2 Minute Medicine Rewind December 4, 2016

Safety and Efficacy of a Dapivirine Vaginal Ring for HIV Prevention in Women

While prophylactic antiretroviral medication has shown promise in prevention of HIV-1 transmission, treatment adherence has remained low with oral medications requiring precoital or daily use. In this multi-center randomized control phase 3 clinical trial, 1959 healthy HIV-negative sexually active women in South Africa and Uganda were randomized in a 2:1 ratio to receive a dapivirine vaginal ring or placebo to study the rate of HIV-1 seroconversion. The incidence of HIV-1 seroconversion was 31% lower in dapivirine group than placebo (hazard ratio 0.69; 95% CI: 0.49 to 0.99; p=0.04). There was no significant difference in efficacy of dapivirine ring between age groups older or younger than 21 (hazard ratio 0.63 vs 0.85, respectively). Interestingly, the protective effect of the ring was not seen in women 18-21 with a non-statistically significant 15% lower acquisition rate of HIV-1 (95% CI: -54.91to 59.70), while it showed a greater protective effect in older women with a 37% lower acquisition rate of HIV-1 (95% CI: -59.49 to-3.49). This difference was attributed to lower rates of adherence, physiologic differences, and more frequent vaginal or anal sex in women aged 18-21 years.  Dapivirine resistance was similar in dapivirine group compared to placebo (18.2% vs. 16.1%). Serious adverse events occurred more in dapivirine group (2.9% vs 0.9%), but no clear pattern was established. Limitations of the study were variable adherence at two sites, which were excluded in various primary analyses. This study shows that in women over age 21, the dapivirine vaginal ring significantly reduces HIV-1 seroconversion, while those women under 21 do not, primarily due to treatment adherence.

US Emergency Department Visits for Outpatient Adverse Drug Events, 2013-2014

Adverse drug reactions in outpatients have recently garnered considerable attention, especially as outpatients have complex regimens with less medication monitoring than inpatient. In this public health surveillance of 58 emergency Departments (ED), investigators analyzed the National Electronic Injury Surveillance System – Cooperative Adverse Drug Event Surveillance (NEISS-CADES). Based on data from 42585 cases, adverse drug events accounted for 4 ED Visits per 100,000 (95% CI: 3.1to5.0), with 27.3% of events resulting in hospitalization (95% CI: 22.3%to32.4%). Patients aged ³ 65 years made up 34.5% of adverse event ED visits compared to 25.6% in 2005-2006. They also faced the highest hospitalization rates 43.6% (95% CI: 36.6%to50.5%). Anticoagulants, diabetic agents, and antibiotics made up 46.9% of all ED adverse events (95% CI: 44.2%to49.7%). Notably, in patients aged ³ 65 years, 59.9% adverse event ED visits were from anticoagulants, diabetic agents, and opioid analgesics, with 1.8% of events from medications on Beers criteria list. In children aged 0-5 years, antibiotics were the most common cause of events (56.4%), whereas in individuals aged 6-19 years, antibiotics were the most common drug (31.8%) followed by antipsychotics (4.5%). Limitations include use of only ED visits, as many adverse drug reactions occur in other settings, and reporting is dependent on specific ED practices. Overall ED adverse events related to anticoagulants and diabetic agents increased from 2005-2006, while antibiotics related events decreased.

Percutaneous coronary angioplasty versus coronary artery bypass grafting in treatment of unprotected left main stenosis (NOBLE): a prospective, randomised, open-label, non-inferiority trial

Significant advancement in the technology of percutaneous coronary intervention (PCI) has brought into question its non-inferiority compared to the standard of care, coronary artery bypass grafting (CABG)in the treatment of left main coronary artery disease. In this prospective, randomized, open-label, non-inferiority trial, 1201 patients with left main coronary artery disease, with either stable/unstable angina pectoris or non-ST-elevation myocardial infarction, were randomized in 1:1 ratio between PCI and CABG. The 5 year estimates for major adverse cardiac or cerebrovascular events (MACCE) were 29% for PCI and 19% for CABG (Hazard Ratio 1.48; 95% CI: 1.11to 1.96), which exceeds the limit for non-inferiority revealing a significant superiority of CABG over PCI (p= 0.0066). While 1 year MACCE were the same(7% for both groups), 5 year estimates for all-cause mortality was 12% in PCI versus 9% in CABG (HR 1.07; 95% CI: 0.67to1.72; p=0.77). Non-procedural myocardial infarction was higher in PCI group (1% versus 0%; p=0.08), and procedural myocardial infarction rates were similar between groups (5% PCI versus 7% CABG, p=0.52). A higher stroke rate after 30 days was found in the CABG group (Absolute risk difference 0.5%; p=0.04), while 5-year estimate stroke rate was higher in PCI group (5% vs 2% in CABG; 95% CI: 0.93 to 5.48; p=0.073). The major limitation of the study was the change to primary endpoint timing, where 5-year Kaplan-Meier estimates could be influenced by those entering early or late into the study. The study revealed increased rates of non-procedural myocardial infarction, repeat revascularization, and stroke associated with PCI, and should be considered with decided between PCI and CABG in left main stenosis.

Effect of the Goals of Care Intervention for Advanced Dementia

In patients with advanced dementia, goals of care (GOC) are particularly challenging, which can lead to more intensive medical care than desired. In this cluster randomized, single blind trial of 302 nursing-home residents and their family decision makers at 22 nursing homes, participants were randomized to GOC intervention of structured discussion with nursing home providers compared to an attention control method (informational video and usual care planning). The primary outcomes of quality of communication was higher in GOC intervention group (QOC, 6.0 vs 5.6; p=0.05), along with better end-of-life communication (QOC end-of-life subscale, 3.7 vs 3.0; p=0.02). Patient and their families reported a higher goal concordance at 9 months or death with intervention (88.4% vs 71.2%, p=0.001), but did not show differences in concordance at 3 months. Family ratings of satisfaction with care and symptom management did not vary between groups, however more palliative care domains were addressed in the intervention group (5.6 vs 4.7, p=0.02). Residents in the GOC intervention group were less likely to experience hospital transfers (0.078 vs 0.163 transfers per 90 person-days; RR, 0.47; 95% CI, 0.26 to 0.88), without affecting survival (HR 0.76; 95% CI, 0.54 to 1.08; P = 0.13). Limitations include single long-stay population site and thus cannot be generalized to short-stay populations. Although the intervention could be easily replicated in other locations. GOC intervention focused on shared decision making in dementia, while future studies could use various practices to address goals-of-care. The study provides an approach for improved quality of communication and palliative for nursing home residents, along with a reduction in hospital transfers for the advanced dementia patients.

Antiviral Therapy Inhibits Viral Reactivation and Improves Survival after Repeat Hepatectomy for Hepatitis B Virus-Related Recurrent Hepatocellular Carcinoma

High incidence of recurrence of Hepatitis-B Virus (HBV) related hepatocellular carcinoma (HCC) often necessitates repeat hepatectomy, with prior studies suggesting higher HBV DNA serum load associated with increased recurrence rate and shorter survival. In this retrospective study of 481 patients who underwent re-hepatectomy for recurrent intrahepatic HCC, investigators reviewed clinical data of Eastern Hepatobiliary Surgery Hospital in Shanghai, China to assess impact of HBV viral load and use of nucleos(t)ide analog antiviral therapy (AVT) on survival and recurrence. AVT was found to improve long-term outcomes compared to non-AVT in patients with viral loads £ or > 2000 IU/mL, where 5-year re-recurrence rate 69% vs. 81% vs. 96%, respectively, while 5-year recurrence to death survival (RTDS) rate: 47% vs. 27% vs. 17%, respectively (all p ≤ 0.016). 5-year overall survival was better in pre-plus postoperative AVT compared to postoperative AVT alone (83% vs 60%, p = 0.045), although 5-year recurrence and RTDS had insignificant differences (61% vs. 77%, p = 0.102; 50% vs. 44%, p = 0.395). Viral reactivation rates after re-hepatectomy were reduced in preoperative AVT, 5.8% for AVT patients, 16.3% and 16.6% for non-AVT patients with viral level ≤ or >2000 IU/mL, respectively, (p ≤ 0.028). Non-AVT and viral reactivation were found as independent risk factors of overall survival (Hazard Ratios: 1.857 and 1.781), RTDS (2.457 and 1.691), and tumor re-recurrence (1.778 and 1.446), while a viral level >2000 IU/mL also was a significant dependent risk factor for all three outcomes. Limitations include use of only one site, only nucleoside analog drugs, failure of using AVT in all patients early in the study, and lack of information on HBV genotypes in the study. The study provides support for the use of perioperative AVT to improve long-term outcomes in patients undergoing repeat hepatectomy for recurrent HBV HCC.

Image: PD

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