Diagnostic Accuracy of a Bacterial and Viral Biomarker Point-of-Care Test in the Outpatient Setting.

Importance: Acute respiratory infections (ARIs) account for most outpatient visits. Discriminating bacterial vs viral etiology is a diagnostic challenge with therapeutic implications. Objective: To investigate whether FebriDx, a rapid, point-of-care immunoassay, can differentiate bacterial- from viral-associated host immune response in ARI through measurement of myxovirus resistance protein A (MxA) and C-reactive protein (CRP) from finger-stick blood. Design, Setting, and Participants: This diagnostic study enrolled adults and children who were symptomatic for ARI and individuals in a control group who were asymptomatic between October 2019 and April 2021. Included participants were a convenience sample of patients in outpatient settings (ie, emergency department, urgent care, and primary care) who were symptomatic, aged 1 year or older, and had suspected ARI and fever within 72 hours. Individuals with immunocompromised state and recent vaccine, antibiotics, stroke, surgery, major burn, or myocardial infarction were excluded. Of 1685 individuals assessed for eligibility, 259 individuals declined participation, 718 individuals were excluded, and 708 individuals were enrolled (520 patients with ARI, 170 patients without ARI, and 18 individuals who dropped out). Exposures: Bacterial and viral immunoassay testing was performed using finger-stick blood. Results were read at 10 minutes, and treating clinicians and adjudicators were blinded to results. Main Outcomes and Measures: Bacterial- or viral-associated systemic host response to an ARI as determined by a predefined comparator algorithm with adjudication classified infection etiology. Results: Among 520 participants with ARI (230 male patients [44.2%] and 290 female patients [55.8%]; mean [SD] age, 35.3 [17.7] years), 24 participants with missing laboratory information were classified as unknown (4.6%). Among 496 participants with a final diagnosis, 73 individuals (14.7%) were classified as having a bacterial-associated response, 296 individuals (59.7%) as having a viral-associated response, and 127 individuals (25.6%) as negative by the reference standard. The bacterial and viral test correctly classified 68 of 73 bacterial infections, demonstrating a sensitivity of 93.2% (95% CI, 84.9%-97.0%), specificity of 374 of 423 participants (88.4% [95% CI, 85.0%-91.1%]), positive predictive value (PPV) of 68 of 117 participants (58.1% [95% CI, 49.1%-66.7%), and negative predictive value (NPV) of 374 of 379 participants (98.7% [95% CI, 96.9%-99.4%]).The test correctly classified 208 of 296 viral infections, for a sensitivity of 70.3% (95% CI, 64.8%-75.2%), a specificity of 176 of 200 participants (88.0% [95% CI, 82.8%-91.8%]), a PPV of 208 of 232 participants (89.7% [95% CI, 85.1%-92.9%]), and an NPV of 176 of 264 participants (66.7% [95% CI, 60.8%-72.1%]). Conclusions and Relevance: In this study, a rapid diagnostic test demonstrated diagnostic performance that may inform clinicians when assessing for bacterial or viral etiology of ARI symptoms.

The ventilatory effect of high velocity nasal insufflation compared to non-invasive positive-pressure ventilation in the treatment of hypercapneic respiratory failure: A subgroup analysis.

PURPOSE: Oxygen delivery by high flow nasal cannula (HFNC) is effective in providing respiratory support. HFNC has utility in clearing the extra-thoracic dead space, making it potentially beneficial in the treatment of hypercapnic respiratory failure. This study compares high velocity nasal insufflation (HVNI), a form of HFNC, to non-invasive positive pressure ventilation (NIPPV) in their abilities to provide ventilatory support for patients with hypercapnic respiratory failure. METHODS: This is a pre-defined subgroup analysis from a larger randomized clinical trial of Emergency Department (ED) patients with respiratory failure requiring NIPPV support. Patients were randomized to HVNI or NIPPV. Subgroup selection was done for patients with discharge diagnoses of acute hypercapnic respiratory failure or acute exacerbation of chronic obstructive pulmonary disease. The primary outcomes were change in pCO2 and pH over time. Secondary outcomes were treatment failure and intubation rate. RESULTS: 65 patients with hypercapnic respiratory failure were compared. 34 were randomized to HVNI and 31 to NIPPV. The therapeutic impact on PCO2 and pH over time was similar in each group. The intubation rate was 5.9% in the HVNI group and 16.1% in the NIPPV group (p = 0.244). The rate of treatment failure was 23.5% in the HVNI group and 25.8% in the NIPPV group (p = 1.0). CONCLUSION: HVNI may provide ventilatory support similar to NIPPV in patients presenting with acute hypercapnic respiratory failure, but further study is needed to corroborate these findings.

Ranolazine Reduces Angina in Women with Ischemic Heart Disease: Results of an Open-Label, Multicenter Trial.

Background: Persistent angina is prevalent in women, who more often present with atypical angina, and experience less relief from antianginal therapies. The impact of ranolazine on female-specific angina is unclear. A single-arm, open-label trial was conducted to quantify the impact of ranolazine on angina in women with ischemic heart disease (IHD). Materials and Methods: Women with IHD and ≥2 angina episodes/week were recruited from 30 U.S. sites. Angina and nitroglycerin (NTG) consumption were assessed using patient-reported diaries, Seattle Angina Questionnaire (SAQ), Duke Activity Score Index (DASI), and Women's Ischemia Symptom Questionnaire (WISQ) at baseline and at 4 weeks of treatment with ranolazine 500 mg twice/day. A modified intent-to-treat analysis and parametric or nonparametric methods were used as appropriate to analyze changes. Results: Of 171 women enrolled, mean age was 65 ± 12 years. Of the 159 women included in the analysis, at week 4 compared to baseline, median angina frequency decreased with ranolazine treatment from 5.0 to 1.5 attacks/week and median change from baseline was -3.3 (95% confidence interval [CI]: -4.0 to -2.5; p ≤ 0.0001). Median NTG consumption decreased from 2.0 to 0.0 per week over the 4 weeks and median change was -1.0 (95% CI: -2.0 to -0.5; p < 0.0001). All five SAQ subscales showed mean improvements: physical limitation 9.2 (standard error [SE] 1.5; p < 0.0001), angina stability 31.8 (SE 2.7; p < 0.0001), angina frequency 17.7 (SE 1.6; p < 0.0001), treatment satisfaction 9.3 (SE 1.6; p < 0.0001), and disease perception 2.9 (SE 0.8; p < 0.0001). DASI score also improved 2.9 (SE 0.8; p = 0.0014). WISQ subscales also showed significant improvements (all p < 0.0001). Thirty-one women reported drug-related adverse events (AEs), predominantly mild to moderate gastrointestinal symptoms. Conclusions: Women with IHD treated with ranolazine for 4 weeks experienced less angina measured by SAQ and WISQ. NTG use decreased, physical activity improved, and treatment satisfaction improved. AEs were consistent with prior reports.

Office-Based HE-TUMT Costs Less than Medication over Four Years in Treating Benign Prostatic Hyperplasia.

OBJECTIVES: Benign prostatic hyperplasia (BPH) can cause lower urinary tract symptoms (LUTS). Medications are first line treatment for mild-moderate BPH. Office-based minimally invasive therapies (MITs) are also acceptable early treatment options but comparisons of MIT to medications are limited. MIT may be equally effective and less costly compared to long-term medical therapy. We compared data from a medication trial to pooled data of high-energy transurethral microwave therapy (HE-TUMT) to evaluate differences in outcomes and costs between the modalities. STUDY DESIGN: Covariate-adjusted comparison of treatments from independent clinical trials. MATERIALS AND METHODS: Data from Medical Therapy of Prostatic Symptoms (MTOPS) study arms were compared to Urologix pooled data from seven HE-TUMT studies at 25 centers. Improvements in voiding symptoms and quality of life (QoL) were determined and a repeated measure logistic regression analysis to control for baseline covariates was performed. Cost data were collected using published outcomes, Medicare 2013 national averages, and discount online pharmacy prices. RESULTS: HE-TUMT provided significant improvement in voiding symptoms and QoL compared to all MTOPS arms through two years. At four years, all therapies maintain similar improvements when adjusting for baseline covariates. Four year cumulative costs of HE-TUMT ($3,620) were less than combination medical therapy ($7,200). CONCLUSIONS: HE-TUMT provides better improvement of LUTS compared to medication for two years. At four years, all therapies provide comparable improvement but HE-TUMT is less expensive with better QoL. This suggests that HE-TUMT is an excellent alternative to medical therapy that should be routinely discussed and offered during detailed management of BPH.

Phrenic nerve stimulation for the treatment of central sleep apnea.

OBJECTIVES: The aim of this study was to evaluate chronic, transvenous, unilateral phrenic nerve stimulation to treat central sleep apnea (CSA) in a prospective, multicenter, nonrandomized study. BACKGROUND: CSA occurs predominantly in patients with heart failure and increases the risk for morbidity and mortality. Established therapies for CSA are lacking, and those available are limited by poor patient adherence. METHODS: Fifty-seven patients with CSA underwent baseline polysomnography followed by transvenous phrenic nerve stimulation system implantation and follow-up. Feasibility was assessed by implantation success rate and therapy delivery. Safety was evaluated by monitoring of device- and procedure-related adverse events. Efficacy was evaluated by changes in the apnea-hypopnea index at 3 months. Quality of life at 6 months was evaluated using a sleepiness questionnaire, patient global assessment, and, in patients with heart failure at baseline, the Minnesota Living With Heart Failure Questionnaire. RESULTS: The study met its primary end point, demonstrating a 55% reduction in apnea-hypopnea index from baseline to 3 months (49.5 ± 14.6 episodes/h vs. 22.4 ± 13.6 episodes/h of sleep; p < 0.0001; 95% confidence interval for change: -32.3 to -21.9). Central apnea index, oxygenation, and arousals significantly improved. Favorable effects on quality of life and sleepiness were noted. In patients with heart failure, the Minnesota Living With Heart Failure Questionnaire score significantly improved. Device- or procedure-related serious adverse events occurred in 26% of patients through 6 months post therapy initiation, predominantly due to lead repositioning early in the study. Therapy was well tolerated. Efficacy was maintained at 6 months. CONCLUSIONS: Transvenous, unilateral phrenic nerve stimulation appears safe and effective for treating CSA. These findings should be confirmed in a prospective, randomized, controlled trial. (Chronic Evaluation of Respicardia Therapy; NCT01124370).

Long-term infection outcomes after original antibiotic impregnated inflatable penile prosthesis implants: up to 7.7 years of followup.

PURPOSE: Although some studies suggest that most infections associated with inflatable penile prosthesis implantation develop within year 1 after surgery, device related infections have been reported 5 years after implantation or later and the infection risk with time is not well characterized. We previously reported a statistically significantly lower infection rate for original inflatable penile prostheses impregnated with antibiotic treatment with minocycline and rifampin vs nonimpregnated inflatable penile prostheses at 1-year followup. Long-term data are now available on infection revision after initial implantation of antibiotic impregnated vs nonimpregnated prostheses. MATERIALS AND METHODS: We retrospectively reviewed patient information forms voluntarily filed with the manufacturer after the initial implantation of more than 39,000 inflatable penile prostheses to compare the revision rate due to infection for antibiotic impregnated vs nonimpregnated implants between May 1, 2001 and December 31, 2008. Life table analysis was used to evaluate device survival from revision surgery. RESULTS: On life table survival analysis initial revision events due to infection were significantly less common in the impregnated vs the nonimpregnated group (log rank p <0.0001). At up to 7.7 years of followup 1.1% of 35,737 vs 2.5% of 3,268 men with impregnated vs nonimpregnated implants underwent initial revision due to infection. CONCLUSIONS: To our knowledge this long-term outcome analysis provides the first substantial clinical evidence of a decrease in costly infection related revision using an antibiotic impregnated inflatable penile prosthesis.

Automated left ventricular capture management.

BACKGROUND: The stimulation thresholds of left ventricular (LV) leads tend to be less reliable than conventional leads. Cardiac resynchronization therapy (CRT) requires continuous capture of both ventricles. OBJECTIVE: The purpose of this study is to evaluate a novel algorithm for the automatic measurement of the stimulation threshold of LV leads in cardiac resynchronization systems. METHODS: We enrolled 134 patients from 18 centers who had existing CRT-D systems. Software capable of automatically executing LV threshold measurements was downloaded into the random access memory (RAM) of the device. The threshold was measured by pacing in the left ventricle and analyzing the interventricular conduction sensed in the right ventricle. Automatic LV threshold measurements were collected and compared with manual LV threshold tests at each follow-up visit and using a Holter monitor system that recorded both the surface electrocardiograph (ECG) and continuous telemetry from the device. RESULTS: The proportion of Left Ventricular Capture Management (LVCM) in-office threshold tests within one programming step of the manual threshold test was 99.7% (306/307) with a two-sided 95% confidence interval of (98.2%, 100.0%). The algorithm measured the threshold successfully in 96% and 97% of patients after 1 and 3 months respectively. Holter monitor analysis in a subset of patients revealed accurate performance of the algorithm. CONCLUSION: This study demonstrated that the LVCM algorithm is safe, accurate, and highly reliable. LVCM worked with different types of leads and different lead locations. LVCM was demonstrated to be clinically equivalent to the manual LV threshold test. LVCM offers automatic measurement, output adaptation, and trends of the LV threshold and should result in improved ability to maintain LV capture without sacrificing device longevity.

Value of pacemaker atrial diagnostic data in patients with paroxysmal atrial fibrillation: an opportunity to improve rates of warfarin utilization.

Atrial diagnostic data within implantable devices provide an opportunity to assess the frequency and quantity of atrial fibrillation (AF) episodes (AF burden) and its impact on appropriate warfarin anticoagulation. Cardiologists were given clinical scenarios to review with different types of pacemaker diagnostic data in an elderly patient with risk factors for stroke. AF specific data was associated with increased warfarin utilization, but only at intermediate rates. Potential reasons and clinical implications are discussed.

Predictors of remodeling in the CRT era: influence of mitral regurgitation, BNP, and gender.

BACKGROUND: We analyzed quantitative echocardiographic data from a large heart failure cohort receiving medical and cardiac resynchronization therapy (CRT) to determine baseline predictors of progressive left ventricular (LV) enlargement. METHODS AND RESULTS: Quantitative echocardiograms were obtained at baseline and after 6 months in 776 outpatients with chronic heart failure who participated in MIRACLE (Multicenter InSync Randomized Clinical Evaluation) and MIRACLE-ICD (Multicenter InSync ICD Randomized Clinical Evaluation). We used multivariable regression to determine clinical, therapeutic, and echocardiographic characteristics that predicted a subsequent change in left ventricular end-diastolic volume (LVEDV). Over 6 months, LVEDV increased in 308 (40%) and decreased in 468 (60%) patients. Baseline mitral regurgitation and levels of plasma brain natriuretic peptide (BNP) independently predicted LV enlargement, whereas CRT predicted a decrease in LVEDV (all P < .01). In all models tested, male gender was an independent risk factor for progressive LV enlargement (P < .0001). CONCLUSION: Men show more prominent LV dilation than women in chronic heart failure despite medical and device therapy. Rates of LV remodeling are influenced further by mitral regurgitation, plasma BNP, and CRT. Future studies should take these clinical factors into account when determining the influence of genetic factors and novel therapies on ventricular remodeling in chronic heart failure.