bluuebunny/crossref_metadata_2025_split huggingface dataset:
Longer term effectiveness of inpatient multidisciplinary rehabilitation on health-related quality of life in MS patients: a pragmatic randomized controlled trial – The Danish MS Hospitals Rehabilitation Study
Authors: Boesen Finn , Nørgaard Michael , Trénel Philipp , Rasmussen Peter Vestergaard , Petersen Thor , Løvendahl Brita , Sørensen Jan 
Published: October 2017

Background: There is insufficient evidence to support the effectiveness of multidisciplinary rehabilitation on the health-related quality of life (HRQoL) of MS patients. Objectives: To evaluate the longer term effectiveness of inpatient multidisciplinary rehabilitation on the HRQoL of MS patients. Methods: The study was a two-hospital, pragmatic, randomized controlled trial with a 6-month follow-up. Patients aged 18–65 years with MS and Expanded Disability Status Scale scores ≤7.5 were randomly assigned (1:1) to 4 weeks of inpatient multidisciplinary rehabilitation (20 days of scheduled rehabilitation) or 6 months on a wait list. The outcome measures were Functional Assessment in Multiple Sclerosis (FAMS), Multiple Sclerosis Impact Scale-29 (MSIS-29), EQ-5D-5L and 15D. Results: We randomized 213 patients to the wait-list control group and 214 patients to the treatment group. Trends in favour of the treatment group were observed across all measures. However, the difference was significant in only two of the six measures. The treatment effect was −2.7 (95% CI: −5.6 to (−0.1)), p = 0.046) for the MSIS-29 Psychological and 0.017 (95% CI: 0.005–0.030, p = 0.008) for the 15D. FAMS, which we used to calculate the sample size, was not significant. Conclusion: The results indicated that inpatient multidisciplinary rehabilitation is effective in improving the HRQoL of MS patients after 6 months.
Dual action by fumaric acid esters synergistically reduces adhesion to human endothelium
Authors: Breuer Johanna , Herich Sebastian , Schneider-Hohendorf Tilman , Chasan Achmet I , Wettschureck Nina , Gross Catharina C , Loser Karin , Zarbock Alexander , Roth Johannes , Klotz Luisa , Wiendl Heinz , Schwab Nicholas 
Published: October 2017

Objective: Dimethyl fumarate (DMF) is prescribed against relapsing-remitting multiple sclerosis (MS). Here, we investigated the effects of DMF and monomethyl fumarate (MMF), its metabolite in vivo, at the (inflamed) blood–brain barrier (BBB). Methods: Effects of fumaric acid esters were analyzed using primary human brain–derived microvascular endothelial cells (HBMECs) in combination with peripheral blood mononuclear cells (PBMCs) derived from DMF-treated MS patients. Results: MMF-binding to brain endothelium cells leads to activation of nuclear factor (erythroid-derived 2)–related factor 2 (Nrf2)–induced downregulation of vascular cell adhesion molecule 1 (VCAM-1). This might be mediated via the G-protein-coupled receptor (GPCR) hydroxycarboxylic acid receptor 2 (HCA2), a known molecular target of MMF, as we could demonstrate its expression and regulation on HBMECs. DMF treatment in vivo led to a strongly reduced expression of VCAM-1’s ligand very late antigen 4 (VLA-4) by selectively reducing integrin high-expressing memory T cells of MS patients, potentially due to inhibition of their maturation by reduced trans-localization of NFκB. Conclusion: DMF-mediated VCAM-1 downregulation on the endothelial side and reduction in T cells with a migratory phenotype on the lymphocyte side result in a synergistic reduction in T-cell adhesion to activated endothelium and, therefore, to reduced BBB transmigration in the setting of MS.
Efficacy of daclizumab beta versus intramuscular interferon beta-1a on disability progression across patient demographic and disease activity subgroups in DECIDE
Authors: Cohan Stanley , Kappos Ludwig , Giovannoni Gavin , Wiendl Heinz , Selmaj Krzysztof , Havrdová Eva Kubala , Rose John , Greenberg Steven , Phillips Glenn , Ma Wei , Wang Ping , Lima Gabriel , Sabatella Guido 
Published: October 2017

Background: Demonstration of clinical benefits on disability progression measures is an important attribute of effective multiple sclerosis (MS) treatments. Objective: Examine efficacy of daclizumab beta versus intramuscular (IM) interferon beta-1a on measures of disability progression in patient subgroups from DECIDE. Methods: Twenty-four-week confirmed disability progression (CDP), 24-week sustained worsening on a modified Multiple Sclerosis Functional Composite (MSFCS) where 3-Second Paced Auditory Serial Addition Test was replaced by Symbol Digit Modalities Test, and proportion of patients with clinically meaningful worsening in 29-Item Multiple Sclerosis Impact Scale physical impact subscale (MSIS-29 PHYS) score from baseline to week 96 were examined in the overall population and subgroups defined by baseline demographic/disease characteristics. Results: Daclizumab beta significantly reduced risk of 24-week CDP (hazard ratio (HR), 0.73; 95% confidence interval (95% CI), 0.55–0.98), risk of 24-week sustained MSFCS progression (HR, 0.80; 95% CI, 0.67–0.95), and odds of clinically meaningful worsening in MSIS-29 PHYS (odds ratio, 0.76; 95% CI, 0.60–0.95) versus IM interferon beta-1a. Point estimates showed trends favoring daclizumab beta over IM interferon beta-1a across several patient subgroups for all three outcome measures. Conclusion: Daclizumab beta showed consistent benefit versus IM interferon beta-1a across measures assessing patient disability/function and across a range of clinical baseline characteristics in patients with relapsing-remitting MS.
Epidemiology of NMOSD in Catalonia: Influence of the new 2015 criteria in incidence and prevalence estimates
Authors: Sepúlveda Maria , Aldea Marta , Escudero Domingo , Llufriu Sara , Arrambide Georgina , Otero-Romero Susana , Sastre-Garriga J , Romero-Pinel Lucía , Martínez-Yélamos Sergio , Sola-Valls N , Armangué Thais , Sotoca Javier , Escartín Antonio , Robles-Cedeño René , Ramió-Torrentà Lluís , Presas-Rodríguez Silvia , Ramo-Tello Cristina , Munteis Elvira , Pelayo Raúl , Gubieras Laura , Brieva Luis , Ortiz Nicolau , Hervás Mariona , Mañé-Martínez Maria Alba , Cano Antonio , Vela Emili , Tintoré Mar , Blanco Yolanda , Montalban Xavier , Graus Francesc , Saiz Albert 
Published: October 2017

Background: Population-based studies on neuromyelitis optica spectrum disorders (NMOSD) are limited, and it is unclear whether the rates have changed with the implementation of the new 2015 criteria. Objectives: To estimate the incidence and prevalence of NMOSD in Catalonia (Spain), using both the 2006 and the 2015 criteria. Methods: In this clinic-based retrospective study, patients diagnosed with NMOSD between 2006 and 2015 were identified using multiple sources, including direct contact to all Catalan hospitals, identification of cases through the Catalan Health Surveillance System, and registry of antibodies to aquaporin-4 (AQP4-IgG) and myelin oligodendrocyte glycoprotein (MOG-IgG) in a reference laboratory. The incidence rate was calculated for the period 1 January 2006–1 January 2016 and prevalence for the date 1 January 2016. Results: We identified 74 patients (by the 2015 criteria). Most patients were Caucasian (81%), and female (76%) with a median age at disease onset of 42 years (range, 10–76 years). In total, 54 (73%) patients were positive for AQP4-IgG, 11 (15%) double-seronegative, and 9 (12%) MOG-IgG-positive. Rates of incidence and prevalence (0.63/1,000,000 person-years and 0.89/100,000, respectively) were 1.5-fold higher than those reported by the 2006 criteria. Lowest rates were seen in children and elder people and highest in women and middle-aged people (40–59 years). The female predominance was lost in incident AQP4-IgG-seronegative children and AQP4-IgG-positive elder people. MOG-IgG and double-seronegativity contributed similarly but did not influence the long-term outcome. Conclusion: The new criteria increase the estimates, but NMOSD remains as a rare disease. The differences in age- and sex-specific estimates highlight the importance of the serologic classification.
Patient satisfaction with chronic HIV care provided through an innovative pharmacist/nurse-managed clinic and a multidisciplinary clinic
Authors: Kielly Jason , Kelly Deborah V. , Asghari Shabnam , Burt Kim , Biggin Jessica 
Published: October 2017

Background: Pharmacist/nurse-led clinics are an established model for many chronic diseases but not yet for HIV. At our centre, patients with HIV are seen by a multidisciplinary team (physician, nurse, pharmacist, social worker) at least yearly. Some attend an HIV-specialist pharmacist/nurse clinic (or “nonphysician clinic,” NPC) for alternate biannual visits. Our objective was to assess patient satisfaction with care received through both clinics. Methods: The Patient Satisfaction Survey for HIV Ambulatory Care (assesses satisfaction with access to care, clinic visits and quality of care) was administered by telephone to adults who attended either clinic between January and July 2014. Descriptive statistics described patient characteristics and satisfaction scores. Fisher’s exact test compared satisfaction scores between the NPC and multidisciplinary clinic (MDC). Multivariate logistic regression examined associations between overall satisfaction with care and clinic type and patient characteristics (e.g., age, disease duration). Results: Respondents were very satisfied with the overall quality of HIV care in both the NPC and MDC (89% vs 93%, respectively, p = 0.6). Patients from both clinics expressed satisfaction with access to care, treatment plan input, their provider’s knowledge of the newest developments in HIV care and explanation of medication side effects, with no significant differences noted. Significantly more MDC patients reported being asked about housing/finances, alcohol/drug use and whether they needed help disclosing their status. Patient characteristics were not significantly associated with satisfaction with overall quality of care. Conclusion: Patients are satisfied with both clinics, supporting NPC as an innovative model for chronic HIV care. Comparison of outcomes between clinics is needed to ensure high-quality care.
Primary care physicians’ attitudes and beliefs about cancer clinical trials
Authors: Bylund Carma L , Weiss Elisa S , Michaels Margo , Patel Shilpa , D’Agostino Thomas A , Peterson Emily B , Binz-Scharf Maria Christina , Blakeney Natasha , McKee M Diane 
Published: October 2017

Background/Aims: Cancer clinical trials give patients access to state-of-the-art treatments and facilitate the translation of findings into mainstream clinical care. However, patients from racial and ethnic minority groups remain underrepresented in clinical trials. Primary care physicians are a trusted source of information for patients, yet their role in decision-making about cancer treatment and referrals to trial participation has received little attention. The aim of this study was to determine physicians’ knowledge, attitudes, and beliefs about cancer clinical trials, their experience with trials, and their interest in appropriate training about trials. Methods: A total of 613 physicians in the New York City area primarily serving patients from ethnic and racial minority groups were invited via email to participate in a 20-min online survey. Physicians were asked about their patient population, trial knowledge and attitudes, interest in training, and personal demographics. Using calculated scale variables, we used descriptive statistical analyses to better understand physicians’ knowledge, attitudes, and beliefs about trials. Results: A total of 127 physicians completed the survey. Overall, they had low knowledge about and little experience with trials. However, they generally had positive attitudes toward trials, with 41.4% indicating a strong interest in learning more about their role in trials, and 35.7% indicating that they might be interested. Results suggest that Black and Latino physicians and those with more positive attitudes and beliefs were more likely to be interested in future training opportunities. Conclusion: Primary care physicians may be an important group to target in trying to improve cancer clinical trial participation among minority patients. Future work should explore methods of educational intervention for such interested providers.
Phase 1 healthy volunteer willingness to participate and enrollment preferences
Authors: Chen Stephanie C , Sinaii Ninet , Bedarida Gabriella , Gregorio Mark A , Emanuel Ezekiel , Grady Christine 
Published: October 2017

Background/aims: Healthy volunteers in phase 1 clinical trials contribute to the development of safe drugs and other biologics and accept risks and burdens without anticipated health benefits from participation. Although emerging data have shown that healthy volunteers are influenced by risk, some still worry that financial incentives lead them to take on unreasonable risk. Yet little is known about healthy volunteers’ preferences and how they make choices about enrolling in research studies. Methods: We surveyed 654 healthy volunteers at the end of their participation in a phase 1 Pfizer trial in the United States, Belgium, and Singapore to examine their reported willingness to enroll in studies of different types, with various procedures, and with possible side-effects. Results: The majority of respondents were willing to join many kinds of studies, but fewer were willing to participate in first-in-human vaccine studies or studies of psychiatric drugs than in other study types. With regard to procedures, a substantial proportion were unwilling to participate in studies that involved invasive procedures, such as a lumbar puncture (45.4%) and bone marrow biopsy (42.3%), but willing to participate in studies with less invasive procedures such as a computed tomography scan of the heart (86.8%), magnetic resonance imaging (87.4%), and skin allergy testing (86.8%). Although there was some variation by gender and region, the majority were willing to participate in studies with side-effects like pain (80%) or nausea and vomiting (64%), but only a minority were willing to join if the research drug would result in their having a one in a million chance of death (34.4%), a small chance of kidney damage (16.7%), or influence how their mind works (23.2%; Figure 4). Conclusion: Our results suggest that healthy volunteers are willing to participate in a wide range of types of phase 1 clinical trials, and express preferences for low risk and familiar studies and study procedures, preferences which are partially affected by offers of payment.
Isotonic designs for phase I trials in partially ordered groups
Authors: Conaway Mark 
Published: October 2017

Background/aims: Dose-finding trials can be conducted such that patients are first stratified into multiple risk groups before doses are allocated. The risk groups are often completely ordered in that, for a fixed dose, the probability of toxicity is monotonically increasing across groups. In some trials, the groups are only partially ordered. For example, one of several groups in a trial may be known to have the least risk of toxicity for a given dose, but the ordering of the risk among the remaining groups may not be known. The aim of the article is to introduce a method for designing dose-finding trials of cytotoxic agents in completely or partially ordered groups of patients. Methods: This article presents a method for dose-finding that combines previously proposed mathematical models, augmented with results using order restricted inference. The resulting method is computationally convenient and allows for dose-finding in trials with completely or partially ordered groups. Extensive simulations are done to evaluate the performance of the method, using randomly generated dose–toxicity curves where, within each group, the risk of toxicity is an increasing function of dose. Results: Our simulations show that the hybrid method, in which order-restricted estimation is applied to parameters of a parsimonious mathematical model, gives results that are similar to previously proposed methods for completely ordered groups. Our method generalizes to a wide range of partial orders among the groups. Conclusion: The problem of dose-finding in partially ordered groups has not been extensively studied in the statistical literature. The proposed method is computationally feasible, and provides a potential solution to the design of dose-finding studies in completely or partially ordered groups.
Time to institutional review board approval with local versus central review in a multicenter pragmatic trial
Authors: Neuman Mark D , Gaskins Lakisha J , Ziolek Tracy ,   the REGAIN Investigators
Published: October 2017

Background/aims: Central institutional review board (IRB) review will be required for National Institutes of Health–funded multisite human subjects research as of January 2018, with similar requirements extending to most US multisite human research in 2020. Nonetheless, little is known regarding the relative efficiency of central versus local IRB review for multicenter studies. We compared the amount of time required for central versus local IRB review and approval for sites in one ongoing multicenter randomized trial. Methods: The REGAIN Trial (Regional versus General Anesthesia for Promoting Independence after Hip Fracture; clinicaltrials.gov number: NCT02507505) is an ongoing randomized trial comparing standard-care spinal anesthesia to standard-care general anesthesia for patients undergoing hip fracture surgery. After approval of the protocol by the sponsor IRB, each participating US site opted either to submit the protocol for local IRB review or to designate the sponsor IRB as the IRB of record (i.e. central IRB) via an authorization agreement after a limited local review. For each US REGAIN site approved through 18 April 2017, we assessed (1) the time in calendar days from protocol receipt to IRB submission, (2) the time in calendar days from IRB submission to IRB approval, and (3) the total time in calendar days from protocol receipt to IRB approval (i.e. time from protocol receipt to IRB submission plus time from IRB submission to IRB approval). Results: The main study protocol was submitted to the sponsor IRB on 25 May 2015 and approved on 8 July 2015 (44 days). Out of 34 sites, 9 received initial approval from the central (sponsor) IRB; 25 sought initial approval via local review. The median time from protocol receipt to IRB submission was 39 days for sites approved by the central IRB (interquartile range: 35–134) versus 58 days for sites approved via local review (interquartile range: 41–105; p = 0.711). The median time from IRB submission to IRB approval for sites approved by the central IRB was 27 days (interquartile range: 14–32) versus 66 days (interquartile range: 29–138) for sites approved via local review (p = 0.026). The median total time from protocol receipt to IRB approval was 100 days (interquartile range: 71–148) for centrally approved sites versus 132 days (interquartile range: 87–209) for locally approved sites (p = 0.191). Conclusion: While central IRB review was associated with a shorter time from IRB submission to IRB approval compared to local IRB review, the total time from protocol receipt to IRB approval varied markedly across sites.
Membrane-like structure in the urinary bladder neck of a young cat: diagnosis and treatment using balloon dilatation and a balloon-expandable metallic stent
Authors: Ruiz-Drebing Matias , Yap Fui , Seth Mayank , Dennis Ruth , Dominguez Elisabet 
Published: October 2017

Case summary A 33-month-old, spayed female domestic shorthair cat was referred to the Animal Health Trust for the investigation of urinary incontinence and straining to urinate. A membrane-like structure was detected in the bladder neck, which caused partial obstruction of the urinary bladder. A combination of different imaging techniques, including ultrasonography, radiography, CT and fluoroscopy, was essential in the diagnosis, surgical planning and treatment of this intravesicular stricture. During retrograde vaginourethrocystogram, unexpected subcapsular accumulation of contrast medium was seen around both kidneys on radiographs and confirmed with CT. Three different treatments were performed, including surgical debridement, balloon dilatation and placement of a self-expanding metallic stent across the stricture. Histopathology of the membrane was unable to differentiate whether the lesion was congenital or acquired. No urinary incontinence was observed 5 months after placement of the metallic stent. Relevance and novel information This is the first reported case using fluoroscopic-guided balloon dilatation of the bladder neck for the treatment of a bladder neck stricture. Presence of renal subcapsular contrast medium secondary to a retrograde vaginourethrocystogram due to partial obstruction at the bladder neck in a cat has not been previously described.
Intubation following high-dose rocuronium in a cat with protracted laryngospasm
Authors: Doodnaught Graeme M , Pang Daniel SJ 
Published: October 2017

Case summary An 11-year-old spayed female domestic shorthair cat with a history of laryngospasm at induction of general anesthesia presented for dental evaluation and treatment. The cat was premedicated with hydromorphone (0.05 mg/kg) and alfaxalone (0.5 mg/kg) intravenously, pre-oxygenated for 5 mins (3 l/min, face mask) and anesthesia was induced with alfaxalone (to effect) intravenously. Lidocaine (0.1 ml, 2%) was applied topically to the arytenoid cartilages following loss of jaw tone. Laryngospasm was not noted during or immediately following lidocaine application. However, after waiting 60 s for the onset of effect of the topical lidocaine, laryngospasm was apparent. Orotracheal intubation by direct visualization was unsuccessful after four attempts by three anesthetists (with increasing levels of experience). At this point, a failed intubation was declared and the non-depolarising neuromuscular blocking agent rocuronium (1 mg/kg IV) given, resulting in arytenoid abduction and appropriate conditions for intubation. Successful intubation occurred 9 mins after induction of anesthesia. Oxygen was continuously supplemented throughout and arterial hemoglobin saturation with oxygen was never <94%. Relevance and novel information To the authors’ knowledge, this is the first report of the use of high-dose rocuronium to successfully resolve prolonged laryngospasm at induction of general anesthesia in a cat. Despite laryngospasm and a delay in achieving orotracheal intubation, low values for arterial hemoglobin saturation with oxygen (indicative of hypoxemia) were not observed, highlighting the benefits of pre-oxygenation and apneic oxygenation. The principles of the Difficult Airway Society 2015 guidelines were followed in managing this difficult intubation.