[Algorithm for flexible decision-making in the intra-hospital management of patients with the changing requirements of the SARS-CoV-2 pandemic]. / Flexibler Entscheidungsalgorithmus zum innerklinischen stationären Patient*innen-Management unter wechselnden Anforderungen der SARS-CoV-2-Pandemie.

After the initial fulminant outbreak, the SARS-CoV­2 pandemic has now taken a more protracted course which, nevertheless, challenges hospitals in returning to a "normal" mode and in preparing for a worst-case scenario of a second wave. Not only the organization of the first contact with the patient and the admission in the emergency department but also the admission as an in-patient and the subsequent management requires both flexibility and clear directions of action for the medical personnel involved. The aim of the algorithm was to develop a structured, easy to implement and easy to follow guideline while simultaneously preserving resources. The algorithm covers some key points of decision making such as clinical signs, first contact, admission for in-patient treatment, consequences of swab and computed tomography (CT) results, and allocation and isolation measures within the hospital. The algorithm is not intended to guide diagnostics, decisions and treatment in the narrower medical sense but to provide more general instructions for the management of in-patients considering specific aspects of SARS-CoV­2.

Simultaneous quantitative susceptibility mapping and Flutemetamol-PET suggests local correlation of iron and ß-amyloid as an indicator of cognitive performance at high age.

The accumulation of ß-amyloid plaques is a hallmark of Alzheimer's disease (AD), and recently published data suggest that increased brain iron burden may reflect pathologies that synergistically contribute to the development of cognitive dysfunction. While preclinical disease stages are considered most promising for therapeutic intervention, the link between emerging AD-pathology and earliest clinical symptoms remains largely unclear. In the current study we therefore investigated local correlations between iron and ß-amyloid plaques, and their possible association with cognitive performance in healthy older adults. 116 older adults (mean age 75 ±â€¯7.4 years) received neuropsychological testing to calculate a composite cognitive score of performance in episodic memory, executive functioning, attention, language and communication. All participants were scanned on a combined PET-MRI instrument and were administered T1-sequences for anatomical mapping, quantitative susceptibility mapping (QSM) for assessing iron, and 18F-Flutemetamol-PET for estimating ß-amyloid plaque load. Biological parametric mapping (BPM) was used to generate masks indicating voxels with significant (p < 0.05) correlation between susceptibility and 18F-Flutemetamol-SUVR. We found a bilateral pattern of clusters characterized by a statistical relationship between magnetic susceptibility and 18F-Flutemetamol-SUVR, indicating local correlations between iron and ß-amyloid plaque deposition. For two bilateral clusters, located in the frontal and temporal cortex, significant relationships (p<0.05) between local ß-amyloid and the composite cognitive performance score could be observed. No relationship between whole-cortex ß-amyloid plaque load and cognitive performance was observable. Our data suggest that the local correlation of ß-amyloid plaque load and iron deposition may provide relevant information regarding cognitive performance of healthy older adults. Further studies are needed to clarify pathological correlates of the local interaction of ß-amyloid, iron and other causes of altered magnetic susceptibility.

Benefit of 18F-fluorocholine PET imaging in parathyroid surgery.

OBJECTIVES: To assess the additional diagnostic value of 18F-fluorocholine PET imaging in preoperative localization of pathologic parathyroid glands in clinically manifest hyperparathyroidism in case of negative or conflicting ultrasound and scintigraphy results. METHODS: A retrospective, single-institution study of 26 patients diagnosed with hyperparathyroidism. In cases where ultrasound and scintigraphy failed to detect the location of an adenoma in order to allow a focused surgical approach, an additional 18F-fluorocholine PET scan was performed and its results were compared with the intraoperative findings. RESULTS: A total of 26 patients underwent 18F-fluorocholine PET/CT (n = 11) or PET/MRI (n = 15). Adenomas were detected in 25 patients (96.2%). All patients underwent surgery, and the location predicted by PET hybrid imaging was confirmed intraoperatively by frozen section and adequate parathyroid hormone drop after removal. None of the patients needed revision surgery during follow-up. CONCLUSIONS: These results demonstrate that 18F-fluorocholine PET imaging is a highly accurate method to detect parathyroid adenomas even in case of previous localization failure by other imaging examinations. KEY POINTS: • With 18 F-fluorocholine PET imaging, parathyroid adenomas could be detected in 96.2%. • 18 F-fluorocholine imaging is a highly accurate method to detect parathyroid adenomas. • We encourage its use, where ultrasound fails to detect an adenoma.

Partitioning taxonomic diversity of aquatic insect assemblages and functional feeding groups in neotropical savanna headwater streams.

Biological diversity can be divided into: alpha (α, local), beta (ß, difference in assemblage composition among locals), and gamma (γ, total diversity). We assessed the partitioning of taxonomic diversity of Ephemeroptera, Plecoptera and Trichoptera (EPT) and of functional feeding groups (FFG) in neotropical savanna (southeastern Brazilian cerrado) streams. To do so, we considered three diversity components: stream site (α), among stream sites (ß1), and among hydrologic units (ß2). We also evaluated the association of EPT genera composition with heterogeneity in land use, instream physical habitat structure, and instream water quality variables. The percentage of EPT taxonomic α diversity (20.7%) was smaller than the ß1 and ß2 diversity percentages (53.1% and 26.2%, respectively). The percentage of EPT FFG collector-gatherer α diversity (26.5%) was smaller than that of ß1 diversity (55.8%) and higher than the ß2 (17.7%) diversity. The collector-gatherer FFG was predominant and had the greatest ß diversity percentage among stream sites (ß1, 55.8%). Our findings support the need for implementing regional scale conservation strategies in the cerrado biome, which has been degraded by anthropogenic activities.

Cardiac SPECT/CCTA hybrid imaging : One answer to two questions?

Noninvasive cardiac imaging has witnessed tremendous advances in the recent past, particularly with regard to coronary computed tomography angiography (CCTA) where substantial improvements in image quality have been achieved while at the same time patients' radiation dose exposure has been reduced to the sub-millisievert range. Similarly, for single-photon emission computed tomography (SPECT) the introduction of novel cadmium-zinc-telluride-based semiconductor detectors has significantly improved system sensitivity and image quality, enabling fast image acquisition within less than 2-3 min or reduction of radiation dose exposure to less than 5 mSv. However, neither imaging modality alone is able to fully cover the two aspects of coronary artery disease (CAD), that is, morphology and function. Both modalities have distinct advantages and shortcomings: While CCTA may prove a superb modality for excluding CAD through its excellent negative predictive value, it does not allow for assessment of hemodynamic relevance if obstructive coronary lesions are detected. Conversely, SPECT myocardial perfusion imaging cannot provide any information on the presence or absence of subclinical coronary atherosclerosis. This article aims to highlight the great potential of cardiac hybrid imaging that allows for a comprehensive evaluation of CAD through combination of both morphological and functional information by fusing SPECT with CCTA.

Recruitment and retention monitoring: facilitating the mission of the National Institute of Neurological Disorders and Stroke (NINDS).

It is commonly accepted that inefficient recruitment and inadequate retention continue to threaten the completion of clinical trials intended to reduce the public health burden of neurological disease. This article will discuss the scientific, economic, and ethical implications of failure to recruit and retain adequate samples in clinical trials, including the consequences of failing to recruit adequately diverse samples. We will also discuss the more common challenges and barriers to efficient and effective recruitment and retention, and the impact these have on successful clinical trial planning. We will explain the newly established efforts within National Institute of Neurological Disorders and Stroke (NINDS) to monitor recruitment and retention with well-defined metrics and implementation of grant awards that include feasibility milestones for continued funding. Finally, we will describe our efforts to address some of the common challenges to recruitment and retention through assistance to investigators and coordinators with evidence-based support, tools, and resources for planning and strategizing recruitment and retention as well as a trans-NIH effort to improve awareness of clinical research in the general public.

Coronary computed tomography angiography indicates complexity of percutaneous coronary interventions.

BACKGROUND: Coronary computed tomography angiography (CCTA) provides information regarding lesion morphology and three-dimensional coronary anatomy incremental to coronary angiography. We addressed the question whether preprocedural CCTA bears potential for guiding percutaneous coronary interventions (PCI). METHODS AND RESULTS: Sixty-six coronary lesions attempted with PCI within 6 months of preprocedural CCTA were retrospectively assessed. Lesion parameters from unenhanced computed tomography (CT) for calcium scoring and CCTA were analyzed and compared with PCI complexity. Complex PCI was defined as use of buddy wire, kissing balloon, necessity of high pressure balloons, or rotablator. Complex PCIs were observed in 32 interventions (48%). Median Agatston score and Hounsfield units were higher in lesions with complex as compared to those with non-complex interventions with 130 (interquartile range, 23-276) vs 29 (0-158; P=.01), and 493 (245-631) vs 341 (68-520 Hounsfield Units; P=.04), respectively. Median local plaque volume and plaque mass were higher in complex PCI with 17 (2-39) vs 5 (0-19.5 mm³; P=.007), and 48 (15-99) vs. 16 (1.5-63 mg hydroxyapatite/mm³; P=.03), respectively. Lesions leading to complex PCI were longer [1.8 (1.2-2.8) vs 1.3 (0.8-1.7) cm; P=.03], and had a higher rate of calcified plaques (23% vs 3%; P=.03). There was a significant correlation between CCTA- and angiography-derived local SYNTAX Scores (P<.001); the CCTA-derived score seems to be predictive for failed and complex PCI (area under curve = 0.75 ± 0.13 and 0.66 ± 0.08, respectively). CONCLUSIONS: Preprocedural lesion assessment by CCTA indicates complexity of PCI. In patients with suspected complex coronary anatomy, prior CCTA adds important information for planning PCI.

Natural history of MELAS associated with mitochondrial DNA m.3243A>G genotype.

OBJECTIVE: To describe the natural history of clinical and laboratory features associated with the m.3243A>G mitochondrial DNA point mutation. Natural history data are needed to obtain prognostic information and for clinical trial planning. METHODS: We included 85 matrilineal relatives from 35 families with at least 2 visits in this prospective cohort study. Thirty-one were fully symptomatic with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), and 54 were carrier relatives. Evaluations included standardized questionnaires (medical history and daily living functioning), physical examination, neuropsychological testing, and a battery of imaging and laboratory tests. We evaluated changes in clinical and laboratory features over time and survival. Outcomes are reported over a follow-up period of up to 10.6 years (mean 3.8 ± 2.2 years for patients and 5.5 ± 3.0 for carrier relatives). RESULTS: Neurologic examination, neuropsychological testing, and daily living scores significantly declined in all patients with MELAS, whereas no significant deterioration occurred in carrier relatives. Cerebral MRI scores declined significantly in patients with MELAS. Magnetic resonance spectroscopy estimates of lactate in the lateral ventricles increased over time, and high lactate was associated with increased mortality. Symptom onset in childhood often was associated with worse outcome. Patients with MELAS had a greater death rate than carrier relatives. CONCLUSIONS: Patients with MELAS carrying the m.3243A>G mutation show a measurable decline in clinical and imaging outcomes. It is hoped that these data will be helpful in anticipating the disease course and in planning clinical trials for MELAS.

Lowering heart rate with an optimised breathing protocol for prospectively ECG-triggered CT coronary angiography.

OBJECTIVES: The aim was to prospectively characterise the effect of the level of breath-hold on heart rate in CT coronary angiography (CTCA) with prospective electrocardiogram (ECG) triggering and its impact on coronary artery attenuation. METHODS: 260 patients (86 women; mean age 59 ± 11 years) underwent 64-slice CTCA using prospective ECG triggering. Prior to CTCA, heart rates were recorded during 15 s of breath-hold at three different levels of inspiration (normal, intermediate and deep). The inspiration level with the lowest heart rate was chosen for actual CTCA scanning. Coronary artery attenuation was measured, and the presence of backflow of contrast material into the inferior vena cava (as an indicator of increased intrathoracic pressure) was recorded. RESULTS: The mean heart rate at breath-hold was significantly different for the three inspiration levels (normal, 60 ± 8 bpm; intermediate, 59 ± 8 bpm; deep, 57 ± 7 bpm; p<0.001). The maximum heart rate reduction in each patient at breath-hold averaged 5.3 ± 5.1 bpm, and was observed at a normal inspiration depth in 23 (9%) patients, at an intermediate inspiration depth in 102 (39%) patients and at deep inspiration in 135 (52%) patients. Overall, there was no association between the level of breath-hold and coronary vessel attenuation (p-value was not significant). However, the backflow of contrast material into the inferior vena cava (n = 26) was found predominantly at deep inspiration levels (p<0.001), and, when it occurred, it was associated with reduced coronary attenuation compared with patients with no backflow (p<0.05). CONCLUSION: The breath-hold level to best reduce heart rate for CTCA should be individually assessed prior to scanning because a mean heart rate reduction of 5 bpm can be achieved.

Six-Minute Walk Test demonstrates motor fatigue in spinal muscular atrophy.

BACKGROUND: In spinal muscular atrophy (SMA), weakness, decreased endurance, and fatigue limit mobility. Scales have been developed to measure function across the wide spectrum of disease severity. However, these scales typically are observer dependent, and scores are based on sums across Likert-scaled items. The Six-Minute Walk Test (6MWT) is an objective, easily administered, and standardized evaluation of functional exercise capacity that has been proven reliable in other neurologic disorders and in children. METHODS: To study the performance of the 6MWT in SMA, 18 ambulatory participants were evaluated in a cross-sectional study. Clinical measures were 6MWT, 10-m walk/run, Hammersmith Functional Motor Scale-Expanded (HFMSE), forced vital capacity, and handheld dynamometry. Associations between the 6MWT total distance and other outcomes were analyzed using Spearman correlation coefficients. A paired t test was used to compare the mean distance walked in the first and sixth minutes. RESULTS: The 6MWT was associated with the HFMSE score (r = 0.83, p < 0.0001), 10-m walk/run (r = -0.87, p < 0.0001), and knee flexor strength (r = 0.62, p = 0.01). Gait velocity decreased during successive minutes in nearly all participants. The average first minute distance (57.5 m) was significantly more than the sixth minute distance (48 m) (p = 0.0003). CONCLUSION: The Six-Minute Walk Test (6MWT) can be safely performed in ambulatory patients with spinal muscular atrophy (SMA), correlates with established outcome measures, and is sensitive to fatigue-related changes. The 6MWT is a promising candidate outcome measure for clinical trials in ambulatory subjects with SMA.

First head-to-head comparison of effective radiation dose from low-dose 64-slice CT with prospective ECG-triggering versus invasive coronary angiography.

BACKGROUND: Reduction of radiation burden of multidetector computed tomography coronary angiography (CTCA) has remained an important task. OBJECTIVE: To compare effective radiation dose of low-dose 64-slice CTCA using prospective ECG-triggering versus diagnostic invasive coronary angiography (CA). METHODS: 42 patients referred for elective invasive CA owing to suspected coronary artery disease (CAD) were prospectively enrolled to undergo a low-dose CTCA without calcium scoring within the same day before CA. Dose-area product of diagnostic invasive CA and dose-length product of CTCA were measured, converted into effective radiation dose and compared using Mann-Whitney U tests. In addition, accuracy of CTCA to detect CAD (coronary artery narrowing > or =50%) was assessed using invasive CA as standard of reference. On an intention-to-diagnose basis all non-evaluative vessels were included in the analysis and censored as positive. RESULTS: The estimated mean effective radiation dose was 8.5 (4.4) mSv (range 1.4-20.5 mSv) for diagnostic invasive CA, and 2.1 (0.7) mSv (range 1.0-3.3 mSv) for CTCA (p<0.001). 19 patients (42.9%) had no CAD by invasive CA. 40 (95.2%) patients have been correctly classified as having CAD (23/23) or no CAD (17/19). Over 97% (551/567) of segments were evaluable. Vessel-based analysis revealed sensitivity, specificity, positive and negative predictive value of 94.2% (CI 0.8% to 1.0%), 94.8% (CI 09% to 1.0%), 89.0% (CI 0.8% to 1.0%), 97.4% (CI 09% to 1.0%) and an accuracy of 94.6%. CONCLUSIONS: Low dose CTCA allows evaluation of CAD with high accuracy, but delivers a significantly less effective radiation dose to patients compared to diagnostic invasive CA.

Multislice computed tomography coronary angiography for risk stratification in patients with an intermediate pretest likelihood.

OBJECTIVES: To assess whether multislice computed tomography coronary angiography (MSCTA) may be useful for risk stratification of patients with suspected coronary artery disease (CAD) at intermediate pretest likelihood according to Diamond and Forrester. DESIGN AND PATIENTS: MSCTA images were evaluated for the presence of significant CAD in 316 patients with suspected CAD (60% male, average (SD) age 57 (11) years) and an intermediate pretest likelihood according to Diamond and Forrester. Patients were followed up to determine the occurrence of an event. MAIN OUTCOME MEASURES: A combined end point of all-cause mortality, non-fatal infarction and unstable angina requiring revascularisation. RESULTS: Significant CAD was seen in 89 patients (28%), whereas normal MSCTA or non-significant CAD was seen in the remaining 227 (72%) patients. During follow-up (median 621 days (25-75th centile 408-835) an event occurred in 13 patients (4.8%). The annualised event rate was 0.8% in patients with normal MSCT, 2.2% in patients with non-significant CAD and 6.5% in patients with significant CAD. Moreover, MSCTA remained a significant predictor (p<0.05) of events after multivariate correction (hazard ratio = 3.460 (95% CI 1.142 to 10.480). CONCLUSIONS: The results suggest that in patients with an intermediate pretest likelihood, MSCTA is highly effective in re-stratifying patients into either a low or high post-test risk group. These results further emphasise the usefulness of non-invasive imaging with MSCTA in this patient population.

Impact of vessel attenuation on quantitative coronary angiography with 64-slice CT.

The aim of the study was to determine the impact of vessel attenuation on quantitative 64-slice computed tomography coronary angiography (CTCA). CTCA and invasive quantitative coronary angiography (QCA) were performed in 100 consecutive patients (42 women, 58 men; mean age 64.4+/-9.4 years; age range 39-87 years). In QCA, stenoses were quantified with dedicated software, whereas in CTCA, stenosis severity was assessed with an electronic caliper tool: stenoses were graded in 10% steps and assigned as either a calcified or non-calcified lesion. Vessel attenuation in the left main (LMA) and the proximal right coronary artery (RCA) were measured and correlated with differences in quantifications of stenosis grade between QCA and CTCA. A total of 113 coronary stenoses were detected by both methods (94 significant and 19 non-significant); 52 stenoses were rated as non-calcified and 61 as calcified lesions. The mean difference between QCA and quantitative CTCA grading was 5.1+/-16.9% (range -27 to 46%) overall; 1.9+/-14.2% (range -27 to 38%) for non-calcified lesions and 7.8+/-18.6% (range -23 to 46%) for calcified lesions. Mean vessel attenuation was 362+/-76 HU (range 191-584 HU) in the LMA and 333+/-81 HU (range 162-564 HU) in the RCA. Attenuation did not significantly correlate with differences in QCA and CTCA gradings, neither overall nor for calcified or non-calcified lesions. When 64-slice CTCA is used, coronary vessel attenuation had no impact on the quantitative grading of stenoses.

Historical underpinnings of the term essential tremor in the late 19th century.

BACKGROUND: The term essential tremor has been in regular use since the second half of the 20th century. To modern neurologists, the word "essential" may seem cryptic. The historical underpinnings of this term have not been examined. OBJECTIVES: To bring to attention early medical reports using the term essential tremor and examine the characteristics of the disorder that contributed to the proposed use of the term. METHODS: Review of 19th and early 20th century medical literature on essential tremor. RESULTS: The term tremore semplice essenziale (simple essential tremor) was first used by Burresi (Italy, 1874) to describe an 18-year-old man with severe, isolated action tremor. Several years later, Maragliano (Italy, 1879), Nagy (Austria, 1890), and Raymond (France, 1892) described similar cases and proposed the terms tremore essenziale congenito (essential congenital tremor), essentieller Tremor (essential tremor), and tremblement essentiel héréditaire (hereditary essential tremor) to define the illness. Mirroring contemporaneous views of constitutional and inherited disease, the key ingredients of the disorder were viewed as the constant presence of tremor in the absence of other neurologic signs and its heritable nature. By the early 20th century, the term began to appear in the medical literature with greater frequency. CONCLUSIONS: Toward the end of the 19th century, several clinicians attempted to provide a nosologic separation for a tremor diathesis that was often familial and occurred in isolation of other neurologic signs. This disorder, which was termed essential tremor, was later recognized as one of the most common neurologic disorders.

Radionuclide PET and PET/CT in coronary artery disease.

In the present review, the basis of non invasive assessment of CAD, the most recent technical developments and results obtained by PET in cardiovascular research and clinical cardiology are described. PET has provided a wealth of new information in the field of cardiac pathophysiology and remains the gold standard for non-invasive measurements of MBF and CFR against which new techniques should be tested. The possibility to combine this relevant functional information with the anatomic details on luminal and arterial wall abnormalities, provided by multislice CT with or without the use of "hybrid" scanners, offers new opportunities for comprehensive non-invasive assessment of CAD and efficacy of new treatments.

Dust-climate couplings over the past 800,000 years from the EPICA Dome C ice core.

Dust can affect the radiative balance of the atmosphere by absorbing or reflecting incoming solar radiation; it can also be a source of micronutrients, such as iron, to the ocean. It has been suggested that production, transport and deposition of dust is influenced by climatic changes on glacial-interglacial timescales. Here we present a high-resolution record of aeolian dust from the EPICA Dome C ice core in East Antarctica, which provides an undisturbed climate sequence over the past eight climatic cycles. We find that there is a significant correlation between dust flux and temperature records during glacial periods that is absent during interglacial periods. Our data suggest that dust flux is increasingly correlated with Antarctic temperature as the climate becomes colder. We interpret this as progressive coupling of the climates of Antarctic and lower latitudes. Limited changes in glacial-interglacial atmospheric transport time suggest that the sources and lifetime of dust are the main factors controlling the high glacial dust input. We propose that the observed approximately 25-fold increase in glacial dust flux over all eight glacial periods can be attributed to a strengthening of South American dust sources, together with a longer lifetime for atmospheric dust particles in the upper troposphere resulting from a reduced hydrological cycle during the ice ages.

Combining dual-source computed tomography coronary angiography and calcium scoring: added value for the assessment of coronary artery disease.

OBJECTIVE: To prospectively investigate the diagnostic accuracy of dual-source 64-slice computed tomography coronary angiography (CTCA), calcium scoring (CS) and both methods combined for assessing significant coronary artery stenoses relative to conventional coronary angiography (CCA). DESIGN, SETTING AND PATIENTS: Prospective, single-centre study conducted in a referral centre enrolling 74 consecutive patients (24 women; mean age 62 (SD 12) years) from August-October 2006. All study participants underwent CS, CTCA and CCA. Diagnostic accuracy was calculated for CS, CTCA and both methods combined relative to CCA. Not-evaluative segments at computed tomography were considered false positive. RESULTS: CCA identified 139 stenoses in 36 patients. Average heart rate during CTCA was 68 (13) bpm (range 35-102 bpm), and 2% of segments (21/1001) in 11% of patients (8/74) were not evaluative. Considering these as false positives, per-patient sensitivity and specificity was 98% and 87%. When using CS cut-off values of 0 to exclude and >or=400 to predict stenosis, sensitivity and specificity of CS was 100% and 70%, respectively. Combining CS and CTCA in all patients correctly reclassified five patients, while six were falsely classified as stenotic, all of them correctly classified with CTCA alone. Using CS only in patients with not-evaluative segments correctly reclassified five patients while avoiding misclassifications (sensitivity 98%, specificity 100%). CONCLUSION: Dual-source CTCA allows the diagnosis of significant stenoses with a high diagnostic accuracy. Selectively combining CS with CTCA in patients with not-evaluative coronary segments improves specificity from 87% to 100% without decreasing the high sensitivity of 98%.

The changing natural history of spinal muscular atrophy type 1.

BACKGROUND: Noninvasive ventilation has become increasingly available to spinal muscular atrophy (SMA) patients since the early 1990 s. This is expected to have improved survival for SMA type 1 patients. OBJECTIVE: To assess whether there has been a change in survival in patients with SMA type 1 between 1980 and 2006. METHODS: We used deidentified, family-reported data from participants in the International Spinal Muscular Atrophy Patient Registry and obtained additional clinical information through a mail-in questionnaire. One hundred forty-three patients with SMA type 1 were included in the analysis. Survival of patients born in 1995-2006 (n = 78) was compared with that of patients born in 1980-1994 (n = 65), using the Kaplan-Meier method and Cox proportional hazards models with age at death as the outcome. RESULTS: Patients born in 1995 though 2006 had significantly increased survival compared with those born in 1980-1994 (log-rank test, p < 0.001). In a Cox model, patients born in 1995-2006 had a 70% reduction in the risk of death compared with those born in 1980-1994 (hazard ratio [HR] 0.3, 95% CI 0.2-0.5, p < 0.001) over a mean follow-up of 49.9 months (SD 61.1, median 22.0). However, when controlling for demographic and clinical care variables, year of birth was no longer significantly associated with age at death (HR 1.0, 95% CI 0.6-1.8, p = 0.9), whereas ventilation for more than 16 h/d, use of a mechanical insufflation-exsufflation device, and gastrostomy tube feeding showed a significant effect in reducing the risk of death. CONCLUSION: Survival in spinal muscular atrophy type 1 patients has increased in recent years, in relation to the growing trend toward more proactive clinical care.