Recommendations for respiratory syncytial virus surveillance at the national level.

Respiratory syncytial virus (RSV) is a common cause of acute lower respiratory tract infections and hospitalisations among young children and is globally responsible for many deaths in young children, especially in infants aged <6 months. Furthermore, RSV is a common cause of severe respiratory disease and hospitalisation among older adults. The development of new candidate vaccines and monoclonal antibodies highlights the need for reliable surveillance of RSV. In the European Union (EU), no up-to-date general recommendations on RSV surveillance are currently available. Based on outcomes of a workshop with 29 European experts in the field of RSV virology, epidemiology and public health, we provide recommendations for developing a feasible and sustainable national surveillance strategy for RSV that will enable harmonisation and data comparison at the European level. We discuss three surveillance components: active sentinel community surveillance, active sentinel hospital surveillance and passive laboratory surveillance, using the EU acute respiratory infection and World Health Organization (WHO) extended severe acute respiratory infection case definitions. Furthermore, we recommend the use of quantitative reverse transcriptase PCR-based assays as the standard detection method for RSV and virus genetic characterisation, if possible, to monitor genetic evolution. These guidelines provide a basis for good quality, feasible and affordable surveillance of RSV. Harmonisation of surveillance standards at the European and global level will contribute to the wider availability of national level RSV surveillance data for regional and global analysis, and for estimation of RSV burden and the impact of future immunisation programmes.

Illness Severity in Hospitalized Influenza Patients by Virus Type and Subtype, Spain, 2010-2017.

We conducted a retrospective cohort study to assess the effect of influenza virus type and subtype on disease severity among hospitalized influenza patients in Spain. We analyzed the cases of 8,985 laboratory-confirmed case-patients hospitalized for severe influenza by using data from a national surveillance system for the period 2010-2017. Hospitalized patients with influenza A(H1N1)pdm09 virus were significantly younger, more frequently had class III obesity, and had a higher risk for pneumonia or acute respiratory distress syndrome than patients infected with influenza A(H3N2) or B (p<0.05). Hospitalized patients with influenza A(H1N1)pdm09 also had a higher risk for intensive care unit admission, death, or both than patients with influenza A(H3N2) or B, independent of other factors. Determining the patterns of influenza-associated severity and how they might differ by virus type and subtype can help guide planning and implementation of adequate control and preventive measures during influenza epidemics.

Transmissibility of influenza during the 21st-century epidemics, Spain, influenza seasons 2001/02 to 2017/18.

BackgroundUnderstanding influenza seasonality is necessary for determining policies for influenza control.AimWe characterised transmissibility during seasonal influenza epidemics, including one influenza pandemic, in Spain during the 21th century by using the moving epidemic method (MEM) to calculate intensity levels and estimate differences across seasons and age groups.MethodsWe applied the MEM to Spanish Influenza Sentinel Surveillance System data from influenza seasons 2001/02 to 2017/18. A modified version of Goldstein's proxy was used as an epidemiological-virological parameter. We calculated the average starting week and peak, the length of the epidemic period and the length from the starting week to the peak of the epidemic, by age group and according to seasonal virus circulation.ResultsIndividuals under 15 years of age presented higher transmissibility, especially in the 2009 influenza A(H1N1) pandemic. Seasons with dominance/co-dominance of influenza A(H3N2) virus presented high intensities in older adults. The 2004/05 influenza season showed the highest influenza-intensity level for all age groups. In 12 seasons, the epidemic started between week 50 and week 3. Epidemics started earlier in individuals under 15 years of age (-1.8 weeks; 95% confidence interval (CI):-2.8 to -0.7) than in those over 64 years when influenza B virus circulated as dominant/co-dominant. The average time from start to peak was 4.3 weeks (95% CI: 3.6-5.0) and the average epidemic length was 8.7 weeks (95% CI: 7.9-9.6).ConclusionsThese findings provide evidence for intensity differences across seasons and age groups, and can be used guide public health actions to diminish influenza-related morbidity and mortality.

[Linkage to care among new human immunodeficiency virus diagnoses in Spain]. / Patrón de inicio del seguimiento clínico en los pacientes con infección por el virus de la inmunodeficiencia humana en España.

OBJETIVE: To describe linkage to care among new HIV diagnoses in Spain; and to estimate factors associated to linkage to care within three months after diagnosis. METHODS: The distribution of the time elapsing between the date of HIV diagnosis and the date of first determination of CD4 (considered to be the date of linkage to care) was calculated among new HIV diagnoses in 2010 in the seven Autonomous Regions participating, where data on date of CD4 count was available. Linkage to care was considered «correct¼ if done within three months after diagnosis. Factors associated to correct linkage to care were estimated using logistic regression. RESULTS: A total of 1769 new HIV diagnoses were included. Of them, 83.1% had evidence of linkage to care within a year, and 75.7% were linked within three months after diagnosis. Being an injectable drug user (IDU) was the only factor inversely associated with linkage to care within 3 months (OR = 0.3; 95% CI: 0.2-0.6). CONCLUSION: In Spain linkage to care after HIV diagnosis is good, but there is still room for improvement, especially among IDUs.

Computational cognitive modeling for the diagnosis of Specific Language Impairment.

Specific Language Impairment (SLI), as many other cognitive deficits, is difficult to diagnose given its heterogeneous profile and its overlap with other impairments. Existing techniques are based on different criteria using behavioral variables on different tasks. In this paper we propose a methodology for the diagnosis of SLI that uses computational cognitive modeling in order to capture the internal mechanisms of the normal and impaired brain. We show that machine learning techniques that use the information of these models perform better than those that only use behavioral variables.

Results of a Surface Roughness Comparison between Stylus Instruments and Confocal Microscopes.

This article presents the results of an LMM-R-2019 interlaboratory comparison. Such comparisons of different families of measuring instruments are one of the activities conducted among the calibration laboratories to maintain their ISO 17025 accreditation. Given that the study of surface roughness is becoming increasingly important in the field of dimensional metrology, the comparison focused on determining the Ra parameter on a pseudorandom metallic roughness standard using two types of measuring instruments: physical contact (stylus instruments) and optical (confocal microscopes). Among the aspects studied was whether the roughness measurements obtained using calibrated confocal microscopes could be compared with those using traditional methods since optical instruments obtain measurements more quickly and responsively than do stylus instruments. The results showed that roughness measurements using confocal microscopes are comparable with those from a traditional stylus instrument.

COVID-19 vaccine effectiveness against hospitalization due to SARS-CoV-2: A test-negative design study based on Severe Acute Respiratory Infection (SARI) sentinel surveillance in Spain.

BACKGROUND: With the emergence of SARS-CoV-2, influenza surveillance systems in Spain were transformed into a new syndromic sentinel surveillance system. The Acute Respiratory Infection Surveillance System (SiVIRA in Spanish) is based on a sentinel network for acute respiratory infection (ARI) surveillance in primary care and a network of sentinel hospitals for severe ARI (SARI) surveillance in hospitals. METHODS: Using a test-negative design and data from SARI admissions notified to SiVIRA between January 1 and October 3, 2021, we estimated COVID-19 vaccine effectiveness (VE) against hospitalization, by age group, vaccine type, time since vaccination, and SARS-CoV-2 variant. RESULTS: VE was 89% (95% CI: 83-93) against COVID-19 hospitalization overall in persons aged 20 years and older. VE was higher for mRNA vaccines, and lower for those aged 80 years and older, with a decrease in protection beyond 3 months of completing vaccination, and a further decrease after 5 months. We found no differences between periods with circulation of Alpha or Delta SARS-CoV-2 variants, although variant-specific VE was slightly higher against Alpha. CONCLUSIONS: The SiVIRA sentinel hospital surveillance network in Spain was able to describe clinical and epidemiological characteristics of SARI hospitalizations and provide estimates of COVID-19 VE in the population under surveillance. Our estimates add to evidence of high effectiveness of mRNA vaccines against severe COVID-19 and waning of protection with time since vaccination in those aged 80 or older. No substantial differences were observed between SARS-CoV-2 variants (Alpha vs. Delta).

Estimating the prevalence of drug injection using a multiplier method based on a register of new HIV diagnoses.

Knowledge of prevalence of illegal drug injection can aid the design and evaluation of services for problem drug users. In this study, prevalence of recent injectors in Spain was estimated with a multiplier method using the number of injectors in a population register of new HIV diagnoses, HIV incidence among injectors from cohort studies and HIV prevalence among injectors in a drug treatment register. Prevalence in 2008 was 38.8 (95% CI 23.8-53.8) per 100,000 population, a 2.8 times reduction compared with 2001. This method permits estimation of both prevalence and trends of drug injection. It is sustainable and routinely applicable in many countries.

[Delayed diagnosis of HIV infection in Spain]. / Retraso diagnóstico de la infección por el virus de la inmunodeficiencia humana en España.

OBJECTIVES: To analyse the prevalence of delayed diagnosis (DD) of human immunodeficiency virus (HIV) infection, the trends over time and its determining factors from the Newly Diagnosed HIV-infected individuals Information System (SINIVIH) data, in process of being implemented in Spain. METHODS: Cross-sectional study of newly diagnosed HIV-infected individuals between 2003 and 2007 in the 8 currently participating Spanish autonomous regions (AR). DD was defined as a CD4 count <200cells/µL at diagnosis. Adjusted odds ratios with 95% confidence interval were calculated using logistic regression (OR; 95%CI). RESULTS: Among the 5785 newly diagnosed HIV cases reported, 4798 had a CD4 cell count at diagnosis. Of these, 37.3% met the DD definition. An additional 19% had between 200 and 350cells/µL. The proportion of DD was lower for women than for men (32.9% versus 38.6%). According to exposure category, it was higher in heterosexuals (42.4%) and injecting drug users (IDUs) (40.1%) than in men who have sex with men (MSM) (26.7%). In the Spanish patient group, in multivariate logistic regression analyses, adjusting for AR and year of diagnosis, men were more likely to have a DD (OR=1.49; 95%CI:1.21-1.85). Compared to younger patients (20-29 years), LD was more frequent in older: 30-39 years (OR=2.08; 95% CI:1.63-2.67), 40-49 years (OR=3.98; 95% CI:3.07-5.16) and >49 years (OR=6.77; 95% CI:5.10-9.00); and compared to MSM, was more frequent in heterosexuals (OR=1.75; 95% CI:1.43-2.15) and IDUs (OR=1.75; 95% CI:1.38-2.22). DD decreased from 2003 to 2007 (OR=1.38; 95% CI:1.08-1.76). The same associated factors were found in immigrants, but with different magnitude: stronger association with men, heterosexuals and IDUs, and weaker association with older age. CONCLUSIONS: DD affects almost four in every ten newly diagnosed HIV-infected individuals, and is significantly more common among men, age group over 30 years, IDUs and heterosexuals. These are associated factors both in Spanish and immigrants, but in the last group the association is stronger. Strategies to increase the perception of risk among these groups are needed, as well as the implementation of the SINIVIH in the whole country to improve and to extend the information on DD.

Design of Industrial Standards for the Calibration of Optical Microscopes.

One of the most important fields of study in material science is surface characterization. This topic is currently a field of growing interest as many functional properties depend on the surface texture. In this paper the authors, after a short a review of different methods for surface topography characterization and the determination of the traceability problems that arise in this type of measurements, propose four different designs of material standards that can be used to calibrate the most common optical measuring instruments used for these tasks, such as measuring microscopes, metallurgical microscopes, confocal microscopes, focus variation microscopes, etc. The authors consider that the use of this type of standards (or others similar to them) could provide a step forward in assuring metrological traceability for different metrological characteristics that enables a more precise measurement of surface features with optical measuring instruments. In addition, authors expect that this work could lay the groundwork for the development of custom standards with specialized features tuned to gain a better metrological control when measuring specific geometrical surface properties.

Industrial Calibration Procedure for Confocal Microscopes.

Coordinate metrology techniques are widely used in industry to carry out dimensional measurements. For applications involving measurements in the submillimeter range, the use of optical, non-contact instruments with suitable traceability is usually advisable. One of the most used instruments to perform measurements of this type is the confocal microscope. In this paper, the authors present a complete calibration procedure for confocal microscopes designed to be implemented preferably in workshops or industrial environments rather than in research and development departments. Therefore, it has been designed to be as simple as possible. The procedure was designed without forgetting any of the key aspects that need to be taken into account and is based on classical reference material standards. These standards can be easily found in industrial dimensional laboratories and easily calibrated in accredited calibration laboratories. The procedure described in this paper can be easily adapted to calibrate other optical instruments (e.g., focus variation microscopes) that perform 3D dimensional measurements in the submillimeter range.

Ghrelin agonist (TZP-101): safety, pharmacokinetics and pharmacodynamic evaluation in healthy volunteers: a phase I, first-in-human study.

The authors evaluate the human safety, tolerability, pharmacokinetics, and pharmacodynamics of TZP-101, an agonist of the hGHS-R1a (ghrelin) receptor. Healthy subjects were randomized to either single-dose TZP-101 (20-600 microg/kg) or placebo by 30-minute intravenous infusion. Subjects underwent continuous cardiac monitoring, 12-lead electrocardiograms, and assessment for orthostatic hypotension, injection site tolerability, vital signs, and adverse events during the 24-hour postdose period. Blood and urine samples were collected for pharmacokinetic/pharmacodynamic assessment for 24 hours. Forty-eight subjects randomly received 1 of 6 TZP-101 doses or placebo. TZP-101 was well tolerated, with single episodes each of headache, lower abdominal pain, diarrhea, and dizziness. At the highest dose, 2 subjects experienced bradycardia. All events were self-limited. Mean arterial blood pressure and heart rate decreased from baseline approximately 45 to 60 minutes after infusion start at higher doses. No other significant changes were observed. Pharmacokinetic analysis revealed less than dose-proportional behavior of drug with low clearance (approximately 7 mL/h/kg), small volume of distribution (approximately 114 mL/kg), and half-life values of approximately 13 hours, which were independent of dose. Pharmacodynamic analyses suggested TZP-101, at doses as low as 40 microg/kg, expressed activity at the receptor. TZP-101 displayed a promising pharmacokinetic, pharmacodynamic, and safety profile for use in gastrointestinal motility disorders.

Estimating the burden of seasonal influenza in Spain from surveillance of mild and severe influenza disease, 2010-2016.

BACKGROUND: Estimating the national burden of influenza disease is challenging. We aimed to estimate the disease burden of seasonal influenza in Spain, at the primary care and hospital level, over the 6 influenza seasons after 2009 pandemic. METHODS: We used data from the Spanish Influenza Sentinel Surveillance System to estimate weekly influenza rates and the number of influenza-like illness (ILI) and mild confirmed influenza cases (MCIC). From the surveillance of severe hospitalized confirmed influenza cases (SHCIC), we obtained hospitalization rates and total number of SHCIC, intensive care unit (ICU) admissions and deaths in influenza hospitalized patients. We estimated both mild and severe influenza cases, overall, and by age-group (<5, 5-14, 15-64, and ≥65 years). RESULTS: The highest cumulative rates of MCIC were observed in <15 years (1395-3155 cases/100 000 population in 5-14 years) and the lowest in ≥65 years (141-608 cases/100 000 population). SHCIC rates revealed a characteristic U-shaped distribution, with annual average hospitalization rates of 16.5 and 18.9 SHCIC/100, 000 p in 0-4 years, and ≥65 years, respectively. We estimated an annual average of 866 868 cases of ILI attended in primary care (55% were MCIC), 3616 SHCIC, 1232 ICU admissions, and 437 deaths in SHCIC. The percentage of ICU admission among SHCIC was highest at 15-64 years (42%), while the hospitalization fatality rate ranged from 1% in 0-4 years to 18% in ≥65 years. CONCLUSIONS: The ongoing Spanish Influenza Surveillance System allowed obtaining crucial information regarding the impact of mild and severe influenza in Spain.

Exploring the risk of severe outcomes and the role of seasonal influenza vaccination in pregnant women hospitalized with confirmed influenza, Spain, 2010/11-2015/16.

Based on previous observations during pandemics and seasonal epidemics, pregnant women are considered at risk of developing severe influenza outcomes after influenza infection. With the aim of preventing severe influenza illness, the World Health Organization (WHO) includes pregnant women as a target group for seasonal influenza vaccination. However, influenza vaccine uptake during pregnancy remains low in many countries, including Spain. The objectives of this study were to increase the evidence of pregnancy as a risk factor for severe influenza illness and to study the potential role of seasonal influenza vaccination in the prevention of severe outcomes in infected pregnant women. Using information from the surveillance of Severe Hospitalized Confirmed Influenza Cases (SHCIC) in Spain, from seasons 2010/11 to 2015/16, we estimated that pregnant women in our study had a relative risk of hospitalization with severe influenza nearly 7.8 times higher than non-pregnant women of reproductive age. Only 5 out of 167 pregnant women with known vaccination status in our study had been vaccinated (3.6%). Such extremely low vaccination coverage only allowed obtaining crude estimates suggesting a protective effect of the vaccine against influenza complications (ICU admission or death). Our overall results support that pregnant women could benefit from seasonal influenza vaccination, in line with national and international recommendations.

Duration of Treatment with Corticosteroids and Recovery of Kidney Function in Acute Interstitial Nephritis.

BACKGROUND AND OBJECTIVES: Drug-induced acute interstitial nephritis represents an emerging cause of acute kidney disease, especially among polymedicated elderly patients. Although corticosteroids are frequently used, controversy exists about the timing of initiation, efficacy, safety, and duration of treatment. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed a retrospective study of 182 patients with biopsy-proven drug-induced acute interstitial nephritis from 13 Spanish centers. Exposure was defined as the length of corticosteroid treatment. The main outcome was the level of serum creatinine at month 6, with respect to baseline values. RESULTS: The most common offending agents were nonsteroidal anti-inflammatory drugs (27%). In 30% of patients, the offending drug could not be identified. The median time to suspected drug withdrawal was 11 days (interquartile range, 5-22). All patients presented with acute kidney disease and were treated with corticosteroids. The mean initial dose of prednisone was 0.8±0.2 mg/kg per day. High-dose corticosteroid treatment was maintained for 2 weeks (interquartile range, 1-4). After 6 months, the mean recovered GFR was 34±26 ml/min per 1.73 m2 and ten patients required maintenance dialysis. Use of high-dose corticosteroids for 3 weeks or treatment duration >8 weeks were not associated with better recovery of kidney function. In the multivariable analysis, delayed onset of steroid treatment (odds ratio, 1.02; 95% confidence interval, 1.0 to 1.04) and the presence of interstitial fibrosis of >50% on the kidney biopsy specimen (odds ratio, 8.7; 95% confidence interval, 2.7 to 27.4) were both associated with serum creatinine level at month 6 of >75%, with respect to baseline values. CONCLUSIONS: High-dose corticosteroid treatment for 3 weeks or prolonged treatment for >8 weeks were not associated with greater kidney function recovery in drug-induced acute interstitial nephritis. A delay in the initiation of corticosteroids resulted in worse recovery of kidney function.

Hot water dipping of olives (Olea europaea) for virgin oil debittering.

Olives (Olea europaea L.) of the Manzanilla, Picual, and Verdial varieties harvested at the green mature stage of ripening were dipped in hot water at a range of temperatures between 60 and 72 degrees C for 3 min. Immediately after treatment, oils were physically extracted from the olives. Olive heating promotes a reduction of oil bitterness in direct relationship to the temperature used. Fruit heating at > or =60 degrees C for 3 min did not cause significant changes in acidity, UV absorption, peroxide index, and panel test score of the oils obtained but decreased its oxidative stability. Oils extracted from heated fruit showed higher concentrations of chlorophylls and carotenes and lower total phenol content.

A methodology for the characterization and diagnosis of cognitive impairments-Application to specific language impairment.

OBJECTIVES: The diagnosis of mental disorders is in most cases very difficult because of the high heterogeneity and overlap between associated cognitive impairments. Furthermore, early and individualized diagnosis is crucial. In this paper, we propose a methodology to support the individualized characterization and diagnosis of cognitive impairments. The methodology can also be used as a test platform for existing theories on the causes of the impairments. We use computational cognitive modeling to gather information on the cognitive mechanisms underlying normal and impaired behavior. We then use this information to feed machine-learning algorithms to individually characterize the impairment and to differentiate between normal and impaired behavior. We apply the methodology to the particular case of specific language impairment (SLI) in Spanish-speaking children. METHODS AND MATERIALS: The proposed methodology begins by defining a task in which normal and individuals with impairment present behavioral differences. Next we build a computational cognitive model of that task and individualize it: we build a cognitive model for each participant and optimize its parameter values to fit the behavior of each participant. Finally, we use the optimized parameter values to feed different machine learning algorithms. The methodology was applied to an existing database of 48 Spanish-speaking children (24 normal and 24 SLI children) using clustering techniques for the characterization, and different classifier techniques for the diagnosis. RESULTS: The characterization results show three well-differentiated groups that can be associated with the three main theories on SLI. Using a leave-one-subject-out testing methodology, all the classifiers except the DT produced sensitivity, specificity and area under curve values above 90%, reaching 100% in some cases. CONCLUSIONS: The results show that our methodology is able to find relevant information on the underlying cognitive mechanisms and to use it appropriately to provide better diagnosis than existing techniques. It is also worth noting that the individualized characterization obtained using our methodology could be extremely helpful in designing individualized therapies. Moreover, the proposed methodology could be easily extended to other languages and even to other cognitive impairments not necessarily related to language.

Predictors of advanced disease and late presentation in new HIV diagnoses reported to the surveillance system in Spain.

OBJECTIVE: To present surveillance data on advanced disease (AD) and late presentation (LP) of HIV in Spain and their determinants. METHODS: We included all new HIV diagnoses notified by the autonomous regions that consistently reported such cases throughout the period 2007-2011. Coverage was 54% of the total Spanish population. Data sources consisted of clinicians, laboratories and medical records. AD was defined as the presence of a CD4 cell count <200cells/µL in the first test after HIV diagnosis, while LP was defined as the presence of a CD4 cell count <350cells/µL after HIV diagnosis. Odds ratios and their 95% confidence intervals (OR, 95% CI) were used as the measure of association. Logistic regressions were fit to identify predictors of AD and LP. RESULTS: A total of 13,021 new HIV diagnoses were included. Among these, data on the outcome variable were available in 87.7%. The median CD4 count at presentation was 363 (interquartile range, 161-565). Overall, 3356 (29.4%) patients met the definition of AD and 5494 (48.1%) were classified as LP. Both AD and LP increased with age and were associated with male sex and infection through drug use or heterosexual contact. All immigrants except western Europeans were more prone to AD and LP. Multivariate models disaggregated by sex showed that the effect of age and region of origin was weaker in women than in men. CONCLUSIONS: Despite universal health care coverage in Spain, men, immigrants and people infected through drug use or heterosexual contact seem to be experiencing difficulties in gaining timely access to HIV care.