Correspondence
2
3
3C Study Collaborative Group, Haynes R, Harden P, et al. Alemtuzumab-base induction treatment versus basilixmab-base induction treatment in kidney transplantation (the 3C Study): a randomised trial. Lancet 2014; 384: 1684–90. Vereerstraeten P, Abramowicz D, de Puaw L, Kinnaert P. Absence of deleterious effect on long-term kidney graft survival of rejection episodes with complete functional recovery. Transplantation 1997; 63: 1739–43. Ciancio G, Gaynor JJ, Guerra G, et al. Randomized trial of three induction antibodies in kidney transplantation: long-term results. Transplantation 2014; 97: 1128–38.
Authors’ reply The 3C Study showed that alemtuzumab-based induction treatment compared with standard basiliximab-based induction treatment reduced the risk of biopsy-proven acute rejection by about a half within the first 6 months of transplantation, without any excess infectious or other complications during this period.1 The 3C Study was designed to reliably investigate the long-term effects of alemtuzumab-based induction treatment on outcomes such as graft survival, which previous studies (including those cited by Andrea Berghofen and colleagues)2 have been too small to do. During the first 6 months, post-hoc analysis shows that allocation to alemtuzumab-based induction treatment was not associated with an increased risk of the composite outcome of graft failure or death within the first six months: 25 (5·9%) vs 16 (3·8%); hazard ratio 1·55 (95% CI 0·83–1·91; p=0·17). We did not note any autoimmune complications in the participants allocated alemtuzumab during the first 6 months of follow-up, but surveillance of such complications will continue. We agree with Neeraj Dhaun and David Kluth that cardiovascular disease is a major clinical problem after kidney transplantation. In post-hoc analyses, we noted no significant differences in blood pressure at 6 months between participants allocated alemtuzumab (mean systolic blood pressure 140·8 mm Hg [SE 0·96]) or basiliximab (140·2 [0·9]), or in proteinuria (mean In protein:creatinine ratio www.thelancet.com Vol 385 February 28, 2015
alemtuzumab 2·91 [0·10]; basiliximab 2·72 [0·11]). The long-term effects of the induction treatments on clinical cardiovascular outcomes will be presented in future reports. We agree with Andrea Berghofen and colleagues that the removal of alemtuzumab from the EU by the manufacturer means that its future use in kidney transplantation is uncertain, although this removal could not have been foreseen when the 3C Study was designed. RH, MJL, and CB receive core support from the UK Medical Research Council, British Heart Foundation, and Cancer Research UK. The Clinical Trial Service Unit and Epidemiological Studies Unit, which is part of the University of Oxford, has a staff policy of not accepting honoraria or consultancy fees. PH has received grants from Sanofi and Astellas. PF reports grants from Pfizer and Novartis during the conduct of this study, and consultancy fees from Sanofi and honoraria from Pfizer, both outside the submitted work.
*Richard Haynes, Colin Baigent, Martin J Landray, Paul Harden, Peter Friend [email protected] Clinical Trial Service Unit, and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford OX3 7LF, UK (RH, CB, MJL); Oxford Kidney Unit, Oxford University Hospitals NHS Trust, Oxford, UK (RH, PH); and Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK (PF) 1
2
3C Study Collaborative Group, Haynes R, Harden P, et al. Alemtuzumab-base induction treatment versus basilixmab-base induction treatment in kidney transplantation (the 3C Study): a randomised trial. Lancet 2014; 384: 1684–90. Ciancio G, Gaynor JJ, Guerra G, et al. Randomized trial of three induction antibodies in kidney transplantation: long-term results. Transplantation 2014; 97: 1128–38.
Post-partum depressive episodes and bipolar disorder With great interest, we read the Lancet Series on perinatal health. Louise Howard and colleagues’ Series paper1 discussed non-psychotic mental disorders in the perinatal period. In the second paper of the Series, Ian Jones and colleagues2 provided a comprehensive overview of post-partum psychotic
episodes occurring in the context of bipolar disorder or schizophrenia. Although Howard and colleagues1 methodically reviewed non-psychotic disorders, including major depressive disorder occurring during the perinatal period, an important topic that is not addressed is post-partum depression arising from an underlying bipolar disorder. In women with bipolar disorder, post-partum depressive episodes are more common than post-partum mania (hypomania) or psychosis. Post-partum episodes of depression last longer than other types of mood episodes, and are associated with substantial functional impairment and a high risk for suicide. Psychosis can result from several different mental disorders, so adequate treatment of psychotic symptoms must take into account their underlying cause. Jones and colleagues2 provide useful information about pharmacological treatment when bipolar disorder and schizophrenia are involved. Depressive episodes in the context of bipolar disorder pose unique treatment challenges. For example, there is the issue of missed identification of emerging episodes. By contrast with the acute nature of psychosis onset, depressive symptoms typically develop more gradually and can be misattributed to anxiety, adjustment, or hormonal factors. Most importantly, failure to consider the underlying cause of post-partum psychotic episodes could lead to improper treatment of depression and psychosis.3 For instance, consider depression or even depression with psychotic features in a woman with bipolar disorder; failure to take the underlying disorder into account can lead to use of antidepressants to treat depression, which would likely worsen the patient’s outcome.
MOLEKUUL/Science Photo Library
1
We declare no competing interests.
*Mustaq Khan, Verinder Sharma [email protected] Western University, Department of Psychiatry and Department of Psychology (MK), and Department of Obstetrics & Gynaecology and Department of Psychiatry (VS) London ON N6A 5C2, Canada
771
Correspondence
1
2
3
Howard LM, Molyneaux E, Dennis C-L, Rochat T, Stein A, Milgrom J. Non-psychotic mental disorders in the perinatal period. Lancet 2014; 384: 1775–88. Jones I, Chandra PS, Dazzan P, Howard LM. Bipolar disorder, affective psychosis, and schizophrenia in pregnancy and the post-partum period. Lancet 2014; 384: 1789–99. Sharma, V, Burt, VK, Ritchie, HL Bipolar II postpartum depression: detection, diagnosis, and treatment. Am J Psychiatry 2009; 166: 1217–21.
agreement with international trends and the Hellenic Society of Obstetrics and Gynecology committee’s opinion, the new guidelines aim to balance clinical effectiveness and cost, reducing unnecessary therapeutic interventions and protecting women from the potential harm of overdiagnosis and overtreatment. We declare no competing interests.
Nikolaos Vrachnis, *Nikolaos Vlachadis
For NHS cancer screening programmes see http://www. cancerscreening.nhs.uk
For the Hellenic Society of Obstetrics and Gynecology see www.hsog.gr
772
Guidelines on cervical and breast cancer screening in Greece
[email protected]
Andreas Tsounis and colleagues (Dec 13, p 2110)1 worry that the new measures from the Hellenic Ministry of Health on cervical and breast cancer screening will increase cancer cases and, as a consequence, social security expenses for cancer treatment in the near future. In fact, the screening regulations in Greece are evidence-based and in accordance with the official guidelines for early detection of cervical and breast cancer of the most authoritative international agencies, including the American Cancer Society, American Society for Colposcopy and Cervical Pathology, American Society for Clinical Pathology, and US Preventive Services Task Force,2,3 and NHS breast and cervical cancer screening programmes. Furthermore, the new cervical and breast cancer presymptomatic check recommendations are in accordance with the official guidelines of the Hellenic Society of Obstetrics and Gynecology.4,5 The Greek population is at a very low risk of both cervical and breast cancer; in 2012, the estimated age-standardised incidence of breast cancer in Greece was the lowest of the 27 EU countries, and cervical cancer the fourth lowest.6 The absence of central guidance in the country has led to burgeoning artificial demand for diagnostic tests, with a noticeable increase in health expenditure. In
1
Hellenic Society of Obstetrics and Gynecology, Athens, Greece, and Second Department of Obstetrics and Gynecology, National and Kapodistrian University of Athens, School of Medicine, Aretaieio Hospital, GR-11528, Athens, Greece
2
3
4
5
6
Tsounis A, Sarafis P, Alexopoulos EC. Austerity and its consequences on cancer screening in Greece. Lancet 2014; 384: 2110. Saslow D, Solomon D, Lawson HW, et al. American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology screening guidelines for the prevention and early detection of cervical cancer. CA Cancer J Clin 2012; 62: 147–72. US Preventive Services Task Force. Breast cancer screening. http://www. uspreventiveservicestaskforce.org/Page/ Document/RecommendationStatementFinal/ breast-cancer-screening (accessed Dec 27, 2014). Hellenic Society of Obstetrics and Gynecology guideline no 13. Primary and secondary prevention of cervical cancer. March, 2014. http://www.hsog-test.com/files/prolipsi_ karkinou_mitras.pdf (accessed Dec 28, 2014). Hellenic Society of Obstetrics and Gynecology guideline no 17. Secondary prevention of breast cancer. March, 2014. http://www.hsogtest.com/files/defterogenis_prolipsi_karninou_ tou_mastou.pdf (accessed Dec 28, 2014). Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, et al. Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer 2013; 49: 1374–403.
Raising awareness against acid attacks Between 2·4% and 10·7% of burns worldwide are due to chemical exposure.1 Raising awareness of the high incidence of acid attacks and ways to care for and prevent future medical complications is important. Although statistics are scarce, incidence of acid attacks seems to be increasing and most of the victims
are women. The increasing occurrence of acid attacks observed in several countries,2 such as Iran,3 is a call for medical, social, and government authorities to explore solutions to prevent such terrible acts from happening and mitigate further complications to their victims, such as burns complications, mental health, and stigma. Mannan and colleagues4 reported that Jamaica, Bangladesh, and Taiwan have the highest incidence of acid assaults. In Iran, of 121 cases of chemical injury that were reported between 2003 and 2008, ten cases were criminal assaults.5 According to Farhad and colleagues,3 acid burns are associated with poverty, larceny, and social issues, such as marital trouble (eg, rejected marriage proposal or divorce). Acid attacks should receive wider media coverage than they do at present: detailed information about the crime’s irreversible and terrible outcomes and the legal penalties should be stressed to the public. Furthermore, education around safety issues could reduce the incidence of chemical burns and their consequences. Prevention strategies have to be coordinated at national level. Victims—often from low socioeconomic areas—should receive the best medical care possible, first locally and then in a specialised centre. The damage caused by an acid burn is dependent on the concentration and quantity of acidic solution used and the duration of contact with the skin. Acid attack injuries are initially treated by neutralising the inciting solution.1 The affected skin should be washed with distilled water for at least 30 min.1 Neutralising agents do not offer an advantage over dilution with water, can delay treatment, and can worsen the injury because of the exothermic reactions that might occur.1 After initial treatment these patients have to be transported to a burns centre for specific surgical and medical management. We declare no competing interests.
www.thelancet.com Vol 385 February 28, 2015
2
3
3C Study Collaborative Group, Haynes R, Harden P, et al. Alemtuzumab-base induction treatment versus basilixmab-base induction treatment in kidney transplantation (the 3C Study): a randomised trial. Lancet 2014; 384: 1684–90. Vereerstraeten P, Abramowicz D, de Puaw L, Kinnaert P. Absence of deleterious effect on long-term kidney graft survival of rejection episodes with complete functional recovery. Transplantation 1997; 63: 1739–43. Ciancio G, Gaynor JJ, Guerra G, et al. Randomized trial of three induction antibodies in kidney transplantation: long-term results. Transplantation 2014; 97: 1128–38.
Authors’ reply The 3C Study showed that alemtuzumab-based induction treatment compared with standard basiliximab-based induction treatment reduced the risk of biopsy-proven acute rejection by about a half within the first 6 months of transplantation, without any excess infectious or other complications during this period.1 The 3C Study was designed to reliably investigate the long-term effects of alemtuzumab-based induction treatment on outcomes such as graft survival, which previous studies (including those cited by Andrea Berghofen and colleagues)2 have been too small to do. During the first 6 months, post-hoc analysis shows that allocation to alemtuzumab-based induction treatment was not associated with an increased risk of the composite outcome of graft failure or death within the first six months: 25 (5·9%) vs 16 (3·8%); hazard ratio 1·55 (95% CI 0·83–1·91; p=0·17). We did not note any autoimmune complications in the participants allocated alemtuzumab during the first 6 months of follow-up, but surveillance of such complications will continue. We agree with Neeraj Dhaun and David Kluth that cardiovascular disease is a major clinical problem after kidney transplantation. In post-hoc analyses, we noted no significant differences in blood pressure at 6 months between participants allocated alemtuzumab (mean systolic blood pressure 140·8 mm Hg [SE 0·96]) or basiliximab (140·2 [0·9]), or in proteinuria (mean In protein:creatinine ratio www.thelancet.com Vol 385 February 28, 2015
alemtuzumab 2·91 [0·10]; basiliximab 2·72 [0·11]). The long-term effects of the induction treatments on clinical cardiovascular outcomes will be presented in future reports. We agree with Andrea Berghofen and colleagues that the removal of alemtuzumab from the EU by the manufacturer means that its future use in kidney transplantation is uncertain, although this removal could not have been foreseen when the 3C Study was designed. RH, MJL, and CB receive core support from the UK Medical Research Council, British Heart Foundation, and Cancer Research UK. The Clinical Trial Service Unit and Epidemiological Studies Unit, which is part of the University of Oxford, has a staff policy of not accepting honoraria or consultancy fees. PH has received grants from Sanofi and Astellas. PF reports grants from Pfizer and Novartis during the conduct of this study, and consultancy fees from Sanofi and honoraria from Pfizer, both outside the submitted work.
*Richard Haynes, Colin Baigent, Martin J Landray, Paul Harden, Peter Friend [email protected] Clinical Trial Service Unit, and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford OX3 7LF, UK (RH, CB, MJL); Oxford Kidney Unit, Oxford University Hospitals NHS Trust, Oxford, UK (RH, PH); and Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK (PF) 1
2
3C Study Collaborative Group, Haynes R, Harden P, et al. Alemtuzumab-base induction treatment versus basilixmab-base induction treatment in kidney transplantation (the 3C Study): a randomised trial. Lancet 2014; 384: 1684–90. Ciancio G, Gaynor JJ, Guerra G, et al. Randomized trial of three induction antibodies in kidney transplantation: long-term results. Transplantation 2014; 97: 1128–38.
Post-partum depressive episodes and bipolar disorder With great interest, we read the Lancet Series on perinatal health. Louise Howard and colleagues’ Series paper1 discussed non-psychotic mental disorders in the perinatal period. In the second paper of the Series, Ian Jones and colleagues2 provided a comprehensive overview of post-partum psychotic
episodes occurring in the context of bipolar disorder or schizophrenia. Although Howard and colleagues1 methodically reviewed non-psychotic disorders, including major depressive disorder occurring during the perinatal period, an important topic that is not addressed is post-partum depression arising from an underlying bipolar disorder. In women with bipolar disorder, post-partum depressive episodes are more common than post-partum mania (hypomania) or psychosis. Post-partum episodes of depression last longer than other types of mood episodes, and are associated with substantial functional impairment and a high risk for suicide. Psychosis can result from several different mental disorders, so adequate treatment of psychotic symptoms must take into account their underlying cause. Jones and colleagues2 provide useful information about pharmacological treatment when bipolar disorder and schizophrenia are involved. Depressive episodes in the context of bipolar disorder pose unique treatment challenges. For example, there is the issue of missed identification of emerging episodes. By contrast with the acute nature of psychosis onset, depressive symptoms typically develop more gradually and can be misattributed to anxiety, adjustment, or hormonal factors. Most importantly, failure to consider the underlying cause of post-partum psychotic episodes could lead to improper treatment of depression and psychosis.3 For instance, consider depression or even depression with psychotic features in a woman with bipolar disorder; failure to take the underlying disorder into account can lead to use of antidepressants to treat depression, which would likely worsen the patient’s outcome.
MOLEKUUL/Science Photo Library
1
We declare no competing interests.
*Mustaq Khan, Verinder Sharma [email protected] Western University, Department of Psychiatry and Department of Psychology (MK), and Department of Obstetrics & Gynaecology and Department of Psychiatry (VS) London ON N6A 5C2, Canada
771
Correspondence
1
2
3
Howard LM, Molyneaux E, Dennis C-L, Rochat T, Stein A, Milgrom J. Non-psychotic mental disorders in the perinatal period. Lancet 2014; 384: 1775–88. Jones I, Chandra PS, Dazzan P, Howard LM. Bipolar disorder, affective psychosis, and schizophrenia in pregnancy and the post-partum period. Lancet 2014; 384: 1789–99. Sharma, V, Burt, VK, Ritchie, HL Bipolar II postpartum depression: detection, diagnosis, and treatment. Am J Psychiatry 2009; 166: 1217–21.
agreement with international trends and the Hellenic Society of Obstetrics and Gynecology committee’s opinion, the new guidelines aim to balance clinical effectiveness and cost, reducing unnecessary therapeutic interventions and protecting women from the potential harm of overdiagnosis and overtreatment. We declare no competing interests.
Nikolaos Vrachnis, *Nikolaos Vlachadis
For NHS cancer screening programmes see http://www. cancerscreening.nhs.uk
For the Hellenic Society of Obstetrics and Gynecology see www.hsog.gr
772
Guidelines on cervical and breast cancer screening in Greece
[email protected]
Andreas Tsounis and colleagues (Dec 13, p 2110)1 worry that the new measures from the Hellenic Ministry of Health on cervical and breast cancer screening will increase cancer cases and, as a consequence, social security expenses for cancer treatment in the near future. In fact, the screening regulations in Greece are evidence-based and in accordance with the official guidelines for early detection of cervical and breast cancer of the most authoritative international agencies, including the American Cancer Society, American Society for Colposcopy and Cervical Pathology, American Society for Clinical Pathology, and US Preventive Services Task Force,2,3 and NHS breast and cervical cancer screening programmes. Furthermore, the new cervical and breast cancer presymptomatic check recommendations are in accordance with the official guidelines of the Hellenic Society of Obstetrics and Gynecology.4,5 The Greek population is at a very low risk of both cervical and breast cancer; in 2012, the estimated age-standardised incidence of breast cancer in Greece was the lowest of the 27 EU countries, and cervical cancer the fourth lowest.6 The absence of central guidance in the country has led to burgeoning artificial demand for diagnostic tests, with a noticeable increase in health expenditure. In
1
Hellenic Society of Obstetrics and Gynecology, Athens, Greece, and Second Department of Obstetrics and Gynecology, National and Kapodistrian University of Athens, School of Medicine, Aretaieio Hospital, GR-11528, Athens, Greece
2
3
4
5
6
Tsounis A, Sarafis P, Alexopoulos EC. Austerity and its consequences on cancer screening in Greece. Lancet 2014; 384: 2110. Saslow D, Solomon D, Lawson HW, et al. American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology screening guidelines for the prevention and early detection of cervical cancer. CA Cancer J Clin 2012; 62: 147–72. US Preventive Services Task Force. Breast cancer screening. http://www. uspreventiveservicestaskforce.org/Page/ Document/RecommendationStatementFinal/ breast-cancer-screening (accessed Dec 27, 2014). Hellenic Society of Obstetrics and Gynecology guideline no 13. Primary and secondary prevention of cervical cancer. March, 2014. http://www.hsog-test.com/files/prolipsi_ karkinou_mitras.pdf (accessed Dec 28, 2014). Hellenic Society of Obstetrics and Gynecology guideline no 17. Secondary prevention of breast cancer. March, 2014. http://www.hsogtest.com/files/defterogenis_prolipsi_karninou_ tou_mastou.pdf (accessed Dec 28, 2014). Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, et al. Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer 2013; 49: 1374–403.
Raising awareness against acid attacks Between 2·4% and 10·7% of burns worldwide are due to chemical exposure.1 Raising awareness of the high incidence of acid attacks and ways to care for and prevent future medical complications is important. Although statistics are scarce, incidence of acid attacks seems to be increasing and most of the victims
are women. The increasing occurrence of acid attacks observed in several countries,2 such as Iran,3 is a call for medical, social, and government authorities to explore solutions to prevent such terrible acts from happening and mitigate further complications to their victims, such as burns complications, mental health, and stigma. Mannan and colleagues4 reported that Jamaica, Bangladesh, and Taiwan have the highest incidence of acid assaults. In Iran, of 121 cases of chemical injury that were reported between 2003 and 2008, ten cases were criminal assaults.5 According to Farhad and colleagues,3 acid burns are associated with poverty, larceny, and social issues, such as marital trouble (eg, rejected marriage proposal or divorce). Acid attacks should receive wider media coverage than they do at present: detailed information about the crime’s irreversible and terrible outcomes and the legal penalties should be stressed to the public. Furthermore, education around safety issues could reduce the incidence of chemical burns and their consequences. Prevention strategies have to be coordinated at national level. Victims—often from low socioeconomic areas—should receive the best medical care possible, first locally and then in a specialised centre. The damage caused by an acid burn is dependent on the concentration and quantity of acidic solution used and the duration of contact with the skin. Acid attack injuries are initially treated by neutralising the inciting solution.1 The affected skin should be washed with distilled water for at least 30 min.1 Neutralising agents do not offer an advantage over dilution with water, can delay treatment, and can worsen the injury because of the exothermic reactions that might occur.1 After initial treatment these patients have to be transported to a burns centre for specific surgical and medical management. We declare no competing interests.
www.thelancet.com Vol 385 February 28, 2015
