Browsing by Subject "Combined Modality Therapy"
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Item Open Access A Combined Patient and Provider Intervention for Management of Osteoarthritis in Veterans: A Randomized Clinical Trial.(Annals of internal medicine, 2016-01) Allen, Kelli D; Yancy, William S; Bosworth, Hayden B; Coffman, Cynthia J; Jeffreys, Amy S; Datta, Santanu K; McDuffie, Jennifer; Strauss, Jennifer L; Oddone, Eugene ZBackground
Management of osteoarthritis requires both medical and behavioral strategies, but some recommended therapies are underused.Objective
To examine the effectiveness of a combined patient and provider intervention for improving osteoarthritis outcomes.Design
Cluster randomized clinical trial with assignment to osteoarthritis intervention and usual care groups. (ClinicalTrials.gov: NCT01130740).Setting
Department of Veterans Affairs Medical Center in Durham, North Carolina.Participants
30 providers (clusters) and 300 outpatients with symptomatic hip or knee osteoarthritis.Intervention
The telephone-based patient intervention focused on weight management, physical activity, and cognitive behavioral pain management. The provider intervention involved delivery of patient-specific osteoarthritis treatment recommendations to primary care providers through the electronic medical record.Measurements
The primary outcome was total score on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at 12 months. Secondary outcomes were WOMAC function and pain subscale scores, physical performance (Short Physical Performance Battery), and depressive symptoms (Patient Health Questionnaire-8). Linear mixed models that were adjusted for clustering of providers assessed between-group differences in improvement in outcomes.Results
At 12 months, WOMAC scores were 4.1 points lower (indicating improvement) in the osteoarthritis intervention group versus usual care (95% CI, -7.2 to -1.1 points; P = 0.009). WOMAC function subscale scores were 3.3 points lower in the intervention group (CI, -5.7 to -1.0 points; P = 0.005). WOMAC pain subscale scores (P = 0.126), physical performance, and depressive symptoms did not differ between groups. Although more patients in the osteoarthritis intervention group received provider referral for recommended osteoarthritis treatments, the numbers who received them did not differ.Limitation
The study was conducted in a single Veterans Affairs medical center.Conclusion
The combined patient and provider intervention resulted in modest improvement in self-reported physical function in patients with hip and knee osteoarthritis.Primary funding source
Department of Veterans Affairs, Health Services Research and Development Service.Item Open Access A curative combination cancer therapy achieves high fractional cell killing through low cross-resistance and drug additivity.(eLife, 2019-11) Palmer, Adam C; Chidley, Christopher; Sorger, Peter KCurative cancer therapies are uncommon and nearly always involve multi-drug combinations developed by experimentation in humans; unfortunately, the mechanistic basis for the success of such combinations has rarely been investigated in detail, obscuring lessons learned. Here, we use isobologram analysis to score pharmacological interaction, and clone tracing and CRISPR screening to measure cross-resistance among the five drugs comprising R-CHOP, a combination therapy that frequently cures Diffuse Large B-Cell Lymphomas. We find that drugs in R-CHOP exhibit very low cross-resistance but not synergistic interaction: together they achieve a greater fractional kill according to the null hypothesis for both the Loewe dose-additivity model and the Bliss effect-independence model. These data provide direct evidence for the 50 year old hypothesis that a curative cancer therapy can be constructed on the basis of independently effective drugs having non-overlapping mechanisms of resistance, without synergistic interaction, which has immediate significance for the design of new drug combinations.Item Open Access Adherence to adjuvant endocrine therapy for breast cancer: importance in women with low income.(Journal of women's health (2002), 2015-05) Ursem, Carling J; Bosworth, Hayden B; Shelby, Rebecca A; Hwang, Wenke; Anderson, Roger T; Kimmick, Gretchen GThere are wide disparities in breast cancer-specific survival by patient sociodemographic characteristics. Women of lower income, for instance, have higher relapse and death rates from breast cancer. One possible contributing factor for this disparity is low use of adjuvant endocrine therapy-an extremely efficacious therapy in women with early stage, hormone receptor positive breast cancer, the most common subtype of breast cancer. Alone, adjuvant endocrine therapy decreases breast cancer recurrence by 50% and death by 30%. Data suggest that low use of adjuvant endocrine therapy is a potentially important and modifiable risk factor for poor outcome in low-income breast cancer patients.Item Open Access Adherence to diabetes guidelines for screening, physical activity and medication and onset of complications and death.(J Diabetes Complications, 2015-11) Chen, Yiqun; Sloan, Frank A; Yashkin, Arseniy PAIMS: Analyze relationships between adherence to guidelines for diabetes care - regular screening; physical activity; and medication - and diabetes complications and mortality. METHODS: Outcomes were onset of congestive heart failure (CHF), stroke, renal failure, moderate complications of lower extremities, lower-limb amputation, proliferative diabetic retinopathy (PDR), and mortality during follow-up. Participants were persons aged 65+ in the Health and Retirement Study (HRS) 2003 Diabetes Study and had Medicare claims in follow-up period (2004-8). RESULTS: Adherence to screening recommendations decreased risks of developing CHF (odds ratio (OR)=0.83; 95% confidence interval (CI): 0.72-0.96), stroke (OR=0.80; 95% CI: 0.68-0.94); renal failure (OR=0. 82; 95% CI: 0.71-0.95); and death (OR=0.86; 95% CI: 0.74-0.99). Adherence to physical activity recommendation reduced risks of stroke (OR=0.64; 95% CI: 0.45-0.90), renal failure (OR=0.71; 95% CI: 0.52-0.97), moderate lower-extremity complications (OR=0.71; 95% CI: 0.51-0.99), having a lower limb amputation (OR=0.31, 95% CI: 0.11-0.85), and death (OR=0.56, 95% CI: 0.41-0.77). Medication adherence was associated with lower risks of PDR (OR=0.35, 95% CI: 0.13-0.93). CONCLUSIONS: Adherence to screening, physical activity and medication guidelines was associated with lower risks of diabetes complications and death. Relative importance of adherence differed among outcome measures.Item Open Access Adjunctive β2-agonists reverse neuromuscular involvement in murine Pompe disease.(FASEB J, 2013-01) Li, Songtao; Sun, Baodong; Nilsson, Mats I; Bird, Andrew; Tarnopolsky, Mark A; Thurberg, Beth L; Bali, Deeksha; Koeberl, Dwight DPompe disease has resisted enzyme replacement therapy with acid α-glucosidase (GAA), which has been attributed to inefficient cation-independent mannose-6-phosphate receptor (CI-MPR) mediated uptake. We evaluated β2-agonist drugs, which increased CI-MPR expression in GAA knockout (KO) mice. Clenbuterol along with a low-dose adeno-associated virus vector increased Rotarod latency by 75% at 4 wk, in comparison with vector alone (P<2×10(-5)). Glycogen content was lower in skeletal muscles, including soleus (P<0.01), extensor digitorum longus (EDL; P<0.001), and tibialis anterior (P<0.05) following combination therapy, in comparison with vector alone. Glycogen remained elevated in the muscles following clenbuterol alone, indicating an adjunctive effect with gene therapy. Elderly GAA-KO mice treated with combination therapy demonstrated 2-fold increased wirehang latency, in comparison with vector or clenbuterol alone (P<0.001). The glycogen content of skeletal muscle decreased following combination therapy in elderly mice (P<0.05). Finally, CI-MPR-KO/GAA-KO mice did not respond to combination therapy, indicating that clenbuterol's effect depended on CI-MPR expression. In summary, adjunctive β2-agonist treatment increased CI-MPR expression and enhanced efficacy from gene therapy in Pompe disease, which has implications for other lysosomal storage disorders that involve primarily the brain.Item Open Access Atypical Fibroxanthoma of the Bulbar Conjunctiva.(Cornea, 2015-12) Shieh, Christine; Daluvoy, Melissa B; Ellington, Kenneth S; Proia, Alan DPURPOSE: To report a rare case of atypical fibroxanthoma (AFX) of the bulbar conjunctiva, and to compare it with previously published cases of conjunctival AFX. METHODS: A 37-year-old woman developed a growth on the bulbar conjunctiva of her left eye that increased in size and redness over 4 months and was associated with blurry vision in the left eye, occasional diplopia, irritation of the eye, and increasing tearing. The mass was surgically excised. RESULTS: Slit-lamp examination disclosed a highly vascularized conjunctival lesion with intact lustrous epithelium and a raised nodular edge encroaching on the nasal corneal limbus of the left eye. Pathological examination and immunohistochemistry were diagnostic of AFX. CONCLUSIONS: AFX of the conjunctiva is rare, with this being only the fifth example of this neoplasm reported at this site. Complete surgical excision is the most appropriate treatment option.Item Open Access Brain structural connectivity increases concurrent with functional improvement: evidence from diffusion tensor MRI in children with cerebral palsy during therapy.(NeuroImage. Clinical, 2015-01-09) Englander, Zoë A; Sun, Jessica; Laura Case; Mikati, Mohamad A; Kurtzberg, Joanne; Song, Allen WCerebral Palsy (CP) refers to a heterogeneous group of permanent but non-progressive movement disorders caused by injury to the developing fetal or infant brain (Bax et al., 2005). Because of its serious long-term consequences, effective interventions that can help improve motor function, independence, and quality of life are critically needed. Our ongoing longitudinal clinical trial to treat children with CP is specifically designed to meet this challenge. To maximize the potential for functional improvement, all children in this trial received autologous cord blood transfusions (with order randomized with a placebo administration over 2 years) in conjunction with more standard physical and occupational therapies. As a part of this trial, magnetic resonance imaging (MRI) is used to improve our understanding of how these interventions affect brain development, and to develop biomarkers of treatment efficacy. In this report, diffusion tensor imaging (DTI) and subsequent brain connectome analyses were performed in a subset of children enrolled in the clinical trial (n = 17), who all exhibited positive but varying degrees of functional improvement over the first 2-year period of the study. Strong correlations between increases in white matter (WM) connectivity and functional improvement were demonstrated; however no significant relationships between either of these factors with the age of the child at time of enrollment were identified. Thus, our data indicate that increases in brain connectivity reflect improved functional abilities in children with CP. In future work, this potential biomarker can be used to help differentiate the underlying mechanisms of functional improvement, as well as to identify treatments that can best facilitate functional improvement upon un-blinding of the timing of autologous cord blood transfusions at the completion of this study.Item Open Access Clinical Insights Into the Biology and Treatment of Pancreatic Cancer.(J Oncol Pract, 2016-01) Mettu, Niharika B; Abbruzzese, James LPancreatic cancer is a devastating disease with a universally poor prognosis. In 2015, it is estimated that there will be 48,960 new cases of pancreatic cancer and that 40,560 people will die of the disease. The 5-year survival rate is 7.2% for all patients with pancreatic cancer; however, survival depends greatly on the stage at diagnosis. Unfortunately, 53% of patients already have metastatic disease at diagnosis, which corresponds to a 5-year survival rate of 2.4%. Even for the 9% of patients with localized disease confined to the pancreas, the 5-year survival is still modest at only 27.1%. These grim statistics highlight the need for ways to identify cohorts of individuals at highest risk, methods to screen those at highest risk to identify preinvasive pathologic precursors, and development of effective systemic therapies. Recent clinical and translational progress has emphasized the relationship with diabetes, the role of the stroma, and the interplay of each of these with inflammation in the pathobiology of pancreatic cancer. In this article, we will discuss these relationships and how they might translate into novel management strategies for the treatment of this disease.Item Open Access Colorectal Cancer Liver Metastases: Multimodal Therapy.(Surgical oncology clinics of North America, 2023-01) Aykut, Berk; Lidsky, Michael EDespite a steady decline in incidence and mortality rates, colorectal cancer (CRC) remains the second most common cancer diagnosis in women and the third most common in men worldwide. Notably, the liver is recognized as the most common site of CRC metastasis, and metastases to the liver remain the primary driver of disease-specific mortality for patients with CRC. Although hepatic resection is the backbone of curative-intent treatment, management of CRLM has become increasingly multimodal during the last decade and includes the use of downstaging chemotherapy, ablation techniques, and locoregional therapy, each of which are reviewed herein.Item Restricted Comparative effectiveness studies to improve clinical outcomes in end stage renal disease: the DEcIDE patient outcomes in end stage renal disease study.(BMC Nephrol, 2012-12-06) Boulware, L Ebony; Tangri, Navdeep; Ephraim, Patti L; Scialla, Julia J; Sozio, Stephen M; Crews, Deidra C; Shafi, Tariq; Miskulin, Dana C; Liu, Jiannong; St Peter, Wendy; Jaar, Bernard G; Wu, Albert W; Powe, Neil R; Navaneethan, Sankar D; Bandeen-Roche, Karen; DEcIDE ESRD Patient Outcomes in Renal Disease Study InvestigatorsBACKGROUND: Evidence is lacking to inform providers' and patients' decisions about many common treatment strategies for patients with end stage renal disease (ESRD). METHODS/DESIGN: The DEcIDE Patient Outcomes in ESRD Study is funded by the United States (US) Agency for Health Care Research and Quality to study the comparative effectiveness of: 1) antihypertensive therapies, 2) early versus later initiation of dialysis, and 3) intravenous iron therapies on clinical outcomes in patients with ESRD. Ongoing studies utilize four existing, nationally representative cohorts of patients with ESRD, including (1) the Choices for Healthy Outcomes in Caring for ESRD study (1041 incident dialysis patients recruited from October 1995 to June 1999 with complete outcome ascertainment through 2009), (2) the Dialysis Clinic Inc (45,124 incident dialysis patients initiating and receiving their care from 2003-2010 with complete outcome ascertainment through 2010), (3) the United States Renal Data System (333,308 incident dialysis patients from 2006-2009 with complete outcome ascertainment through 2010), and (4) the Cleveland Clinic Foundation Chronic Kidney Disease Registry (53,399 patients with chronic kidney disease with outcome ascertainment from 2005 through 2009). We ascertain patient reported outcomes (i.e., health-related quality of life), morbidity, and mortality using clinical and administrative data, and data obtained from national death indices. We use advanced statistical methods (e.g., propensity scoring and marginal structural modeling) to account for potential biases of our study designs. All data are de-identified for analyses. The conduct of studies and dissemination of findings are guided by input from Stakeholders in the ESRD community. DISCUSSION: The DEcIDE Patient Outcomes in ESRD Study will provide needed evidence regarding the effectiveness of common treatments employed for dialysis patients. Carefully planned dissemination strategies to the ESRD community will enhance studies' impact on clinical care and patients' outcomes.Item Open Access Comparison of two minimally invasive surgery strategies to treat adult spinal deformity.(Journal of neurosurgery. Spine, 2015-04) Park, Paul; Wang, Michael Y; Lafage, Virginie; Nguyen, Stacie; Ziewacz, John; Okonkwo, David O; Uribe, Juan S; Eastlack, Robert K; Anand, Neel; Haque, Raqeeb; Fessler, Richard G; Kanter, Adam S; Deviren, Vedat; La Marca, Frank; Smith, Justin S; Shaffrey, Christopher I; Mundis, Gregory M; Mummaneni, Praveen V; International Spine Study GroupObject
Minimally invasive surgery (MIS) techniques are becoming a more common means of treating adult spinal deformity (ASD). The aim of this study was to compare the hybrid (HYB) surgical approach, involving minimally invasive lateral interbody fusion with open posterior instrumented fusion, to the circumferential MIS (cMIS) approach to treat ASD.Methods
The authors performed a retrospective, multicenter study utilizing data collected in 105 patients with ASD who were treated via MIS techniques. Criteria for inclusion were age older than 45 years, coronal Cobb angle greater than 20°, and a minimum of 1 year of follow-up. Patients were stratified into 2 groups: HYB (n = 62) and cMIS (n = 43).Results
The mean age was 60.7 years in the HYB group and 61.0 years in the cMIS group (p = 0.910). A mean of 3.6 interbody fusions were performed in the HYB group compared with a mean of 4.0 interbody fusions in the cMIS group (p = 0.086). Posterior fusion involved a mean of 6.9 levels in the HYB group and a mean of 5.1 levels in the cMIS group (p = 0.003). The mean follow-up was 31.3 months for the HYB group and 38.3 months for the cMIS group. The mean Oswestry Disability Index (ODI) score improved by 30.6 and 25.7, and the mean visual analog scale (VAS) scores for back/leg pain improved by 2.4/2.5 and 3.8/4.2 for the HYB and cMIS groups, respectively. There was no significant difference between groups with regard to ODI or VAS scores. For the HYB group, the lumbar coronal Cobb angle decreased by 13.5°, lumbar lordosis (LL) increased by 8.2°, sagittal vertical axis (SVA) decreased by 2.2 mm, and LL-pelvic incidence (LL-PI) mismatch decreased by 8.6°. For the cMIS group, the lumbar coronal Cobb angle decreased by 10.3°, LL improved by 3.0°, SVA increased by 2.1 mm, and LL-PI decreased by 2.2°. There were no significant differences in these radiographic parameters between groups. The complication rate, however, was higher in the HYB group (55%) than in the cMIS group (33%) (p = 0.024).Conclusions
Both HYB and cMIS approaches resulted in clinical improvement, as evidenced by decreased ODI and VAS pain scores. While there was no significant difference in degree of radiographic correction between groups, the HYB group had greater absolute improvement in degree of lumbar coronal Cobb angle correction, increased LL, decreased SVA, and decreased LL-PI. The complication rate, however, was higher with the HYB approach than with the cMIS approach.Item Open Access Early, Goal-Directed Therapy for Septic Shock - A Patient-Level Meta-Analysis.(The New England journal of medicine, 2017-06) PRISM Investigators; Rowan, Kathryn M; Angus, Derek C; Bailey, Michael; Barnato, Amber E; Bellomo, Rinaldo; Canter, Ruth R; Coats, Timothy J; Delaney, Anthony; Gimbel, Elizabeth; Grieve, Richard D; Harrison, David A; Higgins, Alisa M; Howe, Belinda; Huang, David T; Kellum, John A; Mouncey, Paul R; Music, Edvin; Peake, Sandra L; Pike, Francis; Reade, Michael C; Sadique, M Zia; Singer, Mervyn; Yealy, Donald MBACKGROUND:After a single-center trial and observational studies suggesting that early, goal-directed therapy (EGDT) reduced mortality from septic shock, three multicenter trials (ProCESS, ARISE, and ProMISe) showed no benefit. This meta-analysis of individual patient data from the three recent trials was designed prospectively to improve statistical power and explore heterogeneity of treatment effect of EGDT. METHODS:We harmonized entry criteria, intervention protocols, outcomes, resource-use measures, and data collection across the trials and specified all analyses before unblinding. After completion of the trials, we pooled data, excluding the protocol-based standard-therapy group from the ProCESS trial, and resolved residual differences. The primary outcome was 90-day mortality. Secondary outcomes included 1-year survival, organ support, and hospitalization costs. We tested for treatment-by-subgroup interactions for 16 patient characteristics and 6 care-delivery characteristics. RESULTS:We studied 3723 patients at 138 hospitals in seven countries. Mortality at 90 days was similar for EGDT (462 of 1852 patients [24.9%]) and usual care (475 of 1871 patients [25.4%]); the adjusted odds ratio was 0.97 (95% confidence interval, 0.82 to 1.14; P=0.68). EGDT was associated with greater mean (±SD) use of intensive care (5.3±7.1 vs. 4.9±7.0 days, P=0.04) and cardiovascular support (1.9±3.7 vs. 1.6±2.9 days, P=0.01) than was usual care; other outcomes did not differ significantly, although average costs were higher with EGDT. Subgroup analyses showed no benefit from EGDT for patients with worse shock (higher serum lactate level, combined hypotension and hyperlactatemia, or higher predicted risk of death) or for hospitals with a lower propensity to use vasopressors or fluids during usual resuscitation. CONCLUSIONS:In this meta-analysis of individual patient data, EGDT did not result in better outcomes than usual care and was associated with higher hospitalization costs across a broad range of patient and hospital characteristics. (Funded by the National Institute of General Medical Sciences and others; PRISM ClinicalTrials.gov number, NCT02030158 .).Item Open Access Effective Prevention of Proximal Junctional Failure in Adult Spinal Deformity Surgery Requires a Combination of Surgical Implant Prophylaxis and Avoidance of Sagittal Alignment Overcorrection.(Spine, 2020-02) Line, Breton G; Bess, Shay; Lafage, Renaud; Lafage, Virgine; Schwab, Frank; Ames, Christopher; Kim, Han Jo; Kelly, Michael; Gupta, Munish; Burton, Douglas; Hart, Robert; Klineberg, Eric; Kebaish, Khaled; Hostin, Richard; Mundis, Gregory; Eastlack, Robert; Shaffrey, Christopher; Smith, Justin S; International Spine Study GroupStudy design
Propensity score matched analysis of a multi-center prospective adult spinal deformity (ASD) database.Objective
Evaluate if surgical implant prophylaxis combined with avoidance of sagittal overcorrection more effectively prevents proximal junctional failure (PJF) than use of surgical implants alone.Summary of background data
PJF is a severe form of proximal junctional kyphosis (PJK). Efforts to prevent PJF have focused on use of surgical implants. Less information exists on avoidance of overcorrection of age-adjusted sagittal alignment to prevent PJF.Methods
Surgically treated ASD patients (age ≥18 yrs; ≥5 levels fused, ≥1 year follow-up) enrolled into a prospective multi-center ASD database were propensity score matched (PSM) to control for risk factors for PJF. Patients evaluated for use of surgical implants to prevent PJF (IMPLANT) versus no implant prophylaxis (NONE), and categorized by the type of implant used (CEMENT, HOOK, TETHER). Postoperative sagittal alignment was evaluated for overcorrection of age-adjusted sagittal alignment (OVER) versus within sagittal parameters (ALIGN). Incidence of PJF was evaluated at minimum 1 year postop.Results
Six hundred twenty five of 834 eligible for study inclusion were evaluated. Following PSM to control for confounding variables, analysis demonstrated the incidence of PJF was lower for IMPLANT (n = 235; 10.6%) versus NONE (n = 390: 20.3%; P < 0.05). Use of transverse process hooks at the upper instrumented vertebra (HOOK; n = 115) had the lowest rate of PJF (7.0%) versus NONE (20.3%; P < 0.05). ALIGN (n = 246) had lower incidence of PJF than OVER (n = 379; 12.0% vs. 19.2%, respectively; P < 0.05). The combination of ALIGN-IMPLANT further reduced PJF rates (n = 81; 9.9%), while OVER-NONE had the highest rate of PJF (n = 225; 24.2%; P < 0.05).Conclusion
Propensity score matched analysis of 625 ASD patients demonstrated use of surgical implants alone to prevent PJF was less effective than combining implants with avoidance of sagittal overcorrection. Patients that received no PJF implant prophylaxis and had sagittal overcorrection had the highest incidence of PJF.Level of evidence
3.Item Open Access Effects of the dietary approaches to stop hypertension diet, exercise, and caloric restriction on neurocognition in overweight adults with high blood pressure.(Hypertension, 2010-06) Smith, Patrick J; Blumenthal, James A; Babyak, Michael A; Craighead, Linda; Welsh-Bohmer, Kathleen A; Browndyke, Jeffrey N; Strauman, Timothy A; Sherwood, AndrewHigh blood pressure increases the risks of stroke, dementia, and neurocognitive dysfunction. Although aerobic exercise and dietary modifications have been shown to reduce blood pressure, no randomized trials have examined the effects of aerobic exercise combined with dietary modification on neurocognitive functioning in individuals with high blood pressure (ie, prehypertension and stage 1 hypertension). As part of a larger investigation, 124 participants with elevated blood pressure (systolic blood pressure 130 to 159 mm Hg or diastolic blood pressure 85 to 99 mm Hg) who were sedentary and overweight or obese (body mass index: 25 to 40 kg/m(2)) were randomized to the Dietary Approaches to Stop Hypertension (DASH) diet alone, DASH combined with a behavioral weight management program including exercise and caloric restriction, or a usual diet control group. Participants completed a battery of neurocognitive tests of executive function-memory-learning and psychomotor speed at baseline and again after the 4-month intervention. Participants on the DASH diet combined with a behavioral weight management program exhibited greater improvements in executive function-memory-learning (Cohen's D=0.562; P=0.008) and psychomotor speed (Cohen's D=0.480; P=0.023), and DASH diet alone participants exhibited better psychomotor speed (Cohen's D=0.440; P=0.036) compared with the usual diet control. Neurocognitive improvements appeared to be mediated by increased aerobic fitness and weight loss. Also, participants with greater intima-medial thickness and higher systolic blood pressure showed greater improvements in executive function-memory-learning in the group on the DASH diet combined with a behavioral weight management program. In conclusion, combining aerobic exercise with the DASH diet and caloric restriction improves neurocognitive function among sedentary and overweight/obese individuals with prehypertension and hypertension.Item Open Access Effects of varenicline and cognitive bias modification on neural response to smoking-related cues: study protocol for a randomized controlled study.(Trials, 2014-10-07) Attwood, Angela S; Williams, Tim; Adams, Sally; McClernon, Francis J; Munafò, Marcus RBACKGROUND: Smoking-related cues can trigger drug-seeking behaviors, and computer-based interventions that reduce cognitive biases towards such cues may be efficacious and cost-effective cessation aids. In order to optimize such interventions, there needs to be better understanding of the mechanisms underlying the effects of cognitive bias modification (CBM). Here we present a protocol for an investigation of the neural effects of CBM and varenicline in non-quitting daily smokers. METHODS/DESIGN: We will recruit 72 daily smokers who report smoking at least 10 manufactured cigarettes or 15 roll-ups per day and who smoke within one hour of waking. Participants will attend two sessions approximately one week apart. At the first session participants will be screened for eligibility and randomized to receive either varenicline or a placebo over a seven-day period. On the final drug-taking day (day seven) participants will attend a second session and be further randomized to one of three CBM conditions (training towards smoking cues, training away from smoking cues, or control training). Participants will then undergo a functional magnetic resonance imaging scan during which they will view smoking-related pictorial cues. Primary outcome measures are changes in cognitive bias as measured by the visual dot-probe task, and neural responses to smoking-related cues. Secondary outcome measures will be cognitive bias as measured by a transfer task (modified Stroop test of smoking-related cognitive bias) and subjective mood and cigarette craving. DISCUSSION: This study will add to the relatively small literature examining the effects of CBM in addictions. It will address novel questions regarding the neural effects of CBM. It will also investigate whether varenicline treatment alters neural response to smoking-related cues. These findings will inform future research that can develop behavioral treatments that target relapse prevention. TRIAL REGISTRATION: Registered with Current Controlled Trials: ISRCTN65690030. Registered on 30 January 2014.Item Open Access Faced joint locking.(Journal of neurosurgery. Spine, 2011-01) Shaffrey, Christopher IItem Open Access Factors associated with non-adherence to three hypertension self-management behaviors: preliminary data for a new instrument.(Journal of general internal medicine, 2013-01) Crowley, Matthew J; Grubber, Janet M; Olsen, Maren K; Bosworth, Hayden BBackground
Clinicians have difficulty in identifying patients that are unlikely to adhere to hypertension self-management. Identifying non-adherence is essential to addressing suboptimal blood pressure control and high costs.Objectives
1) To identify risk factors associated with non-adherence to three key self-management behaviors in patients with hypertension: proper medication use, diet, and exercise; 2) To evaluate the extent to which an instrument designed to identify the number of risk factors present for non-adherence to each of the three hypertension self-management behaviors would be associated with self-management non-adherence and blood pressure.Design
Cross-sectional analysis of randomized trial data.Patients
Six hundred and thirty-six primary care patients with hypertension.Measurements
1) Demographic, socioeconomic, psychosocial, and health belief-related factors; 2) measures of self-reported adherence to recommended medication use, diet recommendations, and exercise recommendations, all collected at baseline assessment; 3) systolic blood pressure (SBP) and diastolic blood pressure (DBP).Results
We identified patient factors associated with measures of non-adherence to medications, diet, and exercise in hypertension. We then combined risk factors associated with ≥1 adherence measure into an instrument that generated three composite variables (medication, diet, and exercise composites), reflecting the number of risk factors present for non-adherence to the corresponding self-management behavior. These composite variables identified subgroups with higher likelihood of medication non-adherence, difficulty following diet recommendations, and difficulty following exercise recommendations. Composite variable levels representing the highest number of self-management non-adherence risk factors were associated with higher SBP and DBP.Conclusions
We identified factors associated with measures of non-adherence to recommended medication use, diet, and exercise in hypertension. We then developed an instrument that was associated with non-adherence to these self-management behaviors, as well as with blood pressure. With further study, this instrument has potential to improve identification of non-adherent patients with hypertension.Item Open Access Fear, avoidance and physiological symptoms during cognitive-behavioral therapy for social anxiety disorder.(Behav Res Ther, 2013-07) Aderka, Idan M; McLean, Carmen P; Huppert, Jonathan D; Davidson, Jonathan RT; Foa, Edna BWe examined fear, avoidance and physiological symptoms during cognitive-behavioral therapy (CBT) for social anxiety disorder (SAD). Participants were 177 individuals with generalized SAD who underwent a 14-week group CBT as part of a randomized controlled treatment trial. Participants filled out self-report measures of SAD symptoms at pre-treatment, week 4 of treatment, week 8 of treatment, and week 14 of treatment (post-treatment). Cross-lagged Structural Equation Modeling indicated that during the first 8 weeks of treatment avoidance predicted subsequent fear above and beyond previous fear, but fear did not predict subsequent avoidance beyond previous avoidance. However, during the last 6 weeks of treatment both fear and avoidance predicted changes in each other. In addition, changes in physiological symptoms occurred independently of changes in fear and avoidance. Our findings suggest that changes in avoidance spark the cycle of change in treatment of SAD, but the cycle may continue to maintain itself through reciprocal relationships between avoidance and fear. In addition, physiological symptoms may change through distinct processes that are independent from those involved in changes of fear and avoidance.Item Open Access Feasibility of autologous cord blood cells for infants with hypoxic-ischemic encephalopathy.(The Journal of pediatrics, 2014-05) Cotten, C Michael; Murtha, Amy P; Goldberg, Ronald N; Grotegut, Chad A; Smith, P Brian; Goldstein, Ricki F; Fisher, Kimberley A; Gustafson, Kathryn E; Waters-Pick, Barbara; Swamy, Geeta K; Rattray, Benjamin; Tan, Siddhartha; Kurtzberg, JoanneObjective
To assess feasibility and safety of providing autologous umbilical cord blood (UCB) cells to neonates with hypoxic-ischemic encephalopathy (HIE).Study design
We enrolled infants in the intensive care nursery who were cooled for HIE and had available UCB in an open-label study of non-cyropreserved autologous volume- and red blood cell-reduced UCB cells (up to 4 doses adjusted for volume and red blood cell content, 1-5 × 10(7) cells/dose). We recorded UCB collection and cell infusion characteristics, and pre- and post-infusion vital signs. As exploratory analyses, we compared cell recipients' hospital outcomes (mortality, oral feeds at discharge) and 1-year survival with Bayley Scales of Infant and Toddler Development, 3rd edition scores ≥85 in 3 domains (cognitive, language, and motor development) with cooled infants who did not have available cells.Results
Twenty-three infants were cooled and received cells. Median collection and infusion volumes were 36 and 4.3 mL. Vital signs including oxygen saturation were similar before and after infusions in the first 48 postnatal hours. Cell recipients and concurrent cooled infants had similar hospital outcomes. Thirteen of 18 (74%) cell recipients and 19 of 46 (41%) concurrent cooled infants with known 1-year outcomes survived with scores >85.Conclusions
Collection, preparation, and infusion of fresh autologous UCB cells for use in infants with HIE is feasible. A randomized double-blind study is needed.Item Open Access Gene therapy for glycogen storage diseases.(Human molecular genetics, 2019-10) Kishnani, Priya S; Sun, Baodong; Koeberl, Dwight DThe focus of this review is the development of gene therapy for glycogen storage diseases (GSDs). GSD results from the deficiency of specific enzymes involved in the storage and retrieval of glucose in the body. Broadly, GSDs can be divided into types that affect liver or muscle or both tissues. For example, glucose-6-phosphatase (G6Pase) deficiency in GSD type Ia (GSD Ia) affects primarily the liver and kidney, while acid α-glucosidase (GAA) deficiency in GSD II causes primarily muscle disease. The lack of specific therapy for the GSDs has driven efforts to develop new therapies for these conditions. Gene therapy needs to replace deficient enzymes in target tissues, which has guided the planning of gene therapy experiments. Gene therapy with adeno-associated virus (AAV) vectors has demonstrated appropriate tropism for target tissues, including the liver, heart and skeletal muscle in animal models for GSD. AAV vectors transduced liver and kidney in GSD Ia and striated muscle in GSD II mice to replace the deficient enzyme in each disease. Gene therapy has been advanced to early phase clinical trials for the replacement of G6Pase in GSD Ia and GAA in GSD II (Pompe disease). Other GSDs have been treated in proof-of-concept studies, including GSD III, IV and V. The future of gene therapy appears promising for the GSDs, promising to provide more efficacious therapy for these disorders in the foreseeable future.