Kristin C. Mara

Montelukast Does not Maintain Symptom Remission After Topical Steroid Therapy for Eosinophilic Esophagitis

BACKGROUND & AIMS: Montelukast, a cysteinyl leukotriene type‐1 receptor blocker, has been shown in small retrospective studies to reduce symptoms in patients with eosinophilic esophagitis (EoE). We performed a randomized, placebo‐controlled, double‐blind trial to determine whether montelukast maintains symptomatic remission induced by topical steroid therapy in patients with EoE. METHODS: We performed a prospective study of adult patients with EoE (solid‐food dysphagia and a peak esophageal eosinophil count of >20 cells/high‐powered field) enrolled at the Mayo Clinic in Rochester, Minnesota, from April 2008 through February 2015. All patients had been treated previously for at least 6 weeks with a topical steroid until their symptoms were in remission. Steroids were discontinued and patients then were assigned randomly to groups given montelukast (20 mg/day, n = 20) or placebo (n = 21) for 26 weeks (groups were matched for age, sex, history of allergic disease, reflux symptoms, and endoscopic findings of EoE). Study participants were assessed via a structured telephone interview at weeks 2, 4, 8, 12, 16, 20, and 24. Remission was defined as the absence of solid‐food dysphagia. RESULTS: Based on an intention‐to‐treat analysis, after 26 weeks, 40.0% of subjects in the montelukast group and 23.8% in the placebo group were in remission. The odds ratio for remission in the montelukast group was 0.48 (95% confidence interval, 0.10–2.16) (P = .33). No side effects were reported from either group. CONCLUSIONS: In a randomized controlled trial of the ability of montelukast to maintain remission in patients in remission from EoE after steroid therapy, we found montelukast to be well tolerated; 40% of patients remained in remission, but this proportion did not differ significantly from that of the placebo group. ClinicalTrials.gov no: NCT00511316.

Long-Term Results After Total Knee Arthroplasty with Contemporary Rotating-Hinge Prostheses

Background: Total knee arthroplasty (TKA) with a rotating-hinge prosthesis is considered a salvage procedure. While excellent immediate stability is achieved, the historically high failure rate has tempered its use. The goal of this study was to determine clinical outcomes, radiographic results, and survivorship after TKA with contemporary rotating-hinge components. Methods: We identified 408 consecutive TKAs performed with rotating-hinge components for nononcologic indications from 2002 to 2012 at a single academic institution. Two hundred and sixty-four knees (65%) had rotating-hinge TKA components implanted for aseptic etiologies, while 144 knees (35%) were managed with the components in 2-stage reimplantation following infection. Rotating-hinge TKA implants were used for complex primary procedures in 74 knees (18%) and as a revision construct in 334 knees (82%). Clinical outcomes were assessed with the Knee Society scoring system, survivorship analyses, and cumulative incidence of revision. The mean age of the patients at the time of the index arthroplasty was 69 years, and the mean duration of follow-up was 4 years (range, 2 to 12 years). Results: At the most recent follow-up, the mean Knee Society knee score had increased from 51 points preoperatively to 81 points (p < 0.0001), and the mean Knee Society functional score had increased from 26 to 36 points (p < 0.0001). At a mean of 4 years, loosening of components was observed in 13 (3.7%) of 349 knees. At the most recent follow-up, 59 revision procedures and 25 reoperations had been performed. The cumulative incidence of any revision was 9.7% at 2 years and 22.5% at 10 years. The cumulative incidence of revision for aseptic loosening was 1.7% at 2 years and 4.5% at 10 years. Metaphyseal cones were used in 114 knees (28%). Survivorship analysis revealed a trend toward a lower risk of revision (hazard ratio [HR] = 0.69; 95% confidence interval [CI] = 0.39 to 1.22; p = 0.20) and reoperation (HR = 0.51; 95% CI = 0.22 to 1.19; p = 0.12) in patients with metaphyseal cones, despite their use in the most severe of bone defects. Conclusions: Contemporary rotating-hinge TKA implants had a low 10-year cumulative incidence of revision for aseptic loosening of 4.5%. Greater use of metaphyseal fixation has aided this improvement. Patients can expect substantial improvements in clinical outcomes with this revision strategy. Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Risk of Hypertension among First-Time Symptomatic Kidney Stone Formers

BACKGROUND AND OBJECTIVES Prior work has suggested a higher risk of hypertension in kidney stone formers but lacked disease validation and adjustment for potential confounders. Certain types of stone formers may also be at higher risk of hypertension. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS In our study, incident symptomatic stone formers in Olmsted County from 2000 to 2011 were manually validated by chart review and age and sex matched to Olmsted County controls. We followed up patients through November 20, 2015. Hypertension was also validated by manual chart review, and the risk of hypertension in stone formers compared with controls was assessed both univariately and after adjusting for comorbidities. The risk of hypertension among different subtypes of stone formers was also evaluated. RESULTS Among 3023 coded stone formers from 2000 to 2011, a total of 1515 were validated and matched to 1515 controls (mean age was 45 years old, and 56% were men). After excluding those with baseline hypertension (20% of stone formers and 18% of controls), 154 stone formers and 110 controls developed hypertension. Median follow-up time was 7.8 years in stone formers and 9.6 years in controls. Stone formers were found to have a higher risk of hypertension compared with controls (hazard ratio, 1.50; 95% confidence interval, 1.18 to 1.92), even after adjusting for age, sex, body mass index, serum creatinine, CKD, diabetes, gout, coronary artery disease, dyslipidemia, tobacco use, and alcohol abuse (hazard ratio, 1.58; 95% confidence interval, 1.12 to 2.21). Results were similar after excluding patients who were ever on a thiazide diuretic (hazard ratio, 1.65; 95% confidence interval, 1.16 to 2.38). Stone composition, radiographic stone burden, number of subsequent stone events, and stone removal surgeries were not associated with hypertension (P>0.05 for all). CONCLUSIONS The risk of hypertension was higher after the first symptomatic kidney stone event. However, kidney stone severity, type, and treatment did not associate with hypertension.

Efficacy of Over-the-Scope Clips in Management of High-Risk Gastrointestinal Bleeding

Background & Aims: Standard endoscopic therapies do not control bleeding or produce complications in as many as 20% of patients with nonvariceal gastrointestinal bleeding. Most bleeding comes from ulcers with characteristics such as high‐risk vascular territories and/or large vessels. We evaluated the efficacy of using over‐the‐scope clips (OTSCs) as primary or rescue therapy for patients with bleeding from lesions that have a high risk for adverse outcomes. Methods: We performed a retrospective analysis of data from 67 patients with gastrointestinal bleeding from high‐risk lesions who were treated with OTSCs as primary (n = 49) or rescue therapy (n = 18) at a quaternary center, from December 2011 through February 2015. The definition of high‐risk lesions was lesions that were situated in the area of a major artery and larger than 2 mm in diameter and/or a deep penetrating, excavated, fibrotic ulcer with high‐risk stigmata, in which a perforation could not be ruled out or thermal therapy would cause perforation, or lesions that could not be treated by standard endoscopy. Clinical severity was determined based on the Rockall score and a modified Blatchford score. Our primary outcome was the incidence of rebleeding within 30 days after OTSC placement. We assessed risk factors for rebleeding using univariate hazard models followed by multivariable analysis. Results: Of the 67 patients, 47 (70.1%) remained free of rebleeding at 30 days after OTSC placement. We found no difference in the proportion of patients with rebleeding who received primary or rescue therapy (hazard ratio, 0.639; 95% confidence interval, 0.084–4.860; P =.6653). Only 9 rebleeding events were linked clearly to OTSCs and required intervention, indicating an OTSC success rate of 81.3%. We found no significant associations between rebleeding and clinical scores. However, on multivariable analysis, patients with coronary artery disease had a higher risk of rebleeding after OTSC independent of international normalized ratio and antiplatelet use (hazard ratio, 7.30; P =.0002). Conclusions: In a retrospective analysis of 67 patients with bleeding from high‐risk gastrointestinal lesions, we found OTSCs to prevent rebleeding in more than 80% of cases. In the past, these lesions were treated with surgical or radiologic interventions. Patients with coronary artery disease have an increased risk of rebleeding after OTSCs, suggesting the need for escalated therapies.

Outcomes of Rectovaginal Fistula Repair

Objectives Rectovaginal fistulae (RVF) often represent surgical challenges, and treatment must be individualized. We describe outcomes after primary surgical repair stratified by fistula etiology and surgical approach. Methods This retrospective cohort study included women who underwent surgical management of RVF at a tertiary care center between July 1, 2001 and December 31, 2013. Cases were stratified according to the following etiology: cancer (RVF-C), inflammatory bowel disease or infectious (RVF-I), and other (RVF-O). Patients with prior surgical treatment of RVF were excluded. Surgical approaches included local (seton, plug), transvaginal or endorectal, abdominal, diversion alone, or definitive (completion proctocolectomy with permanent colostomy or pelvic exenteration). Recurrence-free survival was estimated using the Kaplan-Meier method, and comparisons between subgroups were evaluated based on fitting Cox proportional hazards models. Censoring occurred at last relevant clinical follow-up. Factors contributing to recurrence-free survival were evaluated including age, body mass index, smoking status, fistula etiology, ileostomy, and surgical approach. Results During the study period, 107 women underwent surgical repair of RVF. The most common fistula etiology was RVF-I (54.2%), followed by RVF-O (23.4%), and RVF-C (22.4%). Ninety-four women underwent fistula repair by the local (29.9%), transvaginal/endorectal (25.2%), abdominal approach (19.6%), or diversion alone (13.1%), whereas 13 underwent definitive surgery (12.2%). Recurrence-free survival was significantly different depending on surgical approach (P < 0.001), but not etiology (P = 0.71). Recurrence-free survival (95% confidence interval) at 1 year after surgery was 35.2% (21.8%–56.9%) for the local approach, 55.6% (37.0%–83.3%) for the transvaginal or endorectal approach, 95% (85.9%–100%) for the abdominal approach, and 33.3% (15%–74.2%) for those with diversion only. Conclusions Recurrence rates after RVF repair are high and did not differ by fistula etiology. Abdominal repair of RVF had significantly fewer recurrences.

A negative view of menopause: does the type of symptom matter?

Abstract Objectives: To assess the association between the type of symptom and women’s self-reported view of menopause. Methods: The study was conducted at Mayo Clinic, Rochester MN, between January 2006 and October 2014. Women aged 40–64 were included. Data from 1420 women were analyzed in a cross-sectional design. The Menopause Health Questionnaire was used for symptom assessment. Odds ratios (ORs) and population attributable risk (PAR) (OR × percent frequency) were calculated for each symptom. Logistic regression analyses were performed with the view of menopause as the dependent variable. Results: Anxiety (2.34), depressed mood (2.24), irritability (2.22), vaginal itching (2.27), crying spells (2.1) and breast tenderness (2.08) were associated with highest odds of having a negative view of menopause. Highest PAR (population impact) symptoms were anxiety (22.27), weight gain (20.66), fatigue (20.28) and irritability (19.41). Hot flushes and night sweats, although common, were not associated with a negative view of menopause (OR 1.3 and 1.16; PAR 3.85 and 4.42, respectively). Conclusion: Mood symptoms, vaginal itching, weight gain, breast tenderness and fatigue, although less common than hot flushes, were noted to have greater association with a negative view of menopause. Specifically addressing these symptoms during menopausal consultation may improve patient satisfaction and outcomes.

Inhaled Nitric Oxide in Extremely Premature Neonates With Respiratory Distress Syndrome

In this retrospective cohort study, we assessed whether prescription of iNO during the first week of life improved survival among extremely premature neonates. BACKGROUND: Inhaled nitric oxide (iNO) is increasingly prescribed to extremely premature neonates with respiratory distress syndrome (RDS). Most of this off-label use occurs during the first week of life. We studied this practice, hypothesizing that it would not be associated with improved survival. METHODS: We queried the Pediatrix Medical Group Clinical Data Warehouse to identify all neonates born at 22 to 29 weeks’ gestation from 2004 to 2014. In our study sample, we included singletons who required mechanical ventilation for treatment of RDS and excluded those with anomalies. The primary outcome was death before discharge. Through a sequential risk set approach, each patient who received iNO during the first 7 days of life (“case patient”) was matched by using propensity scores to a patient who had not received iNO at a chronological age before the case patient’s iNO initiation age (defined as the index age for the matched pair). The association between iNO status and in-hospital mortality was evaluated in a Cox proportional hazards regression model by using age as the time scale with patients entering the risk set at their respective index age. RESULTS: Among 37 909 neonates in our study sample, we identified 993 (2.6%) who received iNO. The 2 matched cohorts each contained 971 patients. We did not observe a significant association between iNO exposure and mortality (hazard ratio, 1.08; 95% confidence interval, 0.94–1.25; P = .29). CONCLUSIONS: Off-label prescription of iNO is not associated with reduced in-hospital mortality among extremely premature neonates with RDS.

Association of vasomotor symptoms and sleep apnea risk in midlife women

Objective: The aim of the study was to determine the association between self-reported vasomotor symptoms (VMS) and obstructive sleep apnea (OSA) risk. Methods: The STOP-BANG to evaluate OSA and Menopause Rating Scale (MRS) were administered to 2,935 women seen in the Womens Health Clinic at Mayo Clinic in Rochester, MN, between May 2015 and December 2016. Of these, 1,691 women were included in the analysis. Total MRS and VMS ratings were compared using logistic regression, with age, smoking, and body mass index (BMI) included as covariates between women at intermediate/high risk versus low risk for OSA. Results: Total MRS scores were significantly higher in women with intermediate/high-risk OSA scores versus those with low-risk scores [mean (SD): 16.8 (8.0) vs 12.9 (7.0), P < 0.001]. Women at intermediate/high OSA risk were older, had more education, self-reported hypertension, BMI >35 kg/m2, and were less likely to be married or employed. Self-reported severe/very severe VMS were significantly associated with intermediate/high risk versus low risk for OSA (26.6% vs 15.0%; P < 0.001). After adjusting for age, BMI, smoking status, and self-reported hypertension, the odds of having intermediate/high risk for OSA were 1.87 times higher for those with severe/very severe VMS compared with those with none/mild/moderate VMS (95% CI, 1.29-2.71, P < 0.001). This association persisted upon subgroup analysis based on BMI <25 kg/m2 (odds ratio 2.15; 95% CI, 1.12-4.16, P = 0.022). Conclusions: Self-reported severe/very severe VMS were associated with intermediate/high risk for OSA in midlife women, even in women with BMI <25 kg/m2. Given the limitations of the STOP-BANG tool, OSA risk may, however, have been overestimated.

Association of Early Inhaled Nitric Oxide With the Survival of Preterm Neonates With Pulmonary Hypoplasia

Importance Pulmonary hypoplasia affects a very small percentage of preterm neonates, but its presence is associated with high rates of mortality. Objective To determine whether treatment with inhaled nitric oxide during the first week of life was associated with improved in-hospital survival in a cohort of extremely preterm neonates with pulmonary hypoplasia. Design, Setting, and Participants This cohort study used data from the Pediatrix Medical Group’s Clinical Data Warehouse, a data set containing information from more than 350 neonatal intensive care units in 35 US states and Puerto Rico. Since inhaled nitric oxide was not randomly prescribed, we used 1-to-1 propensity score matching to reduce the imbalance of measured covariates between the 2 treatment groups. The initial, unmatched cohort included singleton neonates who were born between 22 and 29 weeks’ gestation, had a birth weight of 400 g or more, were diagnosed with pulmonary hypoplasia as a cause of their respiratory distress, remained free of major anomalies, and were discharged between January 1, 2000, and December 31, 2014. We defined exposure as the initiation of inhaled nitric oxide on day t in days 0 to 7 of the life of a neonate. Each exposed neonate was matched 1-to-1 to a neonate who had not initiated inhaled nitric oxide on a given day. Main Outcomes and Measures The primary outcome was mortality defined as death prior to transfer or discharge home. Secondary outcomes were any-stage necrotizing enterocolitis, retinopathy of prematurity requiring treatment, chronic lung disease, and periventricular leukomalacia. Results Among 92 635 neonates in our study sample, we identified 767 (0.8%) with pulmonary hypoplasia who met all study inclusion criteria, of whom 185 (0.2%) were exposed to inhaled nitric oxide. Among 151 matched pairs of exposed and unexposed neonates, we did not identify a significant association between inhaled nitric oxide use and mortality (hazard ratio [HR], 0.79; 95% CI, 0.57-1.11). Subgroup analyses of neonates with and without persistent pulmonary hypertension (PPHN) likewise revealed no significant association between inhaled nitric oxide use and mortality (pulmonary hypoplasia with PPHN: HR, 0.67; 95% CI, 0.45-1.01; pulmonary hypoplasia without PPHN: HR, 1.11; 95% CI, 0.61-2.02), but these findings may have been influenced by ascertainment bias. Conclusions and Relevance Early treatment with inhaled nitric oxide is not associated with improved survival among extremely preterm neonates with pulmonary hypoplasia. Clinical trials are warranted to clarify the matter.

Factors Influencing Surveillance for Hepatocellular Carcinoma in Patients with Liver Cirrhosis

Objective: Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related mortality worldwide, and a rising cause of cancer mortality in the U.S. Liver cirrhosis is the major risk factor for HCC. Surveillance of persons with cirrhosis facilitates early detection and improves outcomes. We assessed the surveillance rate for HCC within a major academic health system and identified factors influencing surveillance. Patients and Methods: We examined the surveillance rate for HCC using liver ultrasound, CT, or MRI, and factors influencing surveillance in a cohort of 369 Minnesota residents with cirrhosis seen at the Mayo Clinic between 2007 and 2009. Results: Ninety-three percent of cirrhosis patients received at least one surveillance study, but only 14% received the recommended uninterrupted semiannual surveillance. Thirty percent received ≥75% of recommended surveillance, and 59% received ≥50% of recommended surveillance. Factors increasing surveillance included gastroenterology or hepatology specialist visits (p < 0.0001), advanced liver disease as assessed by hepatic encephalopathy (p = 0.0008), and comorbid illness as assessed by diabetes mellitus (p = 0.02). Age, sex, race, residence, cirrhosis etiology, or number of primary care visits did not significantly affect the rate of surveillance. Conclusions: While the rate of surveillance in a major academic health system was higher than reported in other studies, surveillance was heavily dependent on visits to a subspecialist. This suggests a major and urgent national need to improve identification of individuals at risk for HCC in the primary care setting and the initiation and maintenance of surveillance by primary care practitioners.