The bumpy ride to a medical PhD degree: a qualitative study on factors influencing motivation.

INTRODUCTION: In parallel with a tremendous increase in medical PhD enrolments, concerns have risen about PhD candidates' poor well-being, increasing attrition rates for PhD programmes, and, eventually, a decline in clinician-scientists. According to the Self-Determination Theory, autonomous motivation is strongly linked to positive aspects of well-being and other positive outcomes such as study completion and success. In this way, motivation has a pivotal role in successful completion of medical doctoral programmes. In this study we explored factors affecting motivation during the PhD journey and aimed to contribute to engaging doctoral education environments, and, eventually, a sustainable clinician-scientist workforce. METHODS: This constructivist qualitative interview study was conducted among ten medical PhD candidates in the final phase of their PhD. We used timeline assisted interviews to identify meaningful experiences throughout their PhD journey. Thematic analyses as an iterative process resulted in overarching themes. RESULTS: We identified six themes influencing autonomous and controlled motivation along the challenging PhD journey: (1) Initial motivation to start a PhD matters; (2) Autonomy as a matter of the right dose at the right time; (3) PhD as proof of competence and/or learning trajectory?; (4) It takes two to tango; (5) Peers can make or break your PhD; (6) Strategies to stay or get back on track. CONCLUSION: This study revealed factors that contribute positively and/or negatively to autonomous and controlled motivation. Some factors impacted motivation differently depending on the PhD phase and individual strategies. Additionally, some factors could coincide and change from positive to negative and vice versa, showing that a successful journey cannot simply be reduced to an absence of negative experiences.

Values and beliefs on trainee selection: What counts in the eye of the selector? A qualitative study exploring the program director's perspective.

OBJECTIVES: Postgraduate trainee selection is a high-stakes process. While many studies focused on selection methods and psychometrics, little is known about the influence of selectors' personal values and beliefs in the judgment and decision-making process. A better understanding of these factors is vital since selectors determine the future workforce. METHODS: We interviewed programme directors (PDs) from 11 specialties in one University Hospital. Thematic analysis was conducted with a combined approach of generic and in-vivo coding. RESULTS: PDs value excellence, 'fit' and personal characteristics. The content of these values are subject to personal interpretation and differ between PDs. PDs use various 'proxies' as alternative indicators of performance. They consider intuition, teamwork and autonomy important in judgement and decision-making. PDs find selection challenging and feel great accountability towards candidates and society. CONCLUSIONS: Selectors criteria of judgement- and decision-making often remain implicit and focus on prior achievements and 'fit' with the current trainee-pool, possibly compromising the workforce's diversity. Implicit 'proxies' and intuitive decision-making may be an unwitting source of judgemental bias. 'Making the implicit explicit', by increasing awareness of personal values and beliefs and structuring the selection interview, may improve the quality of trainee selection.

Scientific education early in the curriculum using a constructivist approach on learning.

Physicians need to stay up-to-date with new developments in their field of expertise. This expectation has been made explicit by competency-based educational outcomes in the domain of scholar in the Dutch blueprint. There is a great diversity in teaching methods that aim to achieve a better understanding of scientific knowledge. Applying a constructivist approach to learning in acquiring research competencies we wonder how a research-intensive course is evaluated early in the curriculum and what learning gain students perceive. In a collaborative research-intensive course, the class of 300s-year students rated the quality of 150 preselected randomized controlled trials (RCT) using JAMA Users' Guides, and the pharmaceutical advertisements in which they were referenced. Each student rated two RCTs. Data were analyzed to answer a relevant research question. After the course students completed an evaluation survey. We did this in five consecutive years to capture student experience in relation to fostering a scientific mindset (n = 1,500). In addition we studied outcome of this scientific mindset as scientific output (publications) in journals. Survey data indicate that it is feasible to successfully implement a research-intensive course based on a large cohort using a constructivist paradigm early in the curriculum. Students consider it challenging and report high learning gain in several domains. Aggregated data have even led to four publications in journals. Implementing an active learning research experience early in the curriculum can foster student attitudes, provided the level of difficulty correctly matches the learners' prior knowledge. Further research is required to determine how to improve these active research curricula to maximize impact on learners.

Meconium-stained amniotic fluid: discharge vigorous newborns.

BACKGROUND: Most infants born through meconium-stained amniotic fluid (MSAF) are observed clinically for 24 h postnatally. Only 5% of infants born through MSAF develop the meconium aspiration syndrome (MAS), a serious condition requiring medical intervention. OBJECTIVE: To evaluate the value of 24-h postnatal observation of infants born through MSAF. METHODS: A cohort of 394 term neonates born through MSAF was studied. Data were collected on Apgar scores, the development of MAS and other perinatal factors. RESULTS: Nineteen of the 394 (4.8%) infants born through MSAF developed MAS. 298 (76%) infants had a 5-minute Apgar score (5'AS) of >or=9. In this group the number of infants developing MAS (1; 0.3%) was significantly lower compared with the 5'AS

Why does meconium cause meconium aspiration syndrome? Current concepts of MAS pathophysiology.

One in every 7 pregnancies ends with meconium-stained amniotic fluid and approximately 5% of these infants develop the meconium aspiration syndrome (MAS). MAS is a severe disease of the (mainly) term neonate, characterized by respiratory distress, pulmonary inflammation, persistent pulmonary hypertension and chronic hypoxia. The pathophysiology of MAS is multifactorial and complex. In this article, we discuss the mechanical and chemical effects of meconium on a newborn's airway, meconium-induced inflammation, mediated by proinflammatory cytokines and chemokines, the complement system and the proinflammatory enzyme phospholipase A2. Furthermore, we focus on MAS-related apoptotic cell death, causing severe acute lung injury due to damage and detachment of lung airway and alveolar cells. Finally, risk factors for MAS development to identify those newborns that develop MAS and those who do not are discussed.

Secretory phospholipase A(2) in newborn infants with sepsis.

OBJECTIVE: To investigate secretory phospholipase A(2) (sPLA(2)) activity in neonatal sepsis. STUDY DESIGN: Plasma sPLA(2) activity, C-reactive protein (CRP) concentration, leukocyte count and immature/total neutrophil (I/T) ratio were assessed in a group of 156 infants admitted for neonatal intensive care, who were classified as documented sepsis (n=24), suspected infection (n=77) and controls (n=55). Interleukin-6 (IL-6) concentrations were assessed in a subgroup (n=29). RESULT: sPLA(2) activity, CRP concentration and I/T ratio were higher in sepsis than in suspected infection or control groups. sPLA(2) activity advanced with increasing CRP, I/T ratio and IL-6 was highest in infants with respiratory distress syndrome (RDS). Compared to CRP, sPLA(2) had equal sensitivity and lower specificity. Compared to I/T ratio, sensitivity and specificity of sPLA(2) were higher. CONCLUSION: Plasma sPLA(2) activity is increased in neonatal sepsis and highest in infants with RDS. Further studies should assess the potential of sPLA(2) inhibition in neonatal sepsis.

Axillary and rectal temperature measurements poorly agree in newborn infants.

AIM: Evaluation of the agreement between axillary temperature measurements and rectal temperature measurements in neonates. METHODS: Rectal and axillary body temperatures were simultaneously measured for 3 min in 33 neonates (gestational age 25-42 weeks, weight 840-4,005 g). Two investigators performed paired measurements, one in each neonate. A single type of thermometer was used in this study: one thermometer for each rectal and another thermometer for each axillary measurement. The Bland-Altman method was used (95% 'limits of agreement': mean +/- 2 SD) to determine the level of agreement between axillary and rectal measurements. RESULTS: The axillary temperature was significantly lower than the rectal temperature (mean +/- SD 0.27 +/- 0.20 degrees C, p < 0.05). The '95% limits of agreement' ranged from -0.13 to +0.67 degrees C. Increasing postnatal age (days) showed a significant increase in temperature difference (rectal minus axillary; r = 0.54; p < 0.05). CONCLUSIONS: The mean difference between axillary and rectal temperature shows a wide variation. Axillary temperature measurements cannot be used interchangeably with rectal measurements in neonates.

[Serious complications of umbilical venous catheterisation]. / Ernstige complicaties van een navelvenelijn.

Three male newborns, born at 30 weeks, 36 weeks and at term, respectively, developed serious complications related to umbilical venous catheters. The first patient had persistent bacteraemia due to a cardiac thrombus. He recovered after treatment. In the second patient, the umbilical venous catheter was placed in the pericardial sac, causing accumulation of parenteral nutrition and fatal cardiac tamponade. In the third patient, the umbilical catheter was positioned in the liver, leading to extravasation of parenteral nutrition in the liver and peritoneal cavity. At follow-up, he had developed an atrial septum defect, hypotonia and developmental retardation. Umbilical venous catheterisation has been used in neonatal intensive care units for more than 50 years to allow continuous infusion of medication, fluids and nutrition. However, the use of umbilical venous catheters can be associated with severe infectious, thrombotic and traumatic complications. Therefore, umbilical venous catheterisation requires a critical assessment of the need, alternatives and possible complications.

Phospholipase A2 is present in meconium and inhibits the activity of pulmonary surfactant: an in vitro study.

UNLABELLED: Atelectasis, a major contributor to pulmonary dysfunction in meconium aspiration syndrome (MAS), is produced by bronchiolar obstruction and surfactant inactivation. It has been shown that substances in meconium, e.g. fatty acids, inhibit surfactant activity. However, the role of the enzyme phospholipase A2 (PLA2), which hydrolyses surfactant in adult respiratory distress syndrome (ARDS), has not yet been studied. Our objective was to investigate whether PLA2 is present in meconium and inhibits pulmonary surfactant activity in vitro. Therefore, the presence of PLA2 activity in meconium, collected from 10 newborns, was measured by the formation of lysophosphatidylcholine after incubation of meconium with radioactively labelled dipalmitoylphosphatidylcholine. Meconium was fractionated by Sephadex G-100 column chromatography and the fractions were assayed for PLA2 activity. Also, their effect on the surface tension of surfactant (Curosurf) was measured using a pulsating bubble surfactometer (PBS). PLA2 activity was present in all meconium samples. Addition of meconium to surfactant significantly increased surface tension (mean +/- SD: 1.7 +/- 1.6 mN/m to 24.3 +/- 6.7 mN/m, p = 0.0001) and only the addition of the PLA2 containing fraction from meconium to surfactant also significantly increased surface tension (mean 1.7 +/- 1.6 mN/m to 19.0 +/- 3.58 mN/m, p < 0.0001). CONCLUSION: PLA2 is present in meconium and inhibits the activity of pulmonary surfactant in vitro. Therefore, PLA2 in meconium may contribute to surfactant inactivation and alveolar atelectasis in MAS.

The capacity of different infusion fluids to lower the prooxidant activity of plasma iron: an important factor in resuscitation?

BACKGROUND: Prooxidant activity of non-protein-bound iron (NPBI) is an important contributor to reactive oxygen species-induced injury after the resuscitation of critically ill patients. Plasma NPBI occurs in critically ill adults, children, and newborn babies, who often require resuscitation. The ability of the resuscitation fluids to bind iron and lower the patients' NPBI levels in vitro has not previously been studied. STUDY DESIGN AND METHODS: In an in vitro model, highly iron-saturated cord blood plasma from 10 preterm and 10 term babies was mixed with FFP, pasteurized plasma protein solution, and 0.9-percent saline. Plasma from 10 healthy adult volunteers was used as a control. Before and after the mixing with any resuscitation fluid, NPBI levels and ceruloplasmin iron-oxidizing and transferrin iron-binding antioxidant capacities were measured. RESULTS: After the in vitro mixing with FFP, the incidence and concentration of NPBI were markedly decreased and the iron-binding antioxidant capacity was increased in the plasma of the preterm and term babies. Being mixed with pasteurized plasma protein solution and 0.9-percent saline did not influence the iron-binding antioxidant capacity of newborn babies' plasma. In the control plasma, results were not changed after the mixing with any resuscitation fluid. In every group, the iron-oxidizing antioxidant capacity was not changed after the mixing with any fluid. CONCLUSION: Iron-induced oxidative tissue damage may be influenced by resuscitation fluids. In the ongoing debate over the choice of crystalloid or colloid resuscitation fluids, the influence of each fluid on the patient's antioxidant capacity warrants more attention.

[Evaluation of gradual conversion to a less invasive therapeutic strategy for pregnant women with alloimmune thrombocytopenia in the fetus for prevention of intracranial hemorrhage]. / Evaluatie van de geleidelijke overgang naar een minder invasieve strategie voor de behandeling van zwangeren met allo-immuuntrombocytopenie bij de foetus, ter preventie van hersenbloeding.

OBJECTIVE: To evaluate a less invasive management strategy for pregnant women with neonatal alloimmune thrombocytopenia without a history of intracranial haemorrhage. DESIGN: Retrospective and descriptive. METHOD: In Leiden University Medical Centre, the Netherlands, in the period 1994-August 1999, 31 women with 32 pregnancies were treated. Six women had a history of a sibling with thrombocytopenia and intracranial haemorrhage and 26 a history of a sibling with (severe) thrombocytopenia without haemorrhage. Treatment options consisted of weekly administered intravenous immunoglobulin (ivIG) to the mother without diagnostic cordocentesis, cordocentesis with foetal blood sampling and intrauterine platelet transfusions to the fetus. In the group without history of intracranial haemorrhage fetal blood sampling and platelet transfusion were gradually abandoned as much as possible. RESULTS: In the children of the treated pregnant women there were no instances of intracranial haemorrhage. In addition, the platelet count in cord blood was higher, compared with patients treated before 1994 and with literature data. CONCLUSION: A less invasive management strategy in case of a history without intracranial haemorrhage seems justified based on results in our population. Administration of ivIG without diagnostic cordocentesis, however, results in a lost opportunity to verify the indication and the effectiveness of treatment.

Acinetobacter junii causes life-threatening sepsis in preterm infants.

Acinetobacter junii caused sepsis in six preterm infants in our neonatal unit within 48 h. Each infant with clinical signs of systemic infection and activation of the acute phase response had two positive blood cultures with Acinetobacter junii. The sudden onset, the short duration of the outbreak and the fact that none of the infants were colonized by A. junii suggested a common source of A. junii administered directly into the blood. The only feature shared by all six affected newborns was an intravenous fat emulsion (Intralipid 10%), which was shown to be an excellent growth medium for A. junii. Sepsis did not occur in four infants with 20% fat emulsion or amino acids only. Vaminolact did not support growth of the outbreak strain. The immediate source of the outbreak could not be identified: samples of the actual feeds given were not available for investigation, but A. junii was not isolated from parenteral solutions with identical batch numbers used in the septic infants. We conclude that Acinetobacter junii can cause a life-threatening infection in preterm neonates. Contaminated intravenous fat emulsion is implicated as a possible source of the infection. As a part of rigid infection control, intravenous feedings should be prepared under aseptic conditions.

[The stumbling toddler]. / De zwalkende kleuter.

Four previously healthy children, two boys aged 5 and one boy and one girl aged 4 more or less acutely developed a stumbling gait. The causes varied from benign such as postviral acute cerebellar ataxia and benign paroxysmal vertigo to potentially life-threatening such as intoxication with benzodiazepines and medulloblastoma. Treatment led to complete or partial recovery. (Sub)acute balance disorders in previously healthy children can be due to cerebellar ataxia, vestibular disorders and abnormal proprioception. Ancillary investigations are warranted in case of gradually developing ataxia, accompanying neurological deficits, suspicion of intoxication, recurrent or familial ataxia, no spontaneous remission or even progression. In children with an isolated cerebellar ataxia without these features, ancillary investigations may be avoided, although in such cases careful follow-up remains necessary.

Effect of interleukin 8 in meconium on in-vitro neutrophil chemotaxis.

BACKGROUND: Pneumonitis, characterised by large numbers of neutrophils in the lung, is an important feature of the meconium aspiration syndrome. The mechanism underlying the neutrophil influx is not known. We have investigated whether meconium has chemotactic activity and whether such activity is related to the presence of interleukin 8. METHODS: The chemotactic activity of meconium on neutrophils from newborn infants was assessed in a Boyden-chamber assay. Interleukin 8 and formyl-methionyl-leucyl-phenylalanine (f-MLP) served as positive controls. Inhibition of chemotaxis was assessed with monoclonal antibody to interleukin 8. The interleukin-8 concentration was measured by ELISA. FINDINGS: Sterile meconium suspension from seven unrelated newborn babies increased migration of neutrophils from neonates in comparison with random migration (79, 72, 70, 50, 58, 88 microm vs 46 microm; p<0.001). This effect was greatest at a meconium concentration of 5 g/L, although differences between samples from individual babies were observed. Interleukin 8 was present in all meconium suspensions (480-3980 ng/L). Anti-interleukin-8 inhibited neutrophil migration. INTERPRETATION: Interleukin 8 is present in meconium and it induces chemotaxis of neutrophils in vitro. This mechanism may have a role in the pathogenesis of pneumonitis in meconium aspiration syndrome.

[Nitric oxide inhalation in newborn infants with pulmonary hypertension]. / Inhalatie van stikstofmonoxide bij pasgeborenen met pulmonale hypertensie.

Nitric oxide (NO) is an important endogenous vasodilator. NO, produced in the endothelial cell, causes vasodilation by relaxation of the vascular smooth muscle cell. Inhalation of NO plays a role in the treatment of persistent pulmonary hypertension of the newborn, a syndrome with considerable morbidity and mortality. NO inhalation specifically leads to pulmonary vasodilation without systemic hypotension, since NO binds avidly to haemoglobin. Neonates with pulmonary hypertension associated with lung hypoplasia, meconium aspiration syndrome, infantile inspiratory distress syndrome due to surfactant deficiency, and sepsis have been treated with inhaled NO. Literature data on NO inhalation and experience in our units with NO inhalation show an improvement in arterial oxygen tension and a decreased need for extracorporeal membrane oxygenation, but no reduction in mortality. NO toxicity as a result of NO inhalation in the newborn has not been reported yet.

Outbreak of septicaemia in neonates caused by Acinetobacter junii investigated by amplified ribosomal DNA restriction analysis (ARDRA) and four typing methods.

Septicaemia caused by Acinetobacter occurred in six infants in the neonatal unit. A total of 18 acinetobacters were isolated from blood cultures, cultures of intravascular catheters, and surveillance cultures. Twelve isolates from the six affected infants were identified as Acinetobacter junii by the use of a novel method, amplified ribosomal DNA restriction analysis (ARDRA). Typing of the organisms using the biochemical profiles of the API 20NE system, antibiogram typing, cell envelope protein electrophoresis, and PCR fingerprinting with two primer sets, ERIC1/ERIC2 and ERIC2/ 1026, showed that these 12 isolates were indistinguishable, whereas the remaining six isolates were different. The six infants recovered after therapy with ciprofloxacin alone in five cases and with a combination of ciprofloxacin and gentamicin in one case. This study showed that A. junii is capable of causing a serious, though non-fatal infection in neonates. The combined use of genotypic and phenotypic methods allowed the rapid separation of epidemic from non-epidemic isolates. It is concluded that for a better understanding of the role of the various Acinetobacter genomic species in human pathology, identification of acinetobacters according to the recent taxonomy is imperative.

Uric acid and ascorbic acid redox ratios in plasma and tracheal aspirate of preterm babies with acute and chronic lung disease.

This study compared plasma redox ratios of uric acid and ascorbic acid in well preterm babies with those with respiratory distress syndrome (RDS) and chronic lung disease (CLD), and investigated the relationship between these ratios and their respective measurements in tracheal aspirate. On day 1 after birth, plasma allantoin and allantoin/uric acid ratio were elevated in CLD (p < .05), and both markers of oxidative stress enabled early prediction of development of CLD (sensitivity and specificity: 54 and 83%, respectively). The relation between allantoin production and oxidative stress is supported by the correlation between the allantoin level and oxygen therapy in both RDS and CLD (p < .05). Reduced and oxidize ascorbic acid in plasma decreased postnatally in all groups and their redox ratio remained stable. Uric acid and ascorbic acid redox ratios were significantly elevated in tracheal aspirates compared to plasma samples (p < .05), and there was a strong positive correlation between both ratios (p < .005). These markers may be useful in monitoring babies with respiratory distress.