Correspondence
In the past 2·5 years many hospitals and clinics have been damaged or destroyed by the war in Syria.1 To respond to the medical and humanitarian crises, the Syrian medical community used alternative approaches to maintain health care and establish makeshift medical facilities. In cities such as Aleppo and Damascus, medical facilities were built underground to be protected from bombs. Initially named field hospitals, most of these alternative medical facilities were far too basic and lacked necessary medical equipment and professional expertise to adequately respond to mass casualties and increasing risks of infectious diseases epidemics.2,3 A large number of Syrian medical professionals fled the country, and therefore, these field hospitals were crucial for the populations. Indeed, about 2000 physicians were practising in Aleppo before the crisis, now less than 100 remain.4 Medical and pharmacy students took a leading role in taking care of injured people and had to deal with complex injuries. Field hospitals have become more sophisticated with time. However, they cannot replace well-established health-care facilities by any means. With more than 100 000 deaths and about 8 million Syrians displaced internally or in neighbouring countries, local and international medical support by organisations such as the Syrian American Medical Society has been crucial but remains insufficient to meet the needs on the ground. With minimum international medical and humanitarian aid going to those who are in desperate need inside Syria, the situation is likely to worsen in the near future. We declare that we have no conflicts of interest.
*Fares Alahdab, Basel Albitar, Khaled Muhiedeen, Samer Attar, Bassel Atassi [email protected]
www.thelancet.com Vol 383 January 25, 2014
Mayo Clinic, Rochester, MN 55906, USA (FA); University of Kalamoon, Damascus, Syria (BAl); Faculty of Medicine, University of Damascus, Damascus, Syria (KM); Northwestern University, Chicago, IL, USA (SA); and Department of Internal Medicine, Hematology and Oncology, Little Company of Mary Hospital, Evergreen Park, IL, USA (BAt) 1
2
3
4
Kherallah M, Alahfez T, Sahloul Z, Eddin KD, Jamil G. Health care in Syria before and during the crisis. Avicenna J Med 2012; 2: 51–53. Reliefweb. Early Warning and Reporting System (EWARS) Syria, 2013. http://reliefweb. int/sites/reliefweb.int/files/resources/Syria%20 EWARS%20Weekly%20Bulletin%2C%20 Week%20No.%201%2030%20Dec.%20 2012%20-%205%20Jan.%202013.pdf (accessed Oct 22, 2013). WHO. Global Alert and Response. Polio in the Syrian Arab Republic—update. http://www. who.int/csr/don/2013_11_11polio/en/ (accessed Nov 11, 2013). MacFarquhar N. In Syria’s Civil War, Doctors Find Themselves in Cross Hairs. New York Times (New York), March 24, 2013: A6.
At Aleppo City Medical Council, we are doing our best to provide lifesaving care for the people of Aleppo, Syria. We are an independent body of Syrian medical professionals with no political or military affiliation, and it is our mission to help anyone without discrimination. The recent attacks in Aleppo have been relentless and unyielding in scale, and they have surpassed our capability to respond. Over 2 weeks in December, 2013, 4 of our field hospitals documented a total of 2364 patients received (table), People (n) Total received Women Men Children Died Wounded
2364 336 1284 744 386 1965
General surgery
129
Orthopaedic surgery
142
Vascular surgery
13
Urological surgery
12
Chest tube insertions
39
Ophthalmological surgery
20
Amputations
16
Intensive care patients
76
Referred to other hospitals
179
Table: Individuals treated in four field hospitals (M1, M2, M3, and M10) in Aleppo, Syria, Dec 15–28, 2013
744 were children. 386 people were killed, mostly civilians. These numbers record our work over 2 weeks alone and give a glimpse into our daily life over the past year. Our modest facilities have to cope with mass casualty events, and our staff have been working non-stop, with very few resources, and risking their own life. Although our ability to alleviate suffering and save lives is limited, we are at least making a difference for the few people who can make it to us. We hope for peace in Syria. Until this day comes, we will continue to serve those in need.
Fares Alahdab
Field hospitals in Syria
We declare that we have no conflicts of interest.
*Samer Attar, on behalf of the Aleppo City Medical Council [email protected] Northwestern University, Chicago, IL 60611, USA
Research on hormonal contraception and HIV Lauren Ralph and colleagues (Nov 2, p 1467)1 acknowledge the uncertainty of the evidence for the effect of hormonal contraception on increased risk of HIV acquisition, but recommend against investment in a randomised controlled trial. They argue that the observational data are of sufficiently high quality that the expected effect measure for injectable depot medroxyprogesterone acetate (DMPA) would neither lead to product withdrawal nor produce changes in WHO guidance. They also raise ethical and methodological questions about doing a randomised trial. Because hormonal contraceptives are widely used among young women at risk of both HIV and pregnancy in areas of high HIV incidence, this issue has major global health importance and requires the strongest evidence possible to resolve the uncertainty. We have considered the evidence, ethics, and feasibility of a possible experimental design for a randomised trial of hormonal contraception and HIV. First, regarding the evidence, a WHO expert panel reviewed all the available
Submissions should be made via our electronic submission system at http://ees.elsevier.com/ thelancet/
303
Correspondence
studies and judged the aggregate data to be of low quality.2 Specifically, they found the evidence was inconclusive to conclude that DMPA was causally related to HIV acquisition. The experts proposed no new restrictions on the use of injectable progestins in women at high risk of HIV, but because of the uncertainty, recommended the use of condoms for women using these methods. They also recommended that further research was necessary to provide the higher-quality evidence necessary for both greater scientific certainty and informing international guidelines. Only a randomised trial would provide high quality evidence to help resolve this uncertainty. Second, to be ethical, all trials require clinical equipoise among the experimental groups. In a randomised trial, alternative contraceptives would be compared with the DMPA standard to determine if they have different risks for HIV acquisition. This is precisely the ethical foundation for other HIVprevention trials, such as the MIRA trial cited in the Comment,1 which compared alternative prophylactic methods for which little or no data existed with standard products. Third, Ralph and colleagues question whether women will agree to be randomised to different contraceptives, and if so, whether they will continue the family planning methods to which they have been allocated. We agree that these are potential threats to trial quality and generalisability. However, different feasibility studies show the willingness of women to be randomised to similarly effective contraceptive groups.3,4 Through close attention to eligibility criteria, counselling before and after enrolment, contraceptive method continuation, and participant retention, we believe a randomised trial can be successfully implemented. Finally, we agree with Ralph and colleagues that much greater emphasis needs to be placed on increasing the contraceptive method mix, especially WHO Tier 1 methods. Implants and intrauterine devices are usually 304
20 times more effective in preventing unintended pregnancy than are DMPA and oral contraceptive pills.5 Women in countries with high HIV incidence need access to effective contraception and protection against HIV infection. We should simultaneously advance family planning programmes and assure these newer, more effective methods are as safe or safer than are other methods they might replace. The ambiguity of the current situation has left policy makers in countries with high HIV incidence unsure about the safety of continuing to provide DMPA. Any alleged increased risk associated with hormonal methods could be due to a combination of selection bias, different condom usage, or other flaws inherent to observational research. A randomised controlled trial offers the best hope to find out which of the most effective contraceptive methods might lead to the lowest risk of HIV acquisition. The ECHO Consortium is a multiorganisational collaborative team developing a protocol for a randomised controlled trial of hormonal contraception and HIV. The ECHO Consortium comprises: Jared Baeten, Ward Cates, Connie Celum, Tsungai Chipato, Stephanie Combes, Deborah Donnell, Peter Gichangi, G Justus Hofmeyr, Charles Morrison, Nelly Mugo, Kavita Nanda, Sharon Phillips, Helen Rees, Douglas Taylor, and Marleen Temmerman.
*Ward Cates, on behalf of the Evidence for Contraceptive Options and HIV Outcomes (ECHO) Consortium [email protected] FHI 360, Durham, NC 27513, USA 1
2
3
4
5
Ralph LJ, McCoy SI, Hallett T, Padian N. Next steps for research on hormonal contraception and HIV. Lancet 2013; 382: 1467–69. WHO. Hormonal contraception and HIV: technical statement. Geneva, Switzerland; Research DoRHa, 2012. Hubacher D, Raymond ER, Beksinka M, et al. Hormonal contraception and the risks of STI acquisition: results of a feasibility study to plan a future randomized trial. Contraception 2008; 77: 366–70. Feldblum PJ, Caraway J, Bahamondes L, et al. Randomized assignment to copper IUD or depot medroxyprogesterone acetate: feasibility of enrollment, continuation, and disease ascertainment. Contraception 2005; 72: 187–91. Winner B, Peipert JF, Zhao Q, et al. Effectiveness of longer-acting reversible contraception. N Engl J Med 2012; 366: 1998–2007.
Available long-acting reversible contraceptives (LARC)—intrauterine devices, implant, injections, patches— are numerous and highly efficacious against pregnancy. Under ideal conditions of access and quality counselling, they give women the power to control fertility to an extent barely imagined by previous generations. Nevertheless, none of them protect against HIV. In their Comment, Lauren Ralph and colleagues1 integrate this tragic circumstance into their reasoning and recommendations, whereas this theme is given less emphasis by Ward Cates advocating for a randomised controlled trial between these effective contraceptives. 2 Thus, these two very influential and experienced parties debate the ethics and feasibility of carrying out a formal trial to estimate the additional risk of HIV infection incurred by users of depot medroxyprogesterone acetate (DMPA) versus other LARCs, with Ralph and colleagues downplaying its importance compared with Cates.2 We agree with Ralph and colleagues on the difficulties involved in a trial;1 moreover, pilot studies do not promise uniform enrolment across sites (44% in Brazil, 69% in Vietnam, 72% in Guatemala , and 82% in Egypt),3 and at least two studies show more dropouts in DMPA users than in users of other LARCs.4,5 Nor are there any possibilities of blinding—neither among those enrolled in the trial, nor among those assessing adherence. Moreover, recent analyses of the behavioural demands that affect adherence certainly emphasise caution.6 Like Ralph and colleagues,1 we think it is more important to improve the options and coverage for HIV protection, achieved via exploring further oral or vaginal methods, and expanding access and improving adherence to male or female condom. We should focus on these questions and accept as inevitable a level of uncertainty about DMPA, as other LARCs with a better safety profile are developed. www.thelancet.com Vol 383 January 25, 2014
In the past 2·5 years many hospitals and clinics have been damaged or destroyed by the war in Syria.1 To respond to the medical and humanitarian crises, the Syrian medical community used alternative approaches to maintain health care and establish makeshift medical facilities. In cities such as Aleppo and Damascus, medical facilities were built underground to be protected from bombs. Initially named field hospitals, most of these alternative medical facilities were far too basic and lacked necessary medical equipment and professional expertise to adequately respond to mass casualties and increasing risks of infectious diseases epidemics.2,3 A large number of Syrian medical professionals fled the country, and therefore, these field hospitals were crucial for the populations. Indeed, about 2000 physicians were practising in Aleppo before the crisis, now less than 100 remain.4 Medical and pharmacy students took a leading role in taking care of injured people and had to deal with complex injuries. Field hospitals have become more sophisticated with time. However, they cannot replace well-established health-care facilities by any means. With more than 100 000 deaths and about 8 million Syrians displaced internally or in neighbouring countries, local and international medical support by organisations such as the Syrian American Medical Society has been crucial but remains insufficient to meet the needs on the ground. With minimum international medical and humanitarian aid going to those who are in desperate need inside Syria, the situation is likely to worsen in the near future. We declare that we have no conflicts of interest.
*Fares Alahdab, Basel Albitar, Khaled Muhiedeen, Samer Attar, Bassel Atassi [email protected]
www.thelancet.com Vol 383 January 25, 2014
Mayo Clinic, Rochester, MN 55906, USA (FA); University of Kalamoon, Damascus, Syria (BAl); Faculty of Medicine, University of Damascus, Damascus, Syria (KM); Northwestern University, Chicago, IL, USA (SA); and Department of Internal Medicine, Hematology and Oncology, Little Company of Mary Hospital, Evergreen Park, IL, USA (BAt) 1
2
3
4
Kherallah M, Alahfez T, Sahloul Z, Eddin KD, Jamil G. Health care in Syria before and during the crisis. Avicenna J Med 2012; 2: 51–53. Reliefweb. Early Warning and Reporting System (EWARS) Syria, 2013. http://reliefweb. int/sites/reliefweb.int/files/resources/Syria%20 EWARS%20Weekly%20Bulletin%2C%20 Week%20No.%201%2030%20Dec.%20 2012%20-%205%20Jan.%202013.pdf (accessed Oct 22, 2013). WHO. Global Alert and Response. Polio in the Syrian Arab Republic—update. http://www. who.int/csr/don/2013_11_11polio/en/ (accessed Nov 11, 2013). MacFarquhar N. In Syria’s Civil War, Doctors Find Themselves in Cross Hairs. New York Times (New York), March 24, 2013: A6.
At Aleppo City Medical Council, we are doing our best to provide lifesaving care for the people of Aleppo, Syria. We are an independent body of Syrian medical professionals with no political or military affiliation, and it is our mission to help anyone without discrimination. The recent attacks in Aleppo have been relentless and unyielding in scale, and they have surpassed our capability to respond. Over 2 weeks in December, 2013, 4 of our field hospitals documented a total of 2364 patients received (table), People (n) Total received Women Men Children Died Wounded
2364 336 1284 744 386 1965
General surgery
129
Orthopaedic surgery
142
Vascular surgery
13
Urological surgery
12
Chest tube insertions
39
Ophthalmological surgery
20
Amputations
16
Intensive care patients
76
Referred to other hospitals
179
Table: Individuals treated in four field hospitals (M1, M2, M3, and M10) in Aleppo, Syria, Dec 15–28, 2013
744 were children. 386 people were killed, mostly civilians. These numbers record our work over 2 weeks alone and give a glimpse into our daily life over the past year. Our modest facilities have to cope with mass casualty events, and our staff have been working non-stop, with very few resources, and risking their own life. Although our ability to alleviate suffering and save lives is limited, we are at least making a difference for the few people who can make it to us. We hope for peace in Syria. Until this day comes, we will continue to serve those in need.
Fares Alahdab
Field hospitals in Syria
We declare that we have no conflicts of interest.
*Samer Attar, on behalf of the Aleppo City Medical Council [email protected] Northwestern University, Chicago, IL 60611, USA
Research on hormonal contraception and HIV Lauren Ralph and colleagues (Nov 2, p 1467)1 acknowledge the uncertainty of the evidence for the effect of hormonal contraception on increased risk of HIV acquisition, but recommend against investment in a randomised controlled trial. They argue that the observational data are of sufficiently high quality that the expected effect measure for injectable depot medroxyprogesterone acetate (DMPA) would neither lead to product withdrawal nor produce changes in WHO guidance. They also raise ethical and methodological questions about doing a randomised trial. Because hormonal contraceptives are widely used among young women at risk of both HIV and pregnancy in areas of high HIV incidence, this issue has major global health importance and requires the strongest evidence possible to resolve the uncertainty. We have considered the evidence, ethics, and feasibility of a possible experimental design for a randomised trial of hormonal contraception and HIV. First, regarding the evidence, a WHO expert panel reviewed all the available
Submissions should be made via our electronic submission system at http://ees.elsevier.com/ thelancet/
303
Correspondence
studies and judged the aggregate data to be of low quality.2 Specifically, they found the evidence was inconclusive to conclude that DMPA was causally related to HIV acquisition. The experts proposed no new restrictions on the use of injectable progestins in women at high risk of HIV, but because of the uncertainty, recommended the use of condoms for women using these methods. They also recommended that further research was necessary to provide the higher-quality evidence necessary for both greater scientific certainty and informing international guidelines. Only a randomised trial would provide high quality evidence to help resolve this uncertainty. Second, to be ethical, all trials require clinical equipoise among the experimental groups. In a randomised trial, alternative contraceptives would be compared with the DMPA standard to determine if they have different risks for HIV acquisition. This is precisely the ethical foundation for other HIVprevention trials, such as the MIRA trial cited in the Comment,1 which compared alternative prophylactic methods for which little or no data existed with standard products. Third, Ralph and colleagues question whether women will agree to be randomised to different contraceptives, and if so, whether they will continue the family planning methods to which they have been allocated. We agree that these are potential threats to trial quality and generalisability. However, different feasibility studies show the willingness of women to be randomised to similarly effective contraceptive groups.3,4 Through close attention to eligibility criteria, counselling before and after enrolment, contraceptive method continuation, and participant retention, we believe a randomised trial can be successfully implemented. Finally, we agree with Ralph and colleagues that much greater emphasis needs to be placed on increasing the contraceptive method mix, especially WHO Tier 1 methods. Implants and intrauterine devices are usually 304
20 times more effective in preventing unintended pregnancy than are DMPA and oral contraceptive pills.5 Women in countries with high HIV incidence need access to effective contraception and protection against HIV infection. We should simultaneously advance family planning programmes and assure these newer, more effective methods are as safe or safer than are other methods they might replace. The ambiguity of the current situation has left policy makers in countries with high HIV incidence unsure about the safety of continuing to provide DMPA. Any alleged increased risk associated with hormonal methods could be due to a combination of selection bias, different condom usage, or other flaws inherent to observational research. A randomised controlled trial offers the best hope to find out which of the most effective contraceptive methods might lead to the lowest risk of HIV acquisition. The ECHO Consortium is a multiorganisational collaborative team developing a protocol for a randomised controlled trial of hormonal contraception and HIV. The ECHO Consortium comprises: Jared Baeten, Ward Cates, Connie Celum, Tsungai Chipato, Stephanie Combes, Deborah Donnell, Peter Gichangi, G Justus Hofmeyr, Charles Morrison, Nelly Mugo, Kavita Nanda, Sharon Phillips, Helen Rees, Douglas Taylor, and Marleen Temmerman.
*Ward Cates, on behalf of the Evidence for Contraceptive Options and HIV Outcomes (ECHO) Consortium [email protected] FHI 360, Durham, NC 27513, USA 1
2
3
4
5
Ralph LJ, McCoy SI, Hallett T, Padian N. Next steps for research on hormonal contraception and HIV. Lancet 2013; 382: 1467–69. WHO. Hormonal contraception and HIV: technical statement. Geneva, Switzerland; Research DoRHa, 2012. Hubacher D, Raymond ER, Beksinka M, et al. Hormonal contraception and the risks of STI acquisition: results of a feasibility study to plan a future randomized trial. Contraception 2008; 77: 366–70. Feldblum PJ, Caraway J, Bahamondes L, et al. Randomized assignment to copper IUD or depot medroxyprogesterone acetate: feasibility of enrollment, continuation, and disease ascertainment. Contraception 2005; 72: 187–91. Winner B, Peipert JF, Zhao Q, et al. Effectiveness of longer-acting reversible contraception. N Engl J Med 2012; 366: 1998–2007.
Available long-acting reversible contraceptives (LARC)—intrauterine devices, implant, injections, patches— are numerous and highly efficacious against pregnancy. Under ideal conditions of access and quality counselling, they give women the power to control fertility to an extent barely imagined by previous generations. Nevertheless, none of them protect against HIV. In their Comment, Lauren Ralph and colleagues1 integrate this tragic circumstance into their reasoning and recommendations, whereas this theme is given less emphasis by Ward Cates advocating for a randomised controlled trial between these effective contraceptives. 2 Thus, these two very influential and experienced parties debate the ethics and feasibility of carrying out a formal trial to estimate the additional risk of HIV infection incurred by users of depot medroxyprogesterone acetate (DMPA) versus other LARCs, with Ralph and colleagues downplaying its importance compared with Cates.2 We agree with Ralph and colleagues on the difficulties involved in a trial;1 moreover, pilot studies do not promise uniform enrolment across sites (44% in Brazil, 69% in Vietnam, 72% in Guatemala , and 82% in Egypt),3 and at least two studies show more dropouts in DMPA users than in users of other LARCs.4,5 Nor are there any possibilities of blinding—neither among those enrolled in the trial, nor among those assessing adherence. Moreover, recent analyses of the behavioural demands that affect adherence certainly emphasise caution.6 Like Ralph and colleagues,1 we think it is more important to improve the options and coverage for HIV protection, achieved via exploring further oral or vaginal methods, and expanding access and improving adherence to male or female condom. We should focus on these questions and accept as inevitable a level of uncertainty about DMPA, as other LARCs with a better safety profile are developed. www.thelancet.com Vol 383 January 25, 2014
