Technical Factors Contributing to Nonunion in Supracondylar Distal Femur Fractures Treated With Lateral Locked Plating: A Risk-Stratified Analysis.

OBJECTIVE: To identify technical factors associated with nonunion after operative treatment with lateral locked plating. DESIGN: Retrospective cohort study. SETTING: Ten Level I trauma centers. PATIENT SELECTION CRITERIA: Adult patients with supracondylar distal femur fractures (OTA/AO type 33A or C) treated with lateral locked plating from 2010 through 2019. OUTCOME MEASURES AND COMPARISONS: Surgery for nonunion stratified by risk for nonunion. RESULTS: The cohort included 615 patients with supracondylar distal femur fractures. The median patient age was 61 years old (interquartile range: 46 -72years) and 375 (61%) were female. Observed were nonunion rates of 2% in a low risk of nonunion group (n = 129), 4% in a medium-risk group (n = 333), and 14% in a high-risk group (n = 153). Varus malreduction with an anatomic lateral distal femoral angle greater than 84 degrees, was associated with double the odds of nonunion compared to those without such varus [odds ratio, 2.1; 95% confidence interval (CI), 1.1-4.2; P = 0.03]. Malreduction by medial translation of the articular block increased the odds of nonunion, with 30% increased odds per 4 mm of medial translation (95% CI, 1.0-1.6; P = 0.03). Working length increased the odds of nonunion in the medium risk group, with an 18% increase in nonunion per 10-mm increase in working length (95% CI, 1.0-1.4; P = 0.01). Increased proximal screw density was protective against nonunion (odds ratio, 0.71; 95% CI, 0.53-0.92; P = 0.02) but yielded lower mRUST scores with each 0.1 increase in screw density associated with a 0.4-point lower mRUST (95% CI, -0.55 to -0.15; P < 0.001). Lateral plate length and type of plate material were not associated with nonunion. ( P > 0.05). CONCLUSIONS: Malreduction is a surgeon-controlled variable associated with nonunion after lateral locked plating of supracondylar distal femur fractures. Longer working lengths were associated with nonunion, suggesting that bridge plating may be less likely to succeed for longer fractures. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Patient preferences for physical therapy programs after a lower extremity fracture: a discrete choice experiment.

OBJECTIVE: To quantify patients' preferences for physical therapy programmes after a lower extremity fracture and determine patient factors associated with preference variation. DESIGN: Discrete choice experiment. SETTING: Level I trauma centre. PARTICIPANTS: One hundred fifty-one adult (≥18 years old) patients with lower extremity fractures treated operatively. INTERVENTION: Patients were given hypothetical scenarios and asked to select their preferred therapy course when comparing cost, mobility, long-term pain, session duration, and treatment setting. MAIN OUTCOME MEASURES: A multinomial logit model was used to determine the relative importance and willingness to pay for each attribute. RESULTS: Mobility was of greatest relative importance (45%, 95% CI: 40% to 49%), more than cost (23%, 95% CI: 19% to 27%), long-term pain (19%, 95% CI: 16% to 23%), therapy session duration (12%, 95% CI: 9% to 5%) or setting (1%, 95% CI: 0.2% to 2%). Patients were willing to pay US$142 more per session to return to their preinjury mobility level (95% CI: US$103 to US$182). Willingness to pay for improved mobility was higher for women, patients aged 70 years and older, those with bachelor's degrees or higher and those living in less-deprived areas. Patients were willing to pay US$72 (95% CI: US$50 to US$93) more per session to reduce pain from severe to mild. Patients were indifferent between formal and independent home therapy (willingness to pay: -US$12, 95% CI: -US$33 to US$9). CONCLUSIONS: Patients with lower extremity fractures highly value recovering mobility and are willing to pay more for postoperative physical therapy programmes that facilitate returning to their pre-injury mobility level. These patient preferences might be useful when prescribing and designing new techniques for postoperative therapy.

A deep surgical site infection risk score for patients with open tibial shaft fractures treated with intramedullary nail.

OBJECTIVES: To identify deep infection risk factors in patients with open tibial shaft fractures and to develop a scoring algorithm to predict the baseline deep infection risk in this patient population. METHODS: A retrospective cohort study conducted at a single academic trauma center identified patients with open tibial shaft fractures treated with intramedullary nail fixation from December 2006 to October 2020. The primary outcome was a deep surgical site infection requiring surgical debridement. The outcome was identified by Current Procedural Terminology codes and confirmed with a medical chart review documenting evidence of a tibial draining wound or sinus tract. RESULTS: Deep surgical site infection occurred in 13% of patients (97/769). Factors that predicted deep surgical site infection were identified. Gustilo-Anderson type IIIB or IIIC was the strongest predictor with a 12-fold increase in the odds of deep infection (OR 11.8, p < 0.001). Additional factors included age >40 years (OR 1.7, p = 0.03), American Society of Anesthesiologists score ≥3 (OR 1.9, p < 0.01), Gustilo-Anderson type IIIA vs. type I or II (OR 2.8, p = 0.004), and gunshot wounds (OR 2.9, p = 0.02). The risk scoring model predicted patients who would develop an infection with an acceptable level of accuracy (AUC 0.79). The risk score categorized patients from a low probability of deep infection 2%-6% with <10 points to high risk (58%-69%) with >40 points. CONCLUSIONS: This risk score model predicts deep postoperative infection in patients with open tibial shaft fractures treated with intramedullary nails. The ability to accurately estimate deep infection risk at the time of presentation might aid patient expectation management and allow clinicians to focus infection prevention strategies on the high-risk subset of this population.

Financial Toxicity Is Common in Patients After Tibia Fracture.

OBJECTIVES: To evaluate the presence of financial distress and identify risk factors for financial toxicity in patients after tibial shaft fracture. DESIGN: A cross-sectional analysis. SETTING: Level I trauma center. PATIENTS: All patients within 4 years after tibial shaft fracture (open, closed, or fracture that required flap reconstruction). INTERVENTION: Injury-related financial distress. MAIN OUTCOME MEASUREMENTS: Financial distress related to the injury, as reported by the patient in a binary question. Financial toxicity using the LIMB-Q, scored from 0 to 100, with higher scores indicating more financial toxicity. RESULTS: Data were collected from 142 patients after tibial shaft fracture [44% closed (n = 62), 41% open (n = 58), and 15% flap (n = 22)]. The mean age was 44 years (SD 17), 61% were men, and the mean time from injury was 15 months. Financial distress was reported by 64% of patients (95% confidence interval, 56% to 72%). Financial toxicity did not differ by fracture severity ( P = 0.12). Medical complications were associated with a 14-point increase in financial toxicity ( P = 0.04). Age older than 65 years (-15 points, P = 0.03) and incomes of $70,000 or more ($70,000-$99,999, -15 points, P = 0.02; >$100,000, -19 points, P < 0.01) protected against financial toxicity. CONCLUSION: We observed financial distress levels more than twice the proportion observed after cancer. Medical complications, lower incomes, and younger age were associated with increased financial toxicity. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

The Use of Vancomycin Powder in Tibial Plateau Fractures at Lower Risk of Infection.

OBJECTIVE: To determine the effectiveness of vancomycin powder in preventing infection after plate and screw fixation of tibial plateau fractures considered at low risk of infection. DESIGN: Retrospective cohort study. SETTING: Single, Level I trauma center. PATIENTS/PARTICIPANTS: This study included 459 patients with tibial plateau fractures (OTA/AO 41-B/C) who underwent open reduction and internal fixation from 2006 to 2018 and were considered at low risk of infection based on not meeting the "high risk" definition of the VANCO trial. INTERVENTION: Vancomycin powder administration on wound closure at the time of definitive fixation. MAIN OUTCOME MEASUREMENTS: Deep surgical site infection with at least 1 gram-positive bacteria culture. RESULTS: Vancomycin powder administration was associated with reduction in gram-positive infection from 4% to 0% (odds ratio, 0.12; 95% confidence interval, 0.04-0.32; P < 0.01). No significant effect was reported in gram-negative only infections, which were observed in 0.3% in the control group, compared with 0.9% in the intervention group (odds ratio, 2.71; 95% confidence interval, 0.11-69; P = 0.54). Methicillin-resistant Staphylococcus aureus was the most common organism isolated in the control group, growing in 9 of 18 infections (50%). CONCLUSIONS: Among patients with low-risk tibial plateau fractures, vancomycin powder at the time of definitive fixation showed a reduction in the incidence of gram-positive deep surgical site infection. The observed relative effect was relatively larger than that observed in a previous randomized trial on high-risk fractures. These data might support broadening the indication for use of vancomycin powder to include tibial plateau fractures at low risk of infection. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Outcomes of Tibiotalocalcaneal Hindfoot Fusion Nails Used for Acute Lower Extremity Trauma in a High-Risk Patient Population.

OBJECTIVE: To determine the outcomes of high-risk patients treated with tibiotalocalcaneal hindfoot fusion nails. DESIGN: Retrospective case series. SETTING: Level I trauma center. PATIENTS/PARTICIPANTS: Between January 2007 and December 2016, 50 patients with significant medical comorbidities treated with a tibiotalocalcaneal hindfoot fusion nail in the setting of acute distal tibia and ankle trauma considered to be limb-threatening. INTERVENTION: Tibiotalocalcaneal hindfoot fusion nail. MAIN OUTCOME MEASUREMENTS: Two-year cumulative incidence of unplanned reoperation and estimated survival with limb salvage at 2 years. RESULTS: Of the 50 patients, 20 (38%) had an unplanned reoperation (mean: 2.5 reoperations), including 19 for implant removal, 11 for irrigation and debridement and/or placement of an antibiotic delivery device, and 4 for revision fusion. Three patients required amputation and 3 patients died within 2 years of injury, resulting in an estimated survival with limb salvage at 2 years of 79% (95% confidence interval: 67%-91%). After accounting for the competing risk of death and incomplete follow-up, the 2-year cumulative incidence of unplanned reoperation was 64% (95% confidence interval: 62%-67%). CONCLUSIONS: Patients in this series experienced a high rate of return to the operating room but a relatively low rate of amputation. Because patients were indicated for this course of treatment on the basis of comorbidities felt to put them at high risk of loss of limb with traditional treatment, acute hindfoot fusion nailing might represent a viable option in select high-risk patients and injuries. Clinicians should be aware that complications are still common. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Does iliosacral screw removal reduce postoperative pain in unstable pelvic fracture patients? A matched prospective cohort study.

BACKGROUND: To compare pain and function in patients with unstable posterior pelvic fractures stabilized with posterior fixation who undergo iliosacral screw removal versus those who retain their iliosacral screws. METHODS: A prospective observational cohort study identified 59 patients who reported pain at least 4 months after iliosacral screw fixation of an unstable posterior pelvic ring fracture from 2015-2019. The primary intervention was iliosacral screw removal versus a matched iliosacral screw retention control group. Patient-reported pain was measured with the 10-point Brief Pain Inventory, and patient-reported function was measured with the Majeed Pelvic Outcome Score. Both measured within 6 months of the intervention. RESULTS: Before iliosacral screw removal, the mean pain was 4.7 (SD, 3.0) compared with 4.7 (SD, 3.0) in the matched control group. Following iliosacral screw removal, the average pain in the screw removal group was 3.7 (SD, 2.7) and 3.3 (SD, 2.5) in the matched control group. We found no evidence that iliosacral screw removal reduced pain in this population (mean difference, 0.2 points; 95% CI, -1.0 to 1.5; p = 0.71). In addition, the improvement in function after iliosacral screw removal was not statistically indistinguishable from zero (mean difference, 3.1 points; 95% CI, -4.6 to 10.9; p = 0.42). CONCLUSIONS: The results suggest that iliosacral screw removal offers no significant pelvic pain or function benefit when compared with a matched control group. Surgeons should consider these data when managing patients with pelvic pain who are candidates for iliosacral screw removal.

Association of Radial Head Fracture Treatment With Long-Term Function.

BACKGROUND: Radial head fractures are often associated with poor outcomes. Both open reduction and internal fixation (ORIF) and radial head arthroplasty (RHA) might be considered in operative cases. This study aimed to compare long-term patient-reported functional outcomes among patients with operatively treated radial head fractures. METHODS: A cross sectional study conducted at a Level I trauma center was used to identify patients with a radial head fracture who underwent ORIF or RHA between 2006 and 2018, and agreed to complete a survey in 2020. The primary outcome measure was the Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) score. RESULTS: Seventy-six patients participated in the study. No significant differences in outcomes were observed between groups. QuickDASH scores were similar for both groups (ORIF: mean = 15.7, SD = 18.4; RHA: mean = 22.8, SD = 18.6; mean difference = 0.2 [-9.0 to 9.3], P = .97). Nineteen (37%) ORIF patients and 12 (48%) RHA patients reported a need for pain medication (adjusted odds ratio [OR] = 0.8 [0.3-2.4], P = .70). Thirteen (25%) ORIF patients and 6 (24%) RHA patients required additional surgery (adjusted OR = 1.7 [0.5-6.2], P = .39). A subgroup analysis of multi-fragmentary fractures revealed similar findings. CONCLUSION: Patient-reported outcomes, which included a subgroup analysis of multi-fragmentary fractures, were similar between ORIF and RHA groups at an average of 7.5 years from surgery. Reconstructing the radial head might not result in worse outcomes than RHA when both options are employed according to the best judgment of the operating surgeon.

Multiple Sclerosis at Home Access (MAHA): An Initiative to Improve Care in the Community.

BACKGROUND: Caring for individuals with progressive, disabling forms of multiple sclerosis (MS) presents ongoing, complex challenges in health care delivery, especially access to care. Although mobility limitations represent a major hurdle to accessing comprehensive and coordinated care, fragmentation in current models of health care delivery magnify the problem. Importantly, individuals with disabling forms of MS are exceedingly likely to develop preventable secondary complications and to incur significant suffering and increased health care utilization and costs. METHODS: A house call program, Multiple Sclerosis at Home Access (MAHA), was implemented. The program was designed to provide comprehensive services and prevent common complications. Key aspects included monthly house calls, continuity among providers, and a multidisciplinary team led by a comprehensivist, a provider bridging subspecialty and primary care. A total of 21 adult patients (Expanded Disability Status Scale score ≥7.5) completed 1 full year of the program. RESULTS: During the 2-year preevaluation and postevaluation period, half of the hospital admissions were related to secondary and generally preventable complications. Aside from a single outlying individual important to the evaluation, in the year after program implementation, decreases were found in number of individuals hospitalized, hospitalizations/skilled facility admissions, and hospital days; the total number of overall emergency department (ED) visits decreased; and ED-only visits increased (ie, ED visits without hospital admission). Patient satisfaction reports and quality indicators were positive. Fifty percent of patients participated in supplementary televisits. CONCLUSIONS: This program evaluation suggests that a house call-based practice is a viable solution for improving care delivery for patients with advanced MS and disability.

Pattern Recognition of the Multiple Sclerosis Syndrome.

During recent decades, the autoimmune disease neuromyelitis optica spectrum disorder (NMOSD), once broadly classified under the umbrella of multiple sclerosis (MS), has been extended to include autoimmune inflammatory conditions of the central nervous system (CNS), which are now diagnosable with serum serological tests. These antibody-mediated inflammatory diseases of the CNS share a clinical presentation to MS. A number of practical learning points emerge in this review, which is geared toward the pattern recognition of optic neuritis, transverse myelitis, brainstem/cerebellar and hemispheric tumefactive demyelinating lesion (TDL)-associated MS, aquaporin-4-antibody and myelin oligodendrocyte glycoprotein (MOG)-antibody NMOSD, overlap syndrome, and some yet-to-be-defined/classified demyelinating disease, all unspecifically labeled under MSsyndrome. The goal of this review is to increase clinicians' awareness of the clinical nuances of the autoimmune conditions for MS and NMSOD, and to highlight highly suggestive patterns of clinical, paraclinical or imaging presentations in order to improve differentiation. With overlay in clinical manifestations between MS and NMOSD, magnetic resonance imaging (MRI) of the brain, orbits and spinal cord, serology, and most importantly, high index of suspicion based on pattern recognition, will help lead to the final diagnosis.

Errors in the ankle plantarflexor force production are related to the gait deficits of individuals with multiple sclerosis.

BACKGROUND: Individuals with multiple sclerosis (MS) often have limited mobility that is thought to be due to the neuromuscular impairments of the ankle. Greater isometric motor control of the ankle has been associated with better standing postural balance but its relationship to mobility is less understood. The objectives of this investigation were to quantify the motor control of the ankle plantarflexors of individuals with MS during a dynamic isometric motor task, and explore the relationship between the ankle force control and gait alterations. METHODS: Fifteen individuals with MS and 15 healthy adults participated in both a dynamic isometric ankle plantarflexion force matching task and a biomechanical gait analysis. FINDINGS: Our results displayed that the subjects with MS had a greater amount of error in their dynamic isometric force production, were weaker, walked with altered spatiotemporal kinematics, and had reduced maximal ankle moment at toe-off than the control group. The greater amount of error in the dynamic force production was related to the decreases in strength, step length, walking velocity, and maximal ankle moment during walking. INTERPRETATION: Altogether these results imply that errors in the ankle plantarflexion force production may be a limiting factor in the mobility of individuals with MS.

Two Different Types of High-Frequency Physical Therapy Promote Improvements in the Balance and Mobility of Persons With Multiple Sclerosis.

OBJECTIVE: To evaluate the mobility and postural balance improvements that could be achieved in a cohort of persons with multiple sclerosis (MS) who participated in a motor adaptation protocol and a cohort of persons with MS who participated in a therapeutic exercise protocol. DESIGN: A cohort design, where subjects were evaluated before and after a 6-week intervention period. SETTING: Clinical laboratory setting. PARTICIPANTS: Individuals (N=42) with relapsing-remitting or secondary progressive MS (Expanded Disability Status Scale [EDSS] scores, 3.0-6.5) were initially screened for eligibility for participation in the study, from which those who fit the inclusion criteria (n=32) were enrolled in the study. Subjects were pseudorandomly assigned to a treatment group and matched based on EDSS scores. Fourteen individuals in the motor adaptation cohort (MAC) (mean age ± SD, 52.6±9y; mean EDSS score ± SD, 5.5±0.9) and 13 individuals in the therapeutic exercise cohort (TEC) (mean age ± SD, 54.0±9y; mean EDSS score ± SD, 5.3±0.9) completed the entire duration of their respective programs. INTERVENTIONS: Both cohorts completed their therapy twice a day, 5 days each week, for 6 weeks. Each session of the MAC program consisted of balance and gait training that encouraged new ways to adapt to challenging task demands. The TEC program was similar to a traditional exercise program. MAIN OUTCOME MEASURES: The Sensory Organization Test, 6-minute walk test, and gait spatiotemporal kinematics. RESULTS: Collectively, both treatment groups had improvements in postural balance (P=.001), walking endurance (P=.002), walking speed (P=.004), and step length (P<.001) after therapy. However, there were no statistical differences between the 2 treatment groups for any of the outcome variables (P values >.01). CONCLUSIONS: Our exploratory results suggest that a high frequency of physical therapy rather than a specific activity focus might be an important parameter for persons with MS.

A home-based comprehensive care model in patients with Multiple Sclerosis: A study pre-protocol.

Background Disability is prevalent in individuals with multiple sclerosis (MS), leading to difficulty in care access, significant caregiver burden, immense challenges in self-care and great societal burden.  Without highly coordinated, competent and accessible care, individuals living with progressive MS experience psychological distress, poor quality of life, suffer from life-threatening complications, and have frequent but avoidable healthcare utilizations. Unfortunately, current healthcare delivery models present severe limitations in providing easily accessible, patient-centered, coordinated comprehensive care to those with progressive MS. We propose a home-based comprehensive care model (MAHA) to address the unmet needs, challenges, and avoidable complications in individuals with progressive MS with disabling disease. Objective The article aims to describe the study design and methods used to implement and evaluate the proposed intervention.   Method The study will use a randomized controlled design to evaluate the feasibility of providing a 24-month, home-based, patient-centered comprehensive care program to improve quality of life, reduce complications and healthcare utilizations overtime (quarterly) for 24 months. A transdisciplinary team led by a MS-Comprehensivist will carry out this project. Fifty MS patients will be randomly assigned to the intervention and usual care program using block randomization procedures. We hypothesize that patients in the intervention group will have fewer complications, higher quality of life, greater satisfaction with care, and reduced healthcare utilization. The proposed project is also expected to be financially sustainable in fee-for-service models but best suited for and gain financial success in valued-based care systems.   Discussion This is the first study to examine the feasibility and effectiveness of a home-based comprehensive care management program in MS patients living with progressive disability. If successful, it will have far-reaching implications in research, education and practice in terms of providing high quality but affordable care to population living with severe complex, disabling conditions.

Neurorehabilitation Strategies Focusing on Ankle Control Improve Mobility and Posture in Persons With Multiple Sclerosis.

BACKGROUND AND PURPOSE: The neuromuscular impairments seen in the ankle plantarflexors have been identified as a primary factor that limits the mobility and standing postural balance of individuals with multiple sclerosis (MS). However, few efforts have been made to find effective treatment strategies that will improve the ankle plantarflexor control. Our objective was to determine whether an intensive 14-week neurorehabilitation protocol has the potential to improve the ankle plantarflexor control of individuals with MS. The secondary objectives were to determine whether the protocol would also improve postural control, plantarflexion strength, and mobility. METHODS: Fifteen individuals with MS participated in a 14-week neurorehabilitation protocol, and 20 healthy adults served as a comparison group. The primary measure was the amount of variability in the submaximal steady-state isometric torque, which assessed plantarflexor control. Secondary measures were the Sensory Organization Test composite score, maximum plantarflexion torque, and the spatiotemporal gait kinematics. RESULTS: There was less variability in the plantarflexion torques after the neurorehabilitation protocol (preintervention, 4.15% ± 0.5%; postintervention, 2.27% ± 0.3%). In addition, there were less postural sway (preintervention, 51.87 ± 0.2 points; postintervention, 67.8 ± 0.5 points), greater plantarflexion strength (preintervention, 0.46 ± 0.04 Nm/kg; postintervention, 0.57 ± 0.05 Nm/kg), and faster walking speeds (preferred preintervention, 0.71 ± 0.05 m/s; preferred postintervention, 0.81 ± 0.05 m/s; fast-as-possible preintervention, 0.95 ± 0.06 m/s; postintervention, 1.11 ± 0.07 m/s). All of the outcome variables matched or trended toward those seen in the controls. DISCUSSION AND CONCLUSIONS: The outcomes of this exploratory study suggest that the neurorehabilitation protocol employed in this investigation has the potential to promote clinically relevant improvements in the ankle plantarflexor control, standing postural balance, ankle plantarflexion strength, and the mobility of individuals with MS. Video abstract available for more insights from the authors (see Video, Supplemental Digital Content 1, http://links.lww.com/JNPT/A110).

Cervical spinal cord multiple sclerosis: evaluation with 2D multi-echo recombined gradient echo MR imaging.

OBJECTIVE: The two-dimensional multi-echo recombined gradient echo (MERGE) technique automatically acquires and sums multiple gradient echoes at various echo times in cervical spine magnetic resonance (MR) imaging. This technique increases the grey-white matter contrast within the spinal cord and should also improve the depiction of cervical cord lesions. The aim of this study was to qualitatively and quantitatively evaluate MERGE imaging compared with T2-weighted fast spin-echo (T2WFSE) imaging for depicting multiple sclerosis (MS) lesions in the cervical cord. METHODS: Nineteen consecutive patients (10 males and 9 females; age range 22-62 years, mean age 43.6 years) with clinically diagnosed MS were examined with cervical spinal cord MR imaging at 3 T including both MERGE and T2WFSE imaging. Qualitative evaluation for MS lesion conspicuity was performed. The quantitative criterion utilized to compare MERGE imaging with T2WFSE imaging was the lesion-to-background contrast-to-noise ratio (CNR). RESULTS: MERGE imaging showed 79 lesions and missed 1 that was depicted on T2WFSE imaging. T2WFSE imaging showed 46 lesions and missed 34 that were depicted on MERGE imaging. MERGE imaging was markedly superior to T2WFSE imaging in rendering greater lesion conspicuity. In the quantitative evaluation, the lesion-to-background CNR upon MERGE imaging was significantly higher than that upon T2WFSE imaging (P < 0.001, paired t-test). CONCLUSIONS: MERGE imaging in the cervical spinal cord increases detection and conspicuity of MS lesions. Strong consideration should be given to utilizing axial MERGE images in the diagnosis and follow-up study of cervical cord MS.

A randomized open label study of pain medications (naproxen, acetaminophen and ibuprofen) for controlling side effects during initiation of IFN beta-1a therapy and during its ongoing use for relapsing-remitting multiple sclerosis.

Multiple sclerosis (MS) patients initiating IFN beta-1a, Avonex, therapy (Group 1, n = 30) or experiencing side effects after 6 months on therapy (Group 2, n = 30) were randomized for 5 weeks open label adjunct therapy to naproxen (Aleve), acetaminophen (Tylenol) or ibuprofen (Advil). Our hypothesis was that non-prescription pain medications are effective in decreasing or alleviating the side effects associated with IFN beta-1a therapy. Contrary to the hypothesis, most patients in both groups continued to report side effects on all pain medications. After 5 weeks, headache, fever, chills and injection site pain were low in < or = 50% of patients. Moderate to significant fatigue, muscle or joint pain continued in most patients. As a quality of life measure, the Modified Fatigue Impact Scale (mFIS) improved for Group 1 on naproxen or ibuprofen with greatest improvement in physical subset (P = 0.002 for naproxen and P<0.01 for ibuprofen). Total mFIS for Group 1 on acetaminophen improved (P = 0.04) due to improved cognitive subset rather than physical subset. Group 2, with side effects initially, reported less significant fatigue (severity 5-10) but more moderate fatigue (severity 2-4) at study end for all three medications. All medications improved cognitive subset (P = 0.05). Physical mFIS subset did not improve for Group 2 on acetaminophen, but did with naproxen (P = 0.05) or ibuprofen (P = 0.03). Naproxen and ibuprofen were more effective than acetaminophen in minimizing physical side effects of IFN beta-1a. None of the three pain medications tested were as effective as hypothesized for minimizing fatigue or muscle and joint pain.

Discordant functional and inflammatory parameters in multiple sclerosis patients after autologous haematopoietic stem cell transplantation.

This article describes outcomes in four patients with advanced multiple sclerosis up to two years after autologous haematopoietic stem cell transplantation using a total-body irradiation-based preparative regimen. MRI and CSF analyses demonstrated clear suppression of the inflammatory processes. The results demonstrate however, a dissociation of inflammation parameters and functional disability findings raising questions about optimal future stem cell transplantation strategies for this disease.

High-dose cyclophosphamide in multiple sclerosis patients undergoing autologous stem cell transplantation.

High-dose cyclophosphamide (CTX) is commonly used in preparation for autologous and allogeneic stem cell transplantation. CTX is a pro-drug, which undergoes complex oxidative metabolism with the metabolites being eliminated both renally and hepatically. In the following study, we evaluated the pharmacokinetic characteristics of high-dose CTX in three patients undergoing autologous stem cell transplantation for multiple sclerosis. The plasma concentration-time profiles for CTX and its hydroxy-metabolite were similar in multiple sclerosis patients to those reported in cancer patients undergoing stem cell transplantation. There was an increase in drug clearance after the second CTX dose indicating that the drug induced its own metabolism consistent with reports in other populations receiving high-dose CTX. One of the three patients cleared the drug slowly but this was not associated with greater toxicity. The patient with the slow clearance value and therefore highest drug exposure had stable disability scores at 2 years posttransplant compared with baseline values taken prior to transplantation. In conclusion, in this small case series, there was no indication that CTX metabolism was different than that in other populations undergoing transplantation.