8 ± 14 4 months) Among the rotavirus infected children, 58 5% we

8 ± 14.4 months). Among the rotavirus infected children, 58.5% were in the age group of 7–12 months, while 14.5% belonged to ≤6 months. Analysis of the clinical severity scores indicated very severe, severe,

moderate and mild disease in 2.8%, 56.5%, 38.7% and 2.3% of the patients suffering for rotavirus gastroenteritis. As against this, 5%, 47%, 38.3% and 7.7% of the patients tested negative for rotavirus experienced very severe, severe, moderate check details and mild disease, respectively. In general, children with rotavirus diarrhea had significantly less mild and more severe disease than those with rotavirus-negative diarrhea (P < 0.05). Rotavirus infected children had more episodes of vomiting than did uninfected children (P < 0.05). The multiplex PCR conducted for genotyping of rotavirus strains showed amplification of VP7 and VP4 genes in 197 (81.7%) and 190 (78.8%) strains respectively and identified genotypes of both genes in 178 (73.8%) strains (Table 2). 32 (13.2%) strains remained untypeable for both genes. We detected infections with mixed rotavirus strains in 18 (10.1%) of the 178 specimens. Among the strains typed for both VP7 and VP4 genes, G1P[8] strains attained the highest score (31.4%). This was followed by G2P[4] (20.2%); G9P[8] (11.8%); G9P[4]

(10.1%); G12P[6] (6.1%); G12P[8] (3.3%); G2P[8] (2.8%); G2P[6] (2.2%); G3P[8] (0.5%); G4P[4] (0.5%) and G1P[4] (0.5%) rotavirus strains. G1P[8] strains continued to remain prevalent in all the years of study except selleck the year 2009 in

which G9P[8] strains (15.2%) were predominant. G9P[8] strains remained second highest in the year 2010 and Histamine H2 receptor declined markedly in circulation in 2011–2012. We found higher circulation of G9P[4] strains, an unusual combination of G and P types in 2010–2012 as compared to 2009. Mixed infections were highest (27.1%) in the year 2009 and declined drastically in the following years (Table 3). Two rotavirus vaccines, Rotarix™ and RotaTeq® have been licensed in ∼90 to 100 countries to use against rotavirus diarrhea. Both vaccines are recommended by the World Health Organization (WHO) in childhood immunization programs conducted globally [9]. Studies report difference in the efficacies of these vaccines against severe rotavirus diarrhea in high and middle income (85–98%) and low income (39–72%) countries [10]. In countries like India, where the vaccine efficacy data is yet to be acquired, monitoring of rotavirus disease and strains is essential to assess the impact of rotavirus vaccines and circulating rotavirus strains on each other. The data obtained in this direction in the present study reaffirm earlier reports (2005–2009) of the characteristics of rotavirus infections, large rotavirus disease burden and strain diversity among children in Pune, western India [3] and [4]. Our data showed that rotavirus positivity continued to remain significant in each year of the study period (2009–2012) and concurred with recent study reports from India [11].

The statistical analyses were performed using STATISTICA 9 1 soft

The statistical analyses were performed using STATISTICA 9.1 software (Statsoft), using the normalized variables. The effect of each variable was estimated, as was standard error, and was assessed Capmatinib by the t-test, with all results giving p < 0.05 being considered statistically significant. Cell growth was measured by absorbance at 600 nm. This was converted to dry mass of cells using a standard calibration curve. Samples of cells from 1 mL culture were resuspended in a sample buffer (60 mM Tris–HCl, pH 6.8, 10% glycerol, 5% β-mercaptoethanol, 2% SDS, 0.5% Bromophenol Blue) to obtain the total protein extract, at a ratio of 25 μL buffer to each 0.1 Abs600 nm. These samples were added to

12.5% SDS-PAGE [17], stained with Coomassie Blue R-250. The same gel also had 2 μL low molecular weight marker (LMW, Amersham Bioscience) added, with 97 kDa, 66 kDa, 45 kDa, 30 kDa, 20.1 kDa and 14.4 kDa bands and 1340 ng, 1660 ng, 2940 ng, 1660 ng, 1600 ng and 2320 ng protein weight in each band, respectively, for the purpose of comparing with the bands corresponding to ClpP. The amount of protein expressed under each condition was analyzed

by densitometry using a Bio-Rad GS-800 calibrated densitometer and QuantityOne 4.4.1 software. The concentration of expressed protein was obtained using the ratio (mg/L) = (Abs600 nm × band in densitometry)/4, where 4 was the concentration factor used in the preparation selleck chemicals llc of the total protein extract samples. In order to analyze plasmid segregation, 100 μL samples were taken from each experiment at the end of the 4 h expression period, with analysis done on two aliquots from each experiment. Each aliquot was serially diluted in sterile PBS to 10−6 (Fig. 1). 10 μL samples of each dilution with at least three replications were added to LB Agar plates with kanamycin (50 μg/mL) and without it. Plasmid stability was measured as the fraction of plasmid-bearing cells (Φ) by

calculating the ratio between the number of colony forming units (CFU/mL) on the plate with the antibiotic and on the plate without the antibiotic. A statistical evaluation was made with the aim of checking the reproducibility and variability of the procedures not for assessing plasmid stability (serial dilution and colony count). Student’s t-test was used to find out whether the mean values from the colony count were equivalent, while the F-test (Fisher) was used to find out whether the errors made at each stage of the count were equivalent. These tests were done using the values obtained from CFU/mL in the experiments at the center point of the experimental design, comparing different aliquots diluted to the same degree from the same culture, and the same aliquots diluted to different degrees from the same culture, as shown in the diagram in Fig. 1. In order to do the F  -test, F   was calculated using Eq.

5 °C at 100 rpm At different time intervals, sample was withdraw

5 °C at 100 rpm. At different time intervals, sample was withdrawn, diluted and analyzed by UV-spectrophotometer at 335 nm and 210 nm for outer and core tablets respectively. After estimating different drugs contents and in-vitro study results, the optimized tab-in-tab formulation (T3) was retained for 3 months under accelerated stability conditions of temperature and relative humidity (40 ± 2 °C/75 ± 5% RH) in stability chamber (Thermolab, India). The samples were taken out at 30, 60 and 90 days and evaluated for appearance, weight, hardness, drugs content and dissolution study. Three male rabbits of weight 2–2.5 kg

were fasted overnight in each experiment, although free access to water was allowed. During the course of the experiment, water was not given until 2 h after administration of test preparation. The oral doses of the drugs were calculated on the basis of their CHIR-99021 cell line body weights and then accordingly formulated for animals. After oral administration of the test preparation, 3 ml blood samples were collected at predetermined time intervals. Plasma

was immediately separated by centrifugation of the blood samples at 10,000 rpm for 10 min. All plasma samples were immediately frozen at −20 °C until analysis. A sample was extracted with methylene chloride, NIF was separated on ODS column by isocratic elution with acetonitrile- 5 mmol/L ammonium acetate (52:48 v/v) at the flow rate of 1 ml/min, and detected by mass spectrometry Ku-0059436 supplier in the selected ion monitoring (SIM) mode.9 The solid-phase extraction technique was used for the extraction of RAM from the sample. Chromatography was performed on Aquasil column, with the simple reversed isocratic phase consisting of acetonitrile–water (65:35 ratio) and 1.0 ml/L ammonium trifluoroacetate solution (1.0 M) and followed by detection using mass spectrometry.10 Data was statistically evaluated using SPPS software. P value of <0.05 was considered to be significant. The SE micrograph of NIF-loaded gelatin microcapsule was spherical in shape

with smooth surface (Fig. 2). This might be due to proteinaceous nature too of gelatin and decrease surface indentation. The geometric mean diameter of microcapsules was 6.52 ± 0.26 μm. The % EE of NIF in the gelatin microcapsules was 98.01 ± 2.1. The gelatin microcapsules enhance its encapsulation due to increase solubility in ethanol. SLS was used to avoid attaching gelatin microcapsule to the inner wall of spray-drying chamber and to produce free-flowing powder.11 NIF solubility and the amount of encapsulated ethanol increased due to optimum amount of SLS. The amount of NIF dissolved from gelatin microcapsules for 30 min were much higher 85.31 ± 0.96% as shown in Fig. 3. This signifies its solubility increased in SGF. The bioavailability of poorly water-soluble NIF was improved in gelatin microcapsules due to amorphous form of drug and cosolvent effect of ethanol because the gelatin wall of microcapsule was very soluble.

Cost estimates were converted from Year 2005 international dollar

Cost estimates were converted from Year 2005 international dollars to 2010 US dollars using the Consumer Price Index [33] and official exchange rates [34]. Vaccination program costs include

those costs associated with storing, delivering and administering the vaccine once it arrives in the country. The vaccine program costs PS-341 chemical structure were estimated using the WHO Global Immunization Vision and Strategy (GIVS) costing tool [35]. A program cost per dose was estimated for each of the countries, and a regional, weighted average was calculated and used in the analysis. We used updated country estimates of childhood deaths due to diarrhea and rotavirus-specific illness, to revise the baseline disease burden figures for our analysis [1] and [36]. We estimated rotavirus-associated outpatient visits and hospitalizations by multiplying the total diarrhea-related outpatient visits and hospitalizations by the estimated proportion attributable to rotavirus [37]. Rotavirus medical visits and deaths were distributed into

the following age categories: 0–2 months, 3–5 months, 6–8 months, 9–11 months, 12–23 months, 24–35 months, 36–47 months, and 48–59 months [19]. Recent clinical trials of rotavirus vaccine in sub-Saharan Africa and Southeast Asia found lower levels of vaccine efficacy than observed in trials in Latin America that were used in the original model [21], [22] and [23]. As noted by the WHO Strategic Advisory Group of Experts (SAGE), this finding is not unexpected selleckchem [38] and is consistent with results from studies of other live, oral vaccines such as polio, typhoid and cholera that suggest lower efficacy or immunogenicity in developing country populations compared to industrialized countries [39], [40] and [41]. Efficacy estimates against severe rotavirus diarrhea, any rotavirus diarrhea,

and all-cause severe gastroenteritis for countries in the African and Asian regions were calculated and applied by child mortality strata (see Table 1). Pooled random effects mean estimates from the Adenylyl cyclase trials conducted in the high mortality countries of Ghana, Kenya, Bangladesh, South Africa, Malawi and Mali were applied to countries with under-5 mortality rates >30/1000. Estimates from the study in Vietnam were applied to countries with child mortality rates ≤30/1000. Previous estimates from trials in Latin America were still used for Latin American and Caribbean countries. Estimates of efficacy against severe rotavirus gastroenteritis are used as a proxy for efficacy against mortality and hospitalization, and efficacy against any rotavirus gastroenteritis corresponds to efficacy against outpatient visits. Atherly et al. [19] demonstrated that estimates of the impact and cost-effectiveness of vaccination over time depend heavily on assumptions about which countries introduce vaccine, the timing of their introduction and how price changes over time as a result of market factors such as increased demand and the entry of new manufacturers.

As an example,

we published a paper detailing a moderatel

As an example,

we published a paper detailing a moderately large randomised controlled trial (PEDro score 9/10) which tested the hypothesis that customised foot orthotics were no more effective than sham orthotics in people with painful pes cavus (Burns et al 2006). We found a positive effect in terms of pain reduction (the primary outcome) from the customised orthotics compared to the slightly smaller pain reduction found with the sham. We subsequently continued our analysis in an attempt to explain these findings and reported that, while the experimental group did demonstrate AUY 922 significantly greater pain relief, we could not attribute MEK inhibitor this to any change in the patterns or magnitudes of pressure distribution under the foot (Crosbie and Burns 2007). As the whole point of the orthotic was to redistribute pressure away from painful areas, this led us to conclude that the

findings of the original study were the result of something other than a mechanical change, possibly a simple placebo effect. Sadly, although our original paper has been cited 26 times, the important explanatory paper has attracted only four citations, two of which were by one of the original authors. Perhaps greater support for the proposal made by Herbert (2008) that researchers make their data more accessible for others to explore will help make explanatory analysis more widespread, but the evidence to date seems unconvincing. What message does a focus on randomised trials to the exclusion of other designs send to the next generation of physiotherapy researchers and those mentoring them? Research training, whether as part of a formal degree or an informal process, needs to offer as wide an experience

these as possible and to develop skills that are not confined to one specific research design. The Council of Australian Deans and Directors of Graduate Studies (2007) opined that ‘… a best practice doctoral program should include but not be limited by … development of new research methods and new data analysis …. and … research that makes a significant and original contribution to knowledge. It should therefore be necessary for original and significant research to be undertaken in order to earn a doctorate in an Australian university. The systematic review and randomised controlled trial have become, in effect, the sine qua non of many (but thankfully not all) contemporary physiotherapy PhD theses. One must question whether this is limiting the potential to produce original thinkers.


“Le cahier des charges des centres mémoire de ressources e


“Le cahier des charges des centres mémoire de ressources et de recherche (CMRR) leur demande d’assurer un rôle de recours pour les cas difficiles. L’activité de recours représentait 41,7 % de l’activité d’une consultation mémoire neurologique du CMRR de Lyon. “
“La soutenance d’une thèse d’exercice en médecine est nécessaire pour l’obtention du diplôme d’État de docteur en médecine. Le taux de publication indexée MEDLINE des 2150 thèses d’exercice en médecine (TEM) soutenues à la

faculté de médecine de Lille 2, entre 2001 et 2007 était de 11,3 %. “
“L’hyperparathyroïdie MG-132 primaire est associée à une diminution de la masse osseuse. La prévalence du déficit en vitamine D dans une cohorte française de patients avec hyperparathyroïdie primaire est élevée. “
“L’estimation

de la fonction rénale repose sur l’utilisation des modèles de Cockcroft-Gault Kinase Inhibitor Library chemical structure et MDRD. La sous évaluation de la fonction rénale au cours du séjour hospitalier. “
“Les recommandations diagnostiques et thérapeutiques pour l’angine aiguë sont variables selon les pays. Chez l’enfant comme chez l’adulte, l’utilisation du TDR était la stratégie la plus efficiente d’identification et de traitement des patients atteints d’angine à SGA. “
“La formation initiale de tout médecin en France est validée à l’issue d’un travail personnel important (thèse, mémoire de spécialité) dont la valorisation en termes de publication scientifique est mal connue au sein des facultés et des CHU. La production scientifique issue de la formation initiale à la faculté de médecine d’Angers est de qualité mais reste insuffisante quantitativement. “
“La prévalence des troubles psychiatriques sévères parmi les personnes sans abri est entre 30 et 50 %. L’EMPP décrite concentre son action vers une population cible : les personnes sans Oxymatrine chez soi chronique ayant des troubles psychiatriques graves et éloignées du système de soin. “
“Les problématiques addictives (tabac et alcool) sont fréquentes en population hospitalière. Évaluation des consommations d’alcool

et de tabac pour les patients d’un CHG de la région Centre. “
“Peu de lien entre niveau de douleur et niveau de la pression artérielle Il est possible de détecter aux urgences les patients à risque d’HTA secondaire “
“L’évolution de la pandémie grippale A(H1N1) 2009. L’observation de la pandémie de grippe A dans un milieu quasi clos. “
“La neurofibromatose de Recklinghausen a de multiples présentations cliniques : dermatologiques, oculaires, neurologiques et orthopédiques. Les manifestations orthopédiques de cette maladie sont fréquentes et intéressent aussi bien le squelette que les parties molles. “
“Everything you always wanted to know about sarcoidosis… but were afraid to ask D. Valeyre, Bobigny, France and M. Humbert, Kremlin-Bicêtre, France Pathogenesis of Sarcoidosis J. Müller-Quernheim et al. Freiburg, Germany Pulmonary Manifestations of Sarcoidosis R.P. Baughman et al.

Clinical studies were performed in different populations and IFN-

Clinical studies were performed in different populations and IFN-γ was measured using different laboratory assays so direct comparison of the immunogenicity of these vaccine candidates is not possible. Both Aeras 402 and MVA85A have been evaluated using a whole blood ICS assay and in BCG vaccinated adults the median total

VX 770 number of cytokine producing CD4 and CD8 cells in response to Ag85A/B following Aeras 402 was approximately 0.2% of CD4 and 0.3% of CD8 T cells and to the 1 × 108 dose of MVA85A was 0.6% of CD4 and 0.2% of CD8 T cells [14] and [18]. Using a PBMC ICS assay, both MVA85A and MTB72F induce approximately 800 CD3 + CD4 + CD40L + IFN-γ cells per 106 CD4+ T cells [15] and [18]. Using a short-term cultured IFN-γ ELISPOT assay which incorporates an overnight expansion of T cells, Van Dissel et al. reported a response of approximately 500 SFU Ibrutinib in vitro per million sustained to 32 weeks post immunisation [17]. In a direct comparison conducted by four different laboratories the short-term cultured IFN-γ ELISPOT was found to amplify the IFN-γ response 4–10 fold when compared with the 18 h IFN-γ ELISPOT [19]. The IFN-γ response induced by the 1 × 108 dose of MVA85A is therefore higher at weeks 1–4 and at least equivalent at weeks 24 and 52 to the week 32 responses reported for H1 [17] and [19]. The IFN-γ immune response induced by MVA85A is similar to or greater than that induced by

other candidate TB vaccines currently in clinical development, however, IFN-γ alone may not be a correlate of immune protection from disease. MVA85A has now been evaluated in several different populations including those in the UK, Gambia, South Africa and Senegal [4], [5], [7], [8], [9] and [10].

Our studies have shown that the AE profile for MVA85A is highly comparable across different populations tested regardless of dose, BCG immunisation status, MTB infection status, HIV status, age of participant or country of residence. The frequency of mild or moderate systemic AEs was higher in UK volunteers receiving the 1 × 108 PFU MVA85A dose when however compared to the lower doses. Although we have not tested doses higher than 1 × 108 PFU of MVA85A in clinical trials, others have reported an increase in the frequency of severe systemic AEs in adults receiving 5 × 108 PFU of a recombinant MVA construct [16]. An MVA expressing the influenza virus antigens NP and M1 evaluated in UK adults induced severe systemic AEs including nausea/vomiting, malaise or rigours in 5 of 8 volunteers tested [16]. In South African infants a dose finding study with MVA85A found no difference in the magnitude of T cell response induced by 2.5 × 107, 5 × 107 or 1 × 108 PFU of MVA85A up to 6 months following immunisation [4]. In contrast, in UK adults, in the data presented here, we observe a clear dose response relationship with the greatest difference in response observed at 12 months following immunisation.

Most studies evaluating the impact of PPS immunization in the abs

Most studies evaluating the impact of PPS immunization in the absence of additional PCV in infants or children have not shown any impact on pneumococcal disease or carriage [17], [46] and [47]. In contrast, a study in Papua New Guinea, where children aged six months to five years of age were given either the 14 or 23vPPS in one or two doses according to age, there was a (non-significant) 19% reduction in mortality from any cause, and a 50% reduction in pneumonia mortality (95%CI 1–75%) [48]. Natural exposure in a population with

a high incidence of pneumococcal infections, resulting in regular antigenic ABT-737 chemical structure stimulation may explain this finding [20]. However, a Finnish study of the 14-valent PPS in infants aged three months to six years showed significant efficacy against vaccine type recurrent otitis media was 52% for children less than two years of age if serogroup 6 was excluded [13]. A study documenting immunological memory five years after meningococcal A/C conjugate vaccination

in infancy showed that challenge with the meningococcal polysaccharide or conjugate at two years of age induced immunological memory [21]. FDA-approved Drug Library in vitro However, subsequent challenge with polysaccharide at five years of age failed to induce a similar memory response in the polysaccharide group. The authors concluded that the initial polysaccharide immunization at two years of age interfered with the immune response to subsequent polysaccharide vaccination, a finding similar to our current results with 23vPPS [21]. No adverse clinical effects have ever been documented from repeated exposure to the meningococcal polysaccharide vaccine and in this study we demonstrated no increase in clinical adverse effects to the 23vPPS, although the numbers were small and the study was not designed to study

this. There was no increase in nasopharyngeal carriage of non-PCV serotypes five months after receipt of the 12 month 23vPPS (FMR, Astemizole JRC, EKM). We intend to follow the children from this study to assess nasopharyngeal carriage as an increase in carriage of non-PCV types in the 12 month 23vPPS group would indicate that this immunological finding may have a biological effect. This would provide the first indication that these children may have increased susceptibility to pneumococcal disease. Further results documenting the avidity and opsonophagocytic activity post 23vPPS and mPPS, and the impact on nasopharyngeal carriage will follow. In addition, immunological assays to assess B cell subsets will enable a more comprehensive assessment of the impact of 23vPPS on immunological functioning. However, our findings suggest that additional immunization with the 23vPPS following a primary series of PCV does not provide added benefit for antibody production and instead results in impaired immune responses following a subsequent PPS antigen challenge. Whether this observation is associated with adverse clinical effects remains to be determined.

4% (95% confidence interval [CI]: 88 6–95 2) in the TVC-naïve and

4% (95% confidence interval [CI]: 88.6–95.2) in the TVC-naïve and 57.5 (95% CI: 51.7–62.8) in the TVC [23]. While efficacy and rate reduction in the CVT was similar across ages in the ATP cohort, they were age dependent in the ITT cohort, despite the relatively small age range in the trial (Table 6). Efficacy fell from 68.9% in 18–19 year-olds to 21.8% in 24–25 year-olds (p for trend = 0.005). Similarly, the rate reduction in persistent infections per 100 women years fell from 5.2 to 1.6. Similar declines in efficacy and rate reductions

were seen when the women were stratified according to time since first sexual intercourse. These decreases probably are due to a combination of higher prevalent HPV16/18 www.selleckchem.com/products/Imatinib-Mesylate.html infection and decreased acquisition rates (due to immunity and reduced exposure) in the older women. The results exemplify the effectiveness of the vaccine at preventing buy Abiraterone new infection, independent of age, but the decreased overall benefits of vaccination with age in a population of mostly sexually active young women. Protection from persistent infection increased dramatically with time since vaccination in the

ITT cohort in the CVT, where it increased from a non-significant 15.6% in the interval 10–22 months after vaccination to 94.3% after 46 months since vaccination (Table 6) [26]. This finding is likely the result of the resolution of most prevalent infections by 4 years coupled with the durability of protection from incident infection over this time period. Interestingly, there was also a trend for lower efficacy (and also rate reduction) early after vaccination in the ATP cohort, from 71.2% (95% CI: 25.6–90.5) during months 10–22 to 100% (95% CI: 78.6–100) starting 46 months post vaccination. The findings suggest that some prevalent infections were undetected at baseline and then emerged during the first two years of the trial. Undetected prevalent infections likely account for many of the “breakthrough” infections detected in other Cervarix® and Gardasil® trials. However, the

effect might be greater in the CVT because of the greater likelihood of HPV exposure at entry due to the higher minimum age and no limit to the number of lifetime sex partners for enrollees. Protection from cervical HPV infection by less than three doses of Cervarix® was also evaluated in the CVT [27]. Approximately 11% of vaccine and control recipients received found two doses and approximately 5% received only one dose. Perhaps surprisingly, protection in the ATP cohort from 12 month persistent HPV16/18 infection after 4 years of follow-up did not significantly differ depending on number of doses. Vaccine efficacy after three, two, or one dose was 80.9% (95% CI: 71.1–87.7), 84.1% (95% CI, 50.2–96.3) and 100% (95% CI: 66.5–100), p for trend = 0.21. These results must be interpreted with some caution because the number of women receiving less than three doses was limited and the study was not formally randomized by number of doses, nor been followed beyond four years.

Although there were no significant between-group differences rega

Although there were no significant between-group differences regarding shoulder pain, worrisome observations were that in the experimental group some participants reported that they considered the intervention to be very arduous, pain and spasticity medication were prescribed more frequently, and protocol compliance was lower. Combined with the finding that shoulder pain was more likely to occur in participants in the experimental group than in the control group (relative risk 1.44), these findings may indicate

that for some participants the experimental procedure was not well tolerated. During the eight weeks of intervention CP-868596 mw our participants showed increased Leeds Adult/Arm Spasticity Impact Scale sum scores and Fugl-Meyer Assessment arm motor scores – changes that were probably not clinically relevant and caused by a mix of spontaneous post-stroke recovery of function, learned capacity to use compensatory movement strategies

of the nonaffected arm and/or increased Sotrastaurin research buy involvement of the carer. Overall, the prevalence of elbow flexor hypertonia and spasticity jointly increased up to 55% at the end of the treatment period, roughly corresponding to three months post-stroke for our participants. These results are in concordance with previous work (de Jong et al 2011, van Kuijk et al 2007, Urban et al 2010). The unexpected high prevalence of hypertonia and spasticity (62%) and a decreasing prevalence of shoulder subluxation (31%) at follow-up in our sample may be explained by the fact that patients with relatively poor arm motor control have a higher risk of developing hypertonia (de Jong et al 2011). Although we performed an intention-to-treat analysis (ie, using any available data from all randomised subjects), we did not use forward imputation of missing data representing a clinical variable (eg, shoulder passive range of motion) that is worsening over time (de Jong et al 2007), as this might increase the chance of a Type I error. However, for completeness, this stricter intention-to-treat analysis using the data of all randomised subjects (n = 48) was performed. This analysis was similar in outcome

to the original analysis but revealed an additional time effect of wrist extension with flexed fingers. A per Chlormezanone protocol analysis would also have resulted in similar results because no patients crossed over to the other group. We also refrained from performing a sensitivity analysis based on compliance because meaningful conclusions could not be drawn from the resulting limited sample sizes. We furthermore acknowledge that the Leeds Adult/Arm Spasticity Impact Scale lacks psychometric evaluation and our method to standardise the Tardieu Scale’s stretch velocity (V3) using a metronome was not validated and tested for reliability. Therefore, our data regarding basic arm activities, hypertonia, and spasticity should be interpreted with caution.