Patients' Characteristics and General Practitioners' Management of Patients with Symptom Diagnoses.

INTRODUCTION: Symptom diagnoses are diagnoses used in primary care when the relevant diagnostic criteria of a disease are not fulfilled. Although symptom diagnoses often get resolved spontaneously without a clearly defined illness nor treatment, up to 38% of these symptoms persist more than 1 year. It is largely unknown how often symptom diagnoses occur, which symptoms persist, and how general practitioners (GPs) manage them. AIM: Explore morbidity rates, characteristics and management of patients with nonpersistent (≤1 year) and persistent (>1 year) symptom diagnoses. METHODS: A retrospective cohort study was performed in a Dutch practice-based research network including 28,590 registered patients. We selected symptom diagnosis episodes with at least 1 contact in 2018. We performed descriptive statistics, Student's T and χ2 tests to summarize and compare patients' characteristics and GP management strategies in the nonpersistent and persistent groups. RESULTS: The incidence rate of symptom diagnoses was 767 episodes per 1000 patient-years. The prevalence rate was 485 patients per 1000 patient-years. Out of the patients who had a contact with their GPs, 58% had at least 1 symptom diagnosis, from which 16% were persistent (>1 year). In the persistent group, we found significantly more females (64% vs 57%), older patients (mean: 49 vs 36 years of age), patients with more comorbidities (71% vs 49%), psychological (17% vs 12%) and social (8% vs 5%) problems. Prescriptions (62% vs 23%) and referral (62.7% vs 30.6%) rates were significantly higher in persistent symptom episodes. CONCLUSION: Symptom diagnoses are highly prevalent (58%) of which a considerable part (16%) persists more than a year.

[18F]FDG Uptake and Expression of Immunohistochemical Markers Related to Glycolysis, Hypoxia, and Proliferation in Indeterminate Thyroid Nodules.

PURPOSE: The current study explored the association between 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) uptake and the quantitative expression of immunohistochemical markers related to glucose metabolism, hypoxia, and cell proliferation in benign and malignant thyroid nodules of indeterminate cytology. PROCEDURES: Using a case-control design, 24 patients were selected from participants of a randomized controlled multicenter trial (NCT02208544) in which [18F]FDG-PET/CT and thyroid surgery were performed for Bethesda III and IV nodules. Three equally sized groups of [18F]FDG-positive malignant, [18F]FDG-positive benign, and [18F]FDG-negative benign nodules were included. Immunohistochemical staining was performed for glucose transporters (GLUT) 1, 3, and 4; hexokinases (HK) 1 and 2; hypoxia-inducible factor-1 alpha (HIF1α; monocarboxylate transporter 4 (MCT4); carbonic anhydrase IX (CA-IX); vascular endothelial growth factor (VEGF); sodium-iodide symporter (NIS); and Ki-67. Marker expression was scored using an immunoreactive score. Unsupervised cluster analysis was performed. The immunoreactive score was correlated to the maximum and peak standardized uptake values (SUVmax, SUVpeak) and SUVmax ratio (SUVmax of nodule/background SUVmax of contralateral, normal thyroid) of the [18F]FDG-PET/CT using the Spearman's rank correlation coefficient and compared between the three groups using Kruskal-Wallis tests. RESULTS: The expression of GLUT1, GLUT3, HK2, and MCT4 was strongly positively correlated with the SUVmax, SUVpeak, and SUVmax ratio. The expression of GLUT1 (p = 0.009), HK2 (p = 0.02), MCT4 (p = 0.01), and VEGF (p = 0.007) was statistically significantly different between [18F]FDG-positive benign nodules, [18F]FDG-positive thyroid carcinomas, and [18F]FDG-negative benign nodules. In both [18F]FDG-positive benign nodules and [18F]FDG-positive thyroid carcinomas, the expression of GLUT1, HK2, and MCT4 was increased as compared to [18F]FDG-negative benign nodules. VEGF expression was higher in [18F]FDG-positive thyroid carcinomas as compared to [18F]FDG-negative and [18F]FDG-positive benign nodules. CONCLUSIONS: Our results suggest that [18F]FDG-positive benign thyroid nodules undergo changes in protein expression similar to those in thyroid carcinomas. To expand the understanding of the metabolic changes in benign and malignant thyroid nodules, further research is required, including correlation with underlying genetic alterations.

Commonly occurring adversities in families as risk factors for developing psychosocial and psychiatric morbidities: evidence from general practice.

BACKGROUND: Childhood adversity may lead to mental and somatic complications throughout life. General practitioners are equipped to identify and manage adverse events in households. The relationship between adversities and psychiatric symptoms has not been studied in primary care. AIMS: We investigated the relationship of common adversities in families with respect to subsequent development of psychosocial and psychiatric problems in young children. METHOD: We analysed data from seven general practices, including participants between 0 and 9 years of age. Adversity was defined as having a household member who was diagnosed with cancer, psychiatric disease or social problems. We compared these patients with controls matched for gender, age and general practice. The primary outcome was any new episode defined with a psychological and psychiatric label. Secondarily, the encounter rates at the general practices after adversity were analysed. RESULTS: Participants in both groups were followed for an average of 12 years, whereby patients with an adversity were more likely to develop psychiatric morbidities compared with matched references (odds ratio 1.38, 95% CI 1.12-1.68, P = 0.002), also revealing higher encounter rates at general practices. We found no statistically significant association between adversities in the family and increased psychosocial symptoms. CONCLUSIONS: The short- and long-term consequences of exposure to negative events in childhood are of great public health importance. Our data suggest screening more proactively for consequences of commonly occurring adversities in families, as they are a risk factor for subsequent psychiatric symptoms. Enhanced consultation frequency at general practitioners following adversities should be differentiated in more detail.

The impact of an intensive care unit admission on the health status of relatives of intensive care survivors: A prospective cohort study in primary care.

BACKGROUND: Relatives of intensive care unit (ICU) survivors may suffer from various symptoms after ICU admittance of their relative, known as post-intensive care syndrome-family (PICS-F). Studies regarding PICS-F have been performed but its impact in primary care is unknown. OBJECTIVES: To explore health problems of relatives of ICU survivors in primary care. METHODS: This is an exploratory prospective cohort study in which we combined data from two hospitals and a primary care research network in the Netherlands. ICU survivors who had been admitted between January 2005 and July 2017 were identified and matched by sex and age with up to four chronically ill (e.g. COPD, cardiovascular disease) patients. In both groups, relatives living in the same household were identified and included in this study. Primary outcome was the number of new episodes of care (International Classification of Primary Care-2) for up to five years. Hazard ratios (HRs) for the total number of new episodes were calculated. RESULTS: Relatives of ICU survivors (n = 267, mean age 38.1 years, 41.0% male) had significantly more new care episodes compared to the reference group (n = 705, mean age 36.3 years, 41.1% male) 1-2 years (median 0.11 vs. 0.08, HR 1.26; 95% confidence interval (CI) 1.03-1.54) and 2-5 years (median 0.18 vs. 0.13, HR 1.28; 95%CI 1.06-1.56) after ICU discharge. No differences were found in the period before ICU admission. CONCLUSION: Relatives of ICU survivors present more morbidity in primary care than relatives of chronically ill patients up to five years after ICU discharge.

Diagnostic Accuracy of Skin Cancer by Family Physicians.

BACKGROUND: Skin cancer is the most common type of cancer worldwide. Family physicians (FPs) need to differentiate between nonmalignant and malignant skin conditions, but the diagnostic accuracy of FPs has never been studied in primary care. AIM: To assess the accuracy of skin cancer diagnoses by FPs. Our secondary aim was to analyze the number of patients with premalignant lesions and examine the diversity of skin-related questions in Dutch primary care. METHOD: This study is a retrospective cohort of all new skin-related health questions between January 1, 2018, and July 1, 2018, in a Dutch primary care registration network with data from 26 FPs in 6 practices, with a follow-up of at least 1 year. The initial FP diagnosis was dichotomized as malignant or nonmalignant and compared in a crosstab to the final diagnosis registered after the follow-up period (reference standard). RESULTS: Our study population included 2952 patients. During the research period, 35 patients received a final diagnosis of skin cancer. The sensitivity and specificity of the FP diagnosis of malignancy was 74.3% (95% confidence interval [CI], 56.7% to 87.5%) and 97.3% (95% CI, 96.7% to 97.8%), the positive predictive value and negative predictive value was 21.5% (95% CI, 17.2% to 26.5%) and 99.7% (95% CI, 99.5% to 99.8%), respectively. Seventy-two patients were diagnosed with a premalignant lesion. Included patients received 141 different diagnoses. CONCLUSION: The calculated diagnostic accuracy of FPs is high and shows that FPs are especially accurate in excluding malignancy. This research shows the variety of skin problems in primary care and shows that the FP can deliver safe and effective dermatologic care.

Preventing acute kidney injury in high-risk patients by temporarily discontinuing medication - an observational study in general practice.

BACKGROUND: Elderly, patients with chronic kidney disease (CKD) and patients with heart failure who continue using renin-angiotensin-aldosterone-system (RAAS) inhibitors, diuretics, or non-steroidal-anti-inflammatory drugs (NSAIDs) during times of fluid loss have a high risk of developing complications like acute kidney injury (AKI). The aim of this study was to assess how often advice to discontinue high-risk medication was offered to high-risk patients consulting the general practitioner (GP) with increased fluid loss. Furthermore, we assessed the number and nature of the complications that occurred after GP consultation. METHODS: We performed a cross-sectional study with patients from seven Dutch general practices participating in the Family Medicine Network between 1 and 6-2013 and 1-7-2018. We included patients who used RAAS-inhibitors, diuretics, or NSAIDs, and had at least one of the following risk factors: age ≥ 70 years, CKD, or heart failure. From this population, we selected patients with a 'dehydration-risk' episode (vomiting, diarrhoea, fever, chills, or gastrointestinal infection). We manually checked their electronic patient files and assessed the percentage of episodes in which advice to discontinue the high-risk medication was offered and whether a complication occurred in 3 months after the 'dehydration-risk' episode. RESULTS: We included 3607 high-risk patients from a total of 44.675 patients (8.1%). We found that patients were advised to discontinue the high-risk medication in 38 (4.6%) of 816 'dehydration-risk' episodes. In 59 of 816 episodes (7.1%) complications (mainly AKI) occurred. CONCLUSIONS: Dutch GPs do not frequently advise high-risk patients to discontinue high-risk medication during 'dehydration-risk' episodes. Complications occur frequently. Timely discontinuation of high-risk medication needs attention.

Inhibition of CDK4/CDK6 Enhances Radiosensitivity of HPV Negative Head and Neck Squamous Cell Carcinomas.

PURPOSE: Human papillomavirus negative (HPV-ve) head and neck squamous cell carcinoma (HNSCC) has a poor prognosis compared with HPV+ve HNSCCs. Expression of p16 in HPV+ve HNSCC is thought to mediate radiosensitivity via inhibition of cyclin-dependent kinase (CDK) 4/6. We used a clinically approved CDK4/CDK6 inhibitor, palbociclib, and assessed its effect on radiosensitivity in HNSCC. METHODS AND MATERIALS: The effect of palbociclib on radiosensitivity was determined in HPV-ve and HPV+ve HNSCC cell lines using colony survival assays, immunofluorescent staining of repair proteins, homologous recombination assays, cell cycle, and metaphase spread analyses. RESULTS: Only HPV-ve HNSCC cells were radiosensitized by palbociclib, which also occurred at hypoxic levels associated with radioresistance. Palbociclib led to decreased induction of BRCA1 and RAD51 after irradiation. Homologous recombination was diminished and repair of radiation-induced DNA damage was delayed in the presence of palbociclib, leading to increased chromosomal damage. Failure to repair radiation-induced damage led to cell death as a result of mitotic catastrophe. CONCLUSIONS: Here, we highlight a therapeutic strategy to improve the radiosensitivity of HPV-ve HNSCC, a patient group that has an unmet and urgent need for improved radiation therapy efficacy.

Urine cultures and antibiotics for urinary tract infections in Dutch general practice.

BACKGROUND: Urinary tract infections (UTIs) are common in general practice, and antibiotic resistance is often seen. Urine cultures are advised by the Dutch national UTI guideline for patients at high risk of UTI complications. Prudent use of antibiotics and taking into account national guidelines and urine culture results are important to combat antibiotic resistance in general practice. AIM: To identify subgroups of UTI patients in which the use of urine cultures and antibiotic prescriptions deviates from the national guidelines. METHODS: We investigated associations of several characteristics with urine culture orders in patients with UTI in 2015 from seven Dutch general practices (n=1295). These included subgroups at risk for UTI complications, comorbidities, age and history of UTI recurrence. In addition, we assessed the level of adherence to the guideline for antibiotic prescriptions in subgroups at risks for UTI complications. FINDINGS: Urine cultures were ordered in 17% (n=221) of patients, more frequently in high-risk patients (32%) than in low-risk patients (7%), for UTI complications (OR=6.4; 95% CI 4.6-9.0). In low-risk patients, 91% received antibiotics that were recommended in the guideline. For high-risk patients this percentage ranged widely, and was particularly low in the risk groups with signs of tissue invasion (29-50%). Diagnostic and therapeutic adequacy can still be improved by increasing the adherence to the guideline in UTI patients at high risk for complications. This may contribute to containing antibiotic resistance in UTI by ordering urine cultures and use the results to adjust prescriptions to antibiotic susceptibility of the uropathogen.

Incidence, course and risk factors of head injury: a retrospective cohort study.

OBJECTIVES: To assess the incidence of head injury and predictors of complication across the care continuum. DESIGN: Retrospective cohort study using data from a research network. We calculated the incidence of overall head injury in a longitudinal cohort covering 1-year interval (31 369 patient-years), and the incidence of complicated head injury in a longitudinal cohort covering 10 years interval (220 352 patient-ears). Incidence rates were calculated per 1000 patient-years with 95% CI using the Mid-P exact test. We calculated ORs to assess potential risk factors for a complicated head injury. SETTING: A practice-based research network covering a population of >30 000 patients. PARTICIPANTS: All patients listed in practices within the research network during the years 2005-2014. MAIN OUTCOME MEASURES: Incidence of (complicated) head injury and predictors for clinical complications. RESULTS: The incidence of overall head injury was 22.1 per 1000 person-years and the incidence of a complicated course following head injury was 0.16 per 1000 person-years. The following determinants were risk factors for a complicated course: high energy trauma, bicycle accident, traffic accident in general, use of anticoagulants, alcohol intoxication, age above 60 years and low Glasgow Coma Scale at initial presentation. A complicated course was very unlikely when the patients' first encounter with a healthcare professional was in primary care (OR 0.03, 95% CI 0.01 to 0.07). CONCLUSIONS: Complication after head injury are rarely seen in general practice. Patients who do experience complications are often easily identifiable as requiring specialist care. A more reserved referral policy for general practice may be desirable, suggesting that current guidelines are too defensive.

An endstation for resonant inelastic X-ray scattering studies of solid and liquid samples.

A novel experimental setup is presented for resonant inelastic X-ray scattering investigations of solid and liquid samples in the soft X-ray region for studying the complex electronic configuration of (bio)chemical systems. The uniqueness of the apparatus is its high flexibility combined with optimal energy resolution and energy range ratio. The apparatus enables investigation of chemical analyses, which reflects the chemical imprints. The endstation is composed of a main sample chamber, a sample holder for either solid or liquid jet delivery system, and a soft X-ray grating spectrometer for 210-1250 eV with a resolving power of ∼1000. It combines for the first time liquid jet technology with a soft X-ray spectrometer based on the variable line spacing principle. This setup was commissioned at the soft X-ray beamline P04 at PETRA III of the Deutsches Elektronen-Synchrotron in Hamburg which is currently the most brilliant storage-ring-based X-ray radiation source in the world. The first results of liquid and solid samples show that this setup allows the detection of photons across an energy range of ∼300 eV. This covers simultaneously the emission lines of life-important elements like carbon, nitrogen and oxygen in a shot-based procedure.

Scientific uncertainty in media content: Introduction to this special issue.

This introduction sets the stage for the special issue on the public communication of scientific uncertainty that follows by sketching the wider landscape of issues related to the communication of uncertainty and showing how the individual contributions fit into that landscape. The first part of the introduction discusses the creation of media content as a process involving journalists, scientific sources, stakeholders, and the responsive audience. The second part then provides an overview of the perception of scientific uncertainty presented by the media and the consequences for the recipients' own assessments of uncertainty. Finally, we briefly describe the six research articles included in this special issue.

Scientists in the public sphere: Interactions of scientists and journalists in Brazil.

In order to map scientists' views on media channels and explore their experiences interacting with journalists, the authors conducted a survey of about 1,000 Brazilian scientists. Results indicate that scientists have clear and high expectations about how journalists should act in reporting scientific information in the media, but such expectations, in their opinion, do not always seem to be met. Nonetheless, the results show that surveyed scientists rate their relation with the media positively: 67% say that having their research covered by media has a positive impact on their colleagues. One quarter of the respondents expressed that talking to the media can facilitate acquisition of more funds for research. Moreover, 38% of the total respondents believe that writing about an interesting topic for release on media channels can also facilitate research publication in a scientific journal. However, 15% of the respondents outright agree that research reported in the media beforehand can threaten acceptance for publication by a scientific journal. We hope that these results can foster some initiatives for improving awareness of the two cultures, scientists and journalists; increasing the access of journalists to Brazilian scientific endeavors; stimulating scientists to communicate with the public via social networks.

Constructing (un-)certainty: An exploration of journalistic decision-making in the reporting of neuroscience.

Based on 21 individual case studies, this article inventories the ways journalism deals with scientific uncertainty. The study identifies the decisions that impact a journalist's perception of a truth claim as unambiguous or ambiguous and the strategies to deal with uncertainty that arise from this perception. Key for understanding journalistic action is the outcome of three evaluations: What is the story about? How shall the story be told? What type of story is it? We reconstructed the strategies to overcome journalistic decision-making uncertainty in those cases in which they perceived scientific contingency as a problem. Journalism deals with uncertainty by way of omission, by contrasting the conflicting messages or by acknowledging the problem via the structure or language. One finding deserves particular mention: The lack of focus on scientific uncertainty is not only a problem of how journalists perceive and communicate but also a problem of how science communicates.

Taiwanese life scientists less "medialized" than their Western colleagues.

The article presents results from surveys of life scientists in Taiwan (n=270) and in Germany (n=326). Fewer Taiwanese than German researchers have frequent contact with the media and they rate their experiences with journalists less positively. Furthermore, they are less prepared to adapt to journalistic expectations and to a greater extent than German researchers they expect journalists to consider scientific criteria in their reporting. These findings are interpreted in Weingart's "medialization of science" framework as indicators of lower medialization of science in Taiwan than in Germany. However, Taiwanese scientists are more willing than German scientists to accept journalistic simplification at the expense of accuracy. This is explained as an adaptation to the media system and to the perceived scientific literacy of the media audience. We hypothesize that cultural differences regarding the relative priority of relational vs. rational communication goals may also contribute to more tolerance of journalistic simplification in Taiwan.