Factors influencing response to Botulinum toxin type A in patients with idiopathic cervical dystonia: results from an international observational study

Objectives Real-life data on response to Botulinum toxin A (BoNT-A) in cervical dystonia (CD) are sparse. An expert group of neurologists was convened with the overall aim of developing a definition of treatment response, which could be applied in a non-interventional study of BoNT-A-treated subjects with CD. Design International, multicentre, prospective, observational study of a single injection cycle of BoNT-A as part of normal clinical practice. Setting 38 centres across Australia, Belgium, Czech Republic, France, Germany, The Netherlands, Portugal, Russia and the UK. Participants 404 adult subjects with idiopathic CD. Most subjects were women, aged 41–60 years and had previously received BoNT-A. Outcome measures Patients were classified as responders if they met all the following four criteria: magnitude of effect (≥25% improvement Toronto Western Spasmodic Torticollis Rating Scale), duration of effect (≥12-week interval between the BoNT-A injection day and subject-reported waning of treatment effect), tolerability (absence of severe related adverse event) and subject's positive Clinical Global Improvement (CGI). Results High rates of response were observed for magnitude of effect (73.6%), tolerability (97.5%) and subject's clinical global improvement (69.8%). The subjective duration of effect criterion was achieved by 49.3% of subjects; 28.6% of subjects achieved the responder definition. Factors most strongly associated with response were age (<40 years; OR 3.9, p<0.05) and absence of baseline head tremor (OR 1.5; not significant). Conclusions Three of four criteria were met by most patients. The proposed multidimensional definition of response appears to be practical for routine practice. Unrealistically high patient expectation and subjectivity may influence the perception of a quick waning of effect, but highlights that this aspect may be a hurdle to response in some patients. Clinical registration number (NCT00833196; ClinicalTrials.gov)

Constraint Based Hybrid Approach to Parsing Indian Languages

PACLIC 23 / City University of Hong Kong / 3-5 December 200

Evaluation of susceptibility testing methods for polymyxin

SummaryBackgroundThe widespread resistance in Gram-negative bacteria has necessitated evaluation of the use of older antimicrobials such as polymyxins. In the present study we evaluated the different susceptibility testing methods for polymyxins B and E against Gram-negative bacteria using the new Clinical and Laboratory Standards Institute (CLSI) guidelines.MethodsThe susceptibility of 281 multidrug-resistant (MDR) Gram-negative bacteria (GNB) to polymyxin B was evaluated, comparing broth microdilution (BMD; reference method), agar dilution, E-test, and disk diffusion. Disk diffusion testing of polymyxin B was also performed against 723 MDR GNB.ResultsTwenty-four of 281 (8.5%) isolates were found to be resistant to polymyxin B by the reference BMD method. The rates of very major errors for agar dilution and E-test (for polymyxin B) were 0.7% and 1%, respectively, and those for disk diffusion (for polymyxin B and polymyxin E) were 1% and 0.7%, respectively. For the 257 isolates found sensitive by reference BMD, the rates of major errors by agar dilution and E-test (for polymyxin B) were 2.4% and 0%, respectively, and those for disk diffusion (polymyxin B and polymyxin E) were 0% and 0.7%, respectively. Twenty-six (3.6%) of the 723 Gram-negative isolates were resistant to polymyxin B by disk diffusion.ConclusionThe E-test and agar dilution methods showed good concordance with BMD. The disk diffusion method can be useful for initial screening in diagnostic laboratories

The safety of bivalirudin during elective percutaneous coronary interventions in heart transplant patients

Background: Bivalirudin has been shown to be safe and effective during percutaneous coronary interventions (PCI) of native coronary arteries in the REPLACE 2 trial. The safety of bivalirudin during PCIs in heart transplant patients is not known. Methods: Heart transplant patients who had undergone PCI of de novo lesions and received bivalirudin during the procedure were included in the study. Medical records were reviewed for the occurrence of death, myocardial infarction, target vessel revascularization or major bleeding up to 30 days after discharge. The results were compared with the REPLACE 2 trial and with a control group of heart transplant recipients who received heparin during their procedures. Results: There were 51 separate PCIs performed in 30 patients in the study group. The mean age was 56 &plusmn; 12 years and 6 (20%) were women. The control group consisted of 24 patients who had undergone 35 PCIs. There were no deaths, myocardial infarctions or target vessel revascularization during the follow-up period in the study group. The combined endpoint of death, myocardial infarctions, target vessel revascularization and major bleeding requiring two or more units of packed red blood cells occurred in 2 (3.9%) patients compared to 275 (9.2%) patients in the REPLACE 2 trial (p = 0.195) and 5 (14.3%) in the control group (p = 0.115). Conclusion: Bivalirudin is a safe antithrombotic medication to use during elective PCI in heart transplant patients with cardiac allograft vasculopathy. (Cardiol J 2007; 14: 458-462

Oral antiplatelet therapy in diabetes mellitus and the role of prasugrel: an overview

Diabetics have a prothrombotic state that includes increased platelet reactivity. This contributes to the less favorable clinical outcomes observed in diabetics experiencing acute coronary syndromes as well as stable coronary artery disease. Many diabetics are relatively resistant to or have insufficient response to several antithrombotic agents. In the setting of percutaneous coronary intervention, hyporesponsiveness to clopidogrel is particularly common among diabetics. Several strategies have been examined to further enhance the benefits of oral antiplatelet therapy in diabetics. These include increasing the dose of clopidogrel, triple antiplatelet therapy with cilostazol, and new agents such as prasugrel. The large TRITON TIMI 38 randomized trial compared clopidogrel to prasugrel in the setting of percutaneous coronary intervention for acute coronary syndromes. The diabetic subgroup (n = 3146) experienced considerable incremental benefit with a 4.8% reduction in cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke at 15-month follow-up with prasugrel treatment. Among diabetics on insulin this combined endpoint was reduced by 7.9% at 15 months. Major bleeding was not increased in the diabetic subgroup. This confirms the general hypothesis that more potent oral antiplatelet therapy can partially overcome the prothrombotic milieu and safely improve important clinical outcomes in diabetics

Influencing functional outcomes: a look at role performance and satisfaction with life following liver transplant

Abstract 572 The success of orthotopic liver transplantation (OLT), originally measured as survival, now extends to quality of the life saved. Return to work (RTW) is also a desired outcome. Our AIM was to explore the relationship between 5 pre-OLT factors & 5 post-OLT quality of life (QOL) domains with life satisfaction and primary productive role to better understand how to improve both. METHODS: Patients (pts)1-3 yrs post-OLT filled QOL form during follow-up clinic visits between 7/04 to 6/05. The Liver transplantation Database-Quality of life (LTD-QOL) form yielded data on 5 domains: measure of disease (MOD), psychological distress/well-being (PDW), personal function (PF), social/role function (SRF) & general health perception (GHP). Results: 229 pts were first categorized as satisfied overall with life (79%), or dissatisfied, and then assigned to groups based on primary productive role (51%), no primary productive role, or retired. Pre-OLT variables were age, gender, marital status, education, & etiology of liver disease; HCV (33%), alcohol liver disease (ALD)(11%), HCV+ALD (10%), & others (46%). Marital status & age were not significantly related to the outcome variables. Etiology of liver disease, education, and time since OLT and 5 post-OLT QOL domains were significantly associated with both outcome variables; satisfaction and primary productive role (p<.0001).To understand the differences, the 5 physical & men-tal QOL domains were regressed on primary productive role and satisfaction. Pts (mean age 54 yrs (19-74 yrs), males, 70%) fell into the category of primary productive role rates (51%). Pts transplanted for ALD were significantly (p<.05) more likely to be satisfied with life, whereas individuals with HCV±ALD, had lowest satisfaction and were most likely to be unable/uninterested in work. Stepwise logistical regression analysis of satisfaction demonstrated that GHP and SRF correlated most highly. Although satisfaction was significant in bivariate analysis, regression analysis of the influence of domains of QOL, as well as employment, demonstrated that SRF & GHP correlated most highly with life satisfaction. CONCLUSIONS: SRF and GHP correlate with good QOL post OLT. HCV patients have low levels of satisfaction whereas the highest level of satisfaction is in the ALD group. Further studies should address methods to improve satisfaction in those with HCV

Epidemiology and Clinicopathological Profile of Renal Cell Carcinoma: A Review from Tertiary Care Referral Centre

Renal cell carcinoma (RCC) accounts for 3% of all adult cancers and 85% of all kidney tumours. Incidence of RCC is lower in Asian region, particularly in India, probably due to lack of reporting. Most of the data about RCC are from Western countries; and data from India are scarce, especially regarding para-neoplastic syndromes. We sought to determine the epidemiology, clinicopathological profile and management of RCCin a tertiary care centre in Western India. This was a retrospective study that involved data analysis of records of RCC patients who presented to our institution from April 2016 to February 2020. Laboratory investigations, including tests for paraneoplastic syndrome (PNS), and relevant radiologic investigations were performed and treatment was offered according to the stage, patient factors and available modalities. A total 142 RCC patients were included in the study. The median age of presentation was 58 years. Most of the patients (67%) were symptomatic, and 33% of the patients were asymptomatic, and the RCC was diagnosed incidentally. A large number of patients (56.3%) had PNS. The most common histopathologic type of RCC was clear cell carcinoma (68.8%), followed by papillary (20%) and chromophobe (8%) carcinoma. 40% of carcinomas with sarcomatoid differentiation were seen in patients under 50 years of age. Two cases of multicystic RCC were both seen in patients less than 50 years of age. 65.5% of the patients presented at Stage 1 and 2. Most surgeries (71.2%) were done in a minimally invasive manner. A significant number of patients were asymptomatic, in which RCC was detected incidentally. The age of presentation was earlier, yet the patients had a higher tumour stage. More than half of the patients had PNSs. Despite growing trend towards Western data, the significantly higher number of patients with PNSs and early age of presentation suggest inherent differences in tumour biology, possibly related to differences in genetic and environmental factors

MOLECULAR DETECTION OF HUMAN RHINOVIRUS IN RESPIRATORY SAMPLES OF SWINE FLU NEGATIVE NORTH INDIAN CHILDREN WITH FLU-LIKE ILLNESS

Objectives: Flu-like illness may also be caused by different respiratory viruses other than influenza. Human rhinovirus (HRV) shows almost flu-likesymptoms. The purpose of this study is the molecular detection of HRV in throat swab of swine flu negative North Indian children during the years2012 and 2013. Reverse transcriptase (RT) - polymerase chain reaction (PCR) amplification of 5'non-coding region (NCR) was used for HRV detectionfollowed by cell culture isolation of HRV.Methods: PCR confirmed swine flu negative throat swab samples were collected from the Department of Microbiology, Sanjay Gandhi Post GraduateInstitute of Medical Sciences, Lucknow, Uttar Pradesh, India. The RNA isolation of samples was done using the QIAampViral RNA Mini Kit (Qiagen),followed by single step RT-PCR amplification (AgPath-ID, Life Technologies). All PCR positive HRV samples were cell cultured in HeLa and HEp-2 celllines for viral isolation.®Results: 135 swine flu negative throat swab samples were examined. Out of which 34 samples (25.2%) were found HRV positive by RT-PCR, while onlyfour samples (11.8%) were culture positive on HeLa cell line. Younger children (0-4 year) were found more susceptible to HRV infection. This studyindicated the highest prevalence of HRV (37.0%) during the months (September-October) of the Autumn season in 2012 and 57% in Winter-springseason (February-March) during 2013.Conclusion: HRV may be a cause of flu-like symptoms in swine flu suspected North Indian children with a higher rate during Autumn and Springseason. Molecular detection of HRV using RT-PCR is more sensitive than cell culture assay.Keywords: Human rhinovirus, Swine flu, Influenza-like illness, Lower respiratory tract infections