Hepatitis B-CpG vaccine series for healthcare workers who are hepatitis B vaccine nonresponders.

This prospective study enrolled healthcare workers (HCW) who were nonresponders following at least 5 doses of aluminum-adjuvanted hepatitis B vaccine received the 2-dose Heplisav-B (HepB-CpG) series. After two doses of HepB-CpG, 43/47 (91%) participants, and with 1 dose 41/49 (84%) responded. HepB-CpGcould be the preferred vaccine in HCW nonresponders.

High Rates of Seroprotection to Hepatitis B After a Hepatitis B Challenge Dose in Previously Vaccinated Patients with Inflammatory Bowel Disease on Immunosuppressive Therapy.

BACKGROUND: Healthy populations have high rates of sustained vaccine-induced seroprotection to hepatitis B virus, but previous studies in immunosuppressed patients with inflammatory bowel disease (IBD) have shown suboptimal seroprotection rates. A challenge dose of hepatitis B vaccine (HepB) is recommended in previously vaccinated individuals who are seronegative to elicit an anamnestic response and determine if they are seroprotected. The aim of our study was to determine sustained seroprotection rates to hepatitis B vaccine (HepB) in patients with IBD. METHODS: This was a single-center prospective study of patients with IBD previously vaccinated with a three dose HepB series. Patients had a hepatitis B surface antibody (anti-HBs) drawn; if it was below 10 mIU/mL, they received a challenge dose of the HepB vaccine to assess for anamnestic response and sustained seroprotection. The primary outcome was to determine the rate of sustained seroprotection (anti-HBs ≥ 10). RESULTS: A total of 168 patients met inclusion criteria, mean age 35.7 years ± 13.6 standard deviation (SD). Initially 120 (71.4%) had anti-HBs ≥ 10 mIU/mL, with median anti-HBs of 37 mIU/mL (interquartile range 0-234); 48 (28.6%) needed a challenge dose, of which 34 responded with anti-HBs ≥ 10 mIU/mL. In total, 154 (91.7%) demonstrated sustained seroprotection to HepB. Those not seroprotected were more likely to have been vaccinated on immunosuppressive therapy or after their diagnosis of IBD. CONCLUSIONS: Most vaccinated patients with IBD maintain sustained seroprotection to HepB despite prolonged exposure to immunosuppression. This contradicts prior studies and shows that immunosuppression does not lead to loss of seroprotection.

High But Inequitable COVID-19 Vaccine Uptake Among Patients with Inflammatory Bowel Disease.

Coronavirus disease 2019 (COVID-19) vaccines are recommended for all patients with inflammatory bowel disease (IBD).1 Patients with IBD historically have had low vaccine uptake relative to the general population.2 However, a recent survey suggested a rate higher than that of the general population with regard to COVID-19 vaccine intent among the IBD population. Their study was limited being that 96% of the patients surveyed identified as White, and 88% had attained a bachelor's degree or higher level of education.3 Therefore, these findings may not be representative of the IBD population as a whole. Previous studies have indeed identified disparities in influenza vaccine uptake within the IBD population.4,5.

Humoral Immunogenicity of mRNA COVID-19 Vaccines Among Patients With Inflammatory Bowel Disease and Healthy Controls.

INTRODUCTION: Patients with inflammatory bowel disease (IBD) on immune-modifying therapies may have a lower vaccine response to certain vaccines. The aim of our study was to evaluate humoral immunogenicity of mRNA coronavirus disease 2019 (COVID-19) vaccines among patients with IBD and healthy controls (HCs). METHODS: We performed a prospective study to evaluate humoral immunogenicity among patients with IBD and HCs after completion of mRNA COVID-19 vaccines. RESULTS: One hundred twenty-two patients with IBD and 60 HCs were enrolled. All HCs and 97% of patients with IBD developed antibodies. Antibody concentrations were lower in patients with IBD compared with those in HCs (median 31 vs 118 µg/mL; P < 0.001). Those who received the mRNA-1273 (Moderna) COVID-19 (median 38; interquartile range [IQR] 24-75 vs µg/mL) had higher antibody concentrations compared with those who received the Pfizer-BNT vaccine series (median 22; IQR 11-42 µg/mL; P < 0.001). Patients on immune-modifying therapy (median 26; IQR 13-50 µg/mL) had lower antibody concentrations compared with those who were on no treatment, aminosalicylates, or vedolizumab (median 59; IQR 31-75 µg/mL; P = 0.003). DISCUSSION: Almost all patients with IBD in our study mounted an antibody response. Future studies are needed in evaluating sustained humoral immunity and the impact of booster dosing in patients with IBD.

Seroresponse to Inactivated and Recombinant Influenza Vaccines Among Maintenance Hemodialysis Patients.

RATIONALE & OBJECTIVE: High-dose influenza vaccine provides better protection against influenza infection in older adults than standard-dose vaccine. We compared vaccine seroresponse among hemodialysis patients over a period of 4 months after administration of high-dose trivalent inactivated (HD-IIV3), standard-dose quadrivalent inactivated (SD-IIV4), or quadrivalent recombinant quadrivalent (RIV4) influenza vaccine. STUDY DESIGN: Prospective observational study. SETTING & PARTICIPANTS: Patients at 4 hemodialysis clinics who received influenza vaccine. EXPOSURE: Type of influenza vaccine. OUTCOME: Hemagglutination inhibition (HI) titers were measured at baseline and at 1, 2, 3, and 4 months after vaccination. The primary outcome was seroprotection rates at HI titers of at least 1:40 and at least 1:160 (antibody levels providing protection from infection in approximately 50% and 95% of immunocompetent individuals, respectively) at 1, 2, 3, and 4 months after vaccination. ANALYTICAL APPROACH: We calculated geometric mean titer as well as seroprotection and seroconversion rates. Adjusted generalized linear models with additional trend analyses were performed to evaluate the association between vaccine type and outcomes. RESULTS: 254 hemodialysis patients were vaccinated against influenza with HD-IIV3 (n = 141), SD-IIV4 (n = 36), or RIV4 (n = 77). A robust initial seroresponse to influenza A strains was observed after all 3 vaccines. Geometric mean titer and seroprotection (HI titer ≥1:160) rates against influenza A strains were higher and more sustained with HD-IIV3 than SD-IIV4 or RIV4. More than 80% of patients vaccinated with HD-IIV3 were seroprotected (HI titer ≥1:160) at month 4 (P < 0.001), whereas, among patients vaccinated with SD-IIV4 or RIV4, seroprotection rates were similar to those at baseline. Seroprotection rates were lower against B strains for all vaccines. LIMITATIONS: Because of the use of observational data, bias from unmeasured confounders may exist. Some age subgroups were small in number. Clinical outcome data were not available. CONCLUSIONS: Hemodialysis patients exhibited high seroprotection rates after all 3 influenza vaccines. The seroresponse waned more slowly with HD-IIV3 compared with SD-IIV4 and RIV4 vaccines.

The Burden of Vaccine-preventable Diseases in Patients With Inflammatory Bowel Disease.

BACKGROUND: Patients with inflammatory bowel disease (IBD) are at an increased risk of infections, including vaccine-preventable diseases (VPDs). The aim of this study was to explore the inpatient prevalence of VPD in patients with IBD, as well as inpatient outcomes. METHODS: Retrospective study using the 2013-2017 Nationwide Inpatient Sample databases. All patients 18 years of age or older with International Classification of Diseases, Ninth and 10th Revisions , Clinical Modification (ICD-9/10 CM) codes for IBD were included, as well as patients with VPDs as a principal diagnostic code. The primary outcome was the occurrence and odds of VPD in patients with IBD compared with patients with no IBD. Secondary outcomes were inpatient mortality, morbidity, and economic burden compared with patients with IBD and non-vaccine-preventable infections (VPIs). Multivariate regression yielded adjusted odds ratios. RESULTS: Of 1,622,245 (0.9%) patients with a diagnosis of IBD, 3560 (0.2%) had associated VPDs, while 131,150 patients had non-VPI (8.1%). The most common VPDs were influenza, herpes zoster (HZ), pneumococcal pneumonia, and varicella. Only HZ and varicella had increased odds of occurrence in patients with IBD of all ages. Patients with IBD 65 years of age or older had increased odds of VPD compared with patients under 65 years. Patients with IBD and associated VPD had higher odds of intensive care unit stay, systemic inflammatory response syndrome, and multiorgan failure compared with patients with IBD and non-VPI. CONCLUSIONS: VPDs represent a clinically relevant cause of infectious disease-related hospital admissions in patients with IBD. Patients with IBD are at increased risk for hospitalization due to HZ and varicella. Those hospitalized for VPD have higher morbidity compared with patients with IBD and non-VPI. These findings echo the importance of instituting optimal immunization schedules in patients with IBD, particularly in patients 65 years or older.

Accuracy of Self-Reported Vaccination Status in a Cohort of Patients with Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Prevention of vaccine-preventable diseases is important in the care of patients with inflammatory bowel disease (IBD). Thus, accurate immunization histories are critical. Many providers rely on patient self-report when assessing immunization status. The primary aim of our study was to determine the accuracy of self-reported influenza vaccination status in a cohort of patients with IBD. METHODS: We conducted a prospective study of patients with IBD who answered a vaccination status questionnaire and compared their responses to the Wisconsin Immunization Registry, a state-wide electronic immunization information system. The primary outcome was the sensitivity and specificity of self-reported influenza vaccination status. A secondary outcome evaluated the sensitivity and specificity of pneumococcal vaccination status. RESULTS: A total of 200 patients with IBD were included in the study. Documented immunization rates were 74.5% for influenza vaccinations and 79.9% for pneumococcal vaccinations. Influenza vaccination self-report had a sensitivity of 98.7%, a specificity of 90.2%, a positive predictive value (PPV) of 96.7% and a negative predictive value (NPV) of 95.8%. In comparison, the sensitivity for pneumococcal vaccination was 83.5% with a specificity of 86.2%, PPV of 96.4%, and NPV of 54.3%. CONCLUSIONS: Self-reported influenza immunization status is sensitive and specific in patients with IBD. Accuracy for pneumococcal vaccination is slightly lower, but responses were notable for a high PPV. Self-report is an effective way to determine influenza immunization status and provides useful information for receipt of pneumococcal vaccine in patients with IBD.

Influenza vaccination rates and location for receiving the influenza vaccination among older adult Medicare beneficiaries.

OBJECTIVES: The objectives of this study were to (1) assess the trends in older adult influenza vaccination rates and (2) locations at which U.S. older adults received influenza vaccinations for the 2008-2009 to 2017-2018 influenza seasons, and (3) compare the estimates of influenza vaccination rates and locations with the estimates from other sources reported previously. METHODS: Data from the 2009 to 2017 Medicare Current Beneficiary Survey (MCBS) were used in this analysis. The weighted sample included an average of approximately 37 million community-dwelling older Medicare beneficiaries who completed questionnaires per year. The estimates for older adult influenza vaccination rates and the locations that they used to receive the influenza vaccination were weighted and reported for the 2008-2009 to 2017-2018 influenza seasons. RESULTS: The self-reported older adult influenza vaccination rates between 2008-09 and 2017-2018 ranged from 69.6% (24.6 million) to 75.0% (31.3 million). Across the study period, the percentage of older adults receiving the influenza vaccination at a physician office and clinic declined by 10.4%. The decline was more than offset by an increase in older adult influenza vaccination receipt at a community pharmacy, which substantially increased from 16.6% (4.1 million) in 2008-2009 to 34.8% (10.9 million) in 2014-2015. When compared with the estimates from other sources, the absolute value of the MCBS estimates corresponds with National Health Interview Survey estimates. The older adult influenza vaccination rate increased slightly between the 2008-2009 and 2017-2018 influenza seasons but is still below the 90% benchmark. CONCLUSION: Community pharmacies-increasingly important access points for the influenza vaccination for older adults-likely contributed to the growth in the rate of older adults vaccinated with influenza vaccines.

Timeliness of data entry in Wisconsin Immunization Registry by Wisconsin pharmacies.

OBJECTIVE: To assess the association of various immunization- and pharmacy-related factors with the timeliness of pharmacy data entry in a state immunization information system. DESIGN: A cross-sectional study was conducted. SETTING AND PARTICIPANTS: Data for 2,040,248 immunizations administered by pharmacies in Wisconsin during 2012-2017 were collected from the Wisconsin Immunization Registry (WIR). Variables, including the submission method, immunization administration year, vaccine type, and recipient age, were analyzed through multivariate logistic regression to determine if they had a relationship with data entry timeliness. Pharmacists were surveyed on immunization data entry practices to corroborate analysis findings. OUTCOME MEASURES: Timeliness of immunization data entry in WIR was measured as a binary variable: 7 days or fewer or more than 7 days after immunization. RESULTS: Influenza immunizations were statistically significantly less likely to be timely compared with noninfluenza immunizations (odds ratio [OR] 0.719 [95% CI 0.712-0.726]; P < 0.0001). Immunizations administered to individuals aged more than 18 years were less timely compared with immunizations administered to individuals aged 6-18 years. The magnitude showed a slight difference in timeliness but without statistical significance (0.989 [95% CI 0.972-1.006]; P > 0.05). For submission method, flat-file submission was less likely to be timely compared with manual entry (0.48 [95% CI 0.475-0.486]; P < 0.0001). Health Level-7 submission, involving the electronic exchange of information with electronic health systems, was much more likely to be timely compared with manual entry (1.989 [95% CI 1.972-2.007]; P < 0.0001). With each successive year, from 2012 to 2017, immunizations were entered in a less timely manner (0.981 [95% CI 0.979-0.983]; P < 0.0001). CONCLUSIONS: Timeliness of pharmacy data entry in WIR was associated with entry method, vaccine type, and immunization administration year. We hope to identify ways to help pharmacies improve immunization data entry in WIR and facilitate the communication of immunization information among providers.

Immunosuppression Does Not Affect Antibody Concentrations to Measles, Mumps, and Rubella in Patients with Inflammatory Bowel Disease.

BACKGROUND: The Advisory Committee on Immunization Practices (ACIP) recommends using the immunization record and not serologic testing to determine immunity against measles and rubella in the general population, due to potential false negatives. However, it is unknown whether the immune response is less durable among patients who are immunosuppressed. AIMS: The primary aim of this study was to evaluate sustained vaccine-induced measles, mumps, and rubella (MMR) antibody concentrations in immunosuppressed patients with inflammatory bowel disease (IBD). METHODS: We performed a cross-sectional study to compare antibody concentrations following the two-dose (MMR) vaccine among 46 patients with IBD and 20 healthy controls (HC). Three IBD groups stratified by the immunosuppressive regimen that preceded study entry for at least 3 months: (1) thiopurine monotherapy, (2) anti-TNF monotherapy, or (3) combination therapy (anti-TNF agent combined with an immunomodulator) were enrolled. RESULTS: All subjects had measurable antibody concentrations to the three vaccine viruses. Age and time since receipt of MMR series were similar in both groups. There were no difference in the antibody concentration of measles (IBD 667 mIU/ml vs HC 744 mIU/ml; p = 0.45), mumps (IBD 339 EU/ml vs HC 402 EU/ml; p = 0.62), or rubella (IBD 25 mIU/ml vs HC 62 mIU/ml; p = 0.11) among the groups. No differences in antibody concentrations were found among the IBD treatment groups. CONCLUSION: Immunosuppressed patients with IBD have sustained antibody concentrations comparable to healthy controls. Thus, gastroenterologist should follow the ACIP recommendations and use the immunization record when available to determine immunity to measles and rubella in patients with IBD. Clinical Trials Registry # NCT02434133.

Differential Reduction of IP-10 and C-Reactive Protein via Aerobic Exercise or Mindfulness-Based Stress-Reduction Training in a Large Randomized Controlled Trial.

Exercise and meditation improve health and well-being, potentially through decreasing systemic inflammation. In this study, healthy adults (N = 413) were randomized to 8 weeks of training in aerobic exercise, matched mindfulness-based stress reduction, or wait-list control. Three inflammation-related biomarkers (C-reactive protein, interleukin-6, and interferon-gamma-inducible protein-10) were assessed preintervention, directly postintervention, and 17 weeks later. Within-group analyses found that exercise participants had decreased serum interferon-gamma-inducible protein-10 postintervention and 17 weeks later, whereas C-reactive protein was lower in mindfulness-based stress-reduction participants 17 weeks postintervention only. Self-reported physical activity or amount of meditation practice did not predict biomarker changes. This study suggests that (a) training in aerobic exercise can lower interferon-gamma-inducible protein-10, a chemokine associated with interferon activity and illness, and (b) training in mindfulness meditation may have a delayed effect on C-reactive protein, an important inflammatory biomarker. The findings highlight the likelihood of multiple, distinct pathways underlying the health-promoting effects of these lifestyle interventions.

Lower Sustained Diphtheria and Pertussis Antibody Concentrations in Inflammatory Bowel Disease Patients.

BACKGROUND: Patients with inflammatory bowel disease (IBD) are often immunosuppressed, and those patients receiving anti-tumor necrosis factor α (TNF) therapy can have lower antibody responses to vaccines. Pertussis cases are at their highest levels in the post-vaccine era. There is little data regarding responses to the Tdap (tetanus, diphtheria, and acellular pertussis) vaccine in IBD patients. AIMS: The aim of this study was to compare sustained vaccine-induced Tdap antibody concentrations in a cohort of IBD patients stratified by medication regimens with healthy controls (HC) who had received an adult Tdap booster. METHODS: We performed a cross-sectional study evaluating antibody responses to Tdap vaccine among IBD patients compared to HC. Our study consisted of three patient groups: adults with IBD stratified by maintenance medication regimen: (1) thiopurine monotherapy; (2) anti-TNF monotherapy; and (3) combination therapy (anti-TNF and immunomodulator (thiopurine or methotrexate)). RESULTS: Ninety IBD patients and 20 HC participated. Pertussis pertactin antibody concentrations were significantly lower in IBD patients (p = 0.021) compared to HC, and those on anti-TNF agents (monotherapy or combination) had lower antibody concentrations compared to those on thiopurine monotherapy (p = 0.028). Diphtheria antibody concentrations were also lower in IBD patients (p < 0.001), and those on anti-TNF agents (monotherapy or combination) had lower antibody concentrations compared to the thiopurine monotherapy group (p < 0.001). CONCLUSION: IBD patients on anti-TNF agents had lower antibody concentrations to diphtheria and pertussis. These findings suggest a need for different Tdap booster schedules for IBD patients on anti-TNF therapy. Clinical Trials Registry NCT02434133.

Increased Endovascular Staphylococcus aureus Inoculum Is the Link Between Elevated Serum Interleukin 10 Concentrations and Mortality in Patients With Bacteremia.

BACKGROUND: Cell wall peptidoglycan stimulates interleukin 10 (IL-10) production in Staphylococcus aureus bacteremia (SaB) animal models, but clinical data are not available. This study evaluates the impact of intravascular bacterial cell numbers (ie, the level of bacteremia), in patients at the time of clinical presentation on IL-10 production and its association with S. aureus bacteremia (SaB) mortality. METHODS: Blood and isolates were collected in 133 consecutive SaB patients. Serum IL-10 was quantified by an electrochemoluminescence assay. Bacterial inoculum was measured in patient sera with elevated (n = 8) or low (n = 8) IL-10 using a magnetic bacterial capture assay. Staphylococcus aureus from these 2 groups were introduced into whole blood ex vivo to determine IL-10 production with variable inocula. RESULTS: IL-10 serum concentration was higher in SaB patient mortality (n = 27) vs survival (n = 106) (median, 36.0 pg/mL vs 10.4 pg/mL, respectively, P < .001). Patients with elevated IL-10 more often had endovascular SaB sources. The inoculum level of SaB was higher in patients with elevated serum IL-10 vs patients with low IL-10 (35.5 vs 0.5 median CFU/mL; P = .044). Ex vivo studies showed that 108 CFU/mL yielded greater IL-10 than did 103 CFU/mL (4.4 ± 1.8 vs 1.0 ± 0.6 pg/mL; P < .01). CONCLUSIONS: Elevated IL-10 serum concentrations at clinical presentation of SaB were highly associated with mortality. High intravascular peptidoglycan concentration, driven by a higher level of bacteremia, is a key mediator of IL-10 anti-inflammatory response that portends poor clinical outcome. Using IL-10 as an initial biomarker, clinicians may consider more aggressive antimicrobials for rapid bacterial load reduction in high-risk SaB patients.

Insomnia and Relationship With Immunosuppressant Therapy After Lung Transplantation.

BACKGROUND: Lung transplant recipients are at high risk of developing sleep disorders such as insomnia, but the prevalence and features are currently poorly characterized within this population. Since these disorders are associated with increased morbidity and mortality, it is important to identify them to optimize the care of lung transplant recipients. We sought to evaluate the prevalence of insomnia within our university-based lung transplant clinic and determine whether a relationship exists between insomnia and exposure to immunosuppressant medications following transplantation. METHODS: Participants were recruited through the University of Wisconsin Hospital and Clinics Lung Transplant Clinic (N = 125). Participants (n = 92) completed the adult sleep history questionnaire, which included the Insomnia Severity Index (ISI) to assess for insomnia (defined as ISI score >10). Cumulative tacrolimus exposure was determined in 73 patients by performing an area under the curve calculation to assess for a potential relationship between tacrolimus exposure and insomnia. RESULTS: The prevalence of insomnia was 40% within this population. Although no difference in time since transplant was found, cumulative mean ± standard error of the mean tacrolimus exposure was significantly higher in patients with insomnia versus those without insomnia (17 190 ± 1673 ng·d/mL vs 12 130 ± 1630 ng·d/mL, respectively; P = .04). Estimated tacrolimus exposure was not greater with increasing frequency of insomnia complaints (analysis of variance P = .54). CONCLUSION: In our population, insomnia is common after lung transplantation, with prevalence greater than the general population. Higher cumulative exposure to tacrolimus may contribute to insomnia in this group. Future research should investigate the relationship between immunosuppressant therapy and development of sleep disorders.

Antibody responses to influenza vaccine in pre- and post-lung transplant patients.

BACKGROUND: Although pre-transplant immunization is routinely recommended, this recommendation is based on little data. The primary objective of this study was to compare antibody responses in lung transplant patients who received influenza vaccine before the transplant, within the first six months of transplant, between 13 and 60 months post-transplant, and 110 months or beyond transplant. METHODS: This prospective cohort study included 357 total immunization events performed over five yr to measure H1N1, H3N2, and B antibody responses to the influenza vaccine in pre- and post-lung transplant patients. Geometric mean titers, seroprotection (antibody titer at least 1:40), seroconversion (fourfold increase between pre and post), and mean fold increases were compared. RESULTS: The geometric mean titer distributions were different for H3N2 and B (ANOVA; p = 0.002 for both). Pre-transplant antibody concentrations were higher compared to the 13- to 60-month group for H3N2 (corrected p = 0.002) and the healthy group for B (corrected p = 0.001). The ≥110-month group had higher seroconversion rates compared to the 13- to 60-month group for H3N2 and B viruses. CONCLUSION: Lung pre-transplant patients and the long-term survivors have higher responses to the influenza vaccine than early post-transplant and the transplant control groups.

Restless Legs Syndrome Following Lung Transplantation: Prevalence and Relationship With Tacrolimus Exposure.

CONTEXT: Complications following lung transplantation are common and significantly reduce quality of life, and increase morbidity and mortality. Increasing evidence suggests sleep disorders are prevalent following lung transplantation, but factors associated with their development are not known. OBJECTIVES: We sought to evaluate the prevalence of restless legs syndrome (RLS) in a lung transplant population and determine if a relationship exists between RLS and exposure to immunosuppressant medications. DESIGN, SETTING, AND PARTICIPANTS: Subjects were recruited through the University of Wisconsin Hospital and Clinics Lung Transplant Clinic (N = 125). Participants (N = 81) completed sleep questionnaires, including the four RLS diagnostic criteria, insomnia severity index, and Sheehan disability scale. Cumulative tacrolimus exposure was determined in 62 subjects by calculating an area under the curve (AUC) to assess for a relationship with restless legs syndrome. RESULTS: Prevalence of RLS was 35 percent. Cumulative mean ± SEM tacrolimus exposure was similar in patients with RLS versus those without RLS (17446 ± 1855 ng days/mL vs. 15303 ± 1643 ng days/mL, respectively; p = 0.42). Insomnia severity index scores (12.5 ± 1.0 vs 6.8 ± 0.7, p < 0.0001) and Sheehan disability scores (7.8 ± 1.3 vs 3.6 ± 0.6, p = 0.003) were significantly higher in those with vs those without RLS symptoms, respectively. CONCLUSIONS: Our data confirms increased prevalence of RLS following lung transplantation reported by previous studies. RLS symptoms were not related to estimated tacrolimus exposure. Predictors of RLS following lung transplantation need to be further investigated to better identify and control RLS symptoms and reduce associated insomnia and disability.