Catheter-directed thrombolysis for acute limb ischaemia: An audit

Background Acute limb ischaemia (ALI) is commonly managed with surgical intervention but catheter-directed thrombolysis (CDT) is a proven treatment alternative. CDT as a treatment for ALI is not common and is dependent on local practice. All patients receiving urokinase infusions at our institution currently require a bed in the high-dependency unit (HDU). Administering the infusion requires significant nursing time and this can be accommodated in HDU where the nurse-to-patient ratio is higher than it is on general wards. Aims To report the outcomes of the initial admission of patients who received CDT to manage ALI, and to give a cost estimate of their care. Method A retrospective audit was undertaken of all patients who received CDT with urokinase for the management of ALI over a four-year period. Success of thrombolysis was defined as a patient’s survival with no need for any surgical intervention prior to discharge. Outcome measures included the requirement for further vascular procedures in the same admission, the complication rate, and the median urokinase dose and duration. Cost estimates were based on hospital pharmacy and administration data. Results Seventy-three patients (median age 66 years, range 27–93 years) were included in the audit. The median urokinase dose was 2.3 million units (range 0.9–5.0 million units) with a median duration of treatment of 26 hours (range 3–96 hours). Fifty-seven patients did not require any further intervention prior to discharge, 14 had further intervention, and two died (one from a brainstem haemorrhage and one who deteriorated despite thrombolysis). The total cost per CDT case at our institution is currently approximately AUD $4,500 and AUD$6,700 for a patient being treated in HDU for one and two days, respectively. If patients were treated on a general ward, the cost would be approximately AUD $2,600 and AUD$3,000, respectively. Conclusion Rates of clinically acceptable clot lysis were high for patients treated with urokinase for ALI. Complication rates were comparable with published studies. Infusions can be required for prolonged periods of time and given the low complication rate, managing patients on a general ward rather than in the HDU is a feasible alternative and would reduce costs substantially

Clinical handover: An audit from Australia

BackgroundThe Australian National Safety and Quality Health Service (NHQHS) Standards (the “Standards”) provide external criteria for hospitals to assess their practices. Since the introduction of the Standards, no Australian hospital has published a report on how its handover practices compare to these Standards.AimsTo evaluate house medical officer (HMO) shift-to-shift handover practices against the Standards at a large regional hospital.MethodAll HMOs employed by Barwon Health were invited to participate in our qualitative and quantitative study by completing an online questionnaire and taking part in a focus group.ResultsOf the 100 HMOs, 61 completed the questionnaire and 11 HMOs participated in focus groups. Questionnaire results revealed that HMOs were concerned about the quality of shift-to-shift handovers. Fifty-three per cent reported that current shift-to-shift handover practices could be putting patients at risk of adverse events. Ninety-eight per cent indicated that the handover processes could be improved. One hundred per cent of the HMOs stated that the quality of handover varies according to the doctors involved. In the focus groups, issues were raised about current handover structure, documentation, attendance, content, and training.ConclusionHMOs in the current study identified multiple deficiencies in handover practice with regard to structure, documentation, attendance, content, and training. The primary methods to improve handover include making it more structured and standardised, and to provide HMOs with handover training

Multilingual construction of Communicative Development Inventories in Southern Africa

The Communicative Development Inventories (CDIs) are a set of validated, parent-completed questionnaires assessing children's vocabulary, gesture, and grammatical development. They have many benefits but in particular administration does not require a qualified psychologist or speech-language therapist, making them ideal for settings with poor access to professionals. In addition they are cheap to administer at scale, again benefitting low resource settings. Further, they are relatively easy to develop for languages that are not well described in terms of development, meaning they can be adapted easily to under-studied languages. The CDIs have previously been adapted for Asian (1), Indo-European (2), other European (3), Pacific Island (4) and some African languages (5,6). They have been used successfully in studies of health risks (nutrition, infection) in sub-Saharan Africa (7), again meaning they are useful for impoverished settings and child development issues prevalent in such settings. We are in process of developing CDIs for six languages spoken in Southern Africa (IsiXhosa, Setswana, Sesotho, Xitsonga, Afrikaans and South African English). We have developed a common method for each language starting with a long list of words taken from other CDIs, following on to parent/practitioner assessment of face validity of these words in their translations, and continuing to piloting, instrument reduction, and validation. Within validation we look at correlation with age, and relationship to other variables including family socio-economic status, and child language performance measured in the home or lab. We also apply these methods to the assessment of gesture using the CDI. Some of the languages to be studied are related to each other (of the Bantu group of African languages) and to two languages for which CDIs have been developed in East Africa (5); for these we will highlight common grammatical development to be examined that exists in all of the related languages. In the East African setting parents were found to be valid observers of their child's morpheme omissions so this is a particular focus for assessment of grammatical development. To date we have developed four pilot versions (IsiXhosa, Setswana, Sesotho, and Afrikaans). Vocabulary in isiXhosa is found to be significantly related to toddler age, mother education, and first-born status, among other known correlates of child language (8). In Sesotho, toddler vocabulary is also significantly related to age (9). In the other languages (Xitsonga and SA English) we have created pre-pilot word lists and carried out focus groups with parents enabling us to determine the acceptability of the words on our long-lists. We conclude that construction of CDIs in multiple (some unrelated) languages simultaneously is possible with rigorous application of the same methods to each language. Where languages are under-studied, we can benefit from previous research and descriptions of development in related languages. 1.Tardif, J. Child Lang. 36, (2009). 2.Caselli, J. Child Lang. 26, (1999); Bleses, J. Child Lang. 35, (2008). 3.Barrena, in A portrait of the young in the new multilingual Spain. (2008), vol. 9. 4.Reese, First Language 35, (2015). 5.Alcock, J. Child Lang. 42, (2015). 6.Prado, Journal of Health, Population and Nutrition 37, (2018). 7.Prado, J. Child Psychol.Psychi. 58, (2017); Alcock, BMC research notes 9, (2016). 8.Whitelaw, University of Cape Town (2018). 9.Horn, Cape Town (2018)

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

Sociocultural Factors Affecting Vocabulary Development in Young South African Children

Sociocultural influences on the development of child language skills have been widely studied, but the majority of the research findings were generated in Northern contexts. The current crosslinguistic, multisite study is the first of its kind in South Africa, considering the influence of a range of individual and sociocultural factors on expressive vocabulary size of young children. Caregivers of toddlers aged 16 to 32 months acquiring Afrikaans (n = 110), isiXhosa (n = 115), South African English (n = 105), or Xitsonga (n = 98) as home language completed a family background questionnaire and the MacArthur-Bates Communicative Development Inventory (CDI) about their children. Based on a revised version of Bronfenbrenner's (1977) ecological systems theory, information was obtained from the family background questionnaire on individual factors (the child's age and sex), microsystem-related factors (the number of other children and number of adults in the child's household, maternal level of education, and SES), and exosystem-related factors (home language and geographic area, namely rural or urban). All sociocultural and individual factors combined explained 25% of the variance in expressive vocabulary size. Partial correlations between these sociocultural factors and the toddlers' expressive vocabulary scores on 10 semantic domains yielded important insights into the impact of geographic area on the nature and size of children's expressive vocabulary. Unlike in previous studies, maternal level of education and SES did not play a significant role in predicting children's expressive vocabulary scores. These results indicate that there exists an interplay of sociocultural and individual influences on vocabulary development that requires a more complex ecological model of language development to understand the interaction between various sociocultural factors in diverse contexts

Multiple loci on 8q24 associated with prostate cancer susceptibility

Previous studies have identified multiple loci on 8q24 associated with prostate cancer risk. We performed a comprehensive analysis of SNP associations across 8q24 by genotyping tag SNPs in 5,504 prostate cancer cases and 5,834 controls. We confirmed associations at three previously reported loci and identified additional loci in two other linkage disequilibrium blocks (rs1006908: per-allele OR = 0.87, P = 7.9 x 10(-8); rs620861: OR = 0.90, P = 4.8 x 10(-8)). Eight SNPs in five linkage disequilibrium blocks were independently associated with prostate cancer susceptibility

Prospective observational cohort study on grading the severity of postoperative complications in global surgery research

Background The Clavien–Dindo classification is perhaps the most widely used approach for reporting postoperative complications in clinical trials. This system classifies complication severity by the treatment provided. However, it is unclear whether the Clavien–Dindo system can be used internationally in studies across differing healthcare systems in high- (HICs) and low- and middle-income countries (LMICs). Methods This was a secondary analysis of the International Surgical Outcomes Study (ISOS), a prospective observational cohort study of elective surgery in adults. Data collection occurred over a 7-day period. Severity of complications was graded using Clavien–Dindo and the simpler ISOS grading (mild, moderate or severe, based on guided investigator judgement). Severity grading was compared using the intraclass correlation coefficient (ICC). Data are presented as frequencies and ICC values (with 95 per cent c.i.). The analysis was stratified by income status of the country, comparing HICs with LMICs. Results A total of 44 814 patients were recruited from 474 hospitals in 27 countries (19 HICs and 8 LMICs). Some 7508 patients (16·8 per cent) experienced at least one postoperative complication, equivalent to 11 664 complications in total. Using the ISOS classification, 5504 of 11 664 complications (47·2 per cent) were graded as mild, 4244 (36·4 per cent) as moderate and 1916 (16·4 per cent) as severe. Using Clavien–Dindo, 6781 of 11 664 complications (58·1 per cent) were graded as I or II, 1740 (14·9 per cent) as III, 2408 (20·6 per cent) as IV and 735 (6·3 per cent) as V. Agreement between classification systems was poor overall (ICC 0·41, 95 per cent c.i. 0·20 to 0·55), and in LMICs (ICC 0·23, 0·05 to 0·38) and HICs (ICC 0·46, 0·25 to 0·59). Conclusion Caution is recommended when using a treatment approach to grade complications in global surgery studies, as this may introduce bias unintentionally

Critical care admission following elective surgery was not associated with survival benefit: prospective analysis of data from 27 countries

This was an investigator initiated study funded by Nestle Health Sciences through an unrestricted research grant, and by a National Institute for Health Research (UK) Professorship held by RP. The study was sponsored by Queen Mary University of London