- Email: [email protected]
Expansion of the donor lung pool: use of lungs from smokers
Comment
immune system, including dendritic cells, monocytes, neutrophils, and keratinocytes.11 In The Lancet, Kim Papp and colleagues12 report a phase 2 trial of the clinical efficacy and safety of apremilast in treatment of moderate to severe plaque psoriasis. In this double-blind trial done at centres in the USA and Canada, 352 patients with moderate to severe psoriasis were randomly assigned to oral placebo or apremilast 10 mg, 20 mg, or 30 mg twice daily. The primary endpoint was the proportion of patients achieving at least a 75% reduction from baseline psoriasis area and severity index (PASI-75) at week 16. At week 16, PASI-75 was achieved in five (6%) patients assigned placebo, ten (11%) assigned apremilast 10 mg, 25 (29%) assigned apremilast 20 mg, and 36 (41%) assigned apremilast 30 mg. The differences from placebo were significant for both apremilast 20 mg (odds ratio 6·69; 95% CI 2·43–18·5) and apremilast 30 mg (11·5; 4·24–31·2), but not for apremilast 10 mg (2·10; 0·69–6·62).12 Most (96%) adverse events were mild or moderate; at least 5% of patients had nausea, upper respiratory tract infection, diarrhoea, nasopharyngitis, headache, arthralgia (in patients given placebo), gastroenteritis, or dyspepsia. Eight serious adverse events occurred in the whole study cohort, but these were judged to be unrelated to apremilast.12 Papp and colleagues’ study was well controlled and the superiority of apremilast compared with placebo seems convincing. However, before firm conclusions about the efficacy of apremilast can be made, further investigations are needed to compare it with other systemic treatments and to examine the safety of long-term treatment for at least a year. In particular, studies comparing the efficacy and safety of apremilast with a classic systemic treatment (such as methotrexate) and one of the biological agents
would be worthwhile. Future investigations will tell us whether apremilast will lead clinicians to a new path in the long-term treatment of psoriasis. Peter C M van de Kerkhof Department of Dermatology, Radboud University Nijmegen Medical Centre, Nijmegen 6500 HB, Netherlands [email protected] I have provided consultancy services for Schering Plough, Celgene, Centocor, Allmirall, UCB, Pfizer, Soffinova, Abbott, Actelion, Galderma, Novartis, and Janssen-Cilag; and have done clinical trials for Centocor, Schering Plough, Merck, Abbott, and Philips Lighting. 1 2
3
4
5
6
7
8
9 10 11
12
Griffiths CEM, Barker JNWN. Pathogenesis and clinical features of psoriasis. Lancet 2007; 37: 263–71. Pathirana D, Ormerod AD, Saiag P, et al. European S3-guidelines on the systemic treatment of psoriasis vulgaris. J Eur Acad Dermatol Venereol 2009; 23 (suppl 2): 1–70. Davidovici BB, Sattar N, Prinz JC, et al. Psoriasis and systemic inflammatory diseases: potential mechanistic links between skin disease and co-morbid conditions. J Invest Dermatol 2010; 130: 1785–96. Böhm D, Stock Gissendanner S, Bangemann K, et al. Perceived relationships between severity of psoriasis symptoms, gender, stigmatization and quality of life. J Eur Acad Dermatol Venereol 2012; published online Feb 14. DOI:1468-3083.2012.04451.x. Griffiths CE, Gaitanis G, van de Kerkhof P. The unmet treatment need for moderate to severe psoriasis: results of a survey and chart review. J Eur Acad Dermatol Venereol 2006; 20: 921–25. Reich K, Burden AD, Eaton JN, Hawkins NS. Efficacy of biologics in the treatment of moderate to severe psoriasis: a network meta-analysis of randomized controlled trials. Br J Dermatol 2012; 166: 179–88. Van Lümig PP, Driessen RJ, Berends MA, et al. Safety of treatment with biologics for psoriasis in daily practice: 5-year data. J Eur Acad Dermatol Venereol 2012; 26: 283–91. Fonia A, Jackson K, Lereun C, Grant DM, Barker JN, Smith CH. A retrospective cohort study of the impact of biologic therapy initiation on medical resource use and costs in patients with moderate to severe psoriasis. Br J Dermatol 2010; 163: 807–16. Leavy O. Therapeutic targeting of IL-17 for psoriasis. Nat Rev Immunol 2012; 12: 322. Papp KA, Leonardi C, Menter A, et al. Brodalumab, an anti-interleukin-17receptor antibody for psoriasis. N Engl J Med 2012; 366: 1181–89. Schafer P, Parton P, Gandhi A, et al. Apremilast, a cyclic AMP phosphodiesterase-4 inhibitor, demonstrates anti-inflammatory activity in vitro and in a model of psoriasis. Br J Pharmacol 2010; 159: 842–55. Papp K, Cather JC, Rosoph L, et al. Efficacy of apremilast in the treatment of moderate to severe psoriasis: a randomised controlled trial. Lancet 2012; published online June 29. http://dx.doi.org/10.1016/S01406736(12)60642-4.
Expansion of the donor lung pool: use of lungs from smokers In The Lancet, Robert Bonser and colleagues1 investigate whether the use of lungs from donors with positive smoking histories is justifiable in lung transplantation. On the basis of a study of 1295 adult lung transplants done in the UK between July, 1999 and December, 2010, the authors conclude that use of such lungs has a net benefit to the potential transplant recipient since donors with positive smoking histories provide www.thelancet.com Vol 380 August 25, 2012
a substantial proportion of organs for transplantation (nearly 40% of the donor pool), leading to fewer deaths of patients on the waiting list. Benefit was noted in the study despite lower survival for patients who received lung transplants from donors who smoked compared with those who received lungs from donors with negative smoking histories (adjusted hazard ratio for death at 3 years 1·36, 95% CI 1·11–1·67). As expected,
Published Online May 29, 2012 http://dx.doi.org/10.1016/ S0140-6736(12)60650-3 See Articles page 747
709
Comment
Science Photo Library
benefit was most evident for patients with fibrotic lung disease, who usually have rapidly declining functional condition when they go on the waiting list (adjusted HR for a projected comparison of use of lungs from donors with a positive smoking history vs remaining on the waiting list 0·39, 0·28–0·55). The adverse effects on survival after transplantation associated with use of lungs from donors with positive smoking histories seem to be predominantly related to intermediate and long-term outcomes, especially with regard to the development of chronic graft dysfunction. Survival in patients receiving lungs from donors who had smoked more than 20 cigarettes per day was substantially less than that of those receiving lungs from nonsmoking donors. It is important to realise that the relation between risk of dying on the waiting list and the benefit of accepting a transplant from a donor with a substantial smoking history can vary by country and centre. This relation depends on factors such as the organ allocation system (eg, implementation of the lung allocation score in the USA reduced mortality of patients on the waiting list without a substantial increase in lung donors),2 the number and type of patients on the waiting list,3 and the ability of the specific centre to expand the donor pool through use of extended criteria for donor selection.4,5 Much variation exists in usage rates of donor lungs; some centres use 40% of available lungs, whereas others use less than 10%.6–9
710
Smoking-related lung injury is quite variable. Some individuals can have pronounced lung damage leading to obstructive lung disease, whereas others can have preserved lung parenchyma and function despite several years of smoking.10 Bonser and co-workers’ investigation1 does not establish whether a subgroup of donors with positive smoking histories and some degree of hyperinflation or obstruction, or both, could be the cause of lower survival reported in recipients who received lungs from donors who smoked compared with those whose transplants were from non-smoking donors. By contrast, unaffected lungs from donors with positive smoking histories could potentially lead to similar outcomes to those noted in patients receiving lungs from non-smoking donors. Pulmonary function tests, such as forced expiratory volume at 1 s, are not done in donors; portable chest radiography is the only imaging test generally done, which might not detect mild-to-moderate chronic obstructive pulmonary disease. Some centres are exploring the use of CT in donors with substantial positive smoking histories to better assess the parenchyma for early signs of chronic obstructive pulmonary disease (unpublished). The effect of this policy on the acceptance of lungs for transplantation is not yet known. Many transplantation centres commonly use lungs from donors with positive smoking histories, who are thought to be a valuable source of organs.11,12 However, in general more than 80% of lungs from brain death and cardiac death multiorgan donors are declined for transplantation, leading to 34% mortality of patients on the waiting list in the UK, for example.13 Many of these declined lungs are from young and nonsmoking donors without any permanent structural lung damage. These organs are usually rejected because of acute but recoverable injuries, such as neurogenic pulmonary oedema, pneumonia, aspiration pneumonitis, or pulmonary emboli.14 Transplantation teams are understandably reluctant to transplant these organs because of the increased risk of primary graft dysfunction and associated complications.15,16 Once better strategies are developed to select donor lungs accurately with predictable early and late outcomes, many more organs in the donor pool can be used safely and effectively. Novel techniques such as normothermic ex-vivo lung perfusion provide the opportunity to preserve, assess, treat, and repair organs www.thelancet.com Vol 380 August 25, 2012
Comment
requiring specific therapy17,18—a personalised approach to donor organ management. Repair of acutely injured recoverable lungs will be the early gains of this approach. As we develop advanced lung regenerative strategies, use of molecular and cell treatments to repair lungs damaged by smoking is conceivable. Marcelo Cypel, *Shaf Keshavjee
6 7
8
9 10
Toronto Lung Transplant Program, University Health Network, Toronto, Ontario M5G 2C4, Canada [email protected]
11
We declare that we have no conflicts of interest.
12
1
2 3
4
5
Bonser RS, Taylor R, Collett D, Thomas HL, Dark JH, Neuberger J, on behalf of members of the Cardiothoracic Advisory Group to NHS Blood and Transplant and the Association of Lung Transplant Physicians (UK). Effect of donor smoking on survival after lung transplantation: a cohort study of a prospective registry. Lancet 2012; published online May 29. DOI:10.1016/ S0140-6736(12)60160-3. Eberlein M, Garrity ER, Orens JB. Lung allocation in the United States. Clin Chest Med 2011; 32: 213–22. De Meester J, Smits JM, Persijn GG, Haverich A. Listing for lung transplantation: life expectancy and transplant effect, stratified by type of end-stage lung disease, the Eurotransplant experience. J Heart Lung Transplant 2001; 20: 518–24. Botha P, Trivedi D, Weir CJ, et al. Extended donor criteria in lung transplantation: impact on organ allocation. J Thorac Cardiovasc Surg 2006; 131: 1154–60. Aigner C, Winkler G, Jaksch P, et al. Extended donor criteria for lung transplantation—a clinical reality. Eur J Cardiothorac Surg 2005; 27: 757–61.
13
14 15 16
17 18
de Perrot M, Snell GI, Babcock WD, et al. Strategies to optimize the use of currently available lung donors. J Heart Lung Transplant 2004; 23: 1127–34. Angel LF, Levine DJ, Restrepo MI, et al. Impact of a lung transplantation donor-management protocol on lung donation and recipient outcomes. Am J Respir Crit Care Med 2006; 174: 710–16. Klein AS, Messersmith EE, Ratner LE, Kochik R, Baliga PK, Ojo AO. Organ donation and utilization in the United States, 1999–2008. Am J Transplant 2010; 10: 973–86. Snell GI, Westall GP. Donor selection and management. Curr Opin Organ Transplant 2009; 14: 471–76. Castaldi PJ, Demeo DL, Hersh CP, et al. Impact of non-linear smoking effects on the identification of gene-by-smoking interactions in COPD genetics studies. Thorax 2011; 66: 903–09. Berman M, Goldsmith K, Jenkins D, et al. Comparison of outcomes from smoking and nonsmoking donors: thirteen-year experience. Ann Thorac Surg 2010; 90: 1786–92. Schiavon M, Falcoz PE, Santelmo N, Massard G. Does the use of extended criteria donors influence early and long-term results of lung transplantation? Interact Cardiovasc Thorac Surg 2012; 14: 183–87. Titman A, Rogers CA, Bonser RS, Banner NR, Sharples LD. Disease-specific survival benefit of lung transplantation in adults: a national cohort study. Am J Transplant 2009; 9: 1640–49. de Perrot M, Liu M, Waddell T, Keshavjee S. Ischemia-reperfusion-induced lung injury. Am J Respir Cell Mol Biol 2003; 28: 616–25. Christie JD, Sager JS, Kimmel SE, et al. Impact of primary graft failure on outcomes following lung transplantation. Chest 2005; 127: 161–65. Lee JC, Christie JD, Keshavjee S. Primary graft dysfunction: definition, risk factors, short- and long-term outcomes. Semin Respir Crit Care Med 2010; 31: 161–71. Cypel M, Yeung JC, Liu M, et al. Normothermic ex vivo lung perfusion in clinical lung transplantation. N Engl J Med 2011; 364: 1431–40. Cypel M, Liu M, Rubacha M, et al. Functional repair of human donor lungs by IL-10 gene therapy. Sci Transl Med 2009; 1: 1–9.
More than mothers: aligning indicators with women’s lives Just as pregnancy is one of many experiences in a woman’s life, reproductive health is only one crucial aspect of women’s health. Despite the many challenges women face worldwide, with a disproportionate burden in low-income countries, the public health community too often uses only reproductive health indicators when measuring progress in women’s health. This practice is shown most recently in the work of the UN Commission on Information and Accountability for Women’s and Children’s Health, the recommendations of which have the potential to shape how low-income countries collect data and report progress for years to come. The Commission has proposed six core indicators of women’s health: maternal mortality ratio; met need for contraception (proportion of women aged 15–49 years who are married or in union and have met their need for family planning); antiretroviral prophylaxis for HIV-positive pregnant women (prevention of mother-to-child transmission) and antiretroviral therapy for women who are eligible www.thelancet.com Vol 380 August 25, 2012
for treatment; skilled attendant at birth; antenatal care coverage; and postnatal care for mothers and babies.1 Five of these six indicators focus exclusively on women’s health in the context of reproduction. Indeed, the last four measure child health as much as that of women. Antiretroviral prophylaxis for HIVpositive pregnant women, while a highly effective intervention for preventing transmission of HIV to the infant, is not in itself a measure of women’s health.2,3 The inclusion of antiretroviral treatment for all eligible women, an important addition in later drafts, is the only attempt to expand these indicators beyond the reproductive period. Reproduction is a crucial high-risk period for women in low-income countries,4 but pregnancy is by no means the only time women are exposed to risk. In fact, WHO estimated that, in 2004, women in developing nations aged 15–59 years were less likely to die of maternal causes than of injury, including violence, HIV/AIDS, or cardiovascular disease.5 In terms of morbidity, this
Published Online October 4, 2011 http://dx.doi.org/10.1016/ S0140-6736(11)60757-5
711
immune system, including dendritic cells, monocytes, neutrophils, and keratinocytes.11 In The Lancet, Kim Papp and colleagues12 report a phase 2 trial of the clinical efficacy and safety of apremilast in treatment of moderate to severe plaque psoriasis. In this double-blind trial done at centres in the USA and Canada, 352 patients with moderate to severe psoriasis were randomly assigned to oral placebo or apremilast 10 mg, 20 mg, or 30 mg twice daily. The primary endpoint was the proportion of patients achieving at least a 75% reduction from baseline psoriasis area and severity index (PASI-75) at week 16. At week 16, PASI-75 was achieved in five (6%) patients assigned placebo, ten (11%) assigned apremilast 10 mg, 25 (29%) assigned apremilast 20 mg, and 36 (41%) assigned apremilast 30 mg. The differences from placebo were significant for both apremilast 20 mg (odds ratio 6·69; 95% CI 2·43–18·5) and apremilast 30 mg (11·5; 4·24–31·2), but not for apremilast 10 mg (2·10; 0·69–6·62).12 Most (96%) adverse events were mild or moderate; at least 5% of patients had nausea, upper respiratory tract infection, diarrhoea, nasopharyngitis, headache, arthralgia (in patients given placebo), gastroenteritis, or dyspepsia. Eight serious adverse events occurred in the whole study cohort, but these were judged to be unrelated to apremilast.12 Papp and colleagues’ study was well controlled and the superiority of apremilast compared with placebo seems convincing. However, before firm conclusions about the efficacy of apremilast can be made, further investigations are needed to compare it with other systemic treatments and to examine the safety of long-term treatment for at least a year. In particular, studies comparing the efficacy and safety of apremilast with a classic systemic treatment (such as methotrexate) and one of the biological agents
would be worthwhile. Future investigations will tell us whether apremilast will lead clinicians to a new path in the long-term treatment of psoriasis. Peter C M van de Kerkhof Department of Dermatology, Radboud University Nijmegen Medical Centre, Nijmegen 6500 HB, Netherlands [email protected] I have provided consultancy services for Schering Plough, Celgene, Centocor, Allmirall, UCB, Pfizer, Soffinova, Abbott, Actelion, Galderma, Novartis, and Janssen-Cilag; and have done clinical trials for Centocor, Schering Plough, Merck, Abbott, and Philips Lighting. 1 2
3
4
5
6
7
8
9 10 11
12
Griffiths CEM, Barker JNWN. Pathogenesis and clinical features of psoriasis. Lancet 2007; 37: 263–71. Pathirana D, Ormerod AD, Saiag P, et al. European S3-guidelines on the systemic treatment of psoriasis vulgaris. J Eur Acad Dermatol Venereol 2009; 23 (suppl 2): 1–70. Davidovici BB, Sattar N, Prinz JC, et al. Psoriasis and systemic inflammatory diseases: potential mechanistic links between skin disease and co-morbid conditions. J Invest Dermatol 2010; 130: 1785–96. Böhm D, Stock Gissendanner S, Bangemann K, et al. Perceived relationships between severity of psoriasis symptoms, gender, stigmatization and quality of life. J Eur Acad Dermatol Venereol 2012; published online Feb 14. DOI:1468-3083.2012.04451.x. Griffiths CE, Gaitanis G, van de Kerkhof P. The unmet treatment need for moderate to severe psoriasis: results of a survey and chart review. J Eur Acad Dermatol Venereol 2006; 20: 921–25. Reich K, Burden AD, Eaton JN, Hawkins NS. Efficacy of biologics in the treatment of moderate to severe psoriasis: a network meta-analysis of randomized controlled trials. Br J Dermatol 2012; 166: 179–88. Van Lümig PP, Driessen RJ, Berends MA, et al. Safety of treatment with biologics for psoriasis in daily practice: 5-year data. J Eur Acad Dermatol Venereol 2012; 26: 283–91. Fonia A, Jackson K, Lereun C, Grant DM, Barker JN, Smith CH. A retrospective cohort study of the impact of biologic therapy initiation on medical resource use and costs in patients with moderate to severe psoriasis. Br J Dermatol 2010; 163: 807–16. Leavy O. Therapeutic targeting of IL-17 for psoriasis. Nat Rev Immunol 2012; 12: 322. Papp KA, Leonardi C, Menter A, et al. Brodalumab, an anti-interleukin-17receptor antibody for psoriasis. N Engl J Med 2012; 366: 1181–89. Schafer P, Parton P, Gandhi A, et al. Apremilast, a cyclic AMP phosphodiesterase-4 inhibitor, demonstrates anti-inflammatory activity in vitro and in a model of psoriasis. Br J Pharmacol 2010; 159: 842–55. Papp K, Cather JC, Rosoph L, et al. Efficacy of apremilast in the treatment of moderate to severe psoriasis: a randomised controlled trial. Lancet 2012; published online June 29. http://dx.doi.org/10.1016/S01406736(12)60642-4.
Expansion of the donor lung pool: use of lungs from smokers In The Lancet, Robert Bonser and colleagues1 investigate whether the use of lungs from donors with positive smoking histories is justifiable in lung transplantation. On the basis of a study of 1295 adult lung transplants done in the UK between July, 1999 and December, 2010, the authors conclude that use of such lungs has a net benefit to the potential transplant recipient since donors with positive smoking histories provide www.thelancet.com Vol 380 August 25, 2012
a substantial proportion of organs for transplantation (nearly 40% of the donor pool), leading to fewer deaths of patients on the waiting list. Benefit was noted in the study despite lower survival for patients who received lung transplants from donors who smoked compared with those who received lungs from donors with negative smoking histories (adjusted hazard ratio for death at 3 years 1·36, 95% CI 1·11–1·67). As expected,
Published Online May 29, 2012 http://dx.doi.org/10.1016/ S0140-6736(12)60650-3 See Articles page 747
709
Comment
Science Photo Library
benefit was most evident for patients with fibrotic lung disease, who usually have rapidly declining functional condition when they go on the waiting list (adjusted HR for a projected comparison of use of lungs from donors with a positive smoking history vs remaining on the waiting list 0·39, 0·28–0·55). The adverse effects on survival after transplantation associated with use of lungs from donors with positive smoking histories seem to be predominantly related to intermediate and long-term outcomes, especially with regard to the development of chronic graft dysfunction. Survival in patients receiving lungs from donors who had smoked more than 20 cigarettes per day was substantially less than that of those receiving lungs from nonsmoking donors. It is important to realise that the relation between risk of dying on the waiting list and the benefit of accepting a transplant from a donor with a substantial smoking history can vary by country and centre. This relation depends on factors such as the organ allocation system (eg, implementation of the lung allocation score in the USA reduced mortality of patients on the waiting list without a substantial increase in lung donors),2 the number and type of patients on the waiting list,3 and the ability of the specific centre to expand the donor pool through use of extended criteria for donor selection.4,5 Much variation exists in usage rates of donor lungs; some centres use 40% of available lungs, whereas others use less than 10%.6–9
710
Smoking-related lung injury is quite variable. Some individuals can have pronounced lung damage leading to obstructive lung disease, whereas others can have preserved lung parenchyma and function despite several years of smoking.10 Bonser and co-workers’ investigation1 does not establish whether a subgroup of donors with positive smoking histories and some degree of hyperinflation or obstruction, or both, could be the cause of lower survival reported in recipients who received lungs from donors who smoked compared with those whose transplants were from non-smoking donors. By contrast, unaffected lungs from donors with positive smoking histories could potentially lead to similar outcomes to those noted in patients receiving lungs from non-smoking donors. Pulmonary function tests, such as forced expiratory volume at 1 s, are not done in donors; portable chest radiography is the only imaging test generally done, which might not detect mild-to-moderate chronic obstructive pulmonary disease. Some centres are exploring the use of CT in donors with substantial positive smoking histories to better assess the parenchyma for early signs of chronic obstructive pulmonary disease (unpublished). The effect of this policy on the acceptance of lungs for transplantation is not yet known. Many transplantation centres commonly use lungs from donors with positive smoking histories, who are thought to be a valuable source of organs.11,12 However, in general more than 80% of lungs from brain death and cardiac death multiorgan donors are declined for transplantation, leading to 34% mortality of patients on the waiting list in the UK, for example.13 Many of these declined lungs are from young and nonsmoking donors without any permanent structural lung damage. These organs are usually rejected because of acute but recoverable injuries, such as neurogenic pulmonary oedema, pneumonia, aspiration pneumonitis, or pulmonary emboli.14 Transplantation teams are understandably reluctant to transplant these organs because of the increased risk of primary graft dysfunction and associated complications.15,16 Once better strategies are developed to select donor lungs accurately with predictable early and late outcomes, many more organs in the donor pool can be used safely and effectively. Novel techniques such as normothermic ex-vivo lung perfusion provide the opportunity to preserve, assess, treat, and repair organs www.thelancet.com Vol 380 August 25, 2012
Comment
requiring specific therapy17,18—a personalised approach to donor organ management. Repair of acutely injured recoverable lungs will be the early gains of this approach. As we develop advanced lung regenerative strategies, use of molecular and cell treatments to repair lungs damaged by smoking is conceivable. Marcelo Cypel, *Shaf Keshavjee
6 7
8
9 10
Toronto Lung Transplant Program, University Health Network, Toronto, Ontario M5G 2C4, Canada [email protected]
11
We declare that we have no conflicts of interest.
12
1
2 3
4
5
Bonser RS, Taylor R, Collett D, Thomas HL, Dark JH, Neuberger J, on behalf of members of the Cardiothoracic Advisory Group to NHS Blood and Transplant and the Association of Lung Transplant Physicians (UK). Effect of donor smoking on survival after lung transplantation: a cohort study of a prospective registry. Lancet 2012; published online May 29. DOI:10.1016/ S0140-6736(12)60160-3. Eberlein M, Garrity ER, Orens JB. Lung allocation in the United States. Clin Chest Med 2011; 32: 213–22. De Meester J, Smits JM, Persijn GG, Haverich A. Listing for lung transplantation: life expectancy and transplant effect, stratified by type of end-stage lung disease, the Eurotransplant experience. J Heart Lung Transplant 2001; 20: 518–24. Botha P, Trivedi D, Weir CJ, et al. Extended donor criteria in lung transplantation: impact on organ allocation. J Thorac Cardiovasc Surg 2006; 131: 1154–60. Aigner C, Winkler G, Jaksch P, et al. Extended donor criteria for lung transplantation—a clinical reality. Eur J Cardiothorac Surg 2005; 27: 757–61.
13
14 15 16
17 18
de Perrot M, Snell GI, Babcock WD, et al. Strategies to optimize the use of currently available lung donors. J Heart Lung Transplant 2004; 23: 1127–34. Angel LF, Levine DJ, Restrepo MI, et al. Impact of a lung transplantation donor-management protocol on lung donation and recipient outcomes. Am J Respir Crit Care Med 2006; 174: 710–16. Klein AS, Messersmith EE, Ratner LE, Kochik R, Baliga PK, Ojo AO. Organ donation and utilization in the United States, 1999–2008. Am J Transplant 2010; 10: 973–86. Snell GI, Westall GP. Donor selection and management. Curr Opin Organ Transplant 2009; 14: 471–76. Castaldi PJ, Demeo DL, Hersh CP, et al. Impact of non-linear smoking effects on the identification of gene-by-smoking interactions in COPD genetics studies. Thorax 2011; 66: 903–09. Berman M, Goldsmith K, Jenkins D, et al. Comparison of outcomes from smoking and nonsmoking donors: thirteen-year experience. Ann Thorac Surg 2010; 90: 1786–92. Schiavon M, Falcoz PE, Santelmo N, Massard G. Does the use of extended criteria donors influence early and long-term results of lung transplantation? Interact Cardiovasc Thorac Surg 2012; 14: 183–87. Titman A, Rogers CA, Bonser RS, Banner NR, Sharples LD. Disease-specific survival benefit of lung transplantation in adults: a national cohort study. Am J Transplant 2009; 9: 1640–49. de Perrot M, Liu M, Waddell T, Keshavjee S. Ischemia-reperfusion-induced lung injury. Am J Respir Cell Mol Biol 2003; 28: 616–25. Christie JD, Sager JS, Kimmel SE, et al. Impact of primary graft failure on outcomes following lung transplantation. Chest 2005; 127: 161–65. Lee JC, Christie JD, Keshavjee S. Primary graft dysfunction: definition, risk factors, short- and long-term outcomes. Semin Respir Crit Care Med 2010; 31: 161–71. Cypel M, Yeung JC, Liu M, et al. Normothermic ex vivo lung perfusion in clinical lung transplantation. N Engl J Med 2011; 364: 1431–40. Cypel M, Liu M, Rubacha M, et al. Functional repair of human donor lungs by IL-10 gene therapy. Sci Transl Med 2009; 1: 1–9.
More than mothers: aligning indicators with women’s lives Just as pregnancy is one of many experiences in a woman’s life, reproductive health is only one crucial aspect of women’s health. Despite the many challenges women face worldwide, with a disproportionate burden in low-income countries, the public health community too often uses only reproductive health indicators when measuring progress in women’s health. This practice is shown most recently in the work of the UN Commission on Information and Accountability for Women’s and Children’s Health, the recommendations of which have the potential to shape how low-income countries collect data and report progress for years to come. The Commission has proposed six core indicators of women’s health: maternal mortality ratio; met need for contraception (proportion of women aged 15–49 years who are married or in union and have met their need for family planning); antiretroviral prophylaxis for HIV-positive pregnant women (prevention of mother-to-child transmission) and antiretroviral therapy for women who are eligible www.thelancet.com Vol 380 August 25, 2012
for treatment; skilled attendant at birth; antenatal care coverage; and postnatal care for mothers and babies.1 Five of these six indicators focus exclusively on women’s health in the context of reproduction. Indeed, the last four measure child health as much as that of women. Antiretroviral prophylaxis for HIVpositive pregnant women, while a highly effective intervention for preventing transmission of HIV to the infant, is not in itself a measure of women’s health.2,3 The inclusion of antiretroviral treatment for all eligible women, an important addition in later drafts, is the only attempt to expand these indicators beyond the reproductive period. Reproduction is a crucial high-risk period for women in low-income countries,4 but pregnancy is by no means the only time women are exposed to risk. In fact, WHO estimated that, in 2004, women in developing nations aged 15–59 years were less likely to die of maternal causes than of injury, including violence, HIV/AIDS, or cardiovascular disease.5 In terms of morbidity, this
Published Online October 4, 2011 http://dx.doi.org/10.1016/ S0140-6736(11)60757-5
711