Histological examination of choroid plexus epithelia changes in schizophrenia.

BACKGROUND: The choroid plexus (CP) produces and secretes most of the cerebrospinal fluid (CSF) of the central nervous system. The CP is suggested to be regulated by descending neurons and by circulating factors and is involved in the interaction between central and peripheral inflammation. Quantitative imaging has demonstrated volumetric CP changes in psychosis, schizophrenia and depression. This study histologically examines CP epithelial cell morphology in these illnesses to identify the biological source of such volumetric changes. METHODS: Formalin-fixed paraffin-embedded (FFPE) blocks were obtained bilaterally from the lateral ventricles of 13 cases of sex- and age-matched brains from each of schizophrenia (SZ) with psychosis, major depressive disorder (MDD) and matched controls (NPD). FFPE blocks were sectioned at 7 µm and routinely stained for H&E. Morphological analysis of 180 CP epithelia/case was conducted blindly on digital images collected at x600 magnification. Calcification was assessed in all CP regions manually. RESULTS: Analysis with a General Linear Model demonstrated a significant effect of diagnosis on somal width (p = 0.006, R2 = 0.33 R2(adj) = 0.25) demonstrating increased somal width in SZ without psychotic medication versus controls (p = 0.032), but not in medicated SZ cases. No effects were observed in calcification. DISCUSSION: The epithelial cells that were examined were attached to the CP fibrous surface, so width expansion describes the primary methods for these cells to expand with adherence to this surface in SZ. The interaction of antipsychotic medication and diagnosis demonstrates that this is an illness-specific change mediated through the DA-system with likely neuronal origin. CP alterations were not found in MDD where they are instead generally associated with heightened allostatic load that was unknown in this cohort.

The PRO-ACTIVE trial protocol: a randomized study comparing the effectiveness of PROphylACTic swallow InterVEntion for patients receiving radiotherapy for head and neck cancer.

BACKGROUND: Swallowing therapy is commonly provided as a treatment to lessen the risk or severity of dysphagia secondary to radiotherapy (RT) for head and neck cancer (HNC); however, best practice is not yet established. This trial will compare the effectiveness of prophylactic (high and low intensity) versus reactive interventions for swallowing in patients with HNC undergoing RT. METHODS: This multi-site, international randomized clinical trial (RCT) will include 952 adult patients receiving radiotherapy for HNC and who are at high risk for post-RT dysphagia. Participants will be randomized to receive one of three interventions for swallowing during RT: RE-ACTIVE, started promptly if/when dysphagia is identified; PRO-ACTIVE EAT, low intensity prophylactic intervention started before RT commences; or, PRO-ACTIVE EAT+EXERCISE, high intensity prophylactic intervention also started before RT commences. We hypothesize that the PRO-ACTIVE therapies are more effective than late RE-ACTIVE therapy; and, that the more intensive PRO-ACTIVE (EAT + EXERCISE) is superior to the low intensive PRO-ACTIVE (EAT). The primary endpoint of effectiveness is duration of feeding tube dependency one year post radiation therapy, selected as a pragmatic outcome valued equally by diverse stakeholders (e.g., patients, caregivers and clinicians). Secondary outcomes will include objective measures of swallow physiology and function, pneumonia and weight loss, along with various patient-reported swallowing-related outcomes, such as quality of life, symptom burden, and self-efficacy. DISCUSSION: Dysphagia is a common and potentially life-threatening chronic toxicity of radiotherapy, and a priority issue for HNC survivors. Yet, the optimal timing and intensity of swallowing therapy provided by a speech-language pathologist is not known. With no clearly preferred strategy, current practice is fraught with substantial variation. The pragmatic PRO-ACTIVE trial aims to specifically address the decisional dilemma of when swallowing therapy should begin (i.e., before or after a swallowing problem develops). The critical impact of this dilemma is heightened by the growing number of young HNC patients in healthcare systems that need to allocate resources most effectively. The results of the PRO-ACTIVE trial will address the global uncertainty regarding best practice for dysphagia management in HNC patients receiving radiotherapy. TRIAL REGISTRATION: The protocol is registered with the US Patient Centered Outcomes Research Institute, and the PRO-ACTIVE trial was prospectively registered at ClinicalTrials.gov , under the identifier NCT03455608 ; First posted: Mar 6, 2018; Last verified: Jun 17, 2021. Protocol Version: 1.3 (January 27, 2020).

Association between cardiovascular risk-factors and venous thromboembolism in a large longitudinal study of French women.

BACKGROUND: Previous studies have shown conflicting results regarding the influence of cardiovascular risk-factors on venous thromboembolism. This study aimed to determine if these risk-factors, i.e. physical activity, smoking, hypertension, dyslipidaemia, and diabetes, were associated with the risk of venous thromboembolism, and to determine if these associations were confounded by BMI. METHODS: We used data from the E3N cohort study, a French prospective population-based study initiated in 1990, consisting of 98,995 women born between 1925 and 1950. From the women in the study we included those who did not have prevalent arterial disease or venous thromboembolism at baseline; thus 91,707 women were included in the study. Venous thromboembolism cases were self-reported during follow-up, and verified via specific mailings to medical practitioners or via drug reimbursements for anti-thrombotic medications. Hypertension, diabetes and dyslipidaemia were self-reported validated against drug reimbursements or specific questionnaires. Physical activity, and smoking were based on self-reports. Cox-models, adjusted for BMI and other potential risk-factors were used to determine hazard ratios for incident venous thromboembolism. RESULTS: During 1,897,960 person-years (PY), 1, 649 first incident episodes of thrombosis were identified at an incidence rate of 0.9 per 1000 PY. This included 505 cases of pulmonary embolism and 1144 cases of deep vein thrombosis with no evidence of pulmonary embolism. Hypertension, dyslipidaemia, diabetes, smoking and physical activity were not associated with the overall risk of thrombosis after adjustment for BMI. CONCLUSIONS: Traditional cardiovascular risk factors were not associated with the risk of venous thromboembolism after adjustment for BMI. Hypertension, dyslipidaemia and diabetes may not be risk-factors for venous thromboembolism.

Axonal myelin decrease in the splenium in major depressive disorder.

The corpus callosum has become a key area of interest for researchers in severe mental illness. Disruptions in fractional anisotropy in the callosum have been reported in schizophrenia and major depressive disorder. No change has been reported in oligodendrocyte density and overall size of the callosum in either illness, suggesting that gross morphology is unchanged, but subtler organisational disruption may exist within this structure. Using high-resolution oil immersion microscopy, we examined the cross-sectional area of the nerve fibre and the axonal myelin sheath; and using standard high-resolution light microscopy, we measured the density of myelinated axons. These measurements were made in the splenium of the corpus callosum. Measures were taken in the sagittal plane in the callosal splenium to contrast with the previous similar examination of the callosal genu. Cases of major depressive disorder had significantly decreased mean myelin cross-sectional area (p = 0.014) per axon in the splenium than in controls or schizophrenia groups. There was no significant change in the density of myelinated axons. The results suggest a clear decrease of myelin in the axons of the callosal splenium in MDD, although this type of neuropathological study is unable to clarify whether this is caused by changes during life or has a developmental origin. In contrast with increased myelin in the callosal genu, this result suggests a longitudinal change in callosal myelination in major depressive disorder not present in normal or schizophrenic brains.

An observer-blinded randomized controlled pilot trial comparing localized immersion psoralen-ultraviolet A with localized narrowband ultraviolet B for the treatment of palmar hand eczema.

BACKGROUND: Hand eczema is a common inflammatory dermatosis that causes significant patient morbidity. Previous studies comparing psoralen-ultraviolet A (PUVA) with narrowband ultraviolet B (NB-UVB) have been small, nonrandomized and retrospective. OBJECTIVES: To conduct an observer-blinded randomized controlled pilot study using validated scoring criteria to compare immersion PUVA with NB-UVB for the treatment of chronic hand eczema unresponsive to topical steroids. METHODS: Sixty patients with hand eczema unresponsive to clobetasol propionate 0·05% were randomized to receive either immersion PUVA or NB-UVB twice weekly for 12 weeks with assessments at intervals of 4 weeks. The primary outcome measure was the proportion of patients achieving 'clear' or 'almost clear' Physician's Global Assessment (PGA) response at 12 weeks. Secondary outcome measures included assessment of the modified Total Lesion and Symptom Score (mTLSS) and the Dermatology Life Quality index (DLQI). RESULTS: In both treatment arms, 23 patients completed the 12-week assessment for the primary outcome measure. In the PUVA group, five patients achieved 'clear' and eight 'almost clear' [intention-to-treat (ITT) response rate 43%]. In the NB-UVB group, two achieved 'clear' and five 'almost clear' (ITT response rate 23%). For the secondary outcomes, median mTLSS scores were similar between groups at baseline (PUVA 9·5, NB-UVB 9) and at 12 weeks (PUVA 3, NB-UVB 4). Changes in DLQI were similar, with improvements in both groups. CONCLUSIONS: In this randomized pilot trial recruitment was challenging. After randomization, there were acceptable levels of compliance and safety in each treatment schedule, but lower levels of retention. Using validated scoring systems - PGA, mTLSS and DLQI - as measures of treatment response, the trial demonstrated that both PUVA and NB-UVB reduced the severity of chronic palmar hand eczema.

Autologous tolerogenic dendritic cells for rheumatoid and inflammatory arthritis.

OBJECTIVES: To assess the safety of intra-articular (IA) autologous tolerogenic dendritic cells (tolDC) in patients with inflammatory arthritis and an inflamed knee; to assess the feasibility and acceptability of the approach and to assess potential effects on local and systemic disease activities. METHODS: An unblinded, randomised, controlled, dose escalation Phase I trial. TolDC were differentiated from CD14+ monocytes and loaded with autologous synovial fluid as a source of autoantigens. Cohorts of three participants received 1×106, 3×106 or 10×106 tolDC arthroscopically following saline irrigation of an inflamed (target) knee. Control participants received saline irrigation only. Primary outcome was flare of disease in the target knee within 5 days of treatment. Feasibility was assessed by successful tolDC manufacture and acceptability via patient questionnaire. Potential effects on disease activity were assessed by arthroscopic synovitis score, disease activity score (DAS)28 and Health Assessment Questionnaire (HAQ). Immunomodulatory effects were sought in peripheral blood. RESULTS: There were no target knee flares within 5 days of treatment. At day 14, arthroscopic synovitis was present in all participants except for one who received 10×106 tolDC; a further participant in this cohort declined day 14 arthroscopy because symptoms had remitted; both remained stable throughout 91 days of observation. There were no trends in DAS28 or HAQ score or consistent immunomodulatory effects in peripheral blood. 9 of 10 manufactured products met quality control release criteria; acceptability of the protocol by participants was high. CONCLUSION: IA tolDC therapy appears safe, feasible and acceptable. Knee symptoms stabilised in two patients who received 10×106 tolDC but no systemic clinical or immunomodulatory effects were detectable. TRIAL REGISTRATION NUMBER: NCT01352858.

Phase Imaging Using Focused Polycapillary Optics.

Conventional radiographic techniques depend on attenuation, which provides low contrast between soft tissues. However, X rays can accumulate large differential phase delays even in weakly absorbing materials. This can produce significantly higher contrast. One technique for taking advantage of phase effects, propagation-based phase imaging, can yield marked edge enhancement but requires spatially coherent intense sources. Microfocus sources have sizes on the order of tens of microns but necessarily are low power and hence require long exposures. In this project, X-ray optical and computational techniques were explored to develop both edge-enhancement and phase imaging using a large spot conventional source. A polycapillary optic was employed to create a small secondary source from a large spot rotating anode X-ray generator. The secondary spot created by the focusing polycapillary optic was 114 µm ± 50 µm. Images of a 1.6 mm polyethylene rod were taken at varying distances from the optic. Edge enhancement was observed with a maximum edge-enhancement-to-noise ratio of 6.5. Insect images were also acquired and analyzed. Phase reconstructions were computed using two different approaches, weak attenuation and phase attenuation duality. Pure phase images were successfully reconstructed from the phase contrast images by employing the weak attenuation model.

Cadmium and other elements in tissues from four ungulate species from the Mackenzie Mountain region of the Northwest Territories, Canada.

Tissue samples from four ungulate species from the south Mackenzie Mountain region of the Northwest Territories (NT), Canada, were analysed for stable and radioactive elements and (15)N and (13)C stable isotopes. Elevated Cd concentrations in moose (Alces americanus) kidney have been observed in the region and are a health care concern for consumers of traditional foods. This study examined the factors associated with, and potential renal effects from, the accumulation of cadmium, and interactions with other elements in four sympatric ungulate species. Mean renal Cd concentration was highest in moose (48.3mg/kg ww), followed by mountain caribou (Rangifer tarandus caribou) (13.9mg/kg ww) and mountain goat (Oreamnos americanus) (5.78mg/kg ww). No local sources of Cd were evident and the elevated levels in moose are considered to be natural in origin. Conversely, total Hg concentration was significantly higher in mountain caribou kidney (0.21mg/kg ww) than in moose (0.011mg/kg ww). (134)Cs (t½=2.1 y) in mountain goat and Dall's sheep (Ovis dalli) muscle is evidence of deposition from the Fukushima reactor accident in 2011. (137)Cs (t½=30.2 y) in all four ungulates is primarily a remnant of the nuclear weapons tests of the 1960s. The levels of both nuclides are low and the risk to the animals and people consuming them is negligible. Stable isotope δ(15)N and δ(13)C signatures in muscle showed a separation between the mountain caribou, with a lichen-dominated diet, and moose, which browse shrubs and forbs. Isotope signatures for mountain goat and Dall's sheep showed generalist feeding patterns. Differences in elemental and radionuclide levels between species were attributed to relative levels of metal accumulation in the different food items in the diets of the respective species. Kidneys from each species showed minor histological changes in the proximal tubule and glomerulus, although glomerular changes were rare and all changes were rare in mountain goat kidney. Kidney function was not expected to be affected in any species. Provisional Monthly Intake recommendations from the WHO indicate that Cd in moose organs will continue to be a public health care concern. However, traditional foods continue to be an important nutritional component of northern diets, particularly in consideration of the shift towards store-bought food.

Detection of (135) Cs by accelerator mass spectrometry.

RATIONALE: The ability to measure both (135) Cs and (137) Cs can provide an estimate of the age and source of Cs isotopes in an environmental sample. Accelerator mass spectrometry (AMS) consistently reports lower abundance sensitivities than other techniques and, with the addition of an on-line reaction cell, simpler isobaric suppression. Therefore, an AMS methodology was developed to measure Cs isotopes using CsF2- as the initial anion. METHODS: The ion beam is passed through the Isobar Separator for Anions (ISA) where it is captured by radiofrequency quadrupoles in a gas cell before injection into the tandem accelerator. In the ISA, the beam reacts with O2 gas, selectively removing the BaF2- and leaving the Cs analyte to be reaccelerated and sent through the remainder of the AMS system. RESULTS: The BaF2- signal was attenuated by a factor of 10(5) in the ISA while 25% of the original CsF2- current was transmitted into the accelerator. (135) Cs was measured without any interference from (133) Cs to an abundance sensitivity of 1.3 × 10(-10) . The abundances of four stable Ba isotopes (masses 133, 134, 135 and 137) were measured and no isotope-dependent bias was detected using the ISA in vacuum. CONCLUSIONS: The results demonstrate the feasibility of measuring long-lived Cs isotopes without Ba interference by AMS with on-line isobar separation and the ability to use shorter lived Cs isotopes for yield tracing.

Is post-pneumonia chest X-ray for lung malignancy useful? Results of an audit of current practice.

BACKGROUND/AIM: Patients with community-acquired pneumonia (CAP) are often screened with repeat chest X-ray within 6-12 weeks following an admission. This practice is aimed to detect underlying lung malignancy, which can be difficult to identify initially when an acute infiltrate is present on X-ray. We conducted a study on the use of follow-up chest X-rays after an admission with CAP to determine the yield of suspected or diagnosed cancer. METHODS: During the 2-year period, January 2010-January 2012, we evaluated all patients over the age of 50 who had no previous history of lung cancer and were admitted to Hutt Hospital with CAP. RESULTS: A total of 302 patients was included. Of these, 53% received a follow-up chest X-ray within 6-12 weeks after admission. A total of six patients (2.0%) was diagnosed with lung cancer based on a chest X-ray within 6-12 weeks after admission. After a median period of follow up of 19.5 months, a further five patients who had normal chest X-ray were diagnosed with lung malignancy. CONCLUSION: The majority of patients were screened with follow-up X-rays. The yield from a 6- to 12-week chest X-ray following CAP is low, which is consistent with previous studies. The development of clear guidelines to ensure identification of patient groups at significantly high risk of lung cancer is important to increase the sensitivity of screening. High yielding strategies, such as low-dose computed tomography, should be considered as an alternative.

Monochromatic X-ray imaging using a combination of doubly curved crystal and polycapillary X-ray lens.

A monochromatic X-ray imaging setup based on a combination of a doubly curved crystal and a polycapillary focusing X-ray lens was designed. In this setup, the bent crystal optic was used not only to monochromatize but also to focus the divergent X-ray beam from a conventional X-ray source to form a monochromatic X-ray focal spot with a size of 426 × 467 µm2 at 17.5 keV. The beam expanding from this focal point was focused by the polycapillary optic to obtain a focal spot which was then used as the monochromatic X-ray imaging virtual source. The output focal spot size of the focusing polycapillary optic at 17.5 keV was 97 µm. Compared with the beam expansion after the focal spot of the bent crystal optic, the beam expansion after the focal spot of the focusing polycapillary optic was relatively large. This was helpful for magnifying the X-ray image of the sample. The focused beam was helpful to decrease the exposure time for imaging small samples.

A pocket of very high suicide rates in a non-violent, egalitarian and cooperative population of South-East Asia.

BACKGROUND: Extremely high rates of suicide localized within subgroups of populations where suicide is rare have been reported. We investigated this intriguing observation in a population of South-East Asia, where local culture should theoretically be preventative of suicide. METHOD: A team including an anthropologist and a psychiatrist surveyed all cases of suicide that had occurred over 10 years in four isolated regions. A psychological autopsy was carried out comparing each suicide case with two matched control cases. RESULTS: In a region of 1192 inhabitants, 16 suicides occurred, leading to an annual suicide rate of 134/1,000,00 which is 10 times the rate in the USA or Canada. By contrast, three ethnically similar distant communities showed low to null rates. The gender ratio was three males to one female and two-thirds of cases were aged below 35 years. Methods of suicide were poisoning and hanging and motives mainly included interpersonal discord. The pattern of developmental and clinical risk factors was somewhat different from Western countries, showing no childhood maltreatment, only one case of alcohol/substance abuse and impulsive-aggressive personality but elevated rates of social anxiety. Suicide cases had very high frequencies of second-degree biological relatives who committed suicide. CONCLUSIONS: Our study confirms a persistent phenomenon of high suicide rates restricted to a subgroup of a pre-industrialized population. We hypothesized this might be explained by isolation and endogamy, which may have promoted the selection/amplification of genetic vulnerability factors, or a contagion effect. These findings shed light on suicide from both a singular and a universal perspective, suggesting that particular local conditions may significantly modulate the rate of this complex behavior.

Isolation and characterization of chitin-degrading micro-organisms from the faeces of Goeldi's monkey, Callimico goeldii.

AIMS: The objective of this study was the isolation and characterization of chitin-degrading micro-organisms from the faeces of the insectivorous Goeldi's monkey, Callimico goeldii. METHODS AND RESULTS: Faeces samples were screened for chitin-degrading bacteria using basal medium in which chitin was included as the carbon and energy source. Of fifteen bacterial isolates with chitin-degrading activity, fourteen were also capable of degrading cellulose. All isolates were either aerobes or facultative anaerobes. CONCLUSIONS: Phylogenetic analyses of those isolates exhibiting strongest activity, as determined by the most distinctive zones of clearing in chitin-supplemented medium, were identified as Cellulosimicrobium spp., Arthrobacter spp., Staphylococcus spp. and Enterobacteriaceae. SIGNIFICANCE AND IMPACT OF THE STUDY: This study reports on the isolation of chitin-degrading microflora from nonhuman primates. Considering that chitin and cellulose are the most abundant naturally occurring polymers, it is of interest to note that the majority of isolates are capable of digesting both substrates. This may be of significance given that omnivorous primates live in seasonal environments, where the availability of food items varies with the seasons. Furthermore, given the presence of a chitin-degrading microflora, this may have implications, in terms of the inclusion of fungi and/or insects in the diets of these animals in captivity, whether as part of medical research or conservation programmes.

Neuropathological changes in the substantia nigra in schizophrenia but not depression.

Schizophrenia is a chronic, disabling neuropsychiatric disorder characterised by positive, negative and cognitive symptoms. The aetiology is not known, although genetic, imaging and pathological studies have implicated both neurodevelopmental and neurodegenerative processes. The substantia nigra is a basal ganglia nucleus responsible for the production of dopamine and projection of dopaminergic neurons to the striatum. The substantia nigra is implicated in schizophrenia as dopamine has been heavily implicated in the dopamine hypothesis of schizophrenia and the prevalent psychotic symptoms and the monoamine theory of depression, and is a target for the development of new therapies. Studies into the major dopamine delivery pathways in the brain will therefore provide a strong base in improving knowledge of these psychiatric disorders. This post-mortem study examines the cytoarchitecture of dopaminergic neurons of the substantia nigra in schizophrenia (n = 12) and depression (n = 13) compared to matched controls (n = 13). Measures of nucleolar volume, nuclear length and nuclear area were taken in patients with chronic schizophrenia and major depressive disorder against matched controls. Astrocyte density was decreased in schizophrenia compared to controls (p = 0.030), with no change in oligodendrocyte density observed. Significantly increased nuclear cross-sectional area (p = 0.017) and length (p = 0.021), and increased nucleolar volume (p = 0.037) in dopaminergic neurons were observed in schizophrenia patients compared with controls, suggesting nuclear pleomorphic changes. No changes were observed in depression cases compared to control group. These changes may reflect pathological alterations in gene expression, neuronal structure and function in schizophrenia.

The oxidative costs of territory quality and offspring provisioning.

The costs of reproduction are an important constraint that shapes the evolution of life histories, yet our understanding of the proximate mechanism(s) leading to such life-history trade-offs is not well understood. Oxidative stress is a strong candidate measure thought to mediate the costs of reproduction, yet empirical evidence supporting that increased reproductive investment leads to oxidative stress is equivocal. We investigated whether territory quality and offspring provisioning increase oxidative stress in male snow buntings (Plectrophenax nivalis) using a repeated sampling design. We show that arrival oxidative stress is not a constraint on territory quality or the number of offspring fledged. Nevertheless, owners of higher-quality territories experienced an oxidative cost, with this cost increasing more rapidly in younger males. Males that provisioned offspring at a high rate also experienced increased oxidative stress. Together, these findings support the potential role of oxidative stress in mediating life-history trade-offs. Future work should consider that reproductive workload is not limited to offspring care, and other activities - including territory defence - may contribute significantly to the costs of reproduction.

Neuropathological changes in the nucleus basalis in schizophrenia.

The nucleus basalis has not been examined in detail in severe mental illness. Several studies have demonstrated decreases in glia and glial markers in the cerebral cortex in schizophrenia, familial bipolar disorder and recurrent depression. Changes in neocortical neuron size and shape have also been reported. The nucleus basalis is a collection of large cholinergic neurons in the basal forebrain receiving information from the midbrain and limbic system, projecting to the cortex and involved with attention, learning and memory, and receives regulation from serotonergic inputs. Forty-one cases aged 41-60 years with schizophrenia or major depressive disorder with age-matched controls were collected. Formalin-fixed paraffin-embedded coronal nucleus basalis sections were histologically stained for oligodendrocyte identification with cresyl-haematoxylin counterstain, for neuroarchitecture with differentiated cresyl violet stain and astrocytes were detected by glial fibrillary acid protein immunohistochemistry. Cell density and neuroarchitecture were measured using Image Pro Plus. There were larger NB oval neuron soma in the combined schizophrenia and major depression disorder groups (p = 0.038), with no significant change between controls and schizophrenia and major depression disorder separately. There is a significant reduction in oligodendrocyte density (p = 0.038) in the nucleus basalis in schizophrenia. The ratio of gemistocytic to fibrillary astrocytes showed a greater proportion of the former in schizophrenia (18.1 %) and major depressive disorder (39.9 %) than in controls (7.9 %). These results suggest glial cell abnormalities in the nucleus basalis in schizophrenia possibly leading to cortical-limbic disturbance and subcortical dysfunction.

Factors influencing career decisions in internal medicine.

BACKGROUND: Numerous factors influence career decisions for internal medicine trainees and Fellows. There is a perception that a greater emphasis is placed on work-family balance by younger physicians. AIMS: To determine the characteristics of the modern internal medicine workforce and ascertain whether job flexibility is important to career decision-making. We hypothesised that factors which reflect flexibility would be highly influential in decision-making, especially for women and those with young children. METHODS: A questionnaire was mailed to 250 New Zealand internal medicine trainees and Fellows. It focused on factors, including job flexibility, interest and collegial support, and included demographic details which were primarily aimed at ascertaining family responsibilities. RESULTS: Response rate was 54%. The majority of female physicians are the main person responsible for their children (62%), and the majority of their partners work full-time (80%). This contrasts with male physicians, of whom only 4% are the main person responsible for their children. Flexibility was found to be more influential in women, those with young children, trainees and those working in outpatient-based subspecialties. However, contrary to our original hypothesis, flexibility was not reported to be highly influential in any group, with career choice being most influenced by interest and enjoyment, intellectual challenge and variety within the job. CONCLUSION: It is hoped that results will inform employers and those involved with training to enable them to better cater for the needs of the workforce and also encourage trainees to consider future family commitments when making career decisions.

Associations between smoking and blood-group, and the risk of dyslipidaemia amongst French women.

Dyslipidaemia is a major risk factor for cardio-vascular disease, as it promotes atherosclerosis. While cross-sectional studies have identified higher serum cholesterol amongst individuals with the A blood group, there is less evidence from prospective studies whether this translates into a higher risk of dyslipidaemia that requires treatment, nor if this genetic factor interacts with smoking status. This study aimed to prospectively determine potential associations between smoking, ABO blood groups, and risk of incident dyslipidaemia requiring treatment, and to assess associations over strata of blood ABO group. We assessed associations between blood ABO group, smoking and dyslipidaemia in 74,206 women participating in the E3N cohort. We included women who did not have cardiovascular disease at baseline. Logistic regression was used to determine associations between ABO group, smoking and prevalent dyslipidaemia at baseline. Cox proportional hazard models were then used to determine if blood ABO group and smoking were associated with the risk of incident dyslipidaemia, amongst women free of dyslipidaemia at baseline. At baseline 28,281 women with prevalent dyslipidaemia were identified. Compared to the O-blood group, the non-O blood group was associated higher odds of with prevalent dyslipidaemia (ORnon-O = 1.09 [1.06: 1.13]). Amongst the women free of dyslipidaemia at baseline, 6041 incident cases of treated dyslipidaemia were identified during 454,951 person-years of follow-up. The non-O blood groups were associated with an increased risk of dyslipidaemia when compared to the O-group (HRnon-O = 1.16 [1.11: 1.22]), specifically the A blood-group (HRA = 1.18 [1.12: 1.25]). Current smokers were associated with an increased risk of incident dyslipidaemia (HR smokers = 1.27 [1.16: 1.37]), compared to never-smokers. No evidence for effect modification between smoking and ABO blood group was observed (p-effect modification = 0.45), although the highest risk was observed among AB blood group women who smoked (HR = 1.76 [1.22: 2.55]). In conclusion, the non-O blood groups, specifically the A group were associated with an increased risk of dyslipidaemia. Current smokers were associated with a 30% increased risk of dyslipidaemia. These results could aid in personalised approaches to the prevention of cardiovascular risk-factors.

Development of innovative simulation teaching for advanced general practice clinical pharmacists.

BACKGROUND: Advanced General Practice Clinical Pharmacists (GPCPs) are expected to manage patients by undertaking clinical assessment then make safe, competent autonomous decisions. Simulation provides a safe learning environment to develop clinical skills, but is rarely used for postgraduate pharmacist development. AIM: Design and deliver innovative simulation teaching to support Advanced GPCPs in Scotland. SETTING: General Practice. DEVELOPMENT: Experienced clinical pharmacy educators designed a simulation day with ten scenarios based on general practice clinical presentations. Learning objectives were mapped to the National Advanced GPCP competency framework. IMPLEMENTATION: Simulation took place at the National Skills Education Hub, Louisa Jordan National Hospital, Glasgow, November 2020. Participants were briefed prior to each immersive simulation. Mannequins were used if clinical signs were expected to be identified on examination. Verbal and written feedback was given after each simulation. EVALUATION: Pre and post simulation questionnaires were developed. Increase in confidence and competence were reported in all areas pertaining to application of consultation and clinical skills. Qualitative comments from the participants regarding the training course were also favourable with respondents highlighting the value of the training, especially in terms of developing confidence via the real-time feedback. CONCLUSION: This innovative simulation evaluated as being of value to GPCPs in developing clinical confidence and competence when dealing with a variety of typical General Practice scenarios. Plans are underway to establish a Scottish Pharmacy Simulation Faculty which could support this training in each health board.