ß-Blocker Use and Clinical Outcomes in Patients With COPD Following Acute Myocardial Infarction.

Importance: While ß-blockers are associated with decreased mortality in cardiovascular disease (CVD), exacerbation-prone patients with chronic obstructive pulmonary disease (COPD) who received metoprolol in the Beta-Blockers for the Prevention of Acute Exacerbations of Chronic Obstructive Pulmonary Disease (BLOCK-COPD) trial experienced increased risk of exacerbations requiring hospitalization. However, the study excluded individuals with established indications for the drug, raising questions about the overall risk and benefit in patients with COPD following acute myocardial infarction (AMI). Objective: To investigate whether ß-blocker prescription at hospital discharge is associated with increased risk of mortality or adverse cardiopulmonary outcomes in patients with COPD and AMI. Design, Setting, and Participants: This prospective, longitudinal cohort study with 6 months of follow-up enrolled patients aged 35 years or older with COPD who underwent cardiac catheterization for AMI at 18 BLOCK-COPD network hospitals in the US from June 2020 through May 2022. Exposure: Prescription for any ß-blocker at hospital discharge. Main Outcomes and Measures: The primary outcome was time to the composite outcome of death or all-cause hospitalization or revascularization. Secondary outcomes included death, hospitalization, or revascularization for CVD events, death or hospitalization for COPD or respiratory events, and treatment for COPD exacerbations. Results: Among 3531 patients who underwent cardiac catheterization for AMI, prevalence of COPD was 17.1% (95% CI, 15.8%-18.4%). Of 579 total patients with COPD and AMI, 502 (86.7%) were prescribed a ß-blocker at discharge. Among the 562 patients with COPD included in the final analysis, median age was 70.0 years (range, 38.0-94.0 years) and 329 (58.5%) were male; 553 of the 579 patients (95.5%) had follow-up information. Among those discharged with ß-blockers, there was no increased risk of the primary end point of all-cause mortality, revascularization, or hospitalization (hazard ratio [HR], 1.01; 95% CI, 0.66-1.54; P = .96) or of cardiovascular events (HR, 1.11; 95% CI, 0.65-1.92; P = .69), COPD-related or respiratory events (HR, 0.75; 95% CI, 0.34-1.66; P = .48), or treatment for COPD exacerbations (rate ratio, 1.01; 95% CI, 0.53-1.91; P = .98). Conclusions and Relevance: In this cohort study, ß-blocker prescription at hospital discharge was not associated with increased risk of adverse outcomes in patients with COPD and AMI. These findings support use of ß-blockers in patients with COPD and recent AMI.

Factors associated with oral hygiene compliance in patients treated with radiation therapy for head and neck cancer.

BACKGROUND: Patients who are oral hygiene noncompliant (OHNC) are more likely to lose teeth after radiation therapy (RT) for head and neck cancer (HNC), which increases the risk of developing osteoradionecrosis. A previous study revealed that patients who were OHNC at baseline (BL) who became oral hygiene compliant during follow-up had the best tooth-failure outcomes. The purpose of this study was to identify factors associated with oral hygiene compliance (OHC), overall, and among those who were BL OHNC. METHODS: This was an observational, prospective, cohort study of 518 patients with HNC assessed before RT and at post-RT follow-up visits every 6 months for 2 years. Patient and treatment-related information was collected at BL and during follow-up, including self-reported OHC. OHC was defined as toothbrushing at least twice daily and flossing at least once daily. RESULTS: Of the 296 patients who self-reported being BL OHNC, 44 (14.9%) became oral hygiene compliant at all follow-up visits. Among this group, those who had dental insurance (P = .026), surgery before RT (P = .008), limited mouth opening before RT (P = .001), compliant fluoride use (P = .023), primary RT site of oral cavity (P = .004), and primary surgical site of larynx and hypopharynx (P = .042) were more likely to become oral hygiene compliant post-RT. CONCLUSIONS: The reasons for the cohort of patients with HNC in this study being OHNC are multifaceted and relate to socioeconomic factors and cancer characteristics. PRACTICAL IMPLICATIONS: Finding ways to increase OHC and fluoride use among patients with HNC who are at greatest risk of being OHNC should be explored.

Reduced mouth opening in patients with head and neck cancer treated with radiation therapy: an analysis of the Clinical Registry of Dental Outcomes in Head and Neck Cancer Patients (OraRad).

OBJECTIVE: Trismus/reduced mouth opening (RMO) is a common side effect of radiotherapy (RT) for head and neck cancer (HNC). The objective was to measure RMO, identify risk factors for RMO, and determine its impact on quality of life (QOL). STUDY DESIGN: OraRad is an observational, prospective, multicenter cohort study of patients receiving curative intent RT for HNC. Interincisal mouth opening measurements (n = 565) and patient-reported outcomes were recorded before RT and every 6 months for 2 years. Linear mixed-effects models were used to evaluate change in mouth opening and assess the relationship between trismus history and change in QOL measures. RESULTS: Interincisal distance decreased from a mean (SE) of 45.1 (0.42) mm at baseline to 42.2 (0.44) at 6 months, with slight recovery at 18 months (43.3, 0.46 mm) but no additional improvement by 24 months. The odds of trismus (opening <35 mm) were significantly higher at 6 months (odds ratio [OR] = 2.21, 95% CI: 1.30 to 3.76) and 12 months (OR = 1.87, 95% CI: 1.08 to 3.25) compared with baseline. Females were more likely to experience trismus at baseline and during follow-up (P < .01). Patients with oral cavity cancer had the highest risk for trismus at baseline and post-RT (P < .01). RMO was associated with higher RT dose to the primary site and receiving concomitant chemotherapy (P < .01). Trismus was associated with self-reported difficulty opening the mouth and dry mouth (P < .01). CONCLUSIONS: A decrease in mouth opening is a common treatment-related toxicity after RT, with some recovery by 18 months. Trismus has a significant impact on survivor QOL.

Associations Between Coronary Artery Calcium Score and Exacerbation Risk in BLOCK-COPD.

Introduction: In 2019, the Beta-Blockers for the Prevention of Acute Exacerbations of Chronic Obstructive Pulmonary Disease study (BLOCK-COPD) evaluated the effect of metoprolol on exacerbation risk and mortality in a COPD population without indications for beta-blocker use. We hypothesized that an imaging metric of coronary artery disease (CAD), the coronary artery calcium (CAC) score, would predict exacerbation risk and identify a differential response to metoprolol treatment. Methods: The study population includes participants in the BLOCK-COPD study from multiple study sites. Participants underwent clinically indicated thoracic computed tomography (CT) scans ± 12 months from enrollment. The Weston scoring system quantified CAC. Adjusted Cox proportional hazards models evaluated for associations between CAC and time to exacerbation. Results: Data is included for 109 participants. The mean CAC score was 5.1±3.7, and 92 participants (84%) had CAC scores greater than 0. Over a median (interquartile range) follow-up time of 350 (280 to 352) days, there were 61 mild exacerbations and 19 severe/very severe exacerbations. No associations were found between exacerbations of any severity and CAC>0 or total CAC. Associations were observed between total CAC and CAC>0 in the left circumflex (LCx) and time to exacerbation of any severity (adjusted hazard ratio [aHR]=1.39, confidence interval [CI]: 1.08-1.79, p=0.01) and (aHR=1.96, 95% CI: 1.04-3.70, p=0.04), respectively. Conclusions: CAD is a prevalent comorbidity in COPD accounting for significant mortality. Our study confirms the high prevalence of CAD using the CAC score; however, we did not discover an association between CAC and exacerbation risk. We did find novel associations between CAC in the LCx and exacerbation risk which warrant further investigation in larger cohorts.

Association between P-pulmonale and respiratory morbidity in COPD: a secondary analysis of the BLOCK-COPD trial.

RATIONALE: Pulmonary hypertension (PH) in COPD confers increased risk of exacerbations (ECOPD). Electrocardiogram (ECG) indicators of PH are prognostic both in PH and COPD. In the Beta-Blockers for the Prevention of Acute Exacerbations of COPD (BLOCK-COPD) trial, metoprolol increased risk of severe ECOPD through unclear mechanisms. OBJECTIVE: We evaluated whether an ECG indicator of PH, P-pulmonale, would be associated with ECOPD and whether participants with P-pulmonale randomized to metoprolol were at higher risk of ECOPD and worsened respiratory symptoms given the potential detrimental effects of beta-blockers in PH. METHODS: ECGs of 501 participants were analyzed for P-pulmonale (P wave enlargement in lead II). Cox proportional hazards models evaluated for associations between P-pulmonale and time to ECOPD (all and severe) for all participants and by treatment assignment (metoprolol vs. placebo). Linear mixed-effects models evaluated the association between treatment assignment and P-pulmonale on change in symptom scores (measured by CAT and SOBQ). RESULTS: We identified no association between P-pulmonale and risk of any ECOPD or severe ECOPD. However, in individuals with P-pulmonale, metoprolol was associated with increased risk for ECOPD (aHR 2.92, 95% CI: 1.45-5.85). There was no association between metoprolol and ECOPD in individuals without P-pulmonale (aHR 1.01, 95% CI: 0.77-1.31). Individuals with P-pulmonale assigned to metoprolol experienced worsening symptoms (mean increase of 3.95, 95% CI: 1.32-6.58) whereas those assigned to placebo experienced a mean improvement in CAT score of -2.45 (95% CI: -0.30- -4.61). CONCLUSIONS: In individuals with P-pulmonale, metoprolol was associated with increased exacerbation risk and worsened symptoms. These findings may explain the findings observed in BLOCK-COPD.

Sigh Ventilation in Patients With Trauma: The SiVent Randomized Clinical Trial.

Importance: Among patients receiving mechanical ventilation, tidal volumes with each breath are often constant or similar. This may lead to ventilator-induced lung injury by altering or depleting surfactant. The role of sigh breaths in reducing ventilator-induced lung injury among trauma patients at risk of poor outcomes is unknown. Objective: To determine whether adding sigh breaths improves clinical outcomes. Design, Setting, and Participants: A pragmatic, randomized trial of sigh breaths plus usual care conducted from 2016 to 2022 with 28-day follow-up in 15 academic trauma centers in the US. Inclusion criteria were age older than 18 years, mechanical ventilation because of trauma for less than 24 hours, 1 or more of 5 risk factors for developing acute respiratory distress syndrome, expected duration of ventilation longer than 24 hours, and predicted survival longer than 48 hours. Interventions: Sigh volumes producing plateau pressures of 35 cm H2O (or 40 cm H2O for inpatients with body mass indexes >35) delivered once every 6 minutes. Usual care was defined as the patient's physician(s) treating the patient as they wished. Main Outcomes and Measures: The primary outcome was ventilator-free days. Prespecified secondary outcomes included all-cause 28-day mortality. Results: Of 5753 patients screened, 524 were enrolled (mean [SD] age, 43.9 [19.2] years; 394 [75.2%] were male). The median ventilator-free days was 18.4 (IQR, 7.0-25.2) in patients randomized to sighs and 16.1 (IQR, 1.1-24.4) in those receiving usual care alone (P = .08). The unadjusted mean difference in ventilator-free days between groups was 1.9 days (95% CI, 0.1 to 3.6) and the prespecified adjusted mean difference was 1.4 days (95% CI, -0.2 to 3.0). For the prespecified secondary outcome, patients randomized to sighs had 28-day mortality of 11.6% (30/259) vs 17.6% (46/261) in those receiving usual care (P = .05). No differences were observed in nonfatal adverse events comparing patients with sighs (80/259 [30.9%]) vs those without (80/261 [30.7%]). Conclusions and Relevance: In a pragmatic, randomized trial among trauma patients receiving mechanical ventilation with risk factors for developing acute respiratory distress syndrome, the addition of sigh breaths did not significantly increase ventilator-free days. Prespecified secondary outcome data suggest that sighs are well-tolerated and may improve clinical outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT02582957.

Transportability of causal inference under random dynamic treatment regimes for kidney-pancreas transplantation.

A difficult decision for patients in need of kidney-pancreas transplant is whether to seek a living kidney donor or wait to receive both organs from one deceased donor. The framework of dynamic treatment regimes (DTRs) can inform this choice, but a patient-relevant strategy such as "wait for deceased-donor transplant" is ill-defined because there are multiple versions of treatment (i.e., wait times, organ qualities). Existing DTR methods average over the distribution of treatment versions in the data, estimating survival under a "representative intervention." This is undesirable if transporting inferences to a target population such as patients today, who experience shorter wait times thanks to evolutions in allocation policy. We, therefore, propose the concept of a generalized representative intervention (GRI): a random DTR that assigns treatment version by drawing from the distribution among strategy compliers in the target population (e.g., patients today). We describe an inverse-probability-weighted product-limit estimator of survival under a GRI that performs well in simulations and can be implemented in standard statistical software. For continuous treatments (e.g., organ quality), weights are reformulated to depend on probabilities only, not densities. We apply our method to a national database of kidney-pancreas transplant candidates from 2001-2020 to illustrate that variability in transplant rate across years and centers results in qualitative differences in the optimal strategy for patient survival.

The Minnesota attributable risk of kidney donation (MARKD) study: a retrospective cohort study of long-term (> 50 year) outcomes after kidney donation compared to well-matched healthy controls.

BACKGROUND: There is uncertainty about the long-term risks of living kidney donation. Well-designed studies with controls well-matched on risk factors for kidney disease are needed to understand the attributable risks of kidney donation. METHODS: The goal of the Minnesota Attributable Risk of Kidney Donation (MARKD) study is to compare the long-term (> 50 years) outcomes of living donors (LDs) to contemporary and geographically similar controls that are well-matched on health status. University of Minnesota (n = 4022; 1st transplant: 1963) and Mayo Clinic LDs (n = 3035; 1st transplant: 1963) will be matched to Rochester Epidemiology Project (REP) controls (approximately 4 controls to 1 donor) on the basis of age, sex, and race/ethnicity. The REP controls are a well-defined population, with detailed medical record data linked between all providers in Olmsted and surrounding counties, that come from the same geographic region and era (early 1960s to present) as the donors. Controls will be carefully selected to have health status acceptable for donation on the index date (date their matched donor donated). Further refinement of the control group will include confirmed kidney health (e.g., normal serum creatinine and/or no proteinuria) and matching (on index date) of body mass index, smoking history, family history of chronic kidney disease, and blood pressure. Outcomes will be ascertained from national registries (National Death Index and United States Renal Data System) and a new survey administered to both donors and controls; the data will be supplemented by prior surveys and medical record review of donors and REP controls. The outcomes to be compared are all-cause mortality, end-stage kidney disease, cardiovascular disease and mortality, estimated glomerular filtration rate (eGFR) trajectory and chronic kidney disease, pregnancy risks, and development of diseases that frequently lead to chronic kidney disease (e.g. hypertension, diabetes, and obesity). We will additionally evaluate whether the risk of donation differs based on baseline characteristics. DISCUSSION: Our study will provide a comprehensive assessment of long-term living donor risk to inform candidate living donors, and to inform the follow-up and care of current living donors.

Oral health-related quality of life after radiation therapy for head and neck cancer: the OraRad study.

PURPOSE: Head and neck cancer (HNC) treatment results in morbidity impacting quality of life (QOL) in survivorship. This analysis evaluated changes in oral health-related QOL (OH-QOL) up to 2 years after curative intent radiation therapy (RT) for HNC patients and factors associated with these changes. METHODS: 572 HNC patients participated in a multicenter, prospective observational study (OraRad). Data collected included sociodemographic, tumor, and treatment variables. Ten single-item questions and 2 composite scales of swallowing problems and senses problems (taste and smell) from a standard QOL instrument were assessed before RT and at 6-month intervals after RT. RESULTS: The most persistently impacted OH-QOL variables at 24 months included: dry mouth; sticky saliva, and senses problems. These measures were most elevated at the 6-month visit. Aspects of swallowing were most impacted by oropharyngeal tumor site, chemotherapy, and non-Hispanic ethnicity. Problems with senses and dry mouth were worse with older age. Dry mouth and sticky saliva increased more among men and those with oropharyngeal cancer, nodal involvement, and use of chemotherapy. Problems with mouth opening were increased by chemotherapy and were more common among non-White and Hispanic individuals. A 1000 cGy increase in RT dose was associated with a clinically meaningful change in difficulty swallowing solid food, dry mouth, sticky saliva, sense of taste, and senses problems. CONCLUSIONS: Demographic, tumor, and treatment variables impacted OH-QOL for HNC patients up to 2 years after RT. Dry mouth is the most intense and sustained toxicity of RT that negatively impacts OH-QOL of HNC survivors. GOV IDENTIFIER: NCT02057510; first posted February 7, 2014.

Long-term Outcomes Associated With Post-kidney Donation Pregnancy Complications.

BACKGROUND: Kidney donors have increased risk of postdonation gestational hypertension (gHTN) and preeclampsia. In the general population, pregnancy complications are associated with long-term maternal risk. However, little data exist on whether donors with postdonation pregnancy-related complications have similar increased long-term risks. We studied whether postdonation gHTN, preeclampsia/eclampsia, or gestational diabetes (gDM) was associated with increased risk of developing hypertension, DM, cardiovascular disease, or estimated glomerular filtration rate <45 mL/min/1.73 m 2 . METHODS: Postdonation pregnancies with complications were matched to pregnancies without complications based on time from donation. Incidence of outcomes was compared using sequential Cox regression with robust standard errors. Donors with predonation pregnancy complications were excluded. Models were adjusted for age at pregnancy, gravidity, year of donation, and family history of hypertension, DM, and heart disease. RESULTS: Of the 384 donors with postdonation pregnancies (median [quartiles] follow-up of 27.0 [14.2-36.2] y after donation), 39 experienced preeclampsia/eclampsia, 29 gHTN without preeclampsia, and 17 gDM. Median interval from donation to first pregnancy with preeclampsia was 5.1 (2.9-8.6) y; for gHTN, 3.7 (1.9-7.8) y; and for gDM, 7.3 (3.7-10.3) y. Preeclampsia/eclampsia (hazard ratio [HR] 2.70; 95% confidence interval [CI], 1.53-4.77) and gHTN (HR 2.39; 95% CI, 1.24-4.60) were associated with development of hypertension. Preeclampsia/eclampsia (HR 2.15; 95% CI, 1.11-4.16) and gDM (HR 5.60; 95% CI, 1.41-22.15) were associated with development of DM. Pregnancy-related complications were not associated with increased risk of cardiovascular disease or estimated glomerular filtration rate <45 mL/min/1.73 m 2 . CONCLUSIONS: In our single-center study, postdonation preeclampsia, gHTN, or gDM was associated with long-term risk of hypertension or DM.

Development and Validation of a Hypertension Risk Calculator for Living Kidney Donors.

BACKGROUND: Ideally, when deciding whether to donate, kidney donor candidates would understand their long-term risks. Using single-center data (N = 4055; median [quartiles] follow-up: 18 [9-28] y), we developed a calculator for postdonation hypertension and validated it using long-term data from an external single-center cohort (N = 1189, median [quartiles] follow-up: 9 [5-17] y). METHODS: Risk factors considered were routinely obtained at evaluation from donor candidates. Two modeling approaches were evaluated: Cox proportional hazards and random survival forest models. Cross-validation prediction error and Harrell's concordance-index were used to compare accuracy for model development. Top-performing models were assessed in the validation cohort using the concordance-index and net reclassification improvement. RESULTS: In the development cohort, 34% reported hypertension at a median (quartiles) of 16 (8-24) y postdonation; and in the validation cohort, 29% reported hypertension after 17 (10-22) y postdonation. The most accurate model was a Cox proportional hazards model with age, sex, race, estimated glomerular filtration rate, systolic and diastolic blood pressure, body mass index, glucose, smoking history, family history of hypertension, relationship with recipient, and hyperlipidemia (concordance-index, 0.72 in the development cohort and 0.82 in the validation cohort). CONCLUSIONS: A postdonation hypertension calculator was developed and validated; it provides kidney donor candidates, their family, and care team a long-term projection of hypertension risk that can be incorporated into the informed consent process.

Survey of experiences and barriers to dental care post-head and neck cancer in OraRad study participants.

PURPOSE: Dental care after head and neck cancer (HNC) treatment is crucial to maintaining oral health and preventing/treating oral complications. This survey investigated the experiences and barriers to dental care post-radiation therapy (RT). METHODS: Participants of the Clinical Registry of Dental Outcomes in patients with head and neck cancer (OraRad) were surveyed at approximately 4 years post-RT. Participants completed a 20-question survey which assessed perceptions of dental care and education, barriers to receiving care, and ongoing physical symptoms post-RT. RESULTS: One hundred fifty-three of the 505 available OraRad participants completed the survey. Almost all of the respondents (n = 141; 92%) either strongly agreed or agreed that they understand the effects of cancer and its treatment on the teeth, mouth, and jaws. The majority (n = 119; 80%) strongly agreed or agreed that their dentist provided them with information on how to keep teeth, mouth, and jaws healthy after treatment. Most participants reported dry mouth (n = 114; 75%). Other sequelae were problems swallowing (n = 57; 38%), dental caries (n = 33; 22%), and difficulty keeping their mouth open during dental procedures (n = 26; 17%). CONCLUSIONS: The OraRad respondents reported few barriers to dental care post-HNC treatment. Patients continue to suffer oral/maxillofacial side effects of radiation treatment, most notably xerostomia.

Lung Function and the Risk of Exacerbation in the ß-Blockers for the Prevention of Acute Exacerbations of Chronic Obstructive Pulmonary Disease Trial.

Rationale: The BLOCK COPD (ß-Blockers for the Prevention of Acute Exacerbations of Chronic Obstructive Pulmonary Disease) study found that metoprolol was associated with a higher risk of severe exacerbation. Objectives: To determine the mechanism underlying these results, we compared changes in lung function over the course of the study between treatment groups and evaluated whether baseline bronchodilator response or early reduction in forced expiratory volume in 1 second (FEV1) or forced vital capacity (FVC) was associated with exacerbation risk. Methods: We compared changes in lung function (FEV1 and FVC) over the treatment period between treatment groups using linear mixed-effect models. Cox proportional hazards models were used to evaluate the association between baseline bronchodilator responsiveness (FEV1, FVC, and combined FEV1 and FVC), early post-randomization (14 d) change in lung function, and the interaction between treatment assignment and these measures with risk of any or severe or very severe exacerbations. Negative binomial models were used to evaluate the relationship between bronchodilator responsiveness, the interaction between bronchodilator responsiveness and treatment assignment, and exacerbation rate. Results: Over the 336-day treatment period, individuals in the metoprolol group had a significantly greater decrease in logarithmic FEV1 from baseline to visit on Day 28 than individuals in the placebo group. Individuals in the metoprolol group had a significantly greater decrease in FVC from baseline to visits on Days 14 and 28, and also a significantly greater decrease in logarithmic FVC from baseline to visits on Days 42 and 112 than individuals in the placebo group. There were no associations between early lung function reduction or interactions between lung function reduction and treatment assignment and time to any or severe or very severe exacerbations. There were no interactions between treatment arm and baseline bronchodilator responsiveness measures on risk or rate of exacerbations. However, those with baseline FVC bronchodilator responsiveness had a higher rate of severe or very severe exacerbations (adjusted rate ratio, 1.62; 95% confidence interval, 1.04-2.48). Conclusions: Metoprolol was associated with reduced lung function during the early part of the treatment period, but these effects were modest and did not persist. Early lung function reduction and baseline bronchodilator responsiveness did not interact with the treatment arm to predict exacerbations; however, baseline FVC bronchodilator responsiveness was associated with a 60% higher rate of severe or very severe exacerbations. Clinical trial registered with www.clinicaltrials.gov (NCT02587351).

Pre-kidney Donation Pregnancy Complications and Long-term Outcomes.

BACKGROUND: Hypertension and diabetes are contraindications for living kidney donation in young candidates. However, little is known about the long-term outcomes of women who had these pregnancy-related complications and subsequently became donors. In the general population, gestational hypertension (GHtn), preeclampsia/eclampsia, and gestational diabetes (GDM) are associated with long-term risks. METHODS: Donors with the specified predonation complication were matched to contemporary control donors with pregnancies without the complication using nearest neighbor propensity score matching. Propensity scores were estimated using logistic regression with covariates for gravidity, blood pressure, glucose, body mass index, age, and creatinine at donation, donation year, race, relationship with recipient, and family history of disease. Long-term incidence of hypertension, diabetes, cardiovascular disease, and reduced renal function (estimated glomerular filtration rate [eGFR] <30, eGFR <45 mL/min/1.73 m 2 ) were compared between groups using proportional hazards models. RESULTS: Of 1862 donors with predonation pregnancies, 48 had preeclampsia/eclampsia, 49 had GHtn without preeclampsia, and 43 had GDM. Donors had a long interval between first pregnancy and donation (median, 18.5 y; interquartile range, 10.6-27.5) and a long postdonation follow-up time (median, 18.0; interquartile range, 9.2-27.7 y). GHtn was associated with the development of hypertension (hazard ratio, 1.89; 95% confidence interval, 1.26-2.83); GDM was associated with diabetes (hazard ratio, 3.04; 95% confidence interval, 1.33-6.99). Pregnancy complications were not associated with eGFR <30 or eGFR <45 mL/min/1.73 m 2 . CONCLUSIONS: Our data suggest that women with predonation pregnancy-related complications have long-term risks even with a normal donor evaluation. Donor candidates with a history of pregnancy-related complications should be counseled about these risks.

Heart Rate Variability on 10-Second Electrocardiogram and Risk of Acute Exacerbation of COPD: A Secondary Analysis of the BLOCK COPD Trial.

Introduction: Autonomic dysfunction is common in chronic obstructive pulmonary disease (COPD), and worse autonomic function may be a marker of risk for acute exacerbations of COPD (AECOPD). Heart rate variability (HRV) is a measure of autonomic function. Our objective was to test whether lower (worse) HRV is a risk factor for AECOPD. Methods: We measured standard deviation of normal RR intervals (SDNN) and root mean square of successive RR interval differences (RMSSD) on 10-second electrocardiograms (ECGs) performed at screening and day 42 in participants in the Beta Blockers for the Prevention of Acute Exacerbations of COPD trial ( BLOCK-COPD), a placebo-controlled trial of metoprolol for prevention of AECOPD. We used Cox-proportional hazards models to test if these HRV measures were associated with risk of any AECOPD, and separately, hospitalized AECOPD. We tested associations using baseline HRV measures and incorporating HRV measures from day 42 as a time-varying covariate. We also tested for interactions with metoprolol assignment. Results: Of 532 trial participants, 529 (forced expiratory volume in 1 second [FEV1 ]41 ± 16.3 % predicted) were included in this analysis. We did not find a significant association between HRV measures and risk of AECOPD when all participants were analyzed together. There was a significant interaction between RMSSD and assignment to metoprolol on time to first hospitalized AECOPD; in the placebo group greater RMSSD was associated with a lower risk of hospitalized AECOPD (adjusted hazard ratio0.71, 95% confidence interval: 0.52 to 0.96, per 10 ms increase) but there was no association in the metoprolol group. Conclusions: Autonomic dysfunction as measured by HRV may be a risk factor for AECOPD. Future studies should analyze longer HRV recordings and their performance in broader samples of people with COPD, including those on beta-blockers.

Radiation therapy for head and neck cancer leads to gingival recession associated with dental caries.

OBJECTIVE: The aim of this study was to examine effects of radiation therapy (RT) for head and neck cancer (HNC) on periodontal disease and relationships to caries. STUDY DESIGN: A multicenter prospective observational cohort study (OraRad) was conducted in patients undergoing RT for HNC. Assessments were conducted by calibrated examiners at the pre-RT (baseline) visit (n = 533), the 12-month visit (n = 414), and the 24-month visit (n = 365). RESULTS: The average whole mouth mean (standard error (SE)) distance from the cementoenamel junction to the gingival margin (CEJ-GM) decreased significantly from 0.43 (0.04) mm at baseline to 0.24 (0.04) mm at 12 months and 0.11 (0.04) mm at 24 months (P ≤ .001). Whole mouth mean (SE) percentage of sites with CEJ-GM distance of <0 mm increased significantly from 23.3% (1.0%) at baseline to 28.5% (1.0%) at 12 months and 30.5% (1.1%) at 24 months (P ≤ .02). Higher mean radiation dose to the mandible was associated with a greater increase in the percentage of mandibular sites with CEJ-GM distance of <0 mm (P = .003). Both mean CEJ-GM distance and the percentage of sites with a CEJ-GM distance <0 mm were strongly associated with whole mouth mean proportion of decayed, missing, and filled surfaces, as well as proportion of decayed or filled facial/buccal surfaces specifically, (P < .001), with greater gingival recession associated with increased caries. CONCLUSIONS: RT for HNC leads to mandibular gingival recession in a dose-dependent manner. This gingival recession may contribute to increased risk for cervical caries seen in these patients.

The impact of head and neck radiotherapy on salivary flow and quality of life: Results of the ORARAD study.

OBJECTIVES: Salivary hypofunction and xerostomia, are common side effects of radiotherapy, negatively impacting quality of life. The OraRad study presents results on the longitudinal impact of radiotherapy on salivary flow and patient-reported outcomes. PATIENTS AND METHODS: Prospective, multicenter cohort study of 572 patients receiving curative-intent head and neck radiotherapy (RT). Stimulated salivary flow (SSF) rate and patient-reported outcomes were measured prior to RT and at 6- and 18-months post-RT. Linear mixed effects models examined the relationship between RT dose and change in salivary flow, and change in patient-reported outcomes. RESULTS: 544 patients had baseline salivary flow measurement, with median (IQR) stimulated flow rate of 0.975 (0.648, 1.417) g/min. Average RT dose to parotid glands was associated with change in salivary flow post-RT (p < 0.001). Diminished flow to 37% of pre-RT level was observed at 6 months (median: 0.358, IQR: 0.188 to 0.640 g/min, n = 481) with partial recovery to 59% of pre-RT at 18 months (median: 0.575, IQR: 0.338 to 0.884 g/min, n = 422). Significant improvement in patient-reported swallowing, senses (taste and smell), mouth opening, dry mouth, and sticky saliva (p-values < 0.03) were observed between 6 and 18 months post-RT. Changes in swallowing, mouth opening, dry mouth, and sticky saliva were significantly associated with changes in salivary flow from baseline (p-values < 0.04). CONCLUSION: Salivary flow and patient-reported outcomes decreased as a result of RT, but demonstrated partial recovery during follow-up. Continued efforts are needed to improve post-RT salivary function to support quality of life.

A New Analysis Tool for Continuous Glucose Monitor Data.

BACKGROUND: With the development of continuous glucose monitoring systems (CGMS), detailed glycemic data are now available for analysis. Yet analysis of this data-rich information can be formidable. The power of CGMS-derived data lies in its characterization of glycemic variability. In contrast, many standard glycemic measures like hemoglobin A1c (HbA1c) and self-monitored blood glucose inadequately describe glycemic variability and run the risk of bias toward overreporting hyperglycemia. Methods that adjust for this bias are often overlooked in clinical research due to difficulty of computation and lack of accessible analysis tools. METHODS: In response, we have developed a new R package rGV, which calculates a suite of 16 glycemic variability metrics when provided a single individual's CGM data. rGV is versatile and robust; it is capable of handling data of many formats from many sensor types. We also created a companion R Shiny web app that provides these glycemic variability analysis tools without prior knowledge of R coding. We analyzed the statistical reliability of all the glycemic variability metrics included in rGV and illustrate the clinical utility of rGV by analyzing CGM data from three studies. RESULTS: In subjects without diabetes, greater glycemic variability was associated with higher HbA1c values. In patients with type 2 diabetes mellitus (T2DM), we found that high glucose is the primary driver of glycemic variability. In patients with type 1 diabetes (T1DM), we found that naltrexone use may potentially reduce glycemic variability. CONCLUSIONS: We present a new R package and accompanying web app to facilitate quick and easy computation of a suite of glycemic variability metrics.

Oncologists' Perspective on Dental Care Around the Treatment of Head and Neck Cancer: A Pattern of Practice Survey.

PURPOSE: Patients with head and neck cancer are at risk of long-term dental complications. Proper dental assessment pre- and post-treatment can improve outcomes but is logistically challenging. We surveyed oncologists to better understand their perspectives surrounding dental care in this unique population. METHODS: We surveyed oncologists at institutions associated with an ongoing national study of oral health after treatment of head and neck cancer. Seventeen questions were used to assess provider characteristics, patterns of practice, patterns of referral, barriers to referral, and willingness to apply fluoride varnish in the oncology clinic. RESULTS: Ninety-seven oncologists were invited from six institutions, of whom 40 (41%) responded. Surgeons represented 45% of the sample, followed by radiation oncologists (40%) and medical oncologists (15%). Both generalists and subspecialists were included. All practiced in a metropolitan area with an academic dental practice, and many felt that this improved access to care. Despite this, most oncologists thought that financial factors were a significant barrier to obtaining timely dental care. Most oncologists performed a dental assessment during visits. Oncologists felt qualified to identify the most significant complications of treatment, such as exposed bone, but felt underqualified to identify early changes in need of intervention. When asked if the oncology clinic could apply fluoride varnish during follow-ups, most stated that this seemed feasible but would require education and financial support. CONCLUSION: Oncologists often perform limited dental evaluations during their routine visits. Given the challenges associated with access to proper dental care for this population, these oncology visits may provide a window for preventative intervention.