Patient-Reported Symptoms Over 48 Weeks Among Participants in Randomized, Double-Blind, Phase III Non-inferiority Trials of Adults with HIV on Co-formulated Bictegravir, Emtricitabine, and Tenofovir Alafenamide versus Co-formulated Abacavir, Dolutegravir, and Lamivudine

Background: Integrase strand transfer inhibitors (INSTIs) are recommended for first-line antiretroviral therapy in combination with two nucleos(t)ide reverse transcriptase inhibitors. Co-formulated bictegravir, emtricitabine, and tenofovir alafenamide (B/F/TAF), a novel, INSTI-based regimen, is currently approved in the US and EU for the treatment of HIV-1 infection and recommended as first-line treatment in current guidelines. In our current analysis, we aimed to determine changes in patient-reported symptoms over time among HIV-1-infected adults who initiated or switched to B/F/TAF versus another INSTI-based regimen, co-formulated abacavir, dolutegravir, and lamivudine (ABC/DTG/3TC). Methods: A planned secondary analysis of patient-reported outcomes was conducted for two double-blind, randomized, phase III studies in HIV-1-infected adults comparing B/F/TAF with ABC/DTG/3TC: one in treatment-naïve individuals (GS-US-380-1489, ClinicalTrials.gov NCT02607930) and the other in virologically suppressed participants (GS-US-380-1844, ClinicalTrials.gov NCT02603120). In both studies, the HIV symptoms distress module (HIV-SI) was administered at baseline (BL) and weeks 4, 12, and 48. Responses to each of the 20 items were dichotomized as bothersome or not bothersome. Treatment differences were assessed using unadjusted and adjusted logistic regression models (adjusted for BL HIV-SI count, age, sex, BL Veterans Aging Cohort Study [VACS] Index, medical history of serious mental illness, BL Short Form [SF]-36 Physical Component Summary [PCS], BL SF-36 Mental Component Summary [MCS], and, for virologically suppressed participants only, years since HIV diagnosis). We conducted longitudinal modeling of bothersome symptoms using a generalized mixed model including treatment, time, time-by-treatment, and additional covariates from the adjusted logistic regression model as described above. The Pittsburgh Sleep Quality Index (PSQI) was administered at the same frequency as the HIV-SI, and the total score was dichotomized as good or poor sleep quality. Similar models to those used for HIV-SI were applied, using BL sleep quality and BL SF-36 MCS as covariates. Statistical significance was assessed using p < 0.05. Results: Across both studies, bothersome symptoms were reported by fewer participants on B/F/TAF than those on ABC/DTG/3TC. In treatment-naïve adults, fatigue/loss of energy, nausea/vomiting, dizzy/lightheadedness, and difficulty sleeping were reported significantly less with B/F/TAF at two or more time points. Fatigue and nausea were also significantly less common for those receiving B/F/TAF in longitudinal models. In virologically suppressed participants, nausea/vomiting, sad/down/depressed, nervous/anxious, and poor sleep quality (from the PSQI) were reported significantly less with B/F/TAF at two or more time points, as well as in longitudinal models. Conclusions: B/F/TAF was associated with lower prevalence of bothersome symptoms than ABC/DTG/3TC in both treatment-naïve and virologically suppressed adults

Variations in clinical decision-making between cardiologists and cardiac surgeons; a case for management by multidisciplinary teams?

OBJECTIVE: To assess variations in decisions to revascularise patients with coronary heart disease between general cardiologists, interventional cardiologists and cardiac surgeons DESIGN: Six cases of coronary heart disease were presented at an open meeting in a standard format including clinical details which might influence the decision to revascularise. Clinicians (n = 53) were then asked to vote using an anonymous electronic system for one of 5 treatment options: medical, surgical (CABG), percutaneous coronary intervention (PCI) or initially medical proceeding to revascularisation if symptoms dictated. Each case was then discussed in an open forum following which clinicians were asked to revote. Differences in treatment preference were compared by chi squared test and agreement between groups and between voting rounds compared using Kappa. RESULTS: Surgeons were more likely to choose surgery as a form of treatment (p = 0.034) while interventional cardiologists were more likely to choose PCI (p = 0.056). There were no significant differences between non-interventional and interventional cardiologists (p = 0.13) in their choice of treatment. There was poor agreement between all clinicians in the first round of voting (Kappa 0.26) but this improved to a moderate level of agreement after open discussion for the second vote (Kappa 0.44). The level of agreement among surgeons (0.15) was less than that for cardiologists (0.34) in Round 1, but was similar in Round 2 (0.45 and 0.45 respectively) CONCLUSION: In this case series, there was poor agreement between cardiac clinical specialists in the choice of treatment offered to patients. Open discussion appeared to improve agreement. These results would support the need for decisions to revascularise to be made by a multidisciplinary panel

Survival enhancing indications for coronary artery bypass graft surgery in California

<p>Abstract</p> <p>Background</p> <p>Coronary artery bypass graft (CABG) surgery is performed because of anticipated survival benefit, improvement in quality of life, or both. We performed this study to explore variations in clinical indications for CABG surgery among California hospitals and surgeons.</p> <p>Methods</p> <p>Using California CABG Outcomes Reporting Program data, we classified all isolated CABG cases in 2003–2004 as having "probable survival enhancing indications (SEIs)", "possible SEIs" or "non-SEIs." Patient and hospital characteristics associated with SEIs were examined.</p> <p>Results</p> <p>While 82.9% of CABG were performed for probable SEIs, the range extended from 68% to 96% among hospitals and 51% to 100% among surgeons. SEI rates were higher among patients aged ≥ 65 compared with those aged 18–64 (Adjusted Odds Ratio [AOR] > 1.29 for age groups 65–69, 70–74 and ≥ 75; all p < 0.001), among Asians and Native Americans compared with Caucasians (AOR 1.22 and 1.15, p < 0.001); and among patients with hypertension, peripheral vascular disease, diabetes, cerebrovascular disease and congestive heart failure compared to patients without these conditions (AOR > 1.09, all p < 0.001). Variations in indications for surgery were more strongly related to patient mix than to surgeon or hospital effects (intraclass correlation [ICC] = 0.04 for hospital; ICC = 0.01 for surgeon).</p> <p>Conclusion</p> <p>California hospitals and surgeons vary in their distribution of indications for CABG surgery. Further research is required to identify the roles of market factors, referral patterns, patient preferences, and local clinical culture in producing the observed variations.</p