Diagnostic and societal impact of implementing the syncope guidelines of the European Society of Cardiology (SYNERGY study).

BACKGROUND: Syncope management is fraught with unnecessary tests and frequent failure to establish a diagnosis. We evaluated the potential of implementing the 2018 European Society of Cardiology (ESC) Syncope Guidelines regarding diagnostic yield, accuracy and costs. METHODS: A multicentre pre-post study in five Dutch hospitals comparing two groups of syncope patients visiting the emergency department: one before intervention (usual care; from March 2017 to February 2019) and one afterwards (from October 2017 to September 2019). The intervention consisted of the simultaneous implementation of the ESC Syncope Guidelines with quick referral routes to a syncope unit when indicated. The primary objective was to compare diagnostic accuracy using logistic regression analysis accounting for the study site. Secondary outcome measures included diagnostic yield, syncope-related healthcare and societal costs. One-year follow-up data were used to define a gold standard reference diagnosis by applying ESC criteria or, if not possible, evaluation by an expert committee. We determined the accuracy by comparing the treating physician's diagnosis with the reference diagnosis. RESULTS: We included 521 patients (usual care, n = 275; syncope guidelines intervention, n = 246). The syncope guidelines intervention resulted in a higher diagnostic accuracy in the syncope guidelines group than in the usual care group (86% vs.69%; risk ratio 1.15; 95% CI 1.07 to 1.23) and a higher diagnostic yield (89% vs. 76%, 95% CI of the difference 6 to 19%). Syncope-related healthcare costs did not differ between the groups, yet the syncope guideline implementation resulted in lower total syncope-related societal costs compared to usual care (saving €908 per patient; 95% CI €34 to €1782). CONCLUSIONS: ESC Syncope Guidelines implementation in the emergency department with quick referral routes to a syncope unit improved diagnostic yield and accuracy and lowered societal costs. TRIAL REGISTRATION: Netherlands Trial Register, NTR6268.

AI-support for the detection of intracranial large vessel occlusions: One-year prospective evaluation.

Purpose: Few studies have evaluated real-world performance of radiological AI-tools in clinical practice. Over one-year, we prospectively evaluated the use of AI software to support the detection of intracranial large vessel occlusions (LVO) on CT angiography (CTA). Method: Quantitative measures (user log-in attempts, AI standalone performance) and qualitative data (user surveys) were reviewed by a key-user group at three timepoints. A total of 491 CTA studies of 460 patients were included for analysis. Results: The overall accuracy of the AI-tool for LVO detection and localization was 87.6%, sensitivity 69.1% and specificity 91.2%. Out of 81 LVOs, 31 of 34 (91%) M1 occlusions were detected correctly, 19 of 38 (50%) M2 occlusions, and 6 of 9 (67%) ICA occlusions. The product was considered user-friendly. The diagnostic confidence of the users for LVO detection remained the same over the year. The last measured net promotor score was -56%. The use of the AI-tool fluctuated over the year with a declining trend. Conclusions: Our pragmatic approach of evaluating the AI-tool used in clinical practice, helped us to monitor the usage, to estimate the perceived added value by the users of the AI-tool, and to make an informed decision about the continuation of the use of the AI-tool.

[COVID-19 in nursing homes A study of diagnosis, symptomatology and disease course]. / Covid-19 in verpleeghuizen.

OBJECTIVE: To describe the diagnosis, symptomatology and disease course of COVID-19 in nursing home (NH) residents in the Netherlands. DESIGN: Prospective cohort study. METHOD: Data on NH residents with suspected COVID-19 were collected from the electronic patient records. Data were collected on diagnostic status (COVID-19: confirmed/excluded (using the RT-PCR test)), symptomatology (typical/atypical and other symptoms, body temperature and oxygen saturation) and, in the case of confirmed COVID-19, on disease course (recovered/clinically improved/deteriorated, deceased). We described and compared the symptomatology in NH residents with confirmed COVID-19 and NH residents in whom COVID-19 had been excluded. We also analysed mortality risk using survival analysis. We used registrations from the period 18 March to15 April 2020 for this study. RESULTS: We reported on 1,969 NH residents with suspected COVID-19. The diagnosis was confirmed in 857 patients (43.5%); diagnosis was excluded in 1,112 (56.5%) patients. Among patients with confirmed COVID-19, 65% had coughs, 70% had fever, 33% had shortness of breath, 28% had delirium/confusion and 10% had a sore throat; in patients in whom COVID-19 was excluded these symptoms were experienced in 70%, 47%, 45%, 26% and 13% of patients, respectively. Of the patients with confirmed COVID-19, 48% died within 30 days (95% CI: 36-44%), versus 20% of the patients in whom COVID-19 was excluded (95% CI: 11-15%). CONCLUSION: There is a lot of overlap in symptomatology between NH residents with COVID-19 and those with other acute diseases. An RT-PCR test is required to be able to make the distinction better. The mortality risk in patients with confirmed COVID-19 is significantly higher than in patients in whom covid-19 is excluded.

Role of gut microbiota in chronic low-grade inflammation as potential driver for atherosclerotic cardiovascular disease: a systematic review of human studies.

A hallmark of obesity is chronic low-grade inflammation, which plays a major role in the process of atherosclerotic cardiovascular disease (ACVD). Gut microbiota is one of the factors influencing systemic immune responses, and profound changes have been found in its composition and metabolic function in individuals with obesity. This systematic review assesses the association between the gut microbiota and markers of low-grade inflammation in humans. We identified 14 studies which were mostly observational and relatively small (n = 10 to 471). The way in which the microbiome is analysed differed extensively between these studies. Lower gut microbial diversity was associated with higher white blood cell counts and high sensitivity C-reactive protein (hsCRP) levels. The abundance of Bifidobacterium, Faecalibacterium, Ruminococcus and Prevotella were inversely related to different markers of low-grade inflammation such as hsCRP and interleukin (IL)-6. In addition, this review speculates on possible mechanisms through which the gut microbiota can affect low-grade inflammation and thereby ACVD. We discuss the associations between the microbiome and the inflammasome, the innate immune system, bile acids, gut permeability, the endocannabinoid system and TMAO. These data reinforce the importance of human research into the gut microbiota as potential diagnostic and therapeutic strategy to prevent ACVD.

[Guideline on functional abdominal pain in children]. / Richtlijn 'Functionele buikpijn bij kinderen'.

- The guideline entitled 'Functional abdominal pain in children' has been developed by a multidisciplinary working group on behalf of the Dutch Pediatric Association in 2015. - History and physical examination are essential in diagnosing pediatric functional abdominal pain. Additional diagnostic testing is of limited value when alarm symptoms are absent. - Reassurance and education of both the child and parent(s), are the cornerstones in the treatment of pediatric functional abdominal pain. - In case of persisting symptoms, hypnotherapy or cognitive behavioral therapy can be started. There is no evidence for any pharmacological treatment.

[Refeeding syndrome during alcohol detoxification]. / Refeedingsyndroom bij alcoholdetoxificatie.

Refeeding syndrome (RS) can occur when malnourished patients are reintroduced to carbohydrates. The symptoms are caused by a combination of electrolyte shifts and fluid retention. Symptoms are wide-ranging; some patients may suffer from harmless muscle cramps, others from more severe neurological and cardiological symptoms that can even lead to death. Although alcohol dependence is a risk factor for the development of RS, little attention is being given to this problem in addiction treatment. In this article we report a case of RS that occurred during alcohol detoxification. We also present the results of a pilot study on the incidence of RS during the alcohol detoxification of 12 patients.

Pancreas-preserving total duodenectomy versus standard pancreatoduodenectomy for patients with familial adenomatous polyposis and polyps in the duodenum.

BACKGROUND: Pancreas-preserving total duodenectomy (PPTD) was introduced as a replacement for pancreatoduodenectomy (PD) for familial adenomatous polyposis (FAP). This study analysed the results of PPTD in the Netherlands and reviewed the relevant literature. METHODS: All 26 patients who underwent PPTD for FAP in four centres in the Netherlands between January 2000 and January 2007 were compared with a group of 77 patients who had PD for ampulla of Vater adenocarcinoma at one centre during the same interval. RESULTS: Morbidity rates were similar after PPTD for FAP (16 patients, 62 per cent) and PD for ampulla of Vater adenocarcinoma (44 patients, 57 per cent) (P = 0.694). One patient (4 per cent) died after PPTD and two (3 per cent) after PD. A review of the literature, including patients from the present study, found that 71 patients had PPTD, with postoperative morbidity in 36 (51 per cent) and one death (1 per cent). In publications containing a total of 94 patients who underwent PD for FAP, 43 (46 per cent) developed complications and three (3 per cent) died. CONCLUSION: PPTD has similar short-term results to PD in terms of morbidity and mortality.

[Diagnostic and prognostic value of B-type natriuretic peptides in heart failure or signs of heart failure]. / Diagnostische en prognostische waarde van B-type-natriuretische peptiden bij hartfalen of bij aanwijzingen daarvoor.

Biologically active B-type natriuretic peptide or brain natriuretic peptide (BNP) and biologically inactive N-terminal proBNP (NT-proBNP) are secreted into the bloodstream by the heart and provide primarily information regarding the filling pressures in the heart. The accuracy of plasma BNP levels in the diagnosis of heart failure is comparable to that of plasma NT-proBNP levels. Reliable assays have been developed for both peptides, some of which can be used for rapid diagnosis in the emergency clinic. In both groups of patients with heart failure and the general population, there is a relationship between the plasma BNP and NT-proBNP levels and the risk of cardiovascular death, after correction for the traditional risk factors. Screening studies using the determination of BNP or NT-proBNP levels in order to detect patients with heart failure at an early stage cannot be recommended because their specificity is too low: in addition to heart failure, the plasma BNP or NT-proBNP level is affected by age, gender, body mass index, renal function, and pulmonary capacity. There are indications that the introduction ofa rapid BNP determination for patients that present to the emergency clinic with acute dyspnoea will lead to more effective diagnosis and treatment. Sequential determinations ofthe plasma BNP or NT-proBNP levels in inpatients and outpatients with heart failure can help to optimise the treatment, thus decreasing the morbidity and mortality that are associated with heart failure.

Surgical intervention in patients with necrotizing pancreatitis.

BACKGROUND: This study evaluated the various surgical strategies for treatment of (suspected) infected necrotizing pancreatitis (INP) and patient referrals for this condition in the Netherlands. METHODS: This retrospective study included all 106 consecutive patients who had surgical treatment for INP in the period 2000-2003 in one of eight Dutch university medical centres including three teaching hospitals. Surgical approaches included an open abdomen strategy, laparotomy with continuous postoperative lavage, minimally invasive procedures or laparotomy with primary abdominal closure. The National Hospital Registration System was searched to identify patients with acute pancreatitis who were admitted to the 90 Dutch hospitals that did not participate in the present study. RESULTS: The overall mortality rate was 34.0 per cent, 70 per cent (16 of 23) for the open abdomen strategy, 25 per cent (13 of 53) for continuous peritoneal lavage, 11 per cent (two of 18) for minimally invasive procedures and 42 per cent (five of 12) for primary abdominal closure (P < 0.001). During the study interval, 44 (12.2 per cent) of 362 patients with acute pancreatitis who were likely to require surgical intervention had been referred to university medical centres. CONCLUSION: Laparotomy with continuous postoperative lavage is the surgical strategy most often used in the Netherlands. The results of the open abdomen strategy are poor whereas a minimally invasive approach seems promising.

Olfactory function after mild traumatic brain injury.

OBJECTIVE: The aim of this study was to determine the incidence of olfactory dysfunction after mild traumatic brain injury (MTBI). Damage to the olfactory bulbs or frontal cortex has been reported in MTBI, but olfactory dysfunction after MTBI has not been studied in a prospective way before. DESIGN: Patients with first-time MTBI were included. Patients' olfactory threshold values (Hyposmia Utility Kit by Olfacto-Labs) were measured 2 weeks after the trauma. Associations between olfactory threshold values and individual symptoms and S-100B and NSE concentrations were examined, using multiple linear regression analysis, adjusting for the influence of age. RESULTS: Twenty-two per cent of 111 included patients had hyposmia and 4% had anosmia. Thresholds at 2 weeks showed no significant associations with the presence of symptoms at the ER, nor with early concentrations of S-100B or NSE. CONCLUSIONS: Although a high prevalence of olfactory dysfunction was found, no correlation was found between olfactory dysfunction and acute parameters of MTBI.

Prevalence and outcome of paediatric and adolescent limb fractures in rural Zambia.

Little is known about the prevalence and outcome of paediatric limb fractures in rural African children. The objective of our study was to assess the prevalence and outcome of paediatric and adolescent limb fractures in this population. We performed a retrospective population survey of 355 secondary school students with a mean age of 16.9 years in Katete, Zambia. Fracture type and cause were assessed using anamnestic data and physical examination. In the surveyed group 52 students (29 male, 23 female) sustained 56 fractures. We found a fracture prevalence rate of 15-19% in male and 11% in female students. The most common fracture was that of the wrist (39%). Forty-eight fractures (86%) were treated in a general hospital, and 4 (7%) in rural health centres. Only 4 students with a fracture (7%) did not receive medical treatment at all. Sport was the most common cause of fractures in the surveyed group (41%). Of all fractures, 25% led to significant impairment.

Prediction of post-traumatic complaints after mild traumatic brain injury: early symptoms and biochemical markers.

OBJECTIVES: To identify parameters at first presentation after mild traumatic brain injury (MTBI) that are predictive of the severity of post-traumatic complaints (PTC) after six months. Early recognition of patients with MTBI who are at risk of developing PTC would be useful because early follow up at the outpatient clinic may help to reduce the severity of these complaints in the long run. METHODS: The presence of symptoms in the emergency room (ER) (headache, dizziness, nausea, vomiting, and neck pain) and biochemical markers (neurone specific enolase and S-100B) in serum were assessed as possible predictive variables for the severity of PTC. Outcome variables were the severity of 16 PTC six months after the trauma. RESULT: After six months, the severity of most complaints had declined to pretrauma levels but medians for headache, dizziness, and drowsiness were still increased. In a series of 79 patients, 22 (28%) reported one or more PTC after six months. After adjustment for baseline variables, an at least twofold increased severity of all PTC subgroups was reported by those patients reporting headache, dizziness, or nausea in the ER. A twofold increased severity of "cognitive" and "vegetative" PTC was also found in those with increased concentrations of biochemical serum markers at first presentation. The prevalence of full recovery after six months increased from 50% in patients with three symptoms to 78% in those with no symptoms in the ER. Inclusion of biochemical markers showed that all 10 patients with no symptoms in the ER and normal markers recovered fully. CONCLUSIONS: The presence of headache, dizziness, or nausea in the ER after MTBI is strongly associated with the severity of most PTC after six months. Identifying MTBI patients in the ER without headache, dizziness, nausea, or increased serum marker concentrations may be a promising strategy for predicting a good outcome.

Effectiveness of bed rest after mild traumatic brain injury: a randomised trial of no versus six days of bed rest.

BACKGROUND: Outcome after mild traumatic brain injury (MTBI) is determined largely by the appearance of post-traumatic complaints (PTC). The prevalence of PTC after six months is estimated to be between 20 and 80%. Bed rest has been advocated to prevent PTC but its effectiveness has never been established. OBJECTIVE: To evaluate the effect of bed rest on the severity of PTC after MTBI. METHODS: Patients presenting with MTBI to the emergency room were randomly assigned to two intervention strategies. One group was advised not to take bed rest (NO) and the other to take full bed rest (FULL) for six days after the trauma. The primary outcome measures were severity of PTC on a visual analogue scale and physical and mental health on the medical outcomes study 36 item short form health survey (SF-36) at two weeks and three and six months after the trauma. RESULTS: Between October 1996 and July 1999, 107 (54 NO, 53 FULL) patients were enrolled. Outcome variables in both groups clearly improved between two weeks and six months. After adjustment for differences in baseline variables, most PTC tended to be somewhat more severe in the FULL group six months after the trauma, but no significant differences were found. Neither were there any significant differences in the outcome parameters between the two groups after three months. Two weeks after the trauma, most PTC in the FULL group were slightly less severe than those in the NO group, and physical subscores of the SF-36 in the FULL group were slightly better. These differences were not significant. Patients in the FULL group reported significantly less dizziness during the intervention period. CONCLUSIONS: As a means of speeding up recovery of patients with PTC after MTBI, bed rest is no more effective than no bed rest at all. Bed rest probably has some palliative effect within the first two weeks after the trauma.

[Incidence of traumatic head or brain injuries in catchment area of Academic Hospital Maastricht in 1997]. / De incidentie van traumatisch schedel- of hersenletsel in het adherentiegebied van het Academisch Ziekenhuis Maastricht in 1997.

OBJECTIVE: To measure the incidence of traumatic head or brain injury in the catchment area of the Academic Hospital Maastricht (AZM), the Netherlands. DESIGN: Retrospective. METHOD: Data were collected about head injury patients who visited the emergency room of the AZM in 1997 by separate forms that were filled out for each patient who came to the emergency room. Data were added from admission records and radiology records. The AZM had a catchment area of approximately 231,000 people. RESULTS: The emergency room was attended by 1933 patients with traumatic head or brain injury. Head trauma without signs of brain injury was diagnosed in 1440 patients (74%) mild brain injury in 467 (24%) and moderate or severe brain injury in 26 (1%). The mean age was 30 years (range: 0-97) and 29% of all patients were below the age of 15. Two-thirds (67%) of patients were male. An X-ray of the skull was performed in 15% of the cases. In 7% of these X-rays a relevant abnormality was found. Eleven per cent of patients were admitted for observation. The incidence rate of traumatic head or brain injury in 1997 was 836/100,000 and the incidence of admission 88/100,000. The causes were a fall (43%), traffic accident (22%), violence (15%), sports injuries (7%), accidents during work (4%), or other/unknown (9%). CONCLUSION: Most patients with head or brain injury had mild injuries (99%, sole head injury or mild brain injury). Compared with other studies, the annual frequency of hospital admissions was low.

Grapefruit juice increases the bioavailability of artemether.

OBJECTIVE: To evaluate the effect of grapefruit juice on the pharmacokinetics of artemether in plasma and saliva after a single oral dose and to detect concentration-dependent electrocardiographic changes (bradycardia and QTc prolongation). METHODS: Six healthy male subjects were given a standard breakfast followed by two tablets of 50-mg artemether administered with water; 1 week later, the tablets were administered with 350 ml double-strength fresh frozen grapefruit juice. For 8 h, 17 blood- and saliva samples were collected, and 17 electrocardiograms were recorded. Drug and metabolite concentrations were measured by means of high-performance liquid chromatography with electrochemical detection. The pharmacokinetic parameters were determined using a one-compartment model. RESULTS: Grapefruit juice significantly (P = 0.001) increased the mean peak concentration (Cmax) of artemether more then twofold from 42 (SD 17) ng/ml to 107 (28) ng/ml. The time to reach Cmax (tmax) with grapefruit juice was 2.1 (0.6) h compared with 3.6 (17) h with water (P = 0.02). The area under the concentration time curve (AUC) almost doubled with grapefruit juice from 177 ng x h/ml to 336 ng x h/ml (P = 0.003). The elimination half-life remained unchanged (1.0 h vs 1.3 h). No major changes in the kinetics of the metabolite dihydroartemisinin were detected. Low artemether levels and zero dihydroartemisinin levels were found in saliva. No influences of artemether were observed on 17 electrocardiograms during the 8 h after drug intake in particular there were no signs of bradycardia or QTc prolongation. CONCLUSION: Grapefruit juice significantly increases the oral bioavailability of artemether without an effect on the elimination half-life. It suggests a role for intestinal CYP3A4 in the presystemic metabolism of artemether.

The implementation of in vivo dosimetry in a small radiotherapy department.

PURPOSE: In vivo dosimetry has been shown in a number of evaluation studies, generally carried out in larger academic centres, to be a reliable method of checking the overall treatment accuracy. The object of this study was to investigate whether it was possible and useful to perform in vivo dosimetry in a small radiotherapy department and to detect if there were any systematic errors in the overall treatment set-up. MATERIALS AND METHODS: All patients were treated on a cobalt-60 unit equipped with a verification system. Six hundred fifty entrance dose measurements were performed with silicon diodes. RESULTS: The analysis showed a mean deviation of -1.3%. This negative deviation was mainly due to the mean deviation obtained in the treatment of head and neck (-1.6%) or breast (-2.5%) cancer patients. The results for pelvic or lung irradiation showed almost no deviation (-0.8 to 0.43%). Further investigation showed that the negative values for head and neck or breast irradiation were due to the irradiation technique; the lack of scattering material causes a reduction of the dose at the reference point, which is not taken into consideration by the treatment planning system. By performing in vivo dosimetry, we were also able to detect two large errors in 650 measurements and could prevent erroneous treatment. CONCLUSION: Even when the overall treatment set-up is very accurate, in vivo dosimetry is very useful in a small department since only a small effort can detect and prevent errors.

Screening for tamoxifen ocular toxicity: a prospective study.

Specific ocular complications, namely retinopathy, keratopathy and optic neuritis, have been described in women being treated with tamoxifen for metastatic breast cancer or taking this drug as an adjuvant postoperative therapy. We examined 61 patients who had been using tamoxifen for at least one year, in order to detect the incidence of ocular complications. Two patients had retinopathy after having taken high cumulative doses of tamoxifen. Another had corneal deposits and a fourth had optic neuritis. It thus appears that systematic screening of all symptom-free patients using this drug for metastatic breast cancer is superfluous. However, an ophthalmological assessment every two years or earlier in case of visual complaints for patients taking tamoxifen as an adjuvant therapy remains useful, because the oncological therapy can be adjusted if serious ocular complications arise.