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1.
BMJ Open ; 14(4): e081652, 2024 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-38684258

RESUMEN

OBJECTIVES: To use verbal autopsy (VA) data to understand health system utilisation and the potential avoidability associated with fatal injury. Then to categorise any evident barriers driving avoidable delays to care within a Three-Delays framework that considers delays to seeking (Delay 1), reaching (Delay 2) or receiving (Delay 3) quality injury care. DESIGN: Retrospective analysis of existing VA data routinely collected by a demographic surveillance site. SETTING: Karonga Health and Demographic Surveillance Site (HDSS) population, Northern Malawi. PARTICIPANTS: Fatally injured members of the HDSS. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the proportion of fatal injury deaths that were potentially avoidable. Secondary outcomes were the delay stage and corresponding barriers associated with avoidable deaths and the health system utilisation for fatal injuries within the health system. RESULTS: Of the 252 deaths due to external causes, 185 injury-related deaths were analysed. Deaths were predominantly among young males (median age 30, IQR 11-48), 71.9% (133/185). 35.1% (65/185) were assessed as potentially avoidable. Delay 1 was implicated in 30.8% (20/65) of potentially avoidable deaths, Delay 2 in 61.5% (40/65) and Delay 3 in 75.4% (49/65). Within Delay 1, 'healthcare literacy' was most commonly implicated barrier in 75% (15/20). Within Delay 2, 'communication' and 'prehospital care' were the most commonly implicated in 92.5% (37/40). Within Delay 3, 'physical resources' were most commonly implicated, 85.7% (42/49). CONCLUSIONS: VA is feasible for studying pathways to care and health system responsiveness in avoidable deaths following injury and ascertaining the delays that contribute to deaths. A large proportion of injury deaths were avoidable, and we have identified several barriers as potential targets for intervention. Refining and integrating VA with other health system assessment methods is likely necessary to holistically understand an injury care health system.


Asunto(s)
Autopsia , Aceptación de la Atención de Salud , Heridas y Lesiones , Humanos , Malaui/epidemiología , Estudios Retrospectivos , Masculino , Femenino , Heridas y Lesiones/mortalidad , Adulto , Persona de Mediana Edad , Adolescente , Adulto Joven , Niño , Aceptación de la Atención de Salud/estadística & datos numéricos , Causas de Muerte
2.
PLoS Med ; 21(1): e1004344, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38252654

RESUMEN

BACKGROUND: Injuries represent a vast and relatively neglected burden of disease affecting low- and middle-income countries (LMICs). While many health systems underperform in treating injured patients, most assessments have not considered the whole system. We integrated findings from 9 methods using a 3 delays approach (delays in seeking, reaching, or receiving care) to prioritise important trauma care health system barriers in Karonga, Northern Malawi, and exemplify a holistic health system assessment approach applicable in comparable settings. METHODS AND FINDINGS: To provide multiple perspectives on each conceptual delay and include data from community-based and facility-based sources, we used 9 methods to examine the injury care health system. The methods were (1) household survey; (2) verbal autopsy analysis; (3) community focus group discussions (FGDs); (4) community photovoice; (5) facility care-pathway process mapping and elucidation of barriers following injury; (6) facility healthcare worker survey; (7) facility assessment survey; (8) clinical vignettes for care process quality assessment of facility-based healthcare workers; and (9) geographic information system (GIS) analysis. Empirical data collection took place in Karonga, Northern Malawi, between July 2019 and February 2020. We used a convergent parallel study design concurrently conducting all data collection before subsequently integrating results for interpretation. For each delay, a matrix was created to juxtapose method-specific data relevant to each barrier identified as driving delays to injury care. Using a consensus approach, we graded the evidence from each method as to whether an identified barrier was important within the health system. We identified 26 barriers to access timely quality injury care evidenced by at least 3 of the 9 study methods. There were 10 barriers at delay 1, 6 at delay 2, and 10 at delay 3. We found that the barriers "cost," "transport," and "physical resources" had the most methods providing strong evidence they were important health system barriers within delays 1 (seeking care), 2 (reaching care), and 3 (receiving care), respectively. Facility process mapping provided evidence for the greatest number of barriers-25 of 26 within the integrated analysis. There were some barriers with notable divergent findings between the community- and facility-based methods, as well as among different community- and facility-based methods, which are discussed. The main limitation of our study is that the framework for grading evidence strength for important health system barriers across the 9 studies was done by author-derived consensus; other researchers might have created a different framework. CONCLUSIONS: By integrating 9 different methods, including qualitative, quantitative, community-, patient-, and healthcare worker-derived data sources, we gained a rich insight into the functioning of this health system's ability to provide injury care. This approach allowed more holistic appraisal of this health system's issues by establishing convergence of evidence across the diverse methods used that the barriers of cost, transport, and physical resources were the most important health system barriers driving delays to seeking, reaching, and receiving injury care, respectively. This offers direction and confidence, over and above that derived from single methodology studies, for prioritising barriers to address through health service development and policy.


Asunto(s)
Países en Desarrollo , Accesibilidad a los Servicios de Salud , Humanos , Malaui , Calidad de la Atención de Salud , Encuestas y Cuestionarios
3.
BMC Health Serv Res ; 24(1): 131, 2024 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-38268016

RESUMEN

BACKGROUND: Most injury care research in low-income contexts such as Malawi is facility centric. Community-derived data is needed to better understand actual injury incidence, health system utilisation and barriers to seeking care following injury. METHODS: We administered a household survey to 2200 households in Karonga, Malawi. The primary outcome was injury incidence, with non-fatal injuries classified as major or minor (> 30 or 1-29 disability days respectively). Those seeking medical treatment were asked about time delays to seeking, reaching and receiving care at a facility, where they sought care, and whether they attended a second facility. We performed analysis for associations between injury severity and whether the patient sought care, stayed overnight in a facility, attended a second facility, or received care within 1 or 2 h. The reason for those not seeking care was asked. RESULTS: Most households (82.7%) completed the survey, with 29.2% reporting an injury. Overall, 611 non-fatal and four fatal injuries were reported from 531 households: an incidence of 6900 per 100,000. Major injuries accounted for 26.6%. Three quarters, 76.1% (465/611), sought medical attention. Almost all, 96.3% (448/465), seeking care attended a primary facility first. Only 29.7% (138/465), attended a second place of care. Only 32.0% (142/444), received care within one hour. A further 19.1% (85/444) received care within 2 h. Major injury was associated with being more likely to have; sought care (94.4% vs 69.8% p < 0.001), stayed overnight at a facility (22.9% vs 15.4% P = 0.047), attended a second place of care (50.3% vs 19.9%, P < 0.001). For those not seeking care the most important reason was the injury not being serious enough for 52.1% (74/142), followed by transport difficulties 13.4% (19/142) and financial costs 5.6% (8/142). CONCLUSION: Injuries in Northern Malawi are substantial. Community-derived details are necessary to fully understand injury burden and barriers to seeking and reaching care.


Asunto(s)
Asistencia Médica , Calidad de la Atención de Salud , Humanos , Malaui/epidemiología , Pobreza
4.
BMJ Open ; 13(6): e070900, 2023 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-37263691

RESUMEN

OBJECTIVES: We used the process mapping method and Three Delays framework, to identify and visually represent the relationship between critical actions, decisions and barriers to access to care following injury in the Karonga health system, Northern Malawi. DESIGN: Facilitated group process mapping workshops with summary process mapping synthesis. SETTING: Process mapping workshops took place in 11 identified health system facilities (one per facility) providing injury care for a population in Karonga, Northern Malawi. PARTICIPANTS: Fifty-four healthcare workers from various cadres took part. RESULTS: An overall injury health system summary map was created using those categories of action, decision and barrier that were sometimes or frequently reported. This provided a visual summary of the process following injury within the health system. For Delay 1 (seeking care) four barriers were most commonly described (by 8 of 11 facilities) these were 'cultural norms', 'healthcare literacy', 'traditional healers' and 'police processes'. For Delay 2 (reaching care) the barrier most frequently described was 'transport'-a lack of timely affordable emergency transport (formal or informal) described by all 11 facilities. For Delay 3 (receiving quality care) the most commonly reported barrier was that of 'physical resources' (9 of 11 facilities). CONCLUSIONS: We found our novel approach combining several process mapping exercises to produce a summary map to be highly suited to rapid health system assessment identifying barriers to injury care, within a Three Delays framework. We commend the approach to others wishing to conduct rapid health system assessments in similar contexts.


Asunto(s)
Instituciones de Salud , Calidad de la Atención de Salud , Humanos , Malaui , Costos y Análisis de Costo , Personal de Salud , Accesibilidad a los Servicios de Salud
5.
Eur J Trauma Emerg Surg ; 49(1): 227-239, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35900383

RESUMEN

PURPOSE: In military trauma, disaster medicine, and casualties injured in remote locations, times to advanced medical and surgical treatment are often prolonged, potentially reducing survival and increasing morbidity. Since resuscitation with blood/blood components improves survival over short pre-surgical times, this study aimed to evaluate the quality of resuscitation afforded by blood/blood products or crystalloid resuscitation over extended 'pre-hospital' timelines in a porcine model of militarily relevant traumatic haemorrhagic shock. METHODS: This study underwent local ethical review and was done under the authority of Animals (Scientific Procedures) Act 1986. Forty-five terminally anaesthetised pigs received a soft tissue injury to the right thigh, haemorrhage (30% blood volume and a Grade IV liver injury) and fluid resuscitation initiated 30 min later [Group 1 (no fluid); 2 (0.9% saline); 3 (1:1 packed red blood cells:plasma); 4 (fresh whole blood); or 5 (plasma)]. Fluid (3 ml/kg bolus) was administered during the resuscitation period (maximum duration 450 min) when the systolic blood pressure fell below 80 mmHg. Surviving animals were culled with an overdose of anaesthetic. RESULTS: Survival time was significantly shorter for Group 1 compared to the other groups (P < 0.05). Despite the same triggers for resuscitation when compared to blood/blood components, saline was associated with a shorter survival time (P = 0.145), greater pathophysiological burden and significantly greater resuscitation fluid volume (P < 0.0001). CONCLUSION: When times to advanced medical care are prolonged, resuscitation with blood/blood components is recommended over saline due to the superior quality and stability of resuscitation achieved, which are likely to lead to improved patient outcomes.


Asunto(s)
Choque Hemorrágico , Porcinos , Animales , Choque Hemorrágico/tratamiento farmacológico , Resucitación/métodos , Hemorragia/terapia , Transfusión de Componentes Sanguíneos , Hígado/lesiones , Fluidoterapia
6.
Injury ; 53(5): 1690-1698, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35153068

RESUMEN

INTRODUCTION: Injuries disproportionately impact low- and middle-income countries like Malawi. The Lancet Commission on Global Surgery's indicators include the population proportion accessing laparotomy and open fracture care, key trauma interventions, within two hours. The "Golden Hour" for receiving facility-based resuscitation also guides injury care system strengthening. Firstly, we estimated the proportion of the local population able to reach primary, secondary and tertiary facility care within two and one hours using Geographic Information System (GIS) analysis. Secondly, we compared community household-reported with GIS-estimated travel time. METHODS: Using information from a Health and Demographic Surveillance Site (Karonga, Malawi) on road network, facility location, and local staff-estimated travel speeds, we used a GIS-generated friction surface to calculate the shortest travel time from all households to each facility serving the population. We surveyed community households who reported travel time to their preferred, closest, government secondary and tertiary facilities. For recently injured community members, time to reach facility care was recorded. To assess the relationship between community household-reported travel time and GIS-estimated travel time, we used linear regression to generate a proportionality constant. To assess associations and agreement between injured patient-reported and GIS-estimated travel time, we used Kendall rank and Cohen's kappa tests. RESULTS: Using GIS, we estimated 79.1% of households could reach any secondary facility, 20.5% the government secondary facility, and 0% the government tertiary facility, within two hours. Only 28.2% could reach any secondary facility within one hour, 0% for the government secondary facility. Community household-reported travel time exceeded GIS-estimated travel time. The proportionality constant was 1.25 (95%CI 1.21-1.30) for the closest facility, 1.28 (95%CI 1.23-1.34) for the preferred facility, 1.45 (95%CI 1.33-1.58) for the government secondary facility, and 2.12 (95%CI 1.84-2.41) for tertiary care. Comparing injured patient-reported with GIS-estimated travel time, the correlation coefficient was 0.25 (SE 0.047) and Cohen's kappa was 0.15 (95%CI 0.078-0.23), suggesting poor agreement. DISCUSSION: Most households couldn't reach government secondary care within recognised thresholds indicating poor temporal access. Since GIS-estimated travel time was shorter than community-reported travel time, the true proportion may be lower still. GIS derived estimates of population emergency care access in similar contexts should be interpreted accordingly.


Asunto(s)
Servicios Médicos de Urgencia , Sistemas de Información Geográfica , Accesibilidad a los Servicios de Salud , Humanos , Malaui/epidemiología , Viaje
8.
Ann Surg ; 272(4): 564-572, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32657917

RESUMEN

OBJECTIVES: Estimating the likely success of limb revascularization in patients with lower-extremity arterial trauma is central to decisions between attempting limb salvage and amputation. However, the projected outcome is often unclear at the time these decisions need to be made, making them difficult and threatening sound judgement. The objective of this study was to develop and validate a prediction model that can quantify an individual patient's risk of failed revascularization. METHODS: A BN prognostic model was developed using domain knowledge and data from the US joint trauma system. Performance (discrimination, calibration, and accuracy) was tested using ten-fold cross validation and externally validated on data from the UK Joint Theatre Trauma Registry. BN performance was compared to the mangled extremity severity score. RESULTS: Rates of amputation performed because of nonviable limb tissue were 12.2% and 19.6% in the US joint trauma system (n = 508) and UK Joint Theatre Trauma Registry (n = 51) populations respectively. A 10-predictor BN accurately predicted failed revascularization: area under the receiver operating characteristic curve (AUROC) 0.95, calibration slope 1.96, Brier score (BS) 0.05, and Brier skill score 0.50. The model maintained excellent performance in an external validation population: AUROC 0.97, calibration slope 1.72, Brier score 0.08, Brier skill score 0.58, and had significantly better performance than mangled extremity severity score at predicting the need for amputation [AUROC 0.95 (0.92-0.98) vs 0.74 (0.67-0.80); P < 0.0001]. CONCLUSIONS: A BN (https://www.traumamodels.com) can accurately predict the outcome of limb revascularization at the time of initial wound evaluation. This information may complement clinical judgement, support rational and shared treatment decisions, and establish sensible treatment expectations.


Asunto(s)
Algoritmos , Arterias/lesiones , Arterias/cirugía , Sistemas de Apoyo a Decisiones Clínicas , Extremidad Inferior/irrigación sanguínea , Extremidad Inferior/cirugía , Adolescente , Adulto , Amputación Quirúrgica , Humanos , Extremidad Inferior/lesiones , Aprendizaje Automático , Persona de Mediana Edad , Estudios Prospectivos , Resultado del Tratamiento , Procedimientos Quirúrgicos Vasculares , Adulto Joven
9.
J Neurol Neurosurg Psychiatry ; 91(4): 359-365, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-32034113

RESUMEN

INTRODUCTION: Traumatic brain injury (TBI) is the most common cause of death on the modern battlefield. In recent conflicts in Iraq and Afghanistan, the US typically deployed neurosurgeons to medical treatment facilities (MTFs), while the UK did not. Our aim was to compare the incidence, TBI and treatment in US and UK-led military MTF to ascertain if differences in deployed trauma systems affected outcomes. METHODS: The US and UK Combat Trauma Registries were scrutinised for patients with HI at deployed MTFs between March 2003 and October 2011. Registry datasets were adapted to stratify TBI using the Mayo Classification System for Traumatic Brain Injury Severity. An adjusted multiple logistic regression model was performed using fatality as the binomial dependent variable and treatment in a US-MTF or UK-MTF, surgical decompression, US military casualty and surgery performed by a neurosurgeon as independent variables. RESULTS: 15 031 patients arrived alive at military MTF after TBI. Presence of a neurosurgeon was associated with increased odds of survival in casualties with moderate or severe TBI (p<0.0001, OR 2.71, 95% CI 2.34 to 4.73). High injury severity (Injury Severity Scores 25-75) was significantly associated with a lower survival (OR 4×104, 95% CI 1.61×104 to 110.6×104, p<0.001); however, having a neurosurgeon present still remained significantly positively associated with survival (OR 3.25, 95% CI 2.71 to 3.91, p<0.001). CONCLUSIONS: Presence of neurosurgeons increased the likelihood of survival after TBI. We therefore recommend that the UK should deploy neurosurgeons to forward military MTF whenever possible in line with their US counterparts.


Asunto(s)
Lesiones Traumáticas del Encéfalo/mortalidad , Personal Militar , Procedimientos Neuroquirúrgicos , Adulto , Campaña Afgana 2001- , Lesiones Traumáticas del Encéfalo/cirugía , Femenino , Humanos , Puntaje de Gravedad del Traumatismo , Guerra de Irak 2003-2011 , Masculino , Neurocirujanos , Estudios Retrospectivos , Tasa de Supervivencia , Reino Unido , Estados Unidos
10.
BMJ Open ; 9(11): e033557, 2019 11 25.
Artículo en Inglés | MEDLINE | ID: mdl-31772107

RESUMEN

OBJECTIVES: To perform the first direct comparison of the facial injuries sustained and treatment performed at USA and UK deployed medical treatment facilities (MTFs) in support of the military campaigns in Iraq and Afghanistan. SETTING: The US and UK Joint Theatre Trauma Registries were scrutinised for all patients with facial injuries presenting alive to a UK or US deployed MTF between 1 March 2003 and 31 October 2011. PARTICIPANTS: US and UK military personnel, local police, local military and civilians. PRIMARY AND SECONDARY OUTCOME MEASURES: An adjusted multiple logistic regression model was performed using tracheostomy as the primary dependent outcome variable and treatment in a US MTF, US or UK military, mandible fracture and treatment of mandible fracture as independent secondary variables. RESULTS: Facial injuries were identified in 16 944 casualties, with the most common being those to skin/muscle (64%), bone fractures (36%), inner/middle ear (28%) and intraoral damage (11%). Facial injuries were equally likely to undergo surgery in US MTF as UK MTF (OR: 1.06, 95% CI 0.4603 to 1.142, p=0.6656); however, variations were seen in injury type treated. In US MTF, 692/1452 (48%) of mandible fractures were treated by either open or closed reduction compared with 0/167 (0%) in UK MTF (χ2: 113.6; p≤0.0001). US military casualties who had treatment of their mandible fracture (open reduction and internal fixation or mandibulo-maxillary fixation) were less likely to have had a tracheostomy than those who did not undergo stabilisation of the fractured mandible (OR: 0.61, 95% CI 0.44 to 0.86; p=0.0066). CONCLUSIONS: The capability to surgically treat mandible fractures by open or closed reduction should be considered as an integral component of deployed coalition surgical care in the future.


Asunto(s)
Traumatismos Faciales/terapia , Medicina Militar/métodos , Traqueostomía/estadística & datos numéricos , Heridas Relacionadas con la Guerra/terapia , Adolescente , Adulto , Campaña Afgana 2001- , Afganistán/epidemiología , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Traumatismos Faciales/etiología , Traumatismos Faciales/mortalidad , Femenino , Humanos , Lactante , Irak/epidemiología , Guerra de Irak 2003-2011 , Modelos Logísticos , Masculino , Persona de Mediana Edad , Medicina Militar/estadística & datos numéricos , Sistema de Registros/estadística & datos numéricos , Estudios Retrospectivos , Reino Unido/epidemiología , Estados Unidos/epidemiología , Heridas Relacionadas con la Guerra/etiología , Heridas Relacionadas con la Guerra/mortalidad , Adulto Joven
11.
J Vasc Surg ; 70(1): 224-232, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-30786987

RESUMEN

OBJECTIVE: Vascular injury is a leading cause of death and disability in military and civilian settings. Most wartime and an increasing amount of civilian vascular trauma arises from penetrating mechanisms of injury due to gunshot or explosion. The objective of this study was to provide a comprehensive examination of penetrating lower extremity arterial injury and to characterize long-term limb salvage and differences related to mechanisms of injury. METHODS: The military trauma registries of the United States and the United Kingdom were analyzed to identify service members who sustained penetrating lower limb arterial injury (2001-2014). Treatment and limb salvage data were studied and comparisons made of patients whose penetrating vascular trauma arose from explosion (group 1) vs gunshot (group 2). Standardized statistical testing was used, with Bonferroni corrections for multiple comparisons. RESULTS: The cohort consisted of 568 combat casualties (mean age, 25.2 years) with 597 injuries (explosion, n = 416; gunshot, n = 181). Group 1 had higher Injury Severity Score (P < .05) and Mangled Extremity Severity Score (P < .0001), required more blood transfusion (P < .05), and had more tibial (P < .01) and popliteal (P < .05) arterial injuries; group 2 had more profunda femoris injuries (P < .05). Initial surgical management for the whole cohort included vein interposition graft (33%), ligation (31%), primary repair with or without patch angioplasty (16%), temporary vascular shunting (15%), and primary amputation (6%). No difference in patency of arterial reconstruction was found between group 1 and group 2, although group 1 had a higher incidence of primary (13% vs 2%; P < .05) and secondary (19% vs 9%; P < .05) amputation. Similarly, longer term freedom from amputation was lower for group 1 than for group 2 (68% vs 89% at 5.5 years; Cox hazard ratio, 0.30; P < .0001), as was physical functioning (36-Item Short Form Health Survey data; mean, 39.80 vs 43.20; P < .05). CONCLUSIONS: The majority of wartime lower extremity arterial injuries result from an explosive mechanism that preferentially affects the tibial vasculature and results in poorer long-term limb salvage compared with those injured with firearms. The mortality associated with immediate limb salvage attempts is low, and delayed amputations occur weeks later, affording the patient involvement in the decision-making and rehabilitation planning. We recommend assertive attempts at vascular repair and limb salvage for service members injured by explosive and gunshot mechanisms.


Asunto(s)
Amputación Quirúrgica , Arterias/cirugía , Traumatismos por Explosión/cirugía , Procedimientos Endovasculares , Extremidad Inferior/irrigación sanguínea , Injerto Vascular , Heridas por Arma de Fuego/cirugía , Adulto , Amputación Quirúrgica/efectos adversos , Amputación Quirúrgica/mortalidad , Conflictos Armados , Arterias/lesiones , Arterias/fisiopatología , Traumatismos por Explosión/diagnóstico , Traumatismos por Explosión/mortalidad , Traumatismos por Explosión/fisiopatología , Bases de Datos Factuales , Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/mortalidad , Humanos , Puntaje de Gravedad del Traumatismo , Ligadura , Recuperación del Miembro , Medicina Militar , Sistema de Registros , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Reino Unido , Estados Unidos , Injerto Vascular/efectos adversos , Injerto Vascular/métodos , Injerto Vascular/mortalidad , Heridas por Arma de Fuego/diagnóstico , Heridas por Arma de Fuego/mortalidad , Heridas por Arma de Fuego/fisiopatología , Adulto Joven
12.
PLoS One ; 14(1): e0210914, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30677062

RESUMEN

BACKGROUND: Currently, patients receiving vascularized composite allotransplantation (VCA) grafts must take long-term systemic immunosuppressive therapy to prevent immunologic rejection. The morbidity and mortality associated with these medications is the single greatest barrier to more patients being able to receive these life-enhancing transplants. In contrast to solid organs, VCA, exemplified by hand or face transplants, allow visual diagnosis of clinical acute rejection (AR), directed biopsy and targeted graft therapies. Local immunosuppression in VCA could reduce systemic drug exposure and limit adverse effects. This proof of concept study evaluated, in a large animal forelimb VCA model, the efficacy and tolerability of a novel graft-implanted enzyme-responsive, tacrolimus (TAC)-eluting hydrogel platform, in achieving long-term graft survival. METHODS: Orthotopic forelimb VCA were performed in single haplotype mismatched mini-swine. Controls (n = 2) received no treatment. Two groups received TAC hydrogel: high dose (n = 4, 91 mg TAC) and low dose (n = 4, 49 mg TAC). The goal was to find a dose that was tolerable and resulted in long-term graft survival. Limbs were evaluated for clinical and histopathological signs of AR. TAC levels were measured in serial blood and skin tissue samples. Tolerability of the dose was evaluated by monitoring animal feeding behavior and weight. RESULTS: Control limbs underwent Banff Grade IV AR by post-operative day six. Low dose TAC hydrogel treatment resulted in long-term graft survival time to onset of Grade IV AR ranging from 56 days to 93 days. High dose TAC hydrogel also resulted in long-term graft survival (24 to 42 days), but was not well tolerated. CONCLUSION: Graft-implanted TAC-loaded hydrogel delays the onset of Grade IV AR of mismatched porcine forelimb VCA grafts, resulting in long term graft survival and demonstrates dose-dependent tolerability.


Asunto(s)
Aloinjertos Compuestos , Tacrolimus/administración & dosificación , Alotrasplante Compuesto Vascularizado/métodos , Animales , Aloinjertos Compuestos/efectos de los fármacos , Aloinjertos Compuestos/inmunología , Aloinjertos Compuestos/patología , Implantes de Medicamentos , Miembro Anterior/trasplante , Rechazo de Injerto/inmunología , Rechazo de Injerto/prevención & control , Supervivencia de Injerto/efectos de los fármacos , Supervivencia de Injerto/inmunología , Hidrogeles , Inmunosupresores/administración & dosificación , Inmunosupresores/farmacocinética , Modelos Animales , Prueba de Estudio Conceptual , Porcinos , Porcinos Enanos , Tacrolimus/farmacocinética
13.
Ann Plast Surg ; 82(4): 452-458, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30628928

RESUMEN

INTRODUCTION: Vascularized composite allotransplantation can reconstruct devastating tissue loss by replacing like-with-like tissues, most commonly in the form of hand or face transplantation. Unresolved technical and ethical challenges have meant that such transplants remain experimental treatments. The most significant barrier to expansion of this field is the requirement for systemic immunosuppression, its toxicity and effect on longevity.Hydrogen sulfide (H2S) has been shown experimentally to ameliorate the ischemia reperfusion injury associated with composite tissue autotransplantation, which has been linked to acute rejection in solid organ transplantation. In this protocol, a large-animal model was used to evaluate the effect of H2S on acute rejection after composite tissue allotransplantation. MATERIALS AND METHODS: A musculocutaneous flap model in SLA-mismatched swine was used to evaluate acute rejection of allotransplants in 2 groups: control animals (n = 8) and a treatment group in which the allografts were pretreated with hydrogen sulfide (n = 8). Neither group was treated with systemic immunosuppression. Acute rejection was graded clinically and histopathologically by an independent, blinded pathologist. Data were analyzed by t tests with correction for multiple comparisons by the Holm-Sídák method. RESULTS: Clinically, H2S-treated tissue composites showed a delay in the onset of rejection that was statistically significant from postoperative day 6. Histopathologically, this difference between groups was also apparent, although evidence of a difference in groups disappeared beyond day 10. CONCLUSIONS: Targeted hydrogen sulfide treatment of vascularized composite allografts immediately before transplantation can delay acute rejection. This may, in turn, reduce or obviate the requirement for systemic immunosuppression.


Asunto(s)
Aloinjertos Compuestos/trasplante , Rechazo de Injerto/prevención & control , Sulfuro de Hidrógeno/farmacología , Colgajo Miocutáneo/trasplante , Alotrasplante Compuesto Vascularizado/métodos , Enfermedad Aguda , Animales , Modelos Animales de Enfermedad , Supervivencia de Injerto , Análisis Multivariante , Cuidados Preoperatorios/métodos , Distribución Aleatoria , Medición de Riesgo , Porcinos , Resultado del Tratamiento , Alotrasplante Compuesto Vascularizado/efectos adversos , Cicatrización de Heridas/fisiología
15.
J Reconstr Microsurg ; 35(2): 97-107, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30099732

RESUMEN

BACKGROUND: Ischemia-reperfusion injury (IRI) precipitates acute rejection of vascularized composite allografts (VCA). Hyperbaric preservation of tissues ex vivo, between harvest and revascularization, may reduce IRI and mitigate acute rejection of VCA. METHODS: A porcine heterotopic musculocutaneous gracilis flap model was used. In phase 1, control autografts (n = 5) were infused with University of Wisconsin Solution (UWS) and stored at 4°C for 3 hours. Intervention autografts (n = 5) were placed in a hyperbaric oxygen organ preservation system for 5 hours and infused with hyperoxygenated UWS at 20°C and 3 atm. Grafts were replanted into the animals' necks. In phase 2, similarly treated control (n = 8) and intervention grafts (n = 8) were allotransplanted into the necks of animals separated by a typed and standardized genetic mismatch. No systemic immunosuppression was given. Systemic markers of IRI, and clinical and histopathological assessments of necrosis and rejection were performed. RESULTS: Autotransplanted tissue composites preserved in the hyperbaric chamber showed histopathological evidence of less muscle necrosis at 3 hours (p = 0.05). Despite a longer period of ischemia, no evidence was found of a difference in systemic markers of IRI following revascularization in these groups. Allotransplanted tissues supported ex vivo within the hyperbaric perfusion device experienced acute rejection significantly later than corresponding controls. CONCLUSION: Hyperbaric warm perfusion preserves musculocutaneous tissue composites ex vivo for longer than standard cold preservation in this model. This translates into a delay in acute rejection of allotransplanted tissue composites.


Asunto(s)
Aloinjertos/fisiología , Supervivencia de Injerto/fisiología , Oxigenoterapia Hiperbárica/métodos , Preservación de Órganos/métodos , Daño por Reperfusión/prevención & control , Animales , Femenino , Modelos Animales , Perfusión , Porcinos
16.
Injury ; 50(1): 125-130, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30219382

RESUMEN

BACKGROUND: Haemorrhage is the leading cause of death on the battlefield. Seventy percent of injuries are due to explosive mechanisms. Anecdotally, these patients have had poorer outcomes when compared to those with penetrating mechanisms of injury (MOI). We wished to test the hypothesis that outcomes following vascular reconstruction were worse in blast-injured than non blast-injured patients. METHODS: Retrospective cohort study. British and American combat casualties with arterial injuries sustained in Iraq or Afghanistan (2003-2014) were identified from the UK Joint Theatre Trauma Registry (JTTR). Eligibility included explosive or penetrating MOI, with follow-up to UK hospital discharge, or death. Outcomes were mortality, amputation, graft thrombosis, haemorrhage, and infection. Statistical analysis was performed using Pearson Chi-Square test, t-tests, ANOVA or non-parametric equivalent, and survival analyses. RESULTS: One hundred and fifteen patients were included, 80 injured by explosive and 35 by penetrating mechanisms. Evacuation time, ISS, number of arterial injuries, age and gender were comparable between groups. Seventy percent of arterial injuries resulted from an explosive MOI. The explosive injuries group received more blood products (p = 0.008) and suffered more regions injured (p < 0.0001). Early surgical interventions in both were ligation (n = 36, 31%), vein graft (n = 33, 29%) and shunting (n = 9, 8%). Mortality (n = 12, 10%) was similar between groups. Differences in limb salvage rates following explosive (n = 17, 53%) vs penetrating (n = 13, 76.47%) mechanisms approached statistical significance (p = 0.056). Nine (28%) vein grafted patients developed complications. No evidence of a difference in the incidence of vein graft thrombosis was found when comparing explosive with non-explosive cohorts (p = 0.154). CONCLUSIONS: The recorded numbers of vein grafts following combat arterial trauma in are small in the JTTR. No statistically-significant differences in complications, including vein graft thrombosis, were found between cohorts injured by explosive and non-explosive mechanisms.


Asunto(s)
Traumatismos por Explosión , Medicina Militar , Personal Militar , Lesiones del Sistema Vascular/clasificación , Heridas por Arma de Fuego , Adulto , Campaña Afgana 2001- , Traumatismos por Explosión/fisiopatología , Traumatismos por Explosión/cirugía , Femenino , Humanos , Puntaje de Gravedad del Traumatismo , Guerra de Irak 2003-2011 , Recuperación del Miembro , Masculino , Pronóstico , Estudios Retrospectivos , Reino Unido , Estados Unidos , Procedimientos Quirúrgicos Vasculares/estadística & datos numéricos , Lesiones del Sistema Vascular/fisiopatología , Lesiones del Sistema Vascular/cirugía , Heridas por Arma de Fuego/fisiopatología , Heridas por Arma de Fuego/cirugía , Adulto Joven
17.
NPJ Regen Med ; 3: 13, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30155273

RESUMEN

The recent prolonged conflicts in Iraq and Afghanistan saw the advancement of deployed trauma care to a point never before seen in war. The rapid translation of lessons from combat casualty care research, facilitated by an appetite for risk, contributed to year-on-year improvements in care of the injured. These paradigms, however, can only ever halt the progression of damage. Regenerative medicine approaches, in contrast, hold a truly disruptive potential to go beyond the cessation of damage from blast or ballistic trauma, to stimulate its reversal, and to do so from a very early point following injury. The internationally distributed and, in parts austere environments in which operational medical care is delivered provide an almost unique challenge to the development and translation of regenerative medicine technologies. In parallel, however, an inherent appetite for risk means that Defence will always be an early adopter. In focusing our operational priorities for regenerative medicine, the authors conducted a review of the current research landscape in the UK and abroad and sought wide clinical opinion. Our priorities are all applicable very far forward in the patient care pathway, and are focused on three broad and currently under-researched areas, namely: (a) blood, as an engineered tissue; (b) the mechanobiology of deep tissue loss and mechanobiological approaches to regeneration, and; (c) modification of the endogenous response. In focusing on these areas, we hope to engender the development of regenerative solutions for improved functional recovery from injuries sustained in conflict.

18.
J Trauma Acute Care Surg ; 84(6S Suppl 1): S3-S13, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29799823

RESUMEN

The Trauma Hemostasis and Oxygenation Research (THOR) Network has developed a consensus statement on the role of permissive hypotension in remote damage control resuscitation (RDCR). A summary of the evidence on permissive hypotension follows the THOR Network position on the topic. In RDCR, the burden of time in the care of the patients suffering from noncompressible hemorrhage affects outcomes. Despite the lack of published evidence, and based on clinical experience and expertise, it is the THOR Network's opinion that the increase in prehospital time leads to an increased burden of shock, which poses a greater risk to the patient than the risk of rebleeding due to slightly increased blood pressure, especially when blood products are available as part of prehospital resuscitation.The THOR Network's consensus statement is, "In a casualty with life-threatening hemorrhage, shock should be reversed as soon as possible using a blood-based HR fluid. Whole blood is preferred to blood components. As a part of this HR, the initial systolic blood pressure target should be 100 mm Hg. In RDCR, it is vital for higher echelon care providers to receive a casualty with sufficient physiologic reserve to survive definitive surgical hemostasis and aggressive resuscitation. The combined use of blood-based resuscitation and limiting systolic blood pressure is believed to be effective in promoting hemostasis and reversing shock".


Asunto(s)
Fluidoterapia/métodos , Resucitación/métodos , Heridas y Lesiones/terapia , Presión Sanguínea , Fluidoterapia/normas , Humanos , Hipotensión/etiología , Hipotensión/terapia , Resucitación/normas , Choque Hemorrágico/etiología , Choque Hemorrágico/terapia
20.
Tissue Eng Part B Rev ; 23(2): 183-198, 2017 04.
Artículo en Inglés | MEDLINE | ID: mdl-27824295

RESUMEN

Traumatic soft tissue wounds present a significant reconstructive challenge. The adoption of closed-circuit negative pressure wound therapy (NPWT) has enabled surgeons to temporize these wounds before reconstruction. Such systems use porous synthetic foam scaffolds as wound fillers at the interface between the negative pressure system and the wound bed. The idea of using a bespoke porous biomaterial that enhances wound healing, as filler for an NPWT system, is attractive as it circumvents concerns regarding reconstructive delay and the need for dressing changes that are features of the current systems. Porous foam biomaterials are mechanically robust and able to synthesize in situ. Hence, they exhibit potential to fulfill the niche for such a functionalized injectable material. Injectable scaffolds are currently in use for minimally invasive surgery, but the design parameters for large-volume expansive foams remain unclear. Potential platforms include hydrogel systems, (particularly superabsorbent, superporous, and nanocomposite systems), polyurethane-based moisture-cured foams, and high internal phase emulsion polymer systems. The aim of this review is to discuss the design parameters for such future biomaterials and review potential candidate materials for further research into this up and coming field.


Asunto(s)
Hidrogeles/farmacología , Inyecciones , Ingeniería de Tejidos/métodos , Andamios del Tejido/química , Cicatrización de Heridas/efectos de los fármacos , Animales , Fenómenos Biomecánicos/efectos de los fármacos , Humanos , Porosidad
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