Preliminary Trial of Intra-articular LMWF-5A for Osteoarthritis of the Knee.

This study was conducted to investigate the safety and efficacy of 3 intraarticular injections of the low-molecular-weight fraction of 5% human serum albumin (LMWF-5A) administered every 2 weeks for knee pain as a result of osteoarthritis. This single-center, randomized, vehicle-controlled, double-blind, phase II study was designed to ensure the safety of multiple intra-articular injections of LMWF-5A and to explore its efficacy in reducing pain as a result of knee osteoarthritis. Patients were randomized 1:1 to receive 3 biweekly intra-articular knee injections of either 4 mL LMWF-5A or vehicle control (saline), administered at weeks 0 (baseline), 2, and 4. Safety was examined as the incidence and severity of adverse events. Efficacy was assessed by the mean (SD) change between treatment groups in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score from baseline to week 20. A total of 40 patients were randomized and received treatment. No drug-related serious adverse events and no deaths were reported. Adverse events were similar in patients who received saline (18, 90%) and LMWF-5A (19, 95%). Those treated with LMWF-5A had a significant decrease in pain at 20 weeks compared with the saline group (-1.41 [SD, 0.81] vs -0.85 [SD, 0.64], P=.02), corresponding to improvement in pain at week 20 of 64% with LMWF-5A compared with 40% with saline. This preliminary clinical trial showed that repeated intra-articular injections of LMWF-5A are safe when administered at 2-week intervals and are effective in providing relief of the pain of osteoarthritis of the knee at 20 weeks. [Orthopedics. 2017; 40(1):e49-e53.].

Lights and Siren Transport and the Need for Hospital Intervention in Trauma Patients.

Emergent ambulance transportation is associated with increased risk of collision, injury, and death for EMS professionals, patients, and the general public. Time saved using lights and siren (L&S) is typically small, and often provides minimal clinical benefit. Our objective was to investigate the frequency of L&S transports, describe the precision of the decision to employ L&S to predict the need for a time critical hospital intervention (TCHI) within 15 minutes of hospital arrival, identify clinical predictors of a TCHI, and compare clinical outcomes in patients transported by Emergency Medical Services (EMS) with and without L&S in a trauma-specific population. EMS patient care reports and trauma registry data were retrospectively reviewed for trauma patients consecutively transported from the field by three EMS agencies to three trauma centers within urban and suburban settings over a two-year period. TCHIs were collaboratively developed by the study team. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were utilized to report the precision of the decision to employ L&S to predict the need of a TCHI. Univariate and multivariate analyses determined predictors of a TCHI and compared clinical outcomes. 2,091 patients were included in the study. Of the 19.8% of patients transported with L&S, 22.9% received a TCHI. The most common TCHI was airway or respiratory procedures (87.2% of all TCHI's). The sensitivity and specificity of L&S to predict the need for a TCHI was 87.2% (95% CI 79.4-92.8) and 84.0% (95% CI 82.2-85.5), respectively. PPV was 23.0% (95% CI 23.53-38.01); NPV was 99.2% (95% CI 98.6-99.6). L&S was predictive for the need for a TCHI (p < 0.001), as was abnormal Glasgow Coma Score (p < 0.001), abnormal systolic blood pressure and age (p < 0.05 for all). Among patients that received a TCHI, over a third that were transported with L&S (36.8%) expired, compared with two of 14 patients (14.3%) not transported L&S. EMS professionals in this study demonstrated a high ability to discern which trauma patients did not require L&S. Nevertheless, L&S transport resulted in a TCHI less than one quarter of the time, suggesting an opportunity for further reduction of L&S transports in trauma patients.

A randomized clinical trial to evaluate two doses of an intra-articular injection of LMWF-5A in adults with pain due to osteoarthritis of the knee.

OBJECTIVE: The Low Molecular Weight Fraction of 5% human serum Albumin (LMWF-5A) is being investigated as a treatment for knee pain from osteoarthritis. METHODS: This was a multicenter randomized, vehicle-controlled, double-blind, parallel study designed to evaluate the safety and efficacy of two doses of an intra-articular injection of LMWF-5A. Patients with symptomatic knee osteoarthritis were randomized 1∶1∶1∶1 to receive a single 4 mL or 10 mL intra-articular knee injection of either LMWF-5A or vehicle control (saline). The primary efficacy endpoint was the difference between treatment groups in the Western Ontario and McMaster Universities (WOMAC) pain change from baseline over 12 weeks. Safety was examined as the incidence and severity of adverse events (AEs). RESULTS: A total of 329 patients were randomized and received treatment. LMWF-5A resulted in a significant decrease in pain at 12 weeks compared to vehicle control (-0.93 vs -0.72; estimated difference from control: -0.25, p = 0.004); an injection volume effect was not observed (p = 0.64). The effect of LMWF-5A on pain was even more pronounced in patients with severe knee OA (Kellgren Lawrence Grade IV): the estimated difference from control was -0.42 (p = 0.02). Adverse events were generally mild and were similar in patients who received vehicle control (47%) and LMWF-5A (41%). CONCLUSIONS: This clinical trial demonstrated that LMWF-5A is safe and effective at providing relief for the pain of moderate to severe OA of the knee over 12 weeks when administered by intra-articular injection into the knee. TRIAL REGISTRATION: ClinicalTrials.gov NCT01839331.

The relationship between patient volume and mortality in American trauma centres: a systematic review of the evidence.

OBJECTIVE: To synthesise published and unpublished findings examining the relationship between institutional trauma centre volume or trauma patient volume per surgeon and mortality. BACKGROUND: Evidence on the relationship between patient volume and survival in trauma patients is inconclusive in the literature and remains controversial. METHODS: A literature search was performed to identify studies published between 1976 and 2013 via MEDLINE (Pubmed) and the Cumulative Index to Nursing and Allied Health Literature (EbscoHost) as well as footnote chasing. Abstracts from appropriate conferences and ProQuest Dissertations and Theses were also searched. Inclusion criteria required studies to be original research published in English that examined the relationship between mortality and either institutional or per surgeon volume in American trauma centres. We employed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement checklist and flowchart. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was employed to rate the quality of the evidence. RESULTS: Of 1392 studies reviewed, 19 studies met defined inclusion criteria; all studies were retrospective. The definition of volume was heterogeneous across the studies. Patient population and analysis methods also varied across the studies. Sixteen studies (84%) examined the relationship between institutional trauma centre volume and mortality. Of the 16 studies, 12 examined the volume of severely injured patients and eight examined overall trauma patient volume. High institutional volume was associated with at least somewhat improved mortality in ten of 16 studies (63%); however, nearly half of these studies found only some subpopulations experienced benefits. In the remaining six studies, volume was not associated with any benefits. Four studies (25%) analysed the impact of surgeon volume on mortality. High volume per surgeon was associated with improved mortality in only one of four studies (25%). CONCLUSIONS: The studies were extremely heterogeneous, thus definitive conclusions cannot be drawn regarding optimal volume before a clear advantage in survival is observed. A prospective study defining volume as a continuous variable is warranted to support current admission criteria for American trauma patients.

Association between a geriatric trauma resuscitation protocol using venous lactate measurements and early trauma surgeon involvement and mortality risk.

OBJECTIVES: To investigate whether implementing a geriatric resuscitation protocol that uses lactate-guided therapy with early trauma surgeon involvement is associated with lower mortality through the early recognition of occult hypoperfusion (OH). DESIGN: Prospective cohort study. SETTING: Level I trauma center. PARTICIPANTS: All hemodynamically stable individuals with blunt trauma aged 65 and older admitted to the Level I trauma center from October 1, 2008, through December 31, 2011 (n = 1,998). MEASUREMENTS: Mortality over time (according to quarter) was analyzed using an adjusted logarithmic regression model stratified according to the presence of OH. OH was defined as lactate of 2.5 mM or greater. RESULTS: Overall mortality was 3.9% (n = 78). Admission venous lactate was collected in 73.5% of participants, of whom 20.5% had OH (n = 301). In participants with OH, a significant decrease in mortality was observed over time (adjusted coefficient of determination (R(2) ) = 0.66, P = .002). A smaller yet significant decrease in mortality rates in participants with normal perfusion status was also observed (adjusted R(2) = 0.55, P = .01). CONCLUSION: Early identification and treatment of OH in elderly adults with trauma using venous lactate-guided therapy coupled with early trauma surgeon involvement was associated with significantly lower mortality. A protocol that uses lactate-guided therapy with early trauma surgeon involvement should be followed to improve the care of elderly adults with trauma.

Developing a rural trauma outreach program: the experience of a major health care network.

This study describes the process undertaken by a private health care network to develop and implement an outreach program for rural level III to V trauma centers. The program provided individualized trauma program support to 18 rural out-of-network facilities. A case study and participant satisfaction survey demonstrate the experiences of rural trauma nurse coordinators working with the program. The Trauma Outreach Program presents a solution to enhance the effectiveness of regional trauma systems, lift the burden on rural facilities, and improve care for the injured patient.

A retrospective analysis of geriatric trauma patients: venous lactate is a better predictor of mortality than traditional vital signs.

BACKGROUND: Traditional vital signs (TVS), including systolic blood pressure (SBP), heart rate (HR) and their composite, the shock index, may be poor prognostic indicators in geriatric trauma patients. The purpose of this study is to determine whether lactate predicts mortality better than TVS. METHODS: We studied a large cohort of trauma patients age ≥ 65 years admitted to a level 1 trauma center from 2009-01-01 - 2011-12-31. We defined abnormal TVS as hypotension (SBP < 90 mm Hg) and/or tachycardia (HR > 120 beats/min), an elevated shock index as HR/SBP ≥ 1, an elevated venous lactate as ≥ 2.5 mM, and occult hypoperfusion as elevated lactate with normal TVS. The association between these variables and in-hospital mortality was compared using Chi-square tests and multivariate logistic regression. RESULTS: There were 1987 geriatric trauma patients included, with an overall mortality of 4.23% and an incidence of occult hypoperfusion of 20.03%. After adjustment for GCS, ISS, and advanced age, venous lactate significantly predicted mortality (OR: 2.62, p < 0.001), whereas abnormal TVS (OR: 1.71, p = 0.21) and SI ≥ 1 (OR: 1.18, p = 0.78) did not. Mortality was significantly greater in patients with occult hypoperfusion compared to patients with no sign of circulatory hemodynamic instability (10.67% versus 3.67%, p < 0.001), which continued after adjustment (OR: 2.12, p = 0.01). CONCLUSIONS: Our findings demonstrate that occult hypoperfusion was exceedingly common in geriatric trauma patients, and was associated with a two-fold increased odds of mortality. Venous lactate should be measured for all geriatric trauma patients to improve the identification of hemodynamic instability and optimize resuscitative efforts.

A randomized double-blind, placebo-controlled multicenter study to evaluate the efficacy and safety of two doses of the tramadol orally disintegrating tablet for the treatment of premature ejaculation within less than 2 minutes.

BACKGROUND: Premature ejaculation (PE) is a widely observed male sexual dysfunction with a major impact on quality of life for many men and their sexual partners. OBJECTIVE: To assess the safety of tramadol orally disintegrating tablet (ODT) (Zertane) and its efficacy in prolonging intravaginal ejaculation latency time (IELT) and improving Premature Ejaculation Profile (PEP) scores. DESIGN, SETTING, AND PARTICIPANTS: We conducted an integrated analysis of two identical 12-wk randomized double-blind, placebo-controlled phase 3 trials across 62 sites in Europe. Healthy men 18-65 yr of age with a history of lifelong PE according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision, and an IELT ≤ 120 s were included. There were 604 intent-to-treat subjects included in the analysis. INTERVENTION: Subjects were randomized to receive 1:1:1 placebo (n=200), 62 mg tramadol ODT (n=206), or 89 mg tramadol ODT (n=198). MEASUREMENTS: We measured overall change and fold increase in median IELT and the mean change in all four measures of the PEP. Differences across treatment groups were analyzed using Wilcoxon rank-sum tests, analysis of variance, and chi-square analyses. RESULTS AND LIMITATIONS: Tramadol ODT resulted in significant increases in median IELT compared with placebo; increases were 0.6 min (1.6 fold), 1.2 min (2.4 fold), and 1.5 min (2.5 fold) for placebo, 62 mg tramadol ODT, and 89 mg tramadol ODT, respectively (p<0.001 for all comparisons). Men saw significantly greater improvement in all four measures of the PEP in both doses compared with placebo (p<0.05 for all comparisons). Tramadol ODT was well tolerated; study discontinuation occurred in 0%, 1.0%, and 1.6% of subjects in placebo, 62 mg, and 89 mg tramadol ODT groups, respectively. Limitations include study inclusion for men with IELT up to 120 s. CONCLUSIONS: On-demand 62mg tramadol ODT is an effective treatment for PE in a low and safe therapeutic dose and provides a new option for managing mild to severe PE.