Comparison of Pregnancy Preferences Preceding vs Year 1 of the COVID-19 Pandemic.

Importance: Understanding how the COVID-19 pandemic affected people's desire to avoid pregnancy is essential for interpreting the pandemic's associations with access to reproductive health care and reproductive autonomy. Early research is largely cross-sectional and relies on people's own evaluations of how their desires changed. Objective: To investigate longitudinal changes in pregnancy desires during the year before and the first year of the COVID-19 pandemic. Design, Setting, and Participants: In this cohort study, participants reported their pregnancy preferences at baseline and quarterly for up to 18 months between March 2019 and March 2021. An interrupted time series analysis with mixed-effects segmented linear regression was used to examine population-averaged time trends. People were recruited from 7 primary and reproductive health care facilities in Arizona, New Mexico, and Texas. Participants were sexually active, pregnancy-capable people aged 15 to 34 years who were not pregnant or sterilized. Data analysis was performed from September 2021 to January 2022. Exposures: Continuous time, with knots at the onset of the first (July 1, 2020, summer surge) and second (November 1, 2020, fall surge) COVID-19 cases surges in the Southwest. Main Outcomes and Measures: Preferences around potential pregnancy in the next 3 months, measured using the validated Desire to Avoid Pregnancy (DAP) scale (range, 0-4, with 4 indicating a higher desire to avoid pregnancy). Results: The 627 participants in the analytical sample had a mean (SD) age of 24.9 (4.9) years; 320 (51.0%) identified as Latinx and 180 (28.7%) as White. Over the year before the first case surge in the US Southwest in summer 2020, population-averaged DAP scores decreased steadily over time (-0.06 point per quarter; 95% CI, -0.07 to -0.04 point per quarter; P < .001). During the summer 2020 surge, DAP scores stopped declining (0.05 point per quarter; 95% CI, -0.03 to 0.13 point per quarter; change in slope, P < .001). During the fall 2020 surge, however, DAP scores declined again at -0.11 point per quarter (95% CI, -0.26 to 0.04 point per quarter; change in slope, P = .10). Participants aged 15 to 24 years and those who were nulliparous and primiparous experienced greater declines in DAP score before the summer surge, and greater reversals of decline between summer and fall 2020, than did those who were aged 25 to 34 years and multiparous. Conclusions and Relevance: These findings suggest that the COVID-19 pandemic onset was associated with the stalling of a prior trend toward greater desire for pregnancy over time, particularly for people earlier in their reproductive lives.

Efficacy and safety of intramuscular administration of allogeneic adipose tissue derived and expanded mesenchymal stromal cells in diabetic patients with critical limb ischemia with no possibility of revascularization: study protocol for a randomized controlled double-blind phase II clinical trial (The NOMA Trial).

BACKGROUND: Chronic lower limb ischemia develops earlier and more frequently in patients with type 2 diabetes mellitus. Diabetes remains the main cause of lower-extremity non-traumatic amputations. Current medical treatment, based on antiplatelet therapy and statins, has demonstrated deficient improvement of the disease. In recent years, research has shown that it is possible to improve tissue perfusion through therapeutic angiogenesis. Both in animal models and humans, it has been shown that cell therapy can induce therapeutic angiogenesis, making mesenchymal stromal cell-based therapy one of the most promising therapeutic alternatives. The aim of this study is to evaluate the feasibility, safety, and efficacy of cell therapy based on mesenchymal stromal cells derived from adipose tissue intramuscular administration to patients with type 2 diabetes mellitus with critical limb ischemia and without possibility of revascularization. METHODS: A multicenter, randomized double-blind, placebo-controlled trial has been designed. Ninety eligible patients will be randomly assigned at a ratio 1:1:1 to one of the following: control group (n = 30), low-cell dose treatment group (n = 30), and high-cell dose treatment group (n = 30). Treatment will be administered in a single-dose way and patients will be followed for 12 months. Primary outcome (safety) will be evaluated by measuring the rate of adverse events within the study period. Secondary outcomes (efficacy) will be measured by assessing clinical, analytical, and imaging-test parameters. Tertiary outcome (quality of life) will be evaluated with SF-12 and VascuQol-6 scales. DISCUSSION: Chronic lower limb ischemia has limited therapeutic options and constitutes a public health problem in both developed and underdeveloped countries. Given that the current treatment is not established in daily clinical practice, it is essential to provide evidence-based data that allow taking a step forward in its clinical development. Also, the multidisciplinary coordination exercise needed to develop this clinical trial protocol will undoubtfully be useful to conduct academic clinical trials in the field of cell therapy in the near future. TRIAL REGISTRATION: ClinicalTrials.gov NCT04466007 . Registered on January 07, 2020. All items from the World Health Organization Trial Registration Data Set are included within the body of the protocol.

Development of a severity of disease score and classification model by machine learning for hospitalized COVID-19 patients.

BACKGROUND: Efficient and early triage of hospitalized Covid-19 patients to detect those with higher risk of severe disease is essential for appropriate case management. METHODS: We trained, validated, and externally tested a machine-learning model to early identify patients who will die or require mechanical ventilation during hospitalization from clinical and laboratory features obtained at admission. A development cohort with 918 Covid-19 patients was used for training and internal validation, and 352 patients from another hospital were used for external testing. Performance of the model was evaluated by calculating the area under the receiver-operating-characteristic curve (AUC), sensitivity and specificity. RESULTS: A total of 363 of 918 (39.5%) and 128 of 352 (36.4%) Covid-19 patients from the development and external testing cohort, respectively, required mechanical ventilation or died during hospitalization. In the development cohort, the model obtained an AUC of 0.85 (95% confidence interval [CI], 0.82 to 0.87) for predicting severity of disease progression. Variables ranked according to their contribution to the model were the peripheral blood oxygen saturation (SpO2)/fraction of inspired oxygen (FiO2) ratio, age, estimated glomerular filtration rate, procalcitonin, C-reactive protein, updated Charlson comorbidity index and lymphocytes. In the external testing cohort, the model performed an AUC of 0.83 (95% CI, 0.81 to 0.85). This model is deployed in an open source calculator, in which Covid-19 patients at admission are individually stratified as being at high or non-high risk for severe disease progression. CONCLUSIONS: This machine-learning model, applied at hospital admission, predicts risk of severe disease progression in Covid-19 patients.

Adipose-derived mesenchymal stromal cells for the treatment of patients with severe SARS-CoV-2 pneumonia requiring mechanical ventilation. A proof of concept study.

BACKGROUND: Identification of effective treatments in severe cases of COVID-19 requiring mechanical ventilation represents an unmet medical need. Our aim was to determine whether the administration of adipose-tissue derived mesenchymal stromal cells (AT-MSC) is safe and potentially useful in these patients. METHODS: Thirteen COVID-19 adult patients under invasive mechanical ventilation who had received previous antiviral and/or anti-inflammatory treatments (including steroids, lopinavir/ritonavir, hydroxychloroquine and/or tocilizumab, among others) were treated with allogeneic AT-MSC. Ten patients received two doses, with the second dose administered a median of 3 days (interquartile range-IQR- 1 day) after the first one. Two patients received a single dose and another patient received 3 doses. Median number of cells per dose was 0.98 × 106 (IQR 0.50 × 106) AT-MSC/kg of recipient's body weight. Potential adverse effects related to cell infusion and clinical outcome were assessed. Additional parameters analyzed included changes in imaging, analytical and inflammatory parameters. FINDINGS: First dose of AT-MSC was administered at a median of 7 days (IQR 12 days) after mechanical ventilation. No adverse events were related to cell therapy. With a median follow-up of 16 days (IQR 9 days) after the first dose, clinical improvement was observed in nine patients (70%). Seven patients were extubated and discharged from ICU while four patients remained intubated (two with an improvement in their ventilatory and radiological parameters and two in stable condition). Two patients died (one due to massive gastrointestinal bleeding unrelated to MSC therapy). Treatment with AT-MSC was followed by a decrease in inflammatory parameters (reduction in C-reactive protein, IL-6, ferritin, LDH and d-dimer) as well as an increase in lymphocytes, particularly in those patients with clinical improvement. INTERPRETATION: Treatment with intravenous administration of AT-MSC in 13 severe COVID-19 pneumonia under mechanical ventilation in a small case series did not induce significant adverse events and was followed by clinical and biological improvement in most subjects. FUNDING: None.