Plaster cast versus functional brace for non-surgical treatment of Achilles tendon rupture (UKSTAR): a multicentre randomised controlled trial and economic evaluation

This is the final version. Available from Elsevier via the DOI in this record. Background Patients with Achilles tendon rupture who have non-operative treatment have traditionally been treated with immobilisation of the tendon in plaster casts for several weeks. Functional bracing is an alternative non-operative treatment that allows earlier mobilisation, but evidence on its effectiveness and safety is scarce. The aim of the UKSTAR trial was to compare functional and quality-of-life outcomes and resource use in patients treated non-operatively with plaster cast versus functional brace. Methods UKSTAR was a pragmatic, superiority, multicentre, randomised controlled trial done at 39 hospitals in the UK. Patients (aged ≥16 years) who were being treated non-operatively for a primary Achilles tendon rupture at the participating centres were potentially eligible. The exclusion criteria were presenting more than 14 days after injury, previous rupture of the same Achilles tendon, or being unable to complete the questionnaires. Eligible participants were randomly assigned (1:1) to receive a plaster cast or functional brace using a centralised web-based system. Because the interventions were clearly visible, neither patients nor clinicians could be masked. Participants wore the intervention for 8 weeks. The primary outcome was patient-reported Achilles tendon rupture score (ATRS) at 9 months, analysed in the modified intention-to-treat population (all patients in the groups to which they were allocated, excluding participants who withdrew or died before providing any outcome data). The main safety outcome was the incidence of tendon re-rupture. Resource use was recorded from a health and personal social care perspective. The trial is registered with ISRCTN, ISRCTN62639639. Findings Between Aug 15, 2016, and May 31, 2018, 1451 patients were screened, of whom 540 participants (mean age 48·7 years, 79% male) were randomly allocated to receive plaster cast (n=266) or functional brace (n=274). 527 (98%) of 540 were included in the modified intention-to-treat population, and 13 (2%) were excluded because they withdrew or died before providing any outcome data. There was no difference in ATRS at 9 months post injury (cast group n=244, mean ATRS 74∙4 [SD 19∙8]; functional brace group n=259, ATRS 72∙8 [20∙4]; adjusted mean difference –1∙38 [95% CI –4∙9 to 2∙1], p=0·44). There was no difference in the rate of re-rupture of the tendon (17 [6%] of 266 in the plaster cast group vs 13 [5%] of 274 in the functional brace group, p=0·40). The mean total health and personal social care cost was £1181 for the plaster cast group and £1078 for the functional bract group (mean between-group difference –£103 [95% CI –289 to 84]). Interpretation Traditional plaster casting was not found to be superior to early weight-bearing in a functional brace, as measured by ATRS, in the management of patients treated non-surgically for Achilles tendon rupture. Clinicians may consider the use of early weight-bearing in a functional brace as a safe and cost-effective alternative to plaster casting.UK National Institute for Health Research Health Technology Assessment Programm

Stability-indicating methods for the determination of pipazethate HCl in the presence of its alkaline degradation product

Three different accurate, sensitive and reproducible stability-indicating methods for the determination of pipazethate HCl in the presence of its alkaline degradation product are presented. The first method is based on ratio-spectra 1st derivative (RSD1) spectrophotometry of the drug at 305 nm, over a concentration range of 10–70 μg mL−1 with mean percentage recovery of 99.69 ± 1.10. The second method utilises quantitative densitometric evaluation of thin-layer chromatography of pipazethate HCl in the presence of its alkaline degradation product, using methanol: ethyl acetate: ammonia (8:2:0.2, v/v/v) as a mobile phase. Chromatograms are scanned at 251 nm. This method analyses pipazethate HCl in a concentration range of 4–14 μg/spot with mean percentage recovery of 100.19 ± 0.77. The third method is an HPLC method for the simultaneous determination of pipazethate HCl in the presence of its alkaline degradation product. The mobile phase consists of methanol: ammonium sulphate (1%), pH = 5.7, (80:20, v/v). The standard curve of pipazethate HCl shows a good linearity over a concentration range of 5–200 μg mL−1 with mean percentage recovery of 100.67 ± 0.91. These methods were successfully applied to the determination of pipazethate HCl in bulk powder, laboratory-prepared mixtures containing different percentages of the degradation product and pharmaceutical dosage forms. The validity of results was assessed by applying standard addition technique. The results obtained were found to agree statistically with those obtained by a reported method, showing no significant difference with respect to accuracy and precision

ORIGINAL ARTICLES Effect of Heavy Metal (HgCl 2 ) on Accumulation and Production of Total Indole Alkaloids, Vinblastine And/or Vincristine from Egyptian Catharanthus Roseus

ABSTRACT Catharanthus roseus is still the only source for the powerful antitumor drugs vinblastine and vincristine. Effects of mercuric (HgCl 2 ) on enhancement the accumulation rate of total indole alkaloids; antineoplastic agents (vinblastine and/or vincristine) in calli cultures of Egyptian Catharanthus roseus (L.) G. (Don) were studied. Hgcl 2 was used at levels of 0.0, 0.2, 0.4 and 0.8 μm/l, added to modified alkaloid production medium (MAPM). The obtained results showed that: All tested concentrations of Hg significantly decreased the different measured growth parameters of shoot and root derived calli, however, the percentage of dry matter content significantly increased comparing the control treatment. Moreover, the percentage of total indole-alkaloids was significantly increased. The highest values of the accumulation rate of total indole-alkaloids, further, vinblastine and/or vincristine were recorded at the rate of 0.8 mM / Hg in shoot and root derived calli, respectively

Microcurrent skin patches for postoperative pain control in total knee arthroplasty: a pilot study: A pilot study

Pain control following painful orthopaedic procedures such as total knee arthroplasty (TKA) is an ongoing challenge, as current pain management techniques often result in under-medication and/or complications. In a study designed to test the effect of the micro-current skin patch (MCT) on pain relief in patients following TKA, we followed 24 patients, randomly divided into two groups, one group receiving MCT plus tramadol hydrochloride (tramadol) for pain relief and a control group receiving only tramadol, for 10 days postoperatively. Tramadol was given intramuscularly in increment doses of 100 mg, as needed, for the duration of the study period. Pain was assessed daily using a visual analogue score (VAS). Other parameters, including the effect of MCT on the dose of tramadol needed for pain relief, the degree of wound healing measured at the end of the follow-up period, category of the wound 10 days postoperatively (1, 2 or 3) and total drain fluid volume, were also assessed. During the 10-day postoperative period there was a progressive decrease in pain in patients of both groups, however the patients of the MCT group showed a consistently lower VAS throughout the observation period, most markedly on those follow-up days with the highest pain scores in patients of the control group. This effect was monitored on the basis of the average dose of tramadol administered per day: 200.0±7.0 mg/day in the control group and 63.3±15.8 mg/day in the MCT group. Wound healing was better with the application of the MCT patch: grade 1 wounds were observed in 50% of the patients of the MCT group as compared to 8.3% in control group. The total drain volume was lower in patients of the MCT group compared to the controls (1020.8±211.6 and 1170.8±243.5 ml, respectively). None of the patients indicated that they wished to discontinue MCT therapy. This pilot study shows that MCT therapy led to better pain control with a markedly lower need for tramadol as compared to the control group. This better pain control was accompanied by a better healing of the wound and a lower drain volume