Osteoimmunomodulatory GelMA/liposome coatings to promote bone regeneration of orthopedic implants.

Despite being the most widely used biomaterials in orthopedic surgery, metallic implants do not induce new bone growth because they are bioinert. Surface biofunctionalization of implants with immunomodulatory mediators is a recent approach to promote osteogenic factors that facilitate bone regeneration. Liposomes (Lip) can be used as a low-cost, efficient and simple immunomodulator to stimulate immune cells in favor of bone regeneration. Even though liposomal coating systems have been reported previously, their main disadvantage is their limited ability to preserve liposome integrity after drying. In order to address this issue, we developed a hybrid system in which liposomes could be embedded in a polymeric hydrogel namely gelatin methacryloyl (GelMA). Specifically, we have developed a novel versatile coating strategy using electrospray technology to coat implants with GelMA/Liposome without using adhesive intermediate layer. The two differently charged Lip (i.e., anionic and cationic) were blended with GelMA and coated via electrospray technology on the bone-implant surfaces. The results showed that the developed coating withstood mechanical stress during surgical replacement, and Lip inside GelMA coating stayed intact in different storage conditions for a minimum of 4 weeks. Surprisingly, bare Lip, either cationic or anionic, improved the osteogenesis of human Mesenchymal Stem Cells (MSCs) by inducing pro-inflammatory cytokines, even at a low dosage of Lip released from the GelMA coating. More importantly, we showed that the inflammatory response could be fine-tuned by selecting the Lip concentration, Lip/hydrogel ratio, and coating thickness to determine the timing of the release such that we can accommodate different clinical needs. These promising results pave the way to use these Lip coatings to load different types of therapeutic cargo for bone-implant applications.

Extrusion-based 3D printing of biodegradable, osteogenic, paramagnetic, and porous FeMn-akermanite bone substitutes.

The development of biodegradable Fe-based bone implants has rapidly progressed in recent years. Most of the challenges encountered in developing such implants have been tackled individually or in combination using additive manufacturing technologies. Yet not all the challenges have been overcome. Herein, we present porous FeMn-akermanite composite scaffolds fabricated by extrusion-based 3D printing to address the unmet clinical needs associated with Fe-based biomaterials for bone regeneration, including low biodegradation rate, MRI-incompatibility, mechanical properties, and limited bioactivity. In this research, we developed inks containing Fe, 35 wt% Mn, and 20 or 30 vol% akermanite powder mixtures. 3D printing was optimized together with the debinding and sintering steps to obtain scaffolds with interconnected porosity of 69%. The Fe-matrix in the composites contained the γ-FeMn phase as well as nesosilicate phases. The former made the composites paramagnetic and, thus, MRI-friendly. The in vitro biodegradation rates of the composites with 20 and 30 vol% akermanite were respectively 0.24 and 0.27 mm/y, falling within the ideal range of biodegradation rates for bone substitution. The yield strengths of the porous composites stayed within the range of the values of the trabecular bone, despite in vitro biodegradation for 28 d. All the composite scaffolds favored the adhesion, proliferation, and osteogenic differentiation of preosteoblasts, as revealed by Runx2 assay. Moreover, osteopontin was detected in the extracellular matrix of cells on the scaffolds. Altogether, these results demonstrate the remarkable potential of these composites in fulfilling the requirements of porous biodegradable bone substitutes, motivating future in vivo research. STATEMENT OF SIGNIFICANCE: We developed FeMn-akermanite composite scaffolds by taking advantage of the multi-material capacity of extrusion-based 3D printing. Our results demonstrated that the FeMn-akermanite scaffolds showed an exceptional performance in fulfilling all the requirements for bone substitution in vitro, i.e., a sufficient biodegradation rate, having mechanical properties in the range of trabecular bone even after 4 weeks biodegradation, paramagnetic, cytocompatible and most importantly osteogenic. Our results encourage further research on Fe-based bone implants in in vivo.

Additive manufacturing of bioactive and biodegradable porous iron-akermanite composites for bone regeneration.

Advanced additive manufacturing techniques have been recently used to tackle the two fundamental challenges of biodegradable Fe-based bone-substituting materials, namely low rate of biodegradation and insufficient bioactivity. While additively manufactured porous iron has been somewhat successful in addressing the first challenge, the limited bioactivity of these biomaterials hinder their progress towards clinical application. Herein, we used extrusion-based 3D printing for additive manufacturing of iron-matrix composites containing silicate-based bioceramic particles (akermanite), thereby addressing both of the abovementioned challenges. We developed inks that carried iron and 5, 10, 15, or 20 vol% of akermanite powder mixtures for the 3D printing process and optimized the debinding and sintering steps to produce geometrically-ordered iron-akermanite composites with an open porosity of 69-71%. The composite scaffolds preserved the designed geometry and the original α-Fe and akermanite phases. The in vitro biodegradation rates of the composites were improved as much as 2.6 times the biodegradation rate of geometrically identical pure iron. The yield strengths and elastic moduli of the scaffolds remained within the range of the mechanical properties of the cancellous bone, even after 28 days of biodegradation. The composite scaffolds (10-20 vol% akermanite) demonstrated improved MC3T3-E1 cell adhesion and higher levels of cell proliferation. The cellular secretion of collagen type-1 and the alkaline phosphatase activity on the composite scaffolds (10-20 vol% akermanite) were, respectively higher than and comparable to Ti6Al4V in osteogenic medium. Taken together, these results clearly show the potential of 3D printed porous iron-akermanite composites for further development as promising bone substitutes. STATEMENT OF SIGNIFICANCE: Porous iron matrix composites containing akermanite particles were produced by means of multi-material additive manufacturing to address the two fundamental challenges associated with biodegradable iron-based biomaterials, namely very low rate of biodegradation and insufficient bioactivity. Our porous iron-akermanite composites exhibited enhanced biodegradability and superior bioactivity compared to porous monolithic iron scaffolds. The murine bone cells proliferated on the composite scaffolds, and secreted the collagen type-1 matrix that stimulated bony-like mineralization. The results show the exceptional potential of the developed porous iron-based composite scaffolds for application as bone substitutes.

Poly(2-ethyl-2-oxazoline) coating of additively manufactured biodegradable porous iron.

Additively manufacturing of porous iron offers a unique opportunity to increase its biodegradation rate by taking advantage of arbitrarily complex porous structures. Nevertheless, achieving the required biodegradation profile remains challenging due to the natural passivation of iron that decrease the biodegradation rate. Moreover, the biocompatibility of iron is reported to be limited. Here, we address both challenges by applying poly(2-ethyl-2-oxazoline) coating to extrusion-based 3D printed porous iron. We characterized the specimens by performing in vitro biodegradation, electrochemical measurements, time-dependent mechanical tests, and in vitro cytocompatibility assays. The coated porous iron exhibited a biodegradation rate that was 2.6× higher than that of non-coated counterpart and maintained the bone-mimicking mechanical properties throughout biodegradation. Despite the formation of dense biodegradation products, the coating ensured a relatively stable biodegradation (i.e., 17% reduction in the degradation rate between days 14 and 28) as compared to that of non-coated specimens (i.e., 43% drop). Furthermore, the coating could be identified even after biodegradation, demonstrating the longevity of the coating. Finally, the coated specimens significantly increased the viability and supported the attachment and growth of preosteoblasts. Our results demonstrate the great potential of poly(2-ethyl-2-oxazoline) coating for addressing the multiple challenges associated with the clinical adoption of porous iron.

Extrusion-based 3D printed magnesium scaffolds with multifunctional MgF2 and MgF2-CaP coatings.

Additively manufactured (AM) biodegradable magnesium (Mg) scaffolds with precisely controlled and fully interconnected porous structures offer unprecedented potential as temporary bone substitutes and for bone regeneration in critical-sized bone defects. However, current attempts to apply AM techniques, mainly powder bed fusion AM, for the preparation of Mg scaffolds, have encountered some crucial difficulties related to safety in AM operations and severe oxidation during AM processes. To avoid these difficulties, extrusion-based 3D printing has been recently developed to prepare porous Mg scaffolds with highly interconnected structures. However, limited bioactivity and a too high rate of biodegradation remain the major challenges that need to be addressed. Here, we present a new generation of extrusion-based 3D printed porous Mg scaffolds that are coated with MgF2 and MgF2-CaP to improve their corrosion resistance and biocompatibility, thereby bringing the AM scaffolds closer to meeting the clinical requirements for bone substitutes. The mechanical properties, in vitro biodegradation behavior, electrochemical response, and biocompatibility of the 3D printed Mg scaffolds with a macroporosity of 55% and a strut density of 92% were evaluated. Furthermore, comparisons were made between the bare scaffolds and the scaffolds with coatings. The coating not only covered the struts but also infiltrated the struts through micropores, resulting in decreases in both macro- and micro-porosity. The bare Mg scaffolds exhibited poor corrosion resistance due to the highly interconnected porous structure, while the MgF2-CaP coatings remarkably improved the corrosion resistance, lowering the biodegradation rate of the scaffolds down to 0.2 mm y-1. The compressive mechanical properties of the bare and coated Mg scaffolds before and during in vitro immersion tests for up to 7 days were both in the range of the values reported for the trabecular bone. Moreover, direct culture of MC3T3-E1 preosteoblasts on the coated Mg scaffolds confirmed their good biocompatibility. Overall, this study clearly demonstrated the great potential of MgF2-CaP coated porous Mg prepared by extrusion-based 3D printing for further development as a bone substitute.

Extrusion-based 3D printing of ex situ-alloyed highly biodegradable MRI-friendly porous iron-manganese scaffolds.

Additively manufactured biodegradable porous iron has been only very recently demonstrated. Two major limitations of such a biomaterial are very low biodegradability and incompatibility with magnetic resonance imaging (MRI). Here, we present a novel biomaterial that resolves both of those limitations. We used extrusion-based 3D printing to fabricate ex situ-alloyed biodegradable iron-manganese scaffolds that are non-ferromagnetic and exhibit enhanced rates of biodegradation. We developed ink formulations containing iron and 25, 30, or 35 wt% manganese powders, and debinding and sintering process to achieve Fe-Mn scaffolds with 69% porosity. The Fe25Mn scaffolds had the ε-martensite and γ-austenite phases, while the Fe30Mn and Fe35Mn scaffolds had only the γ-austenite phase. All iron-manganese alloys exhibited weakly paramagnetic behavior, confirming their potential to be used as MRI-friendly bone substitutes. The in vitro biodegradation rates of the scaffolds were very much enhanced (i.e., 4.0 to 4.6 times higher than that of porous iron), with the Fe35Mn alloy exhibiting the highest rate of biodegradation (i.e., 0.23 mm/y). While the elastic moduli and yield strengths of the scaffolds decreased over 28 days of in vitro biodegradation, those values remained in the range of cancellous bone. The culture of preosteoblasts on the porous iron-manganese scaffolds revealed that cells could develop filopodia on the scaffolds, but their viability was reduced by the effect of biodegradation. Altogether, this research marks a major breakthrough and demonstrates the great prospects of multi-material extrusion-based 3D printing to further address the remaining issues of porous iron-based materials and, eventually, develop ideal bone substitutes. STATEMENT OF SIGNIFICANCE: 3D printed porous iron biomaterials for bone substitution still encounter limitations, such as the slow biodegradation and magnetic resonance imaging incompatibility. Aiming to solve the two fundamental issues of iron, we present ex-situ alloyed porous iron-manganese scaffolds fabricated by means of multi-material extrusion-based 3D printing. Our porous iron-manganese possessed enhanced biodegradability, non-ferromagnetic property, and bone-mimicking mechanical property throughout the in vitro biodegradation period. The results demonstrated a great prospect of multi-material extrusion-based 3D printing to further address the remaining challenges of porous iron-based biomaterials to be an ideal biodegradable bone substitutes.

Extrusion-based 3D printed biodegradable porous iron.

Extrusion-based 3D printing followed by debinding and sintering is a powerful approach that allows for the fabrication of porous scaffolds from materials (or material combinations) that are otherwise very challenging to process using other additive manufacturing techniques. Iron is one of the materials that have been recently shown to be amenable to processing using this approach. Indeed, a fully interconnected porous design has the potential of resolving the fundamental issue regarding bulk iron, namely a very low rate of biodegradation. However, no extensive evaluation of the biodegradation behavior and properties of porous iron scaffolds made by extrusion-based 3D printing has been reported. Therefore, the in vitro biodegradation behavior, electrochemical response, evolution of mechanical properties along with biodegradation, and responses of an osteoblastic cell line to the 3D printed iron scaffolds were studied. An ink formulation, as well as matching 3D printing, debinding and sintering conditions, was developed to create iron scaffolds with a porosity of 67%, a pore interconnectivity of 96%, and a strut density of 89% after sintering. X-ray diffracometry confirmed the presence of the α-iron phase in the scaffolds without any residuals from the rest of the ink. Owing to the presence of geometrically designed macropores and random micropores in the struts, the in vitro corrosion rate of the scaffolds was much improved as compared to the bulk counterpart, with 7% mass loss after 28 days. The mechanical properties of the scaffolds remained in the range of those of trabecular bone despite 28 days of in vitro biodegradation. The direct culture of MC3T3-E1 preosteoblasts on the scaffolds led to a substantial reduction in living cell count, caused by a high concentration of iron ions, as revealed by the indirect assays. On the other hand, the ability of the cells to spread and form filopodia indicated the cytocompatibility of the corrosion products. Taken together, this study shows the great potential of extrusion-based 3D printed porous iron to be further developed as a biodegradable bone substituting biomaterial.

Additively manufactured biodegradable porous zinc.

Additively manufacturing (AM) opens up the possibility for biodegradable metals to possess uniquely combined characteristics that are desired for bone substitution, including bone-mimicking mechanical properties, topologically ordered porous structure, pore interconnectivity and biodegradability. Zinc is considered to be one of the promising biomaterials with respect to biodegradation rate and biocompatibility. However, no information regarding the biodegradability and biocompatibility of topologically ordered AM porous zinc is yet available. Here, we applied powder bed fusion to fabricate porous zinc with a topologically ordered diamond structure. An integrative study was conducted on the static and dynamic biodegradation behavior (in vitro, up to 4 weeks), evolution of mechanical properties with increasing immersion time, electrochemical performance, and biocompatibility of the AM porous zinc. The specimens lost 7.8% of their weight after 4 weeks of dynamic immersion in a revised simulated body fluid. The mechanisms of biodegradation were site-dependent and differed from the top of the specimens to the bottom. During the whole in vitro immersion time of 4 weeks, the elastic modulus values of the AM porous zinc (E = 700-1000 MPa) even increased and remained within the scope of those of cancellous bone. Indirect cytotoxicity revealed good cellular activity up to 72 h according to ISO 10,993-5 and -12. Live-dead staining confirmed good viability of MG-63 cells cultured on the surface of the AM porous zinc. These important findings could open up unprecedented opportunities for the development of multifunctional bone substituting materials that will enable reconstruction and regeneration of critical-size load-bearing bone defects. STATEMENT OF SIGNIFICANCE: No information regarding the biodegradability and biocompatibility of topologically ordered AM porous zinc is available. We applied selective laser melting to fabricate topologically ordered porous zinc and conducted a comprehensive study on the biodegradation behavior, electrochemical performance, time-dependent mechanical properties, and biocompatibility of the scaffolds. The specimens lost 7.8% of their weight after4 weeks dynamic biodegradation while their mechanical properties surprisingly increased after 4 weeks. Indirect cytotoxicity revealed good cellular activity up to 72 h. Intimate contact between MG-63 cells and the scaffolds was also observed. These important findings could open up unprecedented opportunities for the development of multifunctional bone substituting materials that mimic bone properties and enable full regeneration of critical-size load-bearing bony defects.

Antifungal activity of various essential oils against Rhizoctonia solani and Macrophomina phaseolina as major bean pathogens.

AIMS: The main objective of this study was to investigate the effect of various essential oils (EOs) to decrease the activity of cell wall degrading enzymes (CWDEs) produced by fungal phytopathogens, which are associated with disease progress. Also, effect of seed treatment and foliar application of peppermint EO and its main constituent, menthol, on diseases caused by two necrotrophic pathogens on bean was investigated. METHODS AND RESULTS: Antifungal activity of EOs on Rhizoctonia solani and Macrophomina phaseolina, as bean pathogens, was evaluated. The EOs of Mentha piperita, Bunium persicum and Thymus vulgaris revealed the highest antifungal activity against fungi. The EO of M. piperita had the lowest minimum inhibitory concentration (MIC) for R. solani among the three EOs tested. This pathogen did not grow in the presence of M. piperita, B. persicum and T. vulgaris EOs at 850, 1200 and 1100 ppm concentrations, respectively. The B. persicum EO had the lowest MIC for M. phaseolina as this fungus did not grow in the presence of M. piperita, B. persicum and T. vulgaris EOs at concentrations of 975, 950 and 1150 ppm, respectively. Hyphae exposed to EOs showed structural changes. Activities of cellulase and pectinase, as main CWDEs of pathogens, decreased by EOs at low concentration without effect on fungal growth. Seed treatment and foliar application of peppermint EO and/or menthol significantly reduced the development of bean diseases caused by both fungi. Higher capability of menthol than peppermint EO in decreasing diseases on bean was observed. CONCLUSIONS: Reducing CDWEs activity is a mechanism of EOs' effect on fungi. Higher antifungal activity of menthol compared to peppermint EO was observed not only in vitro but also in vivo. SIGNIFICANCE AND IMPACT OF THE STUDY: Effect of EOs on CWDEs involved in pathogenesis is described in this study for the first time. Menthol can be used as a botanical fungicide to control destructive fungal diseases on bean.

The efficacy of intradermal injection of botulinum toxin in patients with post-herpetic neuralgia.

BACKGROUND: Several treatments have been suggested in shingles viral infection caused by Varicella zoster virus that may lead to complications such as PHN (Post-herpetic neuralgia). Intradermal injection of botulinum toxin was shown with few side effects. This study evaluates the efficacy of intradermal injection of botulinum toxin in patients suffering from PHN. METHODS: Fifteen patients suffering from PHN for more than1 month were enrolled. Data collected were patients' age, sex, and lesion site, the dermatome involved and the duration and severity of pain by visual analog scale (VAS). Botulinum (15 units /every 10 cm(2) of body involved) was injected intradermally. The patients were followed 2, 14 and 30 days after injection. RESULTS: Of participants, 6 were males and 9 females. The mean age was 60 years and the mean duration of neuralgia was 6.5 months. The mean VAS on day 2 was 6.4, on day 14 was 7.2 and after 30 days was 7.6. The overall pain after injection decreased but was not significant. CONCLUSION: It seems that intradermal injection of botulinum toxin decreases pain in PHN patients and this decrease is less prominent by passing time.

Interpretation of non-invasive breath tests using (13)C-labeled substrates--a preliminary report with (13)C-methacetin.

Non-invasive breath tests can serve as valuable diagnostic tools in medicine as they can determine particular enzymatic and metabolic functions in vivo. However, methodological pitfalls have limited the actual clinical application of those tests till today. A major challenge of non-invasive breath tests has remained the provision of individually reliable test results. To overcome these limitations, a better understanding of breath kinetics during non-invasive breaths tests is essential. This analysis compares the breath recovery of a (13)C-methacetin breath test with the actual serum kinetics of the substrate. It is shown, that breath and serum kinetics of the same test are significantly different over a period of 60 minutes. The recovery of the tracer (13)CO(2) in breath seems to be significantly delayed due to intermediate storage in the bicarbonate pool. This has to be taken into account for the application of non-invasive breath test protocols. Otherwise, breath tests might display bicarbonate kinetics despite the metabolic capacity of the particular target enzyme.

How DRGs hurt academic health systems.

BACKGROUND: Academic health centers continue their mission of clinical care, education, and research. This mission predisposes them to accept patients regardless of their individual clinical variation and financial risk. The purpose of this study is to assess the variation in costs and the attendant financial risk associated with these patients. In addition, we propose a new reimbursement methodology for academic health center high-end DRGs that better aligns financial risks. STUDY DESIGN: We reviewed clinical and financial data from the University of Michigan data warehouse for FY1999 (n = 39,804). The diagnosis-related groups were classified by volume (group 1, low volume to group 4, high volume). The coefficient of variation for total cost per admission was then calculated for each DRG classification. A regression analysis was also performed to assess how costs in the first 3 days estimated total costs. A hybrid methodology to estimate costs was then determined and its accuracy benchmarked against actual Medicare and Blue Cross reimbursements. RESULTS: Low-volume DRGs (< 75 annual admissions) had the highest coefficient of variation relative to each of the three other DRG classifications (moderate to high volume, groups 2, 3, and 4). The regression analysis accurately estimated costs (within 25% of actual costs) in 64.7% of patients with a length of stay > or = 4 days (n = 16,287). This regression fared well compared with actual FY 1999 DRG-based Medicare and Blue Cross reimbursements (n = 9,085 with length of stay > or = 4 days), which accurately reimbursed the University of Michigan Health System in only 43.9% of cases. CONCLUSIONS: Academic health centers receive a disproportionate number of admissions to low-volume, high-variation DRGs. This clinical variation translates into financial risk. Traditional risk management strategies are difficult to use in health care settings. The application of our proposed reimbursement methodology better distributes risk between payers and providers, and reduces adverse selection and incentive problems ("moral hazard").

Efficacy of the laparoscopic approach for anterior lumbar spinal fusion.

BACKGROUND: This study compares the immediate postoperative outcomes in patients who undergo laparoscopic and open anterior lumbar spinal fusion and describes the learning curve associated with the performance of this procedure. METHODS: The charts of patients who underwent anterior lumbar spinal fusion between January 1995 and July 1999 were reviewed. Data pertaining to the operation and postoperative course were analyzed and compared. RESULTS: Eighty-nine patients underwent anterior lumbar spinal fusion. Fourteen patients were excluded; a full analysis was performed on the records of the remaining 75 patients. Fifty-five patients underwent an attempted laparoscopic procedure, and 20 patients underwent an open procedure. The conversion rate was 38% (21/55 patients) in the group who underwent the laparoscopic procedure. In the 34 patients whose laparoscopic procedure was completed, there was significantly less blood loss and shorter postoperative ileus, but the operative time was longer, when compared with patients who underwent the open procedure. The laparoscopic procedures performed in 1999 resulted in fewer conversions, less blood loss, and a shorter operating room time, when compared with the laparoscopic procedures in 1998. CONCLUSIONS: Laparoscopic anterior lumbar spinal fusion improves immediate postoperative results when compared with open anterior lumbar spinal fusion.

Prophylactic vena caval filters in trauma: the rest of the story.

OBJECTIVE: The purpose of this study was to describe outcomes for patients with trauma who had vena caval filters placed in the absence of venous thromboembolic disease (group P) and compare them with outcomes for patients with trauma who had filters placed after either deep venous thrombosis or pulmonary embolism (group T). DESIGN: The study is a case series of consecutive patients who received vena caval filters after traumatic injury. Data were collected prospectively at the time of filter placement from reports of diagnostic studies obtained for clinical indications and during the annual follow-up examinations. Event rate findings are based on objective tests. Data were obtained from the Michigan Vena Cava Filter Registry. RESULTS: Filters were placed in 385 patients with trauma; 249 of these filters were prophylactic (group P). Event rates were similar in the two groups. New pulmonary embolism was diagnosed in 1.5% of the patients in group P and 2% of the patients in group T. Caval occlusion rates were 3.5% for group P and 2.3% for group T. In all, 15.6% of the patients in group P had deep venous thrombosis or pulmonary embolism after placement. The frequencies of lower extremity swelling and use of support hose were higher in group T than in group P (43% vs 25% and 25% vs 3.5%, respectively; P <.005). Outcomes were comparable in the two groups with respect to mechanical stability of the filter. CONCLUSIONS: The prophylactic indication for vena caval filter placement in patients with trauma is associated with a low incidence of adverse outcomes while providing protection from fatal pulmonary embolism. The current challenge is to limit the number of unnecessary placements through improved methods of risk stratification.

Length of stay has minimal impact on the cost of hospital admission.

BACKGROUND: Hospital cost containment, cost reduction, and alternative care delivery systems continue to preoccupy health care providers, payers, employers, and policy makers throughout the United States. The universal metric for gauging the success of these efforts is hospital length of stay (LOS). Reducing the LOS purportedly yields large cost savings. The purpose of this study is to assess precisely how much hospitals save by shortening LOS. STUDY DESIGN: We reviewed the cost-accounting records of all surviving patients (n = 12,365) discharged from our academic medical center during fiscal year 1998 with LOS of 4 days or more. Actual costs were identified through the University of Michigan cost-accounting system. Individual patient costs were broken out on a daily basis and then decomposed further into variable direct, fixed direct, and indirect categories. The population was analyzed by determining the incremental resource cost of the last full day of stay versus the total cost for the entire stay. The data were also stratified by LOS and by surgical costs. An analysis of all trauma patients was then performed on all patients discharged from the hospital's adult level I trauma center (n = 665). Costs were determined on specific days, including admission day, each ICU day, day of discharge from the ICU, and each of the last 2 days before the discharge day. RESULTS: The incremental costs incurred by patients on their last full day of hospital stay were $420 per day on average, or just 2.4% of the $17,734 mean total cost of stay for all 12,365 patients. Mean end-of-stay costs represented only a slightly higher percentage of total costs when LOS was short (e.g., 6.8% for patients with LOS of 4 days). Even when the data were stratified to focus on patients without major operations, the $432 average last-day variable direct cost was only 3.4% of the $12,631 average total cost of care. A focus on the trauma center helps to explain this phenomenon. For our trauma center, variable direct costs accounted for 42% of the mean total cost per patient of $22,067. The remaining 58% was hospital overhead (fixed and indirect costs). The median variable direct cost on the first day of admission is $1,246, and the median variable direct cost on discharge is $304. Approximately 40% of the variable costs are incurred during the first 3 days of admission. CONCLUSIONS: For most patients, the costs directly attributable to the last day of a hospital stay are an economically insignificant component of total costs. Reducing LOS by as much as 1 full day reduces the total cost of care on average by 3% or less. Going forward, physicians and administrators must deemphasize LOS and focus instead on process changes that better use capacity and alter care delivery during the early stages of admission, when resource consumption is most intense.

Academic health systems management: the rationale behind capitated contracts.

OBJECTIVE: To determine why hospitals enter into "capitated" contracts, which often generate accounting losses. The authors' hypothesis is that hospitals coordinate contracts to keep beds full and that in principal, capitated contracts reflect sound capacity management. SUMMARY BACKGROUND DATA: In high-overhead industries, different consumers pay different prices for similar services (e.g., full-fare vs. advanced-purchase plane tickets, full tuition vs. financial aid). Some consumers gain access by paying less than total cost. Hospitals, like other high-overhead business enterprises, must optimize the use of their capacity, amortizing overhead over as many patients as possible. This necessity for enhanced throughput forces hospitals and health systems to discount empty beds, sometimes to the point where they incur accounting losses serving some payors. METHODS: The authors analyzed the cost accounting system at their university teaching hospital to compare hospital and intensive care unit (ICU) lengths of stay (LOS), variable direct costs (VDC), overhead of capitated patients, and reimbursement versus other payors for all hospital discharges (n = 29,036) in fiscal year 1998. The data were analyzed by diagnosis-related groups (DRGs), length of stay (LOS), insurance carrier, proximity to hospital, and discharge disposition. Patients were then distinguished across payor categories based on their resource utilization, proximity to the hospital, DRG, LOS, and discharge status. RESULTS: The mean cost for capitated patients was $4,887, less than half of the mean cost of $10,394 for the entire hospitalized population. The mean capitated reimbursement was $928/day, exceeding the mean daily VDC of $616 but not the total cost of $1,445/day. Moreover, the mean total cost per patient day of treating a capitated patient was $400 less than the mean total cost per day for noncapitated patients. The hospital's capitated health maintenance organization (HMO) patients made up 16. 0% of the total admissions but only 9.4% of the total patient days. Both the mean LOS of 3.4 days and the mean ICU LOS of 0.3 days were significantly different from the overall values of 5.8 days and 1 day, respectively, for the noncapitated population. For patients classified with a DRG with complication who traveled from more than 60 miles away, the mean LOS was 10.7 days and the mean total cost was $21,658. This is in contrast to all patients who traveled greater than 60 miles, who had an LOS of 7.2 days and a mean total cost of $12,569. CONCLUSION: The capitated payor directed the bulk of its subscribers to one hospital (other payors transferred their sicker patients). This was reflected in the capitated group's lower costs and LOS. This stable stream of relatively low-acuity patients enhanced capacity utilization. For capitated patients, the hospital still benefits by recovering the incremental cost (VDC) of treating these patients, and only a portion of the assigned overhead. Thus, in the short run, capitated patients provide a positive economic benefit. Other payors' higher-acuity patients arrive more randomly, place greater strains on capacity, and generate higher overhead costs. This results in differential reimbursement to cover this incremental overhead. Having a portfolio of contracts allows the hospital to optimize capacity both in terms of patient flows and acuity. One risk of operating near capacity is that capitated patients could displace other higher-paying patients.

Physician impact on the total cost of care.

BACKGROUND AND OBJECTIVES: Physicians' efforts at cost containment focus on decreased resource utilization and reduced length of stay. Although these efforts appear to be appropriate, little data exist to gauge their success. As such, the goal of this study is to determine trauma service cost allocations and how this information can help physicians to contain costs. MATERIALS AND METHODS: The authors analyzed the costs for 696 trauma admissions at a level I trauma center for fiscal year 1997. Data were obtained from the hospital costing system. Costs analyzed were variable direct, fixed direct, and Indirect costs. Together, the fixed and indirect costs are referred to as "hospital overhead." Total Cost equals variable direct plus fixed direct plus indirect costs. RESULTS: The mean variable, fixed, and indirect costs per patient were $7,998, $3,534, and $11,086, respectively. Mean total cost per patient was $22,618. CONCLUSION: The 35% variable direct cost represents the percentage of total cost that is typically under the immediate influence of physicians, in contrast to the 65% of total cost over which physicians have little control. Physicians must gain a better understanding of cost drivers and must participate in the operations and allocations of institutional fixed direct and indirect costs if the overall cost of care is to be reduced.

Posttraumatic stress disorder after injury: impact on general health outcome and early risk assessment.

OBJECTIVE: To evaluate prospectively components of general health outcome after trauma and to report on the further validation of the Michigan Critical Events Perception Scale (MCEPS), an instrument that predicts increased risk for posttraumatic stress disorder (PTSD). METHODS: Adults without neurologic injury admitted to a Level I trauma center in 1997 were interviewed during hospitalization. Baseline data included demographics, injury mechanism, Injury Severity Score, the Short Form 36 (SF36), and the MCEPS, which measures peri-traumatic dissociation (the sense of depersonalization or derealization during an injury event). Surveys sent by mail and completed 6 months later included the SF36 and civilian Mississippi Scale for PTSD. RESULTS: A total of 140 patients were interviewed; the 70% (n = 100 patients) who completed the 6-month assessment form the study group. Injuries were categorized as 71% blunt, 13% penetrating, and 16% burn. Mean Injury Severity Score was 13.7+/-0.52. PTSD at 6 months occurred in 42% of the patients and was directly related to MCEPS dissociation (p = 0.001; odds ratio = 3.1; 95% confidence interval, 1.6, 5.9). A stepwise linear regression explains 40% of the variance in 6-month SF36 general health outcome (adjusted R2 = 0.402). The model controls for individual factors related to dissociation, PTSD, and general health outcome. Development of PTSD was independently and inversely related to general health outcome as measured by the SF36 at 6 months (p < 0.001, beta = -0.404). The R2 change of 0.132 for PTSD (vs. 0.082 for 6-month physical function) illustrates that PTSD contributes more to the patient's perceived general health at 6 months than the degree of physical function or injury severity. CONCLUSIONS: Within hours of injury, the MCEPS identifies patients who are three times more likely to develop PTSD. PTSD compromises self-reported general health outcome in injured adults independent of baseline status, Injury Severity Score, or degree of physical recovery. These data suggest that psychological morbidity is an important part of the patient's perceived general health.