Graft Choice and the Incidence of Osteoarthritis After Anterior Cruciate Ligament Reconstruction: A Causal Analysis From a Cohort of 541 Patients

BACKGROUND: Anterior cruciate ligament (ACL) reconstruction is important to prevent knee osteoarthritis. Neither of the 2 most common graft techniques-the patellar tendon (PT) or hamstring tendon (HS) graft-has demonstrated superiority in terms of the long-term osteoarthritis rate. HYPOTHESIS: Based on the International Knee Documentation Committee (IKDC) radiographic grading system, PT grafts decrease the incidence of osteoarthritis by providing better knee stability as compared with HS grafts over 12 years of follow-up. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: All adults with a first ACL rupture who underwent surgery with a PT or HS graft technique between January 2002 and December 2003 were included in the 2014 French Society of Orthopedic Surgery and Traumatology Symposium database. Baseline characteristics were collected. The primary endpoint was the occurrence of moderate to severe osteoarthritis in each group. The secondary endpoints included clinical subjective evaluations by the IKDC score and Knee injury and Osteoarthritis Outcome Score. To control the differences in baseline characteristics, the data were analyzed with propensity score matching. RESULTS: In the cohort, 541 patients from 18 centers were included: 311 PT and 230 HS ACL reconstructions. The baseline characteristics were similar after inverse probability weighting treatment (IPWT). The occurrence of osteoarthritis was similar after IPWT (19.3% for PT and 19.6% for HS, P = .94). Age at surgery >29 years and IKDC osteoarthritis stage B at the index surgery were identified as risk factors for moderate to severe osteoarthritis. Most functional outcomes were significantly higher in the HS group; however, the difference between groups remained <10 points. Of the 106 patients who needed a medial meniscectomy, the proportion of patients with moderate to severe osteoarthritis was much higher in the HS group (43.5% vs 18.3%, P = .006). However, after IPWT, the difference was not statistically significant. CONCLUSION: At 12 years of follow-up, neither graft technique was superior to the other in terms of the rate of osteoarthritis

Diagnostic performance of ⁸F-fluorodeoxyglucose positron emission tomography in giant cell arteritis: a systematic review and meta-analysis.

PURPOSE: The aim of this study was to conduct a systematic review and perform a meta-analysis on the diagnostic performances of (18)F-fluorodeoxyglucose positron emission tomography (FDG PET) for giant cell arteritis (GCA), with or without polymyalgia rheumatica (PMR). METHODS: MEDLINE, Embase and the Cochrane Library were searched for articles in English that evaluated FDG PET in GCA or PMR. All complete studies were reviewed and qualitatively analysed. Studies that fulfilled the three following criteria were included in a meta-analysis: (1) FDG PET used as a diagnostic tool for GCA and PMR; (2) American College of Rheumatology and Healey criteria used as the reference standard for the diagnosis of GCA and PMR, respectively; and (3) the use of a control group. RESULTS: We found 14 complete articles. A smooth linear or long segmental pattern of FDG uptake in the aorta and its main branches seems to be a characteristic pattern of GCA. Vessel uptake that was superior to liver uptake was considered an efficient marker for vasculitis. The meta-analysis of six selected studies (101 vasculitis and 182 controls) provided the following results: sensitivity 0.80 [95% confidence interval (CI) 0.63-0.91], specificity 0.89 (95% CI 0.78-0.94), positive predictive value 0.85 (95% CI 0.62-0.95), negative predictive value 0.88 (95% CI 0.72-0.95), positive likelihood ratio 6.73 (95% CI 3.55-12.77), negative likelihood ratio 0.25 (95% CI 0.13-0.46) and accuracy 0.84 (95% CI 0.76-0.90). CONCLUSION: We found overall valuable diagnostic performances for FDG PET against reference criteria. Standardized FDG uptake criteria are needed to optimize these diagnostic performances

Switching from a two-tablet regimen of tenofovir/emtricitabine and efavirenz to a one-tablet regimen may affect patients' perceptions and drug management.

Simplification of antiretroviral therapy enhances a patient's adherence but a new formulation could also lead to new adverse events and changes in daily routine. This study compared medication adherence, tolerance and satisfaction among subjects switching from a two-tablet tenofovir/emtricitabine/efavirenz regimen to a one-tablet regimen. Clinical and sociodemographic data were collected and three surveys were administered at month 0 (=switch), and then 1 and 4-6 months after the switch: the Beliefs about Medicines Questionnaire, the HIV-symptom index questionnaire, the Short HIV Treatment Satisfaction Questionnaire, the Swiss HIV Cohort Study (SHCS) two-item adherence questionnaire, and a questionnaire on daily combination antiretroviral therapy (cART) management. Medication adherence of a subgroup of subjects was routinely monitored using an electronic device (MEMS(™) ). Eighty-eight subjects gave informed consent to participate in the study. The subjects' back-switch rate was 7% (six of 88). Subjects who did not back-switch preferred the one-tablet regimen (median = 2; IQR = 1.3-2.5; on a -3 to 3 scale), but no change in adherence was found (10 of 46 nonadherent subjects; P = 1.00). The perception of treatment necessity score decreased (P = 0.004), the efavirenz blood level increased (14%; P = 0.04), and association/dissociation of cART with food intake evolved (P = 0.01) after the switch. Subjects listed equivalent numbers of symptoms during the three visits. The one-tablet regimen was preferred but the number of back-switches was not negligible. The perception of treatment necessity score decreased with the simplification of the regimen from a two-tablet to a one-tablet formulation, which could negatively impact adherence. Switching is a sensitive time in a patient's treatment life and professionals should pay particular attention to patient's perceptions of treatment during such a transition

Patterns of Adherence to Raltegravir-Based Regimens and the Risk of Virological Failure Among HIV-Infected Patients: The RALTECAPS Cohort Study.

ABSTRACT:: Adherence patterns and their influence on virologic outcome are well characterized for protease inhibitor (PI)- and non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens. We aimed to determine how patterns of adherence to raltegravir influence the risk of virological failure. We conducted a prospective multicenter cohort following 81 HIV-infected antiretroviral-naive or experienced subjects receiving or starting twice-a-day raltegravir-based antiretroviral therapy. Their adherence patterns were monitored using the Medication Events Monitoring System. During follow-up (188 days, ±77), 12 (15%) of 81 subjects experienced virological failure. Longer treatment interruption [adjusted odds ratio per 24-hour increase: 2.4; 95% confidence interval: 1.2 to 6.9; P < 0.02] and average adherence (odds ratio per 5% increase: 0.68; 95% confidence interval: 0.46 to 1.00, P < 0.05) were both independently associated with virological failure controlling for prior duration of viral suppression. Timely interdose intervals and high levels of adherence to raltegravir are both necessary to control HIV replication

An Adherence-Enhancing Program Increases Retention in Care in the Swiss HIV Cohort.

This study tested a theory-based adherence-enhancing intervention: the "Interprofessional Medication Adherence Program" (IMAP) to increase human immunodeficiency virus (HIV) retention in care. We retrospectively compared our intervention center (intervention group [IG]) with a standard of care center (control group [CG]) both participating in the Swiss HIV Cohort Study between 2004 and 2012. Endpoints were defined as >6-month and >12-month gaps in care for intervals of care longer than 6 and 12 months without any blood draw. Inverse probability of treatment weights was used to adjust for differences between patients at the 2 centers. Viral failure was defined as ribonucleic acid ≥50 copies/mL after 24+ weeks on antiretrovirals. The IG included 451 patients, CG 311. In the IG, 179 (40%) patients took part in the IMAP for a median of 27 months (interquartile range, 12-45). Gaps in care of ≥6 months were significantly more likely to happen in the CG versus IG (74.6% vs 57%, P < .001). The median time until the first treatment gap was longer in the IG vs CG (120 vs 84 weeks, P < .001). Gaps in care of ≥12 months evaluated in 709 (93%) patients were significantly more likely to occur in the CG compared with the IG (22.6% vs 12.5%, P < .001). The rate of viral failure was significantly lower in the IG (8.3% vs 15.1%, P = .003). This study, in a real-world setting, shows the effectiveness of the IMAP to reduce 6- and 12-month gaps in follow up among people with HIV. These results should be confirmed by studies in other settings

Forgiveness of Dolutegravir-Based Triple Therapy Compared With Older Antiretroviral Regimens: A Prospective Multicenter Cohort of Adherence Patterns and HIV-RNA Replication.

For many people with HIV (PWH), taking antiretroviral therapy (ARV) every day is difficult. Average adherence (Av-Adh) and log-transformed treatment interruption (TI) to ARV were prospectively measured over 6 months using electronic drug monitoring (EDM) in several cohorts of PWH. Multivariate linear regression models including baseline confounders explored the influence of EDM-defined adherence (R <sup>2</sup> ) on 6-month log <sub>10</sub> HIV-RNA. Multivariate logistic regression models were used to compare the risk of HIV-RNA detection (VR) within subgroups stratified by lower (≤95%) and higher (>95%) Av-Adh. Three hundred ninety-nine PWH were analyzed with different ARVs: dolutegravir (n = 102), raltegravir (n = 90), boosted PI (bPI; n = 107), and NNRTI (n = 100). In the dolutegravir group, the influence of adherence pattern measures on R <sup>2</sup> for HIV-RNA levels was marginal (+2%). Av-Adh, TI, and Av-Adh × TI increased the R <sup>2</sup> for HIV-RNA levels by 54% and 40% in the raltegravir and bPI treatment groups, respectively. TI increased the R <sup>2</sup> for HIV-RNA levels by 36% in the NNRTI treatment group. Compared with the dolutegravir-based regimen, the risk of VR was significantly increased for raltegravir (adjusted odds ratio [aOR], 45.6; 95% CI, 4.5-462.1; P = .001), NNRTIs (aOR, 24.8; 95% CI, 2.7-228.4; P = .005), and bPIs (aOR, 28.3; 95% CI, 3.4-239.4; P = .002) in PWH with Av-Adh ≤95%. Among PWH with >95% Av-Adh, there were no significant differences in the risk of VR among the different ARVs. These findings support the concept that dolutegravir in combination with 2 other active ARVs achieves greater virological suppression than older ARVs, including raltegravir, NNRTI, and bPI, among PWH with lower adherence

Cardiovascular safety of rapidly accelerated fibrosarcoma B-type and/or mitogen-activated extracellular signal-regulated kinase inhibitors: A mixed approach combining a meta-analysis and a pharmacovigilance disproportionality analysis.

The risk of cardiovascular adverse events from rapidly accelerated fibrosarcoma B-type (BRAF) and mitogen-activated extracellular signal-regulated kinase (MEK) inhibitors is not fully characterized. To evaluate the cardiovascular adverse events risks related to BRAF and/or MEK inhibitors in randomized placebo-controlled clinical trials and in the real-life setting. We used two approaches. First, we conducted a systematic review and meta-analysis of randomized placebo-controlled clinical trials reporting the incidence of cardiovascular adverse events for BRAF and/or MEK inhibitors in cancer patients. Second, we performed a disproportionality analysis, using age- and sex-adjusted reporting odds ratios (arORs) and their 95% confidence intervals (CIs) from the World Health Organization's pharmacovigilance database (VigiBase®) of anticancer drug-associated reports, to investigate real-life data. MEK inhibitors increased the risk of ejection fraction decrease (odds ratio [OR] 3.35, 95% CI 1.58-7.07), peripheral oedema (OR 2.87 95% CI 1.93-4.27) and syncope (OR 6.71, 95% CI 3.00-14.99) compared with placebo in randomized placebo-controlled clinical trials. BRAF and MEK inhibitor combination therapy further increased the risk of ejection fraction decrease. In the disproportionality analysis, we found over-reporting of ejection fraction decrease (arOR 8.42, 95% CI 7.03-10.09), peripheral oedema (arOR 1.39, 95% CI 1.17-1.66), syncope (arOR 1.56, 95% CI 1.22-1.99), torsade de pointes/QT prolongation (arOR 6.13, 95% CI 5.04-7.47) and supraventricular arrhythmias (arOR 1.50, 95% CI 1.21-1.85) for BRAF and MEK inhibitors. BRAF and MEK inhibitors were not associated with hypertension in either approach. In conclusion, MEK inhibitors increase the risk of ejection fraction decrease, peripheral oedema and syncope in randomized placebo-controlled clinical trials. Real-life data confirm these findings, and suggested additional risks of torsade de pointes/QT prolongation and supraventricular arrhythmias with BRAF/MEK inhibitors