The safety of liposome bupivacaine, a novel local analgesic formulation.

OBJECTIVE: Pooled safety data from 10 randomized, double-blind studies of liposome bupivacaine, a novel local analgesic formulation, were examined. METHODS: Eight hundred twenty-three patients received liposome bupivacaine (dose, 66 to 532 mg) given locally at the surgical site in 5 different settings (hemorrhoidectomy, bunionectomy, breast augmentation, total knee arthroplasty, and hernia repair); 446 received bupivacaine HCl (dose, 75 to 200 mg) and 190 received placebo. Adverse events (AEs) were monitored for up to 36 days after administration. RESULTS: Overall, 48% of patients were men and 21% were 65 years and older. Incidence of AEs was 62% for patients receiving liposome bupivacaine, versus 75% and 43% for patients receiving bupivacaine HCl and placebo, respectively. The most common AEs (incidence >10%) in the liposome bupivacaine arms were nausea, constipation, and vomiting. One death was reported in the liposome bupivacaine group and 1 in the bupivacaine HCl group; both deemed unrelated to study drug. Serious AEs were reported in 2.7% of patients receiving liposome bupivacaine, versus 5.4% and 1.1% of those receiving bupivacaine HCl and placebo, respectively. In both the liposome bupivacaine and bupivacaine HCl groups, 6% of patients experienced a cardiac AE; these were primarily tachycardia (4% vs. 5%, respectively) and bradycardia (2% vs. 1%, respectively). Overall incidence of treatment-related cardiac AEs was <1%; all were associated with liposome bupivacaine. All of these events were assessed by investigators as possibly related to study drug; all were mild or moderate in severity, and none required therapeutic intervention. DISCUSSION: Liposome bupivacaine exhibited acceptable tolerability across 823 patient exposures.

Time to onset of analgesia following local infiltration of liposome bupivacaine in healthy volunteers: a randomized, single-blind, sequential cohort, crossover study.

BACKGROUND/OBJECTIVE: Bupivacaine liposome injectable suspension is a novel, prolonged-release formulation of bupivacaine. The time to onset of analgesia following an injection of liposome bupivacaine compared with placebo (normal saline) was investigated using a novel incisional pain model. Bupivacaine HCl was used as a positive control, compared with placebo to verify the validity of the study. MATERIALS AND METHODS: In this Phase 1, single-blind, crossover study, healthy volunteers (n = 132) were randomized to four sequential cohorts to receive subcutaneous normal saline in one arm and either liposome bupivacaine 40 mg or bupivacaine HCl 7.5 mg in the other. At 30, 15, 5, and 2 minutes after study drug administration for Cohorts 1 - 4 respectively, an incision was made in each arm and 18% acetic acid solution was applied to elicit pain. The primary outcome measure was a subject's assessment of pain intensity on a 100 mm visual analog scale. RESULTS: Statistically significant differences in pain intensity scores between liposome bupivacaine and normal saline were observed at 30, 15, 5, and 2 minutes postdose; similar findings were reported for bupivacaine HCl vs. normal saline. Both liposome bupivacaine and bupivacaine HCl were well tolerated and achieved > 30% pain reduction, normalized to placebo, within 5 minutes. CONCLUSIONS: These results indicate that liposome bupivacaine offers time to onset characteristics similar to traditional bupivacaine HCl: clinically meaningful analgesia within 2 minutes after administration and substantial analgesia by 5 minutes.

Impact of local administration of liposome bupivacaine for postsurgical analgesia on wound healing: a review of data from ten prospective, controlled clinical studies.

BACKGROUND: Liposome bupivacaine is a liposomal formulation that allows delivery of bupivacaine for 96 hours with a single local administration. It is indicated for the management of postsurgical pain. OBJECTIVE: This retrospective review of 10 clinical trials assessed the potential impact of local anesthetics on wound healing and chondrolysis. Various doses of liposome bupivacaine and bupivacaine hydrochloride (HCl) were evaluated. METHODS: Primary inclusion criteria across the 10 Phase 2 and Phase 3 randomized, double-blind studies required that patients be ≥18 years of age at the screening visit and scheduled to undergo the specified surgical procedure in each study (inguinal hernia repair, total knee arthroplasty, hemorrhoidectomy, breast augmentation, or bunionectomy). Key exclusion criteria were: a history of clinically significant medical conditions (including cardiovascular, hepatic, renal, neurologic, psychiatric, or metabolic disease) or laboratory results that indicated an increased vulnerability to the study drugs and/or procedures; medical condition(s) or concurrent surgery that may have required analgesic treatment in the postoperative period for pain that was not strictly related to the study surgery; and/or any clinically significant event or condition discovered during surgery that could have complicated the patient's postsurgical course. Assessments included the clinician's overall satisfaction with the patient's wound healing, wound status (erythema, drainage, edema, and induration), and wound scarring. Adverse events (AEs) potentially manifesting as wound complications and local AEs were also assessed. RESULTS: In total, 823 patients received liposome bupivacaine at doses ranging from 66 to 532 mg across the 5 different surgical settings; 446 patients received bupivacaine HCl (75-200 mg), and 190 patients received placebo. Few studies showed statistically significant differences between liposome bupivacaine and the comparator (bupivacaine HCl or placebo) with regard to the clinician's overall satisfaction with patient wound healing; the incidence of erythema, drainage, edema, and induration; and wound scarring. The incidences of local AEs were similar between treatments, ranging from 9% to 20% with liposome bupivacaine across the studies compared with 8% to 19% with bupivacaine HCl. CONCLUSIONS: Liposome bupivacaine given locally at the surgical wound site appeared to have no clinically evident impact on wound or bone healing at doses up to 532 mg across different surgical models. The wound-healing profile of liposome bupivacaine was similar to that of bupivacaine HCl.

Pharmacokinetic profile of liposome bupivacaine injection following a single administration at the surgical site.

Local anaesthetics are often used as part of multimodal pain management techniques to manage postsurgical pain and lessen the need for opioid analgesics; however, the duration of action of traditional formulations of local anaesthetics is short. Liposome bupivacaine is a novel, multivesicular formulation designed for rapid absorption, prolonged release of bupivacaine, and analgesia following a single intra-operative administration into the surgical wound. This article provides a summary of the pharmacokinetic profile of liposome bupivacaine compared with bupivacaine HCl based on data compiled from four randomized, active- and placebo-controlled trials that included pharmacokinetic assessments following single administrations of study drug. Each study evaluated the safety, efficacy and pharmacokinetic profile of liposome bupivacaine in separate surgical populations (patients undergoing inguinal hernia repair, total knee arthroplasty, haemorrhoidectomy or bunionectomy). Pharmacokinetic parameters included maximum plasma drug concentration (C(max)), area under the curve (AUC) for plasma bupivacaine concentration over time extrapolated to infinity (AUC(∞)), time to observed C(max) (t(max)) and terminal elimination half-life of bupivacaine (t(½)). The studies assessed single administrations of liposome bupivacaine at dose levels ranging from 106 to 532 mg or bupivacaine HCl 100 to 150 mg or placebo (0.9 % sodium chloride) given locally via wound infiltration at the end of surgery prior to wound closure. Male and non-pregnant female patients (n = 253) aged ≥18 years, scheduled to undergo surgery as per the specific protocol for each study, were enrolled. Patient characteristics were stratified by liposome bupivacaine doses ≤266 mg and >266 mg, and bupivacaine HCl treatment arms. Pharmacokinetic parameters for liposome bupivacaine doses of 106, 266, 399 and 532 mg were compared. Plasma concentration versus time profiles were quantitatively similar across these four dose levels of liposome bupivacaine, with an initial peak occurring within 1 h after administration followed by a second peak about 12-36 h later. The overall incidence of adverse events was lower in the liposome bupivacaine ≤266-mg group than the liposome bupivacaine >266-mg and bupivacaine HCl groups (100- or 150-mg doses). In summary, liposome bupivacaine was well tolerated across the four studies and varied surgical models, and exhibited bimodal kinetics with rapid uptake observed during the first few hours and prolonged release through 96 h after administration.

The pharmacokinetics and pharmacodynamics of liposome bupivacaine administered via a single epidural injection to healthy volunteers.

BACKGROUND AND OBJECTIVES: The objective of this study was to assess the pharmacokinetics, sensory/motor effects, and safety of epidurally administered liposome bupivacaine versus bupivacaine HCl in healthy volunteers. METHODS: Thirty subjects were randomized to receive liposome bupivacaine 89, 155, or 266 mg, or bupivacaine HCl 50 mg in a double-blind fashion. Occurrence/duration of motor blockade, pinprick/cold sensitivity, and plasma bupivacaine levels were assessed for 96 hours after study drug administration. Tolerability parameters were also assessed. RESULTS: All doses of liposome bupivacaine resulted in greater area under the curve and a longer time to observed maximum plasma concentration and terminal elimination half-life than bupivacaine HCl 50 mg. Mean maximum plasma concentration with liposome bupivacaine 89 and 155 mg (but not 266 mg) was statistically significantly lower than with bupivacaine HCl 50 mg (P < 0.001). Median duration of motor blockade with liposome bupivacaine 266 mg was 1 hour versus 2.8 hours for bupivacaine HCl. Of subjects who received liposome bupivacaine 266 mg, 29% (2/7) were unable to ambulate at 4 hours postdose versus 67% (4/6) of those receiving bupivacaine HCl. Median durations of pinprick/cold sensitivity loss were 36 and 69 hours, respectively, in the liposome bupivacaine 266-mg group versus 12 hours for both pinprick and cold in the bupivacaine HCl group. Liposome bupivacaine was well tolerated; the most common adverse event in all treatment groups was injection site pain, which resolved within 30 days for most subjects. CONCLUSIONS: Epidurally administered liposome bupivacaine 266 mg resulted in a longer duration of sensory blockade than liposome bupivacaine 89 or 155 mg or bupivacaine HCl 50 mg. Duration of motor blockade was shorter with liposome bupivacaine 266 mg versus bupivacaine HCl.

A double-blind, randomized, active-controlled study for post-hemorrhoidectomy pain management with liposome bupivacaine, a novel local analgesic formulation.

This randomized, active-controlled study evaluated the extent and duration of analgesia after administration of liposome bupivacaine (LB), a novel formulation of bupivacaine, compared with bupivacaine HCl given via local infiltration in excisional hemorrhoidectomy. One hundred patients were randomly assigned to receive a single dose of bupivacaine HCl 75 mg (0.25% with 1:200,000 epinephrine) or LB 66, 199, or 266 mg upon completion of hemorrhoidectomy. Postoperative pain intensity was assessed using a numeric rating scale at rest to calculate a cumulative pain score (area under the curve). Cumulative pain scores were significantly lower with LB at each study dose (P < 0.05) compared with bupivacaine HCl 72 hours after surgery. Post hoc analysis showed that mean total postoperative opioid consumption was statistically significantly lower for the LB 266-mg group compared with the bupivacaine HCl group during the 12- to 72-hour postoperative period (P = 0.019). Median time to first opioid use was 19 hours for LB 266 mg versus 8 hours for bupivacaine HCl (P = 0.005). Incidence of opioid-related adverse events was 4 per cent for LB 266 mg compared with 35 per cent for bupivacaine HCl (P = 0.007). Local infiltration with LB resulted in significantly reduced postsurgical pain compared with bupivacaine HCl in patients after hemorrhoidectomy surgery.

A randomized, double-blind, dose-ranging study comparing wound infiltration of DepoFoam bupivacaine, an extended-release liposomal bupivacaine, to bupivacaine HCl for postsurgical analgesia in total knee arthroplasty.

INTRODUCTION: DepoFoam bupivacaine is a novel liposomal formulation of bupivacaine designed to provide prolonged postsurgical analgesia. This dose-ranging study evaluated extent and duration of analgesia following administration of DepoFoam bupivacaine in patients undergoing total knee arthroplasty (TKA). METHODS: Efficacy, safety, and pharmacokinetics of DepoFoam bupivacaine doses of 133, 266, 399, or 532 mg were compared with bupivacaine HCl (150 mg) with epinephrine given as single injections via wound infiltration in TKA patients (N=138). Primary efficacy measure was AUC of pain intensity scores assessed by numeric rating scale with activity (NRS-A) through Day 4 postsurgery. Other assessments included pain intensity at rest (NRS-R), postsurgical opioid consumption, and safety, among others. RESULTS: Mean AUC of NRS-A scores through Day 4 were 20.7, 19.5, 18.8, and 19.1 for the 133-mg, 266-mg, 399-mg, and 532-mg DepoFoam bupivacaine groups vs 20.4 for bupivacaine HCl. With DepoFoam bupivacaine 532-mg, differences in NRS-R scores reached statistical significance (P<0.05) vs bupivacaine HCl on Days 1 and 5 and mean AUC NRS-R scores were significantly lower through Days 2-5; a dose-response trend was demonstrated. Mean rating for blinded care provider's satisfaction with analgesia was significantly higher for DepoFoam bupivacaine 532 mg vs bupivacaine HCl (P ≤ 0.05). Other efficacy measures showed no statistically significant differences. CONCLUSION: Exposure to bupivacaine increased in a dose-related manner, as reflected by mean and maximum plasma bupivacaine concentrations, and AUC(0-∞). Treatment with DepoFoam bupivacaine 532 mg was associated with statistically significantly greater analgesia while patients were at rest after surgery compared with bupivacaine HCl.

A two-year observational study assessing the safety of DepoFoam bupivacaine after augmentation mammaplasty.

BACKGROUND: Two-year safety outcomes in patients who received DepoFoam bupivacaine during two prior breast augmentation studies were evaluated. OBJECTIVES: The authors assess the clinical sequelae observed during follow-up examination with respect to the integrity of the breast implants. METHODS: In Study 1, patients received bupivacaine HCl (75 mg) in one breast pocket and DepoFoam bupivacaine (133 or 266 mg) in the other. In Study 2, patients received either bupivacaine HCl (200 mg) or DepoFoam bupivacaine (532 mg), divided equally into each breast pocket. Investigators and patients remained blinded to the treatment administered. Patients completed a questionnaire regarding breast pain, tenderness, tingling, numbness, burning, changes in sensation, and any relevant life events potentially affecting the implants. Patients were also assessed for postoperative healing and implant integrity. RESULTS: Ninety-four women were evaluated. Most patients in all groups had no change in breast size or shape and no changes in the skin or nipple. There were no reports of palpable hard knots or swelling. There was one report of irritation/implant leakage (in a patient who received bupivacaine HCl [75 mg] in the relevant breast). Most patients reported no breast pain, tenderness, tingling, numbness, burning, other changes in sensation, chest wall surgery or trauma, or life events affecting the implant. CONCLUSIONS: At a two-year follow-up assessment, DepoFoam bupivacaine was not associated with any complications that would compromise the integrity of the breast implants. There was no indication of an association between DepoFoam bupivacaine or bupivacaine HCl and changes in sensation or other abnormal findings in these patients. LEVEL OF EVIDENCE: 2.

Bupivacaine extended-release liposome injection exhibits a favorable cardiac safety profile.

BACKGROUND AND OBJECTIVES: Bupivacaine extended-release liposome injection is an investigational local analgesic intended for use in postsurgical pain management. In recognition of the incompletely characterized association of bupivacaine use and cardiac effects, this article reviews the cardiac safety profile of this novel formulation of bupivacaine. METHODS: Findings from paired electrocardiograms (ECGs), corresponding pharmacokinetic assessments, and cardiovascular adverse events (AEs) in a phase 2, randomized, double-blind, dose-ranging study of bupivacaine extended-release (150, 300, 450, or 600 mg) or bupivacaine HCl 150 mg with epinephrine administered intraoperatively via wound infiltration in patients undergoing total knee arthroplasty (n = 138), were assessed for potential causality. Results from 4 phase 1 bupivacaine extended-release studies that also obtained ECG and/or Holter monitor findings (n = 169) were assessed. In addition, incidences of cardiovascular AEs reported across 10 bupivacaine extended-release wound infiltration studies (n = 1459) were pooled and assessed. RESULTS: In the phase 2 study, mean change from baseline in QRS duration and QTcF duration across dose levels of bupivacaine extended-release was similar (range, -1 to +4 milliseconds and -7 to -10 milliseconds) compared with bupivacaine HCl (-1 millisecond and -6 milliseconds). Mean change from baseline in heart rate, PR interval, and QRS interval was similar between treatment groups as well. No clinically relevant ECG changes or cardiac AEs with bupivacaine extended-release were observed in the other clinical studies. CONCLUSIONS: A focused assessment of ECG data from a phase 2 study and cardiac findings/AEs data from other studies in the bupivacaine extended-release development program did not reveal any cardiac safety issues.

The efficacy and safety of DepoFoam bupivacaine in patients undergoing bilateral, cosmetic, submuscular augmentation mammaplasty: a randomized, double-blind, active-control study.

BACKGROUND: Breast augmentation can result in significant postsurgical pain. OBJECTIVES: The authors evaluate the extent and duration of analgesia achieved with extended-release DepoFoam bupivacaine (Pacira Pharmaceuticals, Inc., Parsippany, New Jersey) in patients undergoing bilateral, cosmetic, submuscular augmentation mammaplasty under general anesthesia. METHODS: In this randomized, multicenter, double-blind study, patients received a single dose of DepoFoam bupivacaine 600 mg or bupivacaine HCl 200 mg divided into the implant pockets at the conclusion of surgery. The primary efficacy measure was cumulative pain score with activity through 72 hours postoperatively. Secondary efficacy measures included pain intensity with activity and at rest, postsurgical consumption of rescue opioids, and integrated rank analysis combining pain scores at rest with the amount of opioid used. RESULTS: One hundred thirty-six patients were randomized and treated (DepoFoam bupivacaine, n = 66; bupivacaine HCl, n = 70). Reflecting the underpowered nature of the study, the mean cumulative pain score (numeric rating scale with activity through 72 hours) was 441.5 with DepoFoam bupivacaine versus 468.2 with bupivacaine HCl (P = .3999). Total amounts of opioid consumed were significantly lower in the DepoFoam bupivacaine group through 24 hours (P = .0211) and through 48 hours (P = .0459). The prespecified integrated rank analysis showed statistically-significant differences at multiple time points up to and including 60 hours; results on most other efficacy measures trended in favor of DepoFoam bupivacaine. No serious adverse events were reported, and no patients discontinued the study due to adverse events. CONCLUSIONS: DepoFoam bupivacaine trended toward benefit versus bupivacaine HCl on most efficacy measures. Due to early termination, the study was underpowered to achieve statistical significance.

Bupivacaine extended-release liposome injection for prolonged postsurgical analgesia in patients undergoing hemorrhoidectomy: a multicenter, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Bupivacaine extended-release liposome injection is a novel formulation of bupivacaine designed to achieve long-acting postoperative analgesia. OBJECTIVE: The aim of this study was to compare the magnitude and duration of postoperative analgesia from a single dose of bupivacaine extended-release injection with placebo administered intraoperatively in patients undergoing hemorrhoidectomy. DESIGN: This evaluation was a multicenter, randomized, double-blind, parallel-group, placebo-controlled phase 3 study. SETTINGS: Data were obtained from 13 centers in the Republic of Georgia, Poland, and Serbia. PATIENTS: Included in this study were patients aged 18 to 86 years undergoing excisional hemorrhoidectomy. INTERVENTIONS: All patients received either a single dose of bupivacaine extended-release 300 mg or placebo administered intraoperatively via wound infiltration. MAIN OUTCOME MEASURE: The cumulative pain score was assessed by measurement of the area under the curve of pain intensity through 72 hours after study drug administration. RESULTS: One hundred eighty-nine patients were randomly assigned and treated; 186 completed the study. Pain intensity scores were significantly lower in the bupivacaine extended-release group in comparison with the group receiving placebo (141.8 vs 202.5, P < .0001). More patients in the bupivacaine extended-release group remained opioid free from 12 hours (59%) to 72 hours (28%) after surgery compared with patients receiving placebo (14% and 10%; P < .0008 through 72 h). The mean total amount of opioids consumed through 72 hours was 22.3 mg and 29.1 mg in the bupivacaine extended-release and placebo groups (P ≤ .0006). The median time to first opioid use was 14.3 hours in the bupivacaine extended-release group vs 1.2 hours in the placebo group (P < .0001). A greater proportion of patients in the bupivacaine extended-release group were satisfied with their postsurgical analgesia (95% vs 73%, P = .0007) than in the placebo group. CONCLUSIONS: Bupivacaine extended-release demonstrated a statistically significant reduction in pain through 72 hours, decreased opioid requirements, delayed time to first opioid use, and improved patient satisfaction compared with placebo after hemorrhoidectomy.

A phase 3, randomized, placebo-controlled trial of DepoFoam® bupivacaine (extended-release bupivacaine local analgesic) in bunionectomy.

BACKGROUND: DepoFoam® bupivacaine (Pacira Pharmaceuticals, Inc., San Diego, CA, USA), an extended-release liposomal bupivacaine-based analgesic, was compared with placebo for the prevention of pain after bunionectomy in a randomized, multicenter, double-blind phase 3 clinical study. METHODS: Patients received placebo (n = 96) or DepoFoam bupivacaine 120 mg (n = 97) via wound infiltration prior to closure. Pain intensity was assessed using a numeric rating scale (NRS) from time 0 through to 72 hours postsurgically. The primary efficacy measure was area under the curve (AUC) of NRS scores through 24 hours. Other efficacy measures included AUC of NRS at other time points, proportion of patients who were pain-free, time to first opioid use, and total postsurgical consumption of supplemental opioid medication. Adverse events were also assessed. RESULTS: The AUC for NRS scores was significantly less in patients treated with DepoFoam bupivacaine versus patients receiving placebo at 24 hours (P = 0.0005) and 36 hours (P < 0.0229). More patients treated with DepoFoam bupivacaine avoided use of opioid rescue medication during the first 24 hours (7.2% vs. 1%; P < 0.0404) and were pain-free (NRS ≤ 1) at 2, 4, 8, and 48 hours. Median time-to-first-opioid use was delayed in favor of DepoFoam bupivacaine (4.3 vs. 7.2 hours; P < 0.0001). Fewer adverse events were reported by patients treated with DepoFoam bupivacaine (59.8%) versus placebo (67.7%). CONCLUSIONS: DepoFoam bupivacaine, a long-acting local analgesic, provided extended pain relief and decreased opioid use after bunionectomy, compared with placebo.

Evaluation of DepoFoam(®) bupivacaine for the treatment of postsurgical pain.

SUMMARY An extended-release, multivesicular liposome-encapsulated form of the local anesthetic bupivacaine, DepoFoam(®) bupivacaine (proposed proprietary name EXPAREL™), is in development for use as part of a multimodal regimen for the treatment of postsurgical pain. Placebo- and active-controlled clinical trials in patients who have undergone either orthopedic or soft-tissue procedures indicate that a single local administration into the surgical site results in analgesic activity for up to 3-4 days and decreases the use of opioid rescue medication. The safety profile of DepoFoam bupivacaine appears to be similar to that of bupivacaine HCl, and adverse events are dose-related.

Post-Hoc analysis of a head-to-head hyaluronic acid comparison in knee osteoarthritis using the 2004 OMERACT-OARSI responder criteria.

BACKGROUND AND OBJECTIVE: Several intra-articular hyaluronic acid products are available for treating osteoarthritis (OA) of the knee, including hylan G-F 20 and the bioengineered straight-chain hyaluronic acid (Bio-HA). A recently published study in patients with knee OA demonstrated non-inferiority with regard to efficacy, using the pain subscore of the Western Ontario and McMaster Universities Osteoarthritis Index (safety data favoured Bio-HA with regard to knee effusions). However, the Osteoarthritis Research Society International (OARSI) Standing Committee for Clinical Trials Response Criteria Initiative together with the Outcome Measures in Rheumatology (OMERACT) committee have published new response criteria for OA clinical trials. These criteria focus on change in pain and physical function. The aim of this study was to reanalyse the data from the original comparative study of hylan G-F 20 and Bio-HA in knee OA utilising the new OMERACT-OARSI response criteria. METHODS: The original study was a prospective, multicentre, randomized, double-blind trial of 321 patients with knee OA who received hylan G-F 20 or Bio-HA via three intra-articular injections 1 week apart. This post-hoc analysis of the data using the modified OMERACT-OARSI responder criteria focused only on efficacy. RESULTS: Using the OMERACT-OARSI criteria, 112 of the 157 patients (71%) receiving Bio-HA were considered to have a response compared with 99 of the 158 patients (63%) receiving hylan G-F 20 (p = 0.10). CONCLUSIONS: Application of the new, standardized definition of a responder in OA clinical trials to the existing data reinforces that Bio-HA is non-inferior to hylan G-F 20 for knee OA. Both agents were similarly well tolerated, but Bio-HA was associated with a lower incidence of effusions, suggesting that Bio-HA has an improved risk-benefit profile compared with hylan G-F 20.

Treatment of osteochondritis dissecans of the ankle with hyaluronic acid injections: a prospective study.

BACKGROUND: No studies have evaluated the efficacy of hyaluronic acid (HA) in reducing pain caused by osteochondritis dissecans (OCD) of the ankle. We report our initial results with this treatment. MATERIALS AND METHODS: Fifteen subjects aged 18 to 60 treated for OCD of the talus were followed for 26 weeks, in a pre- and post-treatment repeated measurements design, after receiving three weekly injections of intra-articular HA. The efficacy of HA injections in reducing pain and improving function was assessed at each visit and adverse events were recorded. Efficacy was evaluated by comparing scores determined using a Visual Analog Scale for pain, stiffness and function over time with baseline values. In addition, frequency of symptoms and global function over time were assessed using questionnaires and the AOFAS Ankle-Hindfoot Scale. Data analysis was made using ANCOVA models and paired t-tests. All statistical tests were based on an alpha level of 0.05. RESULTS: The majority of subjects were male (60%) and had Grade 3 lesions (60%). Mean VAS scores, reported on a scale from 1 (e.g., no pain) to 10 (e.g., worst pain) decreased for pain (5.6 to 3.2), stiffness (5.1 to 2.9), and function (5.9 to 3.3) from baseline to week 26. Subjective global function scores, reported on a scale from 0 to 100 (with 100 representing healthy, pre-injury function), improved on average from 57.3 at baseline to 74.3 by week 26. All of these results were statistically significant, as was the decrease in frequency of pain reported by subjects at the end of the study. CONCLUSION: OCD of the ankle treated with intra-articular injections of HA caused a decrease in pain scores and increase in global functioning over a short period of time (within 12 weeks) which then lasted for more than 6 months with minimal adverse events.

The impact of lower urinary tract symptoms and comorbidities on quality of life: the BACH and UREPIK studies.

OBJECTIVES: To investigate the effect of lower urinary tract symptoms (LUTS) on quality of life (QoL) and to determine its extent across a variety of cultures, and the confounding effects of self-reported comorbidities and demographics. SUBJECTS AND METHODS: Data were obtained from two population-based studies in five cities: UREPIK (Boxmeer, the Netherlands; Auxerre, France; Birmingham, UK; and Seoul, Korea) and the Boston Area Community Health (BACH) study (Boston, USA). UREPIK used stratified random samples of men aged 40-79 years. BACH used a multistage stratified cluster sample to randomly select adults aged 40-79 years. QoL was assessed using a standard Medical Outcomes Study-Short Form 12 (SF-12, mental and physical health component scores); LUTS was assessed using the International Prostate Symptom Score (IPSS). The association between QoL and IPSS, associated illnesses, and lifestyle factors was investigated using weighted regression. RESULTS: The UREPIK studied 4800 men aged 40-79 years; BACH recruited 1686 men aged 40-79 years. The prevalence of LUTS, defined as an IPSS of > or =8, varied by city (P < 0.001), with Auxerre reporting a prevalence (SE) of 18.1 (1.2)%, Birmingham 25.6 (1.5)%, Boston 25.1 (1.6)%, Boxmeer 21.2 (1.3)%, and Seoul 19.0 (1.2)%. Overall, this was similar to the reported rate of high blood pressure. Severe LUTS, defined as an IPSS of > or =20, affected approximately 3.3% of the age group; this was roughly similar to stroke (2.2%), cancer (4.5%), or heart attack (4.5%) and less than half as much as diabetes (8.6%). A 10-point increase in IPSS was associated with a 3.3 (0.3)-point reduction in SF-12 physical health component score, with the same effect in all cities (P = 0.682 for the interaction test). This was more than the physical health component score reduction caused by cancer, diabetes, or high blood pressure (2 points each), but less than stroke or heart attack (6 points). The comorbidities had no significant impact on SF-12 mental health component score (other than a heart attack, that had a 1.8-point reduction). A 10-point increase in IPSS was associated with a 3.4 (0.6)-point reduction of the mental health component score in the four western cities and a 1.4 (0.3)-point reduction in Seoul. CONCLUSIONS: Increasingly severe LUTS is associated with a lower QoL. The effect of moderate LUTS on QoL physical health component score is similar to that of having diabetes, high blood pressure or cancer, while the effect of severe LUTS is similar to a heart attack or stroke. These changes were consistent across cultures. This analysis shows the magnitude and consistency of the effects of LUTS on QoL. While these patients might be seen by several types of practitioners, it is likely that urologists will be in the best position to recognize the true impact of LUTS on a patient's QoL, to be aware of the effects of therapies for LUTS on QoL, and to ensure that colleagues in other disciplines recognize the importance of these symptoms and their treatment.