Unmet care needs of patients with advanced cancer and their relatives:multicentre observational study

Objectives: The care needs of patients with advanced cancer and their relatives change throughout the disease trajectory. This study focused on the care-related problems and needs of patients with advanced cancer and their relatives. This was done from the perspective of centres for information and support. Methods: This cross-sectional study used data from the eQuiPe study: an observational cohort study in which 40 Dutch hospitals participated. All adult patients with a diagnosis of a metastasised tumour and their relatives were eligible. Measures included information on the patients' and relatives' care problems and needs, assessed by the short version of the Problems and Needs in Palliative Care questionnaire. Socioeconomic demographics were also collected. Results: 1103 patients with advanced cancer and 831 relatives were included. Both patients (M=60.3, SD=29.0) and relatives (M=59.2, SD=26.6) experienced most problems in the domain of â € psychological issues'. Both patients (M=14.0, SD=24.2) and relatives (M=17.7, SD=25.7) most frequently reported unmet needs within this domain. The most often reported unmet need by patients was â € worrying about the future of my loved ones' (22.0%); for relatives this was â € fear for physical suffering of the patient' (32.8%). There was no clear relationship between socioeconomic demographics and the experienced unmet needs. Conclusions: The most often mentioned unmet needs consisted of fears and worries, followed by a broad range of topics within multiple domains. Centres for information and support may play a role in reducing the unmet needs of (potential) visitors as these centres provide support on a broad range of topics.</p

Development of a portfolio of learning for postgraduate family medicine training in South Africa: a Delphi study

<p>Abstract</p> <p>Background</p> <p>Within the 52 health districts in South Africa, the family physician is seen as the clinical leader within a multi-professional district health team. Family physicians must be competent to meet 90% of the health needs of the communities in their districts. The eight university departments of Family Medicine have identified five unit standards, broken down into 85 training outcomes, for postgraduate training. The family medicine registrar must prove at the end of training that all the required training outcomes have been attained. District health managers must be assured that the family physician is competent to deliver the expected service. The Colleges of Medicine of South Africa (CMSA) require a portfolio to be submitted as part of the uniform assessment of all registrars applying to write the national fellowship examinations. This study aimed to achieve a consensus on the contents and principles of the first national portfolio for use in family medicine training in South Africa.</p> <p>Methods</p> <p>A workshop held at the WONCA Africa Regional Conference in 2009 explored the purpose and broad contents of the portfolio. The 85 training outcomes, ideas from the WONCA workshop, the literature, and existing portfolios in the various universities were used to develop a questionnaire that was tested for content validity by a panel of 31 experts in family medicine in South Africa, via the Delphi technique in four rounds. Eighty five content items (national learning outcomes) and 27 principles were tested. Consensus was defined as 70% agreement. For those items that the panel thought should be included, they were also asked how to provide evidence for the specific item in the portfolio, and how to assess that evidence.</p> <p>Results</p> <p>Consensus was reached on 61 of the 85 national learning outcomes. The panel recommended that 50 be assessed by the portfolio and 11 should not be. No consensus could be reached on the remaining 24 outcomes and these were also omitted from the portfolio. The panel recommended that various types of evidence be included in the portfolio. The panel supported 26 of the 27 principles, but could not reach consensus on whether the portfolio should reflect on the relationship between the supervisor and registrar.</p> <p>Conclusion</p> <p>A portfolio was developed and distributed to the eight departments of Family Medicine in South Africa, and the CMSA, to be further tested in implementation.</p

21 new long-term variables in the GX 339-4 field: two years of MeerKAT monitoring

We present 21 new long-term variable radio sources found commensally in two years of weekly MeerKAT monitoring of the low-mass X-ray binary GX 339-4. The new sources vary on time scales of weeks to months and have a variety of light curve shapes and spectral index properties. Three of the new variable sources are coincident with multi-wavelength counterparts; and one of these is coincident with an optical source in deep MeerLICHT images. For most sources, we cannot eliminate refractive scintillation of active galactic nuclei as the cause of the variability. These new variable sources represent $2.2\pm0.5$ per cent of the unresolved sources in the field, which is consistent with the 1-2 per cent variability found in past radio variability surveys. However, we expect to find short-term variable sources in the field as well as these 21 new long-term variable sources. We present the radio light curves and spectral index variability of the new variable sources, as well as the absolute astrometry and matches to coincident sources at other wavelengths.Comment: 26 pages, 17 figures, 7 tables. Accepted for publication in MNRAS 2022 March 14. Received 2022 February 17; in original form 2021 July 1

Exploring the impact of patient-specific clinical features on osimertinib effectiveness in a real-world cohort of patients with EGFR mutated non-small cell lung cancer

Osimertinib is prescribed to patients with metastatic non-small cell lung cancer (NSCLC) and a sensitizing EGFR mutation. Limited data exists on the impact of patient characteristics or osimertinib exposure on effectiveness outcomes. This was a Dutch, multicenter cohort study. Eligible patients were ≥18 years, with metastatic EGFRm+ NSCLC, receiving osimertinib. Primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS) and safety. Kaplan-Meier analyses and multivariate Cox proportional hazard models were performed. In total, 294 patients were included. Primary EGFR-mutations were mainly exon 19 deletions (54%) and p.L858R point mutations (30%). Osimertinib was given in first-line (40%), second-line (46%) or beyond (14%), with median PFS 14.4 (95% CI: 9.4-19.3), 13.9 (95% CI: 11.3-16.1) and 8.7 months (95% CI: 4.6-12.7), respectively. Patients with low BMI (&lt;20.0 kg/m2) had significantly shorter PFS/OS compared to all other subgroups. Patients with a high plasma trough concentration in steady state (Cmin,SS; &gt;271 ng/mL) had shorter PFS compared to a low Cmin,SS (&lt;163 ng/mL; aHR 2.29; 95% CI: 1.13-4.63). A significant longer PFS was seen in females (aHR = 0.61, 95% CI: 0.45-0.82) and patients with the exon 19 deletion (aHR = 0.58, 95% CI: 0.36-0.92). A trend towards longer PFS was seen for TP53 wild-type patients, while age did not impact PFS. Patients with a primary EGFR exon 19 deletion had longer PFS, while a low BMI, male sex and a high Cmin,SS were indicative for shorter PFS and/or OS. Age was not associated with effectiveness outcomes of osimertinib.</p

Barriers to the uptake and use of feedback in the context of summative assessment

Despite calls for feedback to be incorporated in all assessments, a dichotomy exists between formative and summative assessments. When feedback is provided in a summative context, it is not always used effectively by learners. In this study we explored the reasons for this. We conducted individual interviews with 17 students who had recently received web based feedback following a summative assessment. Constant comparative analysis was conducted for recurring themes. The summative assessment culture, with a focus on avoiding failure, was a dominant and negative influence on the use of feedback. Strong emotions were prevalent throughout the period of assessment and feedback, which reinforced the focus on the need to pass, rather than excel. These affective factors were heightened by interactions with others. The influence of prior learning experiences affected expectations about achievement and the need to use feedback. The summative assessment and subsequent feedback appeared disconnected from future clinical workplace learning. Socio-cultural influences and barriers to feedback need to be understood before attempting to provide feedback after all assessments. A move away from the summative assessment culture may be needed in order to maximise the learning potential of assessments

SecA, a remarkable nanomachine

Biological cells harbor a variety of molecular machines that carry out mechanical work at the nanoscale. One of these nanomachines is the bacterial motor protein SecA which translocates secretory proteins through the protein-conducting membrane channel SecYEG. SecA converts chemically stored energy in the form of ATP into a mechanical force to drive polypeptide transport through SecYEG and across the cytoplasmic membrane. In order to accommodate a translocating polypeptide chain and to release transmembrane segments of membrane proteins into the lipid bilayer, SecYEG needs to open its central channel and the lateral gate. Recent crystal structures provide a detailed insight into the rearrangements required for channel opening. Here, we review our current understanding of the mode of operation of the SecA motor protein in concert with the dynamic SecYEG channel. We conclude with a new model for SecA-mediated protein translocation that unifies previous conflicting data

Assessing fitness-to-practice of overseas-trained health practitioners by Australian registration & accreditation bodies

Assessment of fitness-to-practice of health professionals trained overseas and who wish to practice in Australia is undertaken by a range of organisations. These organisations conduct assessments using a range of methods. However there is very little published about how these organisations conduct their assessments. The purpose of the current paper is to investigate the methods of assessment used by these organisations and the issues associated with conducting these assessments

Direct Visualization by Cryo-EM of the Mycobacterial Capsular Layer: A Labile Structure Containing ESX-1-Secreted Proteins

The cell envelope of mycobacteria, a group of Gram positive bacteria, is composed of a plasma membrane and a Gram-negative-like outer membrane containing mycolic acids. In addition, the surface of the mycobacteria is coated with an ill-characterized layer of extractable, non-covalently linked glycans, lipids and proteins, collectively known as the capsule, whose occurrence is a matter of debate. By using plunge freezing cryo-electron microscopy technique, we were able to show that pathogenic mycobacteria produce a thick capsule, only present when the cells were grown under unperturbed conditions and easily removed by mild detergents. This detergent-labile capsule layer contains arabinomannan, α-glucan and oligomannosyl-capped glycolipids. Further immunogenic and proteomic analyses revealed that Mycobacterium marinum capsule contains high amounts of proteins that are secreted via the ESX-1 pathway. Finally, cell infection experiments demonstrated the importance of the capsule for binding to cells and dampening of pro-inflammatory cytokine response. Together, these results show a direct visualization of the mycobacterial capsular layer as a labile structure that contains ESX-1-secreted proteins