Injuries across a pre-professional ballet and contemporary dance tertiary training program: A retrospective cohort study.

OBJECTIVES: The study aims to analyse the incidence of medical attention injuries, subsequent injuries, and the median time to injury, across tertiary ballet and contemporary dance training programs. DESIGN: Retrospective cohort. METHODS: Consenting ballet and contemporary dance students completing the third/final year of two tertiary programs were included. The three-year programs consisted of six semesters. Access was granted to onsite physiotherapy notes, timetables, and academic enrolment. Injury was defined as requiring medical attention. Injury and exposure data were extracted, injuries coded for location and tissue, and subsequent injuries, occurring after an initial index injury, categorised. Mean, standard deviation, range, injury incidence, risk and rate ratios, proportions and Kaplan-Meier curves were calculated to report participant characteristics, and injury patterns across three years of the dance program. RESULTS: All 17 students (mean age=20.7 years; standard deviation=1.32) from one program consented to participate, of which all were injured across the three-year program, with 2.71 (95% confidence interval: 2.22, 3.20) injury incidence rate per 1000h, and increasing injury incidences seen across the program. The most injured site and tissue were the ankle (17.65%) and muscle (23.53%) respectively. 74.86% of subsequent injuries were different (affecting a different location and tissue), and 4.88% reinjuries (affecting the same location, tissue, and structure after recovery). The median time to the first injury was seven weeks in the first semester, and later in subsequent year levels. CONCLUSIONS: Increasing injury incidences were seen across the program. Most subsequent injuries were different from previous injuries in this cohort. Future research should use exposure measures beyond hours (i.e. intensity) and consider subsequent injuries.

Injuries during transition periods across the year in pre-professional and professional ballet and contemporary dancers: A systematic review and meta-analysis.

OBJECTIVE: To consider the association of injuries with transition periods in the dance year, i.e., when dancers return at the start of the year, and when they transition from rehearsal to performance periods. METHODS: Six electronic databases were searched to November 2019. All English language peer-reviewed studies, of any study design investigating ballet and contemporary pre-professional and professional dance populations were included. Only those studies reporting on the timing of injury were included. RESULTS: Fifteen cohort and two case-series studies were included. A meta-analysis of seven studies revealed the rate of injuries to be significantly higher for the second and third months (1.52; 95% confidence interval [CI]:1.11-2.08; 1.26; 95%CI:1.07-1.48 respectively) after the return to dance. Two further studies report more injuries up to Week 13 of the year. One study showed an increase in injured dancers at three and four weeks after transition from rehearsals to a performance season. Four studies show an increase in injuries at performance times. CONCLUSIONS: Meta-analyses of seven studies shows the second and third months after returning to dance have a significantly higher rate of injuries. More research is needed to quantify training loads in dance. Practitioners should be cognisant of the higher injury rates during periods of transition and consider modifying load, as it is a potential contributing factor.

Impacts of dance on cognition, psychological symptoms and quality of life in Parkinson's disease.

BACKGROUND: While dance may improve motor features in Parkinson's disease (PD), it is not yet clear if the benefits extend to non-motor features. OBJECTIVE: To determine whether dance classes based on Dance for PD®, improve cognition, psychological symptoms and Quality of Life (QoL) in PD. METHODS: Participants were allocated to a Dance Group (DG; n = 17) or Control Group (CG: n = 16). Participants had early-stage PD (Hoehn & Yahr: DG = 1.6±0.7, CG = 1.5±0.8) with no cognitive impairment (Addenbrooke's score: DG = 93.2±3.6, CG = 92.6±4.3). The DG undertook a one-hour class, twice weekly for 12 weeks, while the CG had treatment as usual. Both groups were assessed for disease severity (MDS-UPDRS), cognition (NIH Toolbox® cognition battery, Trail Making Test), psychological symptoms (Hospital Anxiety and Depression Scale, MDS-UPDRS-I) and QoL (PDQ-39, MDS-UPDRS-II). RESULTS: Group comparison of pre-post change scores showed that selected cognitive skills (executive function and episodic memory), psychological symptoms (anxiety and depression) as well as QoL (PDQ-39 summary index) were significantly improved by the intervention (DG > CG, p's < 0.05, Cohen's d > 0.8). DISCUSSIONS AND CONCLUSION: Dance classes had a clear benefit on psychological symptoms, QoL and a limited cognitive benefit. Follow-up assessment is required to confirm the durability of these effects.

Low levels of neurocognitive impairment detected in screening HIV-infected men who have sex with men: The MSM Neurocog Study.

This study aimed to determine the prevalence of HIV neurocognitive impairment in HIV-infected men who have sex with men aged 18-50 years, using a simple battery of screening tests in routine clinical appointments. Those with suspected abnormalities were referred on for further assessment. The cohort was also followed up over time to look at evolving changes. HIV-infected participants were recruited at three clinical sites in London during from routine clinical visits. They could be clinician or self-referred and did not need to be symptomatic. They completed questionnaires on anxiety, depression, and memory. They were then screened using the Brief Neurocognitive Screen (BNCS) and International HIV Dementia Scale (IHDS). Two hundred and five HIV-infected subjects were recruited. Of these, 59 patients were excluded as having a mood disorder and two patients were excluded due to insufficient data, leaving 144 patients for analysis. One hundred and twenty-four (86.1%) had a normal composite z score (within 1 SD of mean) calculated for their scores on the three component tests of the BNCS. Twenty (13.9%) had an abnormal z score, of which seven (35%) were symptomatic and 13 (65%) asymptomatic. Current employment and previous educational level were significantly associated with BNCS scores. Of those referred onwards for diagnostic testing, only one participant was found to have impairment likely related to HIV infection. We were able to easily screen for mood disorders and cognitive impairment in routine clinical practice. We identified a high level of depression and anxiety in our cohort. Using simple screening tests in clinic and an onward referral process for further testing, we were not able to identify neurocognitive impairment in this cohort at levels consistent with published data.

A cross-sectional study to evaluate the association of hyperbilirubinaemia on markers of cardiovascular disease, neurocognitive function, bone mineral density and renal markers in HIV-1 infected subjects on protease inhibitors.

BACKGROUND: Ongoing inflammation in controlled HIV infection contributes to non-AIDS comorbidities. High bilirubin appears to exhibit an anti-inflammatory effect in vivo. We therefore examined whether increased bilirubin in persons with HIV was associated with differences in markers of inflammation and cardiovascular, bone, renal disease, and neurocognitive (NC) impairment. METHODS: This cross-sectional study examined inflammatory markers in individuals with stable HIV infection treated with two nucleoside reverse transcriptase inhibitors and a boosted protease inhibitor. Individuals recruited were those with a normal bilirubin (NBR; 0-17 µmol/L) or high bilirubin (>2.5 × upper limit of normal). Demographic and anthropological data were recorded. Blood and urine samples were taken for analyses. Pulse wave velocity (PWV) measurement, carotid intimal thickness (CIT), and calcaneal stiffness (CSI) were measured. Males were asked to answer a questionnaire about sexual function; NC testing was performed using CogState. RESULTS: 101 patients were screened, 78 enrolled (43 NBR and 35 HBR). Atazanavir use was significantly higher in HBR. Whilst a trend for lower CIT was seen in those with HBR, no significant differences were seen in PWV, bone markers, calculated cardiovascular risk (Framingham), or erectile dysfunction score. VCAM-1 levels were significantly lower in the HBR group. HBR was associated with lower LDL and triglyceride levels. NBR was associated with a calculated FRAX significantly lower than HBR although no associations were found after adjusting for tenofovir use. No difference in renal markers was observed. Component tests of NC testing revealed differences favouring HBR but overall composite scores were similar. DISCUSSION: High bilirubin in the context of boosted PI therapy was found not to be associated with differences in with the markers examined in this study. Some trends were noted and, on the basis of these, a larger, clinical end point study is warranted.

Low-dose growth hormone for 40 weeks induces HIV-1-specific T cell responses in patients on effective combination anti-retroviral therapy.

Recombinant human growth hormone (rhGH) administered to combination anti-retroviral therapy (cART)-treated human immunodeficiency virus-1 (HIV-1)-infected individuals has been found to reverse thymic involution, increase total and naive CD4 T cell counts and reduce the expression of activation and apoptosis markers. To date, such studies have used high, pharmacological doses of rhGH. In this substudy, samples from treated HIV-1(+) subjects, randomized to receive either a physiological dose (0·7 mg) of rhGH (n = 21) or placebo (n = 15) daily for 40 weeks, were assessed. Peptide-based enzyme-linked immunospot (ELISPOT) assays were used to enumerate HIV-1-specific interferon (IFN)-γ-producing T cells at baseline and week 40. Individuals who received rhGH demonstrated increased responses to HIV-1 Gag overlapping 20mer and Gag 9mer peptide pools at week 40 compared to baseline, whereas subjects who received placebo showed no functional changes. Subjects with the most robust responses in the ELISPOT assays had improved thymic function following rhGH administration, as determined using CD4(+) T cell receptor rearrangement excision circle (TREC ) and thymic density data from the original study. T cells from these robust responders were characterized further phenotypically, and showed decreased expression of activation and apoptosis markers at week 40 compared to baseline. Furthermore, CD4 and CD8 T cell populations were found to be shifted towards an effector and central memory phenotype, respectively. Here we report that administration of low-dose rhGH over 40 weeks with effective cART resulted in greater improvement of T lymphocyte function than observed with cART alone, and provide further evidence that such an approach could also reduce levels of immune activation.

Screening for chronic comorbid diseases in people with HIV: the need for a strategic approach.

Among people living with HIV, the proportion of deaths attributed to chronic noninfectious comorbid diseases has increased over the past 15 years. This is partly a result of increased longevity in the era of highly active antiretroviral therapy (HAART), and also because HIV infection is related, causally or otherwise, to several chronic conditions. These comorbidities include conditions that are strongly associated with modifiable risk factors, such as cardiovascular disease (CVD), diabetes, and renal and bone diseases, and increasingly management guidelines for HIV recommend risk evaluation for these conditions. The uptake of these screening approaches is often limited by the resources required for their application, and hence the management of risk reduction in most HIV-infected populations falls below a reasonable standard. The situation is compounded by the fact that few risk calculators have been adjusted for specific use in HIV infection. There is substantial overlap of risk factors for the four common comorbid diseases listed above that are especially relevant in HIV infection, and this offers an opportunity to develop a simple screening approach that encompasses the key risk factors for lifestyle-related chronic disease in people with HIV infection. This would identify those patients who require more in-depth investigation, and facilitate a stepwise approach to targeted management. Such a tool could improve communication between patient and clinician. A significant proportion of people with HIV are sufficiently engaged with their care to participate in health promotion and take the lead in using patient-centric screening measures. Health-based social networking offers a mechanism for dissemination of such a tool and is able to embed educational messages and support within the process.

Longer prior exposure to zidovudine/lamivudine-containing combination antiretroviral therapy, age, and male gender are each associated with reduced subcutaneous adipose tissue.

OBJECTIVES: Whether zidovudine (AZT)-associated lipoatrophy occurrence differs by concomitant exposure to protease (PIs) or non-nucleoside reverse transcriptase inhibitors (NNRTIs) remains unclear. Baseline body composition data from a randomized trial in subjects stable on first-line AZT-based therapy were used to explore this issue. METHODS: In this substudy of the PREPARE trial, centrally read baseline whole-body dual energy x-ray aborptiometry (DXA) and single-slice abdominal CT scans were analyzed with respect to duration and type of prior AZT/lamivudine (3TC) combination antiretroviral therapy (cART), including by multivariate linear regression adjusted for age, gender, ethnicity, body mass index (BMI), and nadir CD4. RESULTS: DXA and CT, from 134 and 136 patients, respectively [87% male; 82% Caucasian; mean (SD) age, 45.6 years (10); BMI, 24.3 kg/m² (3.2)], were analyzed. Prior AZT/3TC cART exposure was 5.5 (2.2) years. Seventy-eight and 27 patients had concomitantly and exclusively used NNRTIs and PIs, respectively. AZT/3TC cART, AZT/3TC/NNRTI, and AZT/3TC/PI, respectively, were associated with the presence of a mean (95% CI) of 247 g (-438 to -56; P = .012), 267 g (-467 to -66; P = .010), and 216 g (-430 to -1.7; P = .048) less baseline limb fat per additional year of prior exposure. Although abdominal subcutaneous (SAT) adipose tissue was likewise less with longer AZT/3TC cART, this was only significant for AZT/3TC/ NNRTI but not AZT/3TC/PI. Visceral adipose tissue (VAT) amount was not clearly associated to prior treatment. Increased age and male gender were independently associated with lower limb fat and SAT, but more VAT. CONCLUSIONS: Longer exposure to AZT/3TC, regardless of whether in combination with PI or NNRTI, as well as increased age and male gender are independently associated with lower limb fat mass.

Randomized comparison of metabolic and renal effects of saquinavir/r or atazanavir/r plus tenofovir/emtricitabine in treatment-naïve HIV-1-infected patients.

OBJECTIVES: The aim of the study was to compare the effects on lipids, body composition and renal function of once-daily ritonavir-boosted saquinavir (SQV/r) or atazanavir (ATV/r) in combination with tenofovir/emtricitabine (TDF/FTC) over 48 weeks. METHODS: An investigator-initiated, randomized, open-label, multinational trial comparing SQV/r 2000/100 mg and ATV/r 300/100 mg once daily, both in combination with TDF/FTC, in 123 treatment-naïve HIV-1-infected adults was carried out. The primary endpoint was to demonstrate noninferiority of SQV/r compared with ATV/r with respect to the change in fasting cholesterol after 24 weeks. Secondary outcome measures were changes in metabolic abnormalities, body composition, renal function, and virological and immunological efficacy over 48 weeks. Patients who had used at least one dose of trial drug were included in the analysis. RESULTS: Data for 118 patients were analysed (57 patients on SQV/r and 61 on ATV/r). At week 24, changes in lipids were modest, without increases in triglycerides, including a significant rise in high-density lipoprotein (HDL) cholesterol and a nonsignificant decrease in the total:HDL cholesterol ratio in both arms with no significant difference between arms. Lipid changes at week 48 were similar to the changes observed up to week 24, with no significant change in the homeostasis model assessment (HOMA) index. Adipose tissue increased regardless of the regimen, particularly in the peripheral compartment and to a lesser extent in the central abdominal compartment, with an increase in adipose tissue reaching statistical significance in the ATV/r arm. A slight decline in the estimated glomerular filtration rate (eGFR) was observed in both arms during the first 24 weeks, with no progression thereafter. The immunological and virological responses were similar over the 48 weeks. CONCLUSIONS: Combined with TDF/FTC, both SQV/r 2000/100 mg and ATV/r 300/100 mg had comparable modest effects on lipids, had little effect on glucose metabolism, conserved adipose tissue, and similarly reduced eGFR. The virological efficacy was similar.

Improvements in cheek volume in lipoatrophic individuals switching away from thymidine nucleoside reverse transcriptase inhibitors.

BACKGROUND: Thymidine nucleoside reverse transcriptase inhibitors (NRTIs) are associated with subcutaneous fat loss. Facial changes cannot be assessed by dual-energy X-ray absorptiometry (DEXA) scans. There are limited objective data on the reversibility of facial lipoatrophy. METHODS: We performed a facial volume substudy of a randomized thymidine NRTI replacement study carried out in HIV-infected subjects with moderate to severe lipoatrophy. Facial volume changes were assessed using validated 3D laser imaging. Changes in body composition were measured using DEXA scans. The association between changes in facial volume and body composition parameters at 48 weeks was measured using Spearman's rank correlation. RESULTS: Forty-seven individuals (46 male), 11 receiving zidovudine and 36 receiving stavudine, switched to either tenofovir disoproxil fumarate (DF) (n=23) or abacavir (ABC) (n=24). Thirty-nine of these 47 patients (84.8%) reported facial lipoatrophy at baseline. The median volume increase in both cheeks from baseline was 1857.3 mm(3). These volume changes and increases in limb fat at 48 weeks were similar in the two groups and correlated significantly (Spearman's r=0.41, P=0.004). CONCLUSIONS: Facial volume in lipoatrophic individuals was found to increase after thymidine NRTI replacement. We demonstrated a significant correlation between improvements in facial and limb fat parameters. Switching from thymidine NRTIs in patients with facial lipoatrophy could potentially reduce the need for cosmetic interventions.

Switching from twice-daily abacavir and lamivudine to the once-daily fixed-dose combination tablet of abacavir and lamivudine improves patient adherence and satisfaction with therapy.

BACKGROUND: Patients prefer fewer pills and once-daily (qd) dosing without food restrictions. We assessed the impact on adherence [by Medication Event Monitoring System (MEMS) cap monitoring] of switching from abacavir (ABC) and lamivudine (3TC) twice daily (bid) to ABC/3TC fixed-dose formulation (FDC, Kivexa) qd to achieve a qd regimen. METHODS: A randomized, open-label, 8-week study comparing adherence, efficacy and safety of immediate vs. delayed switching from ABC/3TC to FDC qd. RESULTS: Ninety-four patients were dosed. Significantly improved adherence was observed at week 4 with qd ABC/3TC across all three adherence variables: taking compliance 99.2% (90.7-100%) vs. 96.6% (60.0-100%) (P=0.017); dosing compliance 97.1% (64.3-100%) vs. 91.9% (33.3-100%) (P=0.016); and timing compliance 95.5% (53.8-100%) vs. 86.3% (4.3-100%) (P=0.006). Treatment satisfaction increased significantly at week 4 with ABC/3TC qd [92% (82-99%) vs. 85% (75-93%) (P=0.004)]. Two patients were withdrawn from the study because of intolerance to ABC/3TC. CONCLUSIONS: Switching from ABC and 3TC bid to ABC/3TC FDC qd significantly improved adherence by MEMS cap monitoring at week 4 and improved patient satisfaction with therapy. The results remain to be confirmed over a longer follow-up. Use of qd regimens supports adherence and improves treatment satisfaction relative to bid regimens.

Pharmacokinetics and safety of saquinavir/ritonavir and omeprazole in HIV-infected subjects.

We investigated the pharmacokinetics and safety of saquinavir/ritonavir when administered with omeprazole simultaneously and 2 h apart to human immunodeficiency virus (HIV) subjects. Saquinavir/ritonavir 12-h pharmacokinetics was assessed with and without omeprazole 40 mg. Subjects were randomized to group A (saquinavir/ritonavir and omeprazole simultaneously/2 h apart) or group B (saquinavir/ritonavir and omeprazole 2 h apart/simultaneously). Saquinavir/ritonavir pharmacokinetics was assessed on days 1, 8, and 22. Within-subject changes were evaluated by geometric mean ratios and 90% confidence interval (CI). Twelve subjects completed the study. GM (90% CI) for saquinavir area under the curve (AUC)(0-12) (ng h/ml), trough concentration (C(trough)) (ng/ml), and maximum concentration (C(max)) (ng/ml) were 14,698 (13,242-20,636), 433 (368-758), 2,513 (2,243-3,329) without omeprazole; 22,646 (18,536-131,861), 750 (619-1,280), 3,890 (3,223-5,133) with omeprazole simultaneously; and 24,549 (20,884-38,894), 851 (720-1,782), 4,141 (3,554-5,992) with omeprazole 2 h earlier. Simultaneous administration of omeprazole significantly increased saquinavir AUC(0-12), C(trough), and C(max) by 54, 73, and 55%, whereas staggered administration by 67, 97, and 65%. No grade 3/4 toxicity or lab abnormalities were observed. In the presence of omeprazole, saquinavir plasma exposure is significantly increased in HIV-infected subjects whether administered simultaneously or 2 h apart.

Relative antiviral efficacy of ritonavir-boosted darunavir and ritonavir-boosted tipranavir vs. control protease inhibitor in the POWER and RESIST trials.

OBJECTIVE: To compare the relative antiviral efficacy of TMC114 with low-dose ritonavir (TMC114/r) and tipranavir with low-dose ritonavir (TPV/r) vs. control protease inhibitor (CPI) in treatment-experienced patients, using data from the POWER 1/2 and RESIST 1/2 trials. These trials recruited antiretroviral-experienced patients with HIV RNA > 1000 HIV-1 RNA copies/mL and at least one primary PI mutation, and used optimized nucleoside reverse transcriptase inhibitors with or without enfuvirtide, plus investigator-selected CPI in the control arms. METHODS: For the POWER trials, data from the 600/100 mg twice a day (bid) dose and CPI arms (n=201) were included, while all data from the RESIST trials (TPV/r 500/200 mg bid and CPI; n=1159) were included. The difference in week 24 efficacy (intent to treat) for the new PI vs. CPI was compared between the trials. RESULTS: Overall baseline characteristics were well matched across the trials. At week 24, 72% of TMC114/r patients achieved a > or =1 log(10) copies/mL reduction in HIV RNA compared with 40% of TPV/r patients (for CPI patients, this percentage was 21 and 18%, respectively, in the POWER and RESIST trials). The treatment benefit of TMC114/r over CPI in the POWER trials was greater (outside the 95% confidence intervals) than the benefit of TPV/r over CPI in the RESIST trials, for the 24-week HIV RNA endpoints of 1 log(10) copies/mL reduction, <400 copies/mL and <50 copies/mL, and also for the mean rise in CD4 count. In sensitivity analysis, this difference in efficacy was strongest for those who did not also use enfuvirtide. CONCLUSIONS: Given the caveats of this type of analysis (for example, possible differences in trial conduct, and undetected differences in baseline resistance profiles), the efficacy benefits of TMC114/r vs. CPI in the POWER trials appear to be greater than the benefits of TPV/r vs. CPI in the RESIST trials, for patients who did not also use enfuvirtide.

Changes in sleep quality and brain wave patterns following initiation of an efavirenz-containing triple antiretroviral regimen.

BACKGROUND: Initiation of efavirenz is commonly associated with sleep disturbances. Assessment of sleep using the electroencephalogram and electromyogram enables sleep staging to be performed and changes following the introduction of therapy to be evaluated. METHODOLOGY: Using standardized sleep-staging methodology, we investigated sleep staging and sleep quality by patient self-report in an open-label cohort pilot study. Assessments were performed prior to the initiation of efavirenz, 2 weeks after the initiation of efavirenz and 3 months after the initiation of efavirenz. The study included HIV-positive individuals without central neurological disease who were naive to antiretroviral treatment. All patients initiated treatment with two nucleoside reverse transcriptase inhibitors in combination with efavirenz. RESULTS: Ten patients completed all three study visits. Patients reported an increase in recollection of dreams and morning sluggishness after the initiation of efavirenz which persisted for 3 months. Sleep-staging data indicated a modest reduction in stage 2 sleep with a corresponding increase in deep sleep stage 4 and a modest increase in rapid eye movement (REM) sleep. Overall sleep maintenance efficiency did not significantly change from baseline. Changes in sleep staging were most marked 2 weeks after the initiation of efavirenz but remained different from baseline patterns at 3 months. CONCLUSION: The data indicate that efavirenz has a modest but persistent impact on the time spent in several key sleep stages. Patients reported persistence of dream recollection but remained satisfied with sleep quality and overall quality of life.

Long-term safety and efficacy of poly-L-lactic acid in the treatment of HIV-related facial lipoatrophy.

OBJECTIVE: We evaluated the long-term safety and efficacy of injectable poly-L-lactic acid (PLLA) for the correction of facial lipoatrophy. METHODS: This was a randomized, open-label, comparative, single-centre study of injected PLLA in patients with HIV-related facial lipoatrophy. Thirty subjects were randomized to immediate or delayed PLLA treatments, administered as three sets of bilateral injections, 2 weeks apart, into the deep dermis above the buccal fat pad. Week 24 results have been published previously (Moyle et al, HIV Medicine 2004, Vol. 5, pp. 82-87). Long-term efficacy was assessed at a recall visit using visual analogue scales (VASs) to record patient satisfaction, and by the Hospital Anxiety and Depression Scale (HADS). Patients also reported any adverse events (AEs) during the treatment period and at the recall visit. RESULTS: Twenty-seven patients returned for the recall visit, a minimum of 18 months post final study treatment. Fourteen of these patients were excluded from the recall visit because of additional treatment with PLLA. Improvements in VAS scores for facial appearance were sustained from baseline to the recall visit in both randomization groups (P<0.05 and P<0.001). Trends in improvement in HADS scores were also noted, with patients in the delayed group experiencing significant improvements in depressive symptoms (P<0.05). One case of injection-site induration and nine cases of injection-site nodules were noted at the recall visit, none of which was described as serious or severe. CONCLUSIONS: Physical and psychological benefits of PLLA are sustained over at least 18 months. Delayed AEs include mild nodularity at the treatment site.

Impact of antiretroviral choice on hypercholesterolaemia events: the role of the nucleoside reverse transcriptase inhibitor backbone.

BACKGROUND: The use of highly active antiretroviral therapy (HAART) has profoundly altered the life expectancy of individuals infected with HIV. Metabolic abnormalities associated with antiretrovirals and cumulative exposure to combination antiretroviral therapy, including dyslipidaemia and insulin resistance, have been linked to an increased risk of myocardial infarction. METHODS: Longitudinal data from a large prospectively collected clinical database were analysed. All patients who commenced first antiretroviral therapy (ART) [two nucleoside reverse transcriptase inhibitors (NRTIs)+one nonnucleoside reverse transcriptase inhibitor (NNRTI) or one active protease inhibitor (PI)] since 1996 were identified. Patients with elevated cholesterol levels [>5.5 mmol/L (215 mg/dL)] prior to therapy initiation were excluded. Quantitative data were categorized into quartiles and presented stratified by individuals developing abnormal levels of cholesterol during first-line HAART. Event time was defined as time from commencing first-line ART to either development of cholesterol level >6.5 mmol/L (254 mg/dL) or switch of first-line therapy. The Kaplan-Meier product limit survival method was used to estimate time to abnormal cholesterol level, and the chi2 test was used for comparisons between drug classes. Cox's proportional hazards regression analysis was used to identify factors predicting a likelihood of raised cholesterol level. RESULTS: A total of 1664 patients were included in the study: 57.1% on two NRTIs+one NNRTI, 38.4% on two NRTIs+one PI, and 4.4% on two NRTIs+a boosted PI regimen. Regimens containing stavudine or PIs were associated with a significantly higher event risk and earlier time to event. No differences between efavirenz and nevirapine or between didanosine and lamivudine were observed. In 28 patients exposed to the combination of tenofovir+lamivudine+efavirenz, there were no episodes of elevated cholesterol level. CONCLUSION: Dyslipidaemia has emerged as an important issue in HIV-infected individuals receiving antiretroviral therapy. This study demonstrates that age at start of therapy, baseline cholesterol level, stavudine use and PI use are all associated with increased risk of hypercholesterolemia on initial therapy. Both NRTI and NNRTI/PI choice influence risk of hypercholesterolaemia.

Better maintained adherence on switching from twice-daily to once-daily therapy for HIV: a 24-week randomized trial of treatment simplification using stavudine prolonged-release capsules.

BACKGROUND: Adherence to antiretroviral therapy is critical to treatment outcomes. Adherence studies in other therapeutic areas of medicine suggest that once-daily regimens support improved adherence when compared to twice-daily therapy. An expansion in the range of once-daily antiretrovirals is making once-daily therapy possible for persons with HIV infection. METHODS: A 24-week randomized open-label simplification study of twice-daily regimens based on stavudine immediate release or zidovudine to an all once-daily regimen based on the stavudine prolonged-release capsule (PRC), in persons with complete virological suppression on regimens also including efavirenz and lamivudine, was carried out. Subjects were assessed for adherence [using the Medication Event Monitoring System (MEMS) cap; Aardex Corporation, Union City, CA, USA], quality of life, tolerability and efficacy. RESULTS: Forty-three patients were randomly assigned: 21 remained on their original regimen and 22 switched to once-daily therapy with stavudine PRC. Although high levels of adherence and good quality of life were present at study enrollment, adherence declined to a significantly lesser extent at week 24 in the group that switched to once-daily therapy. Efficacy was maintained in both groups and there were no differences in tolerability or toxicity. CONCLUSIONS: Subjects switching from twice-daily therapy to once-daily therapy demonstrate less of a decline in adherence over 24 weeks. A once-daily regimen including stavudine PRC is as effective and tolerable as a regimen containing the twice-daily formulation.

Psychological predictors of injury among elite athletes.

OBJECTIVES: To establish injury rates among a population of elite athletes, to provide normative data for psychological variables hypothesised to be predictive of sport injuries, and to establish relations between measures of mood, perceived life stress, and injury characteristics as a precursor to introducing a psychological intervention to ameliorate the injury problem. METHODS: As part of annual screening procedures, athletes at the Queensland Academy of Sport report medical and psychological status. Data from 845 screenings (433 female and 412 male athletes) were reviewed. Population specific tables of normative data were established for the Brunel mood scale and the perceived stress scale. RESULTS: About 67% of athletes were injured each year, and about 18% were injured at the time of screening. Fifty percent of variance in stress scores could be predicted from mood scores, especially for vigour, depression, and tension. Mood and stress scores collectively had significant utility in predicting injury characteristics. Injury status (current, healed, no injury) was correctly classified with 39% accuracy, and back pain with 48% accuracy. Among a subset of 233 uninjured athletes (116 female and 117 male), five mood dimensions (anger, confusion, fatigue, tension, depression) were significantly related to orthopaedic incidents over the preceding 12 months, with each mood dimension explaining 6-7% of the variance. No sex differences in these relations were found. CONCLUSIONS: The findings support suggestions that psychological measures have utility in predicting athletic injury, although the relatively modest explained variance highlights the need to also include underlying physiological indicators of allostatic load, such as stress hormones, in predictive models.

A randomized open-label study of immediate versus delayed polylactic acid injections for the cosmetic management of facial lipoatrophy in persons with HIV infection.

BACKGROUND: Polylactic acid (PLA, New-Fill; Medifill, London, UK and Dermic Labs, a division of Eventis, Strasbourg, France) injections into the deep dermis increase fibroblast numbers and collagen production. The substance is widely used in medical applications including cosmetic procedures. METHODS: HIV-positive individuals with facial lipoatrophy (based on physician assessment) were randomized to immediate (weeks 0, 2 and 4) or delayed (weeks 12, 14 and 16) PLA given as three bilateral injections 2 weeks apart into the deep dermis overlying the buccal fat pad. Assessments included facial ultrasound, visual analogue scales, the Hospital Anxiety and Depression Scale (HADS) and assessment using photographs at weeks 0, 12 and 24. RESULTS: All 30 patients completed 24 weeks of treatment. The median age of the patients was 41 years, with a mean of 80 months of nucleoside reverse transcriptase inhibitor (NRTI) therapy and a mean of 44 months of prior protease inhibitor (PI) therapy. The median CD4 count was 428-460 cells/microL, with 47% of patients in the immediate-treatment group and 93% of patients in the delayed-treatment groups with <50 HIV-1 RNA copies/mL at baseline. No differences in immunological, virological, biochemical, haematological or metabolic parameters emerged during the study. Injections were well tolerated with only two adverse events (cellulitis and bruising) recorded, one of which delayed treatment by 1 week. There were no discontinuations. Patient visual analogue assessments, photographic assessments, and anxiety and depression scores improved with treatment. At week 12, immediate-treatment patients had significantly better visual analogue scores (7 vs. 1, P<0.001) and lower anxiety scores (6 vs. 9, P=0.056) than delayed-treatment patients. Benefits on visual analogue and HADS scores persisted until week 24. CONCLUSIONS: PLA injections led to improvements in patient self-perception, anxiety and depression scores in individuals with facial lipoatrophy. Adverse events were uncommon. The benefits of PLA persisted for at least 18 weeks beyond the last injection.