Retrospective harm benefit analysis of pre-clinical animal research for six treatment interventions

The harm benefit analysis (HBA) is the cornerstone of animal research regulation and is considered to be a key ethical safeguard for animals. The HBA involves weighing the anticipated benefits of animal research against its predicted harms to animals but there are doubts about how objective and accountable this process is.i. To explore the harms to animals involved in pre-clinical animal studies and to assess these against the benefits for humans accruing from these studies; ii. To test the feasibility of conducting this type of retrospective HBA.Data on harms were systematically extracted from a sample of pre-clinical animal studies whose clinical relevance had already been investigated by comparing systematic reviews of the animal studies with systematic reviews of human studies for the same interventions (antifibrinolytics for haemorrhage, bisphosphonates for osteoporosis, corticosteroids for brain injury, Tirilazad for stroke, antenatal corticosteroids for neonatal respiratory distress and thrombolytics for stroke). Clinical relevance was also explored in terms of current clinical practice. Harms were categorised for severity using an expert panel. The quality of the research and its impact were considered. Bateson's Cube was used to conduct the HBA.The most common assessment of animal harms by the expert panel was 'severe'. Reported use of analgesia was rare and some animals (including most neonates) endured significant procedures with no, or only light, anaesthesia reported. Some animals suffered iatrogenic harms. Many were kept alive for long periods post-experimentally but only 1% of studies reported post-operative care. A third of studies reported that some animals died prior to endpoints. All the studies were of poor quality. Having weighed the actual harms to animals against the actual clinical benefits accruing from these studies, and taking into account the quality of the research and its impact, less than 7% of the studies were permissible according to Bateson's Cube: only the moderate bisphosphonate studies appeared to minimise harms to animals whilst being associated with benefit for humans.This is the first time the accountability of the HBA has been systematically explored across a range of pre-clinical animal studies. The regulatory systems in place when these studies were conducted failed to safeguard animals from severe suffering or to ensure that only beneficial, scientifically rigorous research was conducted. Our findings indicate a pressing need to: i. review regulations, particularly those that permit animals to suffer severe harms; ii. reform the processes of prospectively assessing pre-clinical animal studies to make them fit for purpose; and iii. systematically evaluate the benefits of pre-clinical animal research to permit a more realistic assessment of its likely future benefits

Appointment waiting times and education level influence the quality of bowel preparation in adult patients undergoing colonoscopy

<p>Abstract</p> <p>Background</p> <p>Risk factors for poor bowel preparation are recognized to be independent of the type of bowel preparation method used. Patient and administrative factors influencing bowel preparation are known to vary in different healthcare systems.</p> <p>Methods</p> <p>A prospective, cross-sectional study of patients undergoing colonoscopy in an Asian tertiary centre was conducted to identify risk factors associated with poor bowel preparation, and to evaluate the impact of poor bowel preparation on technical performance and patient comfort.</p> <p>Results</p> <p>Data on 501 patients (mean age 60.1 ± 14.0 years old, 51.2% males, 60.9% with secondary education or higher) was available for analysis. Poor bowel preparation was present in 151 patients (30.1%). Lower education level (OR = 2.35, 95% CI = 1.54 - 3.60), colonoscopy appointment waiting time beyond 16 weeks (OR = 1.86, 95% CI = 1.04 - 3.37) and non-adherence to bowel preparation instructions (OR = 4.76, 95% CI = 3.00 - 7.55) were identified as independent risk factors for poor bowel preparation. Poor bowel preparation was associated with a lower cecal intubation rate (78.1% versus 98.3%, p < 0.001), prolonged total colonoscopy time (25.4 ± 12.6 minutes versus 16.7 ± 10.2 minutes, p < 0.001), and increased patient discomfort during colonoscopy (patient with moderate to severe abdominal discomfort 31.8% versus 3.2%, p < 0.001).</p> <p>Conclusions</p> <p>Education levels and appointment waiting times, in addition to non-adherence to bowel preparation instructions, increase the risk of poor bowel preparation in adult patients undergoing colonoscopy. The latter has a significant impact on colonoscopy performance and patient comfort.</p

The do's, don't and don't knows of supporting transition to more independent practice

Introduction: Transitions are traditionally viewed as challenging for clinicians. Throughout medical career pathways, clinicians need to successfully navigate successive transitions as they become progressively more independent practitioners. In these guidelines, we aim to synthesize the evidence from the literature to provide guidance for supporting clinicians in their development of independence, and highlight areas for further research. Methods: Drawing upon D3 method guidance, four key themes universal to medical career transitions and progressive independence were identified by all authors through discussion and consensus from our own experience and expertise: workplace learning, independence and responsibility, mentoring and coaching, and patient perspectives. A scoping review of the literature was conducted using Medline database searches in addition to the authors’ personal archives and reference snowballing searches. Results: 387 articles were identified and screened. 210 were excluded as not relevant to medical transitions (50 at title screen; 160 at abstract screen). 177 full-text articles were assessed for eligibility; a further 107 were rejected (97 did not include career transitions in their study design; 10 were review articles; the primary references of these were screened for inclusion). 70 articles were included of which 60 provided extractable data for the final qualitative synthesis. Across the four key themes, seven do’s, two don’ts and seven don’t knows were identified, and the strength of evidence was graded for each of these recommendations. Conclusion: The two strongest messages arising from current literature are first, transitions should not be viewed as one moment in time: career trajectories are a continuum with valuable opportunities for personal and professional development throughout. Second, learning needs to be embedded in practice and learners provided with authentic and meaningful learning opportunities. In this paper, we propose evidence-based guidelines aimed at facilitating such transitions through the fostering of progressive independence

Reliability of MRI findings in candidates for lumbar disc prosthesis

Introduction: Limited reliability data exist for localised magnetic resonance imaging (MRI) findings relevant to planning of treatment with lumbar disc prosthesis and later outcomes. We assessed the reliability of such findings in chronic low back pain patients who were accepted candidates for disc prosthesis. Methods: On pretreatment MRI of 170 patients (mean age 41 years; 88 women), three experienced radiologists independently rated Modic changes, disc findings and facet arthropathy at L3/L4, L4/L5 and L5/S1. Two radiologists rerated 126 examinations. For each MRI finding at each disc level, agreement was analysed using the kappa statistic and differences in prevalence across observers using a fixed effects model. Results: All findings at L3/L4 and facet arthropathy at L5/S1 had a mean prevalence <10% across observers and were not further analysed, ensuring interpretable kappa values. Overall interobserver agreement was generally moderate or good (kappa 0.40–0.77) at L4–S1 for Modic changes, nucleus pulposus signal, disc height (subjective and measured), posterior high-intensity zone (HIZ) and disc contour, and fair (kappa 0.24) at L4/L5 for facet arthropathy. Posterior HIZ at L5/S1 and severely reduced subjective disc height at L4/L5 differed up to threefold in prevalence between observers (p< 0.0001). Intraobserver agreement was mostly good or very good (kappa 0.60–1.00). Conclusion: In candidates for disc prosthesis, mostly moderate interobserver agreement is expected for localised MRI findings

Colonoscopia com polipectomia: análise crítica de fatores de risco e complicações Colonic snare polipectomy: critical analysis of risk factors and complications

Objetivo: Analisar complicações de polipectomia com alça ditérmica em cólon. Pacientes e Métodos: Estudo retrospectivo de polipectomias em colonoscopias realizadas em dois hospitais de 2001 a 2007. Teste t de Student foi usado para média, desvio padrão e qui-quadrado para números absolutos. P< que 0,05 foi considerado significativo. Resultados: Foram 1687 polipectomias em 8447 colonoscopias. Sangramento imediato em 24 (11,8%) em pólipos maiores do que 2 cm contra 1 (0,07%) em menores p<0,01. Somente 1, maior que 2 cm, (0,49%) necessitou de cirurgia para controle do sangramento p<0,01. Sangramento tardio em 7 (3,4%), todos maiores que 2 cm p<0,01. Perfuração em 6 (2.9%), todas em cólon direito. Não houve necessidade de cirurgia. A idade foi 59,8±6,7 para sangramento imediato, 60±9,8 para tardio e 63,8±16,3 para os que não sangraram p>0,05. Síndrome pós-polipectomia em 6 (0,35%). Ressecção fatiada somente em maiores que 2 cm, 89/116 (77%) sésseis e 11/87 (13%) pediculados p<0,01. Carcinoma invasivo em 40 adenomas maiores que 2 cm (19,7%). Conclusão: Polipectomia com alça é segura, sangramento a complicação mais comum, relacionada ao tamanho da base. Perfuração vem a seguir. Ambas tem tratamento endoscópico prioritário.<br>Purpose: The aim of this study was to evaluate adverse events from snare polypectomy. Methods: We retrospectively analysed the rate of complications of 1687 snare polypectomies carried out in 8447 colonoscopies between 2001 and 2007 at two Medical Institutions. Student t test was used for statistical analysis of mean and chi-square to compare absolute numbers. A significant p-value was defined as < 0,05. Results: Of the 1687 colonoscopic polypectomies 203 were performed in polyps larger than 2 cm in diameter ( range 2-10 cm ). In this group 24 (11,8%) had immediate bleeding, against 1 ( 0,07%) smaller than 2 cm p<0,01. Only one, larger than 2 cm, needed surgery to control bleeding episod p<0,01. Delayed bleeding occurred in 6 (0,35%).None required surgery. The age group for bleeding post-polypectomy did not differ, being 59,8±6,7 for immediate bleeding, 60±9,8 for delayed and 63,8±16,3 for no bleeding p>0,05.Post-polypectomy syndrome occurred in 6 patients (0,35%). In polyps larger than 2 cm, piecemeal resection was performed more often in sessile than in pedunculated ones 89/116 ( 77%) versus 11/87 (13%) p<0,01. Invasive carcinoma was present in 40 adenoma larger than 2 cm (19,7%). Conclusion: Snare polypectomy is safe procedure, being bleeding the most common complication, related with polyp size mainly its base, treated most of the time endoscopically. Perforation being the next, treated too without surgery