Fibrinogenolysis and fibrinolysis in vaccine-induced immune thrombocytopenia and thrombosis.

BACKGROUND: Vaccine-induced immune thrombocytopenia and thrombosis (VITT) is a rare syndrome associated with adenoviral vector vaccines for COVID-19. The syndrome is characterized by thrombosis, anti-platelet factor 4 (PF4) antibodies, thrombocytopenia, high D-dimer, and hypofibrinogenemia. OBJECTIVES: To investigate abnormalities in fibrinolysis that contribute to the clinical features of VITT. METHODS: Plasma samples from 18 suspected VITT cases were tested for anti-PF4 by ELISA and characterized as meeting criteria for VITT (11/18) or deemed unlikely (7/18; non-VITT). Antigen levels of PAI-1, factor XIII (FXIII), plasmin-α2antiplasmin (PAP), and inflammatory markers were quantified. Plasmin generation was quantified by chromogenic substrate. Western blotting was performed with antibodies to fibrinogen, FXIII-A, and plasminogen. RESULTS: VITT patients 10/11 had scores indicative of overt disseminated intravascular coagulation, while 0/7 non-VITT patients met the criteria. VITT patients had significantly higher levels of inflammatory markers, IL-1ß, IL-6, IL-8, TNFα, and C-reactive protein. In VITT patients, both fibrinogen and FXIII levels were significantly lower, while PAP and tPA-mediated plasmin generation were higher compared to non-VITT patients. Evidence of fibrinogenolysis was observed in 9/11 VITT patients but not in non-VITT patients or healthy controls. Fibrinogen degradation products were apparent, with obvious cleavage of the fibrinogen α-chain. PAP complex was evident in those VITT patients with fibrinogenolysis, but not in non-VITT patients or healthy donors. CONCLUSION: VITT patients show evidence of overt disseminated intravascular coagulation and fibrinogenolysis, mediated by dysregulated plasmin generation, as evidenced by increased PAP and plasmin generation. These observations are consistent with the clinical presentation of both thrombosis and bleeding in VITT.

Biomechanical Evaluation of Transverse Patella Fracture Fixation Using Headless Screws: A Comparison of Suture Versus Cable as a Tension Band.

OBJECTIVES: To explore the performance of headless screws with FiberWire Suture as a tension band and headless screws with a mini-cable tension band in patella fixation. METHODS: A transverse osteotomy was created in 6 matched pairs of fresh-frozen cadaver knee joints. One knee was randomly assigned to receive fixation with headless screws plus a cable tension band while the other was fixed with headless screws plus a suture tension band. Using a servo-hydraulic material testing system, the specimens were first tested nondestructively under 20% of the reported mean failure load with a standard technique of cannulated screws with tension band wiring. The specimen was then loaded to 1000 N to test the construct's failure strength. All tests were run under displacement-control with loading threshold. A motion analysis system was used to track the interfragmentary motion to assess fixation stability. RESULTS: In the nondestructive loading test, gap displacement under 150 N was 0.10 mm or less for 11 of 12 specimens, and the difference between the 2 groups was not statistically significant. In the destructive test, 3 of 12 specimens maintained reduction (gap <2 mm) at the maximum load of 1000 N. Of the failed specimens, the mean strength was 648 ± 185 N for suture and 784 ± 228 N for cable. CONCLUSIONS: There was no significant difference in fixation strength or subfailure fragment displacement between the suture and cable tension band techniques when using headless screws.

A cadaveric biomechanical evaluation of anterior posterior compression II injuries.

PURPOSE: Pelvic fractures are associated with high morbidity and often require surgical intervention. An Anterior Posterior Compression (APC) II injury consists of disruption at the pubic symphysis and anterior sacroiliac joint. Studies investigating specific ligamentous contributions would aid in development of novel fixation techniques. The objective of this study is to determine the level of pelvic destabilization from progressive soft tissue disruptions associated with APC II injuries. METHODS: Six fresh-frozen cadaveric pelvises were dissected of soft tissues, preserving joint capsules and ligaments. Each pelvis was secured in a double-leg stance and joint motion was tracked with the specimens cyclically loaded to 60% body weight. Each specimen was measured in the intact state and again following stepwise destabilization to an APC II injury model (PS: sectioned pubic symphysis, IPS JOINT: PS + ipsilateral anterior sacroiliac, sacrotuberous, sacrospinous ligaments sectioned, IPS LIGS: IPS JOINT + ipsilateral interosseous ligaments sectioned, IPS JOINT+CONT ASI: IPS LIGS + contralateral anterior sacroiliac ligament disruption). RESULTS: Compared to the intact state, there was a statistically significant increase in movement in the IPS JOINT (ipsilateral 177%, p<0.001; contralateral 46%, p<0.005) and IPS JOINT+CONT ASI (ipsilateral 184%, p<0.002; and contralateral 62%, p<0.002) states bilaterally. No significant change was demonstrated in the PS or IPS LIGS state. CONCLUSION: Disruption of ipsilateral ligamentous structures destabilized both sacroiliac joints. The interosseous and posterior sacroiliac ligaments provide the majority of stability of the sacroiliac joint and will likely benefit most from surgical stabilization. LEVEL OF EVIDENCE: mechanism-based reasoning.

Outcome comparison between muscle and fasciocutaneous flaps after secondary orthopedic procedures.

Lower extremity wounds associated with fractures and bony defects often require secondary orthopedic procedures after flap coverage has been performed. In this study, we compare complications between muscle and fasciocutaneous flaps after secondary orthopedic procedures. A retrospective chart review study of all lower extremity soft tissue reconstructions by a single surgeon over seven years yielded a subgroup of patients who underwent secondary orthopedic procedures, including hardware removal, hardware revision, and bone grafting after flap reconstruction. Of 355 lower extremity, soft tissue reconstructions for orthopedic coverage performed in the time period studied, 102 patients underwent secondary orthopedic procedures after flap reconstruction. Of these, 54 received muscle flaps (52.94%), and 48 received fasciocutaneous flaps (47.06%). Using this subgroup of 102 patients, we compared muscle and fasciocutaneous flaps using three categories of wound complications following these secondary procedures: There were no superficial wounds requiring local wound care only in the muscle flap group (0%, n = 0) versus 4.17% (n = 2; p = 0.130) in the fasciocutaneous flap group. There were 2 lost flaps requiring surgical debridement and additional skin grafting in the muscle flaps group (3.70%) versus 2 (4.17%; p = 0.904) in the fasciocutaneous flap group. In the third category, flap loss requiring additional soft tissue reconstruction was 18.52% (n = 10) in the muscle group versus 2.08% (n = 1; p = 0.008) in the fasciocutaneous flap group. Our data support the existing literature indicating that fasciocutaneous flaps can tolerate secondary procedures better than muscle flaps and should initially be considered in patients with higher probability of needing additional orthopedic procedures after reconstruction.

Opioid treatment for opioid withdrawal in newborn infants.

BACKGROUND: Neonatal abstinence syndrome (NAS) due to opioid withdrawal may result in disruption of the mother-infant relationship, sleep-wake abnormalities, feeding difficulties, weight loss, seizures and neurodevelopmental problems. OBJECTIVES: To assess the effectiveness and safety of using an opioid for treatment of NAS due to withdrawal from opioids in newborn infants. SEARCH METHODS: We ran an updated search on 17 September 2020 in CENTRAL via Cochrane Register of Studies Web and MEDLINE via Ovid. We also searched clinical trials databases, conference proceedings and the reference lists of retrieved articles for eligible trials. SELECTION CRITERIA: We included randomised controlled trials (RCTs), quasi- and cluster-RCTs which enrolled infants born to mothers with opioid dependence and who were experiencing NAS requiring treatment with an opioid. DATA COLLECTION AND ANALYSIS: Three review authors independently assessed trial eligibility and risk of bias, and independently extracted data. We used the GRADE approach to assess the certainty of evidence. MAIN RESULTS: We included 16 trials (1110 infants) with NAS secondary to maternal opioid use in pregnancy. Seven studies at low risk of bias were included in sensitivity analysis. Opioid versus no treatment / usual care: a single trial (80 infants) of morphine and supportive care versus supportive care alone reported no difference in treatment failure (risk ratio (RR) 1.29, 95% confidence interval (CI) 0.41 to 4.07; very low certainty evidence). No infant had a seizure. The trial did not report mortality, neurodevelopmental disability and adverse events. Morphine increased days hospitalisation (mean difference (MD) 15.00, 95% CI 8.86 to 21.14; very low certainty evidence) and treatment (MD 12.50, 95% CI 7.52 to 17.48; very low certainty evidence), but decreased days to regain birthweight (MD -2.80, 95% CI -5.33 to -0.27) and duration (minutes) of supportive care each day (MD -197.20, 95% CI -274.15 to -120.25). Morphine versus methadone: there was no difference in treatment failure (RR 1.59, 95% CI 0.95 to 2.67; 2 studies, 147 infants; low certainty evidence). Seizures, neonatal or infant mortality and neurodevelopmental disability were not reported. A single study reported no difference in days hospitalisation (MD 1.40, 95% CI -3.08 to 5.88; 116 infants; low certainty evidence), whereas data from two studies found an increase in days treatment (MD 2.71, 95% CI 0.22 to 5.21; 147 infants; low certainty) for infants treated with morphine. A single study reported no difference in breastfeeding, adverse events, or out of home placement. Morphine versus sublingual buprenorphine: there was no difference in treatment failure (RR 0.79, 95% CI 0.36 to 1.74; 3 studies, 113 infants; very low certainty evidence). Neonatal or infant mortality and neurodevelopmental disability were not reported. There was moderate certainty evidence of an increase in days hospitalisation (MD 11.45, 95% CI 5.89 to 17.01; 3 studies, 113 infants), and days treatment (MD 12.79, 95% CI 7.57 to 18.00; 3 studies, 112 infants) for infants treated with morphine. A single adverse event (seizure) was reported in infants exposed to buprenorphine. Morphine versus diluted tincture of opium (DTO): a single study (33 infants) reported no difference in days hospitalisation, days treatment or weight gain (low certainty evidence). Opioid versus clonidine: a single study (31 infants) reported no infant with treatment failure in either group. This study did not report seizures, neonatal or infant mortality and neurodevelopmental disability. There was low certainty evidence for no difference in days hospitalisation or days treatment. This study did not report adverse events. Opioid versus diazepam: there was a reduction in treatment failure from use of an opioid (RR 0.43, 95% CI 0.23 to 0.80; 2 studies, 86 infants; low certainty evidence). Seizures, neonatal or infant mortality and neurodevelopmental disability were not reported. A single study of 34 infants comparing methadone versus diazepam reported no difference in days hospitalisation or days treatment (very low certainty evidence). Adverse events were not reported. Opioid versus phenobarbital: there was a reduction in treatment failure from use of an opioid (RR 0.51, 95% CI 0.35 to 0.74; 6 studies, 458 infants; moderate certainty evidence). Subgroup analysis found a reduction in treatment failure in trials titrating morphine to ≧ 0.5 mg/kg/day (RR 0.21, 95% CI 0.10 to 0.45; 3 studies, 230 infants), whereas a single study using morphine < 0.5 mg/kg/day reported no difference compared to use of phenobarbital (subgroup difference P = 0.05). Neonatal or infant mortality and neurodevelopmental disability were not reported. A single study (111 infants) of paregoric versus phenobarbital reported seven infants with seizures in the phenobarbital group, whereas no seizures were reported in two studies (170 infants) comparing morphine to phenobarbital. There was no difference in days hospitalisation or days treatment. A single study (96 infants) reported no adverse events in either group. Opioid versus chlorpromazine: there was a reduction in treatment failure from use of morphine versus chlorpromazine (RR 0.08, 95% CI 0.01 to 0.62; 1 study, 90 infants; moderate certainty evidence). No seizures were reported in either group. There was low certainty evidence for no difference in days treatment. This trial reported no adverse events in either group. None of the included studies reported time to control of NAS. Data for duration and severity of NAS were limited, and we were unable to use these data in quantitative synthesis. AUTHORS' CONCLUSIONS: Compared to supportive care alone, the addition of an opioid may increase duration of hospitalisation and treatment, but may reduce days to regain birthweight and the duration of supportive care each day. Use of an opioid may reduce treatment failure compared to phenobarbital, diazepam or chlorpromazine. Use of an opioid may have little or no effect on duration of hospitalisation or treatment compared to use of phenobarbital, diazepam or chlorpromazine. The type of opioid used may have little or no effect on the treatment failure rate. Use of buprenorphine probably reduces duration of hospitalisation and treatment compared to morphine, but there are no data for time to control NAS with buprenorphine, and insufficient evidence to determine safety. There is insufficient evidence to determine the effectiveness and safety of clonidine.

Sedatives for opioid withdrawal in newborn infants.

BACKGROUND: Neonatal abstinence syndrome (NAS) due to opioid withdrawal may result in disruption of the mother-infant relationship, sleep-wake abnormalities, feeding difficulties, weight loss, seizures and neurodevelopmental problems. OBJECTIVES: To assess the effectiveness and safety of using a sedative versus control (placebo, usual treatment or non-pharmacological treatment) for NAS due to withdrawal from opioids and determine which type of sedative is most effective and safe for NAS due to withdrawal from opioids. SEARCH METHODS: We ran an updated search on 17 September 2020 in CENTRAL via CRS Web and MEDLINE via Ovid. We searched clinical trials databases, conference proceedings and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. SELECTION CRITERIA: We included trials enrolling infants with NAS born to mothers with an opioid dependence with more than 80% follow-up and using randomised, quasi-randomised and cluster-randomised allocation to sedative or control. DATA COLLECTION AND ANALYSIS: Three review authors assessed trial eligibility and risk of bias, and independently extracted data. We used the GRADE approach to assess the certainty of the evidence. MAIN RESULTS: We included 10 trials (581 infants) with NAS secondary to maternal opioid use in pregnancy. There were multiple comparisons of different sedatives and regimens. There were limited data available for use in sensitivity analysis of studies at low risk of bias. Phenobarbital versus supportive care: one study reported there may be little or no difference in treatment failure with phenobarbital and supportive care versus supportive care alone (risk ratio (RR) 2.73, 95% confidence interval (CI) 0.94 to 7.94; 62 participants; very low-certainty evidence). No infant had a clinical seizure. The study did not report mortality, neurodevelopmental disability and adverse events. There may be an increase in days' hospitalisation and treatment from use of phenobarbital (hospitalisation: mean difference (MD) 20.80, 95% CI 13.64 to 27.96; treatment: MD 17.90, 95% CI 11.98 to 23.82; both 62 participants; very low-certainty evidence). Phenobarbital versus diazepam: there may be a reduction in treatment failure with phenobarbital versus diazepam (RR 0.39, 95% CI 0.24 to 0.62; 139 participants; 2 studies; low-certainty evidence). The studies did not report mortality, neurodevelopmental disability and adverse events. One study reported there may be little or no difference in days' hospitalisation and treatment (hospitalisation: MD 3.89, 95% CI -1.20 to 8.98; 32 participants; treatment: MD 4.30, 95% CI -0.73 to 9.33; 31 participants; both low-certainty evidence). Phenobarbital versus chlorpromazine: there may be a reduction in treatment failure with phenobarbital versus chlorpromazine (RR 0.55, 95% CI 0.33 to 0.92; 138 participants; 2 studies; very low-certainty evidence), and no infant had a seizure. The studies did not report mortality and neurodevelopmental disability. One study reported there may be little or no difference in days' hospitalisation (MD 7.00, 95% CI -3.51 to 17.51; 87 participants; low-certainty evidence) and 0/100 infants had an adverse event. Phenobarbital and opioid versus opioid alone: one study reported no infants with treatment failure and no clinical seizures in either group (low-certainty evidence). The study did not report mortality, neurodevelopmental disability and adverse events. One study reported there may be a reduction in days' hospitalisation for infants treated with phenobarbital and opioid (MD -43.50, 95% CI -59.18 to -27.82; 20 participants; low-certainty evidence). Clonidine and opioid versus opioid alone: one study reported there may be little or no difference in treatment failure with clonidine and dilute tincture of opium (DTO) versus DTO alone (RR 0.09, 95% CI 0.01 to 1.59; 80 participants; very low-certainty evidence). All five infants with treatment failure were in the DTO group. There may be little or no difference in seizures (RR 0.14, 95% CI 0.01 to 2.68; 80 participants; very low-certainty evidence). All three infants with seizures were in the DTO group. There may be little or no difference in mortality after discharge (RR 7.00, 95% CI 0.37 to 131.28; 80 participants; very low-certainty evidence). All three deaths were in the clonidine and DTO group. The study did not report neurodevelopmental disability. There may be little or no difference in days' treatment (MD -4.00, 95% CI -8.33 to 0.33; 80 participants; very low-certainty evidence). One adverse event occurred in the clonidine and DTO group. There may be little or no difference in rebound NAS after stopping treatment, although all seven cases were in the clonidine and DTO group. Clonidine and opioid versus phenobarbital and opioid: there may be little or no difference in treatment failure (RR 2.27, 95% CI 0.98 to 5.25; 2 studies, 93 participants; very low-certainty evidence). One study reported one infant in the clonidine and morphine group had a seizure, and there were no infant mortalities. The studies did not report neurodevelopmental disability. There may be an increase in days' hospitalisation and days' treatment with clonidine and opioid versus phenobarbital and opioid(hospitalisation: MD 7.13, 95% CI 6.38 to 7.88; treatment: MD 7.57, 95% CI 3.97 to 11.17; both 2 studies, 91 participants; low-certainty evidence). There may be little or no difference in adverse events (RR 1.55, 95% CI 0.44 to 5.40; 2 studies, 93 participants; very low-certainty evidence). However, there was oversedation only in the phenobarbital and morphine group; and hypotension, rebound hypertension and rebound NAS only in the clonidine and morphine group. AUTHORS' CONCLUSIONS: There is very low-certainty evidence that phenobarbital increases duration of hospitalisation and treatment, but reduces days to regain birthweight and duration of supportive care each day compared to supportive care alone. There is low-certainty evidence that phenobarbital reduces treatment failure compared to diazepam and very low-certainty evidence that  phenobarbital reduces treatment failure compared to chlorpromazine. There is low-certainty evidence of an increase in days' hospitalisation and days' treatment with clonidine and opioid compared to phenobarbital and opioid. There are insufficient data to determine the safety and incidence of adverse events for infants treated with combinations of opioids and sedatives including phenobarbital and clonidine.

Systematic review of sacroiliac joint motion and the effect of screw fixation.

BACKGROUND: Pelvic injuries that disrupt the sacroiliac joints often require surgical intervention to restore stability. Quantitative characterization of sacroiliac motion in response to physiologic loading provides important metrics of adequate fixation in the evaluation of newly emerged fixation techniques. The objective of this study was to systematically review and evaluate biomechanical evidence on the motion of the sacroiliac joint in its normal, destabilized, and stabilized states. METHODS: We searched the PubMed database for studies available until June 2020 using keywords: sacroiliac, biomechanic*, and fixation. Publications of any in vivo or in vitro biomechanical study that included measurements of the range of motion at the sacroiliac joint were considered. FINDINGS: We identified and screened 176 total records, and 13 articles of them met inclusion criteria and were used in this review. The average sacroiliac joint range of motion of the intact pelvis was 1.88° in flexion/extension, 0.85° in lateral bending, 1.26° in axial rotation. Of the 13 studies, four reported sacroiliac motion from a destabilized state, while seven reported the motion after stabilization. A forest plot of the stabilized data set in flexion/extension showed that while the heterogeneity was poor, the weighted effect size of the changes from the intact state to the stabilized state was 0.0%. INTERPRETATION: Quantitative evidence on sacroiliac joint motion relating to pelvic injuries or fixation is limited. Our results indicate that the pooled intact range of motion from the literature may serve as a viable reference to quantify the effectiveness of new stabilization techniques. LEVEL OF EVIDENCE: Level V, systematic review. STUDY TYPE: Therapeutic- investigating the results of a treatment.

Patient-Reported Outcomes of Femoral Head Fractures with a Minimum 10-Year Follow-Up.

OBJECTIVE: To evaluate the clinical-reported and patient-reported outcomes of patients with femoral head fractures treated at a single level I trauma center with a minimum 10-year follow-up. DESIGN: Retrospective review. SETTING: Academic Level-1 Trauma Center. PATIENTS/PARTICIPANTS: One hundred one consecutive femoral head fractures were identified for this study. The final study group consisted of 28 patients with a minimum of 10 years of clinical follow-up. INTERVENTION: All patients were treated with one or in combination with the following treatments: nonoperative management, open reduction and internal fixation, fragment excision, or total hip arthroplasty (THA). MAIN OUTCOME MEASURES: The Oxford Hip Score (OHS) at final follow-up along with clinical and radiological complications: infection, avascular necrosis, post-traumatic osteoarthritis, heterotopic ossification, and conversion to THA. RESULTS: Twenty-eight patients with greater than 10 years of follow-up were included in this evaluation. The average follow-up was 14 years, and the average age was 39.2 years. Surgical management occurred in 86% of patients, and the mean time to definitive treatment was 3.7 days. Overall, 21 patients (75%) experienced a complication. Seven patients (30%) were later converted to a THA at an average of 6.4 years from initial injury. Three of the 7 late THA conversions (43%) required later revision. OHSs were obtained in all 28 patients at the final follow-up. The average OHS was 36.6. The mean OHS of the native hips was 37 at an average follow-up of 13.6 years. The mean OHS of primary THA was 41, and the mean OHS of secondary THA at final follow-up was 31.4, but this was not statistically significant (P = 0.134). CONCLUSIONS: Patients should be counseled that the long-term results of open reduction and internal fixation may be satisfactory but unfortunately are not predictable. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Biomechanical Comparison of Tension Band Fixation of Patella Transverse Fracture: Headless Screws Versus Headed Screws.

OBJECTIVE: This study aimed to investigate the stability and strength of tension band wire fixation using headless compression screws versus headed screws for transverse patella fractures. METHODS: Six matched pairs of fresh-frozen cadaveric knees with transverse osteotomies created at the midpoint of the patella were surgically fixed, with one knee randomly receiving fixation with headless screws (Acumed Acutrak 4/5) and the other with headed screws (Synthes 4.0 partially threaded cannulated screws). The specimens were mounted onto a servohydraulic load frame in a 45-degree flexed position and loaded through the quadriceps tendon. Interfragmentary movement was recorded with a motion analysis system. The initial fixation stiffness, range of interfragmentary motion, and strength of the headless screw construct were compared with the headed screw construct. Failure was defined as either a sudden drop in applied tendon force or 2 mm of separation on the anterior surface of the patella (ie, clinical failure), whichever occurred first. RESULTS: Mean primary interfragmentary motion was 0.31 ± 0.28 degrees for the headed screws and 0.10 ± 0.06 degrees for headless screws under 150 N load (P = 0.03). Mean construct stiffness was 277 ± 243 N/degrees for the headed screws and 510 ± 362 N/degrees for the headless screws (P = 0.03). None of the constructs from either group displayed structural failure before reaching the clinical failure gap of 2 mm. The mean clinical failure strength was 808 ± 183 N for the headless screws construct and 520 ± 241 N for the headed screws construct (P = 0.03). CONCLUSIONS: Headless screw tension band fixation demonstrated superior biomechanical behaviors over standard headed screw fixation with higher construct rigidity, smaller interfragmentary motion, and greater fixation strength.

Incidence of adverse events with HMG-CoA reductase inhibitors in liver transplant patients.

UNLABELLED: Transplant patients are at increased risk of developing dyslipidemia, which contributes to coronary artery disease and cardiovascular events. The purpose of this study was to explore documented adverse effects of liver transplant recipients receiving lipid-lowering therapies. METHODS: A retrospective chart review of 69 liver transplant patients was conducted to evaluate the incidence of adverse effects, especially rhabdomyolysis and liver function abnormalities, in liver transplant patients treated with a lipid lowering agent (LLA). Data were collected from the time of initiation of LLA to 12 months later, looking at the type, dose, and duration of LLA, concurrent cytochrome P450 inhibitors, immunosuppression used, and laboratory parameters. RESULTS: For HMG-CoA reductase inhibitor therapy, simvistatin was used in five (7.8%) patients, pravastatin in 40 (62.5%), fluvastatin in one (1.6%), atorvastatin in five (7.8%), and lovastatin in three (4.7%). Gemfibrozil, a fibric acid derivative, was employed as monotherapy in 10 (15.6%) of patients. There were five patients who received combination therapy with a fibric acid derivative, four (80%) with gemfibrozil + pravastatin, and one (20%) with gemfibrozil + simvastatin. Six patients studied had adverse effects, five (7.2%) with myalgia and one (1.4%) with myopathy. LLA monotherapy with either pravastatin or atorvastatin was used in these patients. The five patients with myalgia were on concurrent therapy with cyclosporin, and the patient with myopathy was on concurrent cyclosporin + diltiazem therapy, both of which are P450 inhibitors. One out of 23 patients on a non-immunosuppressant P450 inhibitor developed adverse effects. No significant elevation of alanine aminotransferase, aspartate aminotransferase, or alkaline phosphatase was noted in any patient. CONCLUSIONS: Overall, there was a general tolerability with a low incidence of adverse events, no incidence of severe complications, and no alterations in liver function tests in the study population with the use of LLA.

Update on pharmacoeconomics in transplantation.

PURPOSE: To provide current information on pharmacoeconomic outcomes in transplantation for the past 6 years. METHODS: An extensive literature search was undertaken using PubMed and other authenticated Internet sources. Key words used to elicit pertinent studies were "pharmacoeconomics," "transplantation," "cost-effectiveness," "cost-benefit," "cost-minimization" and "cost-utility" analyses. Studies included in the review contain updated pharmacoeconomic data generated during the past 6 years on economic, clinical, and humanistic outcomes. These data are used to describe and analyze the cost of drug therapy used in transplantation. RESULTS: Background information is included in the review to provide a context from which to evaluate new study material. Data extracted from the studies include significant findings and study limitations. Data were stratified into understanding pharmacoeconomic methods and their application to transplantation, maintenance and induction therapies, and management of and costs associated with adverse events and quality-of-life issues. CONCLUSIONS: Continued evolution of pharmacoeconomic analysis is needed so that optimal care can be provided in the most cost-effective manner. Pharmacoeconomic study, done rationally and logically, is an indispensable tool in determining optimal transplantation regimens.

Consequences of vancomycin-resistant Enterococcus in liver transplant recipients: a matched control study.

BACKGROUND: Liver transplant recipients are at high risk for multi-drug resistant infections because of broad-spectrum antibiotic and immunosuppression. This study evaluates the clinical and financial impact of vancomycin resistant Enterococcus (VRE) in liver transplant recipients. METHODS: Liver transplant recipients with VRE from 1995 to 2002 were identified and matched (age, gender, UNOS status, liver disease and transplant date) to controls. Demographics, clinical factors, co-infections, antibiotic use, length of stay, abdominal surgeries, biliary complications, survival and resource utilization were compared with matched controls. RESULTS: Nineteen patients were found to have 28 VRE infections via evaluation of microbiologic culture results of all liver transplant patients in the transplant registry. Thirty-eight non-VRE patients served as matched controls. The four most common sites VRE was cultured from included blood (35%), peritoneal fluid (35%), bile (20%), and urine (12%). Median time from transplant to infection was 48 d (range of 4-348). No significant differences in demographics were observed. The VRE group had a higher incidence of prior antibiotic use than the non-VRE group (95% vs. 34%; p < 0.05). The VRE group also experienced more abdominal surgery (20/19 vs. 3/38; p = 0.029), biliary complications (9/19 vs. 9/38; p = 0.018) and a longer length of stay (42.5 vs. 21.7 d; p = .005). Survival in the VRE group was lower (52% vs. 82%; p = 0.048). Six of the 19 VRE patients were treated with linezolid for eight infection episodes, and four of six patients survived. Eight patients were treated with quinupristin/dalfopristin for nine infections, and two of eight survived. Increased cost of care was observed in the VRE group. Laboratory costs were higher in the VRE group (6500 dollars vs. 1750; p = 0.02) as well. CONCLUSION: VRE was associated with prior antibiotic use, multiple abdominal surgeries, biliary complications and resulted in decreased survival compared to non-VRE control patients. VRE patients also utilized more hospital resources. Linezolid showed a trend toward improved survival.

Laparoscopic donor nephrectomy vs. open live donor nephrectomy: a quality of life and functional study.

BACKGROUND: Few studies have compared the quality of life (QoL) and functional recuperation of laproscopic donor nephrectomy (LDN) vs. open donor nephrectomy (ODN) donors. This study utilized the SF-36 health survey, single-item health-related quality of life (HRQOL) score, and a functional assessment questionnaire ('Donor Survey'). METHODS: Questionnaires were sent to 100 LDN and 50 ODN donors. These donors were patients whose procedures were performed at The University Hospital and The Christ Hospital in Cincinnati, Ohio. RESULTS: A total of 46 (46%) LDN and 21 (42%) ODN donors returned the completed surveys. The demographics of the two groups were similar. LDN patients reported a more rapid return to 100% normal health (69 vs. 116 d; p = 0.24), part-time work (21.9 vs. 23.2 d; p = 0.09), and necessitated fewer physician office visits post-operative (2.8 vs. 4.4; p = 0.01). ODN patients reported shorter duration of oral pain medication use (13.4 vs. 7.2 d; p = 0.02). However, a greater number of ODN patients reported post-surgical chronic pain (3 vs. 6; p < 0.05) and hernia (0 vs. 2; p = 0.19). The overall QoL for both groups was comparable with the general USA population. CONCLUSIONS: The results of this study support the decisions of many kidney transplant centers to adopt LDN programs as standard of care.

The expanding role of the transplant pharmacist in the multidisciplinary practice of transplantation.

INTRODUCTION: The burgeoning clinical discipline and growth of organ transplantation has resulted in an expansion in the number of healthcare specialists to support clinical care and research. The past 10 yrs have seen a dramatic increase in the number of immunosuppressive agents and other medications used in transplantation, resulting in more complex medication regimens and greater potential for interactions, adverse effects and increased costs. PURPOSE: To determine how transplant pharmacists are being integrated into transplant clinical practice. Transplant centres were identified through UNOS Transplant Administrators Committee list serve. A survey was then distributed via e-mail to 159 individuals representing 118 solid organ transplant centres. RESULTS: Forty-one (35%) of the 118 centres responded, with 36 evaluable surveys. Of the 36 centres, 28 (78%) had transplant pharmacist support and eight did not have a pharmacist dedicated to transplant (two of the eight were recruiting). A majority of the respondents had multi-organ transplant responsibilities. Eighty-six per cent of pharmacists were involved in kidney transplant, 71% in liver, 50% in pancreas, 25% in heart, and 7% in lung. Pharmacist salaries were most often funded by a department of pharmacy (74%), followed by college of pharmacy (12%), transplant centre (8%) and department of surgery (6%). Almost all of the pharmacist's clinical practice time focused on post-transplant care (99%). The average percentage of the pharmacist's time was: 43% inpatient, 15% outpatient, 14% research, 6% other transplant related, and 22% non-transplant related. Of the 28 pharmacists, 25 had a PharmD degree, two a BS and one had a PhD in Pharmacy. The average number of organs transplanted among the responding centres was 99 kidneys, 45 livers, 28 pancreas, 14 heart, and 26 lungs. The number of transplants did not differ between the programmes with pharmacist clinical support vs. those without designated pharmacist support. CONCLUSION: The survey indicates that many solid organ transplant centres have incorporated transplant pharmacists into the multidisciplinary transplant clinical team. Transplant pharmacists are funded most often by the hospital pharmacy. Most transplant pharmacists spend the majority of their time in clinical practice, but also play a key role in research.

Total pancreatectomy and autologous islet cell transplantation as a means to treat severe chronic pancreatitis.

Autologous islet cell transplantation after near-total or total pancreatic resection can alleviate pain in patients with severe chronic pancreatitis and preserve endocrine function. From February 2000 to February 2003, a total of 22 patients, whose median age was 38 years, underwent pancreatectomy and autologous islet cell transplantation. Postoperative complications, metabolic studies, insulin usage, pain scores, and quality of life were recorded for all of these patients. The average number of islet cells harvested was 245,457 (range 20,850 to 607,466). Operative data revealed a mean estimated blood loss of 635 ml, an average operative time of 9 hours, and a mean length of hospital stay of 15 days. Sixty-eight percent of the patients had either a minor or major complication. Major complications included acute respiratory distress syndrome (n=2), intra-abdominal abscess (n=1), and pulmonary embolism (n=1). There were no deaths in our series. All patients demonstrated C-peptide and insulin production indicating graft function. Forty-one percent are insulin independent, and 27% required minimal amount of insulin or a sliding scale. All patients had preoperative pain and had been taking opioid analgesics; 82% no longer required analgesics postoperatively. Pancreatectomy with autologous islet cell transplantation can alleviate pain for patients with chronic pancreatitis and preserve endocrine function.