Learning about patient safety: organisational context and culture in the education of health care professionals

Objectives This study investigated the formal and informal ways pre-registration students from medicine, nursing, physiotherapy and pharmacy learn about keeping patients safe. This paper gives an overview of the study and explores findings in relation to organizational context and culture. Methods The study employed a phased design using multiple qualitative methods. The overall approach drew on ‘illuminative evaluation’. Ethical approval was obtained. Phase 1 employed a convenience sample of 13 pre-registration courses across the UK. Curriculum documents were gathered, and course directors interviewed. Phase 2 used eight case studies, two for each professional group, to develop an in-depth investigation of learning across university and practice by students and newly-qualified practitioners in relation to patient safety, and to examine the organizational culture that students and newly-qualified staff are exposed to. Analysis was iterative and ongoing throughout the study, using frameworks agreed by all researchers. Results Patient safety was felt to have become a higher priority for the health care system in recent years. Incident reporting was a key feature of the patient safety agenda within the organizations examined. Staff were often unclear or too busy to report. On the whole, students were not engaged and may not be aware of incident reporting schemes. They may not have access to existing systems in their organization. Most did not access employers' induction programmes. Some training sessions occasionally included students but this did not appear to be routine. Conclusions Action is needed to develop an efficient interface between employers and education providers to develop up-to-date curricula for patient safety

Investigating the structural compaction of biomolecules upon transition to the gas-phase using ESI-TWIMS-MS

Collision cross-section (CCS) measurements obtained from ion mobility spectrometry-mass spectrometry (IMS-MS) analyses often provide useful information concerning a protein’s size and shape and can be complemented by modeling procedures. However, there have been some concerns about the extent to which certain proteins maintain a native-like conformation during the gas-phase analysis, especially proteins with dynamic or extended regions. Here we have measured the CCSs of a range of biomolecules including non-globular proteins and RNAs of different sequence, size, and stability. Using traveling wave IMS-MS, we show that for the proteins studied, the measured CCS deviates significantly from predicted CCS values based upon currently available structures. The results presented indicate that these proteins collapse to different extents varying on their elongated structures upon transition into the gas-phase. Comparing two RNAs of similar mass but different solution structures, we show that these biomolecules may also be susceptible to gas-phase compaction. Together, the results suggest that caution is needed when predicting structural models based on CCS data for RNAs as well as proteins with non-globular folds

A snapshot of electrified nanodroplets

We investigate the size distribution of electrically charged nanodroplets. The droplets were generated using nano- and micro- scale silicon tips. A brief voltage pulse results in a "snapshot" of charged nanodroplets on a metal surface. Atomic force microscopy (AFM) of the snapshot revealed that certain droplet diameters are favored suggesting droplet fission due to Rayleigh instability at nanometer length scales. The most occurring droplet diameters are 85.9(4.1) nm and 167.1 nm (9.7 nm) and for nano- and micro- scale tips respectively indicating that the tip size determines deposition resolution

Osteoarchaeological evidence for medical dissection in 18th to 19th century Aberdeen, Scotland

Open access via T&F agreement ACKNOWLEDGEMENTS: We would like to thank Police Scotland and Detective Sergeant Stephen Beattie for their initial response to the discovery, and to Jamie Grieve, Margaret Bruce and Leighanne Deboys for their assistance and expert advice in identifying the skeletal remains. Thanks to the owners of the property who allowed access. Aberdeenshire Council Archaeology Service kindly facilitated and funded the work.Peer reviewedPublisher PD

Examination of ataxin-3 (atx-3) aggregation by structural mass spectrometry techniques: A rationale for expedited aggregation upon polyglutamine (polyQ) expansion

Expansion of polyglutamine stretches leads to the formation of polyglutamine-containing neuronal aggregates and neuronal death in nine diseases for which there currently are no treatments or cures. This is largely due to a lack in understanding of the mechanisms by which expanded polyglutamine regions contribute to aggregation and disease. To complicate matters further, several of the polyglutamine-disease related proteins, including ataxin-3, have a multistage aggregation mechanism in which flanking domain self-assembly precedes polyglutamine aggregation yet is influenced by polyglutamine expansion. How polyglutamine expansion influences flanking domain aggregation is poorly understood. Here, we use a combination of mass spectrometry and biophysical approaches to investigate this issue for ataxin-3. We show that the conformational dynamics of the flanking Josephin domain in ataxin-3 with an expanded polyglutamine tract are altered in comparison to those exhibited by its nonexpanded counterpart, specifically within the aggregation-prone region of the Josephin domain (amino acid residues 73-96). Expansion thus exposes this region more frequently in ataxin-3 containing an expanded polyglutamine tract, providing a molecular explanation of why aggregation is accelerated upon polyglutamine expansion. Here, harnessing the power of ion mobility spectrometry-mass spectrometry, oligomeric species formed during aggregation are characterized and a model for oligomer growth proposed. The results suggest that a conformational change occurs at the dimer level that initiates self-assembly. New insights into ataxin-3 fibril architecture are also described, revealing the region of the Josephin domain involved in protofibril formation and demonstrating that polyglutamine aggregation proceeds as a distinct second step after protofibril formation without requiring structural rearrangement of the protofibril core. Overall, the results enable the effect of polyglutamine expansion on every stage of ataxin-3 self-assembly, from monomer through to fibril, to be described and a rationale for expedited aggregation upon polyglutamine expansion to be provided

Skp is a multivalent chaperone of outer membrane proteins

The trimeric chaperone Skp sequesters outer-membrane proteins (OMPs) within a hydrophobic cage, thereby preventing their aggregation during transport across the periplasm in Gram-negative bacteria. Here, we studied the interaction between Escherichia coli Skp and five OMPs of varying size. Investigations of the kinetics of OMP folding revealed that higher Skp/OMP ratios are required to prevent the folding of 16-stranded OMPs compared with their 8-stranded counterparts. Ion mobility spectrometry–mass spectrometry (IMS–MS) data, computer modeling and molecular dynamics simulations provided evidence that 10- to 16-stranded OMPs are encapsulated within an expanded Skp substrate cage. For OMPs that cannot be fully accommodated in the expanded cavity, sequestration is achieved by binding of an additional Skp trimer. The results suggest a new mechanism for Skp chaperone activity involving the coordination of multiple copies of Skp in protecting a single substrate from aggregation

Cardiovascular risk and risk factor management in type 2 diabetes mellitus: a population-based cohort study assessing sex disparities

Background: With recent changes in the United Kingdom’s clinical practice for diabetes mellitus care, contemporary estimates of sex disparities in cardiovascular risk and risk factor management are needed. Methods: In this retrospective cohort study, using the Clinical Practice Research Datalink linked to hospital and death records for people in England, we identified 79 985 patients with incident type 2 diabetes mellitus (T2DM) between 2006 to 2013 matched to 386 547 patients without diabetes mellitus. Sex-stratified Cox models were used to assess cardiovascular risk. Results: Compared with women without T2DM, women with T2DM had a higher cardiovascular event risk (adjusted hazard ratio, 1.20 [95% confidence interval, 1.12–1.28]) with similar corresponding data in men (hazard ratio, 1.12 [1.06–1.19]), leading to a nonsignificant higher relative risk in women (risk ratio, 1.07 [0.98–1.17]). However, some important sex differences in the management of risk factors were observed. Compared with men with T2DM, women with T2DM were more likely to be obese, hypertensive, and have hypercholesterolemia, but were less likely to be prescribed lipid-lowering medication and angiotensin-converting enzyme inhibitors, especially if they had cardiovascular disease. Conclusions: Compared with men developing T2DM, women with T2DM do not have a significantly higher relative increase in cardiovascular risk, but ongoing sex disparities in prescribing should prompt heightened efforts to improve the standard and equity of diabetes mellitus care in women and men

Age-, sex- and ethnicity-related differences in body weight, blood pressure, HbA1c and lipid levels at the diagnosis of type 2 diabetes relative to people without diabetes

Aims/hypothesis: To determine how weight patterns together with glycaemia, blood pressure and lipids vary at diagnosis of diabetes by age, sex and ethnicity.Methods: Using the UK Clinical Practice Research Datalink, we identified people with type 2 diabetes (n=187,601) diagnosed 1998-2015, and compared their weights, HbA1c, blood pressure and lipid levels with age-matched people without diabetes (n=906,182), by sex and ethnic group.Results: Younger age at diagnosis was associated with greater adjusted mean difference (95% CI) in weight between those with versus without type 2 diabetes being 18.7 (18.3, 19.1) kg at 20-39 years of age but 5.3 (5.0, 5.5) kg ≥80 years; weight differentials were maximal in white women, and around double in whites compared with South Asians and Blacks. Despite lower absolute values, blood pressure differences were also greatest at younger age of diabetes onset: 7 (6, 7) mmHg at age 20-39 years versus -0.5 (-0.9, -0.2) at ≥80 years of age, and greatest in whites, and especially in women. Triacylglycerol level differences were greatest in younger men. Finally, HbA1c levels were also higher with younger onset diabetes, particularly in Blacks.Conclusions/interpretation: At diagnosis of type 2 diabetes, compared to controls, weight and blood pressure differentials were greater in: younger compared to older people; in women compared to men and in whites compared to South Asians and Blacks. These differences were observed even though South Asians and Blacks tend to develop diabetes a decade earlier with either similar or greater dysglycaemia. These striking patterns may have implications for management and prevention

Incidence and prevalence of psoriasis in multiethnic Johor Bahru, Malaysia: a population-based cohort study using electronic health data routinely captured in the Teleprimary Care (TPC®) clinical information system from 2010 to 2020

Background: There are no population-based epidemiological data on psoriasis in Southeast Asia, including Malaysia. Objectives: To determine the incidence and prevalence of psoriasis over 11 years in multiethnic Johor Bahru, Malaysia. Methods: A population-based cohort study was made using the Teleprimary Care database between January 2010 and December 2020. Cases of psoriasis, identified by ICD-10 diagnostic codes, were validated by dermatologists. Annual prevalence and incidence were estimated and stratified by age, sex and ethnicity. Results: We identified 3932 people with dermatologist-confirmed psoriasis, including 1830 incident cases, among 1 164 724 Malaysians, yielding an 11-year prevalence of 0·34% [95% confidence interval (CI) 0·33–0·35] and incidence of 34·2 per 100 000 person-years (95% CI 32·6–35·8). Rates were higher in Indian patients; the prevalences were 0·54% (0·50–0·58) in Indian, 0·38% (0·36–0·40) in Chinese and 0·29% (0·28–0·30) in Malay patients, and the respective incidences per 100 000 person-years were 52·5 (47·3–57·7), 38·0 (34·1–41·8) and 30·0 (28·2–31·8). Rates were higher in males; the prevalence was 0·39% (0·37–0·41) in males and 0·29% (0·27–0·30) in females, and the respective incidences per 100 000 person-years were 40·7 (38·2–43·2) and 28·3 (26·4–30·3). Between 2010 and 2020, annual psoriasis prevalence and incidence increased steadily from 0·27% to 0·51% and from 27·8 to 60·9 per 100 000 person-years, respectively. Annual rates were consistently higher in male and Indian patients. Overall, psoriasis was significantly more common in males than females [odds ratio (OR) 1·37, 95% CI 1·29–1·46] and in Indian and Chinese patients vs. Malay (OR 1·85, 1·71–2·01 and OR 1·30, 1·20–1·41, respectively). Prevalence increased with age, with the highest rates in the groups aged 50–59 and 60–69 years at 0·67% and 0·66%, respectively. A modest bimodal trend in age of psoriasis onset was observed, with first and second peaks at 20–29 and 50–59 years. Disease onset was significantly earlier in females than males [mean (SD) 36·8 (17·3) vs. 42·0 (17·2) years, P &lt; 0·001] and in Malay vs. Indian and Chinese patients [mean (SD): Malay 36·4 (17·5), Indian 40·8 (15·2), Chinese 47·4 (16·9) years, P &lt; 0·001]. Conclusions: We found that psoriasis incidence and prevalence are increasing and varied by age, sex and ethnicity. Our findings should help inform healthcare planning and management for patients with psoriasis in Malaysia. What is already known about this topic? The incidence and prevalence of psoriasis are generally lower in Asian populations and children. There is a lack of agreement on sex-specific differences in psoriasis incidence and prevalence. There has been no population-based study on the incidence and prevalence of psoriasis in Southeast Asia, including Malaysia. There is no information on differences in psoriasis prevalence and incidence by sex, age and ethnicity in Malaysia. What does this study add? Psoriasis incidence and prevalence are increasing in the multiethnic population of Johor Bahru, Malaysia. Incidence and prevalence rates were higher in male than female patients and were consistently highest among Indian patients, followed by Chinese and Malay. A modest bimodality in the age of psoriasis onset was observed among the groups aged 20–29 and 50–59 years. Psoriasis onset was significantly later in male than female patients and in Chinese vs. Indian and Malay patients.</p

Small molecule probes of protein aggregation

Understanding the mechanisms of amyloid formation and toxicity remain major challenges. Whilst substantial progress has been made in the development of methods able to identify the species formed during self-assembly and to describe the kinetic mechanisms of aggregation, the structure(s) of non-native species, including potentially toxic oligomers, remain elusive. Moreover, how fibrils contribute to disease remains unclear. Here we review recent advances in the development of small molecules and other reagents that are helping to define the mechanisms of protein aggregation in molecular detail. Such probes form a powerful platform with which to better define the mechanisms of structural conversion into amyloid fibrils and may provide the much-needed stepping stone for future development of successful therapeutic agents