An Electronically Delivered Patient-Activation Tool for Intensification of Medications for Chronic Heart Failure With Reduced Ejection Fraction: The EPIC-HF Trial.

BACKGROUND: Major gaps exist in the routine initiation and dose up-titration of guideline-directed medical therapies (GDMT) for patients with heart failure with reduced ejection fraction. Without novel approaches to improve prescribing, the cumulative benefits of heart failure with reduced ejection fraction treatment will be largely unrealized. Direct-to-consumer marketing and shared decision making reflect a culture where patients are increasingly involved in treatment choices, creating opportunities for prescribing interventions that engage patients. METHODS: The EPIC-HF (Electronically Delivered, Patient-Activation Tool for Intensification of Medications for Chronic Heart Failure with Reduced Ejection Fraction) trial randomized patients with heart failure with reduced ejection fraction from a diverse health system to usual care versus patient activation tools-a 3-minute video and 1-page checklist-delivered electronically 1 week before, 3 days before, and 24 hours before a cardiology clinic visit. The tools encouraged patients to work collaboratively with their clinicians to "make one positive change" in heart failure with reduced ejection fraction prescribing. The primary endpoint was the percentage of patients with GDMT medication initiations and dose intensifications from immediately preceding the cardiology clinic visit to 30 days after, compared with usual care during the same period. RESULTS: EPIC-HF enrolled 306 patients, 290 of whom attended a clinic visit during the study period: 145 were sent the patient activation tools and 145 were controls. The median age of patients was 65 years; 29% were female, 11% were Black, 7% were Hispanic, and the median ejection fraction was 32%. Preclinic data revealed significant GDMT opportunities, with no patients on target doses of ß-blocker, sacubitril/valsartan, and mineralocorticoid receptor antagonists. From immediately preceding the cardiology clinic visit to 30 days after, 49.0% in the intervention and 29.7% in the control experienced an initiation or intensification of their GDMT (P=0.001). The majority of these changes were made at the clinician encounter itself and involved dose uptitrations. There were no deaths and no significant differences in hospitalization or emergency department visits at 30 days between groups. CONCLUSIONS: A patient activation tool delivered electronically before a cardiology clinic visit improved clinician intensification of GDMT. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03334188.

A multicenter trial of a shared DECision Support Intervention for Patients offered implantable Cardioverter-DEfibrillators: DECIDE-ICD rationale, design, Medicare changes, and pilot data.

Shared decision making (SDM) facilitates delivery of medical therapies that are in alignment with patients' goals and values. Medicare national coverage decision for several interventions now includes SDM mandates, but few have been evaluated in nationwide studies. Based upon a detailed needs assessment with diverse stakeholders, we developed pamphlet and video patient decision aids (PtDAs) for implantable cardioverter/defibrillator (ICD) implantation, ICD replacement, and cardiac resynchronization therapy with defibrillation to help patients contemplate, forecast, and deliberate their options. These PtDAs are the foundation of the Multicenter Trial of a Shared Decision Support Intervention for Patients Offered Implantable Cardioverter-Defibrillators (DECIDE-ICD), a multicenter, randomized trial sponsored by the National Heart, Lung, and Blood Institute aimed at understanding the effectiveness and implementation of an SDM support intervention for patients considering ICDs. Finalization of a Medicare coverage decision mandating the inclusion of SDM for new ICD implantation occurred shortly after trial initiation, raising novel practical and statistical considerations for evaluating study end points. METHODS/DESIGN: A stepped-wedge randomized controlled trial was designed, guided by the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) planning and evaluation framework using an effectiveness-implementation hybrid type II design. Six electrophysiology programs from across the United States will participate. The primary effectiveness outcome is decision quality (defined by knowledge and values-treatment concordance). Patients with heart failure who are clinically eligible for an ICD are eligible for the study. Target enrollment is 900 participants. DISCUSSION: Study findings will provide a foundation for implementing decision support interventions, including PtDAs, with patients who have chronic progressive illness and are facing decisions involving invasive, preference-sensitive therapy options.

An Electronically delivered, Patient-activation tool for Intensification of medications for Chronic Heart Failure with reduced ejection fraction: Rationale and design of the EPIC-HF trial.

BACKGROUND: Heart failure with reduced ejection fraction (HFrEF) benefits from initiation and intensification of multiple pharmacotherapies. Unfortunately, there are major gaps in the routine use of these drugs. Without novel approaches to improve prescribing, the cumulative benefits of HFrEF treatment will be largely unrealized. Direct-to-consumer marketing and shared decision making reflect a culture where patients are increasingly involved in treatment choices, creating opportunities for prescribing interventions that engage patients. HYPOTHESIS: Encouraging patients to engage providers in HFrEF prescribing decisions will improve the use of guideline-directed medical therapies. DESIGN: The Electronically delivered, Patient-activation tool for Intensification of Chronic medications for Heart Failure with reduced ejection fraction (EPIC-HF) trial randomizes patients with HFrEF to usual care versus patient-activation tools-a 3-minute video and 1-page checklist-delivered prior to cardiology clinic visits that encourage patients to work collaboratively with their clinicians to intensify HFrEF prescribing. The study assesses the effectiveness of the EPIC-HF intervention to improve guideline-directed medical therapy in the month after its delivery while using an implementation design to also understand the reach, adoption, implementation, and maintenance of this approach within the context of real-world care delivery. Study enrollment was completed in January 2020, with a total 305 patients. Baseline data revealed significant opportunities, with <1% of patients on optimal HFrEF medical therapy. SUMMARY: The EPIC-HF trial assesses the implementation, effectiveness, and safety of patient engagement in HFrEF prescribing decisions. If successful, the tool can be easily disseminated and may inform similar interventions for other chronic conditions.

Esophagram should be performed to diagnose esophageal perforation before inter-hospital transfer.

Background: Early recognition of esophageal perforation may prevent morbidity and mortality, and accurate diagnostic imaging facilitates triage. Stable patients with suspected perforation may be transferred to higher levels of care before appropriate work-up and diagnosis confirmation. We reviewed patients transferred for esophageal perforation to critically analyze the diagnostic workflow. Methods: We performed a retrospective review of patients transferred to our tertiary care institution from 2015-2021 for suspected esophageal perforation. Demographics, referring site characteristics, diagnostic studies, and management were analyzed. Bivariate comparisons were performed using Wilcoxon-Mann-Whitney tests for continuous variables and chi-squared or Fisher's exact tests for categorical variables. Results: Sixty-five patients were included. Etiology of suspected perforation was spontaneous in 53.8% and iatrogenic in 33.8%. Most patients were transferred within 24 hours from time of suspected perforation (66.2%). Transferring sites included seven states and were 101-300 miles (32.3%) or >300 miles (26.2%) away. CT imaging was obtained in 96.9% before transfer, most commonly demonstrating pneumomediastinum (46.2%). Only 21.5% of patients had an esophagram before transfer. Following transfer, 36.9% (n=24) were ultimately not found to have esophageal perforation, demonstrated by negative arrival esophagram in 79.1%. In patients with confirmed perforation (n=41), 58.5% had surgery, 26.8% endoscopic intervention, and 14.6% supportive care. Conclusions: After transfer a proportion of patients were ultimately found to not have esophageal perforation, typically demonstrated by negative esophagram upon arrival. We conclude that a recommendation of performing esophagram at the presenting site, when possible, may prevent unnecessary transfers, and will likely reduce costs, conserve resources, and decrease management delays.

Long-Term Patient-Reported Symptom Improvement and Quality of Life after Transthoracic Diaphragm Plication in Adults.

BACKGROUND: Open and robotic-assisted transthoracic approaches for diaphragm plication are accepted surgical interventions for diaphragm paralysis and eventration. However, long-term patient-reported symptom improvement and quality of life (QOL) remains unclear. STUDY DESIGN: A telephone-based survey was developed focusing on postoperative symptom improvement and QOL. Patients who underwent open or robotic-assisted transthoracic diaphragm plication (2008-2020) across three institutions were invited to participate. Patients who responded and provided consent were surveyed. Likert responses on symptom severity were dichotomized and rates before and after surgery were compared using McNemar's test. RESULTS: Forty-one percent of patients participated (43 of 105 responded, mean age 61.0 years, 67.4% male, 37.2% robotic-assisted surgery), with an average time between surgery and survey of 4.1 ± 3.2 years. Patients reported significant improvement in dyspnea while lying flat (67.4% pre- vs 27.9% postoperative, p < 0.001), dyspnea at rest (55.8% pre- vs 11.6% postoperative, p < 0.001), dyspnea with activity (90.7% pre- vs 55.8% postoperative, p < 0.001), dyspnea while bending over (79.1% pre- vs 34.9% postoperative, p < 0.001), and fatigue (67.4% pre- vs 41.9% postoperative, p = 0.008). There was no statistical improvement in chronic cough. 86% of patients reported improved overall QOL, 79% had increased exercise capacity, and 86% would recommend surgery to a friend with a similar problem. Analysis comparing open and robotic-assisted approaches found no statistically significant differences in symptom improvement or QOL responses between the groups. CONCLUSIONS: Patients report significantly improved dyspneic and fatigue symptoms after transthoracic diaphragm plication, regardless of open or robotic-assisted approach. The majority of patients report improved QOL and exercise capacity.

Patient Pill Organization Strategies and Adherence Measured in a Cross-Sectional Study of Hypertension.

Background: The strategies patients use to organize medications (eg, pill dispenser) may be reflected in adherence measured at follow-up. We studied whether medication organization strategies patients use at home are associated with adherence measured using pharmacy-fills, self-report, and pill counts. Design: Secondary analysis of data from a prospective randomized clinical trial. Setting: Eleven US safety-net and community primary care clinics. Patients: Of the 960 enrolled self-identified non-Hispanic Black and White patients prescribed antihypertensive medications, 731 patients reported pill organization strategies and were included. Variable: Patients were asked if they use any of the following medication organization strategies: finish previous refills first; use a pill dispenser; combine same prescriptions; or combine dissimilar prescriptions. Outcomes: Adherence to antihypertensive medications using pill counts (range, 0.0-1.0% of the days covered), pharmacy-fill (proportion of days covered >90%), and self-report (adherent/non-adherent). Results: Of the 731 participants, 38.3% were men, 51.7% were age ≥65, 52.9% self-identified as Black or African American. Of the strategies studied, 51.7% finished previous refills first, 46.5% used a pill dispenser, 38.2% combined same prescriptions and 6.0% combined dissimilar prescriptions. Median (IQR) pill count adherence was 0.65 (0.40-0.87), pharmacy-fill adherence was 75.7%, and self-reported adherence was 63.2%. Those who combined same prescriptions had significantly lower measured pill count adherence than those who did not (0.56 (0.26-0.82) vs 0.70 (0.46-0.90), p<0.01) with no significant difference in pharmacy-fill (78.1% vs 74%, p=0.22) or self-reported adherence (63.0% vs 63.3%, p=0.93). Conclusion: Self-reported medication organization strategies were common. Combining same prescriptions was associated with lower adherence as measured using pill counts but not pharmacy-fills or self-report. Clinicians and researchers should identify the pill organization strategies used by their patients to understand how these strategies may influence measures of patient adherence. Trial Registration: ClinicalTrials.gov NCT03028597; https://clinicaltrials.gov/ct2/show/NCT03028597 (Archived by WebCite at http://www.webcitation.org/72vcZMzAB).

A comparison of short-term outcomes following robotic-assisted vs. open transthoracic diaphragm plication.

Diaphragm paralysis and eventration are rare conditions in adults. Symptomatic patients may benefit from surgical plication of the elevated hemidiaphragm. The objective of this study was to compare short-term outcomes and length of stay following robotic-assisted vs. open diaphragm plication. A multicenter retrospective study was conducted that identified patients undergoing unilateral hemidiaphragm plication from 5/2008 to 12/2020. The first RATS plication was performed in 11/2018. Electronic medical records were reviewed, and outcomes were compared between RATS and open approach. One hundred patients underwent diaphragm plication, including thirty-nine (39.0%) RATS and sixty-one (61.0%) open cases. Patients undergoing RATS diaphragm plication were older (64 years vs. 55 years, p = 0.01) and carried a higher burden of comorbidities (Charlson Comorbidity Index: 2.0 vs. 1.0, p = 0.02). The RATS group had longer median operative times (146 min vs. 99 min, p < 0.01), but shorter median hospital length of stays (3.0 days vs. 6.0 days, p < 0.01). There was a non-significant trend toward a decreased rate of 30-day postoperative complications (20.5% RATS vs. 32.8% open, p = 0.18) and 30-day unplanned readmissions (7.7% RATS vs. 9.8% open, p > 0.99). RATS is a technically feasible and safe option for performing diaphragm plications. This approach increases the surgical candidacy of older patients with a higher burden of comorbid disease without increasing complication rates, while reducing length of hospital stay.

Clinical Inertia Among Outpatients With Heart Failure: Application of Treatment Nonintensification Taxonomy to EPIC-HF Trial.

BACKGROUND: The contribution of clinical inertia to suboptimal guideline-directed medical therapy (GDMT) for patients with heart failure with reduced ejection fraction (HFrEF) remains unclear. OBJECTIVES: This study examined reasons for GDMT nonintensification and characterized clinical inertia. METHODS: In this secondary analysis of EPIC-HF (Electronically Delivered, Patient-Activation Tool for Intensification of Medications for Chronic Heart Failure with Reduced Ejection Fraction), a randomized clinical trial evaluating a patient-activation tool on GDMT utilization, we performed a sequential, explanatory mixed-methods study. Reasons for nonintensification among 4 medication classes were assigned according to an expanded published taxonomy using structured chart reviews. Audio transcripts of clinic encounters were analyzed to further characterize nonintensification reasons. Integration occurred during the interpretation phase. RESULTS: Among 292 HFrEF patients who completed a cardiology visit, 185 (63.4%) experienced no treatment intensification, of whom 90 (48.6%) had at least 1 opportunity for intensification of a medication class with no documented contraindication or barriers (ie, clinical inertia). Nonintensification reasons varied by medication class, and included heightened risk of adverse effects (range 18.2%-31.6%), patient nonadherence (range 0.8%-1.1%), patient preferences and beliefs (range 0.6%-0.9%), comanagement with other providers (range 4.6%-5.6%), prioritization of other issues (range 15.6%-31.8%), multiple categories (range 16.5%-22.7%), and clinical inertia (range 22.7%-31.6%). A qualitative analysis of 32 clinic audio recordings demonstrated common characteristics of clinical inertia: 1) clinician review of medication regimens without education or intensification discussions; 2) patient stability as justification for nonintensification; and 3) shorter encounters for nonintensification vs intensification. CONCLUSIONS: In this comprehensive study exploring HFrEF prescribing, clinical inertia is a main contributor to nonintensification within an updated taxonomy classification for suboptimal GDMT prescribing. This approach should help target strategies overcoming GDMT underuse.

Relationship Between Social Vulnerability Indicators and Trial Participant Attrition: Findings From the HYVALUE Trial.

BACKGROUND: Social vulnerability indicators are associated with health care inequities and may similarly impede ongoing participation in research studies. We evaluated the association of social vulnerability indicators and research participant attrition in a trial focused on reducing health disparities. METHODS: Self-identified White or Black adults enrolled in the HYVALUE trial (Hypertension and VALUEs), a randomized trial testing a values-affirmation intervention on medication adherence, from February 2017 to September 2019 were included. The self-reported measures of social vulnerability indicators included: (1) Black race; (2) female gender; (3) no health insurance; (4) unemployment; (5) a high school diploma or less; and (6) financial-resource strain. Full attrition was defined as not completing at least one 3- or 6-month follow-up study visit. Log-binomial regression models adjusted for age, gender, race, medical comorbidities, and the other social vulnerability indicators to estimate the relative risk of each social vulnerability indicator with study attrition. RESULTS: Among 825 participants, the mean age was 63.3 years (±11.7 years), 60% were women, 54% were Black, and 97% reported at least one social vulnerability. Overall, 21% participants had full attrition after study enrollment. After adjustment for all other social vulnerabilities, only financial-resource strain remained consistently associated with full attrition (relative risk, 1.71 [95% CI, 1.28-2.29]). In a secondary analysis of partial attrition (completed only one follow-up visit), financial-resource strain (relative risk, 1.40 [95% CI, 1.09-1.81]) and being uninsured (relative risk, 1.54 [95% CI, 1.01-2.34]) were associated with partial attrition. CONCLUSIONS: In a trial aimed at reducing disparities in medication adherence, participants who reported financial-resource strain had a higher risk of participant attrition independent of race or gender. Our findings suggest that efforts to retain diverse populations in clinical trials should extend beyond race and gender to consider other social vulnerability indicators. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03028597.

A validated modification of the vaccine hesitancy scale for childhood, influenza and HPV vaccines.

INTRODUCTION: Vaccine hesitancy contributes to outbreaks of preventable disease worldwide. The Vaccine Hesitancy Scale (VHS), developed by the international WHO SAGE Working Group, has been validated previously for measuring hesitancy towards childhood vaccines; some psychometric properties were suboptimal. METHODS: We collected data using large, nationally-representative samples of parents in the U.S. We adapted the VHS items, and additional hesitancy items, to assess hesitancy towards influenza and HPV vaccines in addition to routine childhood vaccines. We then used exploratory and confirmatory factor analysis to identify latent constructs and create modified scales for childhood (VHS-child), influenza (VHS-flu) and HPV (VHS-HPV) vaccines with improved psychometric properties. Finally, we compared hesitancy scores on the VHS-child, VHS-flu, and VHS-HPV, to self-reported receipt of each vaccine category, and compared subscale scores to assess whether drivers of hesitancy differed by vaccine category. RESULTS: 2052 parents of children <18 years old completed the VHS-child and VHS-flu while 2020 parents of adolescents completed the VHS-HPV. A two-factor structure of 'risks' and a 'lack of confidence' was found for each vaccine category. Slight modifications to the VHS improved psychometric properties. Hesitancy was strongly associated with vaccine receipt: e.g., 76% of parents not hesitant towards influenza vaccine had vaccinated their child the past season, versus 9% of hesitant parents (p < 0.0001). Subscale scores also differed significantly between vaccines: lack of confidence was greater towards influenza (Median (IQR): 2.0 (1.2, 3.3)) and HPV (2.0 (1.3, 3.0)) vaccines than childhood (1.2 (1.0, 1.8), p < 0.0001 for both) vaccines; perceived risks of HPV vaccines (2.7 (1.7, 3.7)) were greater than for childhood vaccines (2.0 (1.3, 3.0), p < 0.0001). CONCLUSIONS: Our modified VHS scales perform well psychometrically and allow for consistent measurement of the extent and reasons for hesitancy between vaccine categories. We suggest that future work use these scales to examine hesitancy towards other vaccines and to monitor hesitancy over time.

Prospective evaluation of oral cannabis extracts in children with epilepsy.

PURPOSE: Interest in the use of artisanal cannabinoids in pediatric epilepsy has increased but safety and utility data are lacking. Our aim was to prospectively characterize the use of oral cannabis extracts (OCE) in a refractory pediatric epilepsy population. METHODS: Families considering the use of an OCE were enrolled in a prospective observational study. Baseline seizure frequency was assessed over a period of 4 weeks. Seizure frequency, CBD and THC-COOH levels were assessed every 4 weeks during a 12-week treatment period. Response was defined as at least a 50% reduction in seizure frequency over the final 8 weeks of the study relative to baseline. RESULTS: Consent was obtained in 32 children; 11 were excluded from analysis (3 failed to complete baseline data, 3 started OCE before completing baseline period and 5 did not start OCE) leaving 21 to be included in subsequent analyses. Median age was 10.3 years (IQR 6.8-12.6), 13 (62%) were male and median seizure frequency was 2.7 seizures/day during the baseline period. The median of the high dose of CBD that was administered during the observation period was of 0.9 (0.6-2.2) mg/kg/day. Of the 21 subjects who were included in the analysis, 5 (24%) were responders. OCE was stopped early in 3 subjects (14%) due to a perceived increase in seizures. THC-COOH and CBD blood levels did not have a significant association with response status (p = 0.95 CBD, p = 0.53 THC-COOH, N = 14). CONCLUSION: The observed response rate in this study is similar to placebo rates in prospective randomized trials of pharmaceutical grade products and the withdrawal rate is greater than rates obtained with retrospective methods. Doses of OCE administered were lower than doses used in randomized trials.

End of life for patients with left ventricular assist devices: Insights from INTERMACS.

BACKGROUND: Trial and registry data have reported mortality rates and causes of death in patients with left ventricular assist devices (LVADs); however, a more granular description is needed of end of life, including location of death and quality of life (QOL), to better guide expectations and care. METHODS: To identify where patients with an LVAD died, characterize QOL before death, and cause of death over time, we evaluated patients in the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) implanted with a continuous-flow LVAD. RESULTS: From 18,733 patients implanted with an LVAD during the period 2008 to 2016, 4,916 patients were known to have died, of whom 98% had a recorded location of death. Overall, 76.9% died in the hospital, with progressively more patients dying outside of the hospital further post-LVAD implant: <1 month, 2.3%; 1 to 12 months, and 16.8%; and >12 months, 37.4%. In a multivariable analysis, increased age (RR (risk ratio) 1.06, 95% confidence interval [CI] 1.02 to 1.12, p = 0.01) and destination therapy indication (RR 1.15, 95% CI 1.03 to 1.28, p = 0.01) increased the likelihood of dying outside the hospital. Comparing 3 months post-implant with 6 months before death in a subset of patients, QOL remained clinically stable (EQ-5D Visual Analog Scale [mean ± SD]: 68.3 ± 22.2 to 66.7 ± 21.7, p = 0.11; KCCQ: 61.0 ± 22.2 to 57.8 ± 23.2, p = 0.003). The most common cause of death <1 month post-implant was multiple-organ failure (20.4%) and at >1 month post-implant it was neurologic dysfunction (28.2%). CONCLUSIONS: Most patients with an LVAD died in the hospital. QOL remained stable months before death and causes of death were varied, but increasingly dominated by stroke. By understanding death with an LVAD in place, clinicians are in a better position to educate patients and caregivers about what to expect and provide to support tailored to patient and caregiver needs.

Obstruction reduction: Use of water-soluble contrast challenge to differentiate between partial and complete small bowel obstruction.

Differentiating SBO that will resolve conservatively from those requiring surgery remains challenging. Water-soluble contrast administration may be diagnostic and therapeutic. Our study evaluated use of a WSC challenge protocol. We hypothesize that protocol use discriminates between surgical SBO and obstructions which can be managed non-operatively. Demographics, prior surgeries, time to operation, complications, and LOS were analyzed. 108 patients were admitted with SBO. 13% underwent immediate laparotomy with concern for bowel compromise; these had a median LOS of 8.5 days. 91 received WSC protocol. Of these, 77% had contrast passage to the colon. Of the 48 in whom contrast passed between 0 and 12 h, LOS was 2 days. Of the 22 patients in whom contrast passed between 12 and 24 h, LOS was 4.5 days. 21 had failure of contrast passage; 18 of those underwent surgery after 24 h as a result. Of the 21 patients who failed WSC challenge, median LOS was 8 days. WSC protocol implementation facilitates early recognition of partial from complete obstruction and may decrease LOS. Our findings warrant further evaluation with a multicenter trial.

Evaluation of a water-soluble contrast protocol for small bowel obstruction: A southwestern surgical congress multicenter trial.

Differentiation between SBO that will resolve with supportive measures and those requiring surgery remains challenging. WSC administration may be diagnostic and therapeutic. The purpose of this study was to evaluate use of a SBO protocol using WSC challenge. A protocol was implemented at five tertiary care centers. Demographics, prior surgical history, time to operation, complications, and LOS were analyzed. 283 patients were admitted with SBO; 13% underwent immediate laparotomy; these patients had a median LOS of 7.5 days. The remaining 245 were candidates for WSC challenge. Of those, 80% received contrast. 139 (71%) had contrast passage to the colon. LOS in these patients was 4 days. Sixty-five patients (29%) failed contrast passage within 24 h and underwent surgery. LOS was 9 days. 8% of patients in whom contrast passage was observed at 24 h nevertheless subsequently underwent surgery. 4% of patients who failed WSC challenge did not proceed to surgery. Our multicenter trial revealed that implementation of a WSC protocol may facilitate early recognition of partial from complete obstruction.

Factors Associated with Achievement of Clinically Significant Weight Loss by Women in a National Nonprofit Weight Loss Program.

BACKGROUND: Clinically significant weight loss (CSWL) is ≥5% of initial weight. The purpose of the study is to determine factors associated with women achieving CSWL in Take Off Pounds Sensibly (TOPS), a national, nonprofit weight loss program. METHODS: This is a retrospective analysis of 48,674 females who joined TOPS from 2005 to 2011 and had a birth date in the database. Predictors of CSWL were evaluated using log-binomial regression and adjusted relative risks [99% CI] for participant age, initial weight, number of members per chapter, and chapter age. RESULTS: Older women were more likely to achieve CSWL, with women ≥70 years 1.23 (1.18, 1.28) times more likely to achieve CSWL compared to women 18 to <45 years. Women who weighed 113 to <136 kg and ≥136 kg were 1.06 (1.02, 1.10) and 1.07 (1.02, 1.14) times more likely to achieve CSWL compared to women <80 kg, respectively. Women in chapters with 25 to <35 members and ≥35 members more were 1.09 (1.05, 1.13) and 1.14 (1.10, 1.18) times more likely to achieve CSWL than those in chapters with less than 15 members. Women in older chapters were less likely to achieve CSWL, with women in chapters 10 to 20 years old 0.95 (0.92, 0.99) times as likely to lose weight as those in chapters less than 10 years old. CONCLUSIONS: Women in TOPS were more likely to achieve CSWL if older, ≥113 kg, and in larger, newer chapters. Future studies should address ways to modify the program to improve achievement of CSWL.

Improvements to a class of distance matrix methods for inferring species trees from gene trees.

Among the methods currently available for inferring species trees from gene trees, the GLASS method of Mossel and Roch (2010), the Shallowest Divergence (SD) method of Maddison and Knowles (2006), the STEAC method of Liu et al. (2009), and a related method that we call Minimum Average Coalescence (MAC) are computationally efficient and provide branch length estimates. Further, GLASS and STEAC have been shown to be consistent estimators of tree topology under a multispecies coalescent model. However, divergence time estimates obtained with these methods are all systematically biased under the model because the pairwise interspecific gene divergence times on which they rely must be more ancient than the species divergence time. Jewett and Rosenberg (2012) derived an expression for the bias of GLASS and used it to propose an improved method that they termed iGLASS. Here, we derive the biases of SD, STEAC, and MAC, and we propose improved analogues of these methods that we call iSD, iSTEAC, and iMAC. We conduct simulations to compare the performance of these methods with their original counterparts and with GLASS and iGLASS, finding that each of them decreases the bias and mean squared error of pairwise divergence time estimates. The new methods can therefore contribute to improvements in the estimation of species trees from information on gene trees.