm above the coronary ostia and extended just beyond the origin of left subclavian artery. The aneurysm resulted in clinically significant compression of the superior vena cava (). Our patient had surgery, with insertion of a collagen graft from the aortic sino-tubular junction distally, and an anastomosis of an island of the three major aortic arch vessels. She did not have any complications and was discharged 7 days later.
  
  
• [Comment] The Year of the Lung
  Admittedly we are biased in stating that lung health has been neglected in the public discourse that research has not been adequately funded, and that we have concerns that the political reality generally does not adequately recognise the importance of respiratory diseases. The bias is mainly related to the fact that the European Respiratory Society (ERS) is a prominent member in the Forum of International Respiratory Societies, which, in December, 2009, convened at the 40th Union World Conference on Lung Health in Cancún, Mexico, to declare 2010 The Year of the Lung.
  
  
• [Review] The role of dendritic and epithelial cells as master regulators of allergic airway inflammation
  Lung dendritic cells bridge innate and adaptive immunity, integrating a variety of stimuli from allergens, microbial colonisation, environmental pollution, and innate immune cells into a signal for T lymphocytes of the adaptive immune system. Dendritic cells have a pivotal role in the activation of T helper (Th) 2 cells and allergic inflammation. Lung dendritic cells can also prevent harmful immune responses to innocuous inhaled antigens via induction of regulatory T cells or Th1 cells. In our Review, we discuss how understanding the biology of dendritic cells is crucial for understanding the interaction between allergens, the environment, and genetics, and focus on how dendritic cells conspire with airway epithelial cells and innate pro-Th2 cells to cause allergic sensitisation and asthma.
  
  
• [Comment] Tracking radiation exposure of patients
  As recently as only 6 years ago, it was not possible to come across a radiation-induced skin injury (erythema such as a burn, or hair loss) to a patient resulting from CT. However, in 2009–10, overexposure of about 400 patients undergoing brain-perfusion CT protocols, resulting in hair loss or skin redness in some patients, was brought to the attention of the US Food and Drug Administration and in media reports. 20 years ago, it was not possible to come across a patient who had undergone scores of CT scans in a few years, especially the patient without cancer. Did we see this coming? The answer is largely “no” for visible radiation effects and “probably yes” for usage. In view of these recent events, what might be the scenario in a few years? There are no indications that the increase in CT use will decrease. On the contrary, CT might replace some traditional fluoroscopy-based angiographic procedures. The medical profession has a responsibility to account for radiation exposure from medical imaging.
  
  
• [Correspondence] Community-associated meticillin-resistant Staphylococcus aureus – Authors' reply
  The idea that the meticillin-resistant Staphylococcus aureus (MRSA) clone ST59 originated in the USA is based on studies of the geographic distribution of MRSA clones positive for Panton-Valentine leukocidin by Vandenesch and colleagues and Tristan and colleagues. Vandenesch and colleagues reported that the country of origin for ST59 was the USA, and follow-up studies by Tristan and colleagues suggested that intercontinental exchange of MRSA clones includes movement of ST59 from the USA towards Asia. Inasmuch as ST59 was reported in Singapore by those studies, our map suggests that ST59 originated in the USA and moved towards Asia or Singapore as reported by the two previous studies. Note that we indicate that ST59 is present in Taiwan and it is certainly possible that ST59 originated in Taiwan as Li-Yang Hsu and colleagues suggest. If Hsu and colleagues have data that conclusively show the origin of ST59, this is of course a welcome addition to our understanding of the emergence and epidemiology of important community-associated MRSA clones.
  
  
• [Comment] Offline: A kind of modern American condition
  My favourite decade—the 1970s—is back in fashion. Something happened during that decade, and now people are trying to make sense of it. Martin Amis put it this way (in The Pregnant Widow, 2010): “Something was churning in the world of men and women, a revolution or a sea change, a realignment”. In Britain, our trajectory hit an inflection point. No longer a superpower in splendid isolation, we pledged ourselves to an uncertain entente cordiale with continental Europe. Aristocracy was finally toppled, an imperfect meritocracy taking its place. Being the grandson of a duke was no longer an entry requirement for running the country. The question that faced us then, and still preoccupies us today, became purely existential: what is Britain for? We have secularised, marketised, trivialised, and post-modernised. But our role has contracted, our confidence is more brittle, and our influence has waned. Some historians (and perhaps the more Darwinian among us) argue that we don't need a purpose. We just are. But two contributions (although not unique) do continue to diffuse beyond our boundaries. One is an activity (science) and the other an attitude (internationalism). Together, they combine to give the UK potentially important comparative advantages—if only our political leaders could see what was before their eyes, as they cut, cut, cut.
  
  
• [Correspondence] Antitrypanosomal agents: treatment or threat?
  We congratulate Anis Rassi and colleagues (April 17, p 1388) for their solid review of the neglected Chagas disease. However, we were disappointed by their recommendation of antitrypanosomal treatment for “patients up to 18 years of age with chronic disease” and that “drug treatment should generally be offered to adults aged 19–50 years without advanced Chagas heart disease”. Since more than 7 million individuals are estimated to be infected, unrestricted treatment of such a large population has epidemiological and public health consequences of paramount proportions, and must be based on data from prospective randomised trials.
  
  
• [World Report] Uganda steps up efforts to boost male circumcision
  Ugandan authorities have launched an ambitious new campaign to increase the proportion of adult men circumcised to at least 40% within 5 years. Wairagala Wakabi reports from Kampala.
  
  
• [Correspondence] The International Study of Insulin and Cancer
  Studies have suggested the possibility of an association between use of insulin glargine and cancer, with conflicting results. Among other issues under debate is the role of insulin itself in cancer development and the contribution of confounding factors or analytical methods to observations. The International Study of Insulin and Cancer (ISICA) is an effort to address thoroughly the association of breast cancer with insulin use. ISICA has received an unrestricted grant from Sanofi-Aventis and has been reviewed by the European Medicines Agency.
  
  
• [World Report] German health reform compromise under attack
  The German coalition government pledged sweeping reforms to the health system to avert a projected €11 billion deficit. But fierce political and industrial opposition has forced the coalition to compromise. Rob Hyde reports from Bremen, Germany.
  
  
• [Correspondence] NICE guidelines on neonatal jaundice: at risk of being too nice
  As you summarise in your May 29 Editorial (p 1845), new guidelines on the management of newborn jaundice have been issued by the UK's National Institute for Health and Clinical Excellence (NICE). Although NICE correctly recommends avoidance of parental anxiety, since jaundice is usually a benign condition, the advice seems too parent-centred overall.
  
  
• [Perspectives] Book: The paradoxes of asthma
  In the last chapter in Asthma, Health and Society: A Public Health Perspective, Noreen Clark attempts some of the syntheses the reader was expecting from this interesting but at times out-of-date compendium. She describes asthma as “one of America's most perplexing public health problems”.
  
  
• [Correspondence] The Lancet–Palestinian Health Alliance
  I wholeheartedly commend The Lancet for continuing to publish on Palestine and for its advocacy for justice in health. The most recent Israeli attack on the Gaza Strip, and the less visible, albeit equally inhumane, decades-long occupation of the West Bank and East Jerusalem, are a brutal onslaught on human health, as the abstracts and comments presented at the Second Lancet–Palestinian Health Alliance Conference at Birzeit University compellingly illustrate. They are also an affront on elementary standards of human decency.
  
  
• [Perspectives] Film: Living with asthma
  In his Pulitzer Prize winning history Polio: An American Story, David Oshinsky suggests that the poliomyelitis epidemics of the first half of the 20th century led to the American obsession with cleanliness. Advertisers took advantage of parents' fear that infantile paralysis might visit their household next, and played up the salubrious potential of detergents, soaps, and mouthwash. Early in the century, a janitor named James Murray Spangler sold his idea for an electric vacuum cleaner to William Henry Hoover, who promptly patented the device. In the boom years that followed World War II, the public took to vacuuming in droves.
  
  
• [Articles] Risk assessment for respiratory complications in paediatric anaesthesia: a prospective cohort study
  Perioperative respiratory adverse events in children are one of the major causes of morbidity and mortality during paediatric anaesthesia. We aimed to identify associations between family history, anaesthesia management, and occurrence of perioperative respiratory adverse events.