Evidence-based prescribing for post-traumatic stress disorder

There is strong research evidence to support the pharmacological treatment of post-traumatic stress disorder (PTSD) as a second line to trauma-focused psychological interventions. Fluoxetine, paroxetine, sertraline and venlafaxine are the best-evidenced drugs, with lower-level evidence for other medications. It is important that prescribing for PTSD is evidence-based

Medical student attitudes to mental health and psychiatry: the use of a patient-experience short film

Background: Medical student attitudes to mental illness are significantly influenced by their undergraduate educational experience. Medical education therefore has a key role to play in challenging the stigma associated with mental illness. We developed a short educational film aimed at challenging stigmatising attitudes to mental illness and explored its effects on undergraduate medical student attitudes. We hypothesised that levels of stigmatising attitudes in medical students would reduce after students viewed the educational film. Method: We used a validated scale (Mental Illness: Clinician Attitudes, MICA) to examine undergraduate medical student attitudes to mental illness at two time points - prior to (T1) and following (T2) viewing the short film. The film focused on patient experiences and was designed to highlight personal experiences of mental illness. Results: 92 students completed the MICA before the film and 73 students at both time points. Having a personal history of mental illness was associated with less stigmatising attitudes (t=2.4, df=87, p=0.019). Stigma scores were reduced following the film viewing (t=7.101, df=72, p<0.001). Discussion: This study suggests that patient experience films, used as educational tools, can challenge student perceptions of mental illness and lead to a reduction in stigmatising attitudes, at least in the short term. Future studies are required to examine the longer-term effects of such educational interventions in terms of student perceptions and attitudes towards mental health and psychiatry

Thermally reactive N-(2-hydroxypropyl)methacrylamide (HPMA) amphiphiles for drug solubilisation

Thermally active polymers, can respond structurally to temperature changes, making them interesting as potential drug delivery vehicles. Polymers of N-(3-aminopropyl) methacrylamide hydrochloride (APMA) are cationic with primary amine groups in their structure, which have been explored in biomedical applications via post-polymerisation modifications. In this work, we synthesised amphiphilic APMA monomers using hydrophobic pendant groups via conjugation onto their primary amine group. The pendant groups chosen in this study were palmitoyl, dansyl and cholesteryl moieties. The amphiphilic monomers were subsequently copolymerized with N-(2-hydroxypropyl)methacrylamide (HPMA) using varied monomer feed ratios resulting in a thermo-responsive system. The ability of the resultant aggregates in aqueous solution to encapsulate and liberate model drugs (e.g., propofol, griseofulvin and prednisolone) was then determined. Our data showed that the HPMA based formulations were capable of loading the model drug molecules inside their lipophilic core; HPMA-co-(APMA-Dansyl 2%) exhibited the largest drug encapsulation ability. Subsequently, poly(ethylene glycol) (PEG) was incorporated into the intrinsic polymer structure. This resulted in a more rapid drug release profile, whereby 100% of griseofulvin and prednisolone were liberated after only 4 h, which was only 5% and 10% before the PEG inclusion, respectively. Similarly, propofol showed 70% liberation from the polymer aggregate after 24 h, compared with only 30% liberation pre-PEGylation. These studies give an insight into the potential of the HMPA based amphiphiles as thermally responsive cargo carrier/release systems which could be exploited in the delivery of poorly soluble drugs

Pharmacological-assisted psychotherapy for post-traumatic stress disorder: a systematic review and meta-analysis

Background: Pharmacological-assisted psychotherapies, using conventional and novel drug agents, are increasingly being used both in clinical and experimental research settings, respectively. Objective: To determine the efficacy of conventional and novel pharmacological-assisted psychotherapies in reducing PTSD symptom severity. Method: A systematic review and meta-analysis of randomised-controlled trials were undertaken; 21 studies were included. Results: MDMA-assisted therapy was found to statistically superior to active and inactive placebo-assisted therapy in reduction of PTSD symptoms (standardised mean difference −1.09, 95% CI −1.60 to −0.58). There was no evidence of superiority over placebo for any other intervention. Conclusions: MDMA-assisted therapy demonstrated an impressive effect size; however, it is difficult to have confidence at this stage in this intervention due to the small numbers of participants included, and more research in this area is needed. There was no evidence to support the efficacy of any other drug-assisted interventions

Pharmacological therapy for post-traumatic stress disorder: a systematic review and meta-analysis of monotherapy, augmentation and head-to-head approaches

Background: Pharmacological approaches are widely used for post-traumatic stress disorder (PTSD) despite uncertainty over efficacy. Objectives: To determine the efficacy of all pharmacological approaches, including monotherapy, augmentation and head-to-head approaches (drug versus drug, drug versus psychotherapy), in reducing PTSD symptom severity. Method: A systematic review and meta-analysis of randomised controlled trials were undertaken; 115 studies were included. Results: Selective serotonin reuptake inhibitors (SSRIs) were found to be statistically superior to placebo in reduction of PTSD symptoms but the effect size was small (standardised mean difference −0.28, 95% CI −0.39 to −0.17). For individual monotherapy agents compared to placebo in two or more studies, we found small statistically significant evidence for the antidepressants fluoxetine, paroxetine, sertraline, venlafaxine and the antipsychotic quetiapine. For pharmacological augmentation, we found small statistically significant evidence for prazosin and risperidone. Conclusions: Some medications have a small positive effect on reducing PTSD symptom severity and can be considered as potential monotherapy treatments; these include fluoxetine, paroxetine, sertraline, venlafaxine and quetiapine. Two medications, prazosin and risperidone, also have a small positive effect when used to augment pharmacological monotherapy. There was no evidence of superiority for one intervention over another in the small number of head-to-head comparison studies

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

A case-based medical curriculum for the 21st century: The use of innovative approaches in designing and developing a case on mental health

The introduction of case-based learning (CBL) by the School of Medicine at Cardiff University has encouraged innovation in medical teaching and learning. During years one and two of the modernized MBBCh program, students complete 17 cases as part of the newly developed C21 curriculum that emphasizes a patient-oriented and student-centered approach to learning. The mental health case, which is presented in year 2, incorporates a number of novel teaching resources that aim to enhance the students’ learning experience and to further reinforce the patient-oriented and community-based philosophy of C21. These include the use of fictionalized video diaries, virtual patient cases, e-learning workbooks, an interactive practical session, and community placements. Novel teaching methods and resources were evaluated by students in terms of effectiveness and value as learning resources through the administration of a structured mixed questionnaire. The results revealed that students valued the inclusion of these resources, which they evaluated as having contributed to their understanding of the subject area. Furthermore, the case was found to have had an impact on student interest in psychiatry as a specialty as well as a career choice. The positive student evaluation of this case supports the innovations in teaching delivery inspired by C21

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