RESUMEN
AIM: To estimate the cost-effectiveness of diagnostic management strategies for children with minor head injury and identify an optimal strategy. METHODS: A probabilistic decision analysis model was developed to estimate the costs and quality-adjusted life years (QALYs) accrued by each of six potential management strategies for minor head injury, including a theoretical 'zero option' strategy of discharging all patients home without investigation. The model took a lifetime horizon and the perspective of the National Health Service. RESULTS: The optimal strategy was based on the Children's Head injury Algorithm for the prediction of Important Clinical Events (CHALICE) rule, although the costs and outcomes associated with each strategy were broadly similar. CONCLUSIONS: Liberal use of CT scanning based on a high sensitivity decision rule is not only effective but also cost saving, with the CHALICE rule being the optimal strategy, although there is some uncertainty in the results. Incremental changes in the costs and QALYs are very small when all selective CT strategies are compared. The estimated cost of caring for patients with brain injury worsened by delayed treatment is very high compared with the cost of CT scanning. This analysis suggests that all hospitals receiving children with minor head injury should have unrestricted access to CT scanning for use in conjunction with evidence-based guidelines.
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Traumatismos Craneocerebrales/diagnóstico por imagen , Traumatismos Craneocerebrales/economía , Tomografía Computarizada por Rayos X/economía , Adolescente , Adulto , Niño , Análisis Costo-Beneficio , Técnicas de Apoyo para la Decisión , Femenino , Humanos , Masculino , Calidad de Vida , Sensibilidad y Especificidad , Adulto JovenRESUMEN
Police officers spend large amounts of time performing duties within a police cruiser and report a high prevalence of musculoskeletal problems. This study evaluated the effects of driver seat and duty belt design on posture, pressure and discomfort. Ten male and 10 female university students attended two sessions involving simulated driving in a standard police seat (CV) and an active lumbar support (ALS) seat. Participants wore a full duty belt (FDB) or reduced duty belt (RDB) in each seat. Lumbar postures, driver-seat and driver-duty belt pressures and perceived discomfort were measured. Gender × Seat interactions were found for pelvic (p = 0.0001) and lumbar postures (p = 0.003). Females had more lumbar flexion than males and were more extended in the ALS seat (-9.8 ± 11.3°) than CV seat (-19.8 ± 9.6°). The FDB had greater seat pressure than the RDB (p < 0.0001), which corresponded to increased pelvis discomfort. This study supports the use of an ALS seat and RDB to reduce injury risk associated with prolonged sitting in police officers. PRACTITIONER SUMMARY: Police officers report a high prevalence of musculoskeletal problems to the lower back, associated with prolonged driving and further investigation is needed to reduce injury risk. This simulated driving study investigated seat and duty belt configuration on biomechanical measures and discomfort. Seat design had the greatest impact, regardless of gender and males benefited more from a reduced belt configuration.
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Automóviles , Aplicación de la Ley , Dolor Musculoesquelético/etiología , Postura/fisiología , Adulto , Conducción de Automóvil , Diseño de Equipo , Femenino , Humanos , Vértebras Lumbares/fisiopatología , Masculino , Pelvis/fisiopatología , Presión , Adulto JovenRESUMEN
STUDY OBJECTIVE: To estimate the cost-effectiveness of diagnostic management strategies for adults with minor head injury. METHODS: A mathematical model was constructed to evaluate the incremental costs and effectiveness (Quality Adjusted Life years Gained, QALYs) of ten diagnostic management strategies for adults with minor head injuries. Secondary analyses were undertaken to determine the cost-effectiveness of hospital admission compared to discharge home and to explore the cost-effectiveness of strategies when no responsible adult was available to observe the patient after discharge. RESULTS: The apparent optimal strategy was based on the high and medium risk Canadian CT Head Rule (CCHRhm), although the costs and outcomes associated with each strategy were broadly similar. Hospital admission for patients with non-neurosurgical injury on CT dominated discharge home, whilst hospital admission for clinically normal patients with a normal CT was not cost-effective compared to discharge home with or without a responsible adult at £39 and £2.5 million per QALY, respectively. A selective CT strategy with discharge home if the CT scan was normal remained optimal compared to not investigating or CT scanning all patients when there was no responsible adult available to observe them after discharge. CONCLUSION: Our economic analysis confirms that the recent extension of access to CT scanning for minor head injury is appropriate. Liberal use of CT scanning based on a high sensitivity decision rule is not only effective but also cost-saving. The cost of CT scanning is very small compared to the estimated cost of caring for patients with brain injury worsened by delayed treatment. It is recommended therefore that all hospitals receiving patients with minor head injury should have unrestricted access to CT scanning for use in conjunction with evidence based guidelines. Provisionally the CCHRhm decision rule appears to be the best strategy although there is considerable uncertainty around the optimal decision rule. However, the CCHRhm rule appears to be the most widely validated and it therefore seems appropriate to conclude that the CCHRhm rule has the best evidence to support its use.
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Traumatismos Craneocerebrales/diagnóstico por imagen , Traumatismos Craneocerebrales/economía , Hospitalización/economía , Neoplasias Inducidas por Radiación/economía , Alta del Paciente/economía , Años de Vida Ajustados por Calidad de Vida , Tomografía Computarizada por Rayos X/economía , Adulto , Análisis Costo-Beneficio , Traumatismos Craneocerebrales/epidemiología , Femenino , Escala de Coma de Glasgow , Adhesión a Directriz , Humanos , Masculino , Persona de Mediana Edad , Modelos Teóricos , Neoplasias Inducidas por Radiación/etiología , Neoplasias Inducidas por Radiación/prevención & control , Sensibilidad y Especificidad , Reino Unido/epidemiologíaRESUMEN
OBJECTIVES: This report addressed the question 'What is the clinical and cost-effectiveness of spinal cord stimulation (SCS) in the management of chronic neuropathic or ischaemic pain?' DATA SOURCES: Thirteen electronic databases [including MEDLINE (1950-2007), EMBASE (1980-2007) and the Cochrane Library (1991-2007)] were searched from inception; relevant journals were hand-searched; and appropriate websites for specific conditions causing chronic neuropathic/ischaemic pain were browsed. Literature searches were conducted from August 2007 to September 2007. REVIEW METHODS: A systematic review of the literature sought clinical and cost-effectiveness data for SCS in adults with chronic neuropathic or ischaemic pain with inadequate response to medical or surgical treatment other than SCS. Economic analyses were performed to model the cost-effectiveness and cost-utility of SCS in patients with neuropathic or ischaemic pain. RESULTS: From approximately 6000 citations identified, 11 randomised controlled trials (RCTs) were included in the clinical effectiveness review: three of neuropathic pain and eight of ischaemic pain. Trials were available for the neuropathic conditions failed back surgery syndrome (FBSS) and complex regional pain syndrome (CRPS) type I, and they suggested that SCS was more effective than conventional medical management (CMM) or reoperation in reducing pain. The ischaemic pain trials had small sample sizes, meaning that most may not have been adequately powered to detect clinically meaningful differences. Trial evidence failed to demonstrate that pain relief in critical limb ischaemia (CLI) was better for SCS than for CMM; however, it suggested that SCS was effective in delaying refractory angina pain onset during exercise at short-term follow-up, although not more so than coronary artery bypass grafting (CABG) for those patients eligible for that surgery. The results for the neuropathic pain model suggested that the cost-effectiveness estimates for SCS in patients with FBSS who had inadequate responses to medical or surgical treatment were below 20,000 pounds per quality-adjusted life-year (QALY) gained. In patients with CRPS who had had an inadequate response to medical treatment the incremental cost-effectiveness ratio (ICER) was 25,095 pounds per QALY gained. When the SCS device costs varied from 5000 pounds to 15,000 pounds, the ICERs ranged from 2563 pounds per QALY to 22,356 pounds per QALY for FBSS when compared with CMM and from 2283 pounds per QALY to 19,624 pounds per QALY for FBSS compared with reoperation. For CRPS the ICERs ranged from 9374 pounds per QALY to 66,646 pounds per QALY. If device longevity (1 to 14 years) and device average price (5000 pounds to 15,000 pounds) were varied simultaneously, ICERs were below or very close to 30,000 pounds per QALY when device longevity was 3 years and below or very close to 20,000 pounds per QALY when device longevity was 4 years. Sensitivity analyses were performed varying the costs of CMM, device longevity and average device cost, showing that ICERs for CRPS were higher. In the ischaemic model, it was difficult to determine whether SCS represented value for money when there was insufficient evidence to demonstrate its comparative efficacy. The threshold analysis suggested that the most favourable economic profiles for treatment with SCS were when compared to CABG in patients eligible for percutaneous coronary intervention (PCI), and in patients eligible for CABG and PCI. In these two cases, SCS dominated (it cost less and accrued more survival benefits) over CABG. CONCLUSIONS: The evidence suggested that SCS was effective in reducing the chronic neuropathic pain of FBSS and CRPS type I. For ischaemic pain, there may need to be selection criteria developed for CLI, and SCS may have clinical benefit for refractory angina short-term. Further trials of other types of neuropathic pain or subgroups of ischaemic pain, may be useful.
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Terapia por Estimulación Eléctrica , Manejo del Dolor , Médula Espinal , Enfermedad Crónica , Análisis Costo-Beneficio , Árboles de Decisión , Terapia por Estimulación Eléctrica/efectos adversos , Terapia por Estimulación Eléctrica/economía , Terapia por Estimulación Eléctrica/métodos , Medicina Basada en la Evidencia , Síndrome de Fracaso de la Cirugía Espinal Lumbar/terapia , Humanos , Isquemia/complicaciones , Cadenas de Markov , Neuralgia/terapia , Dolor/etiología , Dolor/psicología , Años de Vida Ajustados por Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Distrofia Simpática Refleja/terapia , Proyectos de Investigación , Sensibilidad y Especificidad , Evaluación de la Tecnología Biomédica , Resultado del Tratamiento , Reino UnidoRESUMEN
Cathepsin K (cat K) is the major cysteine protease expressed in osteoclasts and is thought to play a key role in matrix degradation during bone resorption. However, little is known regarding the synthesis, activation, or turnover of the endogenous enzyme in osteoclasts. In this study, we show that mature cat K protein and enzyme activity are localized within osteoclasts. Pulse-chase experiments revealed that, following the synthesis of pro cat K, intracellular conversion to the mature enzyme occurred in a time-dependent manner. Subsequently, the level of mature enzyme decreased. Little or no cat K was observed in the culture media at any timepoint. Pretreatment of osteoclasts with either chloroquine or monensin resulted in complete inhibition of the processing of newly synthesized cat K. In addition, pro cat K demonstrated susceptibility to treatment with N-glycosidase F, suggesting the presence of high-mannose-containing oligosaccharides. Treatment of osteoclasts with the PI3-kinase inhibitor, Wortmannin (WT), not only prevented the intracellular processing of cat K but also resulted in the secretion of proenzyme into the culture media. Taken together, these results suggest that the biosynthesis, processing, and turnover of cat K in human osteoclasts is constitutive and occurs in a manner similar to that of other known cysteine proteases. Furthermore, cat K is not secreted as a proenzyme, but is processed intracellularly, presumably in lysosomal compartments prior to the release of active enzyme into the resorption lacunae.
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Catepsinas/biosíntesis , Osteoclastos/metabolismo , Procesamiento Proteico-Postraduccional , Androstadienos/farmacología , Anticuerpos/inmunología , Resorción Ósea , Catepsina K , Catepsinas/inmunología , Catepsinas/metabolismo , Células Cultivadas , Cloroquina/farmacología , Inhibidores Enzimáticos/farmacología , Humanos , Inmunohistoquímica , Monensina/farmacología , Osteoclastos/efectos de los fármacos , Inhibidores de las Quinasa Fosfoinosítidos-3 , WortmaninaRESUMEN
Among the causes of life-long cyanosis are congenital methemoglobinemia due to M hemoglobins, congenital methemoglobinemia due to methemoglobin reductase deficiency, a small number of low oxygen affinity hemoglobins, and a small number of unstable hemoglobins that spontaneously form methemoglobin in vivo at an accelerated rate. We report an unstable hemoglobin with these characteristics that was observed in a family of indigenous (native American) origin living near Santiago, Chile. This variant has the substitution beta28(B10)Leu-->Met, unambiguously corresponding to the DNA mutation of CTG-->ATG in beta-globin gene codon 28.
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Anemia Hemolítica/sangre , Hemoglobinas Anormales/genética , Metahemoglobinemia/sangre , Anemia Hemolítica/inducido químicamente , Anemia Hemolítica/genética , Hemoglobinas Anormales/metabolismo , Humanos , Leucina , Masculino , Metahemoglobinemia/genética , Metionina , Azul de Metileno , Persona de Mediana Edad , Mutación Puntual , SulfonamidasRESUMEN
Total tissue content and molecular mass of hyaluronic acid was determined in papain digests of human articular cartilage using a sensitive radiosorbent assay [Laurent & Tengblad (1980) Anal. Biochem. 109, 386-394]. 1) Hyaluronic acid content increased from 0.5 microgram/mg wet wt. to 2.5 micrograms/mg wet wt. between the ages of 2.5 years and 86 years. 2) Hyaluronic acid chain size decreased from Mr 2.0 x 10(6) to 3.0 x 10(5) over the same age range. 3) There was no age-related change in the size of newly-synthesized hyaluronic acid, which was of very high molecular mass, in both immature and mature cartilage. The results are consistent with an age-related decrease in proteoglycan aggregate size and suggest that modification of the hyaluronic acid chain may take place in the extracellular matrix.
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Envejecimiento/metabolismo , Cartílago Articular/metabolismo , Ácido Hialurónico/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Cromatografía en Gel , Humanos , Hidroxiprolina/análisis , Sustancias Macromoleculares , Persona de Mediana Edad , Peso Molecular , Radioinmunoensayo , Ácidos Urónicos/análisisRESUMEN
Glycosaminoglycan production, acid hydrolase activity, proliferation, and morphology were examined in human synovial cells subjected to low environmental pH. The amount and the molecular size of newly synthesised glycosaminoglycan (GAG) were increased without significant change in the rate of cell proliferation. Lowered pH produced an increase in the size of cytoplasmic organelles. Some of these possessed ultrastructural features of lysosomes, but others were clearly nonlysosomal and were of uncertain identity. Intracellular activity of the lysosomal acid hydrolase N-acetyl-beta-glucosaminidase (NAG) was not altered by low pH, but a marked increase occurred in extracellular NAG activity, indicating enhanced release.