- Email: [email protected]
Spinal cord injury: time to move
Comment
Finally, as Belch and colleagues conclude, the absence of benefit in gene therapy trials might indicate challenges “to define the optimum dose, vector, route, and duration of administration” and the need for multiple interventions. Perhaps, in our enthusiasm to find an effective gene therapy for critical limb ischaemia, we have neglected to fully understand the basics before moving into clinical trials. *F Gerry R Fowkes, Jackie F Price Wolfson Unit for Prevention of Peripheral Vascular Diseases (FGRF) and Molecular Epidemiology Research Group (JFP), Centre for Population Health Sciences, University of Edinburgh, Edinburgh EH8 9AG, UK [email protected]
3 4
5
6
7 8
9 10
FGRF has received research support and ad-hoc honoraria from Sanofi-Aventis. JFP declares that she has no conflicts of interest. 1
2
Aboyans V, Criqui MH. The epidemiology of peripheral arterial disease. In: Dieter RS, Dieter RA III, eds. Peripheral arterial disease. New York: McGraw Hill, 2009: 1–25. Norgren L, Hiatt WR, Dormandy JA, Nehler MR, Harris KA, Fowkes FGR, on behalf of the TASC II Working Group. Inter-society consensus for the management of peripheral arterial disease. J Vasc Surg 2007; 45 (suppl S): S5–67.
11
Ruffolo AJ, Romano M, Ciapponi A. Prostanoids for critical limb ischaemia. Cochrane Database Syst Rev 2010; 1: CD006544. Isner JM, Pieczek A, Schainfeld R, et al. Clinical evidence of angiogenesis after arterial gene transfer of phVEGF165 in patient with ischaemic limb. Lancet 1996; 348: 370–74. Lawall H, Bramlage P, Amann B. Stem cell and progenitor cell therapy in peripheral artery disease: a critical appraisal. Thromb Haemost 2010; 103: 696–709. Collinson DJ, Donnelly R. Therapeutic angiogenesis in peripheral arterial disease: can biotechnology produce an effective collateral circulation? Eur J Vasc Endovasc Surg 2004; 28: 9–23. Gupta R, Tongers J, Losordo DW. Human studies of angiogenic gene therapy. Circ Res 2009; 105: 724–36. De Haro J, Acin F, Lopez-Quintana A, Florez A, Martinez-Aguilar E, Varela C. Meta-analysis of randomized, controlled clinical trials in angiogenesis: gene and cell therapy in peripheral arterial disease. Heart Vessels 2009; 24: 321–28. Kalka C, Baumgartner I. Gene and stem cell therapy in peripheral arterial occlusive disease. Vasc Med 2008; 13: 157–72. Belch J, Hiatt WR, Baumgartner I, et al, on behalf of the TAMARIS Committees and Investigators. Effect of fibroblast growth factor NV1FGF on amputation and death: a randomised placebo-controlled trial of gene therapy in critical limb ischaemia. Lancet 2011; published online May 31. DOI:10.1016/S0140-6736(11)60394-2. Nikol S, Baumgartner I, Van Belle E, et al. Therapeutic angiogenesis with intramuscular NV1FGF improves amputation-free survival in patients with critical limb ischaemia. Mol Ther 2008; 16: 972–78.
Spinal cord injury: time to move Published Online May 20, 2011 DOI:10.1016/S01406736(11)60711-3 See Articles page 1938
1896
Progress continues in the development of reparative interventions to enhance recovery after experimental spinal cord injury (SCI) in animal models.1 Although some of these treatments might be translatable to patients with moderate SCI, and are entering phase 1 or 2 clinical trials, evidence for the efficacy of any intervention designed to repair the injured human spinal cord is still lacking.2 Instead, improvement of ambulatory function is routinely observed with activity-based rehabilitation in individuals who retain voluntary movements of the legs after SCI.3,4 However, even intense training programmes have not resulted in functional recovery in patients with clinically motor complete SCI.5 Two contrasting hypotheses have been put forward to explain this failure to ameliorate motor function with training in severely injured individuals. Many argue that, contrary to other mammals, the spinal locomotor system of human beings relies heavily on supraspinal control to generate movement.6 Others have suggested that the markedly depressed state of spinal circuitries after severe SCI dissimulates the intrinsic capacity of these neuronal networks to produce motor output after training.5,7
This conceptual view has sparked the development of strategies to tune the physiological state of spinal circuits to a level sufficient for stepping and standing to occur. The underlying objective is to promote a highly functional state during rehabilitation to steer usedependent plastic changes in the trained sensorimotor pathways. Tonic electrical stimulation applied epidurally over the dorsal aspect of lumbosacral segments emerged as a safe and efficacious intervention to restore hindlimb movements in otherwise paralysed rats,8 rabbits,9 and cats.10 With epidural stimulation, the mammalian lumbosacral circuitry deprived of any supraspinal input can use task-specific sensory information to produce a range of movements, including stepping and standing. As predicted, locomotor training enabled by epidural stimulation substantially improves the capacities of spinal circuitries to produce movement.8 In The Lancet, Susan Harkema and colleagues11 report the first attempt to translate these promising findings in animal models of SCI to a viable application for human beings with motor complete SCI (figure, A). They surgically implanted an epidural electrode array over the www.thelancet.com Vol 377 June 4, 2011
Comment
lumbosacral segments of a 23-year-old man who became paraplegic after a motor-vehicle accident 3·4 years earlier. Before implantation, the patient showed no residual supraspinal control of leg movements despite 2 years of intense locomotor training. In the first weeks after surgery, epidural electrical stimulation enabled full weight-bearing standing when sensory information related to bilateral leg extension and loading was present. With otherwise unchanged stimulation parameters, the patient’s spinal cord was also capable of appropriately adjusting muscle activity in response to dynamic changes in body posture, or when transitioning from sitting to standing. In turn, epidural stimulation, adjusted for stepping, elicited locomotor-like patterns during manually assisted leg movement on a treadmill. As emphasised in animals,8 these combined results reveal that epidural stimulation modulates the physiological state of the spinal circuitry to enable sensory information to become a source of control for movement in the absence of clinically detectable supraspinal input (figure, B). Harkema and colleagues then enabled stand training with epidural stimulation. After several months, the patient regained the striking capacity to consciously control joint-specific movements of the leg, but only when enabled by epidural stimulation. This unexpected recovery of supraspinally mediated movement suggests that activity-dependent mechanisms promoted plasticity of axonal projections that presumably were spared by the injury. Our experiments in rats indeed suggest that activitybased interventions can promote extensive functional recovery and ubiquitous plasticity when boosted with robotic, electrical, and pharmacological enabling factors.12 Improvements in stimulation7 and training technology, with the addition of pharmacological agents,13 are therefore likely to further ameliorate functional recovery in human beings. We think that this novel phenomenon of electrically enabled motor control will inspire new thinking in the future design of strategies to restore function in motorimpaired individuals. Thus far, recovery of function after SCI has widely been interpreted as the need to regenerate severed fibres below the injury. Harkema and colleagues’ work instead suggests that a more immediate intervention might be feasible by capitalising on the impressive capacity of spared neuronal systems to reorganise through activity-dependent mechanisms. www.thelancet.com Vol 377 June 4, 2011
A
Motor-complete SCI Sensory neuron
Dorsal root
Injury
Spinal circuits Non-functional spared descending fibres
Motor neuron
B
Ventral root
Motor training
Supraspinal input: source of control EES
EES Sensory input: source of control
Task-specific sensory input
Sit to stand
Standing
Assisted locomotion
Figure: Electrically enabled motor control and training after SCI (A) Paralysing SCIs in human beings are rarely complete, but instead spare tissue bridges that might support functional recovery. (B) Epidural electrical stimulation facilitates processing of task-specific sensory information to produce movement. Training might promote plasticity of spared descending fibres, restoring some supraspinal control when spinal circuitries are tuned with epidural stimulation. SCI=spinal cord injury. EES=epidural electrical stimulation.
Additionally, therapies that promote nerve growth might substantially increase this plastic remodelling of neuronal circuitries.1 Challenges lie ahead. Harkema and colleagues used dated technology developed for pain management, which is therefore not optimised for motor-related applications. In consequence, these results should 1897
Comment
stimulate a surge of research in high-density spinal cord recording and stimulation interfaces, closed-loop control algorithms, implanted wireless systems, and sensory-based training procedures.7 Harkema and colleagues achieved a level of functional recovery in a paraplegic patient that remains unprecedented in SCI medicine. Although these results need to be confirmed in a clinical trial with a statistically sound number of participants, the exceptional results bring new hope in a field that has remained unsatisfying—with limited progress despite decades of research throughout the world. We are entering a new era when the time has come for spinal-cord-injured people to move. *Grégoire Courtine, Rubia van den Brand, Pavel Musienko Experimental Neurorehabilitation Laboratory, Department of Neurology, University of Zurich, Zurich 8008, Switzerland (GC, RvdB, PM); and Motor Physiology Laboratory, Pavlov Institute of Physiology, St Petersburg, Russia (PM) [email protected] GC and PM have a patent pending for electrode-array stimulator systems. GC has received funds from the European Community’s Seventh Framework Programme (CP-IP 258654, project NeuWALK) for related research. RvdB declares that he has no conflicts of interest. 1
Thuret S, Moon LD, Gage FH. Therapeutic interventions after spinal cord injury. Nat Rev Neurosci 2006; 7: 628–43.
2 3 4 5 6 7
8
9
10
11
12
13
Dietz V. Ready for human spinal cord repair? Brain 2008; 131: 2240–42. Dietz V, Colombo G, Jensen L. Locomotor activity in spinal man. Lancet 1994; 344: 1260–63. Behrman AL, Harkema SJ. Locomotor training after human spinal cord injury: a series of case studies. Phys Ther 2000; 80: 688–700. Harkema SJ. Plasticity of interneuronal networks of the functionally isolated human spinal cord. Brain Res Rev 2008; 57: 255–64. Capaday C. The special nature of human walking and its neural control. Trends Neurosci 2002; 25: 370–76. Musienko P, van den Brand R, Maerzendorfer O, Larmagnac A, Courtine G. Combinatory electrical and pharmacological neuroprosthetic interfaces to regain motor function after spinal cord injury. IEEE Trans Biomed Eng 2009; 56: 2707–11. Courtine G, Gerasimenko Y, van den Brand R, et al. Transformation of nonfunctional spinal circuits into functional states after the loss of brain input. Nat Neurosci 2009; 12: 1333–42. Musienko PE, Zelenin PV, Orlovsky GN, Deliagina TG. Facilitation of postural limb reflexes with epidural stimulation in spinal rabbits. J Neurophysiol 2010; 103: 1080–92. Musienko PE, Bogacheva IN, Gerasimenko YP. Significance of peripheral feedback in the generation of stepping movements during epidural stimulation of the spinal cord. Neurosci Behav Physiol 2007; 37: 181–90. Harkema S, Gerasimenko Y, Hodes J, et al. Effect of epidural stimulation of the lumbosacral spinal cord on voluntary movement, standing, and assisted stepping after motor complete paraplegia: a case study. Lancet 2011; published online May 20. DOI:10.1016/S0140-6736(11)60547-3. van den Brand R, Heustschi J, Friedli L, et al. Neurorehabilitative interventions restore voluntary locomotor activities following severe spinal cord injury. Neuroscience Meeting Planner; San Diego, CA: Society for Neuroscience; Nov 16, 2010: 684.11. http://www.abstractsonline.com/Plan/ ViewAbstract.aspx?sKey=0eca72e6-550f-4aa9-8312-47056d835f71&cKey= 7065db24-49aa-4024-80d0-93c165dc8808&mKey={E5D5C83F-CE2D4D71-9DD6-FC7231E090FB} (accessed May 13, 2011). Musienko PE, Van den Brand R, Märzendorfer O, et al. Controlling specific locomotor behaviors through multidimensional monoaminergic modulation of spinal circuitries. J Neurosci (in press).
Higher education and health care in Brazil Published Online May 9, 2011 DOI:10.1016/S01406736(11)60326-7 See Series pages 1949 and 1962 See Series Lancet 2011; 377: 1778, 1863, and 1877 See Online/Series DOI:10.1016/S01406736(11)60055-X
1898
Until the mid-20th century, there was no health-care system in Brazil.1 Rich patients were treated in private institutions, paying out-of-pocket fees; workers had access to labour-union clinics and hospitals. In urban areas, people who were poor had to seek assistance in overcrowded philanthropic or public institutions that would accept those who were indigent to Brazil. In rural areas, peasants and sharecroppers had to rely on healers or untrained lay caretakers for their health needs. At the peak of the country’s redemocratisation, the Constitution of 1988 declared health care as a citizen’s right and a duty of the State.2 Thereafter the Unified Health System (Sistema Único de Saúde or SUS) was organised with principles of universality, integral care, health promotion, and community participation, with public funds to provide free health care to Brazilian citizens.1 The SUS has two main lines of operation: the Family Health Programme provides primary health care in 5295 municipalities, and a network of public or
SUS-contracted clinics and hospitals delivers secondary and tertiary care nationwide. Along with public health interventions, which started in the 1970s, and with more recently implemented social policies related to employment and conditional cash-transfer, the impact of the SUS after 20 years has been positive.1,3,4 Over the past three decades, infant mortality decreased by about 6·3% a year, and life expectancy increased by 10·6 years.3 Mortality due to infectious disease decreased from 23% of total deaths in 1970 to less than 4% in 2007.4 Despite such achievements, serious problems involving equity, quality, and efficiency need to be acknowledged. Insufficient investment, corruption, and poor management because of governmental bureaucracy are among such problems. The main determinant of low-quality care provided by the SUS network is limited human resources; however, this limitation is qualitative not quantitative. The health-care workforce of Brazil comprises 1·5 million health professionals registered in professional boards www.thelancet.com Vol 377 June 4, 2011
Finally, as Belch and colleagues conclude, the absence of benefit in gene therapy trials might indicate challenges “to define the optimum dose, vector, route, and duration of administration” and the need for multiple interventions. Perhaps, in our enthusiasm to find an effective gene therapy for critical limb ischaemia, we have neglected to fully understand the basics before moving into clinical trials. *F Gerry R Fowkes, Jackie F Price Wolfson Unit for Prevention of Peripheral Vascular Diseases (FGRF) and Molecular Epidemiology Research Group (JFP), Centre for Population Health Sciences, University of Edinburgh, Edinburgh EH8 9AG, UK [email protected]
3 4
5
6
7 8
9 10
FGRF has received research support and ad-hoc honoraria from Sanofi-Aventis. JFP declares that she has no conflicts of interest. 1
2
Aboyans V, Criqui MH. The epidemiology of peripheral arterial disease. In: Dieter RS, Dieter RA III, eds. Peripheral arterial disease. New York: McGraw Hill, 2009: 1–25. Norgren L, Hiatt WR, Dormandy JA, Nehler MR, Harris KA, Fowkes FGR, on behalf of the TASC II Working Group. Inter-society consensus for the management of peripheral arterial disease. J Vasc Surg 2007; 45 (suppl S): S5–67.
11
Ruffolo AJ, Romano M, Ciapponi A. Prostanoids for critical limb ischaemia. Cochrane Database Syst Rev 2010; 1: CD006544. Isner JM, Pieczek A, Schainfeld R, et al. Clinical evidence of angiogenesis after arterial gene transfer of phVEGF165 in patient with ischaemic limb. Lancet 1996; 348: 370–74. Lawall H, Bramlage P, Amann B. Stem cell and progenitor cell therapy in peripheral artery disease: a critical appraisal. Thromb Haemost 2010; 103: 696–709. Collinson DJ, Donnelly R. Therapeutic angiogenesis in peripheral arterial disease: can biotechnology produce an effective collateral circulation? Eur J Vasc Endovasc Surg 2004; 28: 9–23. Gupta R, Tongers J, Losordo DW. Human studies of angiogenic gene therapy. Circ Res 2009; 105: 724–36. De Haro J, Acin F, Lopez-Quintana A, Florez A, Martinez-Aguilar E, Varela C. Meta-analysis of randomized, controlled clinical trials in angiogenesis: gene and cell therapy in peripheral arterial disease. Heart Vessels 2009; 24: 321–28. Kalka C, Baumgartner I. Gene and stem cell therapy in peripheral arterial occlusive disease. Vasc Med 2008; 13: 157–72. Belch J, Hiatt WR, Baumgartner I, et al, on behalf of the TAMARIS Committees and Investigators. Effect of fibroblast growth factor NV1FGF on amputation and death: a randomised placebo-controlled trial of gene therapy in critical limb ischaemia. Lancet 2011; published online May 31. DOI:10.1016/S0140-6736(11)60394-2. Nikol S, Baumgartner I, Van Belle E, et al. Therapeutic angiogenesis with intramuscular NV1FGF improves amputation-free survival in patients with critical limb ischaemia. Mol Ther 2008; 16: 972–78.
Spinal cord injury: time to move Published Online May 20, 2011 DOI:10.1016/S01406736(11)60711-3 See Articles page 1938
1896
Progress continues in the development of reparative interventions to enhance recovery after experimental spinal cord injury (SCI) in animal models.1 Although some of these treatments might be translatable to patients with moderate SCI, and are entering phase 1 or 2 clinical trials, evidence for the efficacy of any intervention designed to repair the injured human spinal cord is still lacking.2 Instead, improvement of ambulatory function is routinely observed with activity-based rehabilitation in individuals who retain voluntary movements of the legs after SCI.3,4 However, even intense training programmes have not resulted in functional recovery in patients with clinically motor complete SCI.5 Two contrasting hypotheses have been put forward to explain this failure to ameliorate motor function with training in severely injured individuals. Many argue that, contrary to other mammals, the spinal locomotor system of human beings relies heavily on supraspinal control to generate movement.6 Others have suggested that the markedly depressed state of spinal circuitries after severe SCI dissimulates the intrinsic capacity of these neuronal networks to produce motor output after training.5,7
This conceptual view has sparked the development of strategies to tune the physiological state of spinal circuits to a level sufficient for stepping and standing to occur. The underlying objective is to promote a highly functional state during rehabilitation to steer usedependent plastic changes in the trained sensorimotor pathways. Tonic electrical stimulation applied epidurally over the dorsal aspect of lumbosacral segments emerged as a safe and efficacious intervention to restore hindlimb movements in otherwise paralysed rats,8 rabbits,9 and cats.10 With epidural stimulation, the mammalian lumbosacral circuitry deprived of any supraspinal input can use task-specific sensory information to produce a range of movements, including stepping and standing. As predicted, locomotor training enabled by epidural stimulation substantially improves the capacities of spinal circuitries to produce movement.8 In The Lancet, Susan Harkema and colleagues11 report the first attempt to translate these promising findings in animal models of SCI to a viable application for human beings with motor complete SCI (figure, A). They surgically implanted an epidural electrode array over the www.thelancet.com Vol 377 June 4, 2011
Comment
lumbosacral segments of a 23-year-old man who became paraplegic after a motor-vehicle accident 3·4 years earlier. Before implantation, the patient showed no residual supraspinal control of leg movements despite 2 years of intense locomotor training. In the first weeks after surgery, epidural electrical stimulation enabled full weight-bearing standing when sensory information related to bilateral leg extension and loading was present. With otherwise unchanged stimulation parameters, the patient’s spinal cord was also capable of appropriately adjusting muscle activity in response to dynamic changes in body posture, or when transitioning from sitting to standing. In turn, epidural stimulation, adjusted for stepping, elicited locomotor-like patterns during manually assisted leg movement on a treadmill. As emphasised in animals,8 these combined results reveal that epidural stimulation modulates the physiological state of the spinal circuitry to enable sensory information to become a source of control for movement in the absence of clinically detectable supraspinal input (figure, B). Harkema and colleagues then enabled stand training with epidural stimulation. After several months, the patient regained the striking capacity to consciously control joint-specific movements of the leg, but only when enabled by epidural stimulation. This unexpected recovery of supraspinally mediated movement suggests that activity-dependent mechanisms promoted plasticity of axonal projections that presumably were spared by the injury. Our experiments in rats indeed suggest that activitybased interventions can promote extensive functional recovery and ubiquitous plasticity when boosted with robotic, electrical, and pharmacological enabling factors.12 Improvements in stimulation7 and training technology, with the addition of pharmacological agents,13 are therefore likely to further ameliorate functional recovery in human beings. We think that this novel phenomenon of electrically enabled motor control will inspire new thinking in the future design of strategies to restore function in motorimpaired individuals. Thus far, recovery of function after SCI has widely been interpreted as the need to regenerate severed fibres below the injury. Harkema and colleagues’ work instead suggests that a more immediate intervention might be feasible by capitalising on the impressive capacity of spared neuronal systems to reorganise through activity-dependent mechanisms. www.thelancet.com Vol 377 June 4, 2011
A
Motor-complete SCI Sensory neuron
Dorsal root
Injury
Spinal circuits Non-functional spared descending fibres
Motor neuron
B
Ventral root
Motor training
Supraspinal input: source of control EES
EES Sensory input: source of control
Task-specific sensory input
Sit to stand
Standing
Assisted locomotion
Figure: Electrically enabled motor control and training after SCI (A) Paralysing SCIs in human beings are rarely complete, but instead spare tissue bridges that might support functional recovery. (B) Epidural electrical stimulation facilitates processing of task-specific sensory information to produce movement. Training might promote plasticity of spared descending fibres, restoring some supraspinal control when spinal circuitries are tuned with epidural stimulation. SCI=spinal cord injury. EES=epidural electrical stimulation.
Additionally, therapies that promote nerve growth might substantially increase this plastic remodelling of neuronal circuitries.1 Challenges lie ahead. Harkema and colleagues used dated technology developed for pain management, which is therefore not optimised for motor-related applications. In consequence, these results should 1897
Comment
stimulate a surge of research in high-density spinal cord recording and stimulation interfaces, closed-loop control algorithms, implanted wireless systems, and sensory-based training procedures.7 Harkema and colleagues achieved a level of functional recovery in a paraplegic patient that remains unprecedented in SCI medicine. Although these results need to be confirmed in a clinical trial with a statistically sound number of participants, the exceptional results bring new hope in a field that has remained unsatisfying—with limited progress despite decades of research throughout the world. We are entering a new era when the time has come for spinal-cord-injured people to move. *Grégoire Courtine, Rubia van den Brand, Pavel Musienko Experimental Neurorehabilitation Laboratory, Department of Neurology, University of Zurich, Zurich 8008, Switzerland (GC, RvdB, PM); and Motor Physiology Laboratory, Pavlov Institute of Physiology, St Petersburg, Russia (PM) [email protected] GC and PM have a patent pending for electrode-array stimulator systems. GC has received funds from the European Community’s Seventh Framework Programme (CP-IP 258654, project NeuWALK) for related research. RvdB declares that he has no conflicts of interest. 1
Thuret S, Moon LD, Gage FH. Therapeutic interventions after spinal cord injury. Nat Rev Neurosci 2006; 7: 628–43.
2 3 4 5 6 7
8
9
10
11
12
13
Dietz V. Ready for human spinal cord repair? Brain 2008; 131: 2240–42. Dietz V, Colombo G, Jensen L. Locomotor activity in spinal man. Lancet 1994; 344: 1260–63. Behrman AL, Harkema SJ. Locomotor training after human spinal cord injury: a series of case studies. Phys Ther 2000; 80: 688–700. Harkema SJ. Plasticity of interneuronal networks of the functionally isolated human spinal cord. Brain Res Rev 2008; 57: 255–64. Capaday C. The special nature of human walking and its neural control. Trends Neurosci 2002; 25: 370–76. Musienko P, van den Brand R, Maerzendorfer O, Larmagnac A, Courtine G. Combinatory electrical and pharmacological neuroprosthetic interfaces to regain motor function after spinal cord injury. IEEE Trans Biomed Eng 2009; 56: 2707–11. Courtine G, Gerasimenko Y, van den Brand R, et al. Transformation of nonfunctional spinal circuits into functional states after the loss of brain input. Nat Neurosci 2009; 12: 1333–42. Musienko PE, Zelenin PV, Orlovsky GN, Deliagina TG. Facilitation of postural limb reflexes with epidural stimulation in spinal rabbits. J Neurophysiol 2010; 103: 1080–92. Musienko PE, Bogacheva IN, Gerasimenko YP. Significance of peripheral feedback in the generation of stepping movements during epidural stimulation of the spinal cord. Neurosci Behav Physiol 2007; 37: 181–90. Harkema S, Gerasimenko Y, Hodes J, et al. Effect of epidural stimulation of the lumbosacral spinal cord on voluntary movement, standing, and assisted stepping after motor complete paraplegia: a case study. Lancet 2011; published online May 20. DOI:10.1016/S0140-6736(11)60547-3. van den Brand R, Heustschi J, Friedli L, et al. Neurorehabilitative interventions restore voluntary locomotor activities following severe spinal cord injury. Neuroscience Meeting Planner; San Diego, CA: Society for Neuroscience; Nov 16, 2010: 684.11. http://www.abstractsonline.com/Plan/ ViewAbstract.aspx?sKey=0eca72e6-550f-4aa9-8312-47056d835f71&cKey= 7065db24-49aa-4024-80d0-93c165dc8808&mKey={E5D5C83F-CE2D4D71-9DD6-FC7231E090FB} (accessed May 13, 2011). Musienko PE, Van den Brand R, Märzendorfer O, et al. Controlling specific locomotor behaviors through multidimensional monoaminergic modulation of spinal circuitries. J Neurosci (in press).
Higher education and health care in Brazil Published Online May 9, 2011 DOI:10.1016/S01406736(11)60326-7 See Series pages 1949 and 1962 See Series Lancet 2011; 377: 1778, 1863, and 1877 See Online/Series DOI:10.1016/S01406736(11)60055-X
1898
Until the mid-20th century, there was no health-care system in Brazil.1 Rich patients were treated in private institutions, paying out-of-pocket fees; workers had access to labour-union clinics and hospitals. In urban areas, people who were poor had to seek assistance in overcrowded philanthropic or public institutions that would accept those who were indigent to Brazil. In rural areas, peasants and sharecroppers had to rely on healers or untrained lay caretakers for their health needs. At the peak of the country’s redemocratisation, the Constitution of 1988 declared health care as a citizen’s right and a duty of the State.2 Thereafter the Unified Health System (Sistema Único de Saúde or SUS) was organised with principles of universality, integral care, health promotion, and community participation, with public funds to provide free health care to Brazilian citizens.1 The SUS has two main lines of operation: the Family Health Programme provides primary health care in 5295 municipalities, and a network of public or
SUS-contracted clinics and hospitals delivers secondary and tertiary care nationwide. Along with public health interventions, which started in the 1970s, and with more recently implemented social policies related to employment and conditional cash-transfer, the impact of the SUS after 20 years has been positive.1,3,4 Over the past three decades, infant mortality decreased by about 6·3% a year, and life expectancy increased by 10·6 years.3 Mortality due to infectious disease decreased from 23% of total deaths in 1970 to less than 4% in 2007.4 Despite such achievements, serious problems involving equity, quality, and efficiency need to be acknowledged. Insufficient investment, corruption, and poor management because of governmental bureaucracy are among such problems. The main determinant of low-quality care provided by the SUS network is limited human resources; however, this limitation is qualitative not quantitative. The health-care workforce of Brazil comprises 1·5 million health professionals registered in professional boards www.thelancet.com Vol 377 June 4, 2011