Feasibility of a Hybrid Web-Based and In-Person Self-management Intervention Aimed at Preventing Acute to Chronic Pain Transition After Major Lower Extremity Trauma (iPACT-E-Trauma): A Pilot Randomized Controlled Trial.

Objective 1) To assess the feasibility of research methods to test a self-management intervention aimed at preventing acute to chronic pain transition in patients with major lower extremity trauma (iPACT-E-Trauma) and 2) to evaluate its potential effects at three and six months postinjury. Design A pilot randomized controlled trial (RCT) with two parallel groups. Setting A supraregional level 1 trauma center. Methods Fifty-six adult patients were randomized. Participants received the intervention or an educational pamphlet. Several parameters were evaluated to determine the feasibility of the research methods. The potential efficacy of iPACT-E-Trauma was evaluated with measures of pain intensity and pain interference with activities. Results More than 80% of eligible patients agreed to participate, and an attrition rate of ≤18% was found. Less than 40% of screened patients were eligible, and obtaining baseline data took 48 hours postadmission on average. Mean scores of mild pain intensity and pain interference with daily activities (<4/10) on average were obtained in both groups at three and six months postinjury. Between 20% and 30% of participants reported moderate to high mean scores (≥4/10) on these outcomes at the two follow-up time measures. The experimental group perceived greater considerable improvement in pain (60% in the experimental group vs 46% in the control group) at three months postinjury. Low mean scores of pain catastrophizing (Pain Catastrophizing Scale score < 30) and anxiety and depression (Hospital Anxiety and Depression Scale scores ≤ 10) were obtained through the end of the study. Conclusions Some challenges that need to be addressed in a future RCT include the small proportion of screened patients who were eligible and the selection of appropriate tools to measure the development of chronic pain. Studies will need to be conducted with patients presenting more serious injuries and psychological vulnerability or using a stepped screening approach.

Argon plasma coagulation treatment of anal high-grade squamous intraepithelial lesions in men who have sex with men living with HIV: results of a 2-year prospective pilot study.

OBJECTIVES: Men who have sex with men (MSM) living with HIV are at high risk for anal high-grade squamous intraepithelial lesions (HSILs) and cancer. The best management of anal HSIL remains unclear. Our objective was to assess whether argon plasma coagulation (APC) could be safe, well tolerated and efficient to treat anal HSILs in MSM living with HIV. METHODS: A prospective phase II, open-label, pilot study was conducted to evaluate APC to treat anal HSILs in 20 HIV-positive MSM. Participants were followed for 2 years after their first treatment. RESULTS: Twenty men with persistent HSILs completed the 2-year study. Their baseline median CD4 count was 490 cells/µL and 85% had undetectable HIV viral loads. Overall, 65% (13/20) of participants were clear of HSILs at their 24-month visit. The initial response rates after the first, second and third APC treatments were 45%, 44% and 67%, respectively, but recurrences were common. The main side effect was pain during and within 1 week after the treatments. There were no long-term side effects, nor serious adverse events related to the procedure. Cost is a drawback. CONCLUSIONS: APC can be used to treat anal HSILs in HIV-seropositive MSM, and requires repeated treatment because of a high recurrence rate. As successful treatment of human papillomavirus (HPV) infection or eradication of the anal transitional zone remains impossible, HSIL treatment is challenging and requires long-term follow-up.

Designing clinical studies in orthopedic traumatology.

The design of clinical studies in orthopedic traumatology is challenging in several respects. In this era of evidence-based medicine, the pressure is high to choose our treatments solely based on randomized controlled studies. This type of study, when well-constructed, makes it possible to discern the best treatment for a specific fracture in a given group of patients and in connection with a specific outcome. Randomized controlled trials require a lot of resources and are not designed to answer all research questions. Observational studies, such as case-control studies, prospective cohort studies, and cross-sectional studies, also have a role to play in improving scientific knowledge in orthopedic trauma. Regardless of the type of study chosen, the researcher must follow a strict methodology that conforms to practice guidelines in order to ensure the study's conclusions are valid. The guidelines for randomized studies can be found at http://www.consort-statement.org and at http://www.strobe-statement.org for cohort studies. It is also very important to register randomized studies before they begin on a website such as http://www.clinicaltrials.gov, since registration is an increasingly common requirement when submitting an article for publication. Although this preparation is relatively cumbersome, it is essential for producing articles that meet modern scientific criteria.

Clinical impact of positive Propionibacterium acnes cultures in orthopedic surgery.

BACKGROUND: The clinical significance of a positive culture to Propionibacterium acnes in orthopedic specimens remains unclear, whether about its role as a contaminant or a pathogen, or its impact as a coinfectant. Therefore, we performed a retrospective study to provide a more accurate description of the clinical impact of P. acnes in an orthopedic population aiming to determine: 1) if there is a clinical difference between P. acnes infection and contamination? 2) If there is a clinical difference between P. acnes monoinfection, and coinfection. HYPOTHESIS: There is a clinical difference between P. acnes infection and contamination. MATERIALS AND METHODS: Patients were selected over a five-year period, and those with a minimum of one positive culture for P. acnes, from any intraoperative orthopedic tissue sample, were included in the study. P. acnes infection was defined as the isolation of P. acnes from≥2 specimens, or in only one specimen, in the presence of typical perioperative findings and/or local signs of infection. RESULTS: A total of 68 patients had a positive P. acnes culture, 35 of which were considered to be infected. The infections affected mostly males (29/35-83%), occurred mostly in shoulders (22/35-63%), and at a site already containing an orthopedic implant (32/35-91%). Local inflammatory signs were present in half of the cases when an infection was diagnosed. Coinfection with other pathogens was present in 31% of patients (11/35). When comparing patients coinfected with P. acnes, and those who were monoinfected, the latter presented less often with local inflammatory signs. Recurrence rate was 24% (8/35) and the only risk factor for recurrence was the presence of a monoinfection. DISCUSSION: This study confirms the pathogenicity of P. acnes in an orthopedic population, as it is present in multiple samples in the same patient, and because it is present in cultures from cases with clinical recurrence. Our study showed that monoinfections differ from coinfections mainly by their higher risk of recurrence. LEVEL OF EVIDENCE: Level IV retrospective case series.

Early Initiation Rather Than Prolonged Duration of Antiretroviral Therapy in HIV Infection Contributes to the Normalization of CD8 T-Cell Counts.

BACKGROUND: CD8 T-cell counts remain elevated in human immunodeficiency virus (HIV) infection even after long-term antiretroviral therapy (ART), which is associated with an increased risk of non-AIDS-related events. We assessed the impact of ART initiation in early versus chronic HIV infection on trajectories of CD8 cell counts over time. METHODS: Of 280 individuals enrolled during primary HIV infection (PHI), 251 were followed up for 24 months; 84 started ART before 6 months of infection (eART), 49 started between 6 and 24 months, and 118 remained untreated. Plasma HIV viral load (VL), CD4 and CD8 cell counts were assessed at each study visit. CD8 counts were also examined in 182 age-matched HIV-infected individuals who started ART during chronic infection and maintained undetectable plasma VL for ≥5 years. RESULTS: At PHI baseline, higher CD8 cell counts were associated with more recent infection (P = .02), higher CD4 cell counts (P < .001), and higher VL (P < .001). The CD8 count in the eART group decreased from 797 to 588 cells/µL over 24 months (P < .001), to a level lower than that in untreated PHI (834 cells/µL; P = .004) or in long-term-treated patients with chronic HIV infection (743 cells/µL; P = .047). More prominent CD4 T-cell recovery was observed in the eART group than in the delayed ART group. CONCLUSIONS: ART initiated in early HIV infection is associated with improved resolution of CD8 T-cell elevation compared with long-term ART initiated in chronic infection. Early ART may help reduce the risk of non-AIDS-related events by alleviating this elevation.

Translation and validation of the PREE (Patient Rated Elbow Evaluation) to a French version.

BACKGROUND: Only a few outcome measures specific to elbow pathology and the assessment of their impacts on function are valid and reliable when used in French speaking populations. The English version of the Patient Rated Elbow Evaluation (PREE) was determined to be an optimal candidate for translation. HYPOTHESIS: A French version of the PREE (PREE-Fr) will be generated and compared to its original version in terms of reliability and responsiveness. MATERIALS AND METHODS: The PREE was translated following the guidelines of the American Academy of Orthopedic Surgeons. Patients with a variety of elbow pathologies completed the French version of the PREE (PREE-Fr), the Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH) and the Mayo Elbow Performance Score (MEPS) on three different occasions. The test-retest reliability of the PREE-Fr was calculated using questionnaires that were filled out with a one-week interval between them. The responsiveness was assessed using questionnaires filled out six months after treatment. RESULTS: A French version of the PREE was generated. Data gathered from 54 patients yielded an intra-class correlation coefficient for reliability of 0.89 (CI95%: 0.79-0.94) for the PREE-Fr. For construct validity, using the Pearson correlation coefficient, we obtained excellent correlation between the PREE-Fr and QuickDASH at day one, one week and six months (0.89-0.96) while that between the PREE and MEPS was good to excellent (0.70-0.95). Responsiveness of the PREE-Fr was assessed and yielded a standardized response mean of 1.03, meaning that a large change was recorded between day one and six months. DISCUSSION: The PREE-Fr should be considered in French speaking populations for patients with elbow pathology, whether it is for research or evaluation purposes as it is valid, reliable and responsive to change.

A new morphological classification for greater tuberosity fractures of the proximal humerus: validation and clinical implications.

In this study, we describe a morphological classification for greater tuberosity fractures of the proximal humerus. We divided these fractures into three types: avulsion, split and depression. We retrospectively reviewed all shoulder radiographs showing isolated greater tuberosity fractures in a Level I trauma centre between July 2007 and July 2012. We identified 199 cases where records and radiographs were reviewed and included 79 men and 120 women with a mean age of 58 years (23 to 96). The morphological classification was applied to the first 139 cases by three reviewers on two occasions using the Kappa statistic and compared with the AO and Neer classifications. The inter- and intra-observer reliability of the morphological classification was 0.73 to 0.77 and 0.69 to 0.86, respectively. This was superior to the Neer (0.31 to 0.35/0.54 to 0.63) and AO (0.30 to 0.32/0.59 to 0.65) classifications. The distribution of avulsion, split and depression type fractures was 39%, 41%, and 20%, respectively. This classification of greater tuberosity fractures is more reliable than the Neer or AO classifications. These distinct fracture morphologies are likely to have implications in terms of pathophysiology and surgical technique.

Validity, reliability and responsiveness of the French language translation of the Western Ontario Shoulder Instability Index (WOSI).

BACKGROUND: The WOSI (Western Ontario Shoulder Instability Index) is a self-administered quality of life questionnaire designed to be used as a primary outcome measure in clinical trials on shoulder instability, as well as to measure the effect of an intervention on any particular patient. It is validated and is reliable and sensitive. As it is designed to measure subjective outcome, it is important that translation should be methodologically rigorous, as it is subject to both linguistic and cultural interpretation. OBJECTIVE: To produce a French language version of the WOSI that is culturally adapted to both European and North American French-speaking populations. MATERIALS AND METHODS: A validated protocol was used to create a French language WOSI questionnaire (WOSI-Fr) that would be culturally acceptable for both European and North American French-speaking populations. Reliability and responsiveness analyses were carried out, and the WOSI-Fr was compared to the F-QuickDASH-D/S (Disability of the Arm, Shoulder and Hand-French translation), and Walch-Duplay scores. RESULTS: A French language version of the WOSI (WOSI-Fr) was accepted by a multinational committee. The WOSI-Fr was then validated using a total of 144 native French-speaking subjects from Canada and Switzerland. Comparison of results on two WOSI-Fr questionnaires completed at a mean interval of 16 days showed that the WOSI-Fr had strong reliability, with a Pearson and interclass correlation of r=0.85 (P=0.01) and ICC=0.84 [95% CI=0.78-0.88]. Responsiveness, at a mean 378.9 days after surgical intervention, showed strong correlation with that of the F-QuickDASH-D/S, with r=0.67 (P<0.01). Moreover, a standardized response means analysis to calculate effect size for both the WOSI-Fr and the F-QuickDASH-D/S showed that the WOSI-Fr had a significantly greater ability to detect change (SRM 1.55 versus 0.87 for the WOSI-Fr and F-QuickDASH-D/S respectively, P<0.01). The WOSI-Fr showed fair correlation with the Walch-Duplay. DISCUSSION: A French-language translation of the WOSI questionnaire was created and validated for use in both Canadian and Swiss French-speaking populations. This questionnaire will facilitate outcome assessment in French-speaking settings, collaboration in multinational studies and comparison between studies performed in different countries. TYPE OF STUDY: Multicenter cohort study. LEVEL OF EVIDENCE: II.

Heterotopic ossification following total hip replacement for acetabular fractures.

Early total hip replacement (THR) for acetabular fractures offers accelerated rehabilitation, but a high risk of heterotopic ossification (HO) has been reported. The purpose of this study was to evaluate the incidence of HO, its associated risk factors and functional impact. A total of 40 patients with acetabular fractures treated with a THR weres retrospectively reviewed. The incidence and severity of HO were evaluated using the modified Brooker classification, and the functional outcome assessed. The overall incidence of HO was 38% (n = 15), with nine severe grade III cases. Patients who underwent surgery early after injury had a fourfold increased chance of developing HO. The mean blood loss and operating time were more than twice that of those whose surgery was delayed (p = 0.002 and p < 0.001, respectively). In those undergoing early THR, the incidence of grade III HO was eight times higher than in those in whom THR was delayed (p = 0.01). Only three of the seven patients with severe HO showed good or excellent Harris hip scores compared with eight of nine with class 0, I or II HO (p = 0.049). Associated musculoskeletal injuries, high-energy trauma and head injuries were associated with the development of grade III HO.The incidence of HO was significantly higher in patients with a displaced acetabular fracture undergoing THR early compared with those undergoing THR later and this had an adverse effect on the functional outcome.

HIV and hepatitis C virus coinfection in Canada: challenges and opportunities for reducing preventable morbidity and mortality.

OBJECTIVES: Hepatitis C virus (HCV) has emerged as an important health problem in the era of effective HIV treatment. However, very few data exist on the health status and disease burden of HIV/HCV-coinfected Canadians. METHODS: HIV/HCV-coinfected patients were enrolled prospectively in a multicentre cohort from 16 centres across Canada between 2003 and 2010 and followed every 6 months. We determined rates of a first liver fibrosis or endstage liver disease (ESLD) event and all-cause mortality since cohort enrolment and calculated standardized mortality ratios compared with the general Canadian population. RESULTS: A total of 955 participants were enrolled in the study and followed for a median of 1.4 (interquartile range 0.5-2.3) years. Most were male (73%) with a median age of 44.5 years; 13% self-identified as aboriginal. There were high levels of current injecting drug and alcohol use and poverty. Observed event rates [per 100 person-years; 95% confidence interval (CI)] were: significant fibrosis (10.21; 8.49, 12.19), ESLD (3.16; 2.32, 4.20) and death (3.72; 2.86, 4.77). The overall standardized mortality ratio was 17.08 (95% CI 12.83, 21.34); 12.80 (95% CI 9.10, 16.50) for male patients and 28.74 (95% CI 14.66, 42.83) for female patients. The primary causes of death were ESLD (29%) and overdose (24%). CONCLUSIONS: We observed excessive morbidity and mortality in this HIV/HCV-coinfected population in care. Over 50% of observed deaths may have been preventable. Interventions aimed at improving social circumstances, reducing harm from drug and alcohol use and increasing the delivery of HCV treatment in particular will be necessary to reduce adverse health outcomes among HIV/HCV-coinfected persons.

Design and implementation of a randomized crossover study of valproic acid and antiretroviral therapy to reduce the HIV reservoir.

BACKGROUND: HIV reservoirs represent the major obstacles for eradication and are defined as a cell type that allows persistence of replication-competent HIV in patients on optimal long-term antiretroviral therapy (HAART). Several pilot clinical trials have been implemented to assess the value of experimental therapy to reduce reservoir size or eradicate HIV. In order to eradicate HIV, valproic acid was used as a new strategy to increase viral gene expression in the nucleus of infected cells with the expectation of generating a direct cell death or destruction by nearby cytotoxic cells. Previous pilot studies using VPA have showed conflicting results on the ability of VPA to reduce the size of HIV reservoirs. PURPOSE: As the role of VPA on HIV reservoirs remains unclear, we conducted a multicenter clinical trial with a specific study design to obtain optimal information on reservoir changes while exposing the smallest number of individuals to the experimental medication. METHOD: To this aim, a randomized, crossover design with 2 different treatment durations was implemented. By doubling the therapeutic period in one study arm, we were in a position to assess the impact of an extended duration of VPA on the size of the HIV reservoir and to evaluate the duration of treatment effects upon VPA withdrawal in the other arm. However, limitations for this type of study design included the logistical complexity of 2 uneven study arms and longer study duration. CONCLUSION: Despite the absence of demonstrable impact of VPA on reservoir size, such crossover study design should be considered in the early stage testing of novel HIV therapeutics targeted to reduce reservoir size or eradicate HIV.

Valproic acid in association with highly active antiretroviral therapy for reducing systemic HIV-1 reservoirs: results from a multicentre randomized clinical study.

OBJECTIVES: Conflicting results have been reported regarding the ability of valproic acid (VPA) to reduce the size of HIV reservoirs in patients receiving suppressive highly active antiretroviral therapy (HAART). In a randomized multicentre, cross-over study, we assessed whether adding VPA to stable HAART could potentially reduce the size of the latent viral reservoir in CD4 T cells of chronically infected patients. METHODS: A total of 56 virologically suppressed patients were randomly assigned either to receive VPA plus HAART for 16 weeks followed by HAART alone for 32 weeks (arm 1; n = 27) or to receive HAART alone for 16 weeks and then VPA plus HAART for 32 weeks (arm 2; n = 29). VPA was administered at a dose of 500 mg twice a day (bid) and was adjusted to the therapeutic range. A quantitative culture assay was used to assess HIV reservoirs in CD4 T cells at baseline and at weeks 16 and 48. RESULTS: No significant reductions in the frequency of CD4 T cells harbouring replication-competent HIV after 16 and 32 weeks of VPA therapy were observed. In arm 1, median (range) values of IU per log(10) billion (IUPB) cells were 2.55 (range 1.20-4.20), 1.80 (range 1.0-4.70) and 2.70 (range 1.0-3.90; P = 0.87) for baseline, week 16 and week 48, respectively. In arm 2, median values of IUPB were 2.55 (range 1.20-4.65), 1.64 (range 1.0-3.94) and 2.51 (range 1.0-4.48; P = 0.50) for baseline, week 16 and week 48, respectively. CONCLUSIONS: Our study demonstrates that adding VPA to stable HAART does not reduce the latent HIV reservoir in virally suppressed patients.

Effect of antiretroviral therapy on HIV-1 genetic evolution during acute infection.

The rapid evolution of HIV-1 is a major obstacle to viral eradication. Early antiretroviral therapy (ART) during primary HIV-1 infection could limit viral diversity. Eighteen patients recently infected with HIV-1 were selected. Nine initiated ART soon after enrolment and nine remained untreated. Replication-competent (RC) viruses were quantified at baseline and after one year of follow-up. Viral diversity in the C2V5 envelope region was evaluated from plasma, peripheral blood mononuclear cells (PBMCs), and cell culture at both time points. The amount of RC virus in the treated group declined (median -5.42 infectious units per million [IUPM]) while it remained stable or increased in the untreated group (median +0.87 IUPM). At one year post infection, we observed a significant increase in diversity for the C2V5 (+0.150%) region, specifically in the hypervariable loops V4 (+0.73%) and V5 (+0.77%), in the untreated group. More importantly, viral diversity did not significantly increase in treated individuals during the first year post infection. Genetic diversity during primary infection remains low through the first year of infection. Early treatment could contribute to a decrease in RC viruses from PBMCs and to limitation of viral diversification in the viral reservoir. These findings may have relevance for the rational design of specific immunotherapeutic strategies.

Internal fixation of osteopenic acetabular fractures involving the quadrilateral plate.

BACKGROUND: Older patients tend to have acetabular fractures with medial displacement patterns and associated comminution, particularly of the quadrilateral surface. Our goal was to investigate the appropriateness of open reduction and internal fixation using an infra-pectineal buttress plate for osteopenic acetabular fractures. MATERIALS AND METHOD: We conducted a retrospective review involving twenty one consecutive patients over the course of 4 years with an acetabular fracture in an academic level 1 trauma centre. We performed the modified Stoppa approach with buttress plating of the quadrilateral surface. Clinical examination radiographs was done using criteria described by Matta. Functional outcome was evaluated using surveys including SF-12, WOMAC, Harris Hip score and modified Postel Merle D'Aubigne. RESULTS: Average follow-up was 4.2 years with a minimum of 2 years. Mean age for patients was 64.3 years. We obtained anatomic reduction in 52.4% (11/21) of cases, imperfect reduction in 38.1% (8/21) of cases and poor reduction in 9.5% (2/21) of cases. Significant loss of reduction was seen in 2 patients. A superior dome impaction (a Gull sign) was correlated to arthroplasty (p=0.02) and reduced quality of initial reduction (p=0.02). Two patients required re-intervention with a total hip arthroplasty. There was one traumatic injury to the obturator nerve and 2 patients were noted to have temporary weakness of the hip adductors postoperatively. CONCLUSION: Internal fixation using the modified Stoppa approach to buttress the quadrilateral plate should be considered a viable alternative to total hip arthroplasty for the initial treatment of acetabular fractures in the elderly.

Lateral compression fractures of the superior pubic ramus with intra-articular extension.

A total of 30 patients with lateral compression fractures of the pelvis with intra-articular extension into the anterior column were followed for a mean of 4.2 years (2 to 6), using the validated functional outcome tools of the musculoskeletal function assessment and the short-form health survey (SF-36). The functional outcome was compared with that of a series of patients who had sustained type-B1 and type-C pelvic fractures. The lateral-compression group included 20 men and ten women with a mean age of 42.7 years (13 to 84) at the time of injury. Functional deficits were noted for the mental component summary score (p = 0.008) and in the social function domain (p < 0.05) of the SF-36. There was no evidence of degenerative arthritis in the lateral-compression group. However, they had high functional morbidity including greater emotional and psychological distress.

Proximal humerus fractures treated by percutaneous locking plate internal fixation.

INTRODUCTION: There is no consensually accepted recommendation for optimum surgical treatment of unstable fractures of the proximal humerus. HYPOTHESIS: Locked and minimally-invasive plating is a promising treatment option. MATERIALS AND METHODS: The aim of this prospective, multicentric study is to describe a recently introduced surgical technique for proximal humeral fractures and to evaluate the radiographic and clinical outcomes of this operation. Closed and minimally-invasive reduction is first performed. A proximal humerus specific locking plate featuring multiple-angle screws is secondly implanted. Proper identification and protection of the axillary nerve with the index finger during plate insertion on the lateral humeral side is highly advisable. If it can't be palpated, a classic delto-pectoral approach should be preferred. Thirty-four patients were included in this study with a 1-year minimal postoperative follow-up. Twenty-two patients presented a two-part surgical neck fracture according to the Neer classification and 12 patients had a three-part valgus-impacted fracture. DASH (Disabilities of the Arm, Shoulder and Hand) and Constant scoring systems were used for functional evaluation. RESULTS: Specifically, no axillary nerve injury and no loss of reduction were observed. The median Constant score and the mean DASH score were 82 and 26 respectively at 1-year follow-up. The age-adjusted functional scores values were satisfactory. Two of the patients (6%) required surgical revision for intra-articular screw penetration. DISCUSSION: Our study suggests that percutaneous plating with angular screw fixation of proximal humeral fractures is a safe and effective method, which produces good functional and radiologic outcomes. These minimally-invasive techniques allowing a better preservation of soft-tissues help promote early functional recovery. This more friendly approach combined to upgraded implants and instruments will also improve early and long-term outcomes of these fractures.

Long-term outcome of surgically-treated habitual patellar dislocation in children with coexistent patella alta. Minimum follow-up of 11 years.

We retrospectively reviewed the operative treatment carried out between 1988 and 1994 of eight patients with habitual patellar dislocation. In four the condition was bilateral. All patients had recurrent dislocation with severe functional disability. The surgical technique involved distal advancement of the patella by complete mobilisation of the patellar tendon, lateral release and advancement of vastus medialis obliquus. The long-term results were assessed radiologically, clinically and functionally using the Lysholm knee score, by an independent observer. The mean age at operation was 10.3 years (7 to 14) with a mean follow-up of 13.5 years (11 to 16). One patient required revision. At the latest follow-up, all patellae were stable and knees functional with a mean Lysholm knee score of 98 points (95 to 100). In those aged younger than ten years at operation there was a statistically significant improvement in the sulcus angle at the latest follow-up (Student's t-test, p = 0.001). Two patients developed asymptomatic patella infera as a late complication. This technique offers a satisfactory treatment for the immature patient presenting with habitual patellar dislocation associated with patella alta. If performed early, we believe that remodelling of the shallow trochlea may occur, adding intrinsic patellofemoral stability.

A large prospective study assessing injection site reactions, quality of life and preference in patients using the Biojector vs standard needles for enfuvirtide administration.

OBJECTIVES: To determine the severity of injection site reactions (ISRs), patient quality of life (QoL) and preference when enfuvirtide is administered by the Biojector (Bioject, Medical Technologies, Inc., Tualatin, OR, USA) relative to standard needles. METHODS: A total of 201 HIV-positive patients on stable enfuvirtide-based therapy (n=184) or initiating such therapy (n=17) were evaluated prospectively after switching from standard needles to the Biojector system. Patients used needles for a minimum of 2 weeks prior to switching to the Biojector. Questionnaires to assess the incidence and severity of ISRs (31-item score) and QoL [Medical Outcomes Study HIV Health Survey (MOS-HIV)] were administered at baseline and following a minimum of 14 days of Biojector use. RESULTS: The median changes in ISR score and number of ISRs following a median of 1.0 month [interquartile range (IQR) 0.9, 1.3] of Biojector use were -3 (IQR -7, 1) and -1 (IQR -3, 1), respectively. The severity of pain (P<0.0001), induration (P<0.0001), pruritus (P<0.0001), nodules (P<0.0001) and erythema (P<0.0001) all decreased with the Biojector. Administration of enfuvirtide with the Biojector was associated with an improved patient QoL (P<0.0001), and was preferred by 72% of patients. CONCLUSIONS: Compared with needles, the Biojector was associated with a decreased severity of ISRs and improved QoL in patients taking enfuvirtide.

Assay of HIV gp41 amino acid sequence to identify baseline variation and mutation development in patients with virologic failure on enfuvirtide.

In this study, we retrospectively assessed a gp41 genotypic assay in 404 enfuvirtide-naïve individuals (340 clade B, 64 non-B clade) to determine the prevalence of baseline polymorphisms and in 41 patients virologically failing enfuvirtide to determine correlates of resistance to this agent. Conserved and polymorphic regions of gp41 were identified in clade B isolates, with 127 of 328 codons (38.7%) being highly conserved (<1.0% variation) and 74 of 328 codons (22.6%) being partially conserved (1.0-5.0% variation). Polymorphisms were observed throughout gp41 in non-B clade virus sequences compared to the clade B reference strain, ranging from 53 natural substitutions in clade D to 76 in clade A. Insertions were common at positions 3, 105, 215 and 276. In the patients failing enfuvirtide, mutations were detected in the 10 amino acid region at positions 36-45 in all plasma virus sequences. Six additional mutations were selected outside of the common region which may be clinically significant at positions 33, 73, 75, 126, and 138. Two or three mutations at positions 36-45 were observed in the majority of plasma virus sequences from patients with virologic failure following the use of enfuvirtide. Further study is required to determine the clinical relevance of the clade related polymorphisms and the new mutations identified in the patients with virologic failure.