Raising positive expectations helps patients with minor ailments: A cross-sectional study

Background: Consultations for minor ailments constitute a large part of the workload of general practitioners (GPs). As medical interventions are not always available, specific communication strategies, such as active listening and positive communication, might help GPs to handle these problems adequately. This study examines to what extent GPs display both strategies during consultations for minor ailments and investigates how each of these relate to the patients' perceived health, consultation frequency and medication adherence. Methods: 524 videotaped consultations between Dutch GPs and patients aged 18 years or older were selected. All patients presented a minor ailment, and none of them suffered from a diagnosed chronic illness. The observation protocol included the validated Active Listening Observation Scale (ALOS-global), as well as three domains of positive communication, i.e. providing reassurance, a clear explanation, and a favourable prognosis. Patients completed several questionnaires before, immediately after, and two weeks after the consultation. These included measures for state anxiety (STAI), functional health status (COOP/ WONCA charts) and medication adherence (MAQ). Consultation frequency was available from an ongoing patient registration. Data were analysed using multivariate regression analyses. Results: Reassurance was related to patients' better overall health. Providing a favourable prognosis was linked to patients feeling better, but only when accompanied by a clear explanation of the complaints. A clear explanation was also related to patients feeling better and less anxious, except when patients reported a low mood pre-visit. Active listening alone was positively associated with patients feeling worse. Among patients in a good mood state, active listening was associated with less adherence. Conclusion: To some extent, it seems helpful when GPs are at the same time clear and optimistic about the nature and course of minor ailments. Yet, it does not seem helpful always and in all cases, e.g. when patients feel low upon entering the consulting room. Although communication strategies might to some extent contribute to the management of minor ailments, the results of this observational study also indicate that it is important for a physician to pay attention to the mood of the patient who enters the consulting room. (aut. ref.

Improving the quality and efficiency of follow-up after curative treatment for breast cancer – rationale and study design of the MaCare trial

BACKGROUND: After curative treatment for breast cancer women frequently attend scheduled follow-up examinations. Usually the follow-up is most frequent in the first 2–3 years (2–4 times a year); thereafter the frequency is reduced to once a year in most countries. Its main aim is to detect local disease recurrence, or a second primary breast cancer, but also to provide information and psychosocial support. However, the cost-effectiveness of these frequent visits is under much debate, leading to a search for less intensive and more cost-effective follow-up strategies. In this paper the design of the MaCare trial is described. This trial compares the cost-effectiveness of four follow-up strategies for curatively treated breast cancer patients. We investigate the costs and effects of nurse-led telephone follow-up and a short educational group programme. METHODS/DESIGN: The MaCare trial is a multi centre randomised clinical trial in which 320 breast cancer patients are randomised into four follow-up strategies, focussed on the first 18 months after treatment: 1) standard follow-up; 2) nurse-led telephone follow-up; 3) arm 1 with the educational group programme; 4) arm 2 with the educational group programme. Data is collected at baseline and 3, 6, 12 and 18 months after treatment. The primary endpoint of the trial is cancer-specific quality of life as measured by the global health/QoL scale of the EORTC QLQ-C30. Secondary outcomes are perceived feelings of control, anxiety, patients' satisfaction with follow-up and costs. A cost-effectiveness analysis will be performed from a societal perspective. DISCUSSION: Reduced follow-up strategies for breast cancer have not yet been widely applied in clinical practice. Improvement of psychosocial support and information to patients could lead to a better acceptance of reduced follow-up. The MaCare trial combines a reduced follow-up strategy with additional psychosocial support. Less frequent follow-up can reduce the burden on medical specialists and costs. The educational group programme can improve QoL of patients, but also less frequent follow-up can improve QoL by reducing the anxiety experienced for each follow-up visit. Results of the trial will provide knowledge on both costs and psychosocial aspects regarding follow-up and are expected in 2009

Effects of fructose restriction on blood pressure: Secondary analysis of a double-blind randomized controlled trial

BACKGROUND: Despite convincing animal data, there is an ongoing debate on whether and how fructose affects blood pressure in humans. The aim of this study was to investigate the effects of fructose restriction on blood pressure, and the role of endothelial function herein. METHODS: forty-four overweight individuals were asked to follow a fructose-restricted diet (<7.5 g/meal and <10 g/day) for 6 weeks. They were randomly assigned to double-blind supplementation with glucose (=intervention group) or fructose (=control group) powder three times daily. Office blood pressure was measured with an automated device, and endothelial function was assessed by reactive hyperemia peripheral arterial tonometry, skin laser doppler flowmetry, and serum sE-selectin. RESULTS: Thirty-seven participants completed the study. Systolic blood pressure decreased significantly in the intervention group (change from baseline: -3.3 mmHg; 95%CI:-8.8,- 0.3), but this change was not statistically different from the control group. In contrast, diastolic blood pressure decreased significantly in the intervention group in comparison to controls (difference: -4.0 mmHg; 95%CI:-9.5,-0.5). Furthermore, the change in fructose intake was associated with the change in diastolic blood pressure (beta: 0.085 mmHg; 95% CI: 0.032;0.138). The endothelial markers were not affected by the intervention. Finally, the effects of the intervention on diastolic blood pressure appeared to be higher in individuals consuming high amounts of salt at baseline (difference: -9.0 mmHg; 95%CI:-14.5,-2.5). CONCLUSIONS: Six-week fructose restriction per se results in a dose-dependent decrease in diastolic blood pressure. Further studies are warranted to elucidate the effects of fructose restriction on salt-sensitive hypertension in humans. TRIAL REGISTRATION: www. CLINICALTRIALS: gov; NCT03067428

Effects of fructose restriction on blood pressure:Secondary analysis of a double-blind randomized controlled trial

Background: Despite convincing animal data, there is an ongoing debate on whether and how fructose affects blood pressure in humans. The aim of this study was to investigate the effects of fructose restriction on blood pressure, and the role of endothelial function herein. Methods: forty-four overweight individuals were asked to follow a fructose-restricted diet (<7.5 g/meal and <10 g/day) for 6 weeks. They were randomly assigned to double-blind supplementation with glucose (=intervention group) or fructose (=control group) powder three times daily. Office blood pressure was measured with an automated device, and endothelial function was assessed by reactive hyperemia peripheral arterial tonometry, skin laser doppler flowmetry, and serum sE-selectin. Results: Thirty-seven participants completed the study. Systolic blood pressure decreased significantly in the intervention group (change from baseline: −3.3 mmHg; 95%CI:-8.8,– 0.3), but this change was not statistically different from the control group. In contrast, diastolic blood pressure decreased significantly in the intervention group in comparison to controls (difference: −4.0 mmHg; 95%CI:-9.5,-0.5). Furthermore, the change in fructose intake was associated with the change in diastolic blood pressure (beta: 0.085 mmHg; 95% CI: 0.032;0.138). The endothelial markers were not affected by the intervention. Finally, the effects of the intervention on diastolic blood pressure appeared to be higher in individuals consuming high amounts of salt at baseline (difference: −9.0 mmHg; 95%CI:-14.5,-2.5). Conclusions: Six-week fructose restriction per se results in a dose-dependent decrease in diastolic blood pressure. Further studies are warranted to elucidate the effects of fructose restriction on salt-sensitive hypertension in humans. Trial registration: www.clinicaltrials.gov; NCT03067428

Arginine does not rescue p.Q188R mutation deleterious effect in classic galactosemia

BackgroundClassic galactosemia is a rare genetic metabolic disease with an unmet treatment need. Current standard of care fails to prevent chronically-debilitating brain and gonadal complications.Many mutations in the GALT gene responsible for classic galactosemia have been described to give rise to variants with conformational abnormalities. This pathogenic mechanism is highly amenable to a therapeutic strategy based on chemical/pharmacological chaperones. Arginine, a chemical chaperone, has shown beneficial effect in other inherited metabolic disorders, as well as in a prokaryotic model of classic galactosemia.The p.Q188R mutation presents a high prevalence in the Caucasian population, making it a very clinically relevant mutation. This mutation gives rise to a protein with lower conformational stability and lower catalytic activity. The aim of this study is to assess the potential therapeutic role of arginine for this mutation.MethodsArginine aspartate administration to four patients with the p.Q188R/p.Q188R mutation, in vitro studies with three fibroblast cell lines derived from classic galactosemia patients as well as recombinant protein experiments were used to evaluate the effect of arginine in galactose metabolism. This study has been registered at https://clinicaltrials.gov (NCT03580122) on 09 July 2018. Retrospectively registered.ResultsFollowing a month of arginine administration, patients did not show a significant improvement of whole-body galactose oxidative capacity (p=0.22), erythrocyte GALT activity (p=0.87), urinary galactose (p=0.52) and urinary galactitol levels (p=0.41). Patients' fibroblasts exposed to arginine did not show changes in GALT activity. Thermal shift analysis of recombinant p.Q188R GALT protein in the presence of arginine did not exhibit a positive effect.ConclusionsThis short pilot study in four patients homozygous for the p.Q188R/p.Q188R mutation reveals that arginine has no potential therapeutic role for galactosemia patients homozygous for the p.Q188R mutation

Arginine does not rescue p.Q188R mutation deleterious effect in classic galactosemia

Abstract Background Classic galactosemia is a rare genetic metabolic disease with an unmet treatment need. Current standard of care fails to prevent chronically-debilitating brain and gonadal complications. Many mutations in the GALT gene responsible for classic galactosemia have been described to give rise to variants with conformational abnormalities. This pathogenic mechanism is highly amenable to a therapeutic strategy based on chemical/pharmacological chaperones. Arginine, a chemical chaperone, has shown beneficial effect in other inherited metabolic disorders, as well as in a prokaryotic model of classic galactosemia. The p.Q188R mutation presents a high prevalence in the Caucasian population, making it a very clinically relevant mutation. This mutation gives rise to a protein with lower conformational stability and lower catalytic activity. The aim of this study is to assess the potential therapeutic role of arginine for this mutation. Methods Arginine aspartate administration to four patients with the p.Q188R/p.Q188R mutation, in vitro studies with three fibroblast cell lines derived from classic galactosemia patients as well as recombinant protein experiments were used to evaluate the effect of arginine in galactose metabolism. This study has been registered at https://clinicaltrials.gov (NCT03580122) on 09 July 2018. Retrospectively registered. Results Following a month of arginine administration, patients did not show a significant improvement of whole-body galactose oxidative capacity (p = 0.22), erythrocyte GALT activity (p = 0.87), urinary galactose (p = 0.52) and urinary galactitol levels (p = 0.41). Patients’ fibroblasts exposed to arginine did not show changes in GALT activity. Thermal shift analysis of recombinant p.Q188R GALT protein in the presence of arginine did not exhibit a positive effect. Conclusions This short pilot study in four patients homozygous for the p.Q188R/p.Q188R mutation reveals that arginine has no potential therapeutic role for galactosemia patients homozygous for the p.Q188R mutation

DNA-testing for BRCA1/2 prior to genetic counselling in patients with breast cancer: design of an intervention study, DNA-direct

Contains fulltext : 110772.pdf (publisher's version ) (Open Access)BACKGROUND: Current practice for patients with breast cancer referred for genetic counseling, includes face-to-face consultations with a genetic counselor prior to and following DNA-testing. This is based on guidelines regarding Huntington's disease in anticipation of high psychosocial impact of DNA-testing for mutations in BRCA1/2 genes. The initial consultation covers generic information regarding hereditary breast cancer and the (im)possibilities of DNA-testing, prior to such testing. Patients with breast cancer may see this information as irrelevant or unnecessary because individual genetic advice depends on DNA-test results. Also, verbal information is not always remembered well by patients. A different format for this information prior to DNA-testing is possible: replacing initial face-to-face genetic counseling (DNA-intake procedure) by telephone, written and digital information sent to patients' homes (DNA-direct procedure). METHODS/DESIGN: In this intervention study, 150 patients with breast cancer referred to the department of Clinical Genetics of the Radboud University Nijmegen Medical Centre are given the choice between two procedures, DNA-direct (intervention group) or DNA-intake (usual care, control group). During a triage telephone call, patients are excluded if they have problems with Dutch text, family communication, or of psychological or psychiatric nature. Primary outcome measures are satisfaction and psychological distress. Secondary outcome measures are determinants for the participant's choice of procedure, waiting and processing times, and family characteristics. Data are collected by self-report questionnaires at baseline and following completion of genetic counseling. A minority of participants will receive an invitation for a 30 min semi-structured telephone interview, e.g. confirmed carriers of a BRCA1/2 mutation, and those who report problems with the procedure. DISCUSSION: This study compares current practice of an intake consultation (DNA-intake) to a home informational package of telephone, written and digital information (DNA-direct) prior to DNA-testing in patients with breast cancer. The aim is to determine whether DNA-direct is an acceptable procedure for BRCA1/2 testing, in order to provide customized care to patients with breast cancer, cutting down on the period of uncertainty during this diagnostic process

Propionic acidemia as a cause of adult-onset dilated cardiomyopathy

Dilated cardiomyopathy (DCM) is extremely heterogeneous with a large proportion due to dominantly inherited disease-causing variants in sarcomeric genes. Recessive metabolic diseases may cause DCM, usually with onset in childhood, and in the context of systemic disease. Whether metabolic defects can also cause adult-onset DCM is currently unknown. Therefore, we performed an extensive metabolic screening in 36 consecutive adult-onset DCM patients. Diagnoses were confirmed by Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA). Measurement of propionyl-CoA carboxylase (PCC) activity was done in fibroblasts. Whole exome sequencing (WES) data of 157 additional DCM patients were analyzed for genetic defects. We found a metabolic profile characteristic for propionic acidemia in a patient with severe DCM from 55 years of age. Genetic analysis demonstrated compound heterozygous variants in PCCA. Enzymatic activity of PCC in fibroblasts was markedly reduced. A targeted analysis of the PCCA and PCCB genes using available WES data from 157 further DCM patients subsequently identified another patient with propionic acidemia. This patient had compound heterozygous variants in PCCB, and developed severe DCM from 42 years of age. Adult-onset DCM can be caused by propionic acidemia, an autosomal recessive inheritable metabolic disorder usually presenting as neonatal or childhood disease. Current guidelines advise a low-protein diet to ameliorate or prevent detrimental aspects of the disease. Long-term follow-up of a larger group of patients may show whether this diet would also ameliorate DCM. Our results suggest that diagnostic metabolic screening to identify propionic acidemia and related disorders in DCM patients is justified