Feasibility of Brief, Hypnotic Enhanced Cognitive Therapy for SCI-related Pain During Inpatient Rehabilitation.

OBJECTIVES: (1) Adapt evidence-based hypnosis-enhanced cognitive therapy (HYP-CT) for inpatient rehabilitation setting; and (2) determine feasibility of a clinical trial evaluating the effectiveness of HYP-CT intervention for pain after spinal cord injury (SCI). STUDY DESIGN: Pilot non-randomized controlled trial. SETTING: Inpatient rehabilitation unit. PARTICIPANTS: English-speaking patients admitted to inpatient rehabilitation after SCI reporting current pain of at least 3 on a 0-10 scale. Persons with severe psychiatric illness, recent suicide attempt or elevated risk, or significant cognitive impairment were excluded. Consecutive sample of 53 patients with SCI-related pain enrolled, representing 82% of eligible patients. INTERVENTION: Up to 4 sessions of HYP-CT Intervention, each 30-60 minutes long. METHODS: Participants were assessed at baseline and given the choice to receive HYP-CT or Usual Care. MAIN OUTCOME MEASURES: Participant enrollment and participation and acceptability of intervention. Exploratory analyses examined the effect of intervention on pain and cognitive appraisals of pain. RESULTS: In the HYP-CT group, 71% completed at least 3 treatment sessions and reported treatment benefit and satisfaction with the treatment; no adverse events were reported. Exploratory analyses of effectiveness found pre-post treatment pain reductions after HYP-CT with large effect (P<.001; ß=-1.64). While the study was not powered to detect significant between-group differences at discharge, effect sizes revealed decreases in average pain (Cohen's d=-0.13), pain interference (d=-0.10), and pain catastrophizing (d=-0.20) in the HYP-CT group relative to control and increases in self-efficacy (d=0.27) and pain acceptance (d=0.15). CONCLUSIONS: It is feasible to provide HYP-CT to inpatients with SCI, and HYP-CT results in substantial reductions in SCI pain. The study is the first to show a psychological-based nonpharmacologic intervention that may reduce SCI pain during inpatient rehabilitation. A definitive efficacy trial is warranted.

Utilization of rehabilitation services in violent versus nonviolent traumatic spinal cord injury.

BACKGROUND: Violence is the third leading cause of spinal cord injury (SCI) in the United States, and people with violence-related SCI have worse long-term outcomes compared to other traumatic SCI etiologies. Little is known, however, about the underlying reasons for these differences. Access to and utilization of rehabilitation services may differ in this population, but their outpatient care has not been previously investigated. OBJECTIVE: To evaluate differences in utilization patterns of outpatient rehabilitation services between people with violence-related SCI and other traumatic SCI etiologies. DESIGN: Retrospective cohort study. SETTING: Academic tertiary care hospital system. PATIENTS: A total of 41 patients with violence-related SCI residing in King County at the time of injury who completed inpatient rehabilitation (IPR) in our institution were identified from the hospital trauma registry and matched with 41 control patients with nonviolent traumatic SCI. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE(S): The number of appointments attended, canceled, and missed during the first year after discharge from IPR were obtained by chart review for physical medicine & rehabilitation (PM&R) physicians and therapy services. RESULTS: People with violence-related SCI had decreased follow-up with outpatient rehabilitation services after IPR discharge compared to non-violent traumatic SCI, including PM&R (2.50 ± 2.44 vs. 3.76 ± 2.21 visits, ß = -1.28, p = .017), physical therapy (8.91 ± 11.02 vs. 17.57 ± 15.26, ß = -9.79, p = .009), occupational therapy (4.28 ± 7.90 vs. 10.04 ± 14.42, ß = -6.18, p = .033), and recreational therapy (0.293 ± 0.955 vs. 1.37 ± 2.86, ß = -1.07, p = .035). The rate of missed appointments was also higher among people with violence-related SCI compared to controls for PM&R (25.2% ± 28.5% vs. 9.9% ± 16.5%, ß = 14.6%, p = .014) and physical therapy (26.0% ± 32.0% vs 4.2% ± 13.2%, ß = 22.1%, p = .009). CONCLUSIONS: Individuals with violence-related SCI had fewer follow-up appointments with PM&R physicians and other allied health professionals and were more likely to miss scheduled appointments compared to other traumatic SCI etiologies. Decreased outpatient follow-up may affect long-term outcomes for people with violence-related SCI.

A Case Study of Hypnosis Enhanced Cognitive Therapy for Pain in a Ventilator Dependent Patient during Inpatient Rehabilitation for Spinal Cord Injury.

Early, acute pain following spinal cord injury (SCI) is common, can negatively impact SCI rehabilitation, and is frequently not responsive to biomedical treatment. Nonpharmacological interventions show promise in reducing pain for individuals with SCI. However, most psychological interventions rely heavily on verbal interaction between the individual being treated and the clinician, making them inaccessible for individuals with impaired verbal output due to mechanical ventilation. This case study aims to describe the adaptation and implementation of hypnotic cognitive therapy (HYP-CT) intervention for early SCI pain in the context of mechanical ventilation dependence and weaning. The participant was a 54-year-old male with C2 AIS A SCI requiring mechanical ventilation. Four sessions of HYP-CT were provided during inpatient rehabilitation with assessment prior to intervention, after the intervention sessions, and prior to discharge. The participant reported immediate reductions in pain intensity following each intervention session. Overall, he reported increases in self-efficacy and pain acceptance. He did not report any negative treatment effects and thought the intervention provided support during mechanical ventilation weaning. During treatment, he discontinued opioid pain medications and reported actively using intervention strategies. Our results support the potential for early, hypnotic cognitive therapy for individuals with SCI experiencing pain or distress while dependent on mechanical ventilation.

Birth Outcomes and Rehospitalizations Among Pregnant Women With Rheumatoid Arthritis and Systemic Lupus Erythematosus and Their Offspring.

OBJECTIVE: To compare obstetric/birth outcomes and rehospitalization among women with and without rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) and their infants. METHODS: This population-based retrospective cohort study identified women with RA (n = 1,223) and SLE (n = 1,354) and unexposed women with singleton births 1987-2014 in Washington State in linked vital hospital discharge records. Outcomes, including cause-specific hospitalizations <2 years postpartum, were compared by estimating adjusted relative risks (RRs) and cause-specific rehospitalization hazard ratios (HRs) with 95% confidence intervals (95% CIs). RESULTS: We observed increased risks of several adverse outcomes; RRs were often greatest for SLE. Women with RA/SLE more often required rehospitalization, most notably at <6 months postpartum (RA: 4% versus 2%; RR 2.22 [95% CI 1.62-3.04]; SLE: 6% versus 2%; RR 2.78 [95% CI 2.15-3.59]). Maternal postpartum rehospitalization was greatest for musculoskeletal conditions (RA: HR 19.1 [95% CI 13.6-26.8]; SLE: HR 29.8 [95% CI 22.1-40.1]). Infants of women with SLE more often had malformations (9% versus 6%; RR 1.46 [95% CI 1.21-1.75]), and increased mortality at <2 years (RR 2.11 [95% CI 1.21-3.67]). Infants of women with SLE also experienced more frequent rehospitalizations in their first year of life. CONCLUSION: Women with RA or SLE and their infants experienced adverse outcomes, particularly infants of women with SLE. Maternal/infant rehospitalization was more common; most marked in the early months postpartum. Close follow-up during these time periods is crucial to minimize adverse outcomes.

Positive predictive value of a sepsis-screening protocol for patients with tetraplegia.

OBJECTIVE: To determine the positive predictive value (PPV) of a sepsis-screening protocol in patients with cervical spinal cord injury (SCI). DESIGN/METHOD: Retrospective review of all patients with cervical SCI who screened positive for two or more systemic inflammatory response syndrome (SIRS) criteria while hospitalized in acute care or inpatient rehabilitation units over a 3.5-year period. Sepsis was defined by the occurrence of (1) any culture order followed by an intravenous (IV) antibiotic within 72 hours or (2) an IV antimicrobial followed by a culture order within 24 hours. RESULTS: A total of 134 patients screened positive for two or more SIRS criteria. Of these, 36 patients (26.9%) were diagnosed with sepsis. Factors associated with a true-positive SIRS screen on multivariable analysis included American Spinal Injury Association Impairment Scale (AIS) grade A-C (vs. D; p < .001). The PPV of the screen was 38% in patients with AIS A-C and 9% in patients with AIS D. Altered mental status (AMS) was strongly associated with a diagnosis of sepsis; 16 of 18 (88.9%) of those with AMS had sepsis (p < .001). Age, sex, and neurologic level of injury were not associated with true-positive screening. For patients with new SCI, the first true-positive screen occurred a median of 31 days post-injury. The most common SIRS criteria combinations in patients with true-positive screens were elevated heart rate and either abnormal white blood cell count (43% of true positives) or abnormal temperature (26% of true positives). Abnormally low body temperature (<36°C) contributed to false-positive screening for 10 of 38 (26%) AIS D patients who screened positive. CONCLUSION: Sepsis screening using SIRS criteria in hospitalized patients with tetraplegia has a PPV of 26.9%; it is significantly higher in patients with AIS A-C versus D injuries. AMS, when combined with a positive SIRS screening, is strongly associated with sepsis.

Morbidity and rehospitalization postpartum among women with epilepsy and their infants: A population-based study.

OBJECTIVE: We compared the relative occurrence of selected pregnancy outcomes and postpartum rehospitalizations among women with and without epilepsy and their infants. Using linked vital-hospital discharge records of women with deliveries in Washington State 1987-2014, comparisons were made overall, by epilepsy type, and by time periods related to antiepileptic drug (AED) marketing changes. METHODS: This population-based retrospective cohort study identified women with, and without epilepsy per diagnosis codes in the hospital discharge record from among all deliveries during 1987-2014 to examine maternal and infant outcomes, rehospitalization and mortality <2 years postpartum. Relative risks (RRs) and 95 % confidence intervals (CI) overall, and by epilepsy type were calculated using Poisson regression. We assessed the validity of epilepsy identification based on diagnosis codes by conducting a medical chart review for a sample of women. RESULTS: Women with epilepsy had increased risks of preeclampsia (RR 1.23; 95 % CI 1.08-1.41) and gestational diabetes (RR 1.18; 95 % CI 1.02-1.36). Their infants had increased malformation (RR 1.23; 95 % C: 1.08-1.42) and small for gestational age (SGA, RR 1.39; 95 % CI 1.25-1.54) risks, and were nearly three times as likely to not be breastfed. Affected mothers (RR 5.25; 95 % CI 2.46-11.23) and their infants (RR 1.64, 95 % CI 1.41-1.89) required more ICU admissions during the delivery hospitalizations, and more postpartum rehospitalization, with greatest risk in the first six months. Maternal mortality < 2 years after delivery was increased (RR 7.11; 95 % CI 2.47-20.49). Increased risks were observed for all epilepsy subtypes for nearly all outcomes examined. Risks of preterm delivery and low birthweight increased over time (p <.05). Suggestive, but not statistically significant temporal decreases in risks of gestational diabetes and malformations and increased risk of preterm labor were noted. We observed high sensitivity of diagnosis codes for identifying pregnant women with epilepsy. CONCLUSION: These population-based results emphasize the need for frequent postpartum monitoring of women with epilepsy. Increases in risks of low birthweight and preterm delivery over time are of concern. Possible temporal changes in other outcomes warrant further investigation.

Pregnancy outcomes among visually impaired women in Washington State, 1987-2014.

BACKGROUND: Women with visual impairment may have reduced ability to access standard care resources, however, information on their pregnancy and neonatal outcomes is limited. OBJECTIVE: To assess risk of adverse pregnancy and neonatal outcomes among visually impaired women in Washington State from 1987 to 2014. METHODS: We conducted a retrospective cohort study using linked Washington State birth/fetal death hospital discharge records to compare outcomes among women with and without visual impairment noted at their delivery hospitalization. Pregnancy conditions and outcomes evaluated included gestational diabetes, pre-eclampsia, labor induction and cesarean delivery. Neonatal outcomes included preterm delivery and birth weight <2500 g. We assessed length of maternal and infant delivery hospitalization. We performed Poisson regression to estimate relative risks (RR) and 95% confidence intervals (CIs) for each outcome, adjusting for year of delivery, maternal age, and parity. RESULTS: Most adverse pregnancy and neonatal outcomes were similar for visually impaired (N = 232) and comparison women (N = 2362). However, visually impaired women had increased risks of severe pre-eclampsia (RR 3.77, 95% CI 1.69-8.43), labor induction (RR 1.33, 95% CI 1.10-1.61) and preterm delivery (RR 1.60, 95% CI 1.06-2.42). They were also more likely to have delivery hospitalizations of 3 or more days following a vaginal (RR 1.86, 95% CI 1.41-2.47). Among cesarean deliveries, infants of visually impaired women had increased risk (RR 1.24, 95% CI 1.02-1.51) of hospitalization for 3 or more days postpartum. CONCLUSION: Our findings may be useful for obstetric providers in counseling their visually impaired patients.

A tele-health intervention to increase physical fitness in people with spinal cord injury and cardiometabolic disease or risk factors: a pilot randomized controlled trial.

STUDY DESIGN: Clinical trial. OBJECTIVES: We used a single-blind parallel-group design to test the feasibility and preliminary efficacy of a telehealth-based physical activity counseling intervention to increase physical fitness in people with SCI. SETTING: Seattle, Washington, United States. METHODS: We recruited under-active, manual wheelchair-using adults at least 1-year post-SCI who had at least two cardiometabolic risk factors/diseases. Participants underwent baseline tests of peak cardiorespiratory fitness; lipids, glucose and insulin; muscle and fat mass; self-reported physical activity, depression, pain and other factors. Participants were assigned 1:1 to treatment vs. usual care (UC) control conditions via concealed computerized randomization. Treatment was delivered via telephone and adapted from the 16-session Diabetes Prevention Program. All baseline tests were repeated at 6 months. Prespecified feasibility goals were to recruit at least nine participants/quarter and retain 85% with complete fitness testing at 6 months. Prespecified efficacy goals were to demonstrate at least a medium treatment effect size (0.50) on fitness, self-reported physical activity, and other outcomes. RESULTS: Seven participants were randomized to treatment, 8 to UC over 15 months. Maximum recruitment was only 5.4 participants/quarter. Thirteen (87%) of participants were retained. The effects of treatment on fitness and most cardiometabolic risk factors did not meet expectations, whereas the effects on self-reported physical activity, depression, and pain did meet expectations. CONCLUSIONS: The study did not meet key efficacy and feasibility objectives, yet there were some promising effects on self-report measures and lessons to be learned for designing future trials.

Interdisciplinary care for spinal cord injured refugees.

INTRODUCTION: For war-injured refugees, spinal cord injury (SCI) is a leading cause of catastrophic neurologic injury and literature focused on the care of this vulnerable population is sparse. This case series describes the unique challenges presented to an outpatient interdisciplinary rehabilitation team in providing SCI care in the USA for refugees who suffered their SCI in their home countries. CASE PRESENTATION: Our interdisciplinary rehabilitation team faced challenges related to language, cultural and educational barriers which impacted the typical standard rehabilitation care offered to these individuals. Many of the individuals were focused on curative treatments. As such, managing expectations and educating individuals to rehabilitation practices for chronic SCI and lack of curative treatments for associated medical complications affected the provision of care across all disciplines of the rehabilitation team. DISCUSSION: This case series showcases the challenges of caring for international refugees with SCI. The care offered to these individuals highlights the benefits that an interdisciplinary SCI rehabilitation approach can provide to comprehensively care for this vulnerable population.

Assessment of the Accuracy of Identification of Selected Disabilities and Conditions in Hospital Discharge Data for Pregnant Women.

BACKGROUND: Linked birth certificate-hospital discharge records are a valuable resource for examining pregnancy outcomes among women with disability conditions. Few studies relying on these data have been able to assess the accuracy of identification of preexisting disability conditions. We assessed the accuracy of International Classification of Diseases version 9 (ICD9) codes for identifying selected physical, sensory, and intellectual conditions that may result in disability. As ICD9 codes were utilized until recently in most states, this information is useful to inform analyses with these records. METHODS: We reviewed 280 of 311 (90%) medical records of pregnant women with disabilities based on ICD9 codes and 390 of 8,337 (5%) records of pregnant women without disabilities who had deliveries at a large university medical center. We estimated sensitivity, specificity, and positive predictive values (PPV) using the medical record as gold standard. We adjusted for verification bias using inverse probability weighting and imputation. RESULTS: The estimated sensitivity of ICD9 codes to identify women with disabilities with deliveries 2009-2012 was 44%; PPV was 98%, improving over time. Although sensitivity was <50% for some conditions, PPVs were 87%-100% for all conditions except intellectual disability (67%). Many physical conditions had complete verification and no underreporting. CONCLUSIONS: These results are helpful for new studies using historical data comparing outcomes among women with and without these conditions and to inform interpretation of results from earlier studies. Assessment of the accuracy of disabilities as identified by ICD version 10 codes is warranted.

Intensive Continuous Positive Airway Pressure Adherence Program During Stroke Rehabilitation.

Background and Purpose- Continuous positive airway pressure (CPAP) for the treatment of obstructive sleep apnea may improve stroke recovery, but adherence is poor. We assessed the effectiveness of an intensive CPAP adherence program during and after inpatient stroke rehabilitation on 3-month adherence and stroke recovery. Methods- In a single-arm study, 90 stroke rehabilitation patients were enrolled into an intensive CPAP adherence program. CPAP was continued after a run-in among qualifying patients with evidence of obstructive sleep apnea. The primary outcome was CPAP adherence, defined as ≥4 hours of use on ≥70% of days, over 3 months. Results- A total of 62 patients qualified for continued CPAP and 52 of these were willing to continue CPAP after discharge from rehabilitation. At 3 months, the average daily CPAP use was 4.7 hours (SD 2.6), and 32/52 (62%) patients were adherent. Factors significantly associated with adherence included more severe stroke, aphasia, and white race. Compared with nonadherent patients, adherent patients experienced greater improvements in the cognitive component of the Functional Independence Measure ( P=0.02) and in the National Institutes of Health Stroke Scale ( P=0.03). Conclusions- This intensive CPAP adherence program initiated during stroke rehabilitation can lead to CPAP adherence in the majority of patients with evidence of obstructive sleep apnea, including those with more severe stroke and aphasia, and may promote recovery. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT02809430.

Pregnancy Outcomes in Women with Spinal Cord Injuries: A Population-Based Study.

BACKGROUND: Pregnant women with congenital or acquired spinal cord injury face challenges due to compromised neurologic function and mobility, factors that may also affect fetal/infant health. Few studies have examined pregnancy course and longer-term outcomes in this population. OBJECTIVE: To assess pregnancy outcomes among women with spinal cord injury, paralysis, or spina bifida using population-based data. DESIGN: Retrospective cohort study. SETTING: Washington state linked birth-hospital discharge records. PARTICIPANTS: All women (N = 529) with spinal cord injury, paralysis, or spina bifida with singleton live birth deliveries 1987-2012, and a comparison group of women without disabilities (N = 5282). METHODS: Diagnosis codes were screened to identify cases and a 10:1 random sample of comparison women. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated overall and separately for each condition using multivariable regression. Subsequent hospitalizations or death were identified via linkage to hospital discharge/death records for 2 years after delivery. MAIN OUTCOME MEASUREMENTS: Pregnancy course (weight gain, gestational diabetes, preeclampsia, infection, venous thromboembolism), delivery/labor characteristics, infant characteristics (birthweight/size, gestational age), and longer-term outcomes (occurrence/reasons for maternal/infant rehospitalization, mortality). RESULTS: Women with these spinal conditions had increased adjusted risks of prenatal urinary tract infection/pyelonephritis (RR 26.43, 95% CI 13.97-49.99), venous thromboembolism (RR 9.16, 95% CI 2.17-38.60), preterm rupture of membranes (RR 2.15, 95% CI 1.18-3.90), and cesarean delivery (RR 1.88, 95% CI 1.70-2.09). They had longer hospitalizations and increased rehospitalization (RR 1.54, 95% CI 1.28-1.87), including for postpartum depression (RR 8.15, 4.29-15.48) or injury (RR 13.05, 95% CI 6.60-25.81). Their infants were more often small for gestational age (RR 1.65, 95% CI 1.33-2.06), but had no increased risk of rehospitalization or death. CONCLUSIONS: We observed no increased long-term morbidity among infants of women with these conditions. Possible increased maternal morbidities during the first postpartum years indicate areas for intervention. LEVEL OF EVIDENCE: III.

Pregnancy course, infant outcomes, rehospitalization, and mortality among women with intellectual disability.

BACKGROUND: Pregnant women with intellectual disability (ID) may have greater levels of comorbidity and decreased care access, social support, or ability to monitor their status and communicate needs, but few studies have examined their pregnancy course and outcome, and little is known about their longer-term maternal and infant health. OBJECTIVE: We compared pre-pregnancy characteristics, pregnancy outcomes, and rehospitalization <2 years after delivery among women with and without ID. METHOD: We identified all women with ID and randomly selected a 10:1 comparison group of women without ID with singleton live birth deliveries in Washington State population-based linked birth-hospital discharge data 1987-2012. Multivariable regressions estimated adjusted odds ratios comparing pre-pregnancy characteristics. In cohort analyses, we estimated relative risks (RR) and 95% confidence intervals (CI) for outcomes. RESULTS: Women with ID (N = 103) more often had gestational diabetes (RR 3.39, 95% CI 1.81-6.37), preeclampsia (RR 1.88, 95% CI 1.03-3.42), and inadequate prenatal care (RR 2.48, 95% CI 1.67-3.70). Their infants more often were small for gestational age (RR 1.78, 95% CI 1.10-2.89). Need for rehospitalization postpartum was not increased among women with ID or their infants. CONCLUSION: Reasons for increased preeclampsia and gestational diabetes among pregnant women with ID are unclear. Barriers to inadequate prenatal care are multifactorial and warrant further study, with consideration that wellness during pregnancy and other times involves social, familial and clinical support systems responsive to each woman's needs.

Temporal Requirement for Pulmonary Resident and Circulating T Cells during Virulent Francisella tularensis Infection.

The lung is a complex organ with anatomically distinct pools of T cells that play specific roles in combating infection. Our knowledge regarding the generation and/or maintenance of immunity by parenchymal or circulating T cells has been gathered from either persistent (>60 d) or rapidly cleared (<10 d) infections. However, the roles of these distinct T cell pools in infections that are cleared over the course of several weeks are not understood. Clearance of the highly virulent intracellular bacterium Francisella tularensis subspecies tularensis (Ftt) following pulmonary infection of immune animals is a protracted T cell-dependent process requiring ∼30-40 d and serves as a model for infections that are not acutely controlled. Using this model, we found that intranasal vaccination increased the number of tissue-resident CD4+ effector T cells, and subsequent challenge of immune mice with Ftt led to a significant expansion of polyfunctional parenchymal CD4+ effector T cells compared with the circulating pool. Despite the dominant in vivo response by parenchymal CD4+ T cells after vaccination and challenge, circulating CD4+ T cells were superior at controlling intracellular Ftt replication in vitro. Further examination in vivo revealed temporal requirements for resident and circulating T cells during Ftt infection. These requirements were in direct contrast to other pulmonary infections that are cleared rapidly in immune animals. The data in this study provide important insights into the role of specific T cell populations that will be essential for the design of novel effective vaccines against tularemia and potentially other agents of pulmonary infection.

The Ability to Acquire Iron Is Inversely Related to Virulence and the Protective Efficacy of Francisella tularensis Live Vaccine Strain.

Francisella tularensis is a highly infectious bacterial pathogen that causes the potentially fatal disease tularemia. The Live Vaccine Strain (LVS) of F. tularensis subsp. holarctica, while no longer licensed as a vaccine, is used as a model organism for identifying correlates of immunity and bacterial factors that mediate a productive immune response against F. tularensis. Recently, it was reported that two biovars of LVS differed in their virulence and vaccine efficacy. Genetic analysis showed that they differ in ferrous iron homeostasis; lower Fe2+ levels contributed to increased resistance to hydrogen peroxide in the vaccine efficacious LVS biovar. This also correlated with resistance to the bactericidal activity of interferon γ-stimulated murine bone marrow-derived macrophages. We have extended these findings further by showing that a mutant lacking bacterioferritin stimulates poor protection against Schu S4 challenge in a mouse model of tularemia. Together these results suggest that the efficacious biovar of LVS stimulates productive immunity by a mechanism that is dependent on its ability to limit the toxic effects of oxidative stress by maintaining optimally low levels of intracellular Fe2+.

Pregnancy Outcomes Among Deaf Women in Washington State, 1987-2012.

OBJECTIVE: To evaluate pregnancy and neonatal outcomes among deaf women using population-based vital records data in Washington State from 1987 to 2012. METHODS: We performed a retrospective cohort study using the Washington State birth and fetal death records linked to state hospital discharge records to identify women with diagnosis codes for deafness indicated at their delivery hospitalization and compared them with randomly selected women without these codes. Pregnancy conditions and outcomes evaluated included gestational diabetes, preeclampsia, placental abruption, labor induction, and cesarean delivery. Neonatal outcomes evaluated included preterm gestational age (less than 28, 28 to less than 37 weeks) at delivery and low birth weight. We also assessed length of maternal and neonatal delivery hospitalization. We performed Poisson regression to estimate relative risks (RRs) and 95% CIs for each outcome, adjusting for birth year, maternal age, and parity. RESULTS: Most adverse pregnancy and neonatal outcomes were similar for deaf and comparison women. Among women who underwent vaginal delivery, deaf women were more than twofold (RR 2.15, 95% CI 1.43-3.22) more likely to have a delivery hospitalization of 4 or more days (6.0% compared with 2.8%). We found a modestly increased risk of cesarean delivery (RR 1.15, 95% CI 1.01-1.30), with 29.9% of deaf compared with 25.6% of nondeaf women having a cesarean delivery. CONCLUSION: Deaf women are not at increased risk of the majority of adverse pregnancy and neonatal outcomes. Obstetric care providers may use our findings in counseling this special population of prenatal patients.

Expansion and retention of pulmonary CD4+ T cells after prime boost vaccination correlates with improved longevity and strength of immunity against tularemia.

Francisella tularensis subsp. tularensis strain SchuS4 (Ftt) is a highly virulent intracellular bacterium. Inhalation of 10 or fewer organisms results in an acute and potentially lethal disease called pneumonic tularemia. Ftt infections occur naturally in the U.S. and Ftt was developed as a bioweapon. Thus, there is a need for vaccines that protect against this deadly pathogen. Although a live vaccine strain of Francisella tularensis (LVS) exists, LVS fails to generate long-lived protective immunity against modest challenge doses of Ftt. We recently identified an important role for high avidity CD4+ T cells in short-term protection and hypothesized that expanding this pool of cells would improve overall vaccine efficacy with regard to longevity and challenge dose. In support of our hypothesis, application of a prime/boost vaccination strategy increased the pool of high avidity CD4+ T cells which correlated with improved survival following challenge with either increased doses of virulent Ftt or at late time points after vaccination. In summary, we demonstrate that both epitope selection and vaccination strategies that expand antigen-specific T cells correlate with superior immunity to Ftt as measured by survival.

Benefits of an exercise wellness program after spinal cord injury.

OBJECTIVE: To describe the initial benefits of a structured group exercise program on exercise frequency and intensity, perceived health, pain, mood, and television watching habits. DESIGN: Pre-test/post-test. PARTICIPANTS/METHODS: Eighty-nine persons with SCI participated voluntarily in a no-cost, twice weekly physical therapy group exercise class over 3 months. Forty-five persons completed pre- and post-participation interviews on exercise frequency and intensity, perceived health, pain, mood, sleep, and television watching habits. RESULTS: Mean participant age of the respondents was 43.82 years. 49% had AIS C or D injuries, 24% had AIS A,B paraplegia, 9% had AIS A,B C1-C4 and 18% had AIS A,B C5-C8. 75.6% of participants were male and 84.4% had a traumatic etiology as the cause of their SCI. There was a significant improvement in days of strenuous and moderate exercise as well as health state. There was an average decrease in pain scores, depression scores, number of hours spent watching television, and days/week of mild exercise. CONCLUSION: Participation in structured, small group exercise as a component of a wellness program after SCI shows promise for improving regular exercise participation and health state, but benefits may also occur across other areas of health and function including mood, pain, and hours spent watching television. Further follow-up is needed to determine whether improvements can be maintained after program completion and across all neurological levels.

Inclusion of Epitopes That Expand High-Avidity CD4+ T Cells Transforms Subprotective Vaccines to Efficacious Immunogens against Virulent Francisella tularensis.

T cells are the immunological cornerstone in host defense against infections by intracellular bacterial pathogens, such as virulent Francisella tularensis spp. tularensis (Ftt). The general paucity of novel vaccines for Ftt during the past 60 y can, in part, be attributed to the poor understanding of immune parameters required to survive infection. Thus, we developed a strategy utilizing classical immunological tools to elucidate requirements for effective adaptive immune responses directed against Ftt. Following generation of various Francisella strains expressing well-characterized lymphocytic choriomeningitis virus epitopes, we found that survival correlated with persistence of Ag-specific CD4(+) T cells. Function of these cells was confirmed in their ability to more effectively control Ftt replication in vitro. The importance of understanding the Ag-specific response was underscored by our observation that inclusion of an epitope that elicits high-avidity CD4(+) T cells converted a poorly protective vaccine to one that engenders 100% protection. Taken together, these data suggest that improved efficacy of current tularemia vaccine platforms will require targeting appropriate Ag-specific CD4(+) T cell responses and that elucidation of Francisella epitopes that elicit high-avidity CD4(+) T cell responses, specifically in humans, will be required for successful vaccine development.

Metabolic Reprogramming of Host Cells by Virulent Francisella tularensis for Optimal Replication and Modulation of Inflammation.

A shift in macrophage metabolism from oxidative phosphorylation to aerobic glycolysis is a requirement for activation to effectively combat invading pathogens. Francisella tularensis is a facultative intracellular bacterium that causes an acute, fatal disease called tularemia. Its primary mechanism of virulence is its ability to evade and suppress inflammatory responses while replicating in the cytosol of macrophages. The means by which F. tularensis modulates macrophage activation are not fully elucidated. In this study, we demonstrate that virulent F. tularensis impairs production of inflammatory cytokines in primary macrophages by preventing their shift to aerobic glycolysis, as evidenced by the downregulation of hypoxia inducible factor 1α and failure to upregulate pfkfb3 We also show that Francisella capsule is required for this process. In addition to modulating inflammatory responses, inhibition of glycolysis in host cells is also required for early replication of virulent Francisella Taken together, our data demonstrate that metabolic reprogramming of host cells by F. tularensis is a key component of both inhibition of host defense mechanisms and replication of the bacterium.