Lloyd D. Fisher

Changes in Brain Natriuretic Peptide and Norepinephrine Over Time and Mortality and Morbidity in the Valsartan Heart Failure Trial (Val-HeFT)

Background—Neurohormones are considered markers of heart failure progression. We examined whether changes in brain natriuretic peptide (BNP) and norepinephrine (NE) over time are associated with corresponding changes in mortality and morbidity in the Valsartan Heart Failure Trial. Methods and Results—Plasma BNP and NE were measured before randomization and during follow-up in ≈4300 patients in the Valsartan Heart Failure Trial. The relation between baseline BNP and NE and all-cause mortality and first morbid event (M&M) was analyzed in subgroups, with values above and below the median, and by quartiles. The change and percent change from baseline to 4 and 12 months in BNP and NE were also analyzed by quartiles for subsequent M&M. Risk ratios for M&M were calculated using a Cox proportional hazard model. Risk ratio of M&M for patients with baseline BNP or NE above the median was significantly higher than that for patients with values below the median. Baseline BNP and NE in quartiles also showed a quartile-dependent increase in M&M. BNP had a stronger association with M&M than NE. Patients with the greatest percent decrease in BNP and NE from baseline to 4 and 12 months had the lowest whereas patients with greatest percent increase in BNP and NE had the highest M&M. Conclusions—Not only are plasma BNP and NE important predictors of heart failure M&M, but changes in these neurohormones over time are associated with corresponding changes in M&M. These data further reinforce their role as significant surrogate markers in HF and underscore the importance of including their measurement in HF trials.

Surrogate end points in heart failure

Because of the increasing number of pharmacologic strategies available for treatment of heart failure (HF), the time has come to reassess the adequacy of end points used to evaluate therapeutic efficacy. Interest in the use of surrogate end points in clinical studies is increasing. A surrogate end point is defined as a measurement that can substitute for a true end point for the purpose of comparing specific interventions or treatments in a clinical trial. A true end point is one that is of clinical importance to the patient (e.g., mortality or quality of life), whereas a surrogate end point is one biologically closer to the disease process (e.g., ejection fraction or left ventricular volume in HF). The prime motivation for the use of a surrogate end point concerns the possible reduction in sample size or trial duration. Such reductions have important cost implications and in some cases may influence trial feasibility. Another, perhaps more important, aspect of measuring surrogate end points is that they increase our understanding of the mechanism of action of drugs and thus may help physicians to take a more enlightened approach in managing their patients. In this article we have analyzed the possible potentials of the surrogate end points in clinical studies of patients with chronic HF. Other uses of possible surrogates are discussed, and the limitations in finding true surrogates are mentioned. At this time we conclude there is no well established surrogate in HF.

Epidemic crack cocaine use linked with epidemics of genital ulcer disease and heterosexual HIV infection in the Bahamas: evidence of impact of prevention and control measures.

Background Epidemic freebase/crack cocaine use began in the Bahamas in 1982, closely followed by epidemics of genital ulcer disease (GUD) and HIV infection. Numbers of new clients receiving ambulatory treatment for cocaine use in Nassau peaked in 1984. Goal To assess interrelations among epidemics of crack use, GUD, and HIV infection. Study Design The study was designed for review and comparison of temporal trends in ambulatory and inpatient treatment of cocaine users and in numbers of cases of sexually transmitted disease (STD) and HIV infection in the Bahamas. A retrospective case–control study of cocaine use and STDs was performed at the Comprehensive Dermatovenereology Clinic in Nassau. Results Ambulatory visits and inpatient admissions for cocaine use peaked in 1984 and 1987, respectively. GUD cases increased 12-fold in the Bahamas from 1983 to the period of 1985–1987 and then declined. At the Comprehensive Dermatovenereology Clinic, gonorrhea cases outnumbered bacterial GUD cases approximately 10:1 in 1982 and 1983, but the latter increased to outnumber gonorrhea cases in 1985 and 1987–1988. Annual HIV seroprevalences at new-problem visits rose from less than 0.3% in 1986 to 12.9% by 1994 and then leveled off. Cocaine use among patients seen with STD from 1985 through 1990 was significantly associated with GUD (odds ratio [OR], 3.3; 95% CI, 2.1–5.1), secondary syphilis (OR 5.5; 95% CI, 2.4–12.6), and HIV infection (OR, 8.1; 95% CI, 4.3–15.2). Conclusions In temporally linked successive epidemics of cocaine use, GUD, and HIV infection, case–control analyses confirmed the association of cocaine use with GUD and with HIV infection. Declining GUD and HIV seroprevalence stabilization followed declines in cocaine use and implementation of syndromic management of GUD, as well as intensified partner-notification efforts.

Internal thoracic artery grafts for the entire heart at a mean of 12 years

BACKGROUND There is consensus today that the long-term results of bypassing the left anterior descending artery with an internal thoracic artery (ITA) graft are superior to those of a saphenous vein graft. Our hypothesis for this study was that three-vessel revascularization with only ITA grafts would also give excellent results. METHODS Using our previously described techniques to enhance the length of ITA grafts by skeletonization and high mediastinal mobilization, we were able to perform tension-free, three-vessel revascularization using only ITA grafts in 125 (83%) of a consecutive series of 150 patients with three-vessel occlusive coronary disease. We followed 100% of these 125 exclusive ITA graft patients (average of 3.9 anastomoses per patient) to their time of death (59; 47.2%) or current living status (66; 52.8%). RESULTS Combined intraoperative graft flows averaged 225 mL/min. Of the 125 patients in this study (average age, 63.5 years), 121 (96.8%) lived beyond 40 days. Of these 121 patients, 55 (45%) died at a mean of 7 years postoperatively and 66 (55%) are still living at a mean of 12.1 years. Of these 121 patients, 112 (93%) had angina at baseline. Of these 112, 92 (85%) were angina free at a mean of 9.1 years postoperatively. Freedom from infarction was 100% at 5 years and 97% at 10 years. Freedom from reintervention was 90% at a mean of 9.8 years. CONCLUSIONS Use of ITA grafts for three-vessel coronary revascularization provides excellent results and is both practical and appropriate for many patients.

Improving Rates of Influenza Vaccination Through Electronic Health Record Portal Messages, Interactive Voice Recognition Calls and Patient-Enabled Electronic Health Record Updates: Protocol for a Randomized Controlled Trial

Background Clinical decision support (CDS), including computerized reminders for providers and patients, can improve health outcomes. CDS promoting influenza vaccination, delivered directly to patients via an electronic health record (EHR) patient portal and interactive voice recognition (IVR) calls, offers an innovative approach to improving patient care. Objective To test the effectiveness of an EHR patient portal and IVR outreach to improve rates of influenza vaccination in a large multispecialty group practice in central Massachusetts. Methods We describe a nonblinded, randomized controlled trial of EHR patient portal messages and IVR calls designed to promote influenza vaccination. In our preparatory phase, we conducted qualitative interviews with patients, providers, and staff to inform development of EHR portal messages with embedded questionnaires and IVR call scripts. We also provided practice-wide education on influenza vaccines to all physicians and staff members, including information on existing vaccine-specific EHR CDS. Outreach will target adult patients who remain unvaccinated for more than 2 months after the start of the influenza season. Using computer-generated randomization and a factorial design, we will assign 20,000 patients who are active users of electronic patient portals to one of the 4 study arms: (1) receipt of a portal message promoting influenza vaccines and offering online appointment scheduling; (2) receipt of an IVR call with similar content but without appointment facilitation; (3) both (1) and (2); or (4) neither (1) nor (2) (usual care). We will randomize patients without electronic portals (10,000 patients) to (1) receipt of IVR call or (2) usual care. Both portal messages and IVR calls promote influenza vaccine completion. Our primary outcome is percentage of eligible patients with influenza vaccines administered at our group practice during the 2014-15 influenza season. Both outreach methods also solicit patient self-report on influenza vaccinations completed outside the clinic or on barriers to influenza vaccination. Self-reported data from both outreach modes will be uploaded into the EHR to increase accuracy of existing provider-directed EHR CDS (vaccine alerts). Results With our proposed sample size and using a factorial design, power calculations using baseline vaccination rate estimates indicated that 4286 participants per arm would give 80% power to detect a 3% improvement in influenza vaccination rates between groups (α=.05; 2-sided). Intention-to-treat unadjusted chi-square analyses will be performed to assess the impact of portal messages, either alone or in combination with the IVR call, on influenza vaccination rates. The project was funded in January 2014. Patient enrollment for the project described here completed in December 2014. Data analysis is currently under way and first results are expected to be submitted for publication in 2016. Conclusions If successful, this study’s intervention may be adapted by other large health care organizations to increase vaccination rates among their eligible patients. ClinicalTrial ClinicalTrials.gov NCT02266277; https://clinicaltrials.gov/ct2/show/NCT02266277 (Archived by WebCite at http://www.webcitation.org/6fbLviHLH).

Improving Rates of Outpatient Influenza Vaccination Through EHR Portal Messages and Interactive Automated Calls: A Randomized Controlled Trial

BackgroundPatient reminders for influenza vaccination, delivered via electronic health record (EHR) patient portal messages and interactive voice response (IVR) calls, offer an innovative approach to improving patient care.ObjectiveTo test the effectiveness of portal and IVR outreach in improving rates of influenza vaccination.DesignRandomized controlled trial of EHR portal messages and IVR calls promoting influenza vaccination.ParticipantsAdults with no documented influenza vaccination 2 months after the start of influenza season (2014–2015).InterventionUsing a factorial design, we assigned 20,000 patients who were active portal users to one of four study arms: (a) receipt of a portal message promoting influenza vaccines, (b) receipt of IVR call with similar content, (c) both a and b, or (d) neither (usual care). We randomized 10,000 non-portal users to receipt of IVR call or usual care. In all intervention arms, information on pneumococcal vaccination was included if the targeted patient was overdue for pneumococcal vaccine.Main MeasuresEHR-documented influenza vaccination during the 2014–2015 influenza season, measured April 2015.Key ResultsAmong portal users, 14.0% (702) of those receiving both portal messages and calls, 13.4% (669) of message recipients, 12.8% (642) of call recipients, and 11.6% (582) of those with usual care received vaccines. On multivariable analysis of portal users, those receiving portal messages alone (OR 1.20, 95% CI 1.06–1.35) or IVR calls alone (OR 1.15 95% CI 1.02–1.30) were more likely than usual care recipients to be vaccinated. Those receiving both messages and calls were also more likely than the usual care group to be vaccinated (ad hoc analysis, using a Bonferroni correction: OR 1.29, 97.5% CI 1.13, 1.48). Among non-portal users, 8.5% of call recipients and 8.6% of usual care recipients received influenza vaccines (p = NS). Pneumococcal vaccination rates showed no significant improvement.ConclusionsOur outreach achieved a small but significant improvement in influenza vaccination rates.Registration: ClinicalTrials.gov Identifier NCT02266277 (https://clinicaltrials.gov/ct2/show/NCT02266277).

Can the Diagnosis of Pelvic Inflammatory Disease be Excluded Without a Bimanual Examination

Now that urine-based tests are available for detection of Chlamydia and gonorrhea, we sought to determine whether history alone could be used to exclude pelvic inflammatory disease (PID) and thus preclude a bimanual examination. The study design was a retrospective chart review. The study population included females aged 15-24 years diagnosed with PID. Outcome measures were documentation of screening symptoms (abdominal pain, dyspareunia, or abnormal vaginal bleeding) in the medical record. Our primary analysis was sensitivity of screening symptoms for identifying patients with PID. At least 1 of the 3 screening symptoms was reported by 93% of the PID group. If absence of all 3 screening symptoms were used as a screening instrument to exclude a bimanual examination, many women with lower genital tract symptoms could be evaluated noninvasively. However, this approach could result in delayed diagnosis of PID in a small number of patients. Before this strategy is adopted, a large prospective study is needed.