Towards inclusive learning environments in post-graduate medical education: stakeholder-driven strategies in Dutch GP-specialty training.

BACKGROUND: A recent study found that ethnic minority General Practice (GP)-trainees receive more negative assessments than their majority peers. Previous qualitative research suggested that learning climate-related factors play a pivotal role in unequal opportunities for trainees in post-graduate medical settings, indicating that insufficient inclusivity had put minority students at risk of failure and dropout. STUDY OBJECTIVES: We aimed to develop broadly supported strategies for an inclusive learning climate in Dutch GP-specialty training. METHODS: We employed Participatory Action Research (PAR)-methods, incorporating Participatory Learning and Action (PLA)-techniques to ensure equal voices for all stakeholders in shaping Diversity, Equity, and Inclusion (DEI)-strategies for GP-specialty training. Our approach engaged stakeholders within two pilot GP-specialty training institutes across diverse roles, including management, support staff, in-faculty teachers, in-clinic supervisors, and trainees, representing ethnic minorities and the majority population. Purposeful convenience sampling formed stakeholder- and co-reader groups in two Dutch GP-specialty training institutes. Stakeholder discussion sessions were based on experiences and literature, including two relevant frameworks, and explored perspectives on the dynamics of potential ethnic minority trainees' disadvantages and opportunities for inclusive strategies. A co-reader group commented on discussion outcomes. Consequently, a management group prioritized suggested strategies based on expected feasibility and compatibility. RESULTS: Input from twelve stakeholder group sessions and thirteen co-readers led to implementation guidance for seven inclusive learning environment strategies, of which the management group prioritized three: • Provide DEI-relevant training programs to all GP-specialty training stakeholders; • Appoint DEI ambassadors in all layers of GP-specialty training; • Give a significant voice to minority GP-trainees in their education. CONCLUSION: The study's participatory approach engaged representatives of all GP-specialty training stakeholders and identified seven inclusive learning climate strategies, of which three were prioritized for implementation in two training institutions.

Anorectal Neisseria gonorrhoeae infections in women with and without reported anal sex and sex workers in sexual health centres in the Netherlands: a retrospective cohort study.

BACKGROUND: Control of Neisseria gonorrhoeae infection (gonorrhoea) depends on effective testing strategies. Anorectal testing in women is often done on indication of anal sex; however, anorectal infections are seen with and without anal exposure, possibly caused by autoinoculation. This study aims to enhance understanding of anorectal infections in women, by identifying risk factors for anorectal diagnosis. METHODS: In this retrospective cohort study we used national surveillance data from Dutch sexual health centres from Jan 1, 2016, to Dec 31, 2021. We included cisgender women having sex with men who were tested urogenitally and anorectally for gonorrhoea. Due to different testing policies, we identified three groups: women who had not reported recent anal sex (in the past 6 months), women who had reported recent anal sex, and sex workers. Extracted data for analyses included demographics, sexual behaviour, and diagnosis of a sexually transmitted infection (STI). Per group, multivariable models using Firth's penalised maximum likelihood logistic regression were constructed, identifying determinants of anorectal gonorrhoea among all women and among gonorrhoea-positive women only. Variables included in model construction were age, education level, migration background, number of partners, condom use, partner notification, STI symptoms, having a partner who has sex with men (MSM) or a migrant partner, previous STI test, anal sex, and chlamydia and gonorrhoea diagnoses per anatomical location. FINDINGS: In total, 117 693 women were included: 43 757 women without reported recent anal sex, 51 728 women with reported recent anal sex, and 22 208 sex workers. In all three groups, around 2% of women were gonorrhoea positive, and 70% or more of women had an anorectal infection. The strongest determinant of anorectal gonorrhoea was a concurrent urogenital gonorrhoea diagnosis (adjusted odds ratios [aOR] 782 [95% CI 605-1018]) among women without reported recent anal sex (612 [490-768] among women with reported recent anal sex, and 464 [335-652] among sex workers). Among gonorrhoea-positive women, determinants of anorectal gonorrhoea were urogenital and anorectal chlamydia co-infection (aOR 2·03 [95% CI 1·38-3·02], for women without reported anal sex) and migration background (1·44 [1·02-2·06], for women with reported anal sex). Determinants among sex workers were condomless sex (2·43 [1·55-3·82]), anal sex (1·71 [1·10-2·66]), MSM or migrant partner (1·78 [1·13-2·79]), and urogenital and anorectal chlamydia co-infection (2·28 [1·11-5·14]). INTERPRETATION: These findings support the possibility of an autoinoculation process from the urogenital to the anorectal location due to the very strong correlation between urogenital and anorectal gonorrhoea, and due to the similarity of results across all three groups. Current testing strategies could miss anorectal infections, which should be considered when developing gonorrhoea prevention and control guidelines. FUNDING: None.

The Malnutrition Awareness Scale for community-dwelling older adults: Development and psychometric properties.

BACKGROUND & AIMS: Qualitative studies suggest that malnutrition awareness is poor in older adults. The aim of this study was to develop a questionnaire to quantitatively assess malnutrition awareness in community-dwelling older adults aged 60+ years. METHODS: The Malnutrition Awareness Scale (MAS) was developed based on the awareness phase of the Integrated-Change model, and included four domains: knowledge, perceived cues, risk perceptions, and cognizance. Twenty-six scale items were developed using results from mainly qualitative research and the expertise of the authors. Items were piloted in 10 Dutch older adults using the Thinking Aloud method to optimize wording. In a feasibility study, annoyance, difficulty and time to complete the MAS and its comprehensibility were tested. After final revisions, the MAS was applied to a large sample to test its psychometric properties (i.e., inter-item correlations, Cronbach's alpha, score distribution) and relevance of the items was rated on a 5-point scale by 12 experts to determine content validity. RESULTS: The feasibility study (n = 42, 55 % women, 19 % 80+ y) showed that the MAS took 12 ± 6 min to complete. Most participants found it not (at all) annoying (81 %) and not (at all) difficult (79 %) to complete the MAS, and found it (very) comprehensible (83 %). Psychometric analyses (n = 216, 63 % women, 28 % 80+ y) showed no redundant items, but two items correlated negatively with other items, and one correlated very low. After removal, the final MAS consists of 23 items with a min-max scoring range from 0 to 22 (with higher scores indicating higher awareness) and an overall Cronbach's alpha of 0.67. The mean MAS score in our sample (n = 216) was 14.8 ± 3.2. The lowest obtained score was 6 (n = 3) and the highest 22 (n = 1), indicating no floor or ceiling effects. Based on the relevance rating, the overall median across all 22 items was 4.0 with IQR 4.0-5.0. CONCLUSION: The Malnutrition Awareness Scale is a novel, feasible and reliable tool with good content validity to quantitively assess malnutrition awareness in community-dwelling older adults. The scale is now ready to identify groups with poor malnutrition awareness, as a basis to start interventions to increase malnutrition knowledge and awareness.

Appropriate medication use in Dutch terminal care: study protocol of a multicentre stepped-wedge cluster randomized controlled trial (the AMUSE study).

BACKGROUND: Polypharmacy is common among patients with a limited life expectancy, even shortly before death. This is partly inevitable, because these patients often have multiple symptoms which need to be alleviated. However, the use of potentially inappropriate medications (PIMs) in these patients is also common. Although patients and relatives are often willing to deprescribe medication, physicians are sometimes reluctant due to the lack of evidence on appropriate medication management for patients in the last phase of life. The aim of the AMUSE study is to investigate whether the use of CDSS-OPTIMED, a software program that gives weekly personalized medication recommendations to attending physicians of patients with a limited life expectancy, improves patients' quality of life. METHODS: A multicentre stepped-wedge cluster randomized controlled trial will be conducted among patients with a life expectancy of three months or less. The stepped-wedge cluster design, where the clusters are the different study sites, involves sequential crossover of clusters from control to intervention until all clusters are exposed. In total, seven sites (4 hospitals, 2 general practices and 1 hospice from the Netherlands) will participate in this study. During the control period, patients will receive 'care as usual'. During the intervention period, CDSS-OPTIMED will be activated. CDSS-OPTIMED is a validated software program that analyses the use of medication based on a specific set of clinical rules for patients with a limited life expectancy. The software program will provide the attending physicians with weekly personalized medication recommendations. The primary outcome of this study is patients' quality of life two weeks after baseline assessment as measured by the EORTC QLQ-C15-PAL questionnaire, quality of life question. DISCUSSION: This will be the first study investigating the effect of weekly personalized medication recommendations to attending physicians on the quality of life of patients with a limited life expectancy. We hypothesize that the CDSS-OPTIMED intervention could lead to improved quality of life in patients with a life expectancy of three months or less. TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov (NCT05351281, Registration Date: April 11, 2022).

The sex difference in self-rated health among older Turkish and Moroccan migrants in the Netherlands: an exploratory study of contributing determinants.

BACKGROUND: Although being a woman and having a migration background are strong predictors of poor self-rated health among (older) adults, research on the sex difference in self-rated health among (older) migrants remains limited. This study therefore aims to investigate this topic and explore the contributing role of determinants of self-rated health. METHODS: Cross-sectional data from 360 Turkish-Dutch and Moroccan-Dutch adults aged 55-65 as part of the Longitudinal Aging Study Amsterdam (LASA) were used. Self-rated health (good versus poor) was measured by a single item question. Univariate age-adjusted logistic regression analysis was used to investigate the sex difference in self-rated health and the contribution of sex differences in sensitivity (strength of the association) and/or exposure (prevalence) to socio-demographic, social, lifestyle or health-related determinants of self-rated health. RESULTS: Women had a 0.53 times lower odds (95%CI:0.40-0.82, p = 0.004) on good self-rated health compared to men. Women more often having a lower education level, living alone and having a higher prevalence of depressive symptoms, chronic diseases and especially functional limitations contributed to the lower self-rated health among women. In contrast, men were more sensitive to the impact of memory complaints, depressive symptoms, visual difficulties and functional limitations. CONCLUSIONS: Older Turkish-Dutch and Moroccan-Dutch women have a significant lower self-rated health compared to men. Women having a higher exposure to both socio-demographic and health-related determinants of self-rated health, which contributed to the sex difference. Future research should take these differences in self-rated health and determinants between women and men into account when investigating health among older migrants.

Systematic review of the effectiveness of innovative, gamified interventions for cognitive training in paediatric acquired brain injury.

Effectiveness of innovative, gamified interventions (i.e., Augmented Reality, Computer-Based Cognitive Retraining [CBCR], and Virtual Reality [VR] in conjunction with a Serious Game) for cognitive training in paediatric ABI was evaluated. Studies were identified on PsycINFO, PubMed and Scopus; last searched 4 January 2022. Eligibility criteria were participants diagnosed with ABI and aged ≤ 18 years, experimental intervention to train cognition, cognition assessed pre- and post-intervention at: (1) The level of function, or (2) The level of activity, and written in English. ROB 2 and ROBINS-I were utilised to assess risk of bias. Extracted study characteristics were methods, participants, interventions, outcomes, and results. Seven studies were included, comprising six CBCR studies and one VR study, with 182 participants. Following CBCR: (1) Improvements were observed in several cognitive functions, but there was inconsistent evidence; (2) Improvements were reported in attention and executive functions (EF) at home and at school. Following VR: (1) Improvements were observed in attention and EF; (2) Not evaluated. Due to the small number of included studies with (relatively) small and heterogeneous samples, only a cautious interpretation of the evidence was provided. There is a need for carefully designed studies with more attention to inter-individual differences and generalisation to daily life.

Responsiveness and meaningful thresholds of PROMIS pain interference, fatigue, and physical function forms in adults with idiopathic inflammatory myopathies: Report from the OMERACT Myositis Working Group.

BACKGROUND: A series of qualitative studies conducted by the OMERACT Myositis Working Group identified pain interference, fatigue, and physical function as highly important life impact domains for adults with idiopathic inflammatory myositis (IIM). In this study, our goal was to assess the responsiveness and minimal important difference of PROMIS pain interference (6a), fatigue (7a), and physical function (8b). METHODS: Adults with IIM from USA, Netherlands, Korea, Sweden, and Australia with two "clinical" visits were enrolled in this prospective study. Anchor questions on a Likert scale were collected at baseline, and manual muscle testing (MMT), physician and patient reported global disease activity, and PROMIS instruments were collected at both visits. Responsiveness was assessed with i) ANOVA, ii) paired t-test, effect size and standardized response mean, and iii) Pearson correlation. Minimal important difference (MID), minimal important change (MIC) and minimal detectable change (MDC) values were calculated. RESULTS: 114 patients with IIM (median age 60, 60 % female) completed both visits. Changes in PROMIS instruments were significantly different among anchor categories. Patients who reported improvement had a significant improvement in their PROMIS scores with at least medium effect size, while patients who reported worsening and stability did not show a significant change with weak effect size. PROMIS instruments had weak to moderate correlations with MMT, patient and physician global disease activity. MID was approximately 2-3 points for Pain Interference and 3-4 points for Fatigue and Physical Function forms based on the method used. MIC was approximately 4-5 for improvement of all the instruments, while MDC was 1.7-2 points for Pain Interference and Physical Function and 3.2-3.9 for Fatigue. CONCLUSION: This study provides evidence towards the responsiveness of the PROMIS instruments in a large international prospective cohort of adults with IIM supporting their use as PROMs in adult myositis.

Can mindful eating buffer against the influence of neighbourhood fast food exposure on unhealthy food intake?

A food-abundant environment is associated with unhealthy food intake, but not everyone is affected to the same degree. Mindful eating, which is eating with attention and awareness, has been associated with less external eating and less food cravings, and could act as a protective factor against influences from the food environment. The current study aimed to investigate whether the association between exposure to fast-food around the home and unhealthy food intake was moderated by mindful eating. The study was conducted in 1086 Dutch adults of 55 years and older of the Longitudinal Aging Study Amsterdam study. The mindful eating domains (Mindful Eating Behavior Scale) were tested as moderating variables in the linear regression models with absolute and relative density of fast-food outlets in the neighbourhood (400, 800 and 1600m) as independent variables and unhealthy food intake (snacks (g/d)) and saturated fat as a percentage of total energy intake (en%)) as dependent variable. Bootstrapping with 5000 samples using the pick-a-point approach showed that after adjustments, only two out of 48 interactions terms were statistically significant: Eating with Awareness (EwA) and Eating without Distraction (EwD) moderated the positive association between the relative density of fast-food outlets and saturated fat (en%) respectively in a buffer of 800m (interaction EwA: B = -0.84, 95% CI [-1.46; -0.22]) and in a buffer of 1600m (interaction EwD: B = -0.82, 95% CI [-1.61; -0.04]). The results of the current study indicate that mindful eating cannot buffer against the influence of the fast-food abundant environment on unhealthy food intake. Future research is needed to confirm these findings, for example in younger populations.

Perspectives of older women in the Netherlands: identifying motivators and barriers for healthy lifestyles and determinants of healthy aging.

BACKGROUND: Women have a higher life expectancy than men but experience more years with physical disabilities in daily life at older ages, especially women with a migration background. This pinpoints older women as an important target group for strategies that stimulate healthy lifestyle, which benefits healthy aging. Our study investigates motivators and barriers for healthy lifestyles and perspectives on determinants of healthy aging of older women. This provides essential information for developing targeted strategies. METHODS: Data was collected by semi-structured digital interviews from February till June 2021. Women aged 55 years and older living in the Netherlands (n = 34) with a native Dutch (n = 24), Turkish (n = 6) or Moroccan (n = 4) migration background were included. Two main subjects were investigated: (1) motivators and barriers on their current lifestyles regarding smoking, alcohol consumption, physical activity, diet and sleep and (2) perspectives on determinants of healthy aging. Interviews were analyzed using Krueger's framework. RESULTS: Personal health was the most common motivator for a healthy lifestyle. In addition, peer pressure and being outdoors were specific motivators for physical activity. Bad weather conditions and personal dislike to be active were specific barriers. The social environment, personal preferences and personal belief to compensate with other healthy lifestyle behaviors were barriers for low alcohol consumption. Personal preferences (liking unhealthy food and not making time) were the main barriers for a healthy diet. Sleep was not perceived as a form of lifestyle behavior, but rather as a personal trait. Since there were no smokers, specific barriers were not mentioned. For Turkish-Dutch and Moroccan-Dutch women, additional barriers and motivators were culture and religion. These were strong motivators to abstain from alcohol consumption and smoking, but a barrier for a healthy diet. With regard to perspectives on determinants of healthy aging, positive views on aging and being physically active were perceived as most important. Women often wanted to increase their physical activity or healthy diet to stimulate healthy aging. Among Turkish-Dutch and Moroccan-Dutch women, healthy aging was also perceived as something in the hands of God. CONCLUSIONS: Although motivators and barriers for a healthy lifestyle and perspectives on healthy aging vary for distinct lifestyles, personal health is a common motivator across all lifestyles. Having a migration background added culture and religion as distinct barriers and motivations. Strategies to improve lifestyle among older women should therefore have a tailored, culture sensitive approach (if applicable) for distinct lifestyle factors.

Effects of reduction technique for acute anterior shoulder dislocation without sedation or intra-articular pain management: a systematic review and meta-analysis.

INTRODUCTION: Anterior shoulder dislocations are commonly seen in the emergency department for which several closed reduction techniques exist. The aim of this systematic review is to identify the most successful principle of closed reduction techniques for an acute anterior shoulder dislocation in the emergency department without the use of sedation or intra-articular lidocaine injection. METHODS: A literature search was conducted up to 15-08-2022 in the electronic databases of PubMed, Embase and CENTRAL for randomized and observational studies comparing two or more closed reduction techniques for anterior shoulder dislocations. Included techniques were grouped based on their main operating mechanism resulting in a traction-countertraction (TCT), leverage and biomechanical reduction technique (BRT) group. The primary outcome was success rate and secondary outcomes were reduction time and endured pain scores. Meta-analyses were conducted between reduction groups and for the primary outcome a network meta-analysis was performed. RESULTS: A total of 3118 articles were screened on title and abstract, of which 9 were included, with a total of 987 patients. Success rates were 0.80 (95% CI 0.74; 0.85), 0.81 (95% CI 0.63; 0.92) and 0.80 (95% CI 0.56; 0.93) for BRT, leverage and TCT, respectively. No differences in success rates were observed between the three separate reduction groups. In the network meta-analysis, similar yet more precise effect estimates were found. However, in a post hoc analysis the BRT group was more successful than the combined leverage and TCT group with a relative risk of 1.33 (95% CI 1.19, 1.48). CONCLUSION: All included techniques showed good results with regard to success of reduction. The BRT might be the preferred technique for the reduction of an anterior shoulder dislocation, as patients experience the least pain and it results in the fastest reduction.

Estimating Density Dependence, Environmental Variance, and Long-Term Selection on a Stage-Structured Life History.

AbstractA method for analyzing long-term demographic data on density-dependent stage-structured populations in a stochastic environment is derived to facilitate comparison of populations and species with different life histories. We assume that a weighted sum of stage abundances, N, exerts density dependence on stage-specific vital rates of survival and reproduction and that N has a small or moderate coefficient of variation. The dynamics of N are approximated as a univariate stochastic process governed by three key parameters: the density-independent growth rate, the net density dependence, and environmental variance in the life history. We show how to estimate the relative weighs of stages in N and the key parameters. Life history evolution represents a stochastic maximization of a simple function of the key parameters. The long-term selection gradient on the life history can be expressed as a vector of sensitivities of this function with respect to density-independent, density-dependent, and stochastic components of the vital rates. To illustrate the method, we analyze 38 years of demographic data on a great tit population, estimating the key parameters, which accurately predict the observed mean, coefficient of variation, and fluctuation rate of N; we also evaluate the long-term selection gradient on the life history.

Improved ROSC rates in out-of-hospital cardiac arrest patients after introduction of a text message alert system for trained volunteers.

OBJECTIVE: To evaluate whether a text message (TM) alert system for trained volunteers contributed to early cardiopulmonary resuscitation, the use of automated external defibrillators (AEDs), return of spontaneous circulation (ROSC) and survival in out-of-hospital cardiac arrest (OHCA) patients in a region with above-average survival rates. DESIGN: Data on all OHCA patients in 2012 (non-TM group) were compared with those of all OHCA patients in 2018 (TM group). The association of the presence of a TM alert system with ROSC and survival was assessed with multivariate regression analyses. RESULTS: TM responders reached 42 OHCA patients (15.9%) earlier than the first responders or ambulance. They connected 31 of these 42 OHCA patients (73.8%) to an AED before the ambulance arrived, leading to a higher percentage of AEDs being attached in 2018 compared to the 2012 non-TM group (55% vs 46%, p = 0.03). ROSC was achieved more often in the TM group (61.0% vs 29.4%, p < 0.01). Three-month and 1­year survival did not differ significantly between the two groups (29.3% vs 24.3%, p = 0.19, and 25.9% vs 23.5%, p = 0.51). Multivariate regression analyses confirmed the positive association of ROSC with the TM alert system (odds ratio 1.49, 95% confidence interval 1.02­2.19, p = 0.04). CONCLUSION: A TM alert system seems to improve the chain of survival; because TM responders reached patients early, AEDs were attached more often and more OHCA patients achieved ROSC. However, the introduction of a TM alert system was not associated with improved 3­month or 1­year survival in a region with above-average survival rates.

A combined cowhide/gelatine soft tissue simulant for ballistic studies.

The ballistic resistance of a combined soft tissue simulant was studied, consisting of gelatine as a simulant for human muscle tissue and tanned cowhide (leather) as a simulant for human skin. The simulant was manufactured by applying cowhide to liquid ballistic gelatine, as the gelatine solidified in its mould. Combining a skin and muscle tissue simulant in this adhered way opens the possibility to produce purpose-built proxies for human body parts in ballistic studies or for forensic shooting incident reconstructions. Ballistic resistance of adhered cowhide - (bonded) to solidifying ballistic gelatine - was compared to that of the same material applied on gelatine blocks in loose condition. Ballistic resistance of tanned cowhide was found to be more consistent in adhered condition. This enhanced consistency is a benefit, increasing reproducibility of results in ballistic studies. Additionally, two ways to assess ballistic resistance of a skin simulant were described and compared. Logistic regression, from a number of measured velocities and associated (non)perforations is recommended for testing ballistic resistance.

Towards developing a Core Outcome Set for malnutrition intervention studies in older adults: a scoping review to identify frequently used research outcomes.

PURPOSE: To conduct a scoping review to provide a systematic overview of outcomes used in nutritional intervention studies focused on the treatment of protein-energy malnutrition in older adults. METHODS: A systematic search of four electronic databases (Medline, EMBASE, CINAHL and Cochrane Central Register of Controlled Trials (CENTRAL) was performed to retrieve randomized controlled trials (RCTs), published until March 9, 2020, that evaluated the effect of nutritional interventions to treat protein-energy malnutrition in older adults and those at risk for malnutrition. Two authors screened titles, abstracts and full texts independently. One author extracted data that were cross-checked by another author. RESULTS: Sixty-three articles reporting 60 RCTs were identified. Most frequently used outcomes included body weight/body mass index (75.0% of RCTs), dietary intake (61.7%), functional limitations (48.3%), handgrip strength (46.7%), and body circumference (40.0%). The frequencies differed by setting (community, hospital and long-term care). For some outcomes there was a preferred assessment method (e.g., Barthel index for functional limitations), while for other outcomes (e.g., functional performance) a much greater variation was observed. CONCLUSION: A large variation in outcomes, not only across but also within settings, was identified in nutritional intervention studies in malnourished older adults and those at risk. Furthermore, for many outcomes there was a large variation in the used assessment method. These results highlight the need for developing a Core Outcome Set for malnutrition intervention studies in older adults to facilitate future meta-analyses that may enhance our understanding on the effectiveness of treatment.

Bovine parafilariosis - New autochthonous cases from Germany and summary of recent reports from Europe.

Bovine parafilariosis is an emerging fly-borne disease in central Europe, characterized by seasonal occurrence of hemorrhagic exudations ('bleeding spots') from the end of winter to end of summer. In two cases from Germany reported here, one animal of a small herd in Bavaria and 20 animals on a farm in Baden-Württemberg presented bleeding spots from late March and late April 2020, respectively. Exudate samples from both cases were positive for larvated Parafilaria eggs. Examination of the skin and trimmed tissue after slaughter of the animal from Bavaria resulted in the collection of 11 nematodes (two males, eight females, one specimen in fragments). The animal's carcass presented typical yellow-greenish areas and bloody spots on the subcutaneous tissue of the flesh side of the skin. The nematodes were microscopically determined as Parafilaria bovicola. Basic morphometric measurements of two (one intact) male and six female nematodes are within the ranges of published data; length (male/female) 28.8/48.0-64.5 mm; width, 397.6 µm/430.7-527.6 µm; distance of cervical papillae to anterior end, 177.6/248.9-337.4; left spiculum/right spiculum (male), 365.3-379.4/149.5-180.3 µm; gubernaculum 45.0-48.1 µm; distance of vulva to anterior end (female), 37.3-66.0 mm. In order to gain information on P. bovicola in its vector, 91 cattle-visiting Musca autumnalis flies were collected from the affected animal in Bavaria (36 flies) and from co-pastured animals (55 flies) for PCR analysis and sequencing. A total of 14 flies were PCR-positive for filarial DNA, and sequencing of a fragment of the cox1 gene resulted in identification of P. bovicola (n = 10) and Thelazia gulosa (n = 5). This report presents further cases of bovine parafilariosis in Germany, provides morphometric data on male and female P. bovicola nematodes retrieved from cattle and identified DNA of P. bovicola and T.gulosa in M. autumnalis flies collected at a site of occurrence of bovine parafilariosis.

Neutral Effects of Combined Treatment With GLP-1R Agonist Exenatide and MR Antagonist Potassium Canrenoate on Cardiac Function in Porcine and Murine Chronic Heart Failure Models.

Background: Ischemia-reperfusion and cardiac remodeling is associated with cardiomyocyte death, excessive fibrosis formation, and functional decline, eventually resulting in heart failure (HF). Glucagon-like peptide (GLP)-1 agonists are reported to reduce apoptosis and myocardial infarct size after ischemia-reperfusion. Moreover, mineralocorticoid receptor antagonists (MRAs) have been described to reduce reactive fibrosis and improve cardiac function. Here, we investigated whether combined treatment with GLP-1R agonist exenatide and MRA potassium canrenoate could minimize cardiac injury and limit HF progression in animal models of chronic HF. Methods and Results: Forty female Topigs Norsvin pigs were subjected to 150 min balloon occlusion of the left anterior descending artery (LAD). Prior to reperfusion, pigs were randomly assigned to placebo or combination therapy (either low dose or high dose). Treatment was applied for two consecutive days or for 8 weeks with a continued high dose via a tunneled intravenous catheter. Using 2,3,5-Triphenyltetrazolium chloride (TTC) staining we observed that combination therapy did not affect the scar size after 8 weeks. In line, left ventricular volume and function assessed by three-dimensional (3D) echocardiography (baseline, 7 days and 8 weeks), and cardiac magnetic resonance imaging (CMR, 8 weeks) did not differ between experimental groups. In addition, 36 C57Bl/6JRj mice underwent permanent LAD-occlusion and were treated with either placebo or combination therapy prior to reperfusion, for two consecutive days via intravenous injection, followed by continued treatment via placement of osmotic mini-pumps for 28 days. Global cardiac function, assessed by 3D echocardiography performed at baseline, 7, 14, and 28 days, did not differ between treatment groups. Also, no differences were observed in cardiac hypertrophy, assessed by heart weight/bodyweight and heart weight/tibia length ratio. Conclusion: In the current study, combined treatment with GLP-1R agonist exenatide and MR antagonist potassium canrenoate did not show beneficial effects on cardiac remodeling nor resulted in functional improvement in a small and large animal chronic HF model.

Germline ATM variants predispose to melanoma: a joint analysis across the GenoMEL and MelaNostrum consortia.

PURPOSE: Ataxia-Telangiectasia Mutated (ATM) has been implicated in the risk of several cancers, but establishing a causal relationship is often challenging. Although ATM single-nucleotide polymorphisms have been linked to melanoma, few functional alleles have been identified. Therefore, ATM impact on melanoma predisposition is unclear. METHODS: From 22 American, Australian, and European sites, we collected 2,104 familial, multiple primary (MPM), and sporadic melanoma cases who underwent ATM genotyping via panel, exome, or genome sequencing, and compared the allele frequency (AF) of selected ATM variants classified as loss-of-function (LOF) and variants of uncertain significance (VUS) between this cohort and the gnomAD non-Finnish European (NFE) data set. RESULTS: LOF variants were more represented in our study cohort than in gnomAD NFE, both in all (AF = 0.005 and 0.002, OR = 2.6, 95% CI = 1.56-4.11, p < 0.01), and familial + MPM cases (AF = 0.0054 and 0.002, OR = 2.97, p < 0.01). Similarly, VUS were enriched in all (AF = 0.046 and 0.033, OR = 1.41, 95% CI = 1.6-5.09, p < 0.01) and familial + MPM cases (AF = 0.053 and 0.033, OR = 1.63, p < 0.01). In a case-control comparison of two centers that provided 1,446 controls, LOF and VUS were enriched in familial + MPM cases (p = 0.027, p = 0.018). CONCLUSION: This study, describing the largest multicenter melanoma cohort investigated for ATM germline variants, supports the role of ATM as a melanoma predisposition gene, with LOF variants suggesting a moderate-risk.

Significant variation in histopathological assessment of endoscopic resections for Barrett's neoplasia suggests need for consensus reporting: propositions for improvement.

Endoscopic resection (ER) is an important diagnostic step in management of patients with early Barrett's esophagus (BE) neoplasia. Based on ER specimens, an accurate histological diagnosis can be made, which guides further treatment. Based on depth of tumor invasion, differentiation grade, lymphovascular invasion, and margin status, the risk of lymph node metastases and local recurrence is judged to be low enough to justify endoscopic management, or high enough to warrant invasive surgical esophagectomy. Adequate assessment of these histological risk factors is therefore of the utmost importance. Aim of this study was to assess pathologist concordance on these histological features on ER specimens and evaluate causes of discrepancy. Of 62 challenging ER cases, one representative H&E slide and matching desmin and endothelial marker were digitalized and independently assessed by 13 dedicated GI pathologists from 8 Dutch BE expert centers, using an online assessment module. For each histological feature, concordance and discordance were calculated. Clinically relevant discordances were observed for all criteria. Grouping depth of invasion categories according to expanded endoscopic treatment criteria (T1a and T1sm1 vs. T1sm2/3), ≥1 pathologist was discrepant in 21% of cases, increasing to 45% when grouping diagnoses according to the traditional T1a versus T1b classification. For differentiation grade, lymphovascular invasion, and margin status, discordances were substantial with 27%, 42%, and 32% of cases having ≥1 discrepant pathologist, respectively. In conclusion, histological assessment of ER specimens of early BE cancer by dedicated GI pathologists shows significant discordances for all relevant histological features. We present propositions to improve definitions of diagnostic criteria.

Distal muscle weakness and optic atrophy without central nervous system involvement in a patient with a homozygous missense mutation in the C19ORF12-gene.

Variants of the C19ORF12-gene have been described in patients with spastic paraplegia type 43 and in patients with mitochondrial membrane protein-associated neurodegeneration (MPAN), a subtype of neurodegeneration associated with brain iron accumulation (NBIA). In both subtypes optic atrophy and neuropathy have been frequently described. This case report describes a patient with bilateral optic atrophy and severe distal muscle weakness based on motor neuropathy without involvement of the central nervous system. Exome sequencing revealed a homozygous pathogenic missense variant (c.187G>C;p.Ala63Pro) of the C19ORF12-gene while iron deposits were absent on repeat MR-imaging of the brain, thus showing that peripheral neuropathy and optic neuropathy can be the sole manifestations of the C19ORF12-related disease spectrum whereby iron accumulation in the brain may be absent.