bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of several von Willebrand factor (VWF) activity assays for monitoring patients undergoing treatment with VWF/FVIII concentrates: improved performance with a new modified automated method
Authors: Hillarp A. , Friedman K. D. , Adcock‐Funk D. , Tiefenbacher S. , Nichols W. L. , Chen D. , Stadler M. , Schwartz B. A. 
Published: July 2015

BackgroundThe ability of von Willebrand factor (VWF) to bind platelet GP Ib and promote platelet plug formation is measured in vitro using the ristocetin cofactor (VWF:RCo) assay. Automated assay systems make testing more accessible for diagnosis, but do not necessarily improve sensitivity and accuracy.ObjectiveWe assessed the performance of a modified automated VWF:RCo assay protocol for the Behring Coagulation System (BCS®) compared to other available assay methods.MethodsResults from different VWF:RCo assays in a number of specialized commercial and research testing laboratories were compared using plasma samples with varying VWF:RCo activities (0–1.2 IU mL−1). Samples were prepared by mixing VWF concentrate or plasma standard into VWF‐depleted plasma. Commercially available lyophilized standard human plasma was also studied. Emphasis was put on the low measuring range. VWF:RCo accuracy was calculated based on the expected values, whereas precision was obtained from repeated measurements.ResultsIn the physiological concentration range, most of the automated tests resulted in acceptable accuracy, with varying reproducibility dependent on the method. However, several assays were inaccurate in the low measuring range. Only the modified BCS protocol showed acceptable accuracy over the entire measuring range with improved reproducibility.ConclusionsA modified BCS® VWF:RCo method can improve sensitivity and thus enhances the measuring range. Furthermore, the modified BCS® assay displayed good precision. This study indicates that the specific modifications − namely the combination of increased ristocetin concentration, reduced platelet content, VWF‐depleted plasma as on‐board diluent and a two‐curve calculation mode − reduces the issues seen with current VWF:RCo activity assays.
Factor for felons: how can we provide haemophilia care to the incarcerated?
Authors: Lambing A. , Kachalsky E. , Mueller L. M. , Kuriakose P. 
Published: July 2015

ObjectivesIn 2011, 6.98‐million offenders were documented in the adult correctional system, with state operating costs designated 12% towards medical care ($11.97 day per inmate) for the general population. Common co‐existing health problems identified are: arthritis (13%), hypertension (11%), asthma (10%) and heart problems (6%). Less than 5% of inmates have health issues related to cancer, diabetes, liver or renal problems and communicable diseases. The leading cause of death is suicide (33.2%), followed by heart disease (26.1%). Despite these statistics quality is lacking. Given these statistics, one would expect that a small proportion of patients from Hemophilia Treatment Center (HTC) will spend some time within the justice system. Currently there are no data addressing haemophilia care needs while incarcerated.MethodsThis article will review the current health care issues in the adult correctional system. Additionally, six case reports of incarcerated haemophiliacs will be highlighted exploring the successes and challenges with maintaining haemophilia care addressing the priority of meeting the haemophilia care needs verses the penal system regulations.SummaryIt can be expected that at some point, the HTC will experience a patient incarcerated for some period of time. The HTC will continue to advocate for their patient within this system, despite the many challenges faced.ConclusionsDespite the challenges outlined, ongoing communication and education with the correctional system, education of the medical personnel and prison personnel remains the priority as we advocate for our patients. Continued strategies in these areas are paramount.
Five in one therapy for graded treatment of haemophilic arthritis
Authors: Liu S. X. , Li P. B. , Liu Y. G. , Wang P. H. 
Published: July 2015

IntroductionHaemophilic arthritis is the most universal clinical appearance of haemophilia. Treatment of this disease has become an important and difficult issue worldwide until recently.ObjectiveTo investigate the efficacy and safety of five in one therapy for graded treatment of haemophilic arthritis.MethodsHaemophilic arthritis was classified into grades I–IV according to severity and the standards of De Palma and Cotler. Under no application of FVIII/FIX replacement therapy state, the effect of five in one therapy (intra‐articular cavity drug injection, oral drug preparation, physiotherapy, and prevention of haemorrhage and infection evoked by puncture) was observed in 1527 affected joints of 750 cases of haemophilic arthritis.ResultsAfter 20 days treatment, all grade I and II, 94.98% of grade III and 56.16% of grade IV affected joints were completely relieved; 5.02% of grade III and 41.47% of grade IV affected joints were basically relieved; and 2.38% of grade IV were partially relieved. This resulted in short‐term complete and basic relief of 98.56% (1505/1527) of all affected joints. After follow‐up of 1–6 years, 86.97% of the affected joints were completely relieved, without any adverse reaction or complication.ConclusionThe results suggest that five in one therapy is safe and effective for treatment of haemophilic arthritis, and provides a convenient, cost‐effective way of preventing and treating deformity caused by haemophilic arthritis.
Generation and optimization of the self‐administered bleeding assessment tool and its validation as a screening test for von Willebrand disease
Authors: Deforest M. , Grabell J. , Albert S. , Young J. , Tuttle A. , Hopman W. M. , James P. D. 
Published: July 2015

Introduction/AimOur aim was to generate, optimize and validate a self‐administered bleeding assessment tool (self‐BAT) for von Willebrand disease (VWD).MethodsIn Phase 1, medical terminology in the expert‐administered International Society on Thrombosis and Haemostasis (ISTH)‐BAT was converted into a Grade 4 reading level to produce the first version of the Self‐BAT which was then optimized to ensure agreement with the ISTH‐BAT. In Phase 2, the normal range of bleeding scores (BSs) was determined and test–retest reliability analysed. In Phase 3, the optimized Self‐BAT was tested as a screening tool for first time referrals to the Haematology clinic.ResultsBleeding score from the final optimized version of the Self‐BAT showed an excellent intra‐class correlation coefficient (ICC) of 0.87 with ISTH‐BAT BS in Phase 1. In Phase 2, the normal range of BSs for the optimized Self‐BAT was determined to be 0 to +5 for females and 0 to +3 for males and excellent test–retest reliability was shown (ICC = 0.95). In Phase 3, we showed that a positive Self‐BAT BS (≥6 for females, ≥4 for males) has a sensitivity of 78%, specificity of 23%, positive predictive value (PPV) of 0.15 and negative predictive value (NPV) of 0.86 for VWD; these figures improved when just the females were analysed; sensitivity of 100%, specificity of 21%, PPV = 0.17 and NPV = 1.0.ConclusionWe show an optimized Self‐BAT can generate comparable BS to the expert‐administered ISTH‐BAT and is a reliable, effective screening tool to incorporate into the assessment of individuals, particularly women, referred for a possible bleeding disorder.
Reimbursement‐Based Economics – What Is It and How Can We Use It to Inform Drug Policy Reform?
Authors: Coyle Doug , Lee Karen M. , Mamdani Muhammad , Sabarre Kelley‐Anne , Tingley Kylie 
Published: July 2015

BackgroundIn Ontario, approximately $3.8 billion is spent annually on publicly funded drug programs. The annual growth in Ontario Public Drug Program (OPDP) expenditure has been limited to 1.2% over the course of 3 years. Concurrently, the Ontario Drug Policy Research Network (ODPRN) was appointed to conduct drug class review research relating to formulary modernization within the OPDP. Drug class reviews by ODPRN incorporate a novel methodological technique called reimbursement‐based economics, which focuses on reimbursement strategies and may be particularly relevant for policy‐makers.ObjectivesTo describe the reimbursement‐based economics approach.MethodsReimbursement‐based economics aims to identify the optimal reimbursement strategy for drug classes by incorporating a review of economic literature, comprehensive budget impact analyses, and consideration of cost‐effectiveness. This 3‐step approach is novel in its focus on the economic impact of alternate reimbursement strategies rather than individual therapies.ResultsThe methods involved within the reimbursement‐based approach are detailed. To facilitate the description, summary methods and findings from a recent application to formulary modernization with respect to the drug class tryptamine‐based selective serotonin receptor agonists (triptans) used to treat migraine headaches are presented.ConclusionsThe application of reimbursement‐based economics in drug policy reforms allows policy‐makers to consider the cost‐effectiveness and budget impact of different reimbursement strategies allowing consideration of the trade‐off between potential cost savings vs increased access to cost‐effective treatments.
BCAT1 overexpression is an indicator of poor prognosis in patients with urothelial carcinomas of the upper urinary tract and urinary bladder
Authors: Chang I‐Wei , Wu Wen‐Jen , Wang Yu‐Hui , Wu Ting‐Feng , Liang Peir‐In , He Hong‐Lin , Yeh Bi‐Wen , Li Chien‐Feng 
Published: July 2015

AimsAmino acid biosynthesis is one of the cardinal events of carcinogenesis that has not been investigated in urothelial carcinoma (UC). By data‐mining a published transcriptomic database of UCs of urinary bladder (UBUCs) (GSE31684), we identified branched‐chain amino acid transaminase 1 (BCAT1) as the most significantly stepwise up‐regulated gene during tumour progression among those associated with the amino acid biosynthetic process (GO:0008652). Accordingly, we analysed BCAT1 transcript and protein expression with their clinicopathological significance.Methods and resultsWe used real‐time reverse transcription–polymerase chain reaction (RT–PCR) to detect BCAT1 transcript levels in 20 UCs of upper tract (UTUCs) and 20 UBUCs, respectively. Immunohistochemical study was performed to determine BCAT1 protein expression in 340 UTUCs and 295 UBUCs. Higher BCAT1 transcript levels were associated with higher pT status in both groups (P < 0.05). BCAT1 protein overexpression was also associated significantly with adverse clinicopathological features, e.g. advanced pT stage, nodal metastasis, high pathological grade, etc. (P < 0.05). BCAT1 overexpression predicted worse disease‐specific survival and metastasis‐free survival in both univariate and multivariate analyses (P ≤ 0.001).ConclusionBCAT1 overexpression is associated with advanced tumour status, and implies adverse clinical outcomes of UCs, suggesting that its role in tumour progression could serve as a prognostic biomarker and a novel therapeutic target in UC.
Anaplastic lymphoma kinase (ALK) translocation in paediatric malignant peritoneal mesothelioma: a case report of novel ALK‐related tumour spectrum
Authors: Loharamtaweethong Kongsak , Puripat Napaporn , Aoonjai Nadda , Sutepvarnon Apisada , Bandidwattanawong Chanyoot 
Published: July 2015

AimsTo report a case of paediatric malignant peritoneal mesothelioma (MPM) with evidence of anaplastic lymphoma kinase (ALK) translocation.Methods and resultsWe describe a 10‐year‐old girl who presented with abdominal pain and progressive abdominal distension. She had no history of asbestos exposure. Histopathological, immunohistochemical and ultrastructural analyses were performed and showed a biphasic malignant mesothelioma. In addition, we also studied on a selected set of immunomarkers which may be the potential therapeutic molecular targets including ALK, c‐kit (CD117), epidermal growth factor receptor (EGFR) and human epidermal growth factor 2 (HER2)/neu, as well as corresponding molecular analysis. Consequently, we identified ALK expression by immunohistochemistry, together with evidence of ALK translocation by fluorescent in‐situ hybridization (FISH) analysis.ConclusionsPaediatric MPM is associated with ALK translocation in our case. The results may open up a new avenue for the study of molecular genesis of paediatric malignant mesothelioma in the future and help to determine whether patients MMs with ALK translocation would benefit from ALK inhibitor treatment.
The ASSURE study: HIV‐1 suppression is maintained with bone and renal biomarker improvement 48 weeks after ritonavir discontinuation and randomized switch to abacavir/lamivudine + atazanavir
Authors: Wohl DA , Bhatti L , Small CB , Edelstein H , Zhao HH , Margolis DA , DeJesus E , Weinberg WG , Ross LL , Shaefer MS 
Published: July 2015

ObjectivesHIV treatment guidelines endorse switching or simplification of antiretroviral therapy in therapy‐experienced patients with suppressed viraemia; ritonavir discontinuation may also enhance tolerability and reduce long‐term adverse events (AEs). This open‐label, multicentre, noninferiority study enrolled HIV‐1‐infected, treatment‐experienced adults with confirmed HIV‐1 RNA ≤ 75 HIV‐1 RNA copies/mL currently receiving tenofovir/emtricitabine + atazanavir/ritonavir (TDF/FTC + ATV/r) for ≥ 6 months with no reported history of virological failure.MethodsParticipants were randomized 1:2 to continue current treatment or switch to abacavir/lamivudine + atazanavir (ABC/3TC + ATV). Endpoints included the proportion of participants with HIV‐1 RNA < 50 copies/mL by time to loss of virological response (TLOVR), AEs, fasting lipids, and inflammatory, coagulation, bone and renal biomarkers.ResultsAfter 48 weeks, 76% (152 of 199) of ABC/3TC + ATV‐treated and 79% (77 of 97) of TDF/FTC + ATV/r‐treated participants had HIV‐1 RNA < 50 copies/mL (TLOVR; P = 0.564). Other efficacy analyses yielded similar results. Rates of new grade 2–4 AEs were 45% in both groups, but an excess of hyperbilirubinaemia made the rate of treatment‐emergent grade 3–4 laboratory abnormalities higher with TDF/FTC + ATV/r (36%) compared with ABC/3TC + ATV (19%). Most fasting lipid levels remained stable over time; high‐density lipoprotein (HDL) cholesterol increased modestly in ABC/3TC + ATV‐treated participants. Bone and renal biomarkers improved significantly between baseline and week 48 in participants taking ABC/3TC + ATV and were stable in participants taking TDF/FTC + ATV/r. No significant changes occurred in any inflammatory or coagulation biomarker within or between treatment groups.ConclusionsThe ABC/3TC + ATV treatment‐switch group had similar viral suppression rates up to 48 weeks to the TDF/FTC + ATV/r comparator group, with lower rates of moderate‐ to high‐grade hyperbilirubinaemia and improvements in bone and renal biomarkers.
Healthcare providers' knowledge of, attitudes to and practice of pre‐exposure prophylaxis for HIV infection
Authors: Desai M , Gafos M , Dolling D , McCormack S , Nardone A ,   PROUD study
Published: July 2015

ObjectivesPre‐exposure prophylaxis (PrEP) has proven biological efficacy in reducing the risk of sexual acquisition of HIV. Healthcare providers' (HCPs) knowledge of and attitudes to PrEP will be key to successful implementation. In England, PrEP is only available to men who have sex with men (MSM) through the open‐label randomized PROUD pilot study of immediate or deferred use.MethodsIn September 2013, a cross‐sectional survey of UK HCPs distributed through sexual health clinics (219) and professional societies' email lists (2599) and at a conference (80) asked about knowledge of, attitudes to and practice of PrEP.ResultsOverall, 328 of 2898 (11%) completed the survey, of whom 160 of 328 (49%) were doctors, 51 (16%) sexual health advisers (SHAs), 44 (14%) nurses and 73 (22%) unspecified. Over a quarter (83 of 311; 27%) were involved in PROUD. Most respondents (260 of 326; 80%) rated their knowledge of PrEP as medium or high. Over half of respondents (166 of 307; 54%) thought PrEP should be available outside of a clinical trial. The main barriers to supporting PrEP availability outside a clinical trial were concerns about current evidence (odds ratio [OR] 0.13), lack of UK‐specific guidance (OR 0.35), concerns about adherence (OR 0.38) and risk of sexual or physical coercion for patients to have condomless or higher risk sex (OR 0.42 in multivariate regression). Just over half (147 of 277; 53%) had been asked about PrEP by patients in the past year, including almost half of those working in a clinic not involved in the PROUD study (86 of 202; 43%).ConclusionsThere is support for PrEP availability outside a clinical trial, but HCPs have residual concerns about its effectiveness and negative consequences, and the absence of UK‐specific implementation guidance.
Predictors of interest in taking pre‐exposure prophylaxis among men who have sex with men who used a rapid HIV‐testing site in Montreal (Actuel sur Rue)
Authors: Lebouché B , Engler K , Machouf N , Lessard D , Thomas R 
Published: July 2015

ObjectivesThe effective use of pre‐exposure prophylaxis (PrEP) as an HIV prevention strategy depends on its uptake by individuals at high risk of infection. Few Canadian data are available on interest in PrEP among men who have sex with men (MSM). This study aimed to identify predictors of interest in PrEP among MSM clients of a rapid HIV‐testing site in Montreal's gay village (Actuel sur Rue).MethodsData were collected using a self‐administered and a community agent‐administered questionnaire. Among men reporting at least one male sexual partner and visiting the site between July 2012 and November 2013, we aimed to identify sociodemographic, sexual and temporal predictors of interest in taking effective PrEP with logistic regression analyses (univariate and multivariable).ResultsOver half (55%; n = 653) of the sample of 1179 MSM were interested in PrEP. Among the 14 variables considered in the univariate analyses, only (younger) age, (greater) number of sexual partners (in the past 3 months), being part of a serodiscordant couple (in the past 12 months), ever combining sex with drugs and temporal events were associated with interest in PrEP at P < 0.20 and were included in the multivariable analyses. In the multivariable model, only being part of a serodiscordant couple [adjusted odds ratio (aOR) 2.56; 95% confidence interval (CI) 1.44–4.58], having > 10 partners (aOR 1.73; 95% CI 1.17–2.55) and responding after the publication of Quebec's interim PrEP guidelines (aOR 1.82; 95% CI 1.22–2.71) proved significant.ConclusionsIn this assessment of predictors of PrEP interest among Canadian MSM, partnering issues and the arrival of PrEP guidelines in Quebec (10 July 2013) were most closely linked to PrEP interest.
Thirty‐day hospital readmissions for adults with and without HIV infection
Authors: Berry SA , Fleishman JA , Moore RD , Gebo KA 
Published: July 2015

ObjectivesRisk‐adjusted 30‐day hospital readmission rate is a commonly used benchmark for hospital quality of care and for Medicare reimbursement. Persons living with HIV (PLWH) may have high readmission rates. This study compared 30‐day readmission rates by HIV status in a multi‐state sample with planned subgroup comparisons by insurance and diagnostic categories.MethodsData for all acute care, nonmilitary hospitalizations in nine states in 2011 were obtained from the Healthcare Costs and Utilization Project. The primary outcome was readmission for any cause within 30 days of hospital discharge. Factors associated with readmission were evaluated using multivariate logistic regression.ResultsA total of 5 484 245 persons, including 33 556 (0.6%) PLWH, had a total of 6 441 695 index hospitalizations, including 45 382 (0.7%) among PLWH. Unadjusted readmission rates for hospitalizations of HIV‐uninfected persons and PLWH were 11.2% [95% confidence interval (CI) 11.2, 11.2%] and 19.7% (95% CI 19.3, 20.0%), respectively. After adjustment for age, gender, race, insurance, and diagnostic category, HIV infection was associated with 1.50 (95% CI 1.46, 1.54) times higher odds of readmission. Predicted, adjusted readmission rates were higher for PLWH within every insurance category, including Medicaid [12.9% (95% CI 12.8, 13.0%) and 19.1% (95% CI 18.4, 19.7%) for HIV‐uninfected persons and PLWH, respectively] and Medicare [13.2% (95% CI 13.1, 13.3%) and 18.0% (95% CI 17.4, 18.7%), respectively], and within every diagnostic category.ConclusionsHIV infection is associated with significantly increased readmission risk independent of demographics, insurance, and diagnostic category. The 19.7% 30‐day readmission rate may serve as a preliminary benchmark for assessing quality of care of PLWH. Policy‐makers may consider adjusting for HIV infection when calculating a hospital's expected readmission rate.
HIV encephalopathy: glial activation and hippocampal neuronal apoptosis, but limited neural repair
Authors: Tauber SC , Staszewski O , Prinz M , Weis J , Nolte K , Bunkowski S , Brück W , Nau R 
Published: July 2015

ObjectivesHIV infection affects the central nervous system (CNS), frequently causing cognitive impairment. Hippocampal injury impedes the ability to transfer information into memory. Therefore, we aimed to examine neuronal injury and repair in the hippocampal formation in HIV encephalopathy.MethodsWe compared neuropathological findings in 14 autopsy cases after death from systemic complications of HIV infection and in 15 age‐matched HIV‐negative control cases after sudden death from nonneurological causes using immunohistochemistry.ResultsThe density of apoptotic granule cells in the dentate gyrus was higher in HIV‐infected than in control cases (P = 0.048). Proliferation of neural progenitor cells in the dentate gyrus was increased in HIV infection (P = 0.028), whereas the density of recently generated TUC‐4 [TOAD (turned on after division)/Ulip/CRMP family 4]‐expressing neurons in this region was not significantly elevated in HIV‐infected cases (P = 0.13). HIV infection caused microglial activation and astrocytosis in the neocortex and hippocampal formation. Conversely, we were unable to detect more pronounced axonal injury in HIV‐infected than in control cases.ConclusionsAs in other infections involving the CNS, apoptosis of hippocampal neurons accompanied by microglial activation and astrocytosis is a prominent feature of HIV encephalopathy. The regenerative potential, assessed using the density of young neurons in the hippocampal dentate gyrus, in HIV infection appears to be lower than in acute bacterial meningitis and septic encephalitis.
A Social Capital Approach to Assisting Veterans Through Recovery and Desistance Transitions in Civilian Life
Authors: ALBERTSON KATHERINE , IRVING JAMIE , BEST DAVID 
Published: July 2015

AbstractWhile only a minority of veterans experience transitional difficulties after military service, there is increasing recognition of the unique challenges that some veterans face, including involvement with the criminal justice system, mental health problems and substance misuse. There is growing acknowledgment that both recovery from substance misuse and desistance from crime are lived transitional processes grounded in social relationships and community. This article reports on the potential of the comradeship and mutual resilience that underpin military life being redirected to support recovery and desistance journeys, through assertive linkage to peer support and community activities, describing a new initiative and an innovative evaluation model.