Browsing by Subject "Treatment Outcome"
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Item Open Access 5-α reductase inhibitors and prostate cancer prevention: where do we turn now?(BMC Med, 2011-09-15) Hamilton, Robert J; Freedland, Stephen JWith the lifetime risk of being diagnosed with prostate cancer so great, an effective chemopreventive agent could have a profound impact on the lives of men. Despite decades of searching for such an agent, physicians still do not have an approved drug to offer their patients. In this article, we outline current strategies for preventing prostate cancer in general, with a focus on the 5-α-reductase inhibitors (5-ARIs) finasteride and dutasteride. We discuss the two landmark randomized, controlled trials of finasteride and dutasteride, highlighting the controversies stemming from the results, and address the issue of 5-ARI use, including reasons why providers may be hesitant to use these agents for chemoprevention. We further discuss the recent US Food and Drug Administration ruling against the proposed new indication for dutasteride and the change to the labeling of finasteride, both of which were intended to permit physicians to use the drugs for chemoprevention. Finally, we discuss future directions for 5-ARI research.Item Open Access A bony Chance fracture through L1 following posterior spinal fusion for adolescent idiopathic scoliosis: a case report.(Spine deformity, 2021-05) Rocos, Brett; Kato, So; Lebel, David; Lewis, StephenStudy design
Case report.Introduction
Instrumented posterior fusion using pedicle screws has been the mainstay of the surgical correction of adolescent idiopathic scoliosis since it was popularised by Roy-Camille in the 1970s. The aim of this case report is to describe the occurrence and salvage of an L1 chance fracture occurring through the lower instrumented vertebra following pedicle screw placement for posterior spinal instrumented fusion in the treatment of adolescent idiopathic scoliosis (AIS).Case report
A 15-year-old female patient underwent T2-L1 posterior instrumented fusion for a Lenke 1b deformity. The selection of fusion levels was made based upon standing and bending radiographs which showed a non-structural lumbar curve. Early recovery was uneventful. At 6 months post-operatively, the patient reported new deformity and pain. A chance fracture at L1 was diagnosed and subsequent extension of instrumentation to L3 was carried out. Final post-operative recovery was uneventful and the patient returned to an active lifestyle.Conclusion
Several factors can contribute to the occurrence of a fracture through an instrumented pedicle. This case shows that there must be due consideration of the small pedicle at L1 when it is chosen as the LIV.Item Open Access A cohort study of 4,190 patients treated with low-intensity pulsed ultrasound (LIPUS): findings in the elderly versus all patients.(BMC Musculoskelet Disord, 2015-03-01) Zura, Robert; Mehta, Samir; Rocca, Gregory J Della; Jones, John; Steen, R GrantBACKGROUND: Patient age is one of many potential risk factors for fracture nonunion. Our hypothesis is that older patients (≥ 60) with fracture risk factors treated with low-intensity pulsed ultrasound (LIPUS) have similar heal rate (HR) to the population as a whole. We evaluate the impact of age in conjunction with other risk factors on HR in LIPUS-treated patients with fresh fracture (≤ 90 days old). METHODS: The Exogen Bone Healing System is a LIPUS device approved in 1994 to accelerate healing of fresh fracture. After approval, the FDA required a Post-Market Registry to assess performance. Patient data collected from October 1994 until October 1998 were individually reviewed and validated by a registered nurse. Four distinct data elements were required to report a patient: date fracture occurred; date treatment began; date treatment ended; and a dichotomous outcome of healed v. failed, by clinical and radiological criteria. Data were used to calculate two derived variables; days to treatment (DTT) and days on treatment (DOT). Every validated fresh fracture patient with DTT, DOT, and outcome is reported. RESULTS: The validated registry had 5,765 patients with fresh fracture; 73% (N = 4,190) are reported, while 13% of patients were lost to follow-up, 11% withdrew or were non-compliant, and 3% died or are missing outcome. Among treatment-compliant patients, HR was 96.2%. Logistic estimates of the odds ratio for healing are equivalent for patients age 30 to 79 years and all age cohorts had a HR > 94%. Open fracture, current smoking, diabetes, vascular insufficiency, osteoporosis, cancer, rheumatoid arthritis, and prescription NSAIDs all reduced HR, but older patients (≥ 60) had similar HRs to the population as a whole. DTT was significantly shorter for patients who healed (p < 0.0001). CONCLUSIONS: Comorbid conditions in conjunction with aging can reduce fracture HR. Patients with fracture who used LIPUS had a 96% HR, whereas the expected HR averages 93%. Time to treatment was significantly shorter among patients who healed (p < 0.0001), suggesting that it is beneficial to begin LIPUS treatment early. Older patients (≥ 60) with fracture risk factors treated with LIPUS exhibit similar heal rates to the population as a whole.Item Open Access A Comparison of Minimally Invasive and Open Transforaminal Lumbar Interbody Fusion for Grade 1 Degenerative Lumbar Spondylolisthesis: An Analysis of the Prospective Quality Outcomes Database.(Neurosurgery, 2020-09) Chan, Andrew K; Bisson, Erica F; Bydon, Mohamad; Foley, Kevin T; Glassman, Steven D; Shaffrey, Christopher I; Wang, Michael Y; Park, Paul; Potts, Eric A; Shaffrey, Mark E; Coric, Domagoj; Knightly, John J; Fu, Kai-Ming; Slotkin, Jonathan R; Asher, Anthony L; Virk, Michael S; Kerezoudis, Panagiotis; Alvi, Mohammed A; Guan, Jian; Haid, Regis W; Mummaneni, Praveen VBackground
It remains unclear if minimally invasive transforaminal lumbar interbody fusion (MI-TLIF) is comparable to traditional, open TLIF because of the limitations of the prior small-sample-size, single-center studies reporting comparative effectiveness.Objective
To compare MI-TLIF to traditional, open TLIF for grade 1 degenerative lumbar spondylolisthesis in the largest study to date by sample size.Methods
We utilized the prospective Quality Outcomes Database registry and queried patients with grade 1 degenerative lumbar spondylolisthesis who underwent single-segment surgery with MI- or open TLIF methods. Outcomes were compared 24 mo postoperatively.Results
A total of 297 patients were included: 72 (24.2%) MI-TLIF and 225 (75.8%) open TLIF. MI-TLIF surgeries had lower mean body mass indexes (29.5 ± 5.1 vs 31.3 ± 7.0, P = .0497) and more worker's compensation cases (11.1% vs 1.3%, P < .001) but were otherwise similar. MI-TLIF had less blood loss (108.8 ± 85.6 vs 299.6 ± 242.2 mL, P < .001), longer operations (228.2 ± 111.5 vs 189.6 ± 66.5 min, P < .001), and a higher return-to-work (RTW) rate (100% vs 80%, P = .02). Both cohorts improved significantly from baseline for 24-mo Oswestry Disability Index (ODI), Numeric Rating Scale back pain (NRS-BP), NRS leg pain (NRS-LP), and Euro-Qol-5 dimension (EQ-5D) (P > .001). In multivariable adjusted analyses, MI-TLIF was associated with lower ODI (β = -4.7; 95% CI = -9.3 to -0.04; P = .048), higher EQ-5D (β = 0.06; 95% CI = 0.01-0.11; P = .02), and higher satisfaction (odds ratio for North American Spine Society [NASS] 1/2 = 3.9; 95% CI = 1.4-14.3; P = .02). Though trends favoring MI-TLIF were evident for NRS-BP (P = .06), NRS-LP (P = .07), and reoperation rate (P = .13), these results did not reach statistical significance.Conclusion
For single-level grade 1 degenerative lumbar spondylolisthesis, MI-TLIF was associated with less disability, higher quality of life, and higher patient satisfaction compared with traditional, open TLIF. MI-TLIF was associated with higher rates of RTW, less blood loss, but longer operative times. Though we utilized multivariable adjusted analyses, these findings may be susceptible to selection bias.Item Open Access A comparison of minimally invasive transforaminal lumbar interbody fusion and decompression alone for degenerative lumbar spondylolisthesis.(Neurosurgical focus, 2019-05) Chan, Andrew K; Bisson, Erica F; Bydon, Mohamad; Glassman, Steven D; Foley, Kevin T; Potts, Eric A; Shaffrey, Christopher I; Shaffrey, Mark E; Coric, Domagoj; Knightly, John J; Park, Paul; Wang, Michael Y; Fu, Kai-Ming; Slotkin, Jonathan R; Asher, Anthony L; Virk, Michael S; Kerezoudis, Panagiotis; Alvi, Mohammed Ali; Guan, Jian; Haid, Regis W; Mummaneni, Praveen VOBJECTIVEThe optimal minimally invasive surgery (MIS) approach for grade 1 lumbar spondylolisthesis is not clearly elucidated. In this study, the authors compared the 24-month patient-reported outcomes (PROs) after MIS transforaminal lumbar interbody fusion (TLIF) and MIS decompression for degenerative lumbar spondylolisthesis.METHODSA total of 608 patients from 12 high-enrolling sites participating in the Quality Outcomes Database (QOD) lumbar spondylolisthesis module underwent single-level surgery for degenerative grade 1 lumbar spondylolisthesis, of whom 143 underwent MIS (72 MIS TLIF [50.3%] and 71 MIS decompression [49.7%]). Surgeries were classified as MIS if there was utilization of percutaneous screw fixation and placement of a Wiltse plane MIS intervertebral body graft (MIS TLIF) or if there was a tubular decompression (MIS decompression). Parameters obtained at baseline through at least 24 months of follow-up were collected. PROs included the Oswestry Disability Index (ODI), numeric rating scale (NRS) for back pain, NRS for leg pain, EuroQol-5D (EQ-5D) questionnaire, and North American Spine Society (NASS) satisfaction questionnaire. Multivariate models were constructed to adjust for patient characteristics, surgical variables, and baseline PRO values.RESULTSThe mean age of the MIS cohort was 67.1 ± 11.3 years (MIS TLIF 62.1 years vs MIS decompression 72.3 years) and consisted of 79 (55.2%) women (MIS TLIF 55.6% vs MIS decompression 54.9%). The proportion in each cohort reaching the 24-month follow-up did not differ significantly between the cohorts (MIS TLIF 83.3% and MIS decompression 84.5%, p = 0.85). MIS TLIF was associated with greater blood loss (mean 108.8 vs 33.0 ml, p < 0.001), longer operative time (mean 228.2 vs 101.8 minutes, p < 0.001), and longer length of hospitalization (mean 2.9 vs 0.7 days, p < 0.001). MIS TLIF was associated with a significantly lower reoperation rate (14.1% vs 1.4%, p = 0.004). Both cohorts demonstrated significant improvements in ODI, NRS back pain, NRS leg pain, and EQ-5D at 24 months (p < 0.001, all comparisons relative to baseline). In multivariate analyses, MIS TLIF-as opposed to MIS decompression alone-was associated with superior ODI change (β = -7.59, 95% CI -14.96 to -0.23; p = 0.04), NRS back pain change (β = -1.54, 95% CI -2.78 to -0.30; p = 0.02), and NASS satisfaction (OR 0.32, 95% CI 0.12-0.82; p = 0.02).CONCLUSIONSFor symptomatic, single-level degenerative spondylolisthesis, MIS TLIF was associated with a lower reoperation rate and superior outcomes for disability, back pain, and patient satisfaction compared with posterior MIS decompression alone. This finding may aid surgical decision-making when considering MIS for degenerative lumbar spondylolisthesis.Item Open Access A cross-site, comparative effectiveness study of an integrated HIV and substance use treatment program.(AIDS Patient Care STDS, 2010-10) Proeschold-Bell, Rae Jean; Heine, Amy; Pence, Brian Wells; McAdam, Keith; Quinlivan, Evelyn ByrdCo-occurrence of HIV and substance abuse is associated with poor outcomes for HIV-related health and substance use. Integration of substance use and medical care holds promise for HIV patients, yet few integrated treatment models have been reported. Most of the reported models lack data on treatment outcomes in diverse settings. This study examined the substance use outcomes of an integrated treatment model for patients with both HIV and substance use at three different clinics. Sites differed by type and degree of integration, with one integrated academic medical center, one co-located academic medical center, and one co-located community health center. Participants (n=286) received integrated substance use and HIV treatment for 12 months and were interviewed at 6-month intervals. We used linear generalized estimating equation regression analysis to examine changes in Addiction Severity Index (ASI) alcohol and drug severity scores. To test whether our treatment was differentially effective across sites, we compared a full model including site by time point interaction terms to a reduced model including only site fixed effects. Alcohol severity scores decreased significantly at 6 and 12 months. Drug severity scores decreased significantly at 12 months. Once baseline severity variation was incorporated into the model, there was no evidence of variation in alcohol or drug score changes by site. Substance use outcomes did not differ by age, gender, income, or race. This integrated treatment model offers an option for treating diverse patients with HIV and substance use in a variety of clinic settings. Studies with control groups are needed to confirm these findings.Item Open Access A lifestyle intervention of weight loss via a low-carbohydrate diet plus walking to reduce metabolic disturbances caused by androgen deprivation therapy among prostate cancer patients: carbohydrate and prostate study 1 (CAPS1) randomized controlled trial.(Prostate cancer and prostatic diseases, 2019-09) Freedland, Stephen J; Howard, Lauren; Allen, Jenifer; Smith, Jordan; Stout, Jennifer; Aronson, William; Inman, Brant A; Armstrong, Andrew J; George, Daniel; Westman, Eric; Lin, Pao-HwaPurpose
The objective of this study was to test a low-carbohydrate diet (LCD) plus walking to reduce androgen deprivation therapy (ADT)-induced metabolic disturbances.Materials and methods
This randomized multi-center trial of prostate cancer (PCa) patients initiating ADT was designed to compare an LCD (≤20g carbohydrate/day) plus walking (≥30 min for ≥5 days/week) intervention vs. control advised to maintain usual diet and exercise patterns. Primary outcome was change in insulin resistance by homeostatic model assessment at 6 months. To detect 20% reduction in insulin resistance, 100 men were required. The study was stopped early after randomizing 42 men due to slow accrual. Secondary outcomes included weight, body composition, lipids, and prostate-specific antigen (PSA). Changes from baseline were compared between arms using rank-sum tests.Results
At 6 months, LCD/walking reduced insulin resistance by 4% vs. 36% increase in control (p = 0.13). At 3 months, vs. control, LCD/walking arm significantly lost weight (7.8kg; p<0.001), improved insulin resistance (↑36%; p = 0.015), hemoglobin A1c (↓3.3%; p = 0.01), high-density lipoprotein (HDL) (↑13%; p = 0.004), and triglyceride (↓37%; p = 0.036). At 6 months, weight loss (10.6kg; p<0.001) and HDL (↑27%; p = 0.003) remained significant. LCD/walking preserved total body bone mineral count (p = 0.025), reduced fat mass (p = 0.002), lean mass (p = 0.036), and percent body fat (p = 0.004). There were no differences in PSA. Limitations include the effect of LCD, weight loss vs. walking instruction are indistinguishable, and small sample size.Conclusions
In an underpowered study, LCD/walking did not improve insulin sensitivity at 6 months. Given most secondary outcomes were improved at 3 months with some remaining improved at 6 months and a secondary analysis showed that LCD/walking reduced insulin resistance over the study, supporting future larger studies of LCD/walking intervention to reduce ADT-induced disturbances.Item Open Access A minimal monitoring approach for the treatment of hepatitis C virus infection (ACTG A5360 [MINMON]): a phase 4, open-label, single-arm trial.(The lancet. Gastroenterology & hepatology, 2022-04) Solomon, Sunil S; Wagner-Cardoso, Sandra; Smeaton, Laura; Sowah, Leonard A; Wimbish, Chanelle; Robbins, Gregory; Brates, Irena; Scello, Christine; Son, Annie; Avihingsanon, Anchalee; Linas, Benjamin; Anthony, Donald; Nunes, Estevão Portela; Kliemann, Dimas A; Supparatpinyo, Khuanchai; Kityo, Cissy; Tebas, Pablo; Bennet, Jaclyn Ann; Santana-Bagur, Jorge; Benson, Constance A; Van Schalkwyk, Marije; Cheinquer, Nelson; Naggie, Susanna; Wyles, David; Sulkowski, MarkBackground
Despite widespread availability of direct-acting antivirals including generic formulations, limited progress has been made in the global adoption of hepatitis C virus (HCV) treatment. Barriers to treatment scale-up include availability and access to diagnostic and monitoring tests, health-care infrastructure, and requirement for frequent visits during treatment.Methods
ACTG A5360 was a phase 4, open-label, single-arm trial across 38 sites in Brazil, South Africa, Thailand, Uganda, and the USA. Key inclusion criteria were age of 18 years or older, evidence of active HCV infection (HCV RNA >1000 IU/mL) and HCV treatment-naive; patients with compensated cirrhosis and HIV/HCV co-infection were included but their enrolment was capped. All participants received a fixed dose combination of oral sofosbuvir (400 mg) and velpatasvir (100 mg) once daily for 12 weeks. The minimal monitoring (MINMON) approach consisted of four components: (1) there was no pre-treatment genotyping; (2) the entire treatment course (84 tablets) was dispensed at entry; (3) there were no scheduled visits or laboratory monitoring; and (4) there were two points of remote contact, at week 4 for adherence and week 22, to schedule outcome assessment at week 24 (-2 weeks to +4 weeks). Participants who missed the week 24 window could return for a visit to assess treatment response any time before week 72. Unplanned visits for any reason were permissible before the week 24 visit. The primary efficacy outcome was sustained virological response (SVR), defined as HCV RNA less than the lower limit of quantification measured at least 22 weeks post-treatment initiation; the primary safety outcome was serious adverse events. The primary efficacy analysis included all participants who initiated treatment, using a missing=failure approach. The primary safety analysis included all participants who initiated treatment and had at least one post-treatment assessment. This trial is registered at ClinicalTrials.gov, NCT03512210.Findings
Between Oct 22, 2018, and July 19, 2019, 400 participants were enrolled across all 38 sites; 399 initiated treatment. At the SVR assessment visit, 355 (89%) of 397 participants reported taking 100% of the trial medication during the 12-week treatment period; two patients did not have any follow-up visits after the entry visit and were excluded from the safety analyses. Overall, 379 of the 399 who initiated treatment had an SVR (95·0%, 95% CI 92·4-96·7). 14 (4%) of 397 participants reported serious adverse events between treatment initiation and week 28; none were treatment related or led to treatment discontinuation or death. 15 (4%) of 399 participants had unplanned visits; none were related to treatment.Interpretation
In this diverse global population of people with HCV, the MINMON approach with sofosbuvir-velpatasvir treatment was safe and achieved SVR comparable to standard monitoring observed in real-world data. Coupled with innovative case finding strategies, this strategy could be crucial to the global HCV elimination agenda.Funding
US National Institutes of Health and Gilead Sciences.Item Open Access A model for predicting the risk of de novo stress urinary incontinence in women undergoing pelvic organ prolapse surgery.(Obstetrics and gynecology, 2014-02) Jelovsek, J Eric; Chagin, Kevin; Brubaker, Linda; Rogers, Rebecca G; Richter, Holly E; Arya, Lily; Barber, Matthew D; Shepherd, Jonathan P; Nolen, Tracy L; Norton, Peggy; Sung, Vivian; Menefee, Shawn; Siddiqui, Nazema; Meikle, Susan F; Kattan, Michael W; Pelvic Floor Disorders NetworkTo construct and validate a prediction model for estimating the risk of de novo stress urinary incontinence (SUI) after vaginal pelvic organ prolapse (POP) surgery and compare it with predictions using preoperative urinary stress testing and expert surgeons' predictions.Using the data set (n=457) from the Outcomes Following Vaginal Prolapse Repair and Midurethral Sling trial, a model using 12 clinical preoperative predictors of de novo SUI was constructed. De novo SUI was determined by Pelvic Floor Distress Inventory responses through 12 months postoperatively. After fitting the multivariable logistic regression model using the best predictors, the model was internally validated with 1,000 bootstrap samples to obtain bias-corrected accuracy using a concordance index. The model's predictions were also externally validated by comparing findings against actual outcomes using Colpopexy and Urinary Reduction Efforts trial patients (n=316). The final model's performance was compared with experts using a test data set of 32 randomly chosen Outcomes Following Vaginal Prolapse Repair and Midurethral Sling trial patients through comparison of the model's area under the curve against: 1) 22 experts' predictions; and 2) preoperative prolapse reduction stress testing.A model containing seven predictors discriminated between de novo SUI status (concordance index 0.73, 95% confidence interval [CI] 0.65-0.80) in Outcomes Following Vaginal Prolapse Repair and Midurethral Sling participants and outperformed expert clinicians (area under the curve 0.72 compared with 0.62, P<.001) and preoperative urinary stress testing (area under the curve 0.72 compared with 0.54, P<.001). The concordance index for Colpopexy and Urinary Reduction Efforts trial participants was 0.62 (95% CI 0.56-0.69).This individualized prediction model for de novo SUI after vaginal POP surgery is valid and outperforms preoperative stress testing, prediction by experts, and preoperative reduction cough stress testing. An online calculator is provided for clinical use.III.Item Open Access A model of sequential heart and composite tissue allotransplant in rats.(Plast Reconstr Surg, 2010-07) Yang, Jun; Erdmann, Detlev; Chang, JC; Komatsu, Issei; Zhang, YiXin; Wang, DanRu; Hodavance, Michael S; Hollenbeck, Scott T; Levinson, Howard; Klitzman, Bruce; Levin, LSBACKGROUND: Some of the 600,000 patients with solid organ allotransplants need reconstruction with a composite tissue allotransplant, such as the hand, abdominal wall, or face. The aim of this study was to develop a rat model for assessing the effects of a secondary composite tissue allotransplant on a primary heart allotransplant. METHODS: Hearts of Wistar Kyoto rats were harvested and transplanted heterotopically to the neck of recipient Fisher 344 rats. The anastomoses were performed between the donor brachiocephalic artery and the recipient left common carotid artery, and between the donor pulmonary artery and the recipient external jugular vein. Recipients received cyclosporine A for 10 days only. Heart rate was assessed noninvasively. The sequential composite tissue allotransplant consisted of a 3 x 3-cm abdominal musculocutaneous flap harvested from Lewis rats and transplanted to the abdomen of the heart allotransplant recipients. The abdominal flap vessels were connected to the femoral vessels. No further immunosuppression was administered following the composite tissue allotransplant. Ten days after composite tissue allotransplantation, rejection of the heart and abdominal flap was assessed histologically. RESULTS: The rat survival rate of the two-stage transplant surgery was 80 percent. The transplanted heart rate decreased from 150 +/- 22 beats per minute immediately after transplant to 83 +/- 12 beats per minute on day 20 (10 days after stopping immunosuppression). CONCLUSIONS: This sequential allotransplant model is technically demanding. It will facilitate investigation of the effects of a secondary composite tissue allotransplant following primary solid organ transplantation and could be useful in developing future immunotherapeutic strategies.Item Open Access A Multi-Center International Analysis of Lung Transplantation Outcomes in Patients With COVID-19.(Clinical transplantation, 2024-09) Kashem, Mohammed Abul; Loor, Gabriel; Emtiazjoo, Amir; Hartwig, Matthew; Van Raemdonck, Dirk; Calvelli, Hannah; Leon Pena, Andres; Salan-Gomez, Marcelo; Zhao, Huaqing; Warnick, Michael; Villavicencio, Mauricio; Ius, Fabio; Ghadimi, Kamrouz; Salman, Jawad; Chandrashekaran, Satish; Machuca, Tiago; Sanchez, Pablo G; Subramaniam, Kathirvel; Neyrinck, Arne; Huddleston, Stephen; Ceulemans, Laurens; Osho, Asishana; D'Silva, Ethan; Ramamurthy, Uma; Shaffer, Andrew; Langer, Nathaniel; Toyoda, YoshiyaIntroduction
Lung transplantation has become increasingly utilized in patients with COVID-19. While several single-center and UNOS database studies have been published on lung transplants (LTs) for end-stage lung disease (ESLD) from Coronavirus disease 2019 (COVID-19), there is a lack of multi-center and international data.Methods
This is a multicenter analysis from 11 high-volume lung transplant centers in the United States and Europe. Data were collected through the Multi-Institutional ECLS Registry and stratified by ESLD due to COVID-19 versus other etiologies. Demographics and clinical variables were compared using Chi-square test and Fisher's exact test. Survival was assessed by Kaplan-Meier curves and compared by log-rank test with propensity score matching.Results
Of 1606 lung transplant recipients, 46 (2.9%) were transplanted for ESLD from COVID-19 compared to 1560 (97.1%) without a history of COVID-19. Among COVID-19 patients, 30 (65.2%) had COVID-19-associated ARDS and 16 (34.8%) had post-COVID-19 fibrosis. COVID-19 patients had higher lung allocation scores (78.0 vs. 44.4, p < 0.0001), had severely limited functional status (37.0% vs. 2.9%, p < 0.0001), had higher preoperative ECMO usage (65.2% vs. 5.4%, p < 0.0001), and spent less time on the waitlist (32 vs. 137 days, p < 0.0001). A 30-day survival was comparable between COVID-19 and non-COVID-19 patients before (100% vs. 98.7%, p = 0.39) and after propensity matching (p = 0.15).Conclusions
Patients who received LTs due to COVID-19 had short-term survival comparable to that of patients without COVID-19. Our findings support the idea that lung transplantation should be considered for select patients with ESLD due to COVID-19.Item Open Access A Multicenter Evaluation of Clinical and Radiographic Outcomes Following High-grade Spondylolisthesis Reduction and Fusion.(Clinical spine surgery, 2017-05) Gandhoke, Gurpreet S; Kasliwal, Manish K; Smith, Justin S; Nieto, JoAnne; Ibrahimi, David; Park, Paul; Lamarca, Frank; Shaffrey, Christopher; Okonkwo, David O; Kanter, Adam SObjective
A retrospective review of the clinical and radiographic outcomes from a multicenter study of surgical treatment for high-grade spondylolisthesis (HGS) in adults. The objective was to assess the safety of surgical reduction, its ability to correct regional deformity, and its clinical effectiveness.Methods
Retrospective, multicenter review of adults (age above 18 y) with lumbosacral HGS (Meyerding grade 3-5) treated surgically with open decompression, attempted reduction, posterior instrumentation, and interbody fusion. Preoperative and postoperative assessment of the Meyerding grade, slip angle, and sacral inclination were performed based on standing radiographs. Preoperative visual analog scale scores were compared with those at the mean follow-up period. Prolo and Oswestry Disability Index scores at most recent follow-up were assessed.Results
A total of 25 patients, aged 19-72 years, met inclusion criteria. Seventeen interbody cages were placed, including 15 transforaminal lumbar interbody fusions, 1 posterior lumbar interbody fusion, and 1 anterior lumbar interbody fusion. Five patients required sacral dome osteotomies. The average follow-up was 21.3 months.At most recent follow-up there was a statistically significant improvement in both the Meyerding grade and the slip angle (P<0.05). There was 1 intraoperative complication resulting in a neurological deficit (4%) and 1 intraoperative vertebral body fracture (4%). No additional surgery was required for any of these patients. There were no cases of nonunion or device failure except for 1 patient who suffered an unrelated traumatic injury 1 year after surgery. The mean Oswestry Disability Index and Prolo scores at mean follow-up of 21.3 months were 20% (minimum disability) and 8.2 (grade 1), respectively.Conclusions
The present study suggests that reduction, when accomplished in conjunction with wide neural element decompression and instrumented arthrodesis, is safe, effective, and durable with low rates of neurological injury, favorable clinical results, and high-fusion rates.Item Open Access A multicenter phase I/II study of obatoclax mesylate administered as a 3- or 24-hour infusion in older patients with previously untreated acute myeloid leukemia.(PloS one, 2014-01) Schimmer, Aaron D; Raza, Azra; Carter, Thomas H; Claxton, David; Erba, Harry; DeAngelo, Daniel J; Tallman, Martin S; Goard, Carolyn; Borthakur, GautamAn open-label phase I/II study of single-agent obatoclax determined a maximum tolerated dose (MTD) and schedule, safety, and efficacy in older patients (≥ 70 yr) with untreated acute myeloid leukemia (AML).Phase I evaluated the safety of obatoclax infused for 3 hours on 3 consecutive days (3 h × 3 d) in 2-week cycles. Initial obatoclax dose was 30 mg/day (3 h × 3 d; n = 3). Obatoclax was increased to 45 mg/day (3 h × 3 d) if ≤ 1 patient had a dose-limiting toxicity (DLT) and decreased to 20 mg/day (3 h × 3 d) if DLT occurred in ≥ 2 patients. In the phase II study, 12 patients were randomized to receive obatoclax at the dose identified during phase I (3 h × 3 d) or 60 mg/day administered by continuous infusion over 24 hours for 3 days (24 h × 3 d) to determine the morphologic complete response rate.In phase I, two of three patients receiving obatoclax 30 mg/day (3 h × 3 d) experienced grade 3 neurologic DLTs (confusion, ataxia, and somnolence). Obatoclax was decreased to 20 mg/day (3 h × 3 d). In phase II, no clinically relevant safety differences were observed between the 20 mg/day (3 h × 3 d; n = 7) and 60 mg/day (24 h × 3 d; n = 5) arms. Neurologic and psychiatric adverse events were most common and were generally transient and reversible. Complete response was not achieved in any patient.Obatoclax 20 mg/day was the MTD (3 h × 3 d) in older patients with AML. In the schedules tested, single-agent obatoclax was not associated with an objective response. Evaluation in additional subgroups or in combination with other chemotherapy modalities may be considered for future study.ClinicalTrials.gov NCT00684918.Item Open Access A Phase II Randomized Clinical Trial of the Safety and Efficacy of Intravenous Umbilical Cord Blood Infusion for Treatment of Children with Autism Spectrum Disorder.(The Journal of pediatrics, 2020-07) Dawson, Geraldine; Sun, Jessica M; Baker, Jennifer; Carpenter, Kimberly; Compton, Scott; Deaver, Megan; Franz, Lauren; Heilbron, Nicole; Herold, Brianna; Horrigan, Joseph; Howard, Jill; Kosinski, Andrzej; Major, Samantha; Murias, Michael; Page, Kristin; Prasad, Vinod K; Sabatos-DeVito, Maura; Sanfilippo, Fred; Sikich, Linmarie; Simmons, Ryan; Song, Allen; Vermeer, Saritha; Waters-Pick, Barbara; Troy, Jesse; Kurtzberg, JoanneObjective
To evaluate whether umbilical cord blood (CB) infusion is safe and associated with improved social and communication abilities in children with autism spectrum disorder (ASD).Study design
This prospective, randomized, placebo-controlled, double-blind study included 180 children with ASD, aged 2-7 years, who received a single intravenous autologous (n = 56) or allogeneic (n = 63) CB infusion vs placebo (n = 61) and were evaluated at 6 months postinfusion.Results
CB infusion was safe and well tolerated. Analysis of the entire sample showed no evidence that CB was associated with improvements in the primary outcome, social communication (Vineland Adaptive Behavior Scales-3 [VABS-3] Socialization Domain), or the secondary outcomes, autism symptoms (Pervasive Developmental Disorder Behavior Inventory) and vocabulary (Expressive One-Word Picture Vocabulary Test). There was also no overall evidence of differential effects by type of CB infused. In a subanalysis of children without intellectual disability (ID), allogeneic, but not autologous, CB was associated with improvement in a larger percentage of children on the clinician-rated Clinical Global Impression-Improvement scale, but the OR for improvement was not significant. Children without ID treated with CB showed significant improvements in communication skills (VABS-3 Communication Domain), and exploratory measures including attention to toys and sustained attention (eye-tracking) and increased alpha and beta electroencephalographic power.Conclusions
Overall, a single infusion of CB was not associated with improved socialization skills or reduced autism symptoms. More research is warranted to determine whether CB infusion is an effective treatment for some children with ASD.Item Open Access A pilot study on mindfulness based stress reduction for smokers.(BMC complementary and alternative medicine, 2007-01-25) Davis, James M; Fleming, Michael F; Bonus, Katherine A; Baker, Timothy BBackground
Mindfulness means paying attention in the present moment, non-judgmentally, without commentary or decision-making. We report results of a pilot study designed to test the feasibility of using Mindfulness Based Stress Reduction (MBSR) (with minor modifications) as a smoking intervention.Methods
MBSR instructors provided instructions in mindfulness in eight weekly group sessions. Subjects attempted smoking cessation during week seven without pharmacotherapy. Smoking abstinence was tested six weeks after the smoking quit day with carbon monoxide breath test and 7-day smoking calendars. Questionnaires were administered to evaluate changes in stress and affective distress.Results
18 subjects enrolled in the intervention with an average smoking history of 19.9 cigarettes per day for 26.4 years. At the 6-week post-quit visit, 10 of 18 subjects (56%) achieved biologically confirmed 7-day point-prevalent smoking abstinence. Compliance with meditation was positively associated with smoking abstinence and decreases in stress and affective distress.Discussions and conclusion
The results of this study suggest that mindfulness training may show promise for smoking cessation and warrants additional study in a larger comparative trial.Item Open Access A Plasmonic Gold Nanostar Theranostic Probe for In Vivo Tumor Imaging and Photothermal Therapy.(Theranostics, 2015) Liu, Yang; Ashton, Jeffrey R; Moding, Everett J; Yuan, Hsiangkuo; Register, Janna K; Fales, Andrew M; Choi, Jaeyeon; Whitley, Melodi J; Zhao, Xiaoguang; Qi, Yi; Ma, Yan; Vaidyanathan, Ganesan; Zalutsky, Michael R; Kirsch, David G; Badea, Cristian T; Vo-Dinh, TuanNanomedicine has attracted increasing attention in recent years, because it offers great promise to provide personalized diagnostics and therapy with improved treatment efficacy and specificity. In this study, we developed a gold nanostar (GNS) probe for multi-modality theranostics including surface-enhanced Raman scattering (SERS) detection, x-ray computed tomography (CT), two-photon luminescence (TPL) imaging, and photothermal therapy (PTT). We performed radiolabeling, as well as CT and optical imaging, to investigate the GNS probe's biodistribution and intratumoral uptake at both macroscopic and microscopic scales. We also characterized the performance of the GNS nanoprobe for in vitro photothermal heating and in vivo photothermal ablation of primary sarcomas in mice. The results showed that 30-nm GNS have higher tumor uptake, as well as deeper penetration into tumor interstitial space compared to 60-nm GNS. In addition, we found that a higher injection dose of GNS can increase the percentage of tumor uptake. We also demonstrated the GNS probe's superior photothermal conversion efficiency with a highly concentrated heating effect due to a tip-enhanced plasmonic effect. In vivo photothermal therapy with a near-infrared (NIR) laser under the maximum permissible exposure (MPE) led to ablation of aggressive tumors containing GNS, but had no effect in the absence of GNS. This multifunctional GNS probe has the potential to be used for in vivo biosensing, preoperative CT imaging, intraoperative detection with optical methods (SERS and TPL), as well as image-guided photothermal therapy.Item Open Access A predictive model and nomogram for predicting return to work at 3 months after cervical spine surgery: an analysis from the Quality Outcomes Database.(Neurosurgical focus, 2018-11) Devin, Clinton J; Bydon, Mohamad; Alvi, Mohammed Ali; Kerezoudis, Panagiotis; Khan, Inamullah; Sivaganesan, Ahilan; McGirt, Matthew J; Archer, Kristin R; Foley, Kevin T; Mummaneni, Praveen V; Bisson, Erica F; Knightly, John J; Shaffrey, Christopher I; Asher, Anthony LOBJECTIVEBack pain and neck pain are two of the most common causes of work loss due to disability, which poses an economic burden on society. Due to recent changes in healthcare policies, patient-centered outcomes including return to work have been increasingly prioritized by physicians and hospitals to optimize healthcare delivery. In this study, the authors used a national spine registry to identify clinical factors associated with return to work at 3 months among patients undergoing a cervical spine surgery.METHODSThe authors queried the Quality Outcomes Database registry for information collected from April 2013 through March 2017 for preoperatively employed patients undergoing cervical spine surgery for degenerative spine disease. Covariates included demographic, clinical, and operative variables, and baseline patient-reported outcomes. Multiple imputations were used for missing values and multivariable logistic regression analysis was used to identify factors associated with higher odds of returning to work. Bootstrap resampling (200 iterations) was used to assess the validity of the model. A nomogram was constructed using the results of the multivariable model.RESULTSA total of 4689 patients were analyzed, of whom 82.2% (n = 3854) returned to work at 3 months postoperatively. Among previously employed and working patients, 89.3% (n = 3443) returned to work compared to 52.3% (n = 411) among those who were employed but not working (e.g., were on a leave) at the time of surgery (p < 0.001). On multivariable logistic regression the authors found that patients who were less likely to return to work were older (age > 56-65 years: OR 0.69, 95% CI 0.57-0.85, p < 0.001; age > 65 years: OR 0.65, 95% CI 0.43-0.97, p = 0.02); were employed but not working (OR 0.24, 95% CI 0.20-0.29, p < 0.001); were employed part time (OR 0.56, 95% CI 0.42-0.76, p < 0.001); had a heavy-intensity (OR 0.42, 95% CI 0.32-0.54, p < 0.001) or medium-intensity (OR 0.59, 95% CI 0.46-0.76, p < 0.001) occupation compared to a sedentary occupation type; had workers' compensation (OR 0.38, 95% CI 0.28-0.53, p < 0.001); had a higher Neck Disability Index score at baseline (OR 0.60, 95% CI 0.51-0.70, p = 0.017); were more likely to present with myelopathy (OR 0.52, 95% CI 0.42-0.63, p < 0.001); and had more levels fused (3-5 levels: OR 0.46, 95% CI 0.35-0.61, p < 0.001). Using the multivariable analysis, the authors then constructed a nomogram to predict return to work, which was found to have an area under the curve of 0.812 and good validity.CONCLUSIONSReturn to work is a crucial outcome that is being increasingly prioritized for employed patients undergoing spine surgery. The results from this study could help surgeons identify at-risk patients so that preoperative expectations could be discussed more comprehensively.Item Open Access A randomized controlled trial comparing two vaso-occlusive episode (VOE) protocols in sickle cell disease (SCD).(American journal of hematology, 2018-02) Tanabe, Paula; Silva, Susan; Bosworth, Hayden B; Crawford, Regina; Paice, Judith A; Richardson, Lynne D; Miller, Christopher N; Glassberg, JeffreyLimited evidence guides opioid dosing strategies for acute Sickle Cell (SCD) pain. We compared two National Heart, Lung and Blood (NHBLI) recommended opioid dosing strategies (weight-based vs. patient-specific) for ED treatment of acute vaso-occlusive episodes (VOE). A prospective randomized controlled trial (RCT) was conducted in two ED's. Adults ≥ 21 years of age with SCD disease were eligible. Among the 155 eligible patients, 106 consented and 52 had eligible visits. Patients were pre-enrolled in the outpatient setting and randomized to one of two opioid dosing strategies for a future ED visit. ED providers accessed protocols through the electronic medical record. Change in pain score (0-100 mm VAS) from arrival to ED disposition, as well as side effects were assessed. 52 patients (median age was 27 years, 42% were female, and 89% black) had one or more ED visits for a VOE (total of 126 ED study visits, up to 5 visits/patient were included). Participants randomized to the patient-specific protocol experienced a mean reduction in pain score that was 16.6 points greater than patients randomized to the weight-based group (mean difference 95% CI = 11.3 to 21.9, P = 0.03). Naloxone was not required for either protocol and nausea and/or vomiting was observed less often in the patient-specific protocol (25.8% vs 59.4%, P = 0.0001). The hospital admission rate for VOE was lower for patients in the patient-specific protocol (40.3% vs 57.8% P = 0.05). NHLBI guideline-based analgesia with patient-specific opioid dosing resulted in greater improvements in the pain experience compared to a weight-based strategy, without increased side effects.Item Open Access A randomized controlled trial of standard versus intensified tuberculosis diagnostics on treatment decisions by physicians in Northern Tanzania.(BMC Infect Dis, 2014-02-20) Reddy, Elizabeth A; Njau, Boniface N; Morpeth, Susan C; Lancaster, Kathryn E; Tribble, Alison C; Maro, Venance P; Msuya, Levina J; Morrissey, Anne B; Kibiki, Gibson S; Thielman, Nathan M; Cunningham, Coleen K; Schimana, Werner; Shao, John F; Chow, Shein-Chung; Stout, Jason E; Crump, John A; Bartlett, John A; Hamilton, Carol DBACKGROUND: Routine tuberculosis culture remains unavailable in many high-burden areas, including Tanzania. This study sought to determine the impact of providing mycobacterial culture results over standard of care [unconcentrated acid-fast (AFB) smears] on management of persons with suspected tuberculosis. METHODS: Adults and children with suspected tuberculosis were randomized to standard (direct AFB smear only) or intensified (concentrated AFB smear and tuberculosis culture) diagnostics and followed for 8 weeks. The primary endpoint was appropriate treatment (i.e. antituberculosis therapy for those with tuberculosis, no antituberculous therapy for those without tuberculosis). RESULTS: Seventy participants were randomized to standard (n = 37, 53%) or intensive (n = 33, 47%) diagnostics. At 8 weeks, 100% (n = 22) of participants in follow up randomized to intensive diagnostics were receiving appropriate care, vs. 22 (88%) of 25 participants randomized to standard diagnostics (p = 0.14). Overall, 18 (26%) participants died; antituberculosis therapy was associated with lower mortality (9% who received antiuberculosis treatment died vs. 26% who did not, p = 0.04). CONCLUSIONS: Under field conditions in a high burden setting, the impact of intensified diagnostics was blunted by high early mortality. Enhanced availability of rapid diagnostics must be linked to earlier access to care for outcomes to improve.Item Open Access A randomized Phase 2 trial of telavancin versus standard therapy in patients with uncomplicated Staphylococcus aureus bacteremia: the ASSURE study.(BMC Infect Dis, 2014-05-23) Stryjewski, Martin E; Lentnek, Arnold; O'Riordan, William; Pullman, John; Tambyah, Paul Anantharajah; Miró, Jose M; Fowler, Vance G; Barriere, Steven L; Kitt, Michael M; Corey, G RalphBACKGROUND: Staphylococcus aureus bacteremia is a common infection associated with significant morbidity and mortality. Telavancin is a bactericidal lipoglycopeptide active against Gram-positive pathogens, including methicillin-resistant S. aureus (MRSA). We conducted a randomized, double-blind, Phase 2 trial in patients with uncomplicated S. aureus bacteremia. METHODS: Patients were randomized to either telavancin or standard therapy (vancomycin or anti-staphylococcal penicillin) for 14 days. Continuation criteria were set to avoid complicated S. aureus bacteremia. The primary end point was clinical cure at 84 days. RESULTS: In total, 60 patients were randomized and 58 received ≥1 study medication dose (all-treated), 31 patients fulfilled inclusion/exclusion and continuation criteria (all-treated target [ATT]) (telavancin 15, standard therapy 16), and 17 patients were clinically evaluable (CE) (telavancin 8, standard therapy 9). Mean age (ATT) was 60 years. Intravenous catheters were the most common source of S. aureus bacteremia and ~50% of patients had MRSA. A similar proportion of CE patients were cured in the telavancin (88%) and standard therapy (89%) groups. All patients with MRSA bacteremia were cured and one patient with MSSA bacteremia failed study treatment in each group. Although adverse events (AEs) were more common in the telavancin ATT group (90% vs. 72%), AEs leading to drug discontinuation were similar (7%) in both treatment arms. Potentially clinically significant increases in serum creatinine (≥1.5 mg/dl and at least 50% greater than baseline) were more common in the telavancin group (20% vs. 7%). CONCLUSIONS: This study suggests that telavancin may have utility for treatment of uncomplicated S. aureus bacteremia; additional studies are warranted. (Telavancin for Treatment of Uncomplicated Staphylococcus Aureus Bacteremia (ASSURE); NCT00062647).