Peritoneal Dialysis Technique Survival: A Cohort Study.

RATIONALE & OBJECTIVE: Reasons for transfer from peritoneal dialysis (PD) to hemodialysis (HD) remain incompletely understood. Among incident and prevalent patients receiving PD, we evaluated the association of clinical factors, including prior treatment with HD, with PD technique survival. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Adults who initiated PD at a Dialysis Clinic, Inc (DCI) outpatient facility between January 1, 2010, and September 30, 2019. EXPOSURE: The primary exposure of interest was timing of PD start, categorized as PD-first, PD-early, or PD-late. Other covariates included demographics, clinical characteristics, and routine laboratory results. OUTCOME: Modality switch from PD to HD sustained for more than 90 days. ANALYTICAL APPROACH: Multivariable Fine-Gray models with competing risks and time-varying covariates, stratified at 9 months to account for lack of proportionality. RESULTS: Among 5,224 patients who initiated PD at a DCI facility, 3,174 initiated dialysis with PD ("PD-first"), 942 transitioned from HD to PD within 90 days ("PD-early"), and 1,108 transitioned beyond 90 days ("PD-late"); 1,472 (28%) subsequently transferred from PD to HD. The PD-early and PD-late patients had a higher risk of transfer to HD as compared with PD-first patients (in the first 9 months: adjusted hazard ratio [AHR], 1.51 [95% CI, 1.17-1.96] and 2.41 [95% CI, 1.94-3.00], respectively; and after 9 months: AHR, 1.16 [95% CI, 0.99-1.35] and AHR, 1.43 [95% CI, 1.24-1.65], respectively). More peritonitis episodes, fewer home visits, lower serum albumin levels, lower residual kidney function, and lower peritoneal clearance calculated with weekly Kt/V were additional risk factors for PD-to-HD transfer. LIMITATIONS: Missing data on dialysis adequacy and residual kidney function, confounded by short PD technique survival. CONCLUSIONS: Initiating dialysis with PD is associated with greater PD technique survival, though many of those who initiate PD-late in their dialysis course still experience substantial time on PD. Peritonitis, lower serum albumin, and lower Kt/V are risk factors for PD-to-HD transfer that may be amenable to intervention. PLAIN-LANGUAGE SUMMARY: Peritoneal dialysis (PD) is an important kidney replacement modality with several potential advantages compared with in-center hemodialysis (HD). However, a substantial number of patients transfer to in-center HD early on, without having experienced the quality-of-life and other benefits that come with sustained maintenance of PD. Using retrospective data from a midsize national dialysis provider, we found that initiating dialysis with PD is associated with longer maintenance of PD, compared with initiating dialysis with HD and a later switch to PD. However, many of those who initiate PD-late in their dialysis course still experience substantial time on PD. Peritonitis, lower serum albumin, and lower small protein removal are other risk factors for PD-to-HD transfer that may be amenable to intervention.

SARS-CoV-2 Vaccine Effectiveness and Breakthrough Infections Among Patients Receiving Maintenance Dialysis.

RATIONALE & OBJECTIVE: SARS-CoV-2 vaccine effectiveness and immunogenicity threshold associated with protection against COVID-19-related hospitalization or death in the dialysis population are unknown. STUDY DESIGN: Retrospective, observational study. SETTING & PARTICIPANTS: Adult patients without COVID-19 history receiving maintenance dialysis through a national dialysis provider and treated between February 1 and December 18, 2021, with follow-up through January 17, 2022. PREDICTOR: SARS-CoV-2 vaccination status. OUTCOMES: All SARS-CoV-2 infections, composite of hospitalization or death following COVID-19. ANALYTICAL APPROACH: Logistic regression was used to determine COVID-19 case rates and vaccine effectiveness. RESULTS: Of 16,213 patients receiving dialysis during the study period, 12,278 (76%) were fully vaccinated, 589 (4%) were partially vaccinated, and 3,346 (21%) were unvaccinated by the end of follow-up. Of 1,225 COVID-19 cases identified, 550 (45%) occurred in unvaccinated patients, and 891 (73%) occurred during the Delta variant-dominant period. Between the pre-Delta period and the Delta-dominant period, vaccine effectiveness rates against a severe COVID-19-related event (hospitalization or death) were 84% and 70%, respectively. In the subset of 3,202 vaccinated patients with at least one anti-spike immunoglobulin G (IgG) assessment, lower anti-spike IgG levels were associated with higher case rates per 10,000 days and higher adjusted hazard ratios for infection and COVID-19-related hospitalization or death. LIMITATIONS: Observational design, residual biases, and confounding may exist. CONCLUSIONS: Among maintenance dialysis patients, SARS-CoV-2 vaccination was associated with a lower risk of COVID-19 diagnosis and associated hospitalization or death. Among vaccinated patients, a low anti-spike IgG level is associated with worse COVID-19-related outcomes.

Improving front-line clinician capacity to address depression and bipolar disorder among perinatal individuals: a longitudinal analysis of the Massachusetts Child Psychiatry Access Program (MCPAP) for Moms.

Perinatal mood disorders (PMDs) are common, yet many patients are undertreated. The Massachusetts Child Psychiatry Access Program (MCPAP) for Moms is designed to increase clinicians' willingness to address PMDs. We examined utilization of MCPAP for Moms and associations with PMDs treatment, including the more complex bipolar disorder (BD). Analyses of MCPAP for Moms data examined utilization from 7/2014 to 6/2020 and associated treatment outcomes. Participants were clinicians (n = 1006) in obstetrics/gynecology, family medicine, and pediatrics. Encounters included (1) resource and referrals and (2) psychiatric consultations (program psychiatrist consultation with clinicians or patients). Utilization sub-groups were identified using group-based trajectory modeling. Higher utilization of MCPAP for Moms was associated with increased rates of treating PMDs (incidence rate ratio [IRR] = 1.07, 95% CI: 1.06-1.07). Examining by encounter type, psychiatric consultations resulted in more frequent rates of clinicians treating PMDs than resource and referral encounters. Utilization of direct patient consultation was associated with the greatest increase in rates of clinicians treating BD (IRR = 2.12, 95% CI: 1.82-2.41). Clinicians with highest utilization rates of psychiatric consultations longitudinally had strongest predictive associations with providing direct mental healthcare to patients with BD (IRR = 13.5, 95% CI: 4.2-43.2). Utilization of MCPAP for Moms facilitates clinicians' ability to provide mental health treatment to patients.

Association of Social Determinants of Health With Adherence to Second-generation Antipsychotics for People With Bipolar Disorders in a Medicaid Population.

BACKGROUND: About 7 million people, 2.8% of US adults, have bipolar disorder (BD). While second-generation antipsychotics (SGA) are indicated as acute and maintenance treatments for BD, therapeutic success requires medication adherence and reported nonadherence estimates to range as high as 60%. Identifying patient risk factors for nonadherence is important for reducing it. OBJECTIVE: The objective of this study was to quantify the associations of risk factors, including social determinants of health, with SGA nonadherence among patients with BD. METHODS: In this cross-sectional study of 2015-2017 MassHealth Medicaid data, we examined several definitions of adherence and used logistic regression to identify risk factors for nonadherence (medication possession ratio <0.8) among all adults aged 18-64 diagnosed with BD who could be followed for 12 months following SGA initiation. RESULTS: Among 5197 patients, the mean (±SD) age was 37.7 (±11.4) years, and 42.3% were men. Almost half (47.7%) of patients were nonadherent to SGAs when measured by medication possession ratio. The prevalence of nonadherence peaked at middle age for men and younger for women. Nonadherence was less common among Massachusetts' Department of Mental Health clients (odds ratio=0.60, 95% confidence limit: 0.48-0.74) and among those who used other psychotropic medications (odds ratios between 0.45 and 0.81); in contrast, increase in neighborhood socioeconomic stress was associated with increased odds of nonadherence. CONCLUSIONS/IMPLICATIONS: Adherence to SGA treatment is suboptimal among people with BD. Recognizing risk factors, including those related to social determinants of health, can help target interventions to improve adherence for people at high risk and has implications for adherence-based quality measures.

Complex Patients Have More Emergency Visits: Don't Punish the Systems That Serve Them.

IMPORTANCE: Better patient management can reduce emergency department (ED) use. Performance measures should reward plans for reducing utilization by predictably high-use patients, rather than rewarding plans that shun them. OBJECTIVE: The objective of this study was to develop a quality measure for ED use for people diagnosed with serious mental illness or substance use disorder, accounting for both medical and social determinants of health (SDH) risks. DESIGN: Regression modeling to predict ED use rates using diagnosis-based and SDH-augmented models, to compare accuracy overall and for vulnerable populations. SETTING: MassHealth, Massachusetts' Medicaid and Children's Health Insurance Program. PARTICIPANTS: MassHealth members ages 18-64, continuously enrolled for the calendar year 2016, with a diagnosis of serious mental illness or substance use disorder. EXPOSURES: Diagnosis-based model predictors are diagnoses from medical encounters, age, and sex. Additional SDH predictors describe housing problems, behavioral health issues, disability, and neighborhood-level stress. MAIN OUTCOME AND MEASURES: We predicted ED use rates: (1) using age/sex and distinguishing between single or dual diagnoses; (2) adding summarized medical risk (DxCG); and (3) further adding social risk (SDH). RESULTS: Among 144,981 study subjects, 57% were women, 25% dually diagnosed, 67% White/non-Hispanic, 18% unstably housed, and 37% disabled. Utilization was higher by 77% for those dually diagnosed, 50% for members with housing problems, and 18% for members living in the highest-stress neighborhoods. SDH modeling predicted best for these high-use populations and was most accurate for plans with complex patients. CONCLUSION: To set appropriate benchmarks for comparing health plans, quality measures for ED visits should be adjusted for both medical and social risks.

Y-Box Binding Protein-1 Promotes Epithelial-Mesenchymal Transition in Sorafenib-Resistant Hepatocellular Carcinoma Cells.

Hepatocellular carcinoma is one of the most common cancer types worldwide. In cases of advanced-stage disease, sorafenib is considered the treatment of choice. However, resistance to sorafenib remains a major obstacle for effective clinical application. Based on integrated phosphoproteomic and The Cancer Genome Atlas (TCGA) data, we identified a transcription factor, Y-box binding protein-1 (YB-1), with elevated phosphorylation of Ser102 in sorafenib-resistant HuH-7R cells. Phosphoinositide-3-kinase (PI3K) and protein kinase B (AKT) were activated by sorafenib, which, in turn, increased the phosphorylation level of YB-1. In functional analyses, knockdown of YB-1 led to decreased cell migration and invasion in vitro. At the molecular level, inhibition of YB-1 induced suppression of zinc-finger protein SNAI1 (Snail), twist-related protein 1 (Twist1), zinc-finger E-box-binding homeobox 1 (Zeb1), matrix metalloproteinase-2 (MMP-2) and vimentin levels, implying a role of YB-1 in the epithelial-mesenchymal transition (EMT) process in HuH-7R cells. Additionally, YB-1 contributes to morphological alterations resulting from F-actin rearrangement through Cdc42 activation. Mutation analyses revealed that phosphorylation at S102 affects the migratory and invasive potential of HuH-7R cells. Our collective findings suggest that sorafenib promotes YB-1 phosphorylation through effect from the EGFR/PI3K/AKT pathway, leading to significant enhancement of hepatocellular carcinoma (HCC) cell metastasis. Elucidation of the specific mechanisms of action of YB-1 may aid in the development of effective strategies to suppress metastasis and overcome resistance.

Emergency Department and Primary Care Use in Massachusetts 5 Years After Health Reform.

OBJECTIVE: Conceptually, access to primary care (through insurance) should reduce emergency department (ED) visits for primary care sensitive (PCS) conditions. We sought to identify characteristics of insured Massachusetts residents associated with PCS ED use, and compare such use for public versus private insurees. POPULATION AND SETTING: People under age 65 in the Massachusetts All-Payer Claims Data, 2011-2012. STUDY DESIGN: Retrospective, observational analysis of PCS ED use with nonurgent, urgent/primary care treatable, and urgent/potentially avoidable visits being considered PCS. We predicted utilization in 2012 using multivariable regression models and data available in 2011 administrative records. PRINCIPAL FINDINGS: Among 2,269,475 nonelderly Massachusetts residents, 40% had public insurance. Among public insurees, PCS ED use was higher than for private (mean, 36.5 vs. 9.0 per 100 persons; adjusted risk ratio, 2.53; 95% confidence limits, 2.49-2.56), while having any primary care visit was less common (70% vs. 83%), as was having any visit to one's own (attributed) primary care provider (38% vs. 44%). CONCLUSIONS: Public insurance was associated with less access to primary care and more PCS ED use; statewide labor shortages and low reimbursement rates from public insurance may have provided inadequate access to care that might otherwise have helped reduce PCS ED use.

Association of Smoking Status With Mortality and Hospitalization in Hemodialysis Patients.

RATIONALE & OBJECTIVE: The relationship between tobacco smoking and comorbid condition outcomes in hemodialysis (HD) patients is not well understood. This study examined the association of tobacco smoking status with hospitalization and mortality in HD patients. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Adult HD patients at 2,223 US dialysis centers with HD vintage of 30 days or less who completed a tobacco smoking status survey as part of standard care between April 2013 and June 2015. PREDICTOR: Tobacco smoking category: never smoked, currently living with smoker, former smoker, moderate smoker (<1 pack per day), or heavy smoker (≥1 pack per day). OUTCOMES: Death and hospital admissions within 2 years of the tobacco smoking survey. ANALYTICAL APPROACH: Kaplan-Meier analysis and Cox proportional hazards regression for time to death; cumulative incidence function and Cox proportional hazards regression for time to first hospitalization; negative-binomial regression for number of hospitalizations. RESULTS: Of 22,230 patients studied, 13% were active smokers. Mortality probabilities increased with greater exposure to smoking (17%, 22%, 23%, and 27% for never, moderate, former, and heavy smokers, respectively; P<0.001), as did incidence rates for first hospitalization (23%, 27%, 27%, and 30%, respectively; P<0.001). Compared to never smoked, heavy smokers had the highest mortality rate (HR for heavy smokers, 1.41 [95% CI, 1.18-1.69]; HR for moderate smokers, 1.39 [95% CI, 1.24-1.55]; HR for former smokers, 1.19 [95% CI, 1.11-1.28]). Living with a smoker was not associated with mortality (HR, 0.93; 95% CI, 0.72-1.22). HRs for first hospitalization followed similar patterns. The incidence rate of mortality for active smokers with diabetes was 173.7/1,000 patient-years and 103.5/1,000 patient-years for those who never smoked (incidence rate ratio, 1.68; P<0.001). LIMITATIONS: Self-reported survey without detailed history of smoking/cessation. CONCLUSIONS: Risks for death and hospitalization are elevated among HD patients who smoke, being highest among younger individuals and those with diabetes. Second-hand smoke was not associated with poor clinical outcomes.

Change in quality of life and one-year mortality risk in maintenance dialysis patients.

BACKGROUND: Quality of life (QOL) is an important metric of high-quality dialysis care. QOL is commonly measured by the Short Form 36 Questionnaire (SF-36), which provides two summary scores: a mental component score (MCS) and a physical component score (PCS). Poor QOL is associated with mortality in dialysis patients. Small studies show that changes in QOL also predicts mortality. We investigated whether changes in QOL over time are associated with mortality in a large cohort of maintenance hemodialysis patients. METHODS: This retrospective study was conducted in 1017 outpatient dialysis facilities. Over 10,000 hemodialysis patients completed two SF-36 surveys. We compared 1-year morality rates in those whose MCS or PCS increased or decreased ±5 vs. those whose did not. RESULTS: For those who completed two surveys, mean score for PCS was unchanged, whereas MCS increased slightly (48.6 vs. 48.9, p = 0.05). Individual patients, however, showed marked variation. On the second survey, more than half of patients demonstrated a ± 5 point change in the PCS and/or MCS. After multivariate adjustment, a ≥ 5 decrease in MCS was associated with an increase in mortality (HR = 1.33, 95 % CI 1.18, 1.50). CONCLUSIONS: Clinicians should be aware that many patients experience a significant change in both the MCS and PCS on dialysis. A MCS decrease of ≥5 was associated with increased mortality. More study is needed to determine whether this is a causal relationship. Physicians should evaluate root causes and seek to mitigate declines in QOL whenever possible.