Recombinant ADAMTS13 in Congenital Thrombotic Thrombocytopenic Purpura.

BACKGROUND: Congenital thrombotic thrombocytopenic purpura (TTP) results from severe hereditary deficiency of ADAMTS13. The efficacy and safety of recombinant ADAMTS13 and standard therapy (plasma-derived products) administered as routine prophylaxis or on-demand treatment in patients with congenital TTP is not known. METHODS: In this phase 3, open-label, crossover trial, we randomly assigned patients in a 1:1 ratio to two 6-month periods of prophylaxis with recombinant ADAMTS13 (40 IU per kilogram of body weight, administered intravenously) or standard therapy, followed by the alternate treatment; thereafter, all the patients received recombinant ADAMTS13 for an additional 6 months. The trigger for this interim analysis was trial completion by at least 30 patients. The primary outcome was acute TTP events. Manifestations of TTP, safety, and pharmacokinetics were assessed. Patients who had an acute TTP event could receive on-demand treatment. RESULTS: A total of 48 patients underwent randomization; 32 completed the trial. No acute TTP event occurred during prophylaxis with recombinant ADAMTS13, whereas 1 patient had an acute TTP event during prophylaxis with standard therapy (mean annualized event rate, 0.05). Thrombocytopenia was the most frequent TTP manifestation (annualized event rate, 0.74 with recombinant ADAMTS13 and 1.73 with standard therapy). Adverse events occurred in 71% of the patients with recombinant ADAMTS13 and in 84% with standard therapy. Adverse events that were considered by investigators to be related to the trial drug occurred in 9% of the patients with recombinant ADAMTS13 and in 48% with standard therapy. Trial-drug interruption or discontinuation due to adverse events occurred in no patients with recombinant ADAMTS13 and in 8 patients with standard therapy. No neutralizing antibodies developed during recombinant ADAMTS13 treatment. The mean maximum ADAMTS13 activity after recombinant ADAMTS13 treatment was 101%, as compared with 19% after standard therapy. CONCLUSIONS: During prophylaxis with recombinant ADAMTS13 in patients with congenital TTP, ADAMTS13 activity reached approximately 100% of normal levels, adverse events were generally mild or moderate in severity, and TTP events and manifestations were rare. (Funded by Takeda Development Center Americas and Baxalta Innovations; ClinicalTrials.gov number, NCT03393975.).

Evolution of the Magnetic Excitations in Electron-Doped La_{2-x}Ce_{x}CuO_{4}.

We investigated the high energy spin excitations in electron-doped La_{2-x}Ce_{x}CuO_{4}, a cuprate superconductor, by resonant inelastic x-ray scattering (RIXS) measurements. Efforts were paid to disentangle the paramagnon signal from non-spin-flip spectral weight mixing in the RIXS spectrum at Q_{∥}=(0.6π,0) and (0.9π,0) along the (1 0) direction. Our results show that, for doping level x from 0.07 to 0.185, the variation of the paramagnon excitation energy is marginal. We discuss the implication of our results in connection with the evolution of the electron correlation strength in this system.

A necessary conversation to develop chatbots for HIV studies: qualitative findings from research staff, community advisory board members, and study participants.

Chatbots increase business productivity by handling customer conversations instead of human agents. Similar rationale applies to use chatbots in the healthcare sector, especially for health coaches who converse with clients. Chatbots are nascent in healthcare. Study findings have been mixed in terms of engagement and their impact on outcomes. Questions remain as to chatbot acceptability with coaches and other providers; studies have focused on clients.To clarify perceived benefits of chatbots in HIV interventions we conducted virtual focus groups with 13 research staff, eight community advisory board members, and seven young adults who were HIV intervention trial participants (clients). Our HIV healthcare context is important. Clients represent a promising age demographic for chatbot uptake. They are a marginalized population warranting consideration to avoid technology that limits healthcare access.Focus group participants expressed the value of chatbots for HIV research staff and clients. Staff discussed how chatbot functions, such as automated appointment scheduling and service referrals, could reduce workloads while clients discussed the after-hours convenience of these functions. Participants also emphasized that chatbots should provide relatable conversation, reliable functionality, and would not be appropriate for all clients. Our findings underscore the need to further examine appropriate chatbot functionality in HIV interventions.

Round ligament management during minimally invasive groin hernia repair in women: a systematic review and meta-analysis.

BACKGROUND: Female sex has been associated with worse outcomes after groin hernia repair (GHR), including a higher rate of chronic pain and recurrence. Most of the studies in GHR are performed in males, and the recommendations for females extrapolate from these studies, even though females have anatomy intricacies. The round ligament of the uterus (RLU) is associated with pelvic stabilization and plays a role in sensory function. Transection of the RLU during GHR is controversial as it can allow easier mesh placement but can favor genitourinary complications and chronic pain. As no previous meta-analysis compared preserving versus transecting the RLU during minimally invasive (MIS) GHR, we aim to perform a systematic review and meta-analysis evaluating surgical outcomes comparing the approaches. METHODS: Cochrane Central, Embase, and PubMed databases were systematically searched for studies comparing transection versus preservation of the RLU in MIS groin hernia surgeries. Outcomes assessed were operative time, bleeding, surgical site events, hospital stay, chronic pain, paresthesia, recurrence rates, and genital prolapse rates. Statistical analysis was performed using RevMan 5.4.1. Heterogeneity was assessed with I2 statistics. A review protocol for this meta-analysis was registered at PROSPERO (CRD 42023467146). RESULTS: 1738 studies were screened. A total of six studies, comprising 1131 women, were included, of whom 652 (57.6%) had preservation of the RLU during MIS groin hernia repair. We found no statistical difference regarding chronic pain, paresthesia, recurrence rates, and postoperative complications. We found a longer operative time for the preservation group (MD 6.84 min; 95% CI 3.0-10.68; P = 0.0005; I2 = 74%). CONCLUSION: Transecting the RLU reduces the operative time during MIS GHR with no difference regarding postoperative complication rates. Although transection appears safe, further prospective randomized studies with long-term follow-up and patient-reported outcomes are necessary to define the optimal management of RLU during MIS GHR.

Making an accurate diagnosis of anterior mediastinal lesions: a proposal for a new diagnostic algorithm from the BTOG Thymic Malignancies Special Interest Group.

Due to the rising demand in cross-sectional thoracic imaging, anterior mediastinal lesions are being identified with increasing frequency. Following iterative and multidisciplinary discussions, the BTOG Thymic Malignancies Special Interest Group have developed an algorithm to standardise the diagnostic approach for these relatively uncommon but important conditions which span from benign (thymic remnant, thymic hyperplasia and thymic cysts) to suspected localised thymomas to suspected more aggressive malignancy (thymic carcinoma, lymphoma and germ cell tumours). For each condition, we provide a brief description, an overview of the key radiological findings and a description of the proposed algorithm including the rationale behind the recommendations. We also highlight the role of magnetic resonance (MR) imaging for the characterisation of anterior mediastinal masses in specific indications when the necessary local resources and expertise exist. In addition, we hope this provides the rationale for service development in MR of the anterior mediastinum where current resource and expertise requires development. Through this standardised pathway, we hope to drive improvements in patient care by rationalising surveillance schedules, avoiding unnecessary resections of benign entities with their associated morbidity and optimising the diagnostic work-up prior to the appropriate treatment of anterior mediastinal malignancies.

Characterization of a model of hindgut acidosis in mid-lactation cows: A pilot study.

The objective of this pilot study was to generate data to support the development of an experimental model of hindgut acidosis to further understand its systemic consequences independently of rumen acidosis. Four ruminally fistulated multiparous Holstein cows (213 ± 11 d in milk) were subjected to 2 consecutive experimental periods (P1 and P2), separated by a 3-d washout. Experimental periods were 96 h long from the baseline to the final measurements but expanded over 5 calendar days (d 0-4). Abomasal infusions of saline and corn starch (2.8 kg/d) were performed for the first 72 h (d 0-3) of P1 and P2, respectively. Final measurements were performed 24 h after the end of the infusions (d 4). Each cow was used as its own control by comparing P2 to P1. Postruminal-intestinal permeability was assessed by Cr appearance in blood after a pulse dose administration of Cr-EDTA into the abomasum on d 2 (48 h after infusion initiation) of each period. Starch infusion during P2 was associated with a milk protein yield increase (3.3%) and a decrease in milk urea nitrogen (11%). Fecal dry matter increased (8.8%), and starch content tended to increase (∼2 fold) during P2. There was a period-by-day interaction for fecal pH as it decreased during starch infusion (1.3 pH points) but remained constant during P1. Although fecal lactate was not detectable during P1, it consistently increased during starch infusion. Fecal alkaline phosphatase activity also increased (∼17 fold) in association with starch infusion. Two hours after Cr-EDTA administration, blood Cr concentration was higher during starch infusion, resulting in a tendency for a treatment-by-hour interaction. Furthermore, blood d-lactate increased (∼2.5 fold), serum Cu decreased (18%), and blood urea nitrogen, cholesterol, and Ca tended to decrease (9.4%, 1.2%, and 2.4%, respectively), relative to P1. The current results suggest that hindgut acidosis was successfully induced by postruminal starch infusion, leading to gut damage and increased intestinal permeability. However, indications of systemic inflammation were not observed. The herein described preliminary results will require confirmation in a properly powered study.

Longitudinal characterization of the metabolome of dairy cows transitioning from one lactation to the next: Investigations in the liver.

This study aimed to investigate the metabolic changes in the livers of dairy cows from 1 wk before dry off to 1 wk after calving. Twelve high-yielding Holstein cows were included in a longitudinal study and housed in a tiestall barn. The cows were dried off at 6 wk before the expected calving date (dry period length = 42 d). During the entire lactation, the cows were milked twice daily at 0600 and 1700 h. Liver biopsies were taken from each cow at 4 different times: wk -7 (before drying off), -5 (after drying off), -1 and +1 relative to calving. A targeted metabolomics approach was performed by liquid chromatography and flow injection with electrospray ionization triple quadrupole mass spectrometry using the MxP Quant 500 kit (Biocrates Life Sciences AG). A total of 185 metabolites in the liver were used for the final data analysis. Principal component analysis revealed a clear separation by days of sampling, indicating a notable shift in metabolic phenotype from late lactation to the dry period and further changes after calving. Changes were observed in several classes of compounds, including AA and biogenic amines. In particular, the changes in acylcarnitines (AcylCN), phosphatidylcholines (PC), sphingomyelins (SM), and bile acids (BA) indicated extensive remodeling of the hepatic lipidome. The changes in AcylCN concentrations in early lactation suggest incomplete fatty acid oxidation in the liver, possibly indicating mitochondrial dysfunction or enzymatic imbalance. In addition, the changes in PC and SM species in early lactation indicate altered cell membrane composition, which may affect cell signaling and functionality. In addition, changes in BA concentrations and profiles indicate dynamic adaptations in BA synthesis, as well as lipid digestion and absorption during the observation period. In particular, principal component analysis showed an overlapping distribution of liver metabolites in primiparous and multiparous cows, indicating no significant difference between these groups. In addition, Volcano plots showed similar liver metabolism between primiparous and multiparous cows, with no significant fold changes (>1.5) in any metabolite at significant P-values (false discovery rate <0.05). These results provide valuable insight into the physiological ranges of liver metabolites during dry period and calving in healthy dairy cows and should contribute to the design and interpretation of future metabolite-based studies of the transition dairy cow.

Features and frequency of use of electronic health records in primary care across 20 countries: a cross-sectional study.

OBJECTIVES: Variation exists in the capabilities of electronic healthcare records (EHRs) systems and the frequency of their use by primary care physicians (PCPs) from different settings. We aimed to examine the factors associated with everyday EHRs use by PCPs, characterise the EHRs features available to PCPs, and to identify the impact of practice settings on feature availability. STUDY DESIGN: Cross-sectional study. METHODS: PCPs from 20 countries completed cross-sectional online survey between June and September 2020. Responses which reported frequency of EHRs use were retained. Associations between everyday EHRs use and PCP and practice factors (country, urbanicity, and digital maturity) were explored using multivariable logistic regression analyses. The effect of practice factors on the variation in availability of ten EHRs features was estimated using Cramer's V. RESULTS: Responses from 1520 out of 1605 PCPs surveyed (94·7%) were retained. Everyday EHRs use was reported by 91·2% of PCPs. Everyday EHRs use was associated with PCPs working >28 h per week, having more years of experience using EHRs, country of employment, and higher digital maturity. EHRs features concerning entering, and retrieving data were available to most PCPs. Few PCPs reported having access to tools for 'interactive patient education' (37·3%) or 'home monitoring and self-testing of chronic conditions' (34·3%). Country of practice was associated with availability of all EHRs features (Cramer's V range: 0·2-0·6), particularly with availability of tools enabling patient EHRs access (Cramer's V: 0·6, P < 0.0001). Greater feature availability of EHRs features was observed with greater digital maturity. CONCLUSIONS: EHRs features intended for patient use were uncommon across countries and levels of digital maturity. Systems-level research is necessary to identify the country-specific barriers impeding the implementation of EHRs features in primary care, particularly of EHRs features enabling patient interaction with EHRs, to develop strategies to improve systems-wide EHRs use.

Psycho-emotional intervention with parents of very preterm babies during the first year: A single-arm pilot study.

Studies of intervention programs that aim to improve the emotional state of parents of children admitted to the neonatal intensive care units (NICU) are scarce in Spain. The aims of this single-arm pilot study are to get to know the emotional profile of parents of high-risk preterm newborns, and to explore parents' patterns of emotional well-being before and after a psychological program called the Parental Empowerment Program, to increase parental readiness levels. The sample was made up of 100 parents (50 couples) who participated in the program. Measurements were taken of post-traumatic stress, depression, and resilience at 1 month and 12 months. Repeated measurements and dyadic data analyses were performed. One month after the birth of the baby and prior to the start of the program, mothers show more symptoms of stress and depression than fathers. After the intervention, both parents experienced improvements in their mood levels. The evidence obtained seems to show that high resilience levels and low post-traumatic stress symptoms are associated with reduced depression levels after implementing the program. However, the heterogeneity of the responses obtained, the observed associations between stress, resilience, and maternal depression, along with the reciprocal influence between maternal and paternal depression 1 year after the intervention, highlight the need for a more in-depth exploration of the interplay between risk and protective factors in this population. Despite the identified potential threats to validity, further work in this direction is recommended, including the implementation of clinical trials to demonstrate intervention efficacy. The adaptation of the parents' mutual emotional adjustment at each stage would allow them to participate more actively in the baby's care.

B-Cell Responses in Chronic Chagas Disease: Waning of Trypanosoma cruzi-Specific Antibody-Secreting Cells Following Successful Etiological Treatment.

BACKGROUND: A drawback in the treatment of chronic Chagas disease (American trypanosomiasis) is the long time required to achieve complete loss of serological reactivity, the standard for determining treatment efficacy. METHODS: Antibody-secreting cells and memory B cells specific for Trypanosoma cruzi and their degree of differentiation were evaluated in adult and pediatric study participants with chronic Chagas disease before and after etiological treatment. RESULTS: T. cruzi-specific antibody-secreting cells disappeared from the circulation in benznidazole or nifurtimox-treated participants with declining parasite-specific antibody levels after treatment, whereas B cells in most participants with unaltered antibody levels were low before treatment and did not change after treatment. The timing of the decay in parasite-specific antibody-secreting B cells was similar to that in parasite-specific antibodies, as measured by a Luminex-based assay, but preceded the decay in antibody levels detected by conventional serology. The phenotype of total B cells returned to a noninfection profile after successful treatment. CONCLUSIONS: T. cruzi-specific antibodies in the circulation of chronically T. cruzi-infected study participants likely derive from both antigen-driven plasmablasts, which disappear after successful treatment, and long-lived plasma cells, which persist and account for the low frequency and long course to complete seronegative conversion in successfully treated participants.

A perspective of fluorescence microscopy for cellular structural biology with EGFR as witness.

The epidermal growth factor receptor (EGFR) is a poster child for the understanding of receptor behaviour, and of paramount importance to cell function and human health. Cloned almost forty years ago, the interest in EGFR's structure/function relationships remains unabated, not least because changes in oncogenic EGFR mutants are key drivers of the formation of lung and brain tumours. The structure of the assemblies formed by EGFR have been comprehensibly investigated by techniques such as high-resolution X-ray crystallography, NMR and all-atom molecular dynamics (MD) simulations. However, the complexity embedded in the portfolio of EGFR states that are only possible in the physiological environment of cells has often proved refractory to cell-free structural methods. Conversely, some key inroads made by quantitative fluorescence microscopy and super-resolution have depended on exploiting the wealth of structures available. Here, a brief personal perspective is provided on how quantitative fluorescence microscopy and super-resolution methods have cross-fertilised with cell-free-derived EGFR structural information. I primarily discuss areas in which my research group has made a contribution to fill gaps in EGFR's cellular structural biology and towards developing new tools to investigate macromolecular assemblies in cells.

Midbrain and pons MRI shape analysis and its clinical and CSF correlates in degenerative parkinsonisms: a pilot study.

OBJECTIVES: To conduct brainstem MRI shape analysis across neurodegenerative parkinsonisms and control subjects (CS), along with its association with clinical and cerebrospinal fluid (CSF) correlates. METHODOLOGY: We collected demographic and clinical variables, performed planimetric and shape MRI analyses, and determined CSF neurofilament-light chain (NfL) levels in 84 participants: 11 CS, 12 with Parkinson's disease (PD), 26 with multiple system atrophy (MSA), 21 with progressive supranuclear palsy (PSP), and 14 with corticobasal degeneration (CBD). RESULTS: MSA featured the most extensive and significant brainstem shape narrowing (that is, atrophy), mostly in the pons. CBD presented local atrophy in several small areas in the pons and midbrain compared to PD and CS. PSP presented local atrophy in small areas in the posterior and upper midbrain as well as the rostral pons compared to MSA. Our findings of planimetric MRI measurements and CSF NfL levels replicated those from previous literature. Brainstem shape atrophy correlated with worse motor state in all parkinsonisms and with higher NfL levels in MSA, PSP, and PD. CONCLUSION: Atypical parkinsonisms present different brainstem shape patterns which correlate with clinical severity and neuronal degeneration. In MSA, shape analysis could be further explored as a potential diagnostic biomarker. By contrast, shape analysis appears to have a rather limited discriminant value in PSP. KEY POINTS: • Atypical parkinsonisms present different brainstem shape patterns. • Shape patterns correlate with clinical severity and neuronal degeneration. • In MSA, shape analysis could be further explored as a potential diagnostic biomarker.

Functional responses to multiple sequential abiotic stress (waterlogging-drought) in three woody taxa with different root systems and stress tolerance.

There is generally a trade-off in the resistance to drought and to waterlogging. However, several species are sequentially subjected to both stressors in many environments. We evaluated the ecophysiological strategies to cope with multiple sequential stress of waterlogging and drought (W + D) of three taxa differing in stress resistance and root morphology: the phreatophic Eucalyptus camaldulensis (Ec) and two shallow-rooted willow clones: Salix matsudana x Salix alba (SmxSa) and Salix nigra (Sn4). Individuals of the three taxa were grown in pots and assigned to either of four treatments: Control (well-watered plants), well-watered followed by drought (C + D); waterlogged for 15 days followed by drought (W15d + D) and waterlogged for 30 days followed by drought (W30d + D). Biomass allocation, growth (diameter, height, length of leaves, and roots), specific leaf area, stomatal conductance, water potential, hydraulic conductivity of roots and branches, leaf C13 and root cortical aerenchyma formation were determined at different stages of the experiment. Ec growth was not affected by W + D, developing tolerance strategies at leaf and whole plant levels. Differential effects of W + D were observed in both Salix clones depending on the time of waterlogging. In Sn4 and SmxSa, the root biomass was affected in W15d + D treatment, but a root tolerance response (aerenchyma and adventitious root formation) was observed in W30d + D. In the three taxa, and contrary to expectations, the previous exposure to a waterlogging period did not increase the susceptibility of the plants to a subsequent drought event. On the contrary, we found tolerance, which depended on the time of waterlogging exposure.

Total synthesis of the natural (-)-205B alkaloid and its activity toward α7 nAChRs.

A new approach to the synthesis of the (-)-205B alkaloid is described in this paper. This work is characterised by the development of an efficient chirality transfer through a silyl tethered intramolecular alkylation reaction, an unprecedented tandem highly selective iridium catalyzed partial reduction of lactam coupled with an acid promoted aza-Prins reaction, and an almost complete stereochemical control in Shenvi's radical hydrogen atom transfer on an exocyclic methylene. The second part of this work demonstrates the positive allosteric behavior of this natural alkaloid toward α7 nAChRs, in contrast to the reported inhibitory effect of the unnatural enantiomer.

The use of alpha 1 thymosin as an immunomodulator of the response against SARS-Cov2.

BACKGROUND: Since the beginning of SARS-CoV2 pandemic, the mortality rate among elderly patients (60-90 years) has been around 50%, so age has been a determining factor of a worse COVID-19 prognosis. Associated with age, the thymic function involution and depletion plays an important role, that could be related to a dysregulated and ineffective innate and adaptive immune response against SARS-CoV2. Our study aims to further in vitro effect of human Thymosin-alpha-1 (α1Thy) treatment on the immune system in population groups with different thymic function levels in the scenario of SARS-CoV2 infection. RESULTS: Activation markers such as CD40, CD80 and TIM-3 were upregulated in α1Thy presence, especially in plasmacytoid dendritic cells (pDCs) and, with increased TNFα production was observed compared to untreated condition. Co-cultures of CD4 + and CD8 + T cells with DCs treated with α1Thy in response to SARS-CoV2 peptides showed a decrease in the cytokine production compared to the condition without α1Thy pre-treated. A decrease in CD40L activation co-receptor expression in CD8 + LTs was also observed, as well as an increase in PD1 in CD4 + TLs expression in both age groups. In fact, there are no age-related differences in the immunomodulatory effect of the hormone, and it seems that effector memory and terminally differentiated memory T lymphocyte subsets were the most actively influenced by the immunomodulatory α1Thy effect. Finally, the polyfunctionality measured in SARS-CoV2 Specific-T cells response was maintained in α1Thy presence in total and memory subpopulations CD4 + and CD8 + T-cells, despite decreased proinflammatory cytokines production. CONCLUSION: The hormone α1Thy could reduce, through the modulation of DCs, the amount of proinflammatory cytokines produced by T cells. Moreover, α1Thy improve lymphocyte functionality and could become a beneficial therapeutic alternative as an adjuvant in SARS-CoV2 treatment either in the acute phase after infection or reinfection. In addition, the effect on the T immune response means that α1Thy can be incorporated into the vaccination regimen, especially in the most immunologically vulnerable individuals such as the elderly. SUBJECTS: Thymosin alpha 1, Dendritic cells, SARS-CoV2-specific T cells response, Immunomodulation.

Pleural effusion in a child with a correctly placed ventricle-peritoneal shunt.

Pleural effusions in children (PE) due to ventricle-peritoneal shunt (VPS) is very rare, with few cases reported. We present a new case of an infant with VPS who had a massive hydrothorax not associated with misplacement or migration of the distal catheter or with ascites. After the evacuation of the PE we managed the patient by adjusting the pressure of the adjustable valve (AV). Sequential thoracic ultrasounds showed a satisfactory outcome. We review the literature thoroughly and describe the possible pathophysiological mechanisms.

Linear thinking does not reflect the newer 21st-century anesthesia concepts. A narrative review.

The brain constitutes a good example of a chaotic, nonlinear biological system where large neuronal networks operate chaotically with random connectivity. This critical state is significantly affected by the anesthetic loss of consciousness induced by drugs whose pharmacological behavior has been classically based on linear kinetics and dynamics. Recent developments in pharmacology and brain monitoring during anesthesia suggest a different view that we tried to explore in this article. The concepts of effect-site for hypnotic drugs modeling a maximum effect, electroencephalographic dynamics during induction, maintenance, and recovery from anesthesia are discussed, integrated into this alternative view, and how it may be applied in daily clinical practice.

Gender and family structures affecting intergenerational support from adult children to older parents: A cross-national study in a developing country.

In Latin America, informal support from adult children to their older parents ("upward support") is crucial with an aging population and insufficient coverage of social protection systems. This article examines variables associated with upward support, distinguishing by gender of parents and their children. The research design is quantitative, correlational, and cross-sectional. It is based on primary survey data collected by the authors for the study. The authors hypothesized that upward support depends on children's opportunities to provide support and on the needs of parents. The results show that upward support depends more on children's opportunities than on parents' needs, although upward support is higher for parents with poorer health. Daughters are more supportive than sons, but sibling characteristics do not moderate associations between children's gender and receipt of support. Cohabiting with the parent, receiving support from the parent, and having a good relationship were also associated with greater upward support. Therefore, policies should consider the gender of adult children when allocating resources to older people.

[Impact of the COVID-19 pandemic above a universal electronic consultation program (e-consultation) between general practitioners and cardiologists]. / Impacto de la pandemia por COVID-19 sobre un programa de consulta electrónica universal (e-consulta) entre médicos de Atención Primaria y cardiólogos.

Blackground and objective: Virtual healthcare models, usually between healthcare professionals and patients, have developed strongly during the coronavirus disease 2019 (COVID-19) pandemic, but there are not data of models between clinicians. Our objective is to analyse the impact of the COVID-19 pandemic on the activity and health outcomes of the universal e-consultation program for patient referrals between primary care physicians and the Cardiology Department in our area. Methods: Patients with at least one e-consultation between 2018 and 2021 were selected. We analysed the impact of the COVID-19 pandemic on activity and waiting time for care, hospitalizations and mortality, taking as a reference the consultations carried out during 2018. Results: We analysed 25,121 patients. Through logistic regression analysis, it was observed that a shorter delay in care and resolution of the e-consultation without the need for face-to-face care were associated with a better prognosis. The COVID-19 pandemic periods (2019-2020 and 2020-2021) were not associated with worse health outcomes compared to 2018. Conclusions: The results of our study show a significant reduction in e-consult referrals during the first year of the COVID-19 pandemic with a subsequent recovery in the demand for care without the pandemic periods being associated with worse outcomes. The reduction in the time elapsed for solving the e-consult and no need for in-person visit were associated with better outcomes.

Recalculating the staff required to run a modern assisted reproductive technology laboratory.

STUDY QUESTION: What number of staff is sufficient to perform increasingly complicated processes in today's modern ART laboratories? SUMMARY ANSWER: The adequate number of personnel required for the efficient and safe operation of modern ART laboratories needs to be calculated. WHAT IS KNOWN ALREADY: In today's modern ART laboratories, the amount of time required to perform increasingly complicated processes has more than doubled, with a downward trend in the amount of work an embryologist can do. Different workload unit values have been used to evaluate each workload task and efficiency in a particular ART laboratory, as well as to occasionally compare one laboratory with another. STUDY DESIGN, SIZE, DURATION: Seven senior embryologists working at different IVF centers, three public and four private centers, participated in this multicenter study conducted between 2019 and 2020. We prepared a survey to create a calculator for staff using the average (of three attempts) time spent in every laboratory by each embryologist of the center to perform any ART process. PARTICIPANTS/MATERIALS, SETTING, METHODS: Different laboratory processes and activities related to quality control, time spent and conventional human double witnessing were included in the survey. To calculate the number of processes that each embryologist can perform per year, an embryologist was considered to be having a full-time contract and working 7 or 8 h/day. The times included in the calculation of each task were those corresponding to the 95th percentile. For the calculations, Microsoft® Office Excel® Professional Plus 2019 was used. MAIN RESULTS AND THE ROLE OF CHANCE: The survey showed that the time needed per embryologist to perform the different processes necessary for a classic IVF cycle without time lapse (TL) was 8.11 h, and with TL, it was 10.27 h. The calculated time also considered the time spent in documentation handling, cycle preparation, database management and conventional human double witnessing verification. An ICSI without TL needed 8.55 h, and with TL, it needed 10.71 h. An ICSI-PGT without a TL cycle needed 11.75 h, and with TL, it needed 13.91 h. Furthermore, 1.81 h should be added for every vitrification support needed. The time needed to control more than 200 critical steps, including equipment control and culture parameters, was 30 min per day plus 3.9 min per device to control.The time spent in semen analysis (including documentation handling, cycle preparation and database management) or intrauterine insemination with a partner sperm was 2.7 h. For donor sperm, an additional hour was required for the management involved. The time required to perform a testicular biopsy and cryopreserve the sample was 4 h. Similarly, the time required to perform seminal cryopreservation was 3.7 h. LIMITATIONS, REASONS FOR CAUTION: The study was conducted considering a full-time contract embryologist working 7 or 8 h/day, 5 days a week, with days off according to the Spanish regulations. However, our findings can be adapted to foreign regulations using the developed online calculation platform. WIDER IMPLICATIONS OF THE FINDINGS: A new advanced staff calculator allows any IVF laboratory to estimate the minimum number of embryologists necessary without compromising the security or success of the results. Nevertheless, we recommend a minimum of two qualified embryologists in every laboratory, regardless of the workload. STUDY FUNDING/COMPETING INTEREST(S): This work was funded by the Asociación para el Estudio de la Biología de la Reproducción (ASEBIR). None of the authors has any conflict of interest to declare. TRIAL REGISTRATION NUMBER: N/A.