Prospective Evaluation of the Frequency and Severity of Symptoms in Lyme Disease Patients With Erythema Migrans Compared With Matched Controls at Baseline, 6 Months, and 12 Months.

BACKGROUND: Erythema migrans is the most common clinical manifestation of Lyme disease. Despite antibiotic therapy, typically at least 10% of adult patients with erythema migrans experience persistence of at least 1 subjective symptom for ≥6 months (posttreatment Lyme disease symptoms [PTLDS]). METHODS: This study was designed to determine whether the frequency and severity (based on a visual analogue scale) of 12 particular symptoms in patients with erythema migrans (n = 52) differed from matched control subjects (n = 104) followed prospectively for 12 months. RESULTS: At baseline, patients with Lyme disease were more likely than controls to have at least 1 symptom (P = .006). Among symptomatic subjects, Lyme disease patients had a higher mean number of symptoms (P < .001) and a higher mean total symptom severity score (P < .001). At both 6 and 12 months, however, there were no significant differences for these variables and no significant differences in the frequency or severity of any of the 12 individual symptoms assessed. However, 10 patients were clinically assessed as having possible PTLDS. CONCLUSIONS: Patients with erythema migrans were more likely than matched control subjects to be symptomatic at baseline with a greater symptom severity score, but this was not found at ≥6 months. Use of symptom survey data alone, however, was less likely to identify patients with possible PTLDS compared with individual clinical assessments. Because it is very challenging to be certain that the presence of long-term symptoms in a particular patient is correctly attributable to having had Lyme disease, an objective biomarker would be highly desirable.

Patients with Erythema Migrans: Characterizing the Impact of Initiation of Antibiotic Therapy Prior to Study Enrollment.

Erythema migrans is the most common clinical manifestation of Lyme disease, with concomitant subjective symptoms occurring in ∼65% of cases in the United States. We evaluated the impact of having been started on antibiotic treatment before study enrollment on 12 particular symptoms for 38 subjects with erythema migrans versus 52 untreated subjects. There were no significant differences in the frequency of having at least one symptom or in the symptom severity score on study entry. However, the frequency of having at least one symptom was significantly greater for those who had received <7 days of antibiotic treatment than for those who had been treated for ≥7 days (23/24 [95.8%] versus 8/14 [57.1%], P = 0.006). In addition, the percentage of subjects who were males was significantly lower among the group on treatment than among the untreated study subjects (13/38 [34.2%] versus 34/52 [65.4%], P = 0.005). In conclusion, based on these findings, combining untreated and treated groups of patients with erythema migrans for research study analyses may have limitations and, depending on the study objectives, might not be preferred. Additional studies are warranted to better understand the day-to-day impact of antibiotic treatment on the presence, type, and severity of symptoms in patients with early Lyme disease.

Combination of Foley and prostaglandins versus Foley and oxytocin for cervical ripening: a network meta-analysis.

BACKGROUND: Trial and meta-analysis data revealed a reduction in time to delivery for Foley and prostaglandins or Foley and oxytocin vs Foley alone. However, there are limited data for the comparison of the 2 combination methods against each other. OBJECTIVE: This study aimed to determine whether Foley and prostaglandins or Foley and oxytocin decrease the time to vaginal delivery using a network meta-analysis. STUDY DESIGN: A network meta-analysis (PROSPERO CRD42018081948) was performed comparing Foley and prostaglandins (prostaglandin E1 or prostaglandin E2) vs Foley and oxytocin for cervical ripening. Foley alone and prostaglandins alone were used as nodes for indirect comparison. Database searches were performed from inception to March 2020 with data abstracted from published manuscripts. Eligibility criteria included randomized trials comparing Foley and oxytocin with Foley and prostaglandins (misoprostol or dinoprostone). Trials that compared Foley catheter or prostaglandins with a combination of Foley and prostaglandins or Foley and concurrent oxytocin were also included. Nulliparous and multiparous women were analyzed together. Foley catheters of any catheter material or size and >24 weeks' gestational age with a live fetus were included. Quasi-randomized, cohorts, and other combination methods for cervical ripening were not included. Prostaglandin E1 and prostaglandin E2 combined methods were analyzed separately in a planned subanalysis. The primary outcome was the mean time from induction to vaginal delivery in hours. Secondary outcomes included time from induction to delivery, delivery within 24 hours, cesarean delivery, chorioamnionitis, endometritis, epidural use, tachysystole, postpartum hemorrhage, meconium, neonatal intensive care unit admission, and 5-minute appearance, pulse, grimace, activity, and respiration score of <7. Data were analyzed as a network meta-analysis using multivariate meta-regression. RESULTS: A total of 30 randomized controlled trials with a total of 6465 women were considered eligible for inclusion in this network meta-analysis. When compared with Foley alone, the use of Foley-oxytocin reduced the time to vaginal delivery by 4.2 hours (mean duration, -4.2 hours; 95% confidence interval, -6.5 to -1.9). Foley-prostaglandins reduced the time to vaginal delivery compared with Foley but did not meet statistical significance (mean duration, -2.9 hours; 95% confidence interval, -5.7 to 0.0; P=.05). When compared head-to-head, there was no difference in the time to vaginal delivery between Foley-prostaglandins and Foley-oxytocin (mean duration, 1.3 hours; 95% confidence interval, -2.0 to 4.7). There was no difference in the rate of cesarean delivery, chorioamnionitis, epidural, tachysystole, postpartum hemorrhage, meconium, neonatal intensive care unit admissions, or 5-minute appearance, pulse, grimace, activity, and respiration score of <7 for Foley-prostaglandins vs Foley-oxytocin, although the rate of endometritis was high for Foley-prostaglandins. In the subanalysis by prostaglandin type, there was no difference in the time to vaginal delivery for Foley-misoprostol vs Foley-dinoprostone vs Foley-oxytocin. However, Foley-dinoprostone had a definite trend toward longer time to all deliveries compared with that of both Foley-misoprostol and Foley-oxytocin (P=.05). CONCLUSION: Time to vaginal delivery was similar when comparing Foley with combined misoprostol, combined dinoprostone, and combined oxytocin. Dinoprostone comparisons are limited by small sample size but suggest longer time to delivery compared with Foley and misoprostol or oxytocin. No significant differences were observed in maternal or neonatal adverse events except for endometritis, but this was limited by the sample size, varied reporting of studies used in the indirect comparisons, and definitions of infectious morbidity use in the studies.

The Benefits of Oral Rehydration on Orthostatic Intolerance in Children with Postural Tachycardia Syndrome.

OBJECTIVE: To evaluate whether equal volumes of oral rehydration solution (ORS) or intravenous (IV) saline provide similar improvements in cardiovascular status during controlled orthostatic challenge when administered to subjects with postural tachycardia syndrome (POTS) with orthostatic intolerance. STUDY DESIGN: We studied the neurovascular response to fluid loading during orthostatic stress using lower body negative pressure (LBNP) in 10 subjects with POTS with orthostatic intolerance and 15 controls, and on subsequent days before and 1 hour after IV saline infusion or ingestion of ORS. RESULTS: Subjects with POTS exhibited reduced tolerance to LBNP (P < .0001) compared with controls (Orthostatic Index of 35 715 ± 3469 vs 93 980 ± 7977, respectively). In POTS, following ORS but not saline infusion, cerebral blood flow velocity (CBFv) was significantly higher than that with no treatment, at -45 mm Hg (P < .0005). Although fluid loading did not confer any advantage in controls, subjects with POTS experienced a significant improvement in orthostatic tolerance following both saline infusion (100 ± 9.7 vs 134.5 ± 17.4; P < .05) and ORS (100 ± 9.7 vs 155.6 ± 15.7; P < .001) when evaluated by normalized orthostatic index (P < .001, compared with untreated baseline). CONCLUSIONS: Maintenance of CBFv may have resulted in the improved short-term orthostatic tolerance exhibited by the subjects with POTS following ORS administration. ORS is a convenient, safe, and effective therapy for short-term relief of orthostatic intolerance.

Evaluation of the National Healthcare Safety Network Hemovigilance Module for transfusion-related adverse reactions in the United States.

INTRODUCTION: The National Healthcare Safety Network (NHSN) Hemovigilance Module (HM) collects data on the frequency, severity, and imputability of transfusion-associated adverse events. These events contribute to significant morbidity and mortality among transfusion patients. We report results from the first systematic assessment of eight attributes of the HM. MATERIALS AND METHODS: Standard methods were used to assess the HM. Evaluation data included training materials, system modification history, and facility survey information. A concordance analysis was performed using data from the Baystate Medical Center's (Springfield, MA) electronic transfusion reporting system. RESULTS: In 2016, system representativeness remained low, with 6% (277 of 4690) of acute care facilities across 43 jurisdictions enrolled in the HM. In 2016, 48% (2147 of 4453) and 89% (3969 of 4,453) of adverse reactions were reported within 30 and 90 days of the reaction date, respectively, compared to 21% (109 of 511) and 56% (284 of 511) in 2010, demonstrating improved reporting timeliness. Data quality from most reactions was adequate, with 10% (45 of 442) misclassified transfusion-associated circulatory overload reactions, and no incomplete transfusion-transmitted infection data reported from 2010 to 2013. When compared to the Baystate system to assess concordance, 43% (24 of 56) of NHSN-reported febrile reactions were captured in both systems (unweighted kappa value, 0.47; confidence interval, 0.33-0.61). CONCLUSION: Since the 2010 HM pilot, improvements have led to enhanced simplicity, timeliness, and strengthened data quality. The HM serves an important and unique role despite incomplete adoption nationwide. Facility efforts to track and prevent transfusion-associated adverse events through systems like the NHSN HM are a key step toward improving transfusion safety in the United States.

Azithromycin vs erythromycin for the management of preterm premature rupture of membranes.

BACKGROUND: Preterm premature rupture of membranes complicates 2-3% of pregnancies. Many institutions have advocated for the use of azithromycin instead of erythromycin. This is secondary to national shortages of erythromycin, ease of administration, better side effect profile, and decreased cost of azithromycin as compared with erythromycin. OBJECTIVE: The objective of the study was to evaluate whether there are differences in the latency from preterm premature rupture of membranes to delivery in patients treated with different dosing regimens of azithromycin vs erythromycin. STUDY DESIGN: This is a multicenter, retrospective cohort of women with singleton pregnancies with confirmed rupture of membranes between 230 and 336 weeks from January 2010 to June 2015. Patients were excluded if there was a contraindication to expectant management of preterm premature rupture of membranes. Patients received 1 of 4 antibiotic regimens: (1) azithromycin 1000 mg per os once (azithromycin 1 day group); (2) azithromycin 500 mg per os once, followed by azithromycin 250 mg per os daily for 4 days (azithromycin 5 day group); (3) azithromycin 500 mg intravenously for 2 days, followed by azithromycin 500 mg per os daily for 5 days (azithromycin 7 day group); or (4) erythromycin intravenously for 2 days followed by erythromycin per os for 5 days (erythromycin group). The choice of macrolide was based on institutional policy and/or availability of antibiotics at the time of admission. In addition, all patients received ampicillin intravenously for 2 days followed by amoxicillin per os for 5 days. Primary outcome was latency from diagnosis of rupture of membranes to delivery. Secondary outcomes included clinical and histopathological chorioamnionitis and neonatal outcomes. RESULTS: Four hundred fifty-three patients who met inclusion criteria were identified. Seventy-eight patients received azithromycin for 1 day, 191 patients received azithromycin for 5 days, 52 patients received azithromycin for 7 days, and 132 patients received erythromycin. Women who received the 5 day regimen were younger and less likely to be non-African American, have hypertension, have sexually transmitted infection, or experienced substance abuse. There was no statistical difference in median latency time of azithromycin 1 day (4.9 days, 95% confidence interval, 3.3-6.4), azithromycin 5 days (5.0, 95% confidence interval, 3.9-6.1), or azithromycin 7 days (4.9 days, 95% confidence interval, 2.8-7.0) when compared with erythromycin (5.1 days, 95% confidence interval, 3.9-6.4) after adjusting for demographic variables (P = .99). Clinical chorioamnionitis was not different between groups in the adjusted model. Respiratory distress syndrome was increased in the azithromycin 5 day group vs azithromycin 1 day vs erythromycin (44% vs. 29% and 29%, P = .005, respectively). CONCLUSION: There was no difference in latency to delivery, incidence of chorioamnionitis, or neonatal outcomes when comparing different dosing regimens of the azithromycin with erythromycin, with the exception of respiratory distress syndrome being more common in the 5 day azithromycin group. Azithromycin could be considered as an alternative to erythromycin in the expectant management of preterm premature rupture of membranes if erythromycin is unavailable or contraindicated. There appears to be no additional benefit to an extended course of azithromycin beyond the single-day dosing, but final recommendations on dosing strategies should rely on clinical trials.

Supplemental thiamine for the treatment of acute heart failure syndrome: a randomized controlled trial.

BACKGROUND: The purpose of this pilot study was to determine if a definitive clinical trial of thiamine supplementation was warranted in patients with acute heart failure. We hypothesized that thiamine, when added to standard of care, would improve dyspnea (primary outcome) in hospitalized patients with acute heart failure. Peak expiratory flow rate, type B natriuretic peptide, free fatty acids, glucose, hospital length of stay, as well as 30-day rehospitalization and mortality were pre-planned secondary outcome measures. METHODS: This was a blinded experimental study at two urban academic hospitals. Consecutive patients admitted from the Emergency Department with a primary diagnosis of acute heart failure were recruited over 2 years. Patients on a daily dietary supplement were excluded. Randomization was stratified by type B natriuretic peptide and diabetes medication categories. Subjects received study drug (100 mg thiamine or placebo) in the evening of their first and second day. Outcome measures were obtained 8 h after study drug infusion. Dyspnea was measured on a 100-mm visual analog scale sitting up on oxygen, sitting up off oxygen, and lying supine off oxygen with 0 indicating no dyspnea. Data were analyzed using mixed-models as well as linear, negative binomial and logistic regression models to assess the impact of group on outcome measures. RESULTS: Of 130 subjects randomized, 118 had evaluable data (55 in the control and 63 in the treatment groups), 89% in both groups were adjudicated to have primarily AHF. Thiamine values increased significantly in the treatment group and were unchanged in the control group. One patient had thiamine deficiency. Only dyspnea measured sitting upright on oxygen differed significantly by group over time. No change was found for the other measures of dyspnea and all of the secondary measures. CONCLUSIONS: In mild-moderate acute heart failure patients without thiamine deficiency, a standard dosing regimen of thiamine did not improve dyspnea, biomarkers, or other clinical parameters. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00680706 , May 20, 2008 (retrospectively registered).

A Hospitalist-Led Team to Manage Patient Boarding in the Emergency Department: Impact on Hospital Length of Stay and Cost.

OBJECTIVES: Admitted patients boarding in the emergency department (ED) while awaiting inpatient beds represent a bottleneck in patient flow. We sought to examine the impact on patient flow and potential for cost savings by an active management of boarded ED medical admissions by a hospitalist-led team, which included a hospitalist, an advanced practitioner, and a case manager. METHODS: This was a retrospectively conducted analysis of a quality improvement pilot intervention implemented at a large tertiary center. We analyzed patients admitted under observation status between April 1, 2016 and June 30, 2016. We calculated the difference for length of stay (in hours) and direct cost between patients in the intervention group and a usual care group from a similar time period in the prior year matched on the all patients refined-diagnosis related groups (APR-DRG) and severity of illness (SOI) level. RESULTS: One hundred seventy-five observation patients were managed by the hospitalist team during the 3-month pilot period. This group had an average hospital stay of 26.0 hours compared with 29.7 hours in the usual care group. Direct costs resulted in the following results: average cost for the intervention patient group $1452 (±$775) versus $2524 (±$894) group, for an average savings of $1072 (P < 0.001), with a total estimated direct cost savings of $187,660. CONCLUSIONS: Active management of ED boarding patients by a hospitalist-led team is feasible and can lead to hospital cost savings and decrease in hospital stay. The findings from this pilot resulted in a decision to make the ED hospitalist-led team permanent in our institution. The evaluation of the program may help other hospitals to decide whether this intervention is worth pursuing in their own organization.

Apparent Mineralocorticoid Excess in the Pediatric Population: Report of a Novel Pathogenic Variant of the 11ß-HSD2 Gene and Systematic Review of the Literature.

Apparent mineralocorticoid excess (AME) is a rare inherited disorder caused by pathogenic variants in the 11ß-HSD2 gene resulting in a deficiency of the 11ß-hydroxysteroid dehydrogenase type 2 (11ß-HSD2) enzyme catalyzing the conversion of cortisol to its inactive metabolite, cortisone. Impaired cortisol metabolism results in a mineralocorticoid excess-like state presenting as low renin, low aldosterone hypertension (HTN) and hypokalemia. Typically, AME is diagnosed in early childhood. Medical treatment to control HTN and hypokalemia often is only partially successful. Herein, we systematically review previously reported AME cases in the pediatric population, focusing on presentation, genetic basis, treatment and outcomes. We demonstrate a negative correlation between the ratio of urinary cortisol to cortisone metabolites, and the age of diagnosis (p=0.0051). We also report a novel causative variant of the 11ß-HSD2 gene and propose an explanation for failure of the mineralocorticoid receptor antogonist, spironolactone, to control hypertension and hypokalemia in a subgroup of patients.

Enhancing hemotherapy safety through pertinent diagnostic testing and electronic "provisional diagnosis" reporting: expanding roles for blood bank technologists in biovigilance and patient safety.

BACKGROUND: Suspected transfusion reaction (STR) investigations are foundational for biovigilance. Diagnostic evaluations performed by blood banks may prolong turnaround times (TATs) for final STR results reporting. We identified a quality improvement opportunity using diagnostic testing reflex algorithms and our hospital's patient electronic health record to enhance TATs regarding one aspect of STR results reporting. STUDY DESIGN AND METHODS: We conducted a descriptive quality improvement study of reported STR cases investigated by our hospital's blood bank from March 1, 2014, to December 31, 2016, using data obtained from consult reports/quality improvement databases examining the number and types of diagnostic algorithm reflex activations performed and the TATs for an electronic provisional diagnosis reporting (PDXR) related to them. RESULTS: A total of 461 STR events occurred during the study interval, of which 150 involved no reflex testing. In the remainder of cases (n = 311), a total of 448 reflex activations occurred. In those cases in which PDXR occurred (n = 446), the median PDXR TAT during the first month of implementation was 325 minutes, which progressively decreased to 70 minutes or less approximately 1 year after implementation. By the last quarter of 2015, median TATs were 60 minutes or less in length, where they remained for the duration of the study. CONCLUSION: Technologists using targeted diagnostic reflex arcs to expedite laboratory testing along with STR electronic PDXR improve communication and timely results/information dissemination, potentially aiding bedside hemotherapy-related clinical decision making.

Key Players in Key Roles: The Baystate Patient Progress Initiative to Improve Emergency Department Efficiency and Productivity.

BACKGROUND: The percentage of patients who leave the emergency department without being seen by a provider is a measure of efficiency and presents risk-management concerns. The number of patients actually "seen" by a provider is a measure of productivity. The opening of our new emergency department in December 2012, resulted in increases in both demand and the percentage of patients who left without being seen. Operational nursing leadership managed ED patient flow, but the structure was loosely organized on an ad hoc basis. METHODS: Operational nursing leadership roles were re-assigned to personnel with management aptitude and interest. The charge nurse coordinated care throughout all sections (pods) of the department while the pod lead nurse coordinated care in each pod. The flow coordinator nurse accepted transfers and emergency medical services arrivals. Nursing and physician staffing remained unchanged, and measures were calculated over a 3-year period (December 3, 2012, to December 2, 2015). The number of patients seen per day was analyzed using simple linear regression. The percentage of patients who left without being seen was analyzed using fractional logistic regression; P< 0.05 was considered statistically significant. RESULTS: The weekly mean number of patients seen per day rose 13% from 265 to 299 patients. The weekly mean percentage of patients who left without being seen declined 45% from 8.2% to 4.5%. The regression lines for both measures were significant at P < 0.001. CONCLUSION: Measures of efficiency and productivity can be improved significantly with a dedicated operational nursing leadership structure without adding nursing or physician staffing.

Oscillatory lower body negative pressure impairs working memory task-related functional hyperemia in healthy volunteers.

Neurovascular coupling (NVC) describes the link between an increase in task-related neural activity and increased cerebral blood flow denoted "functional hyperemia." We previously showed induced cerebral blood flow oscillations suppressed functional hyperemia; conversely functional hyperemia also suppressed cerebral blood flow oscillations. We used lower body negative pressure (OLBNP) oscillations to force oscillations in middle cerebral artery cerebral blood flow velocity (CBFv). Here, we used N-back testing, an intellectual memory challenge as a neural activation task, to test the hypothesis that OLBNP-induced oscillatory cerebral blood flow can reduce functional hyperemia and NVC produced by a working memory task and can interfere with working memory. We used OLBNP (-30 mmHg) at 0.03, 0.05, and 0.10 Hz and measured spectral power of CBFv at all frequencies. Neither OLBNP nor N-back, alone or combined, affected hemodynamic parameters. 2-Back power and OLBNP individually were compared with 2-back power during OLBNP. 2-Back alone produced a narrow band increase in oscillatory arterial pressure (OAP) and oscillatory cerebral blood flow power centered at 0.0083 Hz. Functional hyperemia in response to 2-back was reduced to near baseline and 2-back memory performance was decreased by 0.03-, 0.05-, and 0.10-Hz OLBNP. OLBNP alone produced increased oscillatory power at frequencies of oscillation not suppressed by added 2-back. However, 2-back preceding OLBNP suppressed OLBNP power. OLBNP-driven oscillatory CBFv blunts NVC and memory performance, while memory task reciprocally interfered with forced CBFv oscillations. This shows that induced cerebral blood flow oscillations suppress functional hyperemia and functional hyperemia suppresses cerebral blood flow oscillations.NEW & NOTEWORTHY We show that induced cerebral blood flow oscillations suppress functional hyperemia produced by a working memory task as well as memory task performance. We conclude that oscillatory cerebral blood flow produces causal reductions of memory task neurovascular coupling and memory task performance. Reductions of functional hyperemia are constrained by autoregulation.

Comparison of antithrombotic agents during urgent percutaneous coronary intervention following thrombolytic therapy: A retrospective cohort study.

BACKGROUND: The optimal antithrombotic regimen for urgent percutaneous coronary interventions (PCI) following thrombolytic therapy for ST segment myocardial infarction (STEMI) is currently unknown. METHODS: We performed a retrospective analysis of all patients referred to our institution from January 2005 to July 2014 who underwent urgent PCI within 24 hr after receiving thrombolytic therapy. The patients were divided into three cohorts based on the anticoagulation strategy during PCI-bivalirudin, heparin alone or heparin plus Glycoprotein IIb/IIIa inhibitor (GPI). The primary end point of major adverse cardiovascular events (MACE) was defined as a composite of inpatient death, myocardial infarction (MI) and stroke. Net adverse clinical events (NACE) were defined as a combination of MACE plus major bleeding complications. Univariable, multivariable and propensity-weighted modeling were used to compare MACE and NACE between the three treatment groups. RESULTS: A total of 695 patients met the inclusion criteria during the study period. In the univariable analysis, there was no significant difference treatment in MACE between the three groups (Bivalirudin: 1.2% vs. Heparin + GPI: 4.4%; Heparin alone: 2.7%, P = 0.11). In the reduced logistic regression model, compared to bivalirudin, the odds of NACE was significantly higher with heparin alone (OR: 3.58, 95% CI: 1.21, 10.54, P = 0.02) or with heparin plus GPI (OR: 9.0, 95% CI: 2.83, 28.64, P <0.001). CONCLUSION: In STEMI patients undergoing PCI within 24 hr after thrombolytic therapy, bivalirudin was associated with a strong trend toward reduced bleeding complications as compared to heparin alone or heparin plus GPI. The optimal antithrombotic regiment for urgent PCI following thrombolytic therapy is currently unknown. Our study demonstrated that use of bivalirudin during PCI following thrombolytic therapy is associated with a trend toward reduced bleeding complications compared to heparin alone or heparin plus GPI. Large randomized trials of adjunctive anticoagulation during PCI in this complex post-thrombolytic population are warranted. © 2017 Wiley Periodicals, Inc.

Oscillatory lower body negative pressure impairs task related functional hyperemia in healthy volunteers.

Neurovascular coupling refers to the link between an increase in neural activity in response to a task and an increase in cerebral blood flow denoted "functional hyperemia." Recent work on postural tachycardia syndrome indicated that increased oscillatory cerebral blood flow velocity (CBFv) was associated with reduced functional hyperemia. We hypothesized that a reduction in functional hyperemia could be causally produced in healthy volunteers by using oscillations in lower body negative pressure (OLBNP) to force oscillations in CBFv. CBFv was measured by transcranial Doppler ultrasound of the left middle cerebral artery. We used passive arm flexion applied during eight periodic 60-s flexion/60-s relaxation epochs to produce 120-s periodic changes in functional hyperemia (at 0.0083 Hz). We used -30 mmHg of OLBNP at 0.03, 0.05, and 0.10 Hz, the range for cerebral autoregulation, and measured spectral power of CBFv at all frequencies. Arm flexion power performed without OLBNP was compared with arm flexion power during OLBNP. OLBNP power performed in isolation was compared with power during OLBNP plus arm flexion. Cerebral flow velocity oscillations at 0.05 Hz reduced and at 0.10 Hz eliminated functional hyperemia, while 0.03 Hz did not reach significance. In contrast, arm flexion reduced OLBNP-induced oscillatory power at all frequencies. The interactions between OLBNP-driven CBFv oscillations and arm flexion-driven CBFv oscillations are reciprocal. Thus induced cerebral blood flow oscillations suppress functional hyperemia, and functional hyperemia suppresses cerebral blood flow oscillations. We conclude that oscillatory cerebral blood flow produces a causal reduction of functional hyperemia.

Can One Predict Resolution of Neonatal Hyperthyrotropinemia?

OBJECTIVE: To identify predictors of transience vs permanence of neonatal hyperthyrotropinemia. We hypothesized that infants with greater severity of perinatal stress are more likely to have transient thyrotropin elevations. STUDY DESIGN: We retrospectively studied infants diagnosed with hyperthyrotropinemia between 2002 and 2014, following them for up to 12 years after diagnosis. Patients were divided into 3 groups: transient hyperthyrotropinemia (treatment was never prescribed), transient congenital hypothyroidism (treatment started but discontinued), and permanent congenital hypothyroidism (withdrawal unsuccessful or not attempted). We performed univariate and multiple logistic regression analyses, including and excluding infants with maternal thyroid disease. RESULTS: We included 76 infants, gestational age mean (±SD) 34.2 (±5.7) weeks, evaluated for hyperthyrotropinemia. Thirty-five (46%) were never treated, and 41 (54%) received levothyroxine. Of the treated patients, 16 successfully discontinued levothyroxine, and for 25 withdrawal either failed or was not attempted. We found that male patients were almost 5 times more likely than female patients to have transient neonatal hyperthyrotropinemia (OR 4.85; 95% CI 1.53-15.37). We documented greater maternal age (31.5 ± 5.48 years vs 26 ± 6.76 years, mean ± SD, P = .02), greater rate of cesarean delivery (86.7% vs 54.2%; P = .036), and retinopathy of prematurity (37.5% vs 8%; P = .02) in the group with transient congenital hypothyroidism vs the group with permanent congenital hypothyroidism. CONCLUSION: The results show transience of neonatal thyrotropin elevations in a majority of patients and suggest a possible association of hyperthyrotropinemia with maternal and perinatal risk factors.

Ambulatory Morning Report: A Case-Based Method of Teaching EBM Through Experiential Learning.

OBJECTIVES: Evidence-based medicine (EBM) skills are important to daily practice, but residents generally feel unskilled incorporating EBM into practice. The Kolb experiential learning theory, as applied to curricular planning, offers a unique methodology to help learners build an EBM skill set based on clinical experiences. We sought to blend the learner-centered, case-based merits of the morning report with an experientially based EBM curriculum. We describe and evaluate a patient-centered ambulatory morning report combining the User's Guides to the Medical Literature approach to EBM and experiential learning theory in the internal medicine department at Baystate Medical Center. METHODS: The Kolb experiential learning theory postulates that experience transforms knowledge; within that premise we designed a curriculum to build EBM skills incorporating residents' patient encounters. By developing structured clinical questions based on recent clinical problems, residents activate prior knowledge. Residents acquire new knowledge through selection and evaluation of an article that addresses the structured clinical questions. Residents then apply and use new knowledge in future patient encounters. RESULTS: To assess the curriculum, we designed an 18-question EBM test, which addressed applied knowledge and EBM skills based on the User's Guides approach. Of the 66 residents who could participate in the curriculum, 61 (92%) completed the test. There was a modest improvement in EBM knowledge, primarily during the first year of training. CONCLUSIONS: Our experiential curriculum teaches EBM skills essential to clinical practice. The curriculum differs from traditional EBM curricula in that ours blends experiential learning with an EBM skill set; learners use new knowledge in real time.

Long-term Assessment of Post-Treatment Symptoms in Patients With Culture-Confirmed Early Lyme Disease.

BACKGROUND: Lyme disease patients with erythema migrans are said to have post-treatment Lyme disease symptoms (PTLDS) if there is persistence of subjective symptoms for at least 6 months following antibiotic treatment and resolution of the skin lesion. The purpose of this study was to characterize PTLDS in patients with culture-confirmed early Lyme disease followed for >10 years. METHODS: Adult patients with erythema migrans with a positive skin or blood culture for Borrelia burgdorferi were enrolled in a prospective study beginning in 1991 and followed up at 6 months and annually thereafter to determine the long-term outcome of this infection. The genotype of the infecting strain of B. burgdorferi was evaluated in subjects with PTLDS. RESULTS: One hundred twenty-eight subjects with culture-confirmed early Lyme disease, of whom 55% were male, were followed for a mean ± SD of 14.98 ± 2.71 years (median = 15 years; range = 11-20 years). Fourteen (10.9%) were regarded as having possible PTLDS, but only 6 (4.7%) had PTLDS documented at their last study visit. Nine (64.3%) had only a single symptom. None of the 6 with PTLDS at their last visit was considered to be functionally impaired by the symptom(s). PTLDS was not associated with a particular genotype of B. burgdorferi. CONCLUSIONS: PTLDS may persist for >10 years in some patients with culture-confirmed early Lyme disease. Such long-standing symptoms were not associated with functional impairment or a particular strain of B. burgdorferi.

Long-term assessment of health-related quality of life in patients with culture-confirmed early Lyme disease.

The health-related quality of life of 100 subjects with culture-confirmed early Lyme disease enrolled in a prospective study with annual follow-up visits was evaluated using the 36-Item Short Form General Health Survey version 2 (SF-36v2) questionnaire at 11-20 years after diagnosis. The mean summary scores of physical and mental health were similar to those of the general population.