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1.
Sci Adv ; 9(39): eadg4015, 2023 09 29.
Article in English | MEDLINE | ID: mdl-37774017

ABSTRACT

Dysbiosis of skin microbiota drives the progression of atopic dermatitis (AD). The contribution of bacteriophages to bacterial community compositions in normal and inflamed skin is unknown. Using shotgun metagenomics from skin swabs of healthy individuals and patients with AD, we found 13,586 potential viral contiguous DNA sequences, which could be combined into 164 putative viral genomes including 133 putative phages. The Shannon diversity index for the viral metagenome-assembled genomes (vMAGs) did not correlate with AD. In total, we identified 28 vMAGs that differed significantly between normal and AD skin. Quantitative polymerase chain reaction validation of three complete vMAGs revealed their independence from host bacterium abundance. Our data indicate that normal and inflamed skin harbor distinct phageomes and suggest a causative relationship between changing viral and bacterial communities as a driver of skin pathology.


Subject(s)
Microbiota , Virome , Humans , Skin/microbiology , Metagenome , Bacteria/genetics , DNA, Viral/genetics
2.
BMC Med Educ ; 23(1): 196, 2023 Mar 29.
Article in English | MEDLINE | ID: mdl-36991413

ABSTRACT

BACKGROUND: Medical schools are reported to be less accessible to students with non-traditional backgrounds. These students face barriers when applying for and transitioning to medical school, which may be reduced by offering free preparatory activities. By equalizing access to resources, these activities are expected to reduce disparities in selection outcomes and early academic performance. In the present study, four free institutionally-provided preparatory activities were evaluated by comparing the demographic composition of participating and non-participating applicants. Additionally, the association between participation and selection outcomes and early academic performance was investigated for subgroups (based on sex, migration background and parental education). METHODS: Participants were applicants to a Dutch medical school in 2016-2019 (N = 3592). Free preparatory activities included Summer School (N = 595), Coaching Day (N = 1794), Pre-Academic Program (N = 217), and Junior Med School (N = 81), supplemented with data on participation in commercial coaching (N = 65). Demographic compositions of participants and non-participants were compared using chi-squared tests. Regression analyses were performed to compare selection outcomes (curriculum vitae [CV], selection test score, probability of enrolment) and early academic performance (first-course grade) between participants and non-participants of demographic subgroups, controlling for pre-university grades and participation in other activities. RESULTS: Generally, no differences in sociodemographic compositions of participants and non-participants were found, but males participated less often in Summer School and Coaching Day. Applicants with a non-Western background participated less often in commercial coaching, but the overall participation rate was low and participation had negligible effects on selection outcomes. Participation in Summer School and Coaching Day were stronger related with selection outcomes. In some cases, this association was even stronger for males and candidates with a migration background. After controlling for pre-university grades, none of the preparatory activities were positively associated with early academic performance. CONCLUSIONS: Free institutionally-provided preparatory activities may contribute to student diversity in medical education, because usage was similar across sociodemographic subgroups, and participation was positively associated with selection outcomes of underrepresented and non-traditional students. However, since participation was not associated with early academic performance, adjustments to activities and/or curricula are needed to ensure inclusion and retention after selection.


Subject(s)
Education, Medical , School Admission Criteria , Male , Humans , Cohort Studies , Educational Status , Ethnicity , Schools, Medical
3.
BMC Med Educ ; 23(1): 103, 2023 Feb 09.
Article in English | MEDLINE | ID: mdl-36759816

ABSTRACT

BACKGROUND: An increase in the demand for general practitioners is expected in many countries, but only a minority of medical students consider a career in general practice. More detailed and up-to-date knowledge about medical student's perception of general practice would be helpful for efforts to encourage medical students to consider a career in general practice. METHODS: We performed a cross-sectional single center survey among Dutch medical students to evaluate their perception of general practice at three different stages in their study: Ba1: first-year bachelor students; Ba3: third-year bachelor students; Ma3: third-year master students. The impact of different factors on their attitudes and perceptions was quantified. A multivariate logistic regression was performed with 'interest in general practice' as the outcome variable. RESULTS: The median age for Ba1 was 18 (IQR: 18-19) and 71.5% were female, for Ba3 the median age was 20 (IQR: 20-21) and 70.6% were female and for Ma3 the median age was 25 years (IQR: 24-26) and 73.3% were female. On average, 31.2% of the respondents had a migration background. The mean response rate for this study was 77.1%. Of the participating Ba1 students (n = 340) only 22.4% considered working as a GP after medical school; for Ba3 students (n = 231) this percentage was 33.8%, and for Ma3 students (n = 210) it was significantly higher at 70.5%; in the final multivariate model this corresponded to an odds ratio (OR) of 4.3 (95%-CI:2.6-6.9) compared to Ba1 students. The strongest predictor in the final model was the opinion that general practice provides a pleasant working environment (OR 9.5; 95%-CI: 6.2-14.5). CONCLUSION: This study showed that multiple factors are significantly related to medical students' interest in general practice. Although students believed that general practice does not have a high status within the medical profession, they acknowledged the social importance and the pleasant working environment of general practice. Knowledge obtained in this study can be used when designing a medical curriculum or a general practice course.


Subject(s)
General Practice , Students, Medical , Humans , Female , Young Adult , Adult , Male , Cross-Sectional Studies , Career Choice , General Practice/education , Perception , Surveys and Questionnaires
4.
Adv Health Sci Educ Theory Pract ; 28(4): 1027-1052, 2023 10.
Article in English | MEDLINE | ID: mdl-36653557

ABSTRACT

Student diversity in health professions education (HPE) can be affected by selection procedures. Little is known about how different selection tools impact student diversity across programs using different combinations of traditional and broadened selection criteria. The present multi-site study examined the chances in selection of subgroups of applicants to HPE undergraduate programs with distinctive selection procedures, and their performance on corresponding selection tools. Probability of selection of subgroups (based on gender, migration background, prior education, parental education) of applicants (N = 1935) to five selection procedures of corresponding Dutch HPE undergraduate programs was estimated using multilevel logistic regression. Multilevel linear regression was used to analyze performance on four tools: prior-education grade point average (pe-GPA), biomedical knowledge test, curriculum-sampling test, and curriculum vitae (CV). First-generation Western immigrants and applicants with a foreign education background were significantly less likely to be selected than applicants without a migration background and with pre-university education. These effects did not vary across programs. More variability in effects was found between different selection tools. Compared to women, men performed significantly poorer on CVs, while they had higher scores on biomedical knowledge tests. Applicants with a non-Western migration background scored lower on curriculum-sampling tests. First-generation Western immigrants had lower CV-scores. First-generation university applicants had significantly lower pe-GPAs. There was a variety in effects for applicants with different alternative forms of prior education. For curriculum-sampling tests and CVs, effects varied across programs. Our findings highlight the need for continuous evaluation, identifying best practices within existing tools, and applying alternative tools.


Subject(s)
School Admission Criteria , Students , Male , Humans , Female , Educational Measurement , Educational Status , Health Occupations
5.
Int J Pharm ; 630: 122466, 2023 Jan 05.
Article in English | MEDLINE | ID: mdl-36493969

ABSTRACT

The standard of care for patients with Adrenal Insufficiency (AI) is suboptimal. Administration of hydrocortisone three times a day produces plasma cortisol fluctuations associated with negative health outcomes. Furthermore, there is a high inter-individual variability in cortisol need, necessitating a personalized approach. It is hypothesized that a personalized, sustained release formulation would enhance the pharmacotherapy by mimicking the physiological cortisol plasma concentration at a higher level. Therefore, a novel 24 h sustained release 3D printed (3DP) hydrocortisone formulation has been developed (M3DICORT) by coupling hot-melt extrusion with fused deposition modeling. A uniform drug distribution in the 3DP tablets is demonstrated by a content of 101.66 ± 1.60 % with an acceptance value of 4.01. Furthermore, tablets had a stable 24 h dissolution profile where the intra-batch standard deviation was ± 2.8 % and the inter-batch standard deviation was ± 6.8 %. Tablet height and hydrocortisone content were correlated (R2 = 0.996), providing a tool for easy dose personalization. Tablets maintained critical quality attributes, such as dissolution profile (f2 > 60) and content uniformity after process transfer from a single-screw extruder to a twin-screw extruder. Impurities were observed in the final product which should be mitigated before clinical assessment. To our knowledge, M3DICORT is the first 3DP hydrocortisone formulation specifically developed for AI.


Subject(s)
Adrenal Insufficiency , Hydrocortisone , Humans , Delayed-Action Preparations/therapeutic use , Adrenal Insufficiency/drug therapy , Tablets , Printing, Three-Dimensional , Drug Liberation , Technology, Pharmaceutical
6.
Inn Med (Heidelb) ; 63(11): 1194-1199, 2022 Nov.
Article in German | MEDLINE | ID: mdl-35925122

ABSTRACT

A 66-year-old female patient with the initial diagnosis of acute myeloid leukemia is reported. Paraneoplastic syndrome manifested as hypernatremia due to central diabetes insipidus (CDI), which could be controlled with the administration of desmopressin. After initiation of the induction therapy, the required desmopressin administration could be reduced and terminated. In the further course, the early increasing polyuria and hypernatremia indicated the primary refractory acute myeloid leukemia.


Subject(s)
Diabetes Insipidus, Neurogenic , Hypernatremia , Leukemia, Myeloid, Acute , Neoplasms, Second Primary , Humans , Female , Aged , Polyuria/diagnosis , Hypernatremia/diagnosis , Deamino Arginine Vasopressin/therapeutic use , Diabetes Insipidus, Neurogenic/diagnosis , Leukemia, Myeloid, Acute/complications , Neoplasms, Second Primary/complications
7.
J Thromb Haemost ; 16(10): 1953-1963, 2018 10.
Article in English | MEDLINE | ID: mdl-30063819

ABSTRACT

Essentials Mortality due to bleeding vs. arterial thrombosis in dialysis patients is unknown. We compared death causes of 201 918 dialysis patients with the general population. Dialysis was associated with increased mortality risks of bleeding and arterial thrombosis. Clinicians should be aware of the increased bleeding and thrombosis risks. SUMMARY: Background Dialysis has been associated with both bleeding and thrombotic events. However, there is limited information on bleeding as a cause of death versus arterial thrombosis as a cause of death. Objectives To investigate the occurrence of bleeding, myocardial infarction and stroke as causes of death in the dialysis population as compared with the general population. Methods We included 201 918 patients from 11 countries providing data to the ERA-EDTA Registry who started dialysis treatment between 1994 and 2011, and followed them for 3 years. Age-standardized and sex-standardized mortality rate ratios for bleeding, myocardial infarction and stroke as causes of death were calculated in dialysis patients as compared with the European general population. Associations between potential risk factors and these causes of death in dialysis patients were investigated by calculating hazard ratios (HRs) with 95% confidence intervals (CIs) by the use of Cox proportional-hazards regression. Results As compared with the general population, the age-standardized and sex-standardized mortality rate ratios in dialysis patients were 12.8 (95% CI 11.9-13.7) for bleeding as a cause of death (6.2 per 1000 person-years among dialysis patients versus 0.3 per 1000 person-years in the general population), 13.4 (95% CI 13.0-13.9) for myocardial infarction (22.5 versus 0.9 per 1000 person-years), and 12.4 (95% CI 11.9-12.9) for stroke (14.3 versus 0.7 per 1000 person-years). Conclusion Dialysis patients have highly increased risks of death caused by bleeding and arterial thrombosis as compared with the general population. Clinicians should be aware of the increased mortality risks caused by these conditions.


Subject(s)
Hemorrhage/mortality , Kidney Diseases/therapy , Myocardial Infarction/mortality , Renal Dialysis/adverse effects , Stroke/mortality , Adult , Age Distribution , Aged , Aged, 80 and over , Cause of Death , Europe/epidemiology , Female , Humans , Kidney Diseases/mortality , Male , Middle Aged , Prognosis , Registries , Risk Assessment , Risk Factors , Sex Distribution , Time Factors
8.
Reprod Domest Anim ; 53(3): 784-792, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29603438

ABSTRACT

Increased concentrations of Anti-Muellerian hormone (AMH) can indicate a granulosa cell tumour as shown in women, mares and cows. To investigate AMH to differentiate canine granulosa cell tumour from other ovarian pathologies, we evaluated the ovaries of 63 bitches. Blood serum samples were collected before surgery for AMH analysis. Ovaries were submitted for histopathological examination. Fourteen bitches showed normal ovaries. These bitches had AMH values between 0.12 and 0.99 ng/ml. In 20 bitches ovarian cysts i.e., follicular cysts (n = 8), corpora lutea cysts (n = 7), subsurface cysts (n = 5) were diagnosed. These dogs had AMH values of 0.11-2.09 ng/ml. Bitches with small luteinized follicular cysts had slightly higher AMH values than those without ovarian alteration. In 29 cases ovarian neoplasms i.e., granulosa cell tumour (n = 9), epithelial tumours (n = 16), dysgerminomas (n = 3) and one sarcoma were identified. Anti-Muellerian hormone values of bitches with an ovarian neoplasm except granulosa cell tumour ranged from 0.18 to 1.18 ng/ml. The AMH values of bitches with granulosa cell tumour ranged from 1.12 to ≤23 ng/ml and were significantly higher (p < .05) than in all of the other bitches. The cut-off of 0.99 ng/ml gave a sensitivity of 100% and a specificity of 94.44% to diagnose granulosa cell tumour. In conclusion, markedly elevated AMH concentrations in bitches are indicative for a granulosa cell tumour. However, negative testing does not rule out the existence of small one. Differentiation of GCT from luteinized follicular cysts may especially be difficult.


Subject(s)
Anti-Mullerian Hormone/blood , Dog Diseases/blood , Ovarian Cysts/veterinary , Ovarian Neoplasms/veterinary , Animals , Carcinoma/blood , Carcinoma/veterinary , Dogs , Dysgerminoma/blood , Dysgerminoma/veterinary , Female , Granulosa Cell Tumor/blood , Granulosa Cell Tumor/diagnosis , Granulosa Cell Tumor/veterinary , Ovarian Cysts/blood , Ovarian Neoplasms/blood , Sarcoma/blood , Sarcoma/veterinary
9.
Adv Health Sci Educ Theory Pract ; 22(2): 243-265, 2017 May.
Article in English | MEDLINE | ID: mdl-27757558

ABSTRACT

Situational Judgment Tests (SJTs) are increasingly used for medical school selection. Scoring an SJT is more complicated than scoring a knowledge test, because there are no objectively correct answers. The scoring method of an SJT may influence the construct and concurrent validity and the adverse impact with respect to non-traditional students. Previous research has compared only a small number of scoring methods and has not studied the effect of scoring method on internal consistency reliability. This study compared 28 different scoring methods for a rating SJT on internal consistency reliability, adverse impact and correlation with personality. The scoring methods varied on four aspects: the way of controlling for systematic error, and the type of reference group, distance and central tendency statistic. All scoring methods were applied to a previously validated integrity-based SJT, administered to 931 medical school applicants. Internal consistency reliability varied between .33 and .73, which is likely explained by the dependence of coefficient alpha on the total score variance. All scoring methods led to significantly higher scores for the ethnic majority than for the non-Western minorities, with effect sizes ranging from 0.48 to 0.66. Eighteen scoring methods showed a significant small positive correlation with agreeableness. Four scoring methods showed a significant small positive correlation with conscientiousness. The way of controlling for systematic error was the most influential scoring method aspect. These results suggest that the increased use of SJTs for selection into medical school must be accompanied by a thorough examination of the scoring method to be used.


Subject(s)
College Admission Test , Judgment , Personality , Schools, Medical/standards , Adolescent , Female , Humans , Male , Minority Groups , Observer Variation , Reproducibility of Results , Socioeconomic Factors , Young Adult
10.
Ned Tijdschr Geneeskd ; 160: D597, 2016.
Article in Dutch | MEDLINE | ID: mdl-27650021

ABSTRACT

OBJECTIVE: To investigate underperformance across ethnic minority groups and by first-generation university students in different types of examinations during pre-clinical training. DESIGN: Prospective cohort study METHODS: Participants included Erasmus MC students from the 2008-2013 cohorts (n=2432). Outcome measures were pass/fail on three types of written examinations: 1) theoretical knowledge: clinical problem solving tests (CPSTs) (Year 1-3) and end-of-block tests (Year 1c2-c3), 2) language skills test (Year 1) and 3) writing skills tests (Year 1-3), and OSCEs (Year 2-3). Odds ratios with 95% confidence intervals were estimated by logistic regression analysis for ethnic subgroups (Surinamese/Antillean, Turkish/Moroccan/African, Asian, Western) compared with Dutch students, adjusted for age, gender, pre-university Grade Point Average (pu-GPA), additional socio-demographic variables (first-generation immigrant, urban background, first-generation university student, first language, medical doctor as parent). Similar analyses were conducted for first-generation university students. RESULTS: Compared with Dutch students, the three non-Western ethnic minority groups underperformed in the CPSTs, the language test and the OSCEs. Findings on the end-of-block and writing skills tests, and results for Western minority students were less consistent. Age, gender, pu-GPA and additional socio-demographic variables could explain the ethnicity-related differences in theoretical examinations, but not in language, clinical and writing skills examinations. First-generation university students only underperformed in the language test. CONCLUSION: Ethnic minority students underperform in pre-clinical training, but there are differences both across ethnic subgroups and between different types of examinations. In designing assessment programs care should be taken to avoid unintended effects of certain types of examinations for certain groups of students.


Subject(s)
Education, Medical, Undergraduate , Educational Measurement/statistics & numerical data , Ethnicity , Minority Groups , Social Class , Students, Medical/statistics & numerical data , Emigrants and Immigrants , Humans , Logistic Models , Netherlands , Odds Ratio , Prospective Studies
11.
Anaesthesist ; 65(7): 499-506, 2016 Jul.
Article in German | MEDLINE | ID: mdl-27324155

ABSTRACT

BACKGROUND: Perioperative care demands consideration of individual treatment goals. We evaluated the attitudes of medical staff towards a short standardized advance directive (SSAD) as a means of improving patient-orientated care at the transition from operating theater to general or intensive care wards. METHOD: Multicenter anonymized standardized multiple-choice questionnaire among physicians and nurses from various operative and anesthesiology departments. Questions addressing demographic parameters and attitudes towards advance directives in acute care settings (eleven 4­stepped Likert items). Univariate analysis of group comparisons using the chi-square and Kruskal-Wallis rank-sum test. Multivariable analysis of significant differences employing ordinal logistic regression. RESULTS: The overall return rate was 28.2 % (169 questionnaires). Of these, 19.5 % said that existing advance directives were regularly reassessed preoperatively. SSAD was expected to provide improved emergency care by 82.3 and 76.6 % thought that it would help to better focus intensive care resources according to patients' needs. DISCUSSION: Our study shows the dilemma of insufficiently structured directives for changing treatment goals as well as a high number of legal procedures to obtain proxy decisions due to missing out-patient advance health planning. From a medical staff perspective there is strong support for the concept of SSAD based on medical, ethical, economic and organizational reasons.


Subject(s)
Documentation , Inpatients , Patient Care/standards , Preoperative Care/methods , Adult , Advance Directive Adherence , Aged , Aged, 80 and over , Attitude of Health Personnel , Critical Care/ethics , Critical Care/standards , Female , Goals , Humans , Male , Medical Staff , Middle Aged , Personnel, Hospital , Preoperative Care/standards , Surveys and Questionnaires
12.
Neth J Med ; 74(4): 162-70, 2016 May.
Article in English | MEDLINE | ID: mdl-27185775

ABSTRACT

Guidelines provide recommendations for antithrombotic treatment to prevent stroke in people with atrial fibrillation, but oral anticoagulant prescriptions in Dutch primary care are often discordant with these recommendations. Suboptimal guideline features (i.e. format and content) have been suggested as a potential explanatory factor for this type of discordance. Therefore, we systematically appraised features of the Dutch general practitioners' (NHG) atrial fibrillation guideline to identify guidelinerelated barriers that may hamper its use in practice. We appraised the guideline's methodological rigour and transparency using the Appraisal of Guidelines, Research and Evaluation (AGREE) II tool. Additionally, we used the Guideline Implementability Appraisal (GLIA) tool to assess the key recommendations on oral anticoagulant prescription. The editorial independence of the guideline group scored highly (88%); scores for other aspects of the guideline's methodological quality were acceptable, ranging from 53% for stakeholder involvement to 67% for clarity of presentation. At the recommendation level, the main implementation obstacles were lack of explicit statements on the quality of underlying evidence, lack of clarity around the strength of recommendations, and the use of ambiguous terms which may hamper operationalisation in electronic systems. Based on our findings we suggest extending stakeholder involvement in the guideline development process, standardising the layout and language of key recommendations, providing monitoring criteria, and preparing electronic implementation parallel with guideline development. We expect this to contribute to optimising the NHG atrial fibrillation guideline, facilitating its implementation in practice, and ultimately to improving antithrombotic treatment and stroke prevention in people with atrial fibrillation.


Subject(s)
Anticoagulants/therapeutic use , Atrial Fibrillation/drug therapy , Guideline Adherence , Guidelines as Topic , Stroke/prevention & control , Clinical Competence , Consensus , Drug Prescriptions , Humans , Netherlands , Primary Health Care
13.
Adv Health Sci Educ Theory Pract ; 21(5): 1023-1046, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27015959

ABSTRACT

Medical schools are increasingly faced with a more diverse student population. Generally, ethnic minority students are reported to underperform compared with those from the ethnic majority. However, there are inconsistencies in findings in different types of examinations. Additionally, little is known about the performance of first-generation university students and about performance differences across ethnic minority groups. This study aimed to investigate underperformance across ethnic minority groups and by first-generation university students in different types of written tests and clinical skills examinations during pre-clinical training. A longitudinal prospective cohort study of progress on a 3-year Dutch Bachelor of Medicine course was conducted. Participants included 2432 students who entered the course over a consecutive 6-year period (2008-2013). Compared with Dutch students, the three non-Western ethnic minority groups (Turkish/Moroccan/African, Surinamese/Antillean and Asian) underperformed in the clinical problem solving tests, the language test and the OSCEs. Findings on the theoretical end-of-block tests and writing skills tests, and results for Western minority students were less consistent. Age, gender, pre-university grade point average and additional socio-demographic variables (including first-generation university student, first language, and medical doctor parent) could explain the ethnicity-related differences in theoretical examinations, but not in language, clinical and writing skills examinations. First-generation university students only underperformed in the language test. Apparently, underperformance differs both across ethnic subgroups and between different types of written and clinical examinations. Medical schools should ensure their assessment strategies create a level playing field for all students and explore reasons for underperformance in the clinical and writing skills examinations.


Subject(s)
Education, Medical, Undergraduate , Educational Measurement/methods , Ethnicity/education , Ethnicity/psychology , Students, Medical/psychology , Curriculum , Female , Humans , Longitudinal Studies , Male , Netherlands , Prospective Studies , Schools, Medical , Socioeconomic Factors , Surveys and Questionnaires , Underachievement , Young Adult
14.
Am J Transplant ; 16(7): 2097-105, 2016 07.
Article in English | MEDLINE | ID: mdl-26783738

ABSTRACT

Inequalities between genders in access to transplantation have been demonstrated. We aimed to validate this gender inequality in a large pediatric population and to investigate its causes. This cohort study included 6454 patients starting renal replacement therapy before 18 years old, in 35 countries participating in the European Society for Paediatric Nephrology/European Renal Association-European Dialysis and Transplant Association Registry. We used cumulative incidence competing risk and proportional hazards frailty models to study the time to receive a transplant and hierarchical logistic regression to investigate access to preemptive transplantation. Girls had a slower access to renal transplantation because of a 23% lower probability of receiving preemptive transplantation. We found a longer follow-up time before renal replacement therapy in boys compared with girls despite a similar estimated glomerular filtration rate at first appointment. Girls tend to progress faster toward end-stage renal disease than boys, which may contribute to a shorter time available for pretransplantation workup. Overall, medical factors explained only 70% of the gender difference. In Europe, girls have less access to preemptive transplantation for reasons that are only partially related to medical factors. Nonmedical factors such as patient motivation and parent and physician attitudes toward transplantation and organ donation may contribute to this inequality. Our study should raise awareness for the management of girls with renal diseases.


Subject(s)
Health Services Accessibility , Healthcare Disparities , Kidney Failure, Chronic/surgery , Kidney Transplantation , Registries/statistics & numerical data , Adolescent , Child , Child, Preschool , Cohort Studies , Female , Follow-Up Studies , Humans , Male , Prognosis , Sex Factors
15.
Hear Res ; 332: 61-72, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26619750

ABSTRACT

Efferent auditory feedback on cochlear hair cells is well studied regarding olivocochlear brainstem mechanisms. Less is known about how the descending corticofugal system may shape efferent feedback and modulate cochlear mechanics. Distortion-product otoacoustic emissions (DPOAEs) are a suitable tool to assess outer hair cell function, as they are by-products of the nonlinear cochlear amplification process. The present project investigates the effects of cortical activity on cubic and quadratic DPOAEs in mongolian gerbils, Meriones unguiculatus, through cortical deactivation using the sodium-channel blocker lidocaine. Contralateral cortical microinjections of lidocaine can lead to either an increase or decrease of median DPOAE levels of up to 10.95 dB. The effects are reversible and comparable at all tested frequencies (0.5-40 kHz). They are not restricted to the preferred frequency of the cortical site of injection. Recovery times are between 20 and 120 min depending on stimulation levels and emission type. When the injection is performed in the ipsilateral hemisphere, DPOAE level shifts are lower in amplitude compared to those after injection in the contralateral hemisphere. No significant changes in DPOAE levels are obtained after saline microinjections. Results indicate that deactivation of auditory cortex activity through lidocaine has a considerable impact on peripheral auditory responses in form of DPOAEs, probably through cortico-olivocochlear pathways.


Subject(s)
Auditory Cortex/physiology , Cochlea/physiology , Hair Cells, Auditory/physiology , Hearing , Otoacoustic Emissions, Spontaneous , Acoustic Stimulation , Animals , Audiometry, Pure-Tone , Auditory Cortex/drug effects , Auditory Pathways/physiology , Cochlea/drug effects , Female , Gerbillinae , Hair Cells, Auditory/drug effects , Hearing/drug effects , Lidocaine/administration & dosage , Male , Microinjections , Olivary Nucleus/physiology , Otoacoustic Emissions, Spontaneous/drug effects , Recovery of Function , Sodium Channel Blockers/administration & dosage , Sound Spectrography , Time Factors
16.
Nephrol Dial Transplant ; 31(4): 609-19, 2016 04.
Article in English | MEDLINE | ID: mdl-25925700

ABSTRACT

BACKGROUND: Growth retardation in paediatric end-stage renal disease (ESRD) has a serious impact on adult life. It is potentially treatable with recombinant growth hormone (rGH). In this study, we aimed to quantify the variation in rGH policies and actual provided care in these patients across Europe. METHODS: Renal registry representatives of 38 European countries received a structured questionnaire on rGH policy. Cross-sectional data on height and actual use of rGH on children with ESRD aged <18 years were retrieved from the ESPN/ERA-EDTA Registry. RESULTS: In 21 (75%) of 28 responding countries, rGH is reimbursed for children with ESRD. The specific conditions for reimbursement (minimum age, maximum age and chronic kidney disease stage) vary considerably. Mean height standard deviation scores (SDS) at renal replacement therapy (RRT) [95% confidence interval (CI)] were significantly higher in countries where rGH was reimbursed -1.80 (-2.06; -1.53) compared with countries in which it was not reimbursed [-2.34 (-2.49;-2.18), P < 0.001]. Comparison of the mean height SDS at onset of RRT and final height SDS yielded similar results. Among the 13 countries for which both data on actual rGH use between 2007 and 2011 and data from the questionnaire were available, 30.1% of dialysis and 42.3% of transplanted patients had a short stature, while only 24.1 and 7.6% of those short children used rGH, respectively. CONCLUSION: Reimbursement of rGH associates with a less compromised final stature of ESRD children. In many countries with full rGH reimbursement, the actual rGH prescription in growth-retarded ESRD children is low and obviously more determined by the doctor's and patients' attitude towards rGH therapy than by financial hurdles.


Subject(s)
Human Growth Hormone/therapeutic use , Kidney Failure, Chronic/therapy , Practice Patterns, Physicians'/legislation & jurisprudence , Prescription Drugs/administration & dosage , Adolescent , Adult , Body Height , Child , Child, Preschool , Cross-Sectional Studies , Europe , Female , Humans , Infant , Infant, Newborn , Male , Registries , Renal Replacement Therapy/statistics & numerical data , Surveys and Questionnaires , Young Adult
17.
Thromb Haemost ; 111(3): 531-8, 2014 Mar 03.
Article in English | MEDLINE | ID: mdl-24226257

ABSTRACT

There is a need to validate risk assessment tools for hospitalised medical patients at risk of venous thromboembolism (VTE). We investigated whether a predefined cut-off of the Geneva Risk Score, as compared to the Padua Prediction Score, accurately distinguishes low-risk from high-risk patients regardless of the use of thromboprophylaxis. In the multicentre, prospective Explicit ASsessment of Thromboembolic RIsk and Prophylaxis for Medical PATients in SwitzErland (ESTIMATE) cohort study, 1,478 hospitalised medical patients were enrolled of whom 637 (43%) did not receive thromboprophylaxis. The primary endpoint was symptomatic VTE or VTE-related death at 90 days. The study is registered at ClinicalTrials.gov, number NCT01277536. According to the Geneva Risk Score, the cumulative rate of the primary endpoint was 3.2% (95% confidence interval [CI] 2.2-4.6%) in 962 high-risk vs 0.6% (95% CI 0.2-1.9%) in 516 low-risk patients (p=0.002); among patients without prophylaxis, this rate was 3.5% vs 0.8% (p=0.029), respectively. In comparison, the Padua Prediction Score yielded a cumulative rate of the primary endpoint of 3.5% (95% CI 2.3-5.3%) in 714 high-risk vs 1.1% (95% CI 0.6-2.3%) in 764 low-risk patients (p=0.002); among patients without prophylaxis, this rate was 3.2% vs 1.5% (p=0.130), respectively. Negative likelihood ratio was 0.28 (95% CI 0.10-0.83) for the Geneva Risk Score and 0.51 (95% CI 0.28-0.93) for the Padua Prediction Score. In conclusion, among hospitalised medical patients, the Geneva Risk Score predicted VTE and VTE-related mortality and compared favourably with the Padua Prediction Score, particularly for its accuracy to identify low-risk patients who do not require thromboprophylaxis.


Subject(s)
Research Design/statistics & numerical data , Venous Thromboembolism/diagnosis , Venous Thromboembolism/epidemiology , Aged , Female , Follow-Up Studies , Hospitalization , Humans , Male , Middle Aged , Predictive Value of Tests , Prognosis , Prospective Studies , Research Design/standards , Risk Assessment , Survival Analysis , Switzerland , Venous Thromboembolism/mortality
19.
Diabetologia ; 56(9): 1949-57, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23771173

ABSTRACT

AIMS/HYPOTHESIS: A previous study in Dutch dialysis patients showed no survival difference between patients with diabetes as primary renal disease and those with diabetes as a co-morbid condition. As this was not in line with our hypothesis, we aimed to verify these results in a larger international cohort of dialysis patients. METHODS: For the present prospective study, we used data from the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry. Incident dialysis patients with data on co-morbidities (n = 15,419) were monitored until kidney transplantation, death or end of the study period (5 years). Cox regression was performed to compare survival for patients with diabetes as primary renal disease, patients with diabetes as a co-morbid condition and non-diabetic patients. RESULTS: Of the study population, 3,624 patients (24%) had diabetes as primary renal disease and 1,193 (11%) had diabetes as a co-morbid condition whereas the majority had no diabetes (n = 10,602). During follow-up, 7,584 (49%) patients died. In both groups of diabetic patients mortality was higher compared with the non-diabetic patients. Mortality was higher in patients with diabetes as primary renal disease than in patients with diabetes as a co-morbid condition, adjusted for age, sex, country and malignancy (HR 1.20, 95% CI 1.10, 1.30). An analysis stratified by dialysis modality yielded similar results. CONCLUSIONS/INTERPRETATION: Overall mortality was significantly higher in patients with diabetes as primary renal disease compared with those with diabetes as a co-morbid condition. This suggests that survival in diabetic dialysis patients is affected by the extent to which diabetes has induced organ damage.


Subject(s)
Diabetes Mellitus/mortality , Kidney Diseases/mortality , Renal Dialysis/statistics & numerical data , Aged , Female , Humans , Male , Middle Aged
20.
Article in German | MEDLINE | ID: mdl-23765322

ABSTRACT

The case report describes a narrowing of the spinal canal in the lumbar and sacroiliac regions with entailing acute recumbency in a nearterm 17-year-old Welsh B Pony mare. The reason for recumbency was metastases of a malignant melanoma in the spinal canal of the lumbo-sacral region, where the tumour had invaded the dura mater and applied severe pression on the spinal cord over a length of 10 cm. Clinical findings, laboratory diagnostics, pathological-anatomical and histopathological findings are presented.


Subject(s)
Horse Diseases/pathology , Melanoma/veterinary , Pregnancy Complications, Neoplastic/veterinary , Spinal Cord Compression/veterinary , Spinal Cord/pathology , Spinal Neoplasms/veterinary , Animals , Female , Horse Diseases/diagnosis , Horse Diseases/etiology , Horses , Melanoma/complications , Melanoma/diagnosis , Melanoma/pathology , Posture , Pregnancy , Pregnancy Complications, Neoplastic/diagnosis , Pregnancy Complications, Neoplastic/pathology , Radiography , Spinal Cord/diagnostic imaging , Spinal Cord Compression/diagnosis , Spinal Cord Compression/etiology , Spinal Cord Compression/pathology , Spinal Neoplasms/complications , Spinal Neoplasms/diagnosis , Spinal Neoplasms/pathology
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