Investigation of turning points in the effectiveness of Covid-19 social distancing.

Covid-19 is the first digitally documented pandemic in history, presenting a unique opportunity to learn how to best deal with similar crises in the future. In this study we have carried out a model-based evaluation of the effectiveness of social distancing, using Austria and Slovenia as examples. Whereas the majority of comparable studies have postulated a negative relationship between the stringency of social distancing (reduction in social contacts) and the scale of the epidemic, our model has suggested a varying relationship, with turning points at which the system changes its predominant regime from 'less social distancing-more cumulative deaths and infections' to 'less social distancing-fewer cumulative deaths and infections'. This relationship was found to persist in scenarios with distinct seasonal variation in transmission and limited national intensive care capabilities. In such situations, relaxing social distancing during low transmission seasons (spring and summer) was found to relieve pressure from high transmission seasons (fall and winter) thus reducing the total number of infections and fatalities. Strategies that take into account this relationship could be particularly beneficial in situations where long-term containment is not feasible.

Accuracy of gradient diffusion method for susceptibility testing of dalbavancin and comparators.

OBJECTIVES: This multicenter study aimed to assess the performances of gradient diffusion (GD) method in comparison to broth microdilution (BMD) method for susceptibility testing of dalbavancin, daptomycin, vancomycin, and teicoplanin. METHODS: Minimum Inhibitory Concentrations (MICs) were retrospectively determined concomitantly by BMD and GD methods, for 93 staphylococci and enterococci isolated from clinical samples. BMD was considered as the gold standard. Essential (EA) and categorical agreements (CA) were calculated. Discordant categorical results were categorized as major (ME) and very major errors (VME). RESULTS: EA and CA were 95.7% and 96.8%, 82.8% and 100%, 97.8% and 96.8%, and 94.6% and 95.7% for dalbavancin, daptomycin, vancomycin, and teicoplanin respectively. Concerning dalbavancin, 3 ME without any VME were observed and discrepancies were low (≤ to 2 two-fold dilutions) between both methods. VME were noted in 1 and 3 cases for vancomycin and teicoplanin, respectively, and resulted from 1 two-fold dilution discrepancy in each case. EA was lower for daptomycin. When they were discrepant, BMD MICs were systematically higher than GD ones. Nevertheless, no categorical discrepancy was noted. CONCLUSIONS: GD appears as an acceptable and convenient alternative for dalbavancin, vancomycin, and teicoplanin MICs determination. Our study also emphasizes how achieving accurate daptomycin MICs remains challenging.

Development of a database for the rapid and accurate routine identification of Achromobacter species by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS).

OBJECTIVES: Achromobacter spp. are emerging pathogens in respiratory samples from cystic fibrosis patients. The current reference methods (nrdA-sequencing or multilocus sequence typing) can identify 18 species which are often misidentified by conventional techniques as A. xylosoxidans. A few studies have suggested that matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF/MS) provides accurate identification of the genus but not of species. The aims of this study were (a) to generate a database for MALDI-TOF/MS Bruker including the 18 species, (b) to evaluate the suitability of the database for routine laboratory identification, and (c) to compare its performance with that of the currently available Bruker default database. METHODS: A total of 205 isolates belonging to the 18 species identified by nrdA sequencing were used to build a local database. Main spectra profiles (MSPs) were created according to Bruker's recommendations for each isolate with the Biotyper software. Performance of the default Bruker database and ours for routine use were compared by testing 167 strains (including 38 isolates used from MSP creation) belonging to the 18 species identified by nrdA sequencing directly from colonies cultivated on various media. RESULTS: Our new database accurately identified 99.4% (166/167) of the isolates from the 18 species (score ≥2.0) versus only 50.9% (85/167) with the Bruker database. In the Bruker database 17.3% of the isolates (29/167) were incorrectly identified as another species despite a score of ≥2.0. CONCLUSIONS: The use of MALDI-TOF/MS in combination with a database developed with samples from 18 Achromobacter species provides rapid and accurate identification. This tool could be used to help future clinical studies.

Investigating duration and intensity of Covid-19 social-distancing strategies.

The exponential character of the recent Covid-19 outbreak requires a change in strategy from containment to mitigation. Meanwhile, most countries apply social distancing with the objective to keep the number of critical cases below the capabilities of the health care system. Due to the novelty and rapid spread of the virus, an a priori assessment of this strategy was not possible. In this study, we present a model-based systems analysis to assess the effectiveness of social distancing measures in terms of intensity and duration of application. Results show a super-linear scaling between intensity (percent contact reduction) and required duration of application to have an added value (a lower number of fatalities). This holds true for an effective reproduction of [Formula: see text] and is reverted for [Formula: see text]. If R is not reduced below 1, secondary effects of required long-term isolation are likely to unravel the added value of disease mitigation. If an extinction is not feasible, we recommend moderate social-distancing that is well balanced against capability limits of national health-care systems.

Measuring Outcomes in Adults with Spinal Muscular Atrophy - Challenges and Future Directions - Meeting Report.

Spinal muscular atrophy (SMA) is a progressive autosomal recessive motor neuron disease which affects 1 in 6,000-10,000 live births, caused by loss of the survival motor neuron 1 gene (SMN1). A major focus of therapeutic developments has been on increasing the full-length SMN protein by increasing the inclusion of exon 7 in SMN2 transcripts, enhancing SMN2 gene expression, stabilizing the SMN protein or replacing the SMN1 gene.In June 2017, FDA and EMA have approved the antisense oligonucleotide Nusinersen as the first treatment for all SMA subtypes without age restriction. While prominent treatment effects have been observed in the earlier stages of the disease and in patients up to 15 years of age, there is only limited data from clinical trials in adult SMA patients. First real-world data from neuromuscular clinical centers suggest a therapeutic benefit of nusinersen with a favourable safety profile also in adult SMA patients: in several cases, relevant improvements of motor function is achieved, which might lead to enhanced autonomy in daily life activities and improved quality of life. Systematic follow-up of the motor status with validated instruments is crucial for an adequate monitoring of the therapeutic effects but most of the widely used scales and scores have been developed and evaluated for the pediatric population only. International neuromuscular experts have met in Frankfurt/Main, Germany in May 2019 to discuss relevant aspects of the diagnostic pathway and patient management in adult SMA. The recommendations and challenges in this patient population are discussed.

16S rRNA PCR on clinical specimens: Impact on diagnosis and therapeutic management.

OBJECTIVE: 16S rRNA PCR (16S PCR) performed on clinical samples contributes to bacterial identification in cases of negative culture due to an antibiotic therapy. Sensitivity of the 16S PCR is low (19-42%). Little data is available on its impact on the management of patients. We aimed to evaluate the contribution of 16S PCR to diagnosis and therapeutic management at the university hospital of Dijon, France. PATIENTS AND METHODS: 16S PCR was performed on the clinical specimens of 132 patients. Clinical settings, laboratory results, and data on antibiotic therapy were collected, as well as conclusions drawn from the 16S PCR result by physicians. Each case was analyzed to determine if the 16S PCR was helpful. The relevance of the 16S PCR was also assessed. RESULTS: The 16S PCR yield was 27.3%, ranging from 14.3% to 64.3% depending on the type of specimen. 16S PCR had a positive impact on diagnosis in 28.8% of cases. Five negative 16S PCR results were considered helpful as they contributed to ruling out bacterial infection. 16S PCR led to treatment changes in six patients (4.5%): three narrower spectrums, two treatment adaptations, and one discontinuation. The 16S PCR was considered "non-relevant" in 35 cases (26.5%). None of these 35 PCRs contributed to the patient's management. CONCLUSION: Physicians should be aware of performances of 16S PCR. Dialogue between physicians and bacteriologists is essential for appropriate selection of indications and correct interpretation of results.

Diagnostic criteria for amyotrophic lateral sclerosis: A multicentre study of inter-rater variation and sensitivity.

OBJECTIVE: This study assesses inter-rater agreement and sensitivity of diagnostic criteria for amyotrophic lateral sclerosis (ALS). METHODS: Clinical and electrophysiological data of 399 patients with suspected ALS were collected by eleven experienced physicians from ten different countries. Eight physicians classified patients independently and blinded according to the revised El Escorial Criteria (rEEC) and to the Awaji Criteria (AC). Inter-rater agreement was assessed by Kappa coefficients, sensitivity by majority diagnosis on 350 patients with follow-up data. RESULTS: Inter-rater agreement was generally low both for rEEC and AC. Agreement was best on the categories "Not-ALS", "Definite", and "Probable", and poorest for "Possible" and "Probable Laboratory-supported". Sensitivity was equal for rEEC (64%) and AC (63%), probably due to downgrading of "Probable Laboratory-supported" patients by AC. However, AC was significantly more effective in classifying patients as "ALS" versus "Not-ALS" (p < 0.0001). CONCLUSIONS: Inter-rater variation is high both for rEEC and for AC probably due to a high complexity of the rEEC inherent in the AC. The gain of AC on diagnostic sensitivity is reduced by the omission of the "Probable Laboratory-supported" category. SIGNIFICANCE: The results highlight a need for initiatives to develop simpler and more reproducible diagnostic criteria for ALS in clinical practice and research.

Achromobacter xylosoxidans is the predominant Achromobacter species isolated from diverse non-respiratory samples.

Achromobacter spp. are emerging opportunistic Gram-negative rods responsible for diverse nosocomial or community-acquired infections. We describe, for the first time, the distribution of Achromobacter spp., defined by nrdA gene sequencing, and their antimicrobial susceptibility in a variety of non-respiratory samples recovered from hospitalized patients from 2010 to 2015. Of the 63 isolates studied, A. xylosoxidans was the most prevalent (41 isolates), and with the exception of A. insuavis (four isolates), the remaining 10 species identified were represented by one or two isolates only. All isolates were uniformly susceptible to piperacillin and piperacillin-tazobactam and 97% to meropenem, but 76% showed resistance to ciprofloxacin. This study confirms the diversity of Achromobacter spp. in non-cystic fibrosis (CF) isolates and the predominance of A. xylosoxidans, as previously reported for CF sputum isolates. There was no apparent link between the clinical site of infection and the species of Achromobacter.

Distribution of innate efflux-mediated aminoglycoside resistance among different Achromobacter species.

Achromobacter spp. are emerging respiratory pathogens in cystic fibrosis patients. Since 2013 the genus Achromobacter includes 15 species for which innate antibiotic resistance is unknown. Previously the AxyXY-OprZ efflux system has been described to confer aminoglycoside (AG) resistance in A. xylosoxidans. Nevertheless, some Achromobacter spp. strains are susceptible to AG. This study including 49 Achromobacter isolates reveals that AG resistance is correlated with different Achromobacter spp. It is noteworthy that the axyXY-oprZ operon is detected only in AG-resistant species, including the most frequently encountered in cystic fibrosis patients: A. xylosoxidans, A. ruhlandii, A. dolens and A. insuavis.

Modeling structural change in spatial system dynamics: A Daisyworld example.

System dynamics (SD) is an effective approach for helping reveal the temporal behavior of complex systems. Although there have been recent developments in expanding SD to include systems' spatial dependencies, most applications have been restricted to the simulation of diffusion processes; this is especially true for models on structural change (e.g. LULC modeling). To address this shortcoming, a Python program is proposed to tightly couple SD software to a Geographic Information System (GIS). The approach provides the required capacities for handling bidirectional and synchronized interactions of operations between SD and GIS. In order to illustrate the concept and the techniques proposed for simulating structural changes, a fictitious environment called Daisyworld has been recreated in a spatial system dynamics (SSD) environment. The comparison of spatial and non-spatial simulations emphasizes the importance of considering spatio-temporal feedbacks. Finally, practical applications of structural change models in agriculture and disaster management are proposed.

The Motor Unit Number Index (MUNIX) in sarcopenic patients.

INTRODUCTION: The cause of sarcopenia is still not fully understood. A multifactorial aetiology is discussed. Neurodegenerative aspects in the genesis of sarcopenia, such as loss of motoneurons, have not yet been explored to a sufficient extent. METHOD: The Motor Unit Number Index (MUNIX) is a method for assessing the number and size (Motor Unit Size Index - MUSIX) of Motor Units (MUs) using the Compound Muscle Action Potential (CMAP) and the Surface electromyographic Interference Pattern (SIP). This method was used to study the hypothenar muscle in the right hand of 27 sarcopenic patients. RESULTS: The mean MUNIX (111±51) of all investigated sarcopenic patients lies between the mean MUNIX of healthy persons and the mean MUNIX of ALS patients. 25% of sarcopenic patients exhibit pathologic values for both MUNIX (<80) and MUSIX (>100 µV). A strong correlation (r=0.75, p<0.001) between MUSIX and the reciprocal value of MUNIX was identified. CONCLUSION: It was demonstrated for the first time by applying the MUNIX technique that loss of motoneurons plays a pathogenic role in the onset of sarcopenia. This was shown in 25% of sarcopenic participants who exhibited pathologic values for both MUNIX and MUSIX. Nerve sprouting seems to be an important mechanism of compensation for loss of motoneurons, reflected by the strong correlation between MUNIX and MUSIX. Use of MUNIX leads to the identification of a distinct subgroup of sarcopenic patients, which might have a major impact on future diagnostic and therapeutic concepts.

Phenotypes in Swiss patients with familial ALS carrying TARDBP mutations.

BACKGROUND: Recently, mutations in the TARDBP gene encoding the TAR DNA-binding protein 43 (TDP-43) have been identified in some familial amyotrophic lateral sclerosis (ALS) and sporadic ALS patients. The phenotype and frequency of TARDBP mutation carriers reportedly varies greatly among European populations. OBJECTIVE: To define the phenotypic spectrum of TARDBP mutations and their frequency in a Swiss population. METHODS: A total of 225 patients diagnosed with ALS (182 sporadic cases, 43 familial cases) were screened for TARDBP mutations. All patients were carefully examined and interviewed for a familial predisposition. Except for 1 patient who was followed at the University of Geneva, all patients were followed at the Kantonsspital St. Gallen. RESULTS: 43 patients (19.5%) had a definite family history for ALS. A TARDBP mutation was identified in 4 of these (9.3%). Two female ALS patients carried the p.Asn352Ser mutation. Both had limb onset and a slowly progressive course of the disease. A novel mutation (p.Gly376Asp) was identified in a 44-year-old female patient. Survival amongst affected family members varied between 6 and 18 months. The patient and also the other siblings affected with ALS had an accessory nipple. A fourth male patient carried the p.Ala90Val mutation. None of the patients had overt cognitive impairment. TARDBP mutations were not found among patients with sporadic forms of ALS. CONCLUSION: In this Swiss population, the frequency of familial ALS is higher than reported earlier in other populations. The novel p.Gly376Asp TARDBP mutation is associated with rapid disease progression and may be associated with an accessory nipple while the p.Asn352Ser mutation is associated with slow disease progression.

[Nasopharyngeal carriage, antibiotic susceptibility and serotyping of Streptococcus pneumoniae and Haemophilus influenzae in children attending day care centers]. / Portage nasopharyngé, sensibilités et sérotypes de Streptococcus pneumoniae et Haemophilus influenzae chez les enfants de crèches.

UNLABELLED: The aim of this study was to investigate the nasal carriage of Streptococcus pneumoniae (SP) and Haemophilus influenzae (HI) in children. METHODS: Nasal samples were swabbed from children 3 months to 3 years of age, between December 2006 and April 2007, in 10 day-care centers in Dijon. RESULTS: Three hundred and eighty-five children, 22.7 ± 8.4 months, were included. All were vaccinated against H1 and 92% had received at least one dose of PCV7 vaccine. HI colonization (55%) was associated with young age and concomitant pneumococcal carriage (52.4% vs. 39%). Amoxicillin/clavulanate and cefotaxime resistance rates were 17% and 0.5%. Pneumococcal carriage (48%) was increased in case of prior hospitalization. The rate of PDSP, 50%, was increased in case of recent infection (91% vs. 81%), previous antibiotherapy (64% vs. 41%), and decreased if PCV7 was completed (40.2% vs. 61,8%). There was no resistance to amoxicillin. The erythromycin resistance rate was 50.5%. 15% of the strains were vaccinal serotypes. Thirty-six and 41% of the strains were related and non-related to vaccine serotypes. Twenty-four and 11.6% of the strains were serotypes 19A and 6A respectively. CONCLUSION: Over the last 10 years the global antibiotic resistance in children decreased for SP (22.9%) but nasal colonization remained stable due to the increase of some serotypes, such as 19A, most often resistant to antibiotics. The vaccine effectiveness against HI is optimal since no HIb serotypes were detected; resistance to betalactam is currently due equally to enzymatic mechanism and alteration of protein binding penicillin.

Cephalosporin and fluoroquinolone combinations are highly associated with CTX-M ß-lactamase-producing Escherichia coli: a case-control study in a French teaching hospital.

The aim of this study was to investigate the risk factors associated with CTX-M-producing Escherichia coli strains isolated from infected or colonized patients. From 191 clinical samples, a case-control study was designed. From January 2005 to December 2007, 98 hospitalized patients infected or colonized with CTX-M-producing E. coli were included in the study. They were matched 1 : 1 with controls that had a non-CTX-M-producing E. coli infection on the basis of the site of sample, the unit of hospitalization and the time at risk. The rate of CTX-M-producing E. coli among those producing extended spectrum ß-lactamases was always ≥90% from 2005 to 2008. All strains were susceptible to carbapenems. However, we observed a high rate of co-resistance to ciprofloxacin (61%), sulphonamides (86%) and gentamicin (34%). Significant risk factors identified by multivariate analysis were recurrent infections (OR = 2.93), presence of artificial nutrition (OR = 3.99), and recent exposure to quinolones (OR = 4.39), third- or fourth-generation cephalosporin (OR = 3.49) and the combination of both antibiotic classes (OR = 5.50). This report highlights the dramatic increase of CTX-M-producing E. coli and the need for changes in the use of antimicrobial drugs and in infection control measures to manage this major health concern.

[105 cases of post-tonsillectomy hemorrhage revisited]. / Untersuchungen an 105 Fällen von Nachblutungen nach Tonsillektomie.

BACKGROUND: There is only little systematic evidence about blood-loss and management of cases of post-tonsillectomy hemorrhage. METHOD: 105 cases of post-tonsillectomy hemorrhage were identified and data as gender, age, time of hemorrhage, amount of blood loss, circumstances of hemorrhage and management of hemorrhage were detailed by chart review. RESULTS: The typical two points of hemorrhage are the day of surgery and the fifth to eighth postoperative day, the latter as the time of debridement of the fibrin layers. The distribution of gender and age were similar to the cases operated on. In Germany tonsillectomy-patients are kept as inpatients until the fifth to seventh day after sugery to care for pain-management, food-intake and possible hemorrhage. It must be noted that 77 patients experienced hemorrhage after dismission from the ward. Concerning the blood loss, estimated from the hemoglobin-concentration before tonsillectomy and at the time of hemorrhage, we found declines of up to 5 g/dl. Plotted against the time of hemorrhage or against the age of the patient we must state, that blood-loss does not correlate to the time after sugery nor to the age. CONCLUSIONS: We saw severe blood-loss even two weeks after surgery, whereas the events of hemorrhage around the time of debridement of fibrinlayers showed no accumulation of severe outcomes.

Efficacy criteria and cholesterol targets for LDL apheresis.

Low density lipoprotein (LDL) apheresis is now accepted as the treatment of choice for patients with homozygous familial hypercholesterolaemia and for heterozygotes with cardiovascular disease refractory to lipid-lowering drug therapy. However, a paucity of evidence has meant that detailed guidance on the extent of cholesterol reduction required to prevent the onset or progression of cardiovascular disease in these high risk patients is lacking. This review defines criteria for expressing the efficacy of apheresis, proposes target levels of total and LDL cholesterol for homozygotes and heterozygotes based on recent follow-up studies and suggests a scheme for monitoring cardiovascular disease in these patients. Establishing a uniform approach to data collection would facilitate the setting up of national or multi-national registers and might eventually provide the information needed to formulate evidence-based guidelines for LDL apheresis.

White matter brain lesions in midlife familial hypercholesterolemic patients at 3-Tesla magnetic resonance imaging.

BACKGROUND: Patients with hypercholesterolemia of 60 years and older have an increased risk for white matter brain lesions and dementia. PURPOSE: To investigate whether patients with familial hypercholesterolemia (FH) develop white matter lesions at 3-Tesla (T) MRI as early as in midlife. MATERIAL AND METHODS: Non-diabetic, nonsmoking, and non-hypertensive heterozygous FH patients on treatment with maximally tolerated dose of a statin for more than 5 years (n = 14) and matched controls (n = 22) aged 25 to 60 years of age were studied. Imaging was performed at 3T with a fluid-attenuated T2-weighted MR pulse sequence and a T1-weighted spin-echo pulse sequence following 10 ml of i.v. gadopentetate dimeglumine. Images were evaluated by two independent readers. Fasting blood samples were taken. Student's t test was employed at P<0.05. RESULTS: Three volunteers and one FH patient had white matter lesions (P<0.53). No other evidence of past ischemic stroke was observed. Mean total serum cholesterol and low-density lipoprotein (LDL) cholesterol were significantly higher in the FH group (6.0+/-1.1 vs. 5.1+/-0.9 mmol/l, P<0.02 and 4.1+/-0.9 vs. 3.1+/-0.8 mmol/l, P<0.004, respectively). CONCLUSION: Heterozygous FH patients on statin treatment in the age range of 25 to 60 years are not at increased risk of white matter lesions at 3T MRI.