Double versus single stimulation in young low prognosis patients followed by a fresh embryo transfer: a randomized controlled trial (DUOSTIM-fresh).

STUDY QUESTION: Does double stimulation, followed by a fresh embryo transfer (DUOSTIM fresh) give a higher number of good-quality blastocysts as compared with a single stimulation in young low prognosis patients? SUMMARY ANSWER: Compared to single stimulation, DUOSTIM fresh leads to a significantly higher number of good quality blastocysts, without hindering fresh embryo transfer outcomes. WHAT IS KNOWN ALREADY: DUOSTIM (ovarian stimulation both in the follicular and luteal phase of the same cycle) is an innovative strategy to retrieve a higher number of oocytes in a shorter time frame, thus it is particularly appealing for poor ovarian responders. Three current limitations of dual stimulation are: (i) it is unclear whether outcomes of the second (luteal) wave result from the second stimulation, or a carry-over effect from previous follicular stimulation; (ii) the desynchronization between endometrium and ovaries and, (iii) lack of robust evidence. No previous studies explored DUOSTIM starting from the luteal phase, and with a fresh embryo transfer (DUOSTIM fresh). STUDY DESIGN, SIZE, DURATION: This study is a randomized, controlled, single-center, superiority clinical trial comparing two different ovarian stimulation protocols: a double stimulation cycle versus a single stimulation cycle followed by fresh embryo transfer. The primary outcome was the number of good quality blastocysts obtained, while secondary outcomes included results from fresh embryo transfer (clinical pregnancy, miscarriage). A total of 120 women were enrolled in this study between October 2020 and October 2022, with a 1:1 allocation. PARTICIPANTS/MATERIALS, SETTING, METHODS: Only young (<40 years old) low prognosis (anti-Müllerian hormone <1.2 ng/ml) patients were recruited in the Reproductive Medicine Department of Dexeus University Hospital. In the investigational group, DUOSTIM fresh, the first stimulation was initiated in the luteal phase (Day 18-21 cycle) followed by a second stimulation 5 days post first oocyte retrieval, initiated in the follicular phase and a fresh embryo transfer of the best blastocyst generated (first or second cycle). The control group performed a follicular phase single stimulation cycle with a fresh embryo transfer. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, 107 patients were analyzed, 53 in the investigational (DUOSTIM fresh) and 54 in the control arm (single stimulation). DUOSTIM fresh resulted in a significantly higher number of good quality blastocysts as compared to single stimulation (difference of mean 0.81, 95% CI 0.12-1.49). The mean percentage of cycles with embryo transfer was comparable (62.3% and 51.9%, respectively for double versus single stimulation). No significant differences were found for clinical outcomes following fresh embryo transfer with an ongoing pregnancy rate of 24.5% for DUOSTIM fresh versus 22.2%, for conventional IVF. Of interest comparisons between different stimulation cycles (A: luteal-phase DUOSTIM fresh, B: follicular-phase DUOSTIM fresh, and C: single stimulation) did not demonstrate any significant difference in terms of ovarian response with the mean (SD) number of mature oocytes being (A: 3.3 (2.9), B: 3.4 (3.4), and C: 3.5 (2.9), respectively). LIMITATIONS, REASONS FOR CAUTION: Study sample size was calculated to detect differences on the mean number of good quality blastocysts. Therefore, results for secondary outcomes (embryo transfer rates and clinical pregnancy rates) should be interpreted with caution as exploratory findings that deserve future investigations. WIDER IMPLICATIONS OF THE FINDINGS: Although DUOSTIM fresh results in a higher number of blastocysts as compared with a single stimulation in young low prognosis patients, the decision of performing dual stim should be evaluated with caution, considering that whether this may improve embryo transfers rate and pregnancy outcomes is still unclear. Results on cumulative-live-birth-rate are warranted. STUDY FUNDING/COMPETING INTEREST(S): The study was an investigator-initiated study supported by an unrestricted grant by Organon. N.P.P. has received grants from Merck Serono, Organon, Ferring Pharmaceutical, Theramex, and Besins Healthcare. N.P.P. has received consulting fees from Merck Serono, Organon, Besins Healthcare, and IBSA. N.P.P. has received honoraria for lectures from Merck Serono, Organon, Theramex, Roche Diagnostics, IBSA, Besins Healthcare, and Ferring. A.R. has received Research grants, honoraria for lectures from Merck Serono, MSD/Organon, Ferring Pharmaceuticals, Besins International, IBSA, Guerbet. The other authors declare that there is no conflict of interest to disclose with respect to the content of this article. TRIAL REGISTRATIO NUMBER: NCT04446845. TRIAL REGISTRATION DATE: 25 June 2020. DATE OF FIRST PATIENT'S ENROLMENT: 30 October 2020.

Validation of ADNEX and IOTA two-step strategy and estimation of risk of complications during follow-up of adnexal masses in low-risk population.

OBJECTIVES: The aim is to evaluate the ability of the Assessment of Different NEoplasias in the adneXa model (ADNEX) and the International Ovarian Tumour Analysis (IOTA) two-step strategy to predict malignancy in adnexal masses detected in an outpatient low-risk setting, and to estimate the risk of complications in masses with benign ultrasound morphology managed with clinical and ultrasound follow-up. METHODS: This single center (Hospital Universitari Dexeus Barcelona) study was performed using interim data of the ongoing prospective observational IOTA phase 5 study. The primary aim of the IOTA 5 study is to describe the cumulative incidence of complications during follow-up of adnexal masses classified as benign on ultrasound. Consecutive patients with adnexal masses detected between June 2012 and September 2016 in a private center offering screening for gynecological cancers were included and followed-up until February 2020. Tumors were classified as benign or malignant based on histology (if patients underwent surgery) or outcome of clinical and ultrasound follow-up at 12 (±2) months. Multiple imputation was used when follow-up information was uncertain. The ability of the ADNEX model without CA125 and of the IOTA two-step strategy to distinguish benign from malignant masses was evaluated retrospectively using the prospectively collected data. We describe performance as discrimination (area under the receiver operating characteristic curve, AUC), calibration, classification (sensitivity and specificity) and clinical utility (Net Benefit). In the group of patients with a benign looking mass selected for conservative management we evaluated the occurrence of spontaneous resolution or any mass complication during the first 5 years of follow-up by assessing the cumulative incidence for malignancy, torsion, cyst rupture, or minor mass complications (inflammation, infection, or adhesions) and the time to occurrence of an event. RESULTS: A total of 2654 patients were recruited to the study. After application of exclusion criteria, 2039 patients with a newly detected mass were included for the model validation. 1684 (82.6%) masses were benign, 49 (2.4%) masses were malignant and for 306 (15.0%) masses the outcome was uncertain and imputed. The AUC was 0.95 (95% CI 0.89-0.98) for ADNEX and 0.94 (95% CI 0.88-0.97) for the two-step strategy. Calibration performance could not be meaningfully interpreted due to few malignancies resulting in very wide confidence intervals. The two-step strategy had better clinical utility than ADNEX at malignancy risk thresholds < 3%. 1472 (72%) patients had a mass judged to be benign based on pattern recognition by an experienced ultrasound examiner and were managed with clinical and ultrasound follow-up. In this group, the 5-year cumulative incidence was 66% for spontaneous resolution of the mass (95% CI 63-69), 0% for torsion (95%CI 0-0.002), 0.1% for cyst rupture (<0.1-0.6), 0.2% for a borderline tumor (<0.1-0.6), and 0.2% (0.1-0.6) for invasive malignancy. CONCLUSIONS: The ADNEX model and IOTA two-step strategy performed well to distinguish benign from malignant adnexal masses detected in a low-risk population. Conservative management is safe for masses with benign ultrasound appearance in such a population. This article is protected by copyright. All rights reserved.

External validation of Fetal Medicine Foundation competing-risks model for midgestation prediction of small-for-gestational-age neonates in Spanish population.

OBJECTIVE: To examine the external validity of the new Fetal Medicine Foundation (FMF) competing-risks model for prediction in midgestation of small-for-gestational-age (SGA) neonates. METHODS: This was a single-center prospective cohort study of 25 484 women with a singleton pregnancy undergoing routine ultrasound examination at 19 + 0 to 23 + 6 weeks' gestation. The FMF competing-risks model for the prediction of SGA combining maternal factors and midgestation estimated fetal weight by ultrasound scan (EFW) and uterine artery pulsatility index (UtA-PI) was used to calculate risks for different cut-offs of birth-weight percentile and gestational age at delivery. The predictive performance was evaluated in terms of discrimination and calibration. RESULTS: The validation cohort was significantly different in composition compared with the FMF cohort in which the model was developed. In the validation cohort, at a 10% false-positive rate (FPR), maternal factors, EFW and UtA-PI yielded detection rates of 69.6%, 38.7% and 31.7% for SGA < 10th percentile with delivery at < 32, < 37 and ≥ 37 weeks' gestation, respectively. The respective values for SGA < 3rd percentile were 75.7%, 48.2% and 38.1%. Detection rates in the validation cohort were similar to those reported in the FMF study for SGA with delivery at < 32 weeks but lower for SGA with delivery at < 37 and ≥ 37 weeks. Predictive performance in the validation cohort was similar to that reported in a subgroup of the FMF cohort consisting of nulliparous and Caucasian women. Detection rates in the validation cohort at a 15% FPR were 77.4%, 50.0% and 41.5% for SGA < 10th percentile with delivery at < 32, < 37 and ≥ 37 weeks, respectively, which were similar to the respective values reported in the FMF study at a 10% FPR. The model had satisfactory calibration. CONCLUSION: The new competing-risks model for midgestation prediction of SGA developed by the FMF performs well in a large independent Spanish population. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Primary Cutaneous Lymphoma Registry of the Spanish Academy of Dermatology and Venereology (AEDV): Data for the First 5 Years. / Registro de linfomas cutáneos primarios (RELCP) de la AEDV: datos tras 5 años de funcionamiento.

BACKGROUND AND OBJECTIVE: Primary cutaneous lymphomas (PCL) are uncommon. Observations based on the first year of data from the Spanish Registry of Primary Cutaneous Lymphomas (RELCP, in its Spanish abbreviation) of the Spanish Academy of Dermatology and Venereology (AEDV) were published in February 2018. This report covers RELCP data for the first 5 years. PATIENTS AND METHODS: RELCP data were collected prospectively and included diagnosis, treatments, tests, and the current status of patients. We compiled descriptive statistics of the data registered during the first 5 years. RESULTS: Information on 2020 patients treated at 33 Spanish hospitals had been included in the RELCP by December 2021. Fifty-nine percent of the patients were men; the mean age was 62.2 years. The lymphomas were grouped into 4 large diagnostic categories: mycosis fungoides/Sézary syndrome, 1112 patients (55%); primary B-cell cutaneous lymphoma, 547 patients (27.1%); primary CD30+lymphoproliferative disorders, 222 patients (11%), and other T-cell lymphomas, 116 patients (5.8%). Nearly 75% of the tumors were registered in stage I. After treatment, 43.5% achieved complete remission and 27% were stable at the time of writing. Treatments prescribed were topical corticosteroids (1369 [67.8%]), phototherapy (890 patients [44.1%]), surgery (412 patients [20.4%]), and radiotherapy (384 patients [19%]). CONCLUSION: The characteristics of cutaneous lymphomas in Spain are similar to those reported for other series. The large size of the RELCP registry at 5 years has allowed us to give more precise descriptive statistics than in the first year. This registry facilitates the clinical research of the AEDV's lymphoma interest group, which has already published articles based on the RELCP data.

Solid-phase extraction and fractionation of multiclass pollutants from wastewater followed by liquid chromatography tandem-mass spectrometry analysis.

Herein, we describe a modular solid-phase extraction (SPE) setup, combining three sorbents, for the effective extraction of neutrals, acidic, and basic micropollutants from wastewater, followed by their further elution in three independent extracts. The performance of this approach was demonstrated for a suite of 64 compounds, corresponding to different chemical families, using liquid chromatography tandem-mass spectrometry (LC-MS/MS). Target compounds were effectively extracted from wastewater samples; moreover, 62 out of 64 species were isolated in just one of the three fractions (neutrals, acids, and bases) obtained from the combination of sorbents. Globally, the efficiency and the selectivity of the SPE methodology improved the features obtained using generic SPE polymers, displaying just reversed-phase interactions. The overall recoveries of the analytical method, calculated against solvent-based calibration standards, stayed between 80 and 120% for 57 and 60 compounds, in raw and treated wastewater, respectively. Procedural limits of quantification (LOQs) varied from 1 to 20 ng L-1. Analysis of urban wastewater samples identified a group of 19 pollutants showing either negligible median removal efficiencies (± 20%) during wastewater treatment, or even a noticeable enhancement (case of the biodegradation product of the drug valsartan), which might be useful as markers of wastewater discharges in the aquatic environment.

Approaches to liquid chromatography tandem mass spectrometry assessment of glyphosate residues in wine.

The performance of two different analytical methodologies to investigate the presence of glyphosate (GLY) and aminomethylphosphonic acid (AMPA) residues in wine samples was evaluated. Transformation of compounds in their fluorene-9-methyloxycarbonyl derivatives permitted their separation under reversed-phase liquid chromatography with tandem mass spectrometry (LC-MS/MS) determination. Although the wine matrix severely impaired the efficiency of GLY derivatization, this drawback was solved using a molecularly imprinted sorbent for the previous, selective extraction of GLY and AMPA from wine. Alternatively, the use of a strong anionic exchange, polyvinyl alcohol-based LC column, turned to be the most effective alternative for direct determination of both compounds in diluted wine samples. The chromatographic behavior of this column and the magnitude of matrix effects observed during analysis of diluted wine samples were significantly affected by the composition of the mobile phase. Under final working conditions, this column permitted the separation of AMPA and the fungicide fosetyl (which shows common transitions in tandem MS/MS methods), it improved significantly the sample throughput versus extraction-derivatization-purification method, and it allowed the use of solvent-based calibration standards. Both analytical procedures provided similar limits of quantification (LOQs) for GLY (0.5-1.0 ng mL-1), while the multistep method was 8 times more sensitive to AMPA than the direct procedure. GLY residues stayed above method LOQs in 70% of the processed wines; however, concentrations measured in 95% of positive samples remained 100 times below the maximum residue limit (MRL) set for GLY in vinification grapes.

Evaluation of the relationship between homocysteine levels and bone mineral density in postmenopausal women.

OBJECTIVE: The current study aimed to evaluate the relationship between homocysteine (Hcy) levels and bone mineral density (BMD) in postmenopausal women. METHODS: The present, cross-sectional study included 760 postmenopausal women. The following variables were recorded: age, age at menopause, body mass index (BMI), BMD (measured by dual-energy X-ray absorptiometry [DXA] scanning and expressed as lumbar, femoral neck and total hip T-scores), smoking status, biochemical parameters (Hcy, creatinine, calcium, phosphorus, vitamin D and parathormone levels) and vitamin D supplementation. RESULTS: The mean age of the sample population was 56.4 ± 5.77 years and the mean age at menopause was 49.9 ± 3.62 years. The mean BMI was 25.2 ± 4.49 kg/m2. In the current study, a comparison of the subjects with osteoporosis, osteopenia and normal BMD revealed that the subjects in the low BMD group were significantly older (p < 0.001), had a lower age at menopause (p < 0.001) and had lower BMI (p < 0.001). There was no statistically significant difference among the groups with regard to the plasma levels of Hcy (p = 0.946). The levels of Hcy were positively correlated to the creatinine levels (r = 0.21). The present study did not observe any significant correlations between the Hcy levels and other parameters. CONCLUSIONS: In the present study, 15.3% of the subjects had hyperhomocysteinemia and 62.11% had low BMD. The current results obtained from a group of postmenopausal women suggest that the plasma levels of Hcy are not related to BMD in the lumbar spine (L1-L4), femoral neck and total hip. In the current study, age, age at menopause and low BMI were observed to be associated with low BMD.

Plasma homocysteine levels and handgrip strength in postmenopausal women.

OBJECTIVE: This study evaluated handgrip strength (HGS), circulating homocysteine levels and related factors in postmenopausal women. METHODS: This study is a sub-analysis of a prospective cohort of 303 postmenopausal women aged 62.7 ± 6.9 years who had HGS measures with a digital dynamometer as the primary outcome, and plasma homocysteine and creatinine levels and glomerular filtration rate (GFR) measures as the secondary outcomes. RESULTS: The average HGS was 22.5 ± 4.0 kg, 29.4% of women had dynapenia (HGS < 20 kg), adiposity was 40.3 ± 5.4% and 9.57% of women had hyperhomocysteinemia (homocysteine >15 µmol/l). There were no differences between tertiles of homocysteine and HGS (p = 0.641). Plasma homocysteine levels were unrelated to HGS (r = -0.06) and correlated with age (r = 0.17), GFR (r = -0.28) and creatinine (r = 0.23). Hyperhomocysteinemia was not associated with HGS (odds ratio [OR] = 0.98 [95% confidence interval (CI): 0.89; 1.08]) or dynapenia (OR = 1.10 [95% CI: 0.45; 2.47]). The risk of presenting low HGS were not significantly associated with homocysteine (OR = -0.08 [95% CI: -0.21; 0.06]) and were associated with age (OR = -0.23 [95% CI: -0.29; -0.17]), adiposity (OR = -6.52 [95% CI: -9.53; -3.50]) and creatinine (OR = 6.22 [95% CI: 2.48; 9.97]). CONCLUSIONS: HGS and dynapenia were unrelated to hyperhomocysteinemia. Age, GFR and creatinine were significantly associated with plasma homocysteine levels.

HepCCATT: a multilevel intervention for hepatitis C among vulnerable populations in Chicago.

BACKGROUND: Hepatitis C infection could be eliminated. Underdiagnosis and lack of treatment are the barriers to cure, especially for vulnerable populations (i.e. unable to pay for health care). METHODS: A multilevel intervention from September 2014 to September 2019 focused on the providers and organizations in 'the safety net' (providing health care to populations unable to pay), including: (i) public education, (ii) training for primary care providers (PCPs) and case managers, (iii) case management for high-risk populations, (iv) policy advice and (v) a registry (Registry) for 13 health centers contributing data. The project tracked the number of PCPs trained and, among Registry sites, the number of people screened, engaged in care (i.e. clinical follow-up after diagnosis), treated and/or cured. RESULTS: In Chicago, 215 prescribing PCPs and 56 other health professionals, 86% of whom work in the safety net, were trained to manage hepatitis C. Among Registry sites, there was a 137% increase in antibody screening and a 32% increase in current hepatitis C diagnoses. Engagement in care rose by 18%. CONCLUSIONS: Hepatitis C Community Alliance to Test and Treat (HepCCATT) successfully targeted safety net providers and organizations with a comprehensive care approach. While there were challenges, HepCCATT observed increased hepatitis C screening, diagnosis and engagement in care in the Chicago community.

[Mechanical thrombectomy in a Chilean public hospital. Experience in 149 patients]. / Manejo avanzado del infarto cerebral en un hospital público chileno: trombectomía mecánica en el Hospital Barros Luco Trudeau.

BACKGROUND: Mechanical thrombectomy is the accepted treatment for acute ischemic stroke in Large Vessel Occlusion. The Barros Luco Trudeau hospital developed endovenous thrombolysis in 2010, and since 2012, implemented endovascular management, becoming the neurovascular center in the southern area of the metropolitan region. AIM: To describe endovascular management of acute ischemic stroke in a Chilean public hospital. MATERIAL AND METHODS: Analysis of patients with acute ischemic stroke that were treated with mechanical throm-bectomy from 2012 to 2019 in the Barros Luco Hospital. RESULTS: In the study period, a mechanical thrombectomy was carried out in 149 patients aged 61 ± 15 years (46% females). The average National institute of Health Stroke Scale (NIHSS) at presentation was 19 ± 4-5. Anterior or posterior circulation involvement was present in 89.9 and 10.1 % of patients. Twenty-five percent of patients were referred from other public centers. The mean lapse between onset of symptoms and thrombectomy was 266 ± 178 in. Ninety days after the procedure, 58% of patients had minimal or absent disability (Modified Ranson score of 0-2), and 19,2% died. CONCLUSIONS: Mechanical thrombectomy, according to this experience, has favorable clinical outcomes in patients with high NIHSS scores at entry.

Assessment of direct analysis in real time accurate mass spectrometry for the determination of triclosan in complex matrices.

In this work, the applicability of direct analysis in real time coupled to accurate mass spectrometry (DART-MS) to the quantitative determination of triclosan (TCS) in samples with increasing complexity, from personal care products to extracts from sewage, is investigated. In the first term, DART-MS spectra of TCS as free phenol and as derivatized species are characterized; thereafter, the effects of several instrumental variables in the detectability of TCS (i.e., temperature, solvent, and compound holder) are discussed. Under final selected conditions, TCS was determined from its [M-H]- ions, without need of derivatization, attaining an instrumental limit of quantification of 5 ng mL-1, with a linear response range up to 1000 ng mL-1. Complex matrices, such as solid-phase extracts obtained from environmental water samples, moderately inhibited the ionization efficiency of TCS, with signal attenuation percentages in the range of 6 to 57%, depending on the sample type and on the concentration factor provided by the SPE procedure. The accuracy of results obtained by DART-MS was evaluated using liquid chromatography (LC) with MS detection; in both cases, a time-of-flight (TOF) MS instrument was employed for the selective determination of the [M-H]- ions of TCS (m/z values 286.9439 and 288.9410) using a mass window of 20 ppm. DART-MS did not only provide enough sensitivity to detect the presence of TCS in environmental samples (raw and treated wastewater as well as freeze-dried sludge), but also measured concentrations matched those determined by LC-ESI-TOF-MS, with only slightly higher standard deviations. During analysis of personal care products, containing much higher concentrations of TCS in a less complex matrix, both techniques were equivalent in terms of accuracy and precision. Graphical abstract.

Dry eye disease symptoms and quality of life in perimenopausal and postmenopausal women.

OBJECTIVE: This study aimed to evaluate dry eye disease (DED) symptoms and quality of life (QoL) in a group of perimenopausal and postmenopausal women, based on the Ocular Surface Disease Index (OSDI) questionnaire. METHODS: An observational study was performed in a group of 1947 perimenopausal and postmenopausal women, aged between 45 and 79 years. The personal data collected were age, menopause status, age at menopause, and OSDI score. RESULTS: The mean age of the group was 54.18 ± 6.84 years, with a mean age at menopause of 49.45 ± 4.02 years. The average OSDI score was 29.20 ± 19.4. The overall prevalence of DED symptoms was 79%, increasing significantly in postmenopausal women, 76.4% vs. 80.5% (p = 0.029). In our group, 37.7% had severe DED symptoms. Ocular symptoms, vision-related functions, and environmental trigger scores were higher in postmenopausal women, leading to a lower QoL. The severity of OSDI score increases with age (ß coefficient: 0.15 [95% confidence interval: 0.02; -0.28]), while the severity of OSDI score decreases with a later onset age of menopause (ß coefficient: -0.27 [95% confidence interval: -0.55; -0.01]). CONCLUSIONS: DED symptoms are highly prevalent in perimenopausal and postmenopausal women. Postmenopausal women had a higher prevalence of symptoms and higher OSDI scores than perimenopausal women. The severity of DED symptoms and vision-related functions leads to poorer QoL.

Nanotechnology against human cytomegalovirus in vitro: polyanionic carbosilane dendrimers as antiviral agents.

BACKGROUND: Human cytomegalovirus (HCMV) is a worldwide infection, causing different troublesome in immunosupressed patients and very related to Human Immunodeficiency Virus 1 (HIV-1) infection, mainly in developing countries, with a co-infection rate of 80% in Africa. The high cost of present treatments and the lack of routinely tests in these countries urge the necessity to develop new molecules or strategies against HCMV. The new treatments should be low-cost and capable of avoiding the emerging problem of resistant virus. Nanoparticles play an important role in several viral infections. Our main focus is to study the potential activity of polyanionic carbosilane dendrimers (PDC), which are hyperbranched molecules with several sulfonate or sulfate groups in their periphery, against different viruses. RESULTS: We studied the activity of G1-S4, G2-S16 and G2-S24P PDCs in MRC-5 cell line against HCMV infection by several plaque reduction assays. Our results show that dendrimers present good biocompatibility at the concentrations tested (1-50 µM) for 6 days in cell culture. Interestingly, both G2-S16 and G2-S24P showed a remarked inhibition at 10 µM against HCMV infection. Results on attachment and virucidal assays indicated that the inhibition was not directed to the virus or the virus-cell attachment. However, results of time of addition, showed a longer lasting activity of these dendrimers in comparison to ganciclovir, and the combination of G2-S16 or G2-S24P with ganciclovir increases the HCMV inhibition around 90 %. CONCLUSIONS: Nanotechnology, in particular polyanionic carbosilane dendrimers, have proved their potential application against HCMV, being capable of inhibiting the infection by themselves or enhancing the activity of ganciclovir, the actual treatment. These compounds represent a low-cost approach to fight HCMV infections.

Factors associated with workability in Spanish health centre workers.

BACKGROUND: The concept of workability provides a conceptual framework and proposes measures for the evaluation of relevant actions focused on a healthy workforce. In Spain, one of the countries with the highest life expectancy, there are practically no scientific studies on workability and its associated factors. AIMS: The objective of this study is to examine the associations between workability and variables related to health and work in a sample of workers from Spanish health centres. METHODS: Cross-sectional study including 1184 health centre workers who completed a questionnaire at baseline, comprising measures of workability, health and other work-related factors. Workability has been analysed as a one-factor construct, and as a two-factor construct. Multinomial logistic regression models were used to analyse factors associated with workability. RESULTS: As a one-dimensional construct, workability is associated with physical and mental health, number of hours of worked, insomnia, work and family life balance, adequate training, never having had an accident and type of contract. When the two-factor measure was used, sensitivity of findings increased, and it was identified that those participants who were older, lived alone and have more years of service in their profession also show worse workability. CONCLUSIONS: The present study identified factors associated with the workability of health centre workers. The two-factor workability index (WAI) has better psychometric properties and used in combination with the global measure of WAI, identifies important additional aspects, specifically, age and years of professional experience as additional considerations for the intervention.

Preliminary study of the Craniofacial Pain and Disability Inventory-11: validation for patients with head and neck cancer.

BACKGROUND: Cancer involves numerous physical, psychological and emotional changes and has a negative impact on patients. Although there are a wide variety of questionnaires for general use in patients with cancer, very few are available that assess the pain, disability and craniomandibular functionality of patients with head and neck cancer (HNC) in a more specific manner. The purpose of this study is to present the preliminary behavior of the CF-PDI in its reduced version adapted for patients with HNC. MATERIAL AND METHODS: A total of 61 patients with HNC were included in a study to preliminarily analyze the internal consistency of the instrument, the convergent validity and the floor and ceiling effects. All the patients completed the informed consent document and a battery of 5 questionnaires: The Numerical Rating Scale (NRS), the Tampa Scale for Kinesiophobia for Temporomandibular Disorders (TSK-TMD), the Pain Catastrophizing Scale (PCS), the Quality of Life Questionnaire in patients with HNC (QLQ-HN) and the reduced version of the Craniofacial Pain and Disability Inventory (CF-PDI-11). Patients also performed 2 physical tests: measurements of the pain threshold on the masseter muscle and on the distal phalanx of the first finger; and the maximum mouth opening in neutral head position. RESULTS: Cronbach's α coefficient showed a very high internal consistency of 0.92. In terms of convergent validity, a statistically significant correlation was found between the CF-PDI-11 and the following variables: NRS, TSK-TMD, PCS, QLQ-HN, the threshold of pain in the distal phalanx of the first finger and the maximum interincisal opening. However, 21.3% of patients obtained the lowest possible score. The strongest correlation was found between the CF-PDI-11 and the QLQ-HN (r = 0.85, p <0.01). CONCLUSIONS: The preliminary version of the CF-PDI-11 shows that it could be a valid and reliable instrument to measure pain, disability and quality of life in patients with HNC.

Impact of COVID-19 outbreak in reperfusion therapies of acute ischaemic stroke in northwest Spain.

BACKGROUND AND PURPOSE: Spain has been one of the countries more heavily stricken by SARS-CoV-2, which has had huge implications for stroke care. The aim was to analyse the impact of the COVID-19 epidemic outbreak on reperfusion therapies for acute ischaemic stroke in the northwest of Spain. METHODS: This was a Spanish multicentre retrospective observational study based on data from tertiary hospitals of the NORDICTUS network. All patients receiving reperfusion therapy for ischaemic stroke between 30 December 2019 and 3 May 2020 were recorded, and their baseline, clinical and radiological characteristics, extra- and intra-hospital times of action, Code Stroke activation pathway, COVID-19 status, reperfusion rate, and short-term outcome before and after the setting of the emergency state were analysed. RESULTS: A total of 796 patients received reperfusion therapies for ischaemic stroke. There was a decrease in the number of patients treated per week (46.5 patients per week vs. 39.0 patients per week, P = 0.043) and a delay in out-of-hospital (95.0 vs. 110.0 min, P = 0.001) and door-to-needle times (51.0 vs. 55.0, P = 0.038). Patients receiving endovascular therapy obtained less successful reperfusion rates (92.9% vs. 86.6%, P = 0.016). COVID-19 patients had more in-hospital mortality. CONCLUSION: A decrease in the number of patients benefiting from reperfusion therapies was found, with a delay in out-of-hospital and door-to-needle times and worse reperfusion rates in northwest Spain. COVID-19 patients had more in-hospital mortality.

Two-dimensional transvaginal sonography vs saline contrast sonohysterography for diagnosing endometrial polyps: systematic review and meta-analysis.

OBJECTIVE: To compare the diagnostic performance of two-dimensional transvaginal sonography (TVS) and saline contrast sonohysterography (SCSH) for the diagnosis of endometrial polyps in studies that used both tests in the same group of patients. METHODS: This was a systematic review and meta-analysis. An extensive search was conducted of Medline (PubMed), Cochrane Library and Web of Science, for studies comparing the diagnostic performance of TVS and SCSH for identifying endometrial polyps, published between January 1990 and December 2019, that reported a definition of endometrial polyp on TVS and SCSH and used pathologic analysis as the reference standard. Quality of the included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. A random-effects model was used to determine pooled sensitivity, specificity and positive and negative likelihood ratios of TVS and SCSH in the detection of endometrial polyps. Subanalysis according to menopausal status was performed. RESULTS: In total, 1278 citations were identified; after exclusions, 25 studies were included in the meta-analysis. In the included studies, the risk of bias evaluated using QUADAS-2 was low for most of the four domains, except for flow and timing, which had an unclear risk of bias in 13 studies. Pooled sensitivity, specificity and positive and negative likelihood ratios for TVS in the detection of endometrial polyps were 55.0% (95% CI, 46.0-64.0%), 91.0% (95% CI, 86.0-94.0%), 5.8 (95% CI, 3.9-8.7) and 0.5 (95% CI, 0.41-0.61), respectively. The corresponding values for SCSH were 92.0% (95% CI, 87.0-95.0%), 93.0% (95% CI, 91.0-95.0%), 13.9 (95% CI, 9.9-19.5) and 0.08 (95% CI, 0.05-0.14), respectively. Significant differences were found when comparing the methods in terms of sensitivity (P < 0.001), but not for specificity (P = 0.0918). Heterogeneity was high for TVS and moderate for SCSH. On subanalysis according to menopausal status, SCSH was found to have higher diagnostic accuracy in both pre- and postmenopausal women; sensitivity and specificity did not differ significantly between the groups for either TVS or SCSH. CONCLUSION: Given that SCSH has better diagnostic positive and negative likelihood ratios than does TVS in both pre- and postmenopausal women, those with clinical suspicion of endometrial polyps should undergo SCSH if TVS findings are inconclusive. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Ecografía transvaginal bidimensional vs histerosonografía con contraste salino para el diagnóstico de pólipos endometriales: revisión sistemática y metaanálisis OBJETIVO: Comparar el desempeño del diagnóstico de la ecografía transvaginal bidimensional (TVS, por sus siglas en inglés) y la histerosonografía con contraste salino (SCSH, por sus siglas en inglés) para el diagnóstico de pólipos endometriales en estudios que utilizaron ambas pruebas en el mismo grupo de pacientes. MÉTODOS: Este estudio fue una revisión sistemática y metaanálisis. El estudio realizó una extensa búsqueda en Medline (PubMed), Cochrane Library y Web of Science de estudios en los que se había comparado el desempeño del diagnóstico de la TVS y la SCSH para identificar pólipos endometriales, publicados entre enero de 1990 y diciembre de 2019, que incluyeran una definición de pólipo endometrial en la TVS y la SCSH y utilizaran el análisis patológico como estándar de referencia. La calidad de los estudios incluidos se evaluó mediante la herramienta de Evaluación de Calidad de los Estudios de Precisión en el Diagnóstico-2 (QUADAS-2, por sus siglas en inglés). Se utilizó un modelo de efectos aleatorios para determinar la sensibilidad combinada, la especificidad, los cocientes de verosimilitud positivos y negativos de la TVS y la SCSH en la detección de pólipos endometriales. Se realizó un subanálisis en función del estatus de la menopausia. RESULTADOS: Se identificaron un total de 1278 citas, de las cuales se incluyeron 25 estudios en el metaanálisis. En los estudios incluidos, el riesgo de sesgo evaluado mediante QUADAS-2 fue bajo para la mayoría de los cuatro dominios, excepto para el flujo y el tiempo, que tuvieron un riesgo de sesgo poco claro en 13 estudios. La sensibilidad combinada, la especificidad y los cocientes de verosimilitud positivos y negativos para la TVS en la detección de pólipos endometriales fueron del 55,0% (IC 95%, 46,0-64,0%), 91,0% (IC 95%, 86,0-94,0%), 5,8 (IC 95%, 3,9-8,7) y 0,5 (IC 95%, 0,41-0,61), respectivamente. Los valores correspondientes para la SCSH fueron 92,0% (IC 95%, 87,0-95,0%), 93,0% (IC 95%, 91,0-95,0%), 13,9 (IC 95%, 9,9-19,5) y 0,08 (IC 95%, 0,05-0,14), respectivamente. Se encontraron diferencias significativas al comparar los métodos respecto a la sensibilidad (P<0,001), pero no respecto a la especificidad (P=0,0918). La heterogeneidad fue alta para la TVS y moderada para la SCSH. En el subanálisis según el estado menopáusico, se determinó que la SCSH tenía una mayor precisión en el diagnóstico en las mujeres pre- y posmenopáusicas, mientras que la sensibilidad y la especificidad no difirieron significativamente entre ambos grupos, tanto para la TVS como para la SCSH. CONCLUSIÓN: Dado que la SCSH tiene mejores coeficientes de verosimilitud positivos y negativos de diagnóstico que la TVS en las mujeres pre- y posmenopáusicas, las mujeres con sospecha clínica de pólipos endometriales deberían someterse a una SCSH si los hallazgos de la TVS no son concluyentes.

Ultrasonographic soft markers for detection of rectosigmoid deep endometriosis.

OBJECTIVES: The aim of this study was to evaluate the use of ultrasound (US) soft markers as a first-line imaging tool to raise suspicion of rectosigmoid (RS) involvement in women suspected of having deep endometriosis. METHODS: We included in this prospective observational study all patients with clinical suspicion of deep endometriosis who underwent diagnostic transvaginal US evaluation at our unit from January 2016 to February 2017. Several US soft markers were evaluated for prediction of RS involvement (presence of US signs of uterine adenomyosis, presence of an endometrioma, adhesion of the ovary to the uterus (reduced ovarian mobility), presence of 'kissing ovaries' (KO) and absence of the 'sliding sign'), using as the gold standard expert US examination for the presence of RS endometriosis. RESULTS: Included were 333 patients with clinical suspicion of deep endometriosis. Of these, 106 had an US diagnosis of RS endometriosis by an expert. The only significant variables found in the prediction model were absence of the sliding sign (odds ratio (OR), 13.95; 95% CI, 7.7-25.3), presence of KO (OR, 22.5; 95% CI, 4.1-124.0) and the interaction between these two variables (OR, 0.03; 95% CI, 0.004-0.28). Regarding their interaction, RS endometriosis was present when KO was absent and the sliding sign was present in 10% (19/190) of cases, when both KO and the sliding sign were present in 71.4% (5/7) of cases, when both KO and the sliding sign were absent in 60.8% (76/125) of cases and when KO was present and the sliding sign was absent in 54.5% (6/11) of cases. Thus, when the sliding sign was absent and/or KO was present, transvaginal US showed a specificity of 75% (95% CI, 69-80%) and a sensitivity of 82% (95% CI, 73-88%). CONCLUSIONS: US findings of absence of the sliding sign and/or presence of KO in patients with clinical suspicion of endometriosis should raise suspicion of RS involvement and indicate referral for expert US examination, with a low rate of false-negative diagnosis. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Characterization of the flow of patients in a hospital from complex networks.

We study the efficiency of operations management in a hospital from the dynamics of the flow of patients. Our principal aim is to characterize strategic departments and seasonal patterns in a hospital from a complex networks approach. Process mining techniques are developed to track out-patients' pathways along different departments for the purpose of building weekly networks. In these networks, departments act as nodes with multiple out/in-going arrows connecting other departments. Strategic departments are classified into target and critical departments. On the one hand, target departments, which in this study belong to the oncology area, correspond to those affected by new management policies whose impact is to be assessed. On the other hand, critical departments correspond to the most active departments, the hubs of the networks. Using suitable networks parameters, strategic departments are shown to be highly efficient regardless of the season, which naturally translates into a high level of service offered to patients. In addition, our results show conformance with the new objectives concerning target departments. The methodology presented is shown to be successful in evaluating the efficiency of hospital services in order to enhance process performances, and moreover, it is suitable to be implemented in healthcare management systems at a greater scale and the service industry whenever the flow of clients or customers are involved.

Atmospheric wind and temperature profiles inversion using infrasound: An ensemble model context.

This paper presents an inversion methodology where acoustic observations of infrasound waves are used to update an atmospheric model. This paper sought a flexible parameterization that permits to incorporate physical and numerical constraints without the need to reformulate the inversion. On the other hand, the optimization conveys an explicit search over the solution space, making the solver computationally expensive. Nevertheless, through a parallel implementation and the use of tight constraints, this study demonstrates that the methodology is computationally tractable. Constraints to the solution space are derived from the spread (variance) of ERA5 ensemble reanalysis members, which summarize the best current knowledge of the atmosphere from assimilated measurements and physical models. Similarly, the initial model temperature and winds for the inversion are chosen to be the average of these parameters in the ensemble members. The performance of the inversion is demonstrated with the application to infrasound observations from an explosion generated by the destruction of ammunition at Hukkakero, Finland. The acoustic signals are recorded at an array station located at 178 km range, which is within the classical shadow zone distance. The observed returns are assumed to come from stratospheric reflections. Thus, the reflection altitude is also an inverted parameter.