Poor adherence during adolescence is a risk factor for becoming lost-to-follow-up in patients with phenylketonuria.

Purpose: A high rate of lost to follow-up (LTFU) in patients with phenylketonuria (PKU) represents a main challenge. In this study, we investigated potential risk factors for becoming LTFU related to adolescence as a critical period of life. Methods: We retrospectively analyzed longitudinal data collected from 1993 to 2019 of patients diagnosed with classic PKU that were followed at our center during adolescence (14-18 y) and at least once in adulthood (>18 y). Patients who interrupted their contact with our center after the 18th birthday for at least 2 years were classified as LTFU. We performed a multivariate regression analysis to investigate following potential risk factors for becoming LTFU in adult life: sex, dietary compliance during adolescence assessed through the mean of the annual medians of phenylalanine plasma values, average number of contacts with the center during adolescence and age at first visit after the 18th birthday. Results: 93 patients (52 males, 41 females) were included in the study. 58% became LTFU during adulthood. The mean age at the last visit before becoming LTFU was 26.2 ± 5.1 years. In the multivariate Cox regression analysis we found that poor dietary compliance during adolescence was significantly associated with a higher risk of becoming LTFU during adulthood (p-value = 0.028). Discussion: Adult patients who displayed poor treatment adherence during adolescence should be identified and carefully monitored to prevent loss of contact.

Combining environmental DNA and remote sensing for efficient, fine-scale mapping of arthropod biodiversity.

Arthropods contribute importantly to ecosystem functioning but remain understudied. This undermines the validity of conservation decisions. Modern methods are now making arthropods easier to study, since arthropods can be mass-trapped, mass-identified, and semi-mass-quantified into 'many-row (observation), many-column (species)' datasets, with homogeneous error, high resolution, and copious environmental-covariate information. These 'novel community datasets' let us efficiently generate information on arthropod species distributions, conservation values, uncertainty, and the magnitude and direction of human impacts. We use a DNA-based method (barcode mapping) to produce an arthropod-community dataset from 121 Malaise-trap samples, and combine it with 29 remote-imagery layers using a deep neural net in a joint species distribution model. With this approach, we generate distribution maps for 76 arthropod species across a 225 km2 temperate-zone forested landscape. We combine the maps to visualize the fine-scale spatial distributions of species richness, community composition, and site irreplaceability. Old-growth forests show distinct community composition and higher species richness, and stream courses have the highest site-irreplaceability values. With this 'sideways biodiversity modelling' method, we demonstrate the feasibility of biodiversity mapping at sufficient spatial resolution to inform local management choices, while also being efficient enough to scale up to thousands of square kilometres. This article is part of the theme issue 'Towards a toolkit for global insect biodiversity monitoring'.

Novel community data in ecology-properties and prospects.

New technologies for monitoring biodiversity such as environmental (e)DNA, passive acoustic monitoring, and optical sensors promise to generate automated spatiotemporal community observations at unprecedented scales and resolutions. Here, we introduce 'novel community data' as an umbrella term for these data. We review the emerging field around novel community data, focusing on new ecological questions that could be addressed; the analytical tools available or needed to make best use of these data; and the potential implications of these developments for policy and conservation. We conclude that novel community data offer many opportunities to advance our understanding of fundamental ecological processes, including community assembly, biotic interactions, micro- and macroevolution, and overall ecosystem functioning.

Fixed or random? On the reliability of mixed-effects models for a small number of levels in grouping variables.

Biological data are often intrinsically hierarchical (e.g., species from different genera, plants within different mountain regions), which made mixed-effects models a common analysis tool in ecology and evolution because they can account for the non-independence. Many questions around their practical applications are solved but one is still debated: Should we treat a grouping variable with a low number of levels as a random or fixed effect? In such situations, the variance estimate of the random effect can be imprecise, but it is unknown if this affects statistical power and type I error rates of the fixed effects of interest. Here, we analyzed the consequences of treating a grouping variable with 2-8 levels as fixed or random effect in correctly specified and alternative models (under- or overparametrized models). We calculated type I error rates and statistical power for all-model specifications and quantified the influences of study design on these quantities. We found no influence of model choice on type I error rate and power on the population-level effect (slope) for random intercept-only models. However, with varying intercepts and slopes in the data-generating process, using a random slope and intercept model, and switching to a fixed-effects model, in case of a singular fit, avoids overconfidence in the results. Additionally, the number and difference between levels strongly influences power and type I error. We conclude that inferring the correct random-effect structure is of great importance to obtain correct type I error rates. We encourage to start with a mixed-effects model independent of the number of levels in the grouping variable and switch to a fixed-effects model only in case of a singular fit. With these recommendations, we allow for more informative choices about study design and data analysis and make ecological inference with mixed-effects models more robust for small number of levels.

Linking functional traits and demography to model species-rich communities.

It has long been anticipated that relating functional traits to species demography would be a cornerstone for achieving large-scale predictability of ecological systems. If such a relationship existed, species demography could be modeled only by measuring functional traits, transforming our ability to predict states and dynamics of species-rich communities with process-based community models. Here, we introduce a new method that links empirical functional traits with the demographic parameters of a process-based model by calibrating a transfer function through inverse modeling. As a case study, we parameterize a modified Lotka-Volterra model of a high-diversity mountain grassland with static plant community and functional trait data only. The calibrated trait-demography relationships are amenable to ecological interpretation, and lead to species abundances that fit well to the observed community structure. We conclude that our new method offers a general solution to bridge the divide between trait data and process-based models in species-rich ecosystems.

High incidence of tachyarrhythmias detected by an implantable loop recorder in patients with unexplained syncope.

BACKGROUND: Syncope is a complex clinical syndrome that may be challenging with respect to a definite diagnosis. The implantable loop recorder (ILR) is a useful tool to define but also to exclude an arrhythmic aetiology. AIM: To investigate the causes of recurrent syncope or near-syncope with respect to underlying arrhythmias in non-selected consecutive patients monitored with an ILR. METHODS: A retrospective study was conducted including 55 patients (34 men, 21 women; age 60+/-19 years) with unexplained syncope who received an ILR for prolonged monitoring at our institution between April 1998 and October 2006. RESULTS: Forty (73%) patients had a recurrence of syncope or near-syncope. Structural heart disease was present in 18 (33%) patients, 4 of them having an ejection fraction <35%. An arrhythmia was detected as the cause of syncope in 25 (46%) patients. The ILR was successful in establishing a symptom-rhythm correlation in 63%. The mean follow-up period from implantation to occurrence of the detected arrhythmias was 9+/-8 months. Bradyarrhythmias were recorded in 12 (22%) patients, whereas tachyarrhythmias were found in 13 (24%) patients. Narrow QRS tachycardia was the underlying arrhythmia in 6 patients and wide QRS tachycardia in 7 patients. A pacemaker was implanted in all 12 patients with bradyarrhythmias. Implantable cardioverter defibrillator (ICD) therapy was indicated in 6 patients with adjunctive catheter ablation in 3 of them. Four patients presenting with paroxysmal supraventricular tachycardia were treated with radiofrequency catheter ablation. CONCLUSION: The ILR helped efficaciously to determine the correct diagnosis and appropriate treatment of recurrent syncope. A considerably high proportion of tachyarrhythmias was detected in this non-selected consecutive population. The majority of patients with tachyarrhythmic syncope required defibrillator implantation and/or radiofrequency ablation.

Gender-specific effect of metabolic syndrome on rate adjusted QT interval in middle-aged participants of an atherosclerosis prevention program.

INTRODUCTION: The metabolic syndrome is a matter of immense public concern for atherosclerosis prevention. Key features are visceral obesity, dyslipidemia, hyperglycemia in the non-diabetic range, and arterial hypertension. Subclinical atherosclerosis is the clinical consequence of metabolic syndrome, which may influence the QT interval. The aim was to investigate the rate corrected QT interval in subjects with metabolic syndrome in comparison to those without cardiometabolic risk factor clusters, and to explore gender differences in cardiac repolarization between the two groups. PATIENTS, MATERIALS AND METHODS: Heart rate and QT interval were automatically measured from surface ECG in 1086 participants (767 men, 319 women) from the Salzburg-Atherosclerosis-Prevention-program-in-subjects-at-High-Individual-Risk (SAPHIR). To omit the QT adjustment bias inherent in Bazett's formula we used a QT adjustment method with linear scaling as described by Rautaharju. RESULTS: The prevalence of metabolic syndrome was 13.8% among males and 10% among females. Mean rate adjusted QT (QTa) intervals were longer in women than in men. Presence of metabolic syndrome, however, was associated with significantly prolonged QTa only in men but not in women. Adjustment for relevant confounders reduced the difference of mean QTa in men from 9.24 to 5.83 ms (95% CI 0.9-10.8), but this difference was still statistically significant (p = 0.021). The effect of metabolic syndrome on QTa was only partly mediated by hypertension and insulin resistance. In females, however, no relevant differences were detected for QTa interval between subjects categorized by presence or absence of metabolic syndrome. CONCLUSIONS: The findings indicate a significant association between metabolic syndrome and rate-invariant QT in middle-aged men after adjustment for other risk factors. QT measurement may provide additive diagnostic and prognostic information in populations undergoing cardiovascular risk screening. However, the effect of metabolic and hormonal factors on ventricular repolarization seems to differ between the sexes.

Lower body mass index and atrial fibrillation as independent predictors for mortality in patients with implantable cardioverter defibrillator.

AIM: To evaluate risk factors related to total mortality in an unselected population of patients implanted with a cardioverter defibrillator. METHODS: Survival analysis was performed retrospectively investigating the records of 77 consecutive patients implanted with defibrillators (median 67 years, range 38-83 years; 63 men). All patients were followed regularly in 3-month intervals. The cause of mortality was assessed clinically, including post-mortem examination of device to assess possible arrhythmogenic death. Predictors were assessed by Kaplan-Meier analysis with log-rank tests and by Cox regression analysis (proportional hazards). RESULTS: Defibrillator recipients had a mean (+/-standard deviation) ejection fraction of 34+/-13%, left ventricular end-diastolic dimension (LVEDD) of 6.24+/-0.8 cm, QRS duration of 129+/-34 ms, and body mass index (BMI) of 26.4+/-4.3 kg/m(2). Atrial fibrillation was present in 32 patients, paroxysmal fibrillation in 23, and permanent fibrillation in 9 patients. The estimate of mean survival time for all patients was 51.5 (95% confidence interval 46.6-56.5) months. During the study period 11/77 (14%) patients died. Mean follow-up time was 24.5 months (range 0.2-60.7) for survivors and 7.6 months (range 1.5-42) for non-survivors. Independent predictors of mortality were the NYHA class (P=0.004), BMI< or =26 kg/m(2) (P=0.024), presence of paroxysmal or permanent atrial fibrillation (P=0.014), and absence of arterial hypertension (P=0.010). LVEDD showed a weak significant effect on survival (P=0.049). CONCLUSION: Patients with implantable cardioverter defibrillator and a normal to lower BMI or atrial fibrillation had a significantly higher overall mortality. These factors may be indicative of end stage heart failure or diseases associated with high sympathetic activation.

Limited dose-effect relationship of adenosine for detection of atrioventricular nodal duality in patients with supraventricular tachycardias.

OBJECTIVE: The purpose of the study was to test the dose-effect relationship of adenosine for the diagnosis of dual atrioventricular (AV) nodal physiology in patients presenting with supraventricular tachycardia. SUBJECTS AND METHODS: The study population consisted of 57 patients (mean age 50 +/- 14 years; 36 females, 21 males) with palpitations related to supraventricular tachycardia. Adenosine was injected as bolus during sinus rhythm at rest in order to unmask dual AV nodal physiology by a PR jump on surface ECG (defined as a sudden increase by > or = 50 ms measured from the onset of the P-wave to the R-wave between two consecutive sinus beats). According to a stepwise clinical approach, adenosine was administered as bolus in incremental dosages (6 mg followed by 12 mg, if necessary up to 18 mg). Once a PR jump > or = 50 ms or a high-grade AV block was noted on surface ECG, the injection was stopped at that dose. RESULTS: A significant PR jump was noted after injection of 6 mg (n = 21, 99 +/- 30 ms) or 12 mg (n = 13, 94 +/- 35 ms), but not after 18 mg (n = 4, 35 +/- 10 ms) adenosine. Provocation of temporary first-grade AV block (n = 13) was associated with the longest increment of PR interval, whereas high-grade AV block (n = 36) produced a significantly shorter PR jump (105 +/- 35 vs. 65 +/- 40 ms, p = 0.0024). Electrophysiological study and ablation were performed in 37 highly symptomatic patients. AV nodal reentrant tachycardia was diagnosed in 33 patients and orthodromic AV reentrant tachycardia in 4 patients. CONCLUSION: The adenosine test was characterized by a reverse dose-effect relationship as far as identification of AV nodal duality was concerned.

Chest wall defect and chronic pleural infection: surgical treatment with thoracomyoplasty and open window thoracostomy.

We report a rare case of a 75-year-old hemiplegic man with a chronic pleural infection, a bronchopleural fistula, and a full-thickness defect of the chest. In one operation we performed open-window thoracostomy and pleural decortication as well as reconstruction of the chest defect and reclosure of the bronchopleural fistula with a latissimus dorsi muscle flap. The patient made a good recovery and was sent for rehabilitation in good condition. Surgical treatment was essential to control and ultimately halt the septic process. Use of a muscle transplant in a hemiplegic patient did not reduce mobility.

Multiple appropriate and spurious defibrillator shocks in a patient with right ventricular cardiomyopathy.

An implantable cardioverter defibrillator (ICD) has been implanted in a 69-year-old patient with arrhythmogenic right ventricular cardiomyopathy (ARVC) for treatment of syncopal ventricular tachycardia (VT). Two types of ICD-related emergencies complicated the clinical course within 15 months. The first arrhythmic event occurred 3 months after ICD implantation as electrical storm with repetitive fast VT, resulting in 87 consecutive shocks at maximal output. Intravenous administration of amiodarone and reprogramming of the device were the measures to control VT. A year later, the patient experienced a cluster of 97 inappropriate shocks. Lead insulation failure produced electrical noise on the ventricular sensing channel and was misidentified as ventricular fibrillation (VF). The depleted ICD and the dual-coil lead were explanted and replaced by a new system. Multiple ICD shocks constitute a medical emergency in ICD patients, which requires immediate device interrogation for differentiation of appropriate and spurious discharges.

Atrial fibrillation and prominent J (Osborn) waves in critical hypothermia.

The J wave is a deflection that appears on the surface ECG as a late delta wave following the QRS complex. Also known as an Osborn wave, the J wave has been observed in various conditions and diseases. Our case highlights the typical electrocardiographic manifestations of hypothermia including the J deflection and ST segment elevation during atrial fibrillation. Thorough knowledge of these findings is important for prompt diagnosis and treatment of hypothermic states.

A new approach of extracting embolized venous catheters using a large-diameter steerable sheath under biplane fluoroscopy.

To report the efficacy of a new percutaneous technique for extraction of embolized catheters, five female patients (62 ± 14 years) referred to our institution were analyzed. With the combination of a large-diameter steerable sheath with a sizeable snare system, three dislodged Port-A-Cath tubes and two ventriculoatrial shunts were retrieved successfully. Mean procedure time was 51 ± 23 min, biplane fluoroscopy time was 22 ± 21 min, and dose area product was 1188 ± 992 dGy cm(2). Percutaneous extraction of embolized venous catheters is highly effective with the help of this novel, self-assembled system. The presented technique provides major advantages with respect to three-dimensional steerability and should be considered for complex cases.

Rehospitalization rates after transcatheter aortic valve implantation.

AIMS: Comorbidities pose a major challenge to screening, selection and follow-up of transcatheter aortic valve implantation (TAVI) patients as well as to the procedure itself. The aim of the present study was to assess cardiac and non-cardiac readmission rates besides clinical endpoint data in the first 50 patients of a single center TAVI programme. METHODS AND RESULTS: TAVI was performed using the transfemoral CoreValve system. Procedural success rate was 94%; intraprocedural mortality was 2%. 82% of the patients remained free of a combined safety endpoint at 30 days, and 76.1% remained free of a combined efficacy endpoint at six months (modified criteria of the Valve Academic Research Consortium). At six months, among all surviving patients, 10.3% had experienced readmissions for cardiac causes, and 43.6% had experienced readmissions for non-cardiac causes. Causes of non-cardiac readmissions showed a wide distribution over various medical disciplines, reflecting the high rate of comorbidities. Beyond six months until a predefined reference date (mean follow up 9.9 months), the probability of hospitalization fell by half (1.54 vs. 0.74 hospital days per patient per month), driven by a decrease of non-cardiac readmissions. Karnofsky score before and after TAVI yielded a significant and sustained improvement of performance status, as assessed retrospectively at reference date. CONCLUSION: The findings of the present study suggest that the high prevalence of comorbidities in high-risk TAVI patients results in a high rate of non-cardiac rehospitalizations during the first 6 months of follow-up. Despite this fact, improvement of global everyday performance following TAVI as perceived by the patients seems to be substantial.

PLAATO (Percutaneous Left Atrial Appendage Transcatheter Occlusion) for prevention of cardioembolic stroke in non-anticoagulation eligible atrial fibrillation patients: results from the European PLAATO study.

AIMS: The European PLAATO (Percutaneous Left Atrial Appendage Transcatheter Occlusion) study was performed to determine the safety and efficacy of left atrial appendage occlusion by catheter technique. Embolic stroke due to atrial fibrillation is a common observation, especially in the elderly. Most thrombi in atrial fibrillation form in the left atrial appendage (LAA), its occlusion may therefore reduce the incidence of stroke in these patients. METHODS AND RESULTS: One hundred and eighty patients with non-rheumatic atrial fibrillation and contraindication to warfarin therapy were enrolled in the PLAATO study. Patients were eligible if they had a?history of transient ischaemic attack (TIA) or stroke or at least two independent risk factors for stroke such as age > or =75 years, hypertension, congestive heart failure or diabetes. The primary endpoint was LAA closure as determined by transesophageal echocardiography (TEE) two months after the procedure and stroke rate at 150 patient years. Left atrial appendage occlusion was successful in 162/180 patients (90%, 95% CI 83.1% to 92.9%). Two patients died within 24 hours of the procedure (1.1%, 95% CI 0.3% to 4%). Six cardiac tamponades were observed (3.3%, 95% CI 1.5% to 7.1%). In two cases, surgical drainage of the tamponade was necessary (1.1%, 95% CI 0.3% to 4%). In one patient, the device that was chosen was too small and embolised into the aorta after its release (0.6%, 95% CI 0.1% to 3.1%). It was snared and replaced without further complications. Successful occlusion of the LAA was achieved in 126/ 140 (90%, 95% CI 83.5% to 94.2%) of patients as noted by TEE at the two months follow-up. In a follow-up time of 129 documented patient years, three strokes occurred (2.3% per year). The expected incidence of stroke according to the CHADS2-Score was 6.6% per year. The trial was halted prematurely during the follow-up phase for financial considerations. CONCLUSIONS: Left atrial appendage closure is relatively safe and effective. However, severe complications can occur. It might become an alternative for atrial fibrillation patients who are ineligible for long-term anticoagulation therapy.

[Sudden cardiac death 43 months after fulminant myocarditis and two-peaked myositis in non-typhoid salmonellosis]. / Plötzlicher Herztod 43 Monate nach fulminanter Myokarditis und zweizeitiger Myositis bei Salmonella-enteritidis-Infektion.

HISTORY AND CLINICAL FINDINGS: A previously healthy 29-year-old male was hospitalized due to acute myalgia and high temperature following an uncomplicated gastroenteritis. Within 24 hours, he developed life-threatening hemodynamic shock with the need for inotropic support and sustained ventricular tachycardia. INVESTIGATIONS: Echocardiography and electrocardiogram as well as lab tests were consistent with the diagnosis of fulminant myocarditis and acute myositis. Serological and bacteriological analysis yielded an acute infection with salmonella D. TREATMENT AND COURSE: The patient's condition stabilized under conservative supportive care within a few days. Apart from a histologically confirmed recurrent myositis four weeks later, no further complications occurred and the patient was clinically and echocardiographically considered to be in complete functional remission. Three and a half years later, however, the patient unexpectedly and suddenly died. CONCLUSIONS: Although fulminant myocarditis is a life-threatening condition in its initial phase, the prognosis after recovery is considered to be good. However, this case study suggests that sudden cardiac death as a late complication of fulminant myocarditis may occur.

Gender-specific comparison of five QT correction formulae in middle-aged participants in an atherosclerosis prevention program.

BACKGROUND: Analysis of QT duration limited to a single heart rate correction formula might be problematic in cross-sectional studies. The aim of this study was to investigate five frequently used equations with respect to over- and under-correction of QT intervals in a middle-aged population without manifest atherosclerotic disease. MATERIAL/METHODS: A total of 1199 individuals (851 males, 348 females, aged 39 to 66 years) of the SAPHIR study (Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk) were investigated. Heart rate, RR, and QT intervals were measured automatically from resting ECGs with the 12SL ECG Analysis Program (GE Medical Systems). Five methods (Bazett, Fridericia, Framingham, Hodges, and Rautaharju) were used to correct the QT interval for heart rate. RESULTS: Females had shorter RR intervals than males (963+/-141 vs. 1022+/-158 ms, p<0.0005), with longer QT (410+/-28 vs. 404+/-28 ms, p=0.003) and QTc intervals using all five formulae (p<0.0005). No significant differences were observed between the gender groups for the QTc/RR slopes regardless of the formula. The Bazett formula performed the worst and the Fridericia the best in terms of rate adjustment success (slope B=-0.001). The optimal alpha of the best-fit equation (QTc=QT/RRalpha) was calculated as 0.326 for males and 0.328 for females. CONCLUSIONS: These results demonstrate that automatic QT measurements can be used reliably in cardiovascular prevention programs, encouraging further investigation of their clinical value in risk stratification. From an epidemiological perspective, however, the selected QT correction formula applied to a specific population has to be evaluated for appropriateness.

Blanked atrial flutter in patients with cardiac resynchronization therapy: clinical significance and implications for device programming.

BACKGROUND: Atrial arrhythmias are frequently observed in patients with heart failure and may be a primary cause for decompensation during cardiac resynchronization therapy (CRT). The accurate detection of organized atrial tachyarrhythmias poses a challenge to the function of mode-switching biventricular pacemakers/defibrillators. METHODS: The purpose of the study was to determine retrospectively the incidence of blanked atrial flutter and mode switch failure (2:1 lock-in), and to look for factors predisposing to this problem. A total number of 65 patients with CRT devices has been followed regularly over 18 +/- 12 months. Five patients were excluded because of chronic atrial fibrillation and reprogramming to VVIR mode. RESULTS: Seven out of 60 patients (12%) were diagnosed with blanked atrial flutter at unscheduled device interrogation. Sustained biventricular pacing at a median rate of 125/min-mimicking sinus tachycardia-resulted in rapid deterioration of heart failure and hospitalization. Mode switch failure occurred due to coincidence of every second flutter wave with atrial blanking. The group with 2:1 lock-in was programmed to longer atrial blanking times (143 +/- 34 ms vs 105 +/- 32 ms; P = 0.026) and AV intervals (126 +/- 8 ms vs 107 +/- 29; P = 0.001) than the group without lock-in. Other clinical characteristics examined did not differ between the two groups apart from a previous history of atrial fibrillation (P = 0.032). CONCLUSION: Blanked atrial flutter with rapid ventricular pacing is a clinically important problem in heart failure patients treated with CRT devices. Efforts should be made to avoid this complication by atrial lead implantation without ventricular farfield oversensing, by programming short PVAB and AV intervals, and by implementation of dedicated device algorithms.