Association of Atrial Fibrillation and/or Flutter With Adverse Cardiac Outcomes and Mortality in Patients With Wolff-Parkinson-White Syndrome.

Background: Wolff-Parkinson-White (WPW) syndrome is characterized by the presence of accessory pathways and development of potentially malignant arrhythmias that can lead to sudden cardiac death. We aimed to determine the impact of atrial fibrillation and/or flutter (AF/AFL) on adverse cardiac outcomes and mortality in patients with WPW syndrome. Methods: This study identified a cohort of Military Health System patients with WPW syndrome from January 1, 2014, to December 31, 2019. The cohort was divided into 2 subgroups by the presence or absence of AF/AFL. Cardiac composite outcome and mortality were assessed. Kaplan-Meier curves were constructed to assess the bivariate association between exposure and these 2 study outcomes. Cox proportional models were used to estimate the hazard ratios and 95% CIs associated with the cardiac composite outcome and mortality. Results: Of 35,539 patients included in the study, 19,961 were female (56.2%), the mean (SD) age was 62.9 (18.0) years, and 5291 patients (14.9%) had AF/AFL. The cardiac composite outcome and mortality incidence rates per 100 person-years in the AF/AFL vs non-AF/AFL subgroups were 8.18 vs 4.90, and 4.09 vs 2.13, respectively (P < .001). There were 3130 (8.8%) deaths. After adjusting for confounding variables, the AF/AFL subgroup maintained a 12% and 16% higher association with the composite outcome and mortality, respectively. Conclusions: Patients with WPW syndrome and AF/AFL have a higher association with adverse cardiac outcomes and death. Consideration for more aggressive electrophysiology screening and ablation strategies may be warranted in this population.

The Military Health System: Minimizing Disparities in Breast Cancer Treatment.

BACKGROUND: The Military Health System (MHS) is a universal health care system, in which health care disparities are theoretically minimized. This study aimed to identify disparities and assess their impact on the initiation of timely treatment for breast cancer within a universally insured population. METHODS: A retrospective cohort study was performed to evaluate the treatment of female breast cancer patients ≥18 years of age within the MHS from January 1, 2014, to December 31, 2018. Incident breast cancer was defined as ≥2 breast cancer diagnoses without a prior diagnosis of breast cancer during the three continuous years before index diagnosis. Time from index diagnosis to initial treatment was calculated and dichotomized as receiving treatment within a clinically acceptable time course. Poisson regression was used to estimate relative risk (RR) with 95% CIs. RESULTS: Among the 30,761 female breast cancer patients identified in the MHS, only 6% of patients had a prolonged time to initial treatment. Time to initial treatment decreased during the study period from a mean (SD) of 63.2 (152.0) days in 2014 to 37.1 (28.8) days in 2018 (P < 0.0001). Age, region, and military characteristics remained significantly associated with receiving timely treatment even after the adjustment of confounders. Patients 70-79 years old were twice as likely as 18-39 years olds to receive timely treatment (RR: 2.0100, 95% CI, 1.52-2.6563, P < 0.0001). Senior officers and their dependents were more likely to receive timely initial treatment compared to junior enlisted patients and their dependents (RR: 1.5956, 95% CI, 1.2119-2.1005, P = 0.004). CONCLUSIONS: There have been significant improvements in the timely initiation of breast cancer treatment within the MHS. However, demographic and socioeconomic disparities can be identified that affect the timely initiation of therapy.

New mental health diagnoses in parents of infants admitted to a neonatal intensive care unit-a retrospective review of the Military Health System database.

OBJECTIVE: Studies suggest that parents of NICU infants are at increased risk of mental health disorders. We sought to characterize this risk using a large database. STUDY DESIGN: The Military Health System was used to retrospectively link records between parents and infants admitted to a NICU over 5 years and were matched to similar families without NICU exposure. The total study population included 35,012 infants. Logistic regression was used to estimate the association between NICU exposure and parental mental health diagnoses within 5 years of infant birth. RESULTS: Maternal NICU exposure was associated with incident diagnoses of depression (OR: 1.18-1.27, p < 0.0001), anxiety (OR: 1.06-1.18, p = 0.0151), alcohol/opiate dependence (OR: 1.29-1.52, p = 0.0079), and adjustment disorder (OR: 0.97-1.18, p = 0.0224). Paternal NICU exposure was associated with alcohol/opiate dependence (OR: 0.78-1.42, p = 0.0339). CONCLUSION: Parents of NICU infants are at risk of developing mental health disorders. Future work should identify characteristics that predict highest risk to develop effective interventions.

Cardiovascular outcomes and mortality after initiation of canagliflozin: Analyses from the EASEL Study.

INTRODUCTION: In the EASEL study of patients with type 2 diabetes and high cardiovascular risk, initiation of sodium glucose co-transporter 2 inhibitors (SGLT2i) was associated with lower risk of cardiovascular events and mortality and higher risk of below-knee lower extremity (BKLE) amputation versus non-SGLT2i therapies. This analysis further examined risk of cardiovascular events, cardiovascular and noncardiovascular death and BKLE amputation with the SGLT2i canagliflozin versus non-SGLT2i. METHODS: New user cohorts were constructed from Department of Defense Military Health System patients initiating canagliflozin or non-SGLT2i (4/1/2013-12/31/2016). Propensity score matching (1:1) controlled for imbalances in baseline covariates. Incidence rates, hazard ratios and 95% confidence intervals for time to first composite outcome of all-cause mortality (ACM) and hospitalization for heart failure (HHF), composite major adverse cardiovascular events (MACE) and individual components were evaluated using conditional Cox models. The National Death Index was used to differentiate cardiovascular from noncardiovascular death. The exploratory safety end-point was BKLE amputation. RESULTS: After propensity matching, 15 394 patients with well-balanced baseline covariates were followed for a median of 2.03 years (intent-to-treat). Canagliflozin showed significant benefit for ACM and HHF (P < .0001), MACE (P = .0001), cardiovascular death (P < .0001) and noncardiovascular death (P = .0018). No significant difference in risk of BKLE amputation was observed (P = .20), though few events were observed. Results were generally consistent in on-treatment analyses. CONCLUSIONS: In this high cardiovascular risk cohort studied in routine clinical practice, canagliflozin was associated with lower risk of cardiovascular events, cardiovascular death and all-cause mortality with no significant increase in BKLE amputation risk versus non-SGLT2i.

Comparative safety and effectiveness of dabigatran vs. rivaroxaban and apixaban in patients with non-valvular atrial fibrillation: a retrospective study from a large healthcare system.

AIMS: We used the US Department of Defense Military Health System database to compare the safety and effectiveness of direct oral anticoagulants (DOACs) in patients with non-valvular atrial fibrillation (NVAF) initiating dabigatran vs. rivaroxaban or apixaban. METHODS AND RESULTS: Two cohorts of adults with NVAF, newly initiated on standard-dose DOAC, were identified based on clinical approval dates: July 2011-June 2016 for dabigatran (150 mg b.i.d.) or rivaroxaban (20 mg QD) and January 2013-June 2016 for dabigatran (150 mg b.i.d.) or apixaban (5 mg b.i.d.). Propensity score matching (1:1) identified two well-balanced cohorts (dabigatran vs. rivaroxaban n = 12 763 per treatment group; dabigatran vs. apixaban n = 4802 per treatment group). In both cohorts, baseline characteristics and follow-up duration were similar between treatment groups. Patients newly initiating dabigatran had significantly lower risk of major bleeding vs. rivaroxaban [2.08% vs. 2.53%; hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.70-0.97; P = 0.018], while stroke risk was similar (0.60% vs. 0.78%; HR 0.77, 95% CI 0.57-1.04; P = 0.084). The dabigatran vs. apixaban cohort analysis found no differences in risk of major bleeding (1.60% vs. 1.21%; HR 1.37, 95% CI 0.97-1.94; P = 0.070) or stroke (0.44% vs. 0.35%; HR 1.26, 95% CI 0.66-2.39; P = 0.489). CONCLUSION: Among NVAF patients newly initiated on standard-dose DOAC therapy in this study, dabigatran was associated with significantly lower major bleeding risk vs. rivaroxaban, and no significant difference in stroke risk. For dabigatran vs. apixaban, the reduced sample size limited the ability to draw definitive conclusions.

A plateau in new onset type 1 diabetes: Incidence of pediatric diabetes in the United States Military Health System.

OBJECTIVES: To describe the incidence and prevalence of type 1 diabetes among pediatric dependents of the US Department of Defense. METHODS: The Military Health System (MHS) data repository was used to identify pediatric patients (≤17 years of age) with type 1 diabetes from January 1, 2007 to December 31, 2012. Annual incidence, annual prevalence and adjusted incidence were calculated and stratified by sex, age group, and region of residence. RESULTS: Within a 6-year study period from 2007 to 2012, 5616 pediatric patients with type 1 diabetes were identified; 57% male, mean (SD) age of 10.9 (4.2) years. Annual type 1 diabetes incidence (per 100 000 persons) over the 5-year time period ranged from 20.7/100 000 to 21.3/100 000. Incidence for each year was highest in the 10 to 14 years age group and ranged from 30.9/100 000 in 2008 to 35.2/100 000 in 2011. Annual type 1 diabetes prevalence (per 1000 persons) remained stable throughout the study period at 1.5/1000. Adjusted incidence for males was significantly higher compared to females (21.0/100 000 vs 18.1/100 000; P = .001). During the study period, annual incidence remained steady (test for trend, P = .984). CONCLUSIONS: The incidence of type 1 diabetes among children appears to plateau during the study period, suggesting a steady state of type 1 diabetes within this pediatric population. The MHS provides an accurate and up to date look at incidence of type 1 diabetes and may reflect broader trends of incidence of pediatric disease for the United States as a whole.

Factors associated with persistent posttraumatic stress disorder among U.S. military service members and veterans.

BACKGROUND: Posttraumatic stress disorder (PTSD) can have long-term and far-reaching impacts on health and social and occupational functioning. This study examined factors associated with persistent PTSD among U.S. service members and veterans. METHODS: Using baseline and follow-up (2001-2013) questionnaire data collected approximately every 3 years from the Millennium Cohort Study, multivariable logistic regression was conducted to determine factors associated with persistent PTSD. Participants included those who screened positive for PTSD using the PTSD Checklist-Civilian Version at baseline (N = 2409). Participants were classified as having remitted or persistent PTSD based on screening negative or positive, respectively, at follow-up. RESULTS: Almost half of participants (N = 1132; 47%) met criteria for persistent PTSD at the first follow-up; of those, 804 (71%) also screened positive for PTSD at the second follow-up. Multiple factors were independently associated with persistent PTSD in an adjusted model at the first follow-up, including older age, deployment with high combat exposure, enlisted rank, initial PTSD severity, depression, history of physical assault, disabling injury/illness, and somatic symptoms. Among those with persistent PTSD at the first follow-up, additional factors of less sleep, separation from the military, and lack of social support were associated with persistent PTSD at the second follow-up. CONCLUSIONS: Combat experiences and PTSD severity were the most salient risk factors for persistent PTSD. Comorbid conditions, including injury/illness, somatic symptoms, and sleep problems, also played a significant role and should be addressed during treatment. The high percentage of participants with persistent PTSD supports the need for more comprehensive and accessible treatment, especially after separation from the military.

Cardiovascular Outcomes and Risks After Initiation of a Sodium Glucose Cotransporter 2 Inhibitor: Results From the EASEL Population-Based Cohort Study (Evidence for Cardiovascular Outcomes With Sodium Glucose Cotransporter 2 Inhibitors in the Real World).

BACKGROUND: Clinical trials have shown cardiovascular benefits and potential risks from sodium glucose cotransporter 2 inhibitors (SGLT2i). Trials may have limited ability to address individual end points or safety concerns. METHODS: We performed a population-based cohort study among patients with type 2 diabetes mellitus with established cardiovascular disease newly initiated on antihyperglycemic agents within the US Department of Defense Military Health System between April 1, 2013, and December 31, 2016. Incidence rates, hazard ratios (HRs), and 95% confidence intervals (CIs) for time to first composite end point of all-cause mortality and hospitalization for heart failure event, major adverse cardiovascular events (defined as all-cause mortality, nonfatal myocardial infarction, and nonfatal stroke), and individual end points were evaluated using conditional Cox models comparing new SGLT2i users with other antihyperglycemic agents. The exploratory safety end point was below-knee lower extremity amputation. Intent-to-treat and on-treatment analyses were performed. RESULTS: After propensity matching, 25 258 patients were followed for a median of 1.6 years. Compared with non-SGLT2i, initiation of SGLT2i was associated with a lower rate of all-cause mortality and hospitalization for heart failure (1.73 versus 3.01 events per 100 person-years; HR, 0.57; 95% CI, 0.50-0.65) and major adverse cardiovascular events (2.31 versus 3.45 events per 100 person-years; HR, 0.67; 95% CI, 0.60-0.75). SGLT2i initiation was also associated with an ≈2-fold higher risk of below-knee lower extremity amputation (0.17 versus 0.09 events per 100 person-years; HR, 1.99; 95% CI, 1.12-3.51). Because of the disproportionate canagliflozin exposure in the database, the majority of amputations were observed on canagliflozin. Results were consistent in the on-treatment analysis. CONCLUSIONS: In this high-risk cohort, initiation of SGLT2i was associated with lower risk of all-cause mortality, hospitalization for heart failure, and major adverse cardiovascular events and higher risk of below-knee lower extremity amputation. Findings underscore the potential benefit and risks to be aware of when initiating SGLT2i. It remains unclear whether the below-knee lower extremity amputation risk extends across the class of medication, because the study was not powered to make comparisons among individual treatments.

Public unawareness of physician reimbursement.

OBJECTIVES: To assess subjects' perception of healthcare costs and physician reimbursement. BACKGROUND: The lack of transparency in healthcare reimbursement leaves patients and physicians unaware of the distribution of health care dollars. METHODS: Anonymous survey-based study by means of convenience sampling. Participants were asked to estimate the total hospital cost and physician fee for one of the six medical procedures (n = 250). RESULTS: On the average for all 6 procedures, patients estimated the total cost was $36,177, ∼1,540% more than the actual Medicare rate of $7,333. Similarly, patients estimated the physician fee was $7,694, 1,474% more the actual Medicare rate of $589. CONCLUSION: Patients' perception of the total cost and physician fee are significantly higher than Medicare rates for all 6 procedures. This lack of insight may have widespread negative implications on the patient-physician relationship, on political trends to reduce physician reimbursement, and on a physician's desire to continue practicing medicine.

Obesity and associated adverse health outcomes among US military members and veterans: Findings from the millennium cohort study.

OBJECTIVE: To assess the prevalence of obesity and associated health outcomes among US service members and veterans. METHODS: Data from three survey cycles (2001-2008) of the Millennium Cohort Study were used to examine the prevalence of obesity and associated health outcomes. RESULTS: Of the 42,200 individuals, 25% were of normal weight in 2007/2008. Rates of obesity were significantly higher among veterans (32%) compared with service members (20%). Over a 7-year period, obesity rates doubled among both service members (10%-20%) and veterans (14%-32%). Participants with obesity were significantly more likely to be male, older, less educated, in the Army or Navy, and separated/retired from the military. Hypertension, diabetes, and sleep apnea were significantly more common among individuals with obesity compared with participants with normal weight (all P < 0.05). Individuals with obesity also had significantly higher rates of depression and post-traumatic stress disorder than individuals with normal weight and had lower mental and physical functional scores (all P < 0.05). CONCLUSIONS: These findings indicate an urgent need to enhance strategies for preventing and reducing excess weight gain within the military and veteran populations. Such strategies should aim to ensure a fit military force and promote health after military service.

Outcomes of follow-up care after an emergency department visit among pediatric asthmatics in the military health system.

BACKGROUND AND OBJECTIVES: Asthma exacerbations frequently trigger emergency department (ED) visits. Guidelines recommend timely follow-up after an ED visit for asthma, however, other studies have questioned the quality of follow-up care and their effect on subsequent ED utilization. We evaluated follow-up care on asthma outcomes in pediatric asthmatics enrolled in the Military Health System (MHS) after an ED visit for asthma. METHODS: This retrospective study utilized MHS data to evaluate 2-17-year-old persistent asthmatics with an ED visit for asthma between 2010-2012. Demographics, medication dispensing, and subsequent asthma related ED and hospital utilization were compared between those with or without a 28-day follow-up appointment. RESULTS: 10,460 of 88,837 persistent asthmatics met inclusion criteria for an asthma ED visit. 4,964 (47.5%) had ≥ 1 follow-up visit. In the 29-365 days after their ED visit, 21.1% of the follow-up cohort required an ED re-visit compared to 24.0% of the patients without follow-up. Follow-up care was associated with a reduction in ED re-visits (adjusted hazard ratio 0.86; 95% confidence interval 0.79, 0.93). Controller medications were dispensed to 76.0% of the follow-up cohort within 90 days of their ED visit compared to 49.7% in the group without follow-up. CONCLUSIONS: Despite universal access to healthcare, less than half of pediatric MHS asthma patients had follow-up within 28 days of an ED visit. Those with follow-up were more likely to fill a controller medication within 90 days post-ED visit, and less likely to have an asthma ED re-visit in the subsequent year.

Concurrent intrathecal methotrexate and liposomal cytarabine for leptomeningeal metastasis from solid tumors: a retrospective cohort study.

Leptomeningeal metastasis (LM) from solid tumors is typically a late manifestation of systemic cancer with limited survival. Randomized trials comparing single agent intrathecal methotrexate to liposomal cytarabine have shown similar efficacy and tolerability. We hypothesized that combination intrathecal chemotherapy would be a safe and tolerable option in solid tumor LM. We conducted a retrospective cohort study of combination IT chemotherapy in solid tumor LM at a single institution between April 2010 and July 2012. In addition to therapies directed at active systemic disease, each subject received IT liposomal cytarabine plus IT methotrexate with dexamethasone premedication. Patient characteristics, survival outcomes and toxicities were determined by systematic chart review. Thirty subjects were treated during the study period. The most common cancer types were breast 15 (50 %), glioblastoma 6 (20 %), and lung 5 (17 %). Cytologic clearance was achieved in 6 (33 %). Median non-glioblastoma overall survival was 30.2 weeks (n = 18; range 3.9-73.4), and did not differ significantly by tumor type. Median time to neurologic progression was 7 weeks (n = 8; range 0.9-57), with 10 subjects (56 %) experiencing death from systemic disease without progression of LM. Age less than 60 was associated with longer overall survival (p = 0.01). Six (21 %) experienced grade III toxicities during treatment, most commonly meningitis 2 (7 %). Combination IT chemotherapy was feasible in this small retrospective cohort. Prospective evaluation is necessary to determine tolerability, the impact on quality of life and neurocognitive outcomes or any survival benefit when compared to single agent IT chemotherapy.

Assembly of filamentous tau aggregates in human neuronal cells.

Intraneuronal deposition of microtubule-associated protein tau in filamentous aggregates constitutes a pathological hallmark of neurofibrillary degeneration that is characteristic of Alzheimer's disease (AD) and related disorders known collectively as tauopathies. Formation of such fibril inclusions, consisting of hyperphosphorylated tau in multiple isoforms, correlates with the severity of cognitive decline in AD. How neurofibrillary pathology evolves in tauopathy remains unclear at present, but availability of a cellular model with robust tau aggregation will permit experimental scrutiny of the mechanistic process leading to such neurodegeneration. Through the use of a serial transfection strategy in conjunction with a tau minigene construct, we succeeded in generating conditional transfectants of human neuronal lineage that overproduce wild-type human brain tau in isoforms 4R0N, 3R1N and 4R1N via TetOff and ecdysone inducible expression mechanisms. Such transgenic overexpression of tau in multiple isoforms facilitated the assembly of filamentous tau aggregates that exhibit immunoreactivities, physicochemical properties, and ultrastructural attributes reminiscent of those found in human tauopathies. The conditional tau transfectants thus provide us with a useful tool to elucidate the molecular and cellular events leading to neurofibrillary degeneration and a convenient means to test hypothetical mechanisms implicated in the etiopathogenesis of AD and related tauopathies.