Geriatric assessment-derived deficit accumulation and patient-reported treatment burden in older adults with bladder cancer.

BACKGROUND: When a person's workload of healthcare exceeds their resources, they experience treatment burden. At the intersection of cancer and aging, little is known about treatment burden. We evaluated the association between a geriatric assessment-derived Deficit Accumulation Index (DAI) and patient-reported treatment burden in older adults with early-stage, non-muscle-invasive bladder cancer (NMIBC). METHODS: We conducted a cross-sectional survey of older adults with NMIBC (≥65 years). We calculated DAI using the Cancer and Aging Research Group's geriatric assessment and measured urinary symptoms using the Urogenital Distress Inventory-6 (UDI-6). The primary outcome was Treatment Burden Questionnaire (TBQ) score. A negative binomial regression with LASSO penalty was used to model TBQ. We further conducted qualitative thematic content analysis of responses to an open-ended survey question ("What has been your Greatest Challenge in managing medical care for your bladder cancer") and created a joint display with illustrative quotes by DAI category. RESULTS: Among 119 patients, mean age was 78.9 years (SD 7) of whom 56.3% were robust, 30.3% pre-frail, and 13.4% frail. In the multivariable model, DAI and UDI-6 were significantly associated with TBQ. Individuals with DAI above the median (>0.18) had TBQ scores 1.94 times greater than those below (adjusted IRR 1.94, 95% CI 1.33-2.82). Individuals with UDI-6 greater than the median (25) had TBQ scores 1.7 times greater than those below (adjusted IRR 1.70, 95% CI 1.16-2.49). The top 5 themes in the Greatest Challenge question responses were cancer treatments (22.2%), cancer worry (19.2%), urination bother (18.2%), self-management (18.2%), and appointment time (11.1%). CONCLUSIONS: DAI and worsening urinary symptoms were associated with higher treatment burden in older adults with NMIBC. These data highlight the need for a holistic approach that reconciles the burden from aging-related conditions with that resulting from cancer treatment.

Evaluation of Malignant Hyperthermia Features in Patients with Pathogenic or Likely Pathogenic RYR1 Variants Disclosed through a Population Genomic Screening Program.

BACKGROUND: Malignant hyperthermia (MH) susceptibility is a heritable musculoskeletal disorder that can present as a potentially fatal hypermetabolic response to triggering anesthesia agents. Genomic screening for variants in MH-associated genes RYR1 and CACNA1S provides an opportunity to prevent morbidity and mortality. There are limited outcomes data from disclosing variants in RYR1, the most common MH susceptibility gene, in unselected populations. The authors sought to identify the rate of MH features or fulminant episodes after triggering agent exposure in an unselected population undergoing genomic screening including actionable RYR1 variants. METHODS: The MyCode Community Health Initiative by Geisinger (USA) is an electronic health record-linked biobank that discloses pathogenic and likely pathogenic variants in clinically actionable genes to patient-participants. Available electronic anesthesia and ambulatory records for participants with actionable RYR1 results returned through December 2020 were evaluated for pertinent findings via double-coded chart reviews and reconciliation. Descriptive statistics for observed phenotypes were calculated. RESULTS: One hundred fifty-two participants had an actionable RYR1 variant disclosed during the study period. None had previous documented genetic testing for MH susceptibility; one had previous contracture testing diagnosing MH susceptibility. Sixty-eight participants (44.7%) had anesthesia records documenting triggering agent exposure during at least one procedure. None received dantrolene treatment or had documented muscle rigidity, myoglobinuria, hyperkalemia, elevated creatine kinase, severe myalgia, or tea-colored urine. Of 120 possibly MH-related findings (postoperative intensive care unit admissions, hyperthermia, arterial blood gas evaluation, hypercapnia, or tachycardia), 112 (93.3%) were deemed unlikely to be MH events; 8 (6.7%) had insufficient records to determine etiology. CONCLUSIONS: Results demonstrate a low frequency of classic intraanesthetic hypermetabolic phenotypes in an unselected population with actionable RYR1 variants. Further research on the actionability of screening for MH susceptibility in unselected populations, including economic impact, predictors of MH episodes, and expanded clinical phenotypes, is necessary.

Association between missed appointments and hospitalization for child physical abuse.

Missed cases of child physical abuse (CPA) persist despite known risk factors. Prior studies have not evaluated missed medical appointments as a risk factor for CPA. The objective of this study was to determine if an association exists between missed appointments and hospitalization for CPA. We conducted a 20-year, single health system, retrospective chart review of hospitalized patients ≤36 months of age meeting International Classification of Diseases (ICD) 9/10 criteria for CPA with ≥1 scheduled appointment in our system prior to their admission. Cases were categorized as definite CPA, high likelihood, or no concern for CPA/unable to be determined. Cases identified as definite or high likelihood of CPA were matched (5:1) with controls based on age, distance to primary care provider's (PCP's) office, sex, prior hospitalization, and race. Missed appointments were compared between cases (n = 146) and controls (n = 730). A significant difference was identified between cases and controls (26 % vs 9 %, p < 0.001) for the median proportion of missed appointments. After adjusting for matched and significant covariates, there was a 3 % increase in a patient's odds of admission for CPA for every 1 % increase in missed appointments. We found an association between missed appointments and future admission for CPA. This finding has potential to assist clinicians with CPA risk stratification and future child abuse research. Limitations include single healthcare system, ICD criteria determined by research team, and narrow definition of definite CPA.

Testing and Management of Iron Overload After Genetic Screening-Identified Hemochromatosis.

Importance: HFE gene-associated hereditary hemochromatosis type 1 (HH1) is underdiagnosed, resulting in missed opportunities for preventing morbidity and mortality. Objective: To assess whether screening for p.Cys282Tyr homozygosity is associated with recognition and management of asymptomatic iron overload. Design, Setting, and Participants: This cross-sectional study obtained data from the Geisinger MyCode Community Health Initiative, a biobank of biological samples and linked electronic health record data from a rural, integrated health care system. Participants included those who received a p.Cys282Tyr homozygous result via genomic screening (MyCode identified), had previously diagnosed HH1 (clinically identified), and those negative for p.Cys282Tyr homozygosity between 2017 and 2018. Data were analyzed from April 2020 to August 2023. Exposure: Disclosure of a p.Cys282Tyr homozygous result. Main Outcomes and Measures: Postdisclosure management and HFE-associated phenotypes in MyCode-identified participants were analyzed. Rates of HFE-associated phenotypes in MyCode-identified participants were compared with those of clinically identified participants. Relevant laboratory values and rates of laboratory iron overload among participants negative for p.Cys282Tyr homozygosity were compared with those of MyCode-identified participants. Results: A total of 86 601 participants had available exome sequences at the time of analysis, of whom 52 994 (61.4%) were assigned female at birth, and the median (IQR) age was 62.0 (47.0-73.0) years. HFE p.Cys282Tyr homozygosity was disclosed to 201 participants, of whom 57 (28.4%) had a prior clinical HH1 diagnosis, leaving 144 participants who learned of their status through screening. There were 86 300 individuals negative for p.Cys282Tyr homozygosity. After result disclosure, among MyCode-identified participants, 99 (68.8%) had a recommended laboratory test and 36 (69.2%) with laboratory or liver biopsy evidence of iron overload began phlebotomy or chelation. Fifty-three (36.8%) had iron overload; rates of laboratory iron overload were higher in MyCode-identified participants than participants negative for p.Cys282Tyr homozygosity (females: 34.1% vs 2.1%, P < .001; males: 39.0% vs 2.9%, P < .001). Iron overload (females: 34.1% vs 79.3%, P < .001; males: 40.7% vs 67.9%, P = .02) and some liver-associated phenotypes were observed at lower frequencies in MyCode-identified participants compared with clinically identified individuals. Conclusions and Relevance: Results of this cross-sectional study showed the ability of genomic screening to identify undiagnosed iron overload and encourage relevant management, suggesting the potential benefit of population screening for HFE p.Cys282Tyr homozygosity. Further studies are needed to examine the implications of genomic screening for health outcomes and cost-effectiveness.

His-Purkinje Conduction System Pacing Optimized Trial of Cardiac Resynchronization Therapy vs Biventricular Pacing: HOT-CRT Clinical Trial.

BACKGROUND: His-Purkinje conduction system pacing (HPCSP) using His bundle pacing (HBP) or left bundle branch pacing (LBBP) has emerged as an alternative to biventricular pacing (BVP) in patients requiring cardiac resynchronization therapy (CRT). OBJECTIVES: The aim of the study was to compare the feasibility and clinical efficacy of HOT-CRT (His-Purkinje conduction system pacing Optimized Trial of Cardiac Resynchronization Therapy) with BVP in patients with heart failure, reduced ejection fraction, and indication for CRT. METHODS: This was a prospective, randomized, controlled trial of HOT-CRT and BVP in patients with LVEF <50% and indications for CRT. If HPCSP resulted in incomplete electrical resynchronization, a coronary sinus (CS) lead was added. The primary outcome was the change in left ventricular ejection fraction (LVEF) at 6 months. The primary safety endpoint was freedom from major complications. RESULTS: A total of 100 patients (female 31%, aged 70 ± 12 years, LVEF 31.5% ± 9.0%) were randomized. HOT-CRT was successful in 48 of 50 (96%) and BVP-CRT in 41 of 50 (82%) patients (P = 0.03). QRS duration significantly decreased from 164 ± 26 ms to 137 ± 20 ms with HOT-CRT and 166 ± 28 ms to 141 ± 19 ms with BVP. Fluoroscopy results (18.8 ± 12.4 min vs 23.8 ± 12.4 min, P = 0.05) and procedure duration (119 ± 42 min vs 114 ± 36 min, P = 0.5) were similar. The primary outcome of change in LVEF at 6 months was greater in HOT-CRT than in BVP (12.4% ± 7.3% vs 8.0% ± 10.1%, P = 0.02). The primary safety endpoint was similar (98% vs 94%, P = 0.62). Echocardiographic response of improvement in LVEF >5% occurred in 80% vs 61% (P = 0.06). Complications occurred in 3 (6%) in HOT-CRT vs 10 (20%) in BVP (P = 0.03). CONCLUSIONS: HPCSP-guided CRT resulted in greater change in LVEF compared with BVP. Randomized clinical trials with long-term follow-up are necessary. (His-Purkinje Conduction System Pacing Optimized Trial of Cardiac Resynchronization Therapy [HOT-CRT]; NCT04561778).

Low adenoma burden in unselected patients with a pathogenic APC variant.

PURPOSE: Genomic screening can improve clinical outcomes, but presentation of individuals with risk for polyposis identified via genomic screening is unknown. To inform assessment of clinical utility of genomic screening for polyposis risk, clinical presentation of individuals in an unselected health care system cohort with an APC pathogenic or likely pathogenic (P/LP) variant causative of familial adenomatous polyposis are described. METHODS: Electronic health records of individuals with an APC P/LP variant identified via the MyCode program (MyCode APC+) were reviewed to assess adenoma burden and compare it among individuals with a clinical diagnosis of familial adenomatous polyposis and matched variant-negative controls. RESULTS: The prevalence of APC P/LP variants in this health care cohort is estimated to be 1 in 2800. Twenty-four MyCode APC+ individuals were identified during the study period. Median age at result disclosure was 53 years. Rate of clinical polyposis was 8%. Two of six participants with a classic region variant and none of those with an attenuated region variant had polyposis. MyCode APC+ participants did not differ from controls in cumulative adenoma count. CONCLUSION: APC P/LP variant prevalence estimate in the MyCode cohort is higher than prior published prevalence rates. Individuals with APC P/LP variants identified via genomic screening had a low adenoma burden.

Non-invasive assessment of ventricular electrical heterogeneity to optimize left bundle branch area pacing.

BACKGROUND: Left bundle branch area pacing (LBBAP) is a novel therapeutic option for bradycardia and heart failure patients. ECG belt is a novel technology for assessment of ventricular electrical heterogeneity (VEH) using multi-electrode ECG. A metric of overall VEH based on standard deviation of activation times (SDAT) from all electrodes in the ECG belt has been previously shown to predict cardiac resynchronization therapy (CRT) response. The aim of the study is to evaluate non-invasive assessment of VEH using ECG belt to optimize LBBAP. METHODS: VEH from a 40-electrode ECG belt was characterized in 20 patients (male 15, EF 33 ± 13%, NYHA class 3.05 ± 0.6; CRT indication 18) during LBBAP (20) and LBBAP-Optimized CRT (LOT-CRT-7), anodal capture (16), NS-LBBP (18), S-LBBP (5), LVSP (9). In addition to SDAT, regional (LV/RV) VEH was assessed with average left ventricular activation times (LVAT), SDAT of left-sided (LV dispersion) and right-sided (RV dispersion) electrodes. Optimal LBBAP was determined based on maximal SDAT and QRS duration (d) change. RESULTS: All metrics were significantly reduced (p < 0.0001 for ECG belt metrics, p = 0.0027 for QRSd) during LBBAP and LOT-CRT compared to intrinsic. QRSd, SDAT, LVAT, and LV and RV dispersion during optimal LBBAP were significantly lower (133 ± 20/157 ± 24; 20.5 ± 7.5/38.6 ± 9; 44.4 ± 14.3/61.4 ± 21; 11.6 ± 11.6/29.5 ± 15; 21.1 ± 7.8/42.5 ± 9.3; p < 0.0001) compared to intrinsic rhythm. However, they were not significantly different among selective, non-selective, anodal, and LV septal captures. EF and NYHA class improved to 46 ± 11% and 1.9 ± 0.6 (p < 0.001). CONCLUSIONS: LBBAP significantly reduced overall and regional (RV/LV) VEH, irrespective of the mechanism of capture. Detailed assessment of electrical heterogeneity using ECG belt may add valuable insights on effects of LBBAP. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04583709.

Investigating Psychological Impact after Receiving Genetic Risk Results-A Survey of Participants in a Population Genomic Screening Program.

Genomic screening programs have potential to benefit individuals who may not be clinically ascertained, but little is known about the psychological impact of receiving genetic results in this setting. The current study sought to further the understanding of individuals' psychological response to receiving an actionable genetic test result from genomic screening. Telephone surveys were conducted with patient-participants at 6 weeks and 6 months post genetic result disclosure between September 2019 and May 2021 and assessed emotional response to receiving results via the FACToR, PANAS, and decision regret scales. Overall, 354 (29.4%) study participants completed both surveys. Participants reported moderate positive emotions and low levels of negative emotions, uncertainty, privacy concern, and decision regret over time. There were significant decreases in negative emotions (p = 0.0004) and uncertainty (p = 0.0126) between time points on the FACToR scale. "Interested" was the highest scoring discrete emotion (T1 3.6, T2 3.3, scale 0−5) but was significantly lower at 6 months (<0.0001). Coupled with other benefits of genomic screening, these results of modest psychological impact waning over time adds support to clinical utility of population genomic screening programs. However, questions remain regarding how to elicit an emotional response that motivates behavior change without causing psychological harm.

Patient reported data integration for management of Eosinophilic Esophagitis.

Eosinophilic Esophagitis (EoE) is an esophageal allergic inflammatory disorder triggered by food proteins. Symptoms of EoE are variable within and between individuals. Presenting symptoms may include dysphagia, food bolus impaction, dyspepsia, or more subtle symptoms such as feeding disorders, regurgitation sensation, or nausea. The development and validation of a pediatric EoE patient self-reported and parent proxy-reported outcome symptom scoring tool was created by Franciosi et al. published in BMJ 2011, titled the Pediatric Eosinophilic Esophagitis Symptom Score (PEESS™ v2.0). To date, its use is largely for research purposes. We propose to evaluate the implementation of the PEESS™ v2.0 in a prospective interventional controlled clinical practice. The study included 620 patients over an 18-month period. Surveys were delivered and administered digitally every month through the MyGeisinger.org Patient Portal. Our analysis demonstrated symptom severity and symptom frequency scores significantly improved over time. However, counter to our hypothesis, patients who completed the PEESS™v2.0 ultimately had higher EoE-related health care utilization of office visits and endoscopies compared with those who did not complete the PEESS™v2.0. This could be related to greater awareness of disease activity and/or increased willingness to seek care. Our study, in the context of mobile health tool and patient-reported outcome trends, represents an opportunity for improved disease monitoring at-home within the field of eosinophilic gastrointestinal diseases.

A comparative evaluation of robotic and laparoscopic Roux-en-Y gastric bypass: a critical evaluation on the impact of postoperative pain and opioid requirements.

INTRODUCTION: The benefits of minimally invasive surgery using laparoscopy on postoperative pain and opioid use are well established. Our goal was to determine whether patients who underwent Roux-en-Y gastric bypass using a robotic approach (RA-RYGB) had lower postoperative pain and required less opioids than those undergoing laparoscopic Roux-en-Y gastric bypass (L-RYGB). Secondary outcomes evaluated included length of stay, operative time, and readmissions. METHODS AND PROCEDURES: This was a retrospective cohort study from a tertiary academic medical center. Patients who underwent L-RYGB or RA-RYGB between 5/1/2018 and 10/31/2019 were included. Cases with concomitant hernia repair, chronic opioid use, and those who did not receive a TAP block or multimodal pain control were excluded. Baseline demographics were compared. Inpatient and outpatient opioid use in Morphine Milligram Equivalents (MME) and pain scores (10-point Likert scale) were compared. RESULTS: There were 573 RY patients included (462 L-RYGB; 111 RA-RYGB). Median and maximum inpatient pain scores were similar for L-RYGB and RA-RYGB (3.0 vs 3.1, p = 0.878; 7.0 vs 7.0, p = 0.688). Median inpatient opioid use and maximum single day use were similar for L-RYGB and RA-RYGB (40.0 MME vs. 42.0 MME, p = 0.671; 30.0 MME vs 30.0 MME, p = 0.648). Both the outpatient prescribing of opioids (50.2% vs. 42.3%, p = 0.136) and outpatient opioid MME at 2 weeks (L-RYGB 30.0 MME vs. 33.8 MME, p = 0.854) were comparable between cohorts. Patient reported pain at 2-week follow-up was significantly higher for RA-RYGB (68.1%) than L-RYGB (55.6%) (p = 0.030). RA-RYGB had a higher rate of 30-day readmission and longer operative times compared to the L-RYGB (6.3% vs 13.5%, p = 0.010; 144.5 vs 200.0 min, p < 0.001). CONCLUSION: This study identified no benefit for postoperative pain or opioid requirements in patients undergoing RA-RYGB compared to L-RYGB. The RA-RYGB group was significantly more likely to report pain at the two-week follow-up.

Medical manifestations and health care utilization among adult MyCode participants with neurodevelopmental psychiatric copy number variants.

PURPOSE: Recurrent pathogenic copy number variants (pCNVs) have large-effect impacts on brain function and represent important etiologies of neurodevelopmental psychiatric disorders (NPDs), including autism and schizophrenia. Patterns of health care utilization in adults with pCNVs have gone largely unstudied and are likely to differ in significant ways from those of children. METHODS: We compared the prevalence of NPDs and electronic health record-based medical conditions in 928 adults with 26 pCNVs to a demographically-matched cohort of pCNV-negative controls from >135,000 patient-participants in Geisinger's MyCode Community Health Initiative. We also evaluated 3 quantitative health care utilization measures (outpatient, inpatient, and emergency department visits) in both groups. RESULTS: Adults with pCNVs (24.9%) were more likely than controls (16.0%) to have a documented NPD. They had significantly higher rates of several chronic diseases, including diabetes (29.3% in participants with pCNVs vs 20.4% in participants without pCNVs) and dementia (2.2% in participants with pCNVs vs 1.0% participants without pCNVs), and twice as many annual emergency department visits. CONCLUSION: These findings highlight the potential for genetic information-specifically, pCNVs-to inform the study of health care outcomes and utilization in adults. If, as our findings suggest, adults with pCNVs have poorer health and require disproportionate health care resources, early genetic diagnosis paired with patient-centered interventions may help to anticipate problems, improve outcomes, and reduce the associated economic burden.

Cost and clinical impact of a nonmedical DPP-4 inhibitor switch in patients with diabetes.

BACKGROUND: Nonmedical formulary switches (NMFS) routinely occur in managed health care plans and involve changing preferred medications for reasons outside of clinical considerations. The cost implications of NMFS are infrequently published and the clinical outcomes rarely assessed. OBJECTIVE: To assess the real-world clinical and cost implications of an NMFS involving sitagliptin and linagliptin. METHODS: An NMFS was made to the Geisinger Health Plan (GHP) commercial, health care reform, and Medicaid formularies on February 1, 2018, involving a change in preferred medication from sitagliptin to linagliptin. Claims data from GHP and clinical information from electronic health records of the Geisinger Health System were used to evaluate the cost and clinical impact of this change. Patients aged 18 years or older who were continuously enrolled in a GHP commercial, health care reform, or Medicaid plan throughout the entire study period and had at least 1 fill for sitagliptin during the preswitch phase were included in the study. We investigated the differences in various clinical and economic outcomes from pre- to postswitch among those who switched and remained adherent to the new preferred therapy throughout the 12-month postperiod ("linagliptin switch" group) and patients who did not ("other switch" group). Clinical outcomes included all-cause hospitalization, diabetes-related hospitalization, and glycosylated hemoglobin (HbA1c), while economic measures included changes in per member per month (PMPM) spending. The negative binomial regression model was used to estimate utilization counts. A generalized linear model with a log link and gamma distribution was used to analyze cost data. RESULTS: 1,203 patients met the inclusion criteria. Of these, 501 (41.6%) individuals switched to and remained at least 80% adherent to linagliptin in the postperiod, while 702 (58.4%) did not. No difference between groups was found when comparing the pre- to postswitch change in all-cause hospitalization (incidence rate ratio (IRR) = 1.46, 95% CI = 0.66-3.23, P = 0.3436) or diabetes-related hospitalization (IRR = 1.39, 95% CI = 0.62-3.10, P = 0.4203). Additionally, no difference was found between groups regarding the change in HbA1c 12-month postswitch compared with baseline (difference between groups = -0.10%, 95% CI = -0.39%-0.19%, P = 0.4962). Total PMPM spending was 43% higher in the other switch group compared with the linagliptin switch group (IRR = 1.43, 95% CI = 1.25-1.63, P < 0.0001). This trend was driven by 92% higher medical PMPM spending in the other switch group compared with the linagliptin switch group (IRR = 1.92, 95% CI = 1.58-2.33, P < 0.0001) but was offset by 12% lower pharmacy PMPM spending in the other switch group (IRR = 0.88, 95% CI = 0.82-0.95, P = 0.0009). CONCLUSIONS: An NMFS from sitagliptin to linagliptin resulted in overall health plan savings with no significant changes in health outcomes. DISCLOSURES: Funding for this study was provided by Geisinger Health System, which had no role in the study outside of a final review of the submitted manuscript. Johns and Gionfriddo are Geisinger employees. The authors report no financial conflicts of interest.

Geriatric conditions and treatment burden following diagnosis of non-muscle- invasive bladder cancer in older adults: A population-based analysis.

INTRODUCTION: Treatment burden is emerging as an important patient-centered outcome for older adults with cancer who concurrently manage geriatric conditions. Our objective was to evaluate the contribution of geriatric conditions to treatment burden in older adults with non-muscle invasive bladder cancer (NMIBC). METHODS: We identified 73,395 Medicare beneficiaries age 66+ diagnosed with NMIBC (Stage

Impact of the Centers for Medicare and Medicaid Services Sepsis Core Measure on Antibiotic Use.

BACKGROUND: The Centers for Medicare and Medicaid Services (CMS) implemented a core measure sepsis (SEP-1) bundle in 2015. One element was initiation of broad-spectrum antibiotics within 3 hours of diagnosis. The policy has the potential to increase antibiotic use and Clostridioides difficile infection (CDI). We evaluated the impact of SEP-1 implementation on broad-spectrum antibiotic use and CDI occurrence rates. METHODS: Monthly adult antibiotic data for 4 antibiotic categories (surgical prophylaxis, broad-spectrum for community-acquired infections, broad-spectrum for hospital-onset/multidrug-resistant [MDR] organisms, and anti-methicillin-resistant Staphylococcus aureus [MRSA]) from 111 hospitals participating in the Clinical Data Base Resource Manager were evaluated in periods before (October 2014-September 2015) and after (October 2015-June 2017) policy implementation. Interrupted time series analyses, using negative binomial regression, evaluated changes in antibiotic category use and CDI rates. RESULTS: At the hospital level, there was an immediate increase in the level of broad-spectrum agents for hospital-onset/MDR organisms (+2.3%, P = .0375) as well as a long-term increase in trend (+0.4% per month, P = .0273). There was also an immediate increase in level of overall antibiotic use (+1.4%, P = .0293). CDI rates unexpectedly decreased at the time of SEP-1 implementation. When analyses were limited to patients with sepsis, there was a significant level increase in use of all antibiotic categories at the time of SEP-1 implementation. CONCLUSIONS: SEP-1 implementation was associated with immediate and long-term increases in broad-spectrum hospital-onset/MDR organism antibiotics. Antimicrobial stewardship programs should evaluate sepsis treatment for opportunities to de-escalate broad therapy as indicated.

Communicating Mammography Results: By What Method and How Quickly Do Women Want Their Screening Mammogram Results?

The purpose of the survey study was to understand the majority preference with regards to the wait time for screening mammogram results, whether prompt communication of mammogram results was of importance to patients, whether the time frame to schedule an additional imaging follow-up appointment after an abnormal screening mammogram was important to patients, and how patients preferred to be given their screening mammogram results. There were 2,245 patients who participated in the survey. A majority of patients preferred to receive screening mammogram results on Friday (n = 1,868, 85.4%), even if their mammogram was abnormal, requiring a follow-up appointment that could not be scheduled until the following week. Most individuals preferred to schedule their follow-up appointments soon after their initial appointment, preferring either the next day or within 1 to 2 days. Finally, over half of the sample preferred to be contacted via a telephone call, with letter and text messaging being the next most preferred methods and e-mail being the least preferred. Survey results suggest that the preferred wait time for screening mammogram results was either to wait at the time of screening mammogram appointment or to receive results within 48 hours. These suggestions can help clinics and providers make changes to how they communicate screening mammogram results. The strong preference of patients receiving their screening mammogram results more promptly should help trigger alternative methods toward improving communication between the radiologist and the patient.

Long-Term Parathyroid Hormone 1-34 Replacement Therapy in Children with Hypoparathyroidism.

OBJECTIVE: To determine whether multiple daily injections of parathyroid hormone (PTH) 1-34 are safe and effective as long-term therapy for children with hypoparathyroidism. STUDY DESIGN: Linear growth, bone accrual, renal function, and mineral homeostasis were studied in a long-term observational study of PTH 1-34 injection therapy in 14 children. METHODS: Subjects were 14 children with hypoparathyroidism attributable to autoimmune polyglandular syndrome type 1 (N = 5, ages 7-12 years) or calcium receptor mutation (N = 9, ages 7-16 years). Mean daily PTH 1-34 dose was 0.75 ± 0.15 µg/kg/day. Treatment duration was 6.9 ± 3.1 years (range 1.5-10 years). Patients were evaluated semiannually at the National Institutes of Health Clinical Center. RESULTS: Mean height velocity and lumbar spine, whole body, and femoral neck bone accretion velocities were normal throughout the study. In the first 2 years, distal one-third radius bone accrual velocity was reduced compared with normal children (P < .003). Serum alkaline phosphatase correlated with PTH 1-34 dose (P < .006) and remained normal (235.3 ± 104.8 [SD] U/L, N: 51-332 U/L). Mean serum and 24-hour urine calcium levels were 2.05 ± 0.11 mmol/L (N: 2.05-2.5 mmol/L) and 6.93 ± 1.3 mmol/24 hour (N: 1.25-7.5 mmol/24 hour), respectively-with fewer high urine calcium levels vs baseline during calcitriol and calcium treatment (P < .001). Nephrocalcinosis progressed in 5 of 12 subjects who had repeated renal imaging although renal function remained normal. CONCLUSIONS: Twice-daily or thrice-daily subcutaneous PTH 1-34 injections provided safe and effective replacement therapy for up to 10 years in children with hypoparathyroidism because of autoimmune polyglandular syndrome type 1 or calcium receptor mutation.

Longitudinal changes in gestational weight gain and the association with intrauterine fetal growth.

OBJECTIVE: Total pregnancy weight gain has been associated with infant birthweight; however, most prior studies lacked repeat ultrasound measurements. Understanding of the longitudinal changes in maternal weight gain and intrauterine changes in fetal anthropometrics is limited. STUDY DESIGN: Prospective data from 1314 Scandinavian singleton pregnancies at high-risk for delivering small-for-gestational-age (SGA) were analyzed. Women had ≥1 (median 12) antenatal weight measurements. Ultrasounds were targeted at 17, 25, 33, and 37 weeks of gestation. Analyses involved a multi-step process. First, trajectories were estimated across gestation for maternal weight gain and fetal biometrics [abdominal circumference (AC, mm), biparietal diameter (BPD, mm), femur length (FL, mm), and estimated fetal weight (EFW, g)] using linear mixed models. Second, the association between maternal weight changes (per 5 kg) and corresponding fetal growth from 0 to 17, 17 to 28, and 28 to 37 weeks was estimated for each fetal parameter adjusting for prepregnancy body mass index, height, parity, chronic diseases, age, smoking, fetal sex, and weight gain up to the respective period as applicable. Third, the probability of fetal SGA, EFW <10th percentile, at the 3rd ultrasound was estimated across the spectrum of maternal weight gain rate by SGA status at the 2nd ultrasound. RESULTS: From 0 to 17 weeks, changes in maternal weight were most strongly associated with changes in BPD [ß=0.51 per 5 kg (95%CI 0.26, 0.76)] and FL [ß=0.46 per 5 kg (95%CI 0.26, 0.65)]. From 17 to 28 weeks, AC [ß=2.92 per 5 kg (95%CI 1.62, 4.22)] and EFW [ß=58.7 per 5 kg (95%CI 29.5, 88.0)] were more strongly associated with changes in maternal weight. Increased maternal weight gain was significantly associated with a reduced probability of intrauterine SGA; for a normal weight woman with SGA at the 2nd ultrasound, the probability of fetal SGA with a weight gain rate of 0.29 kg/w (10th percentile) was 59%, compared to 38% with a rate of 0.67 kg/w (90th percentile). CONCLUSION: Among women at high-risk for SGA, maternal weight gain was associated with fetal growth throughout pregnancy, but had a differential relationship with specific biometrics across gestation. For women with fetal SGA identified mid-pregnancy, increased antenatal weight gain was associated with a decreased probability of fetal SGA approximately 7 weeks later.