The UPHILL study: A nutrition and lifestyle intervention to improve quality of life for patients with pulmonary arterial hypertension.

The aim of the UPHILL study (a nutrition and lifestyle intervention in patients with pulmonary arterial hypertension [PAH]: effect on quality of life [QoL]), was to determine the effect of innovative nutritional interventions on adjustments in nutritional intake and QoL. In this study a group of prevalent PAH patients at a single center in Amsterdam (the Netherlands) was informed about healthy nutrition using a newly designed video e-learning. They were subsequently instructed to follow a healthy diet during dietary intervention. Nutritional intake was assessed using a food frequency questionnaire (HELIUS) and QoL by the short-form (SF)-36 questionnaire. Nutritional parameters were determined in blood samples. Seventeen patients stable under treatment, who had been diagnosed with PAH 7.0 [3.0-14.0] years before, started and completed the intervention (2 males, 15 females; 45.35 ± 13.57 years). Since all patients in the intervention group made behavioral changes in nutritional intake, during study and follow-up, nutritional and lifestyle adaptations persisted. Despite the fact that patients had already high mean scores at baseline for both mental (74.10 [60.51-84.25]) and physical QoL (66.46 [50.21-73.84]), scores improved further during e-learning. Furthermore, patients who realized most nutritional adaptations, had the best improvement in QoL. This pilot study showed that e-learning modules on nutrition provide an unique opportunity to change nutritional intake in PAH patients and by that improve QoL.

Nutritional status in pulmonary arterial hypertension.

Nutritional deficiencies have been described in patients with pulmonary arterial hypertension (PAH), such as in iron and vitamin D. However, an extensive description of vitamin and mineral status is lacking and until now there is no data on dietary intake in PAH patients. We analyzed blood samples and determined nutritional intake using a food frequency questionnaire (HELIUS) in a cohort of prevalent PAH patients at a single center in Amsterdam, the Netherlands. Quality of life (QoL) was assessed by the SF-36 questionnaire. In total, 37 patients were included (6 males, 31 females; 48 ± 16 years). The dietary intake of sugar was above 25 g in 87% of the patients and fluid intake was above 1500 ml in 78% of the patients. Sodium intake was below 1800 mg in the majority (56%) of the patients. Sugar and fluid intake were linear related. We confirm previously observed deficiencies of iron and vitamin D in our study population. In addition, we observed a functional vitamin B12 deficiency in 29% of patients, which coincided with an increased expression of methylmalonic acid. 60% of patients had a low vitamin K1 status (<0.8 nmol/L). Finally, 40% of patients had selenium levels below <100 µg/L and low selenium levels associated with reduced vitality in these patients. Besides the known deficiencies in iron and vitamin D levels, we observed in a subset of patients signs of vitamin B12, vitamin K1 and selenium deficiencies. There is room for improving dietary intake. Future research aims to demonstrate the clinical importance and reveal the effect of nutritional interventions.

Measuring vitamin C in critically ill patients: clinical importance and practical difficulties-Is it time for a surrogate marker?

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2021. Other selected articles can be found online at  https://www.biomedcentral.com/collections/annualupdate2021 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from  https://link.springer.com/bookseries/8901 .

Short-term effect of low-dose colchicine on inflammatory biomarkers, lipids, blood count and renal function in chronic coronary artery disease and elevated high-sensitivity C-reactive protein.

AIMS: Inflammation plays a pivotal role in atherothrombosis. Colchicine is an anti-inflammatory drug that may attenuate this process. Cardiovascular protective effects of anti-inflammatory drugs, however, seem to be limited to patients with a biochemical response. We therefore investigated whether short-term exposure to colchicine reduced inflammatory markers and whether additional laboratory changes occur in patients with chronic coronary artery disease. METHODS & RESULTS: In 138 consecutive patients with chronic coronary artery disease and a high sensitivity C-reactive Protein (hs-CRP) ≥ 2 mg/L, inflammatory markers, lipids, haematologic parameters and renal function were measured at baseline and after 30 days exposure to colchicine 0.5mg once daily. Hs-CRP decreased from baseline 4.40 mg/L (interquartile range [IQR] 2.83-6.99 mg/L) to 2.33 mg/L (IQR 1.41-4.17, median of the differences -1.66 mg/L, 95% confidence interval [CI] -2.17 - -1.22 mg/L, p-value <0.01), corresponding to a median change from baseline of -40%. Interleukin-6 decreased from 2.51 ng/L (IQR 1.59-4.32 ng/L) to 2.22 ng/L (median of the differences -0.36 ng/L, 95%CI -0.70 - -0.01 ng/L, p-value 0.04), corresponding to a median change from baseline of -16%. No clinically relevant changes in lipid fractions were observed. Both leukocyte and thrombocyte count decreased (median change from baseline -7% and -4% respectively). Estimated glomerular filtration rate decreased with a mean change from baseline of -2%. CONCLUSION: In patients with chronic coronary artery disease and elevated hs-CRP, one-month exposure to colchicine 0.5 mg once daily was associated with a reduction of inflammatory markers. A small effect was seen on white blood cell count and platelet count, as well as a small decrease in estimated glomerular filtration rate.

Postoperative parathyroid hormone levels as a predictor for persistent hypoparathyroidism.

OBJECTIVE: Hypoparathyroidism is a common complication after thyroidectomy. It is not yet possible to predict in which patients hypoparathyroidism will persist. We aim to determine whether a decrease in PTH levels, measured at the first postoperative day, can identify patients with a high risk for persistent hypoparathyroidism one year after thyroidectomy. DESIGN: Prospective multi-center cohort study. METHODS: Patients undergoing total or completion thyroidectomy were included. We measured PTH levels preoperatively and on the first postoperative day. Primary outcome is the proportion of patients with persistent hypoparathyroidism, defined as the need for calcium supplementation one year after surgery. RESULTS: We included 110 patients of which 81 were used for analysis of the primary outcome. At discharge 72.8% of patients were treated with calcium supplementation. Persistent hypoparathyroidism was present in 14 patients (17.3%) at one-year follow-up, all of them had a decrease in PTH >70% at the first postoperative day. These 14 were 43.8% of the 32 patients who had such a decrease. In the group of 49 patients (59.8%) without a PTH >70% decrease, none had persistent hypoparathyroidism one year after surgery (P-value <0.001). A decrease of >70% in PTH levels had a sensitivity of 100.0% (95% CI: 85.8-100.0%), a specificity of 73.1% (95% CI: 62.5-83.7%) and an area under the curve of 0.87 (95% CI: 0.79-0.94) to predict the risk for persistent hypoparathyroidism. CONCLUSION: In our study a decrease in PTH levels of >70% after total or completion thyroidectomy is a reliable predictor for persistent hypoparathyroidism, and this should be confirmed in larger cohorts.

Reducing Inter-Laboratory Differences between Semen Analyses Using Z Score and Regression Transformations.

BACKGROUND: Standardization of the semen analysis may improve reproducibility. We assessed variability between laboratories in semen analyses and evaluated whether a transformation using Z scores and regression statistics was able to reduce this variability. MATERIALS AND METHODS: We performed a retrospective cohort study. We calculated between-laboratory coefficients of variation (CVB) for sperm concentration and for morphology. Subsequently, we standardized the semen analysis results by calculating laboratory specific Z scores, and by using regression. We used analysis of variance for four semen parameters to assess systematic differences between laboratories before and after the transformations, both in the circulation samples and in the samples obtained in the prospective cohort study in the Netherlands between January 2002 and February 2004. RESULTS: The mean CVBwas 7% for sperm concentration (range 3 to 13%) and 32% for sperm morphology (range 18 to 51%). The differences between the laboratories were statistically significant for all semen parameters (all P<0.001). Standardization using Z scores did not reduce the differences in semen analysis results between the laboratories (all P<0.001). CONCLUSION: There exists large between-laboratory variability for sperm morphology and small, but statistically significant, between-laboratory variation for sperm concentration. Standardization using Z scores does not eliminate between-laboratory variability.

Predictive value of sperm morphology and progressively motile sperm count for pregnancy outcomes in intrauterine insemination.

OBJECTIVE: To investigate the value of sperm parameters to predict an ongoing pregnancy outcome in couples treated with intrauterine insemination (IUI), during a methodologically stable period of time. DESIGN: Retrospective, observational study with logistic regression analyses. SETTING: University hospital. PATIENT(S): A total of 1,166 couples visiting the fertility laboratory for their first IUI episode, including 4,251 IUI cycles. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Sperm morphology, total progressively motile sperm count (TPMSC), and number of inseminated progressively motile spermatozoa (NIPMS); odds ratios (ORs) of the sperm parameters after the first IUI cycle and the first finished IUI episode; discriminatory accuracy of the multivariable model. RESULT(S): None of the sperm parameters was of predictive value for pregnancy after the first IUI cycle. In the first finished IUI episode, a positive relationship was found for ≤4% of morphologically normal spermatozoa (OR 1.39) and a moderate NIPMS (5-10 million; OR 1.73). Low NIPMS showed a negative relation (≤1 million; OR 0.42). The TPMSC had no predictive value. The multivariable model (i.e., sperm morphology, NIPMS, female age, male age, and the number of cycles in the episode) had a moderate discriminatory accuracy (area under the curve 0.73). CONCLUSION(S): Intrauterine insemination is especially relevant for couples with moderate male factor infertility (sperm morphology ≤4%, NIPMS 5-10 million). In the multivariable model, however, the predictive power of these sperm parameters is rather low.

Collecting and validating experiential expertise is doable but poses methodological challenges.

OBJECTIVES: To give an overview of important methodological challenges in collecting, validating, and further processing experiential expertise and how to address these challenges. STUDY DESIGN AND SETTING: Based on our own experiences in studying the concept, operationalization, and contents of experiential expertise, we have formulated methodological issues regarding the inventory and application of experiential expertise. RESULTS: The methodological challenges can be categorized in six developmental research stages, comprising the conceptualization of experiential expertise, methods to harvest experiential expertise, the validation of experiential expertise, evaluation of the effectiveness, how to translate experiential expertise into acceptable guidelines, and how to implement these. The description of methodological challenges and ways to handle those are illustrated using diabetes mellitus as an example. CONCLUSION: Experiential expertise can be defined and operationalized in terms of successful illness-related behaviors and translated into recommendations regarding life domains. Pathways have been identified to bridge the gaps between the world of patients' daily lives and the medical world.

Imprecision and limit of quantification of the new architect 25-hydroxyvitamin D assay.

We examined imprecision and limit of quantification (LOQ) of the new Architect 25-hydroxyvitamin D immunoassay in a multicenter setting. Mean intracenter interlot imprecision varied from 22.0 to 5.0%CV in the concentration range of 16 - 92 nmol/L. LOQs were locally determined as 10.8, 11.2, and 13.5 nmol/L. We conclude that the Architect 25(OH)D assay provides a precise and analytically sensitive method for routine measurement of 25(OH)D.

Supporting people with diabetes mellitus in applying for and participating effectively in paid work: validation of successful diabetes-related behaviors by experiential experts and professional care providers.

OBJECTIVE: To validate successful diabetes-related behaviors, proposed by a group of experiential experts, and to support people with diabetes in applying for and participating effectively in work. METHODS: In a survey among 77 experiential experts and 21 professional care providers, the behaviors were critically appraised regarding several key characteristics. RESULTS: Experiential experts (median scores: 91%, 86%, and 86%) and professionals (median scores: 76%, 76%, and 81%) mostly agreed with these behaviors in terms of clarity, content, and relevance, respectively. Feasibility was seen as somewhat problematic, with median scores by experiential experts and professionals of 65% and 52%, respectively. CONCLUSION: Both groups confirmed the validity of the proposed work-related behaviors that were expected to support people with diabetes. The challenge is to implement these behaviors in practice, by effective dissemination and incorporation in work-related self-management programs.

Harvesting experiential expertise to support safe driving for people with diabetes mellitus: a qualitative study evaluated by peers in a survey.

BACKGROUND: Hypoglycemia is a frequent phenomenon in people being treated for diabetes mellitus, which can acutely disrupt driving performance. For the benefit of personal and public traffic safety, we decided to identify successful diabetes-related (SDR) behaviors to support safe driving for people with diabetes, from the perspective of experiential experts with diabetes mellitus. Experiential experts are people who can manage their own illness and conditions by developing expertise relevant to maintaining health and countering illness, and who are able to use this expertise to the benefit of peers. OBJECTIVE: The aim of our study was to objectify and systematize experiential expertise in terms of SDR behaviors, based on reports by experiential experts, to support safe driving for people with type 1 and type 2 diabetes mellitus. The emphasis was on preventing hypoglycemia as a short-term complication during driving. METHODS: We performed a mixed-methods study involving (i) semi-structured in-depth interviews with 33 experiential experts with diabetes mellitus from the Dutch Diabetes Association (DVN; Diabetesvereniging Nederland), in order to identify SDR behaviors regarding safe driving, and (ii) a validation study by means of a survey among a panel of 98 experiential experts (peers) from the DVN, to determine the extent to which they agreed with the communicability, importance, and feasibility of these behaviors for drivers with diabetes mellitus. RESULTS: We identified a comprehensive set of 11 SDR behaviors, differentiated into seven general and four specific behaviors, to support safe driving. The general behaviors concern the following topics: (i) acquiring knowledge and information; (ii) acquiring and using self-measuring of blood glucose (SMBG) equipment; (iii) knowing one's physical response pattern; (iv) obtaining knowledge about the medication used; (v) preventing long-term eye complications; (vi) influencing factors that can affect blood glucose; and (vii) renewal procedure for driving license. The four specific behaviors refer to the following topics: (i) measures to be taken before driving; (ii) responding effectively to hypoglycemia while driving; (iii) informing and instructing passengers; and (iv) preventing hypoglycemia in drivers with type 2 diabetes mellitus not using SMBG equipment. Key factors for safe driving proved to be the ability of drivers to anticipate and respond effectively to hypoglycemia while driving and to inform and instruct fellow passengers. Participants of the validation survey agreed to a considerable degree with the communicability, importance, and feasibility of these behaviors to support safe driving for people with diabetes mellitus. CONCLUSIONS: This study resulted in the identification and description of SDR behaviors to support safe driving. It proved possible to operationalize experiential expertise in terms of such behaviors. The next step is to have these behaviors validated by professional care providers in the field of diabetes, followed by translation into recommendations in self-management programs.

Multicenter comparison study of current methods to measure 25-hydroxyvitamin D in serum.

OBJECTIVES: Measurement of serum 25-hydroxyvitamin D [25(OH)D] is generally considered to be a reliable indicator of vitamin D status. The recent increase in diversity of 25(OH)D assays prompted us to evaluate the performance of chromatographic methods (two in-house ID-LC-MS/MS and HPLC (ClinRep, Recipe)), a protein binding method (Cobas-25(OH)D-total, Roche) and immunochemical methods (Liaison and RIA (Diasorin), iSYS (IDS), ADVIA Centaur (Siemens), and Architect i1000 and i2000 (Abbott)). METHODS: Blood was drawn from randomly selected outpatients (N=60) at one site after informed consent. DEQAS and SRM 972 samples were obtained from the scheme organizer and NIST, respectively. Serum aliquots were prepared, frozen and transported to participating centers. Method comparison was performed according to CLSI-EP9 specifications. RESULTS: With these patient samples, and in comparison with ID-LC-MS/MS, Deming regression parameters slope, intercept and R were found to be within the ranges [0.57-1.07], [-1.7 to 6.9 nmol/L] and [0.88-0.98], respectively. 25(OH)D2 in DEQAS and SRM samples was fully recognized by chromatographic methods, but only partially by protein binding and immunochemical methods. Chromatographic methods, and to a lesser extent the protein binding assay, showed cross-reactivity with 3-epi-25(OH)D3. Agreement of 25(OH)D assays to ID-LC-MS/MS in sorting patients into distinct 25(OH)D categories varied between 53% and 88%. CONCLUSIONS: Significant bias exists between ID-LC-MS/MS and many, but not all, other 25(OH)D assays. The variable response among different assays for 25(OH)D metabolites impedes the use of uniform cut-off values for defining vitamin D status. Our results indicate the need towards further standardizing assays for 25(OH)D measurement.

Identifying experiential expertise to support people with diabetes mellitus in applying for and participating effectively in paid work: a qualitative study.

OBJECTIVE: Identifying and describing successful diabetes-related (SDR) behaviors from reports by experiential experts to support people with diabetes in applying for and participating effectively in paid work. METHODS: Data were collected by conducting in-depth interviews with experiential experts with diabetes (N = 47). RESULTS: A comprehensive set of SDR behaviors that can help people with diabetes apply for and participate in paid work. The most important factors were reported to be the ability to anticipate problems in job applications, effective self-management activities to prevent and/or respond to hypoglycemia and hyperglycemia at work, informing relevant others in the workplace, and successfully negotiating with employers about adjustments to work conditions. CONCLUSIONS: A set of work-related SDR behaviors was identified. After validation by experiential experts and professionals, these could be translated into recommendations and tested in experiments in self-management programs.

Barriers and facilitating factors in the professional careers of international medical graduates.

OBJECTIVES: Social and cultural diversity are increasingly important characteristics of the medical professional workforce. Every year, substantial numbers of international medical graduates (IMGs) seek jobs outside the countries in which they were educated. This article concerns IMGs who enter the Netherlands as refugees or as spouses of Dutch citizens. As their non-European medical qualifications are not considered equivalent to the Dutch qualifications, they are required to undertake additional medical training. Because little is known about their professional careers, we set out to identify the barriers that confront and the facilitating factors that support IMGs before, during and after their supplementary medical training. METHODS: We invited 58 IMGs who had successfully completed their additional medical training requirements in Maastricht, the Netherlands (1996-2007) to participate in in-depth interviews. They were identified by the university's Institute of Medical Education and from its alumni database. RESULTS: Thirty-two IMGs participated and reported a range of issues affecting their attempts to practise medicine in the Netherlands. Reported barriers included difficulties in accessing information on complementary medical education and lack of (financial) support. Perseverance was reported to be essential. Financial and social support were also reported as facilitating factors. Lack of command of the Dutch language and age were seen as barriers to securing employment and entrance to specialisation. CONCLUSIONS: The barriers identified have major implications for IMGs wishing to practise medicine in the Netherlands. Better support to overcome the difficulties inherent in migration and career change will result in better trained and acculturated doctors who will be more motivated to contribute to society.

Prevalence of habitual refractive errors and anisometropia among Dutch schoolchildren and hospital employees.

PURPOSE: Refractive error (RE) is suggested to cause not only visual impairment, but also functional problems such as aspecific health complaints and lower levels of school achievement. During the last few decades the prevalence of myopia has increased worldwide, especially in Asia. We investigated the prevalence of habitual RE and anisometropia in a Dutch population of children and employees. METHODS: In a cross-sectional study, RE in both eyes of 520 children (aged 11-13 years) and 444 hospital employees (aged 17-60 years) were measured using an autorefractometer. The measurements were performed without using a cycloplegium. Pearson's correlation coefficient (r) was used to analyse correlations between the right and left eyes. Chi-square tests were used to test the differences between subgroups according to gender and age. RESULTS: In schoolchildren 28% of right eyes were myopic (> 0.50 D) and 8% hyperopic (> 0.50 D). Pearson's r between right and left eyes for spherical equivalent power (SEP) was 0.93. The mean cylinder deviation in right eyes was 0.26 D (range 0.00-4.50 D). Anisometropia > 1.00 D was present in 4.6% of children; 22% of children were not optimally (> 0.50 D) corrected. In hospital employees, 30% of right eyes were myopic (> 0.50 D) and 10% hyperopic (> 0.50 D). Pearson's r between right and left eyes for SEP was 0.53. The mean cylinder deviation in right eyes was 0.35 D (range 0.00-5.75 D). Anisometropia > 1.00 D was present in 25% of employees. Anisometropia was more frequently present in employees aged 40-60 years, than in those aged 17-39 years (30% versus 18%; p = 0.02, Cramer's V = 0.15). CONCLUSIONS: Refractive errors are common in children aged 11-13 years and in working adults aged 17-60 years. Distributions of sphere and cylinder deviations are similar for Dutch schoolchildren and hospital employees. Surprisingly, anisometropia proved to be more prevalent with age. In children many eyes are not optimally corrected. Increased attention should be paid to uncorrected and miscorrected REs.

Decision-analytic modeling to assist decision making in organizational innovation: the case of shared care in hearing aid provision.

OBJECTIVE: To illustrate the use of decision-analytic modeling to assist decision making in organizational innovations. STUDY SETTING/DATA SOURCES: Regarding an organizational innovation (shared care in hearing aid provision) available evidence from different sources was synthesized. STUDY DESIGN: A probabilistic Markov model was constructed. DATA COLLECTION/EXTRACTION: We modeled the long-term cost-effectiveness of different organizational formats of shared care as opposed to the current organization. We assessed the expected value of perfect information (EVPI) for several groups of parameters in the model. PRINCIPAL FINDINGS: The current organization had the highest probability of being cost-effective. Additional research is worthwhile, especially on access to care and safety (sensitivity to detect pathology). CONCLUSIONS: Decision-analytic modeling in an early stage of organizational innovation is a valuable tool to facilitate evidence-based decision making.

Choosing between measures: comparison of EQ-5D, HUI2 and HUI3 in persons with hearing complaints.

OBJECTIVES: To generate insight into the differences between utility measures EuroQol 5D (EQ-5D), Health Utilities Index Mark II (HUI2) and Mark III (HUI3) and their impact on the incremental cost-effectiveness ratio (ICER) for hearing aid fitting METHODS: Persons with hearing complaints completed EQ-5D, HUI2 and HUI3 at baseline and, when applicable, after hearing aid fitting. Practicality, construct validity, agreement, responsiveness and impact on the ICER were examined. RESULTS: All measures had high completion rates. HUI3 was capable of discriminating between clinically distinctive groups. Utility scores (n = 315) for EQ-5D UK and Dutch tariff (0.83; 0.86), HUI2 (0.77) and HUI3 (0.61) were significantly different, agreement was low to moderate. Change after hearing aid fitting (n = 70) for HUI2 (0.07) and HUI3 (0.12) was statistically significant, unlike the EQ-5D UK (0.01) and Dutch (0.00) tariff. ICERs varied from 647,209 euros/QALY for the EQ-5D Dutch tariff to 15,811 euros/QALY for HUI3. CONCLUSION: Utility scores, utility gain and ICERs heavily depend on the measure that is used to elicit them. This study indicates HUI3 as the instrument of first choice when measuring utility in a population with hearing complaints, but emphasizes the importance of a clear notion of what constitutes utility with regard to economic analyses.

Exclusive, idiosyncratic and collective expertise in the interprofessional arena: the case of optometry and eye care in The Netherlands.

This paper addresses expertise as the foundation of professional boundaries and domains through a comparative study of four eye care occupations in the Netherlands. Claims of expertise are explored with an analysis of whether practitioners believe that expertise is exclusive to their profession. Results show that (a) established professions display a stronger sense of the 'exclusiveness' of expertise; (b) idiosyncratic expertise is more common among encroaching professions than among established ones. These findings substantiate trends towards professionalism, as jurisdictional disputes on professional domains and boundaries usually occur between more established medical professions seeking to protect their knowledge area, and encroaching ones trying to expand theirs. The study next addresses the ways in which claims to expertise influence practitioners' attitudes towards professional status and professional practice. Attitudes to expertise are influenced by age, and affect professional work in the workplace. Practitioners who considered expertise as a collective characteristic were younger, undertook more examinations, more diagnoses, gave more treatments, referred less, and perceived more problems regarding inter-professional recognition of their professional status.