2 Minute Medicine Rewind January 30, 2017
A Recombinant Vesicular Stomatitis Virus Ebola Vaccine
The 2014 Ebola virus outbreak lead to 28,000 cases and 11,000 reported deaths and renewed interest in the development of a vaccine for pre-exposure prophylaxis. A vaccine candidate was created based on attenuated, replication-competent, recombinant vesicular stomatitis virus (rVSV), using a glycoprotein from the Zaire strain of Ebola virus (ZEBOV). In this prospective cohort, phase 1, double-blind, placebo-controlled, dose-escalation trial of the rVSV-ZEBOV vaccine, 78 healthy adults were randomized to receive either 3 million, 20 million, or 100 million PFU of the vaccine or placebo to assess safety, immunogenicity, and reactogenicity of the vaccine. 100% of vaccinated volunteers seroconverted by day 28, using ELISA for Ebola Glycoprotein. On first visit after vaccination, all volunteers had vaccine viremia, but was undetectable after day 14 in all vaccine levels tested. On day 14, 80% of 3 million PFU, 95% of 20 million PFU, and 90% of 100 million PFU volunteers had seroconverted, with those receiving a dose of 20 million PFU and 100 million PFU having higher titers than a dose of 3 million PFU (857 and 888 vs 283; p = 0.001 and p < 0.001, respectively). There was no significant difference between mean titer of those in dose group of 20 million versus 100 million. There were no deaths, serious adverse events, or adverse events causing withdrawal from the study. Nor was there an association with vaccine dose and frequency or severity of adverse effects. This vaccine is promising in eliciting an anti-Ebola antibody response, although transient rVSV viremia occurred frequently. The lack of variation between 20 million and 100 million PFU doses suggests the use of 20 million PFU dose, and that a second dose may boost response.
The majority of adults with Type 1 Diabetes use insulin injections, however prior clinical studies have only shown the benefit of continuous glucose monitoring (CGM) in improving glycemic control in patients using an insulin pump compared to self-monitoring blood glucose management. In this randomized clinical trial, 158 randomized participants with Type 1 Diabetes and using insulin injections were randomized in 2:1 to CGM or home blood glucose monitoring 4 times daily to study the effect on change in central-laboratory-measured hemoglobin A1c (HbA1c) from baseline to 24 weeks. By month 6, CGM use was 6 or more days/week for 93% of the participants. The primary outcome, mean reduction from baseline HbA1clevels were 1.1% at 12 weeks and 1.0% at 24 weeks in the CGM group versus 0.5% and 0.4%, respectively, in the control group (repeated-measures model p < 0.001). Adjusted treatment-group difference in mean change in HbA1c level from baseline was –0.6% at 24 weeks (95% CI: –0.8% to –0.3%; p < 0.001). Notably, the median duration of hypoglycemia of less than 70 mg/dL was 43 minutes/d (IQR 27-69) in the CGM group vs 80 minutes/d (IQR, 36-111) in the control group (p = 0.002), which proved favorable in the CGM group in both daytime and nighttime. Patient satisfaction was higher amongst CGM users and there was a greater decrease in HbA1c level during 24 weeks in CGM. This study showed not to be applicable to those younger than 26 years, with HbA1c levels outside range of 7.5% to 9.9%, or to type 2 diabetics who frequently use injectable insulin. As adherence was an excludable factor, patient adherence to CGM could impact results.
The growing number of limited-English proficiency (LEP) Latinos with diabetes provides a challenge to providers who aim to provide cultural competent and effective care; a concern that could be mitigated by care from Spanish-speaking language-concordant primary care physicians (PCPs). This retrospective cohort pre-post, differences-in-differences study of 1605 adult patients, who self-identified as Latino and whose preferred language was Spanish, who switched PCPs from either language-discordant to language-concordant PCP (English to Spanish-speaking PCP) or language-discordant to another language-discordant (English to another English- speaking PCP) to study the effect on glycemic control (HbA1c levels < 8%), poor glycemic control (HbA1c levels> 9%), low-density lipoprotein (LDL) control (LDL < 100mg/dL), and systolic blood pressure (SBP) control (SBP < 140mmHg). A significant net improvement in glycemic and LDL control was found among patients who switched to language-concordant PCPs compared to those patients who continued to have language-discordant PCPs. The prevalence of glycemic control increased by 10% (95% CI: 2% to 17%; P = .01), poor glycemic control decreased by 4% (95% CI: −10% to 2%; p = 0.16) and LDL control increased by 9% (95% CI: 1% to 17%; p = 0.03), after adjusting for secular trends. The change in mean HbA1c was −0.22 (95% CI: −0.45 to 0.01; p = 0.06) in patients who switched to language-concordant PCPs. There was no significant change in SBP control. Surprisingly, there was an increase of 24% in prevalence of good LDL control in patients that switched from language-concordant to language-discordant PCPs (95% CI: 12% to 35%;p < 0.001).There was no decrease in prevalence of control for any outcomes when patients switched PCPs. Ultimately, this longitudinal study revealed the value of facilitating language-concordant care as a strategy for diabetes management in LEP Latinos. In addition, health care centers that provide language-concordant culturally competent care improves patient satisfaction while facilitating communication in their healthcare needs.
Chemotherapy Use and Survival Among Young and Middle-Aged Patients With Colon Cancer
There is variation in the use of aggressive treatment plans for colorectal cancer not entirely explained by patient’s performance status, and in this study, investigators sought to identify age associated trends in the use of post-surgical chemotherapy. Using the U.S. Department of Defense’s Central Cancer Registry and MHS Data Repository, investigators identified 3143 patients with colon adenocarcinoma and compared clinical outcomes by patient age. In this cohort, 671 were young (18 – 49 years), 1599 were middle-aged (50 – 64 years), and 873 were older (65+ years). Young patients were more likely to receive postoperative systemic chemotherapy compared to older patients across all tumor stages with OR 7.98 (95% CI: 2.88-22.11), 4.22 (95% CI: 2.23-7.98), 2.30 (95% CI: 1.01-5.22), and 2.43 (95% CI: 1.26-4.70) for tumors of stages I, II, III, and IV, respectively. Middle-aged patients were also more likely to receive this scheme of chemotherapy compared to older patients,with stage I (OR, 5.04; 95% CI: 2.30-11.05) and stage II (OR, 2.42; 95% CI: 1.58-3.72) disease. There was no significant difference in survival between age groups in patients who received surgery and postoperative systemic chemotherapy, as the 95% CIs of hazard ratios included 1 when comparing younger and middle-aged patients to older patients. Nor were the hazard ratios lower in the surgery with adjuvant chemotherapy group compared to surgery alone ratios. Limitations included use of all-cause mortality rather than disease specific, although comorbidities were adjusted for. Ultimately, this study suggests that there is a possible overuse of postoperative systemic chemotherapy in younger patients with colon cancer with no appreciable improvement in survival. The notable impact of chemotherapy on the patient’s quality of life, along with its economic impacts, must be taken into account in younger patients.
Liver transaminases, notably alanine transaminase (ALT) and aspartate aminotransferase (AST), are commonly tested and have been of increased interest in predicting cardiac-related mortality risk and morbidity. Few studies have assessed the association of hepatic dysfunction and mortality in patients with ST-segments elevation myocardial infarction (STEMI). This retrospective cohort study of 2417 consecutive STEMI patients with no preexisting liver disease and who were treated with primary percutaneous coronary intervention (PCI) compared baseline serum transaminases levels with the outcomes of all-cause mortality in the first month and at 2 years following PCI. All-cause mortality significantly increased in patients with both AST and ALT ≥95th percentile (p < 0.001). The odds ratio of all-cause mortality at 2 years for participants with ALT ≥95th percentile was 5.370 (95% CI: 2.899–9.948) unadjusted, 7.034 (95% CI: 3.718–13.307) after adjustment for age and gender and 1.051 (95% CI: 0.302–3.652) after adjustment for all covariables. For participants with AST ≥95th percentile, the unadjusted OR was 5.370 (95% CI 2.899–9.948) and 5.699 (95% CI 3.030–10.718) after adjustment for age and gender and 1.796 (95% CI: 0.588–5.481) after adjustment for all covariables. There was significant correlation between elevated liver transaminases and Killip classification (p < 0.001 for ALT;p < 0.001 for AST), cardiac troponin I (P = 0.002 for ALT; P < 0.001 for AST), infarct-related coronary artery (p = 0.036 for ALT; p = 0.011 for AST), and pre-thrombolysis-in-myocardial-infarction (pre-TIMI) flow (p < 0.001 for ALT and AST). This study is the first to suggest the predictive value of liver transaminases on mortality in STEMI patients following PCI: and reveals its clinical value. Although, these factors are non-specific, liver transaminases could be useful predictive markers in STEMI patients with extremely high AST and ALT.
Image: PD
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