Challenges and recommendations for high quality research using electronic health records.

Harnessing Real World Data is vital to improve health care in the 21st Century. Data from Electronic Health Records (EHRs) are a rich source of patient centred data, including information on the patient's clinical condition, laboratory results, diagnoses and treatments. They thus reflect the true state of health systems. However, access and utilisation of EHR data for research presents specific challenges. We assert that using data from EHRs effectively is dependent on synergy between researchers, clinicians and health informaticians, and only this will allow state of the art methods to be used to answer urgent and vital questions for patient care. We propose that there needs to be a paradigm shift in the way this research is conducted - appreciating that the research process is iterative rather than linear. We also make specific recommendations for organisations, based on our experience of developing and using EHR data in trusted research environments.

Training residents in patient-centred communication and empathy: evaluation from patients, observers and residents.

BACKGROUND: Patient-centred communication and empathy are key enablers for patient-centred care. However, several studies suggest a downward trend regarding the empathic communication skills of physicians during medical residency. It is known that communication training can have a positive effect on patient-centred communication, empathy and relational skills. Training residents in patient-centred communication and empathy can be an opportunity to improve the patient-centred care. To evaluate the training a tri-focal perspective will be used. METHODS: A 3-day training was developed to improve residents' patient-centred communication and empathy skills at an academic medical health centre, in the Netherlands. The training included: (1) the basics of patient-centred communication and empathy (through presentations, scientific literature), (2) practicing with actors, and (3) reflecting on residents' video recorded consultations (by themselves and communication experts). A pilot study with a pre-post design was conducted to evaluate the training from patient and observer perspectives. Semi-structured interviews were used to get insight into residents' perspective. Nine residents from different specialities followed the training and enrolled in the pilot study. During two random days consultations between residents and patients were video recorded. Patients were asked to fill in two questionnaires, indicating their perspective on residents' empathy and communication skills before as well as after the consultation. All video recorded consultations were coded to rate residents' communication skills, empathy, computer use and agenda-setting. Statistical analysis were performed using multilevel analysis. RESULTS: A total of 137 eligible patients took part in the pilot study. Trained residents showed significant improvement in patient-rated empathy scores. According to observers, residents' computer use improved significantly after the training. The communication skills of trained residents did not improve significantly. Agenda setting by residents showed a downward trend. Almost all residents were satisfied with the training, especially with the video-feedback. CONCLUSIONS: A brief training significantly increased residents' empathy scores according to patients and significantly decreased residents' computer use according to observers. These findings indicate that the quality of patient-centred care can be improved by integrating patient-centred communication into residency programs, at an academic medical health centre. The ultimate goal is to structurally embed the training in residents' education program.

[Shared decision-making: dilemmas in daily practice]. / Samen beslissen: dilemma's in de praktijk.

Shared decision-making is an essential - but often neglected - component of evidence-based medicine. In practice, doctors, nurses and patients encounter dilemmas which are understandable, but not insurmountable. We illustrate this by means of a complex decision concerning therapy in the advanced stage of Parkinson's disease. Evidence of effectiveness differs with each individual therapy, and, in practice, the experiences of neurologists also vary widely. In addition, the various treatment strategies all require a different sort of daily care, and have differing impacts on people's lives. It is time that we worked towards a realistic view of shared decision-making. Shared decision-making cannot be generalised to a 'one size fits all' strategy that we can choose to apply or not to apply at will. It should be a flexible instrument which, depending on the individual and the specific situation, can be put to use to deliver the best tailored care.

Protocol of a randomised delayed-start double-blind placebo-controlled multi-centre trial for Levodopa in EArly Parkinson's disease: the LEAP-study.

BACKGROUND: The aim of this study is to investigate if early treatment with levodopa has a beneficial disease modifying effect on Parkinson's disease (PD) symptoms and functional health, improves the ability to (maintain) work, and reduces the use of (informal) care, caregiver burden, and costs. Additionally, cost-effectiveness and cost-utility of early levodopa treatment will be assessed. METHODS: To differentiate between the direct symptomatic effects and possible disease modifying effects of levodopa, we use a randomised delayed-start double-blind placebo-controlled multi-centre trial design. Patients with early stage PD whose functional health does not yet necessitate initiation of PD-medication will be randomised to either 40 weeks of treatment with levodopa/carbidopa 100/25 mg TID including 2 weeks of dose escalation or to 40 weeks placebo TID. Subsequently, all patients receive levodopa/carbidopa 100/25 mg TID for 40 weeks. There are 8 assessments: at baseline and at 4, 22, 40, 44, 56, 68, and 80 weeks. The primary outcome measure is the difference in the mean total Unified Parkinson's Disease Rating Scale scores between the early- and delayed-start groups at 80 weeks. Secondary outcome measures are rate of progression, the AMC Linear Disability Score, side effects, perceived quality of life with the Parkinson's Disease Questionnaire-39, the European Quality of Life-5 Dimensions (EQ-5D), ability to (maintain) work, the use of (informal) care, caregiver burden, and costs. 446 newly diagnosed PD patients without impaired functional health need to be recruited in order to detect a minimal clinical relevant difference of 4 points on the total UPDRS at 80 weeks. DISCUSSION: The LEAP-study will provide insights into the possible disease modifying effects of early levodopa. TRIAL REGISTRATION: ISRCTN30518857, EudraCT number 2011-000678-72.

Neurostimulation for Parkinson's disease with early motor complications.

BACKGROUND: Subthalamic stimulation reduces motor disability and improves quality of life in patients with advanced Parkinson's disease who have severe levodopa-induced motor complications. We hypothesized that neurostimulation would be beneficial at an earlier stage of Parkinson's disease. METHODS: In this 2-year trial, we randomly assigned 251 patients with Parkinson's disease and early motor complications (mean age, 52 years; mean duration of disease, 7.5 years) to undergo neurostimulation plus medical therapy or medical therapy alone. The primary end point was quality of life, as assessed with the use of the Parkinson's Disease Questionnaire (PDQ-39) summary index (with scores ranging from 0 to 100 and higher scores indicating worse function). Major secondary outcomes included parkinsonian motor disability, activities of daily living, levodopa-induced motor complications (as assessed with the use of the Unified Parkinson's Disease Rating Scale, parts III, II, and IV, respectively), and time with good mobility and no dyskinesia. RESULTS: For the primary outcome of quality of life, the mean score for the neurostimulation group improved by 7.8 points, and that for the medical-therapy group worsened by 0.2 points (between-group difference in mean change from baseline to 2 years, 8.0 points; P=0.002). Neurostimulation was superior to medical therapy with respect to motor disability (P<0.001), activities of daily living (P<0.001), levodopa-induced motor complications (P<0.001), and time with good mobility and no dyskinesia (P=0.01). Serious adverse events occurred in 54.8% of the patients in the neurostimulation group and in 44.1% of those in the medical-therapy group. Serious adverse events related to surgical implantation or the neurostimulation device occurred in 17.7% of patients. An expert panel confirmed that medical therapy was consistent with practice guidelines for 96.8% of the patients in the neurostimulation group and for 94.5% of those in the medical-therapy group. CONCLUSIONS: Subthalamic stimulation was superior to medical therapy in patients with Parkinson's disease and early motor complications. (Funded by the German Ministry of Research and others; EARLYSTIM ClinicalTrials.gov number, NCT00354133.).

Determinants of disability and quality of life in mild to moderate Parkinson disease.

OBJECTIVE: To identify factors that independently contribute to disability and quality of life (QoL) in patients with mild to moderate Parkinson disease (PD). METHODS: A group of 190 patients with PD recruited from outpatient clinics and the Dutch Parkinson's Disease Association participated in this cross-sectional study. Data on demographic and clinical factors, motor symptoms, cognitive functions, affective symptoms, comorbidity, and social support were collected during neurologic and neuropsychological examinations. Disability was rated using the Schwab and England Activities of Daily Living Scale (SE-ADL), the AMC Linear Disability Score (ALDS), and the Functional Independence Measure (FIM). QoL was assessed with the Parkinson's Disease Quality of Life questionnaire (PDQL) and the Medical Outcome Study Short Form (SF-36). Multiple linear regression analyses were conducted to identify determinants of disability and poor QoL. RESULTS: Axial impairment (postural instability and gait difficulty) explained the largest proportion of variance in disability. Bradykinesia and comorbidity contributed to disability, but to a lesser extent. Self-reported mood symptoms and axial impairment were the two factors most closely associated with poorer QoL, but comorbidity and bradykinesia additionally contributed to the explanatory power. Semantic fluency and psychomotor skills were the only cognitive variables related to some aspects of functional outcome. CONCLUSION: Axial impairment is strongly associated with disability in patients with mild to moderate Parkinson disease (PD). Self-report indices of mood status and axial impairment are identified as the main determinants of poor quality of life (QoL). The results of this study may help to identify patients with PD at risk for functional dependence and reduced QoL.

The AMC Linear Disability Score in patients with newly diagnosed Parkinson disease.

OBJECTIVE: The aim of this study was to examine the clinimetric properties of the AMC Linear Disability Score (ALDS), a new generic disability measure based on Item Response Theory, in patients with newly diagnosed Parkinson disease (PD). METHODS: A sample of 132 patients with PD was evaluated using the Hoehn and Yahr (H&Y), the Unified PD Rating Scale motor examination, the Schwab and England scale (S&E), the Short Form-36, the PD Quality of Life Questionnaire, and the ALDS. RESULTS: The internal consistency reliability of the ALDS was good (alpha = 0.95) with 55 items extending the sufficient item-total correlation criterion (r > 0.20). The ALDS was correlated with other disability measures (r = 0.50 to 0.63) and decreasingly associated with measures reflecting impairments (r = 0.36 to 0.37) and mental health (r = 0.23 to -0.01). With regard to know-group validity, the ALDS indicated that patients with more severe PD (H&Y stage 3) were more disabled than patients with mild (H&Y stage 1) or moderate PD (H&Y stage 2) (p < 0.0001). The ALDS discriminated between more or less severe extrapyramidal symptoms (p = 0.001) and patients with postural instability showed lower ALDS scores compared to patients without postural instability (p = or< 0.0001). Compared to the S&E (score 100% = 19%), the ALDS showed less of a ceiling effect (5%). CONCLUSION: The AMC Linear Disability Score is a flexible, feasible, and clinimetrically promising instrument to assess the level of disability in patients with newly diagnosed Parkinson disease.

Motor procedural learning in Parkinson's disease.

Functional neuroimaging research has repeatedly implicated the striatum in motor procedural learning, but attempts to explore this relation in patients with Parkinson's disease (PD) have yielded inconsistent results. Furthermore, the functional impact of procedural learning impairment is unknown. The present study sought to examine the effects of PD on procedural learning and to determine whether impaired procedural learning affects functional status. The performance of 95 non-demented PD patients on the serial reaction time task (SRTT) was compared with that of 44 demographically matched control subjects. The SRTT is a four-choice reaction time task in which visual stimuli are presented in six blocks of 100 trials either in a repeating sequence of 10 stimuli or randomly. Learning was inferred from the reduction of response times over five successive blocks of repeating sequence trials and from the increase in response times in the sixth random block. In addition, neuropsychological tests of declarative memory, executive and visuospatial functions were administered to all participants. Patients also received quantitative ratings of functional outcome. The two groups did not differ in the learning rate across blocks of repeating sequence trials. However, PD patients were significantly less efficient than controls in acquiring sequence-specific knowledge, although this impairment was relatively small (d = 0.38). Patients with more advanced clinical symptoms tended to show worse performance. Separate analyses of a subgroup of 24 non-medicated patients in the early stages of PD revealed no differences in SRTT performance relative to controls. Neuropsychological testing showed impairments in attention and executive functions, immediate and delayed explicit memory and visuospatial skills in the PD group, but none of the cognitive measures were related to procedural learning. Reduced motor sequence learning in PD patients did not influence their functional status. These findings indicate that procedural learning impairment is not an early feature of PD, but is likely to emerge with progression of the disease, independently of cognitive dysfunction or dopaminergic medication.

Visually perceived eye level with reversible pitch stimuli: implications for the great circle and implicit surface models.

Visually perceived eye level (VPEL) and perceived pitch were measured while subjects viewed two sets of stimuli that were either upright or pitched top-toward or top-away from them. The first set of stimuli, a pair of vertical lines viewed at various angles of pitch, caused systematic changes in perceived pitch and upward and downward VPEL shifts for the top-toward and top-away pitches, respectively. Neither the perceived pitch nor the VPEL measures with these stimuli differed between monocular and binocular viewing. The second set of stimuli was constructed so that, when viewed at the appropriate pitch angle, the projected orientations of the lines in the retinal image of each stimulus were similar to those generated by a pair of vertical lines pitched by a lesser amount in the opposite direction. When viewed monocularly, these stimuli appeared pitched in the direction opposite their physical pitch, yet produced VPEL shifts consistent with the direction of their physical pitch. These results clearly demonstrate a dissociation between perceived pitch and VPEL. The same stimuli, when viewed binocularly, appeared pitched in the direction of their physical pitch and caused VPEL shifts indistinguishable from those obtained monocularly. The retinal image orientations of these stimuli, however, corresponded to those of vertical line stimuli pitched in the opposite direction. This finding is therefore consistent with the hypothesis that VPEL and perceived pitch are processed independently, but inconsistent with the specific version of this hypothesis which states that differences in VPEL are determined solely on the basis of the orientation of lines in the retinal image.

The importance of socioeconomic and nutritional conditions rather than altitude on the physical growth of prepubertal Andean highland boys.

The aim of this work was to study the effect of hypoxic stress on the physical growth of prepubertal Bolivian boys (10-11.5 years of age) of the same socioeconomic and nutritional conditions. The subjects consisted of 143 boys living in La Paz (altitude 3600 m, n = 67) and Santa Cruz de la Sierra (altitude 420 m, n = 76). Among the boys studied at high altitude, 23 were from a high socioeconomic background (HA1) and 44 from a low socioeconomic background (HA2). The group studied at low altitude consisted of 47 boys from a high socioeconomic background (LA1) and 29 from a low socioeconomic background (LA2). A scientific evaluation of the nutritional status of the boys was realized from specific anthropometric characteristics (height, body weight, upper arm muscle circumference, body fat mass and body mass index) and haematological (haematocrit, haemoglobin, serum iron, serum ferritin, red cell protoporphyrin, transferrin saturation) and biochemical (total serum protein, albumin and prealbumin) parameters. At high as at low altitudes, the biometric characteristics of boys from a low socioeconomic background were significantly lower than those of boys from a high socioeconomic background. The physical growth of HA2 and LA2 boys was delayed by approximately 2 years. All the boys had biochemical and haematological parameters within the normal range. Boys from a low socioeconomic background were considered as marginally undernourished and those from a high socioeconomic background as well-nourished. Within the same socioeconomic class there was no nutritional difference between highland and lowland boys. Similarly, and this is the most important feature of this study, there was no difference for the overall biometric characteristics between highland and lowland boys of the same socioeconomic and nutritional status. Therefore, it appears that when socioeconomic and nutritional conditions are taken into account, there is no effect of hypoxic stress on the physical growth of prepubertal Andean highland boys.

Michaelis-Menten kinetics determine cyclosporine steady-state concentrations: a population analysis in kidney transplant patients.

Dosage adjustments of cyclosporine are confounded with an unexpected degree of variability, thus invalidating a direct proportionality between the oral dose rate and the steady-state concentration. In 1033 observations of dose rate and average steady-state concentration collected during therapeutic monitoring (area under the curve method) in 134 adult kidney transplant patients, a population pharmacokinetic analysis showed that a Michaelis-Menten model fitted the data better than a linear clearance model. It was further shown that the Michaelis-Menten constant (Km) parameter of the Michaelis-Menten model (the average steady-state concentration at half-maximal dose rate) increased during the first 4 months after transplantation whereas the maximal dose rate of the Michaelis-Menten model (Vmax) remained constant. The following parameters with interindividual variation in parenthesis were estimated: Vmax = 852 mg/24 hr (43%) and Km at 114 days after transplantation = 349 ng/ml (117%). An algorithm was derived from this population model that guides the clinician during the adjustment of oral cyclosporine dose rates.

Effect of chronic hypoxia and socioeconomic status on VO2max and anaerobic power of Bolivian boys.

The aim of this work was to analyze the effects of altitude and socioeconomic and nutritional status on maximal oxygen uptake (VO2max) and anaerobic power (P) in 11-yr-old Bolivian boys. At both high (HA) (3,600 m) and low (LA) (420 m) altitudes, the boys were divided into high (HA1, n = 23, LA1, n = 48) and low (HA2, n = 44, LA2, n = 30) socioeconomic levels. Anthropometric characteristics, VO2max, and P [maximal P (Pmax) during a force-velocity test and mean P (P) during a 30-s Wingate test] were measured. Results showed that 1) anthropometric parameters were not different between HA1 and LA1 and HA2 and LA2 boys, but HA2 and LA2 boys were two years behind HA1 and LA1 boys in development; 2) VO2max was not different in boys from the same altitude, but at HA VO2max was 10% lower than at LA (HA1 = 37.2 +/- 5.6, HA2 = 38.9 +/- 6.4, LA1 = 42.5 +/- 5.8, LA2 = 42.5 +/- 5.3 ml.min-1 x kg-1 body wt); and 3) Pmax and P were higher in well-nourished than in undernourished boys, but there was no difference in Pmax and P between HA1 and LA1 and HA2 and LA2 boys (HA1 = 6.8 +/- 1.0, HA2 = 5.5 +/- 0.8, LA1 = 7.1 +/- 1.0, LA2 = 5.3 +/- 0.9 W/kg for Pmax; HA1 = 5.2 +/- 0.8, HA2 = 4.5 +/- 0.9, LA1 = 5.2 +/- 0.7, LA2 = 4.0 +/- 0.6 W/kg for P).(ABSTRACT TRUNCATED AT 250 WORDS)

Do corticosteroids prevent postherpetic neuralgia? A review of the evidence.

A short course of corticosteroids is frequently used in herpes zoster to prevent postherpetic neuralgia. To clarify the evidence behind this routine practice, we reviewed the three randomized controlled trials on this subject. Although in all three similar dosages of corticosteroids (40 mg to 60 mg prednisone daily for 2 to 4 weeks) were used, deficiencies in reported clinical characteristics of study subjects, the potential for bias in the ascertainment of pain duration, and the inability to exclude type II error make it impossible to determine whether or not this practice is effective. More research on this subject is needed, with greater attention to good study methodology.

Propolis allergy. (II). The sensitizing properties of 1,1-dimethylallyl caffeic acid ester.

As shown in the preceding paper, propolis or bee-glue is the cause of an increasing number of allergic reactions in persons using it in external preparations and cosmetics. Propolis and its main contact allergen, 1,1-dimethylallyl caffeic acid ester, designated LB-1, show strong sensitizing properties in patients as well as in guinea pig experiments. 9 patients have been patch tested with this compound, 8 of whom reacted strongly. Chemical separation of different propolis samples and poplar bud extracts reveal that LB-1 is always present. Poplar bud secretion is the bee's major source for propolis and hence the origin of LB-1. A warning is indicated, in agreement with several other authors, that propolis should not be used in topical products because of its strong sensitizing properties.

Propolis allergy. (I). Origin, properties, usage and literature review.

Propolis or bee-glue, a resinous bee-hive product, is the cause of an increasing number of cases of allergic contact dermatitis. Formerly only observed in bee-keepers, propolis allergy today is mainly seen in individuals who use propolis in bio-cosmetics and self treatment of various diseases. Nearly 200 cases are summarized in an overview, including the first description of 'poplar bud' contact dermatitis from 1887. As practically all flavonoid aglycones and most of the other phenolics present in propolis are identical with the bud secretion of poplars, evidence is given that the poplar bud constituents are responsible for propolis hypersensitivity.

Longitudinal changes in nutritional habits of teenagers: differences in intake between schooldays and weekend days.

Longitudinal changes in nutritional habits were studied in Dutch adolescents from 12 to 17 years of age (131 girls and 102 boys). The dietary differences on schooldays and weekend days are reported. In girls only small changes in nutritional habits were seen as they grew older. In boys there was a gradual increase in food intake with age. Overall, higher nutrient intakes could be seen on weekend days. The energy intake on weekend days was consistently higher for girls and boys in all age-groups. The proportional intakes of fat and sugar were rather high, especially on weekend days. The alcohol consumption increased with age for girls as well as boys, and was for some individuals extremely high (boys) on weekend days. The observed levels of intake compared with the recommendations showed a rather low intake of polyunsaturated fatty acids, polysaccharides and iron.