Introduction to "Sixty Years of Modern Tsunami Science, Volume 2: Challenges".

Fifteen papers are included in this PAGEOPH topical issue "Sixty Years of Modern Tsunami Science, Volume 2: Challenges." The issue starts with a general introduction, and then briefly summarizes all contributions, first papers addressing general topics, and then articles grouped on a regional basis: Northern Pacific, Southeast Pacific, Southwest Pacific and Indonesia, and Mediterranean regions.

Survey on initial management of acute pancreatitis in Latin America.

OBJECTIVE: The population of Latin America harbors the highest incidence of gallstones and acute biliary pancreatitis, yet little is known about the initial management of acute pancreatitis in this large geographic region. PARTICIPANTS AND METHODS: We performed a post hoc analysis of responses from physicians based in Latin America to the international multidisciplinary survey on the initial management of acute pancreatitis. The questionnaire asked about management of patients during the first 72h after admission, related to fluid therapy, prescription of prophylactic antibiotics, feeding and nutrition, and timing of cholecystectomy. Adherence to clinical guidelines in this region was compared with the rest of the world. RESULTS: The survey was completed by 358 participants from 19 Latin American countries (median age, 39 years [33-47]; women, 27.1%). The proportion of participants in Latin America vs. the rest of the world who chose non-compliant options with clinical guidelines were: prescription of fluid therapy rate other than moderate (42.2% vs 34.3%, P=.02); prescription of prophylactic antibiotics for severe (10.6% vs 18.0%, P=.002), necrotizing (28.5% vs 36.9%, P=.008), or systemic inflammatory response syndrome-associated (21.2% vs 30.6%, P=.002) acute pancreatitis; not starting an oral diet to patients with oral tolerance (77.9% vs 71.1%, P=.02); and delayed cholecystectomy (16.2% vs 33.8%, P<.001). CONCLUSIONS: Surveyed physicians in Latin America are less likely to prescribe antibiotics and to delay cholecystectomy when managing patients in the initial phase of acute pancreatitis compared to physicians in the rest of the world. Feeding and nutrition appear to require the greatest improvement.

Pan American League of Associations for Rheumatology Guidelines for the Treatment of Takayasu Arteritis.

OBJECTIVE: To develop the first evidence-based Pan American League of Associations for Rheumatology (PANLAR) guidelines for the treatment of Takayasu arteritis (TAK). METHODS: A panel of vasculitis experts developed a series of clinically meaningful questions addressing the treatment of TAK patients in the PICO (population/intervention/comparator/outcome) format. A systematic literature review was performed by a team of methodologists. The evidence quality was assessed according to the GRADE (Grading of Recommendations/Assessment/Development/Evaluation) methodology. The panel of vasculitis experts voted each PICO question and made recommendations, which required ≥70% agreement among the voting members. RESULTS: Eleven recommendations were developed. Oral glucocorticoids are conditionally recommended for newly diagnosed and relapsing TAK patients. The addition of nontargeted synthetic immunosuppressants (e.g., methotrexate, leflunomide, azathioprine, or mycophenolate mofetil) is recommended for patients with newly diagnosed or relapsing disease that is not organ- or life-threatening. For organ- or life-threatening disease, we conditionally recommend tumor necrosis factor inhibitors (e.g., infliximab or adalimumab) or tocilizumab with consideration for short courses of cyclophosphamide as an alternative in case of restricted access to biologics. For patients relapsing despite nontargeted synthetic immunosuppressants, we conditionally recommend to switch from one nontargeted synthetic immunosuppressant to another or to add tumor necrosis factor inhibitors or tocilizumab. We conditionally recommend low-dose aspirin for patients with involvement of cranial or coronary arteries to prevent ischemic complications. We strongly recommend performing surgical vascular interventions during periods of remission whenever possible. CONCLUSION: The first PANLAR treatment guidelines for TAK provide evidence-based guidance for the treatment of TAK patients in Latin American countries.

Argentine Guidelines for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis in Postmenopausal Women and Men Aged 50 Years and Older.

OBJECTIVE: The aim of this study was to provide an evidence-based framework to guide health care professionals treating patients under glucocorticoid (GC) therapy and develop guidelines for the prevention and treatment of glucocorticoid-induced osteoporosis (GIO) in postmenopausal women and men aged ≥50 years. METHODS: An expert panel on bone diseases designed a series of clinically meaningful questions following the PICO (Population, Intervention, Comparator, and Outcome) structure. Using GRADE (Grading of Recommendations Assessment, Development, and Evaluation) methodology, we made a systematic literature review, extracted and summarized the effect estimates, and graded the quality of the evidence. The expert panel voted each PICO question and made recommendations after reaching an agreement of at least 70%. RESULTS: Seventeen recommendations (9 strong and 8 conditional) and 8 general principles were developed for postmenopausal women and men aged ≥50 years under GC treatment. Bone mineral density (BMD), occurrence of fragility fractures, probability of fracture at 10 years by Fracture Risk Assessment Tool, and other screening factors for low BMD are recommended for patient evaluation and stratification according to fragility fracture risk. The treatment of patients under GC therapy should include counseling on lifestyle habits and strict control of comorbidities. The goal of GIO treatment is the nonoccurrence of new fragility fractures as well as to increase or maintain BMD in certain clinical situations. This was considered for the therapeutic approach in different clinical scenarios. CONCLUSIONS: This GIO guideline provides evidence-based guidance for health care providers treating patients.

Validation and cultural adaptation of the qualisex questionnaire in patients with axial spondyloarthritis in Argentina.

The Qualisex questionnaire was developed and validated to assess sexuality in patients with rheumatoid arthritis. To the best of our knowledge, there is no instrument to evaluate sexuality in axial spondyloarthritis (axSpA). For this reason, the objective of this study was to validate and adapt the Qualisex questionnaire in axSpA and evaluate the impact of the disease on patients' sexuality. Cross sectional study. Consecutive patients, with ≥ 21 years of age, diagnosed with axSpA according to ASAS'09 criteria were included. Sexual health was assessed using the Qualisex questionnaire. The original version was translated to Spanish and adapted to axSpA. Internal consistency, and test re-test reliability was calculated. Criterion and construct validity were assessed by comparing the Qualisex with parameters of disease activity functional capacity and quality of life. 61 patients were invited to participate in the study, 11 of whom refused. 50 patients were included; 40 (80%) were males, with a median age of 47 years (IQR 21-72) and a median disease duration of 13 years (IQR 1-46). Reproducibility was excellent with an ICC of 0.99 (95% CI 0.65-1). The Qualisex had a good correlation with different disease evaluation parameters. The Qualisex was significantly higher among women (5.4 in women vs. 2.5 in men, p = 0.02), unemployed (4.7 in unemployed vs. 2.3 in employed, p = 0.01), in patients with higher disease activity (4.2 in active patients vs. 1.6 in inactive patients, p = 0.01), and it was lower in patients receiving biologic therapy (BT) (1.9 with BT vs. 3.8 without BT, p = 0.01). Multivariable analysis showed that female sex, longer disease duration and higher disease activity were independently associated with a greater impact on sexuality. The Qualisex adapted to axSpA is a valid and reliable questionnaire. Female axSpA patients, those with longer disease duration and higher disease activity presented a worse sexual life.

Latin American consensus on diagnosis of gastroesophageal reflux disease.

BACKGROUND: Diagnosing gastroesophageal reflux disease (GERD) can be challenging given varying symptom presentations, and complex multifactorial pathophysiology. The gold standard for GERD diagnosis is esophageal acid exposure time (AET) measured by pH-metry. A variety of additional diagnostic tools are available. The goal of this consensus was to assess the individual merits of GERD diagnostic tools based on current evidence, and provide consensus recommendations following discussion and voting by experts. METHODS: This consensus was developed by 15 experts from nine countries, based on a systematic search of the literature, using GRADE (grading of recommendations, assessment, development and evaluation) methodology to assess the quality and strength of the evidence, and provide recommendations regarding the diagnostic utility of different GERD diagnosis tools, using AET as the reference standard. KEY RESULTS: A proton pump inhibitor (PPI) trial is appropriate for patients with heartburn and no alarm symptoms, but nor for patients with regurgitation, chest pain, or extraesophageal presentations. Severe erosive esophagitis and abnormal reflux monitoring off PPI are clearly indicative of GERD. Esophagram, esophageal biopsies, laryngoscopy, and pharyngeal pH monitoring are not recommended to diagnose GERD. Patients with PPI-refractory symptoms and normal endoscopy require reflux monitoring by pH or pH-impedance to confirm or exclude GERD, and identify treatment failure mechanisms. GERD confounders need to be considered in some patients, pH-impedance can identify supragrastric belching, impedance-manometry can diagnose rumination. CONCLUSIONS: Erosive esophagitis on endoscopy and abnormal pH or pH-impedance monitoring are the most appropriate methods to establish a diagnosis of GERD. Other tools may add useful complementary information.

Effectiveness of methotrexate and leflunomide as corticoid-sparing drugs in patients with polymyalgia rheumatica.

Objectives: The need for glucocorticoid-sparing drugs (GCSD) remains an important issue and is an unmet need in the treatment of polymyalgia rheumatica (PMR). We therefore aimed to assess the effectiveness and safety of methotrexate (MTX) and of leflunomide (LEF) in daily clinical practice in PMR patients from Argentina. Methods: A multicentre and observational study (medical records review) of PMR patients seen between 2007 and 2023, who had at least three months of follow-up after starting a GCSD, either MTX or LEF, was performed. Results are expressed as medians and interquartile ranges [25th-75th (IQR)] for continuous variables and percentages for categorical ones. The two treatment groups were compared using χ2 test for categorical variables, Mann-Whitney U test for continuous variables and the log-rank test for time-to-event data. Crude and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using logistic regression. In all cases, a p-value <0.05 was considered statistically significant. Results: One-hundred and eighty-six patients (79% female) with a median age of 72 years (IQR, 65-77 years) were included. One-hundred and forty-three patients (77%) were prescribed MTX (15, IQR 10-15) and 43 (23%) LEF (20 mg, fixed dose). Flare-ups (relapses and recurrences) occurred in 13 patients (7%) and were comparable between both groups. Persistent GCSD intake was observed in 145 patients (78%). Glucocorticoid (GC) withdrawal was achieved in 67 of these 145 patients (46%) and this occurred more frequently in the LEF group (P = 0.001). Furthermore, time until prednisone discontinuation was shorter in the LEF-treated patients (4.7 months, IQR 3-20 on LEF versus 31.8 months, IQR 10-82 on MTX, P = 0.000). Remission was found more frequently in the LEF group (P = 0.003). In the multivariate analysis, the probability of remission was higher with LEF therapy (P = 0.010) and this finding persisted in the subgroup analysis who were followed up < 40 months (OR 3.12, 95% CI = 1.30-7.47, P = 0.011). Conclusions: This study demonstrated the clinical effectiveness of LEF and even its superiority in achieving remission when compared with MTX as GCSD in PMR patients. Further research is needed to support these findings.

A new 3D method for measuring cranio-facial relationships with cone beam computed tomography (CBCT).

OBJECTIVES: CBCT systems, with their high precision 3D reconstructions, 1:1 images and accuracy in locating cephalometric landmarks, allows us to evaluate measurements from craniofacial structures, so enabling us to replace the anthropometric methods or bidimensional methods used until now. The aims are to analyse cranio-facial relationships in a sample of patients who had previously undergone a CBCT and create a new 3D cephalometric method for assessing and measuring patients. STUDY DESIGN: 90 patients who had a CBCT (i-Cat®) as a diagnostic register were selected. 12 cephalometric landmarks on the three spatial planes (X,Y,Z) were defined and 21 linear measurements were established. Using these measurements, 7 triangles were described and analysed. With the sides of the triangles: (CdR-Me-CdL); (FzR-Me-FzL); (GoR-N-GoL); and the Gl-Me distance, the ratios between them were analysed. In addition, 4 triangles in the mandible were measured (body: GoR-DB-Me and GoL-DB-Me and ramus: KrR-CdR-GoR and KrL-CdL-GoL). RESULTS: When analyzing the sides of the CdR-Me-CdL triangle, it was found that the 69.33% of the patients could be considered symmetric. Regarding the ratios between the sides of the following triangles: CdR-Me-CdL, FzR-Me-FzL, GoR-N-GoL and the Gl-Me distance, it was found that almost all ratios were close to 1:1 except between the CdR-CdL side with respect the rest of the sides. With regard to the ratios of the 4 triangles of the mandible, it was found that the most symmetrical relationships were those corresponding to the sides of the body of the mandible and the most asymmetrical ones were those corresponding to the base of such triangles. CONCLUSIONS: A new method for assessing cranio-facial relationships using CBCT has been established. It could be used for diverse purposes including diagnosis and treatment planning.

Study between anb angle and Wits appraisal in cone beam computed tomography (CBCT).

OBJECTIVES: To analyse the ANB and Wits values and to study correlations between those two measurements and other measurements in diagnosing the anteroposterior maxilo-mandibular relationship with CBCT. STUDY DESIGN: Ninety patients who had previously a CBCT (i-CAT®) as a diagnostic register were selected. A 3D cephalometry was designed using one software package, InVivo5®. This cephalometry included 3 planes of reference, 3 angle measurements and 1 linear measurement. The means and standard deviations of the mean of each measurement were assessed. After that, a Pearson's correlation coefficient has been performed to analyse the significance of each relationship. RESULTS: When classifying the sample according to the anteroposterior relationship, the values obtained of ANB (Class I: 53%; Class II: 37%; Class III: 10%) and Wits (Class I: 35%; Class II: 56%; Class III: 9%) did not coincide, except for the Class III group. However, of the patients classified differently (Class I and Class II patients) by ANB and Wits, a high percentage of individuals (n=22; 49%), had a mesofacial pattern with a mandibular plane angle within normal values. A correlation has been found between ANB and Wits (r=0,262), occlusal plane angle and ANB (r=0,426), and mandibular plane angle and Wits (r=0,242). No correlation was found between either Wits or ANB in relation with the age of the individuals. CONCLUSIONS: ANB and Wits must be included in 3D cephalometric analyses as both are necessary to undertake a more accurate diagnosis of the maxillo-mandibular relationship of the patients.

Patient perspectives on long-term outcomes in rheumatoid arthritis. A qualitative study from the OMERACT patient outcomes in longitudinal studies working group.

OBJECTIVES: To identify patient-centered domains with long-term relevance to people with rheumatoid arthritis (RA). METHODS: We conducted semi-structured individual cognitive interviews of patients with RA with at least five years of disease duration, sampled from five different countries (United States, Italy, Spain, Mexico, and Argentina). Participants were encouraged to discuss their long-term concerns regarding RA. Interviews were transcribed and analyzed using qualitative content analysis within a constructivist/interpretivist theoretical framework. RESULTS: Twenty-eight participants were interviewed, 24 were women. Six main themes, representing important aspects of the daily life of people with RA were generated: (i) Living with symptoms and functional limitations, (ii) Lack of participation, (iii) Partner and family issues, (iv) Risk of damage to vital organs, (v) Coping strategies, and (vi) Healthcare concerns, primarily expressed by participants from non-European countries lacking universal healthcare coverage. In addition, participants discussed the importance of contextual factors and how they impact long-term outcomes. These included attitudes towards disease, social support, or financial burdens. CONCLUSIONS: We identified six domains of importance to people with RA that are seldom measured in longitudinal registries and should be considered in patient-centered longitudinal studies.

Safety of COVID-19 vaccines during pregnancy: A systematic review and meta-analysis.

BACKGROUND: Assessment of COVID-19 vaccines safety during pregnancy is urgently needed. METHODS: We conducted a systematic review and meta-analysis to evaluate the safety of COVID-19 vaccines, including their components and technological platforms used in other vaccines during pregnancy and animal studies to complement direct evidence. We searched literature databases from its inception to September 2021 without language restriction, COVID-19 vaccine websites, and reference lists of other systematic reviews and the included studies. Pairs of reviewers independently selected, data extracted, and assessed the risk of bias of the studies. Discrepancies were resolved by consensus. (PROSPERO CRD42021234185). RESULTS: We retrieved 8,837 records from the literature search; 71 studies were included, involving 17,719,495 pregnant persons and 389 pregnant animals. Most studies (94%) were conducted in high-income countries, were cohort studies (51%), and 15% were classified as high risk of bias. We identified nine COVID-19 vaccine studies, seven involving 309,164 pregnant persons, mostly exposed to mRNA vaccines. Among non-COVID-19 vaccines, the most frequent exposures were AS03 and aluminum-based adjuvants. A meta-analysis of studies that adjusted for potential confounders showed no association with adverse outcomes, regardless of the vaccine or the trimester of vaccination. Neither the reported rates of adverse pregnancy outcomes nor reactogenicity exceeded expected background rates, which was the case for ASO3- or aluminum-adjuvanted non-COVID-19 vaccines in the proportion meta-analyses of uncontrolled studies/arms. The only exception was postpartum hemorrhage after COVID-19 vaccination (10.40%; 95% CI: 6.49-15.10%), reported by two studies; however, the comparison with non-exposed pregnant persons, available for one study, found non-statistically significant differences (adjusted OR 1.09; 95% CI 0.56-2.12). Animal studies showed consistent results with studies in pregnant persons. CONCLUSION: We found no safety concerns for currently administered COVID-19 vaccines during pregnancy. Additional experimental and real-world evidence could enhance vaccination coverage. Robust safety data for non-mRNA-based COVID-19 vaccines are still needed.

Pan American League of Associations for Rheumatology Guidelines for the treatment of ANCA-associated vasculitis.

Considerable variability exists in the way health-care providers treat patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis in Latin America. The most frequently used treatments for ANCA-associated vasculitis are cyclophosphamide and prolonged glucocorticoid tapers; however, randomised controlled trials conducted over the past 30 years have led to the development of several evidence-based treatment alternatives for these patients. Latin America faces socioeconomic challenges that affect access to care, and the use of certain costly medications with proven efficacy ANCA-associated vasculitis is often restricted. For these reasons, the Pan American League of Associations for Rheumatology developed the first ANCA-associated vasculitis treatment guidelines tailored for Latin America. A panel of local vasculitis experts generated clinically meaningful questions related to the treatment of ANCA-associated vasculitis using the Population, Intervention, Comparator, and Outcome (PICO) format. Following the Grading of Recommendations Assessment, Development, and Evaluation methodology, a team of methodologists conducted a systematic literature review. The panel of vasculitis experts voted on each PICO question and made recommendations, which required at least 70% agreement among the voting members. 21 recommendations and two expert opinion statements for the treatment of ANCA-associated vasculitis were developed, considering the current evidence and the socioeconomic characteristics of the region. These recommendations include guidance for the use of glucocorticoids, non-glucocorticoid immunosuppressants, and plasma exchange.

A study on the reproducibility of cephalometric landmarks when undertaking a three-dimensional (3D) cephalometric analysis.

OBJECTIVES: Cone Beam Computerized Tomography (CBCT) allows the possibility of modifying some of the diagnostic tools used in orthodontics, such as cephalometry. The first step must be to study the characteristics of these devices in terms of accuracy and reliability of the most commonly used landmarks. The aims were 1- To assess intra and inter-observer reliability in the location of anatomical landmarks belonging to hard tissues of the skull in images taken with a CBCT device, 2- To determine which of those landmarks are more vs. less reliable and 3- To introduce planes of reference so as to create cephalometric analyses appropriated to the 3D reality. STUDY DESIGN: Fifteen patients who had a CBCT (i-CAT) as a diagnostic register were selected. To assess the reproducibility on landmark location and the differences in the measurements of two observers at different times, 41 landmarks were defined on the three spatial axes (X,Y,Z) and located. 3.690 measurements were taken and, as each determination has 3 coordinates, 11.070 data were processed with SPSS statistical package. To discover the reproducibility of the method on landmark location, an ANOVA was undertaken using two variation factors: time (t1, t2 and t3) and observer (Ob1 and Ob2) for each axis (X, Y and Z) and landmark. The order of the CBCT scans submitted to the observers (Ob1, Ob2) at t1, t2, and t3, were different and randomly allocated. Multiple comparisons were undertaken using the Bonferroni test. The intra- and inter-examiner ICC's were calculated. RESULTS: Intra- and interexaminer reliability was high, both being ICC ≥ 0.99, with the best frequency on axis Z. CONCLUSIONS: The most reliable landmarks were: Nasion, Sella, Basion, left Porion, point A, anterior nasal spine, Pogonion, Gnathion, Menton, frontozygomatic sutures, first lower molars and upper and lower incisors. Those with less reliability were the supraorbitals, right zygion and posterior nasal spine.

Discriminating the occurrence of inundation in tsunami early warning with one-dimensional convolutional neural networks.

Tsunamis are natural phenomena that, although occasional, can have large impacts on coastal environments and settlements, especially in terms of loss of life. An accurate, detailed and timely assessment of the hazard is essential as input for mitigation strategies both in the long term and during emergencies. This goal is compounded by the high computational cost of simulating an adequate number of scenarios to make robust assessments. To reduce this handicap, alternative methods could be used. Here, an enhanced method for estimating tsunami time series using a one-dimensional convolutional neural network model (1D CNN) is considered. While the use of deep learning for this problem is not new, most of existing research has focused on assessing the capability of a network to reproduce inundation metrics extrema. However, for the context of Tsunami Early Warning, it is equally relevant to assess whether the networks can accurately predict whether inundation would occur or not, and its time series if it does. Hence, a set of 6776 scenarios with magnitudes in the range [Formula: see text] 8.0-9.2 were used to design several 1D CNN models at two bays that have different hydrodynamic behavior, that would use as input inexpensive low-resolution numerical modeling of tsunami propagation to predict inundation time series at pinpoint locations. In addition, different configuration parameters were also analyzed to outline a methodology for model testing and design, that could be applied elsewhere. The results show that the network models are capable of reproducing inundation time series well, either for small or large flow depths, but also when no inundation was forecast, with minimal instances of false alarms or missed alarms. To further assess the performance, the model was tested with two past tsunamis and compared with actual inundation metrics. The results obtained are promising, and the proposed model could become a reliable alternative for the calculation of tsunami intensity measures in a faster than real time manner. This could complement existing early warning system, by means of an approximate and fast procedure that could allow simulating a larger number of scenarios within the always restricting time frame of tsunami emergencies.

Pan American League of Associations for Rheumatology guidelines for the treatment of giant cell arteritis.

Considerable variability exists in the way that health-care providers treat patients with giant cell arteritis in Latin America, with patients commonly exposed to excessive amounts of glucocorticoids. In addition, large health disparities prevail in this region due to socioeconomic factors, which influence access to care, including biological treatments. For these reasons, the Pan American League of Associations for Rheumatology developed the first evidence-based giant cell arteritis treatment guidelines tailored for Latin America. A panel of vasculitis experts from Mexico, Colombia, Peru, Brazil, and Argentina generated clinically meaningful questions related to the treatment of giant cell arteritis in the population, intervention, comparator, and outcome (PICO) format. Following the grading of recommendations, assessment, development, and evaluation methodology, a team of methodologists did a systematic literature search, extracted and summarised the effects of the interventions, and graded the quality of the evidence. The panel of vasculitis experts voted on each PICO question and made recommendations, which required at least 70% agreement among the voting members to be included in the guidelines. Nine recommendations and one expert opinion statement for the treatment of giant cell arteritis were developed considering the most up-to-date evidence and the socioeconomic characteristics of Latin America. These recommendations include guidance for the use of glucocorticoids, tocilizumab, methotrexate, and aspirin for patients with giant cell arteritis.

Outcomes Reported in Prospective Long-Term Observational Studies and Registries of Patients With Rheumatoid Arthritis Worldwide: An Outcome Measures in Rheumatology Systematic Review.

OBJECTIVE: Prospective long-term observational studies (LOS) in rheumatoid arthritis (RA) lack a core set of universally collected outcome measures, particularly patient-centered outcomes, precluding accurate comparisons across studies. Our aim was to identify long-term outcome measures collected and reported in these studies. METHODS: We conducted a systematic review of registries and LOS of patients with RA, searching in ClinicalTrials.gov, the Agency for Healthcare Research and Quality Registry of Patient Registries, and Google Scholar. The names and acronyms of registries and LOS were further searched in the Medline and Embase databases to retrieve published articles. Two independent reviewers undertook data collection, quality appraisal, and data extraction. RESULTS: We identified 88 registries/LOS that met our eligibility criteria. These were divided into 2 groups: disease-based (52 [59%]) and therapy-based (36 [41%]). Methodologic and reporting standards varied across the eligible studies. For clinical outcomes, disease activity was recorded in 88 (100%) of all LOS/registries. The most commonly reported measure (86 [98%]) was the composite outcome Disease Activity Score using 28 joints. Of the patient-centered outcomes collected, physical functioning was most frequently reported (75 [85%]) with the Health Assessment Questionnaire (75 [85%]) as the most commonly used instrument within this domain. Other domains of patient-centered outcomes were comparatively infrequently recorded: mental (29 [33%]), social (20 [23%]), and health-related quality of life (37 [42%]). CONCLUSION: Most registries/LOS collect measures of disease activity and physical function. However, there is substantial heterogeneity in the collection of relevant patient-centered outcomes that measure symptom burden and mental and social ramifications of RA.

COVID-19 and pregnancy: An umbrella review of clinical presentation, vertical transmission, and maternal and perinatal outcomes.

BACKGROUND: We conducted an overview of systematic reviews (SRs) summarizing the best evidence regarding the effect of COVID-19 on maternal and child health following Cochrane methods and PRISMA statement for reporting (PROSPERO-CRD42020208783). METHODS: We searched literature databases and COVID-19 research websites from January to October 2020. We selected relevant SRs reporting adequate search strategy, data synthesis, risk of bias assessment, and/or individual description of included studies describing COVID-19 and pregnancy outcomes. Pair of reviewers independently selected studies through COVIDENCE web-software, performed the data extraction, and assessed its quality through the AMSTAR-2 tool. Discrepancies were resolved by consensus. Each SR's results were synthesized and for the most recent, relevant, comprehensive, and with the highest quality, by predefined criteria, we presented GRADE evidence tables. RESULTS: We included 66 SRs of observational studies out of 608 references retrieved and most (61/66) had "critically low" overall quality. We found a relatively low degree of primary study overlap across SRs. The most frequent COVID-19 clinical findings during pregnancy were fever (28-100%), mild respiratory symptoms (20-79%), raised C-reactive protein (28-96%), lymphopenia (34-80%), and pneumonia signs in diagnostic imaging (7-99%). The most frequent maternal outcomes were C-section (23-96%) and preterm delivery (14-64%). Most of their babies were asymptomatic (16-93%) or presented fever (0-50%), low birth weight (5-43%) or preterm delivery (2-69%). The odds ratio (OR) of receiving invasive ventilation for COVID-19 versus non-COVID-19 pregnant women was 1.88 (95% Confidence Interval [CI] 1.36-2.60) and the OR that their babies were admitted to neonatal intensive care unit was 3.13 (95%CI 2.05-4.78). The risk of congenital transmission or via breast milk was estimated to be low, but close contacts may carry risks. CONCLUSION: This comprehensive overview supports that pregnant women with COVID-19 may be at increased risk of adverse pregnancy and birth outcomes and low risk of congenital transmission.

Safety of COVID-19 vaccines, their components or their platforms for pregnant women: A rapid review.

BACKGROUND: Pregnant women with COVID-19 are at an increased risk of severe COVID-19 illness as well as adverse pregnancy and birth outcomes. Many countries are vaccinating or considering vaccinating pregnant women with limited available data about the safety of this strategy. Early identification of safety concerns of COVID-19 vaccines, including their components, or their technological platforms is therefore urgently needed. METHODS: We conducted a rapid systematic review, as the first phase of an ongoing full systematic review, to evaluate the safety of COVID-19 vaccines in pregnant women, including their components, and their technological platforms (whole virus, protein, viral vector or nucleic acid) used in other vaccines, following the Cochrane methods and the PRISMA statement for reporting (PROSPERO-CRD42021234185).We searched literature databases, COVID-19 and pregnancy registries from inception February 2021 without time or language restriction and explored the reference lists of relevant systematic reviews retrieved. We selected studies of any methodological design that included at least 50 pregnant women or pregnant animals exposed to the vaccines that were selected for review by the COVAX MIWG in August 2020 or their components or platforms included in the COVID-19 vaccines, and evaluated adverse events during pregnancy and the neonatal period.Pairs of reviewers independently selected studies through the COVIDENCE web software and performed the data extraction through a previously piloted online extraction form. Discrepancies were resolved by consensus. RESULTS: We identified 6768 records, 256 potentially eligible studies were assessed by full-text, and 37 clinical and non-clinical studies (38 reports, involving 2,397,715 pregnant women and 56 pregnant animals) and 12 pregnancy registries were included.Most studies (89%) were conducted in high-income countries. The most frequent study design was cohort studies (n=21), followed by surveillance studies, randomized controlled trials, and registry analyses. Most studies (76%) allowed comparisons between vaccinated and unvaccinated pregnant women (n=25) or animals (n=3) and reported exposures during the three trimesters of pregnancy.The most frequent exposure was to AS03 adjuvant in the context of A/H1N1 pandemic influenza vaccines (n=24), followed by aluminum-based adjuvants (n=11). Aluminum phosphate was used in Respiratory Syncytial Virus Fusion candidate vaccines (n=3) and Tdap vaccines (n=3). Different aluminum-based adjuvants were used in hepatitis vaccines. The replication-deficient simian adenovirus ChAdOx1 was used for a Rift Valley fever vaccine. Only one study reported exposure to messenger RNA (mRNA) COVID-19 vaccines that also used lipid nanoparticles. Except for one preliminary report about A/H1N1 influenza vaccination (adjuvant AS03) - corrected by the authors in a more thorough analysis, all studies concluded that there were no safety concerns. CONCLUSION: This rapid review found no evidence of pregnancy-associated safety concerns of COVID-19 vaccines that were selected for review by the COVAX MIWG or of their components or platforms when used in other vaccines. However, the need for further data on several vaccine platforms and components is warranted given their novelty. Our findings support current WHO guidelines recommending that pregnant women may consider receiving COVID-19 vaccines, particularly if they are at high risk of exposure or have comorbidities that enhance the risk of severe disease.

Safety of components and platforms of COVID-19 vaccines considered for use in pregnancy: A rapid review.

BACKGROUND: Rapid assessment of COVID-19 vaccine safety during pregnancy is urgently needed. METHODS: We conducted a rapid systematic review, to evaluate the safety of COVID-19 vaccines selected by the COVID-19 Vaccines Global Access-Maternal Immunization Working Group in August 2020, including their components and their technological platforms used in other vaccines for pregnant persons. We searched literature databases, COVID-19 vaccine pregnancy registries, and explored reference lists from the inception date to February 2021 without language restriction. Pairs of reviewers independently selected studies through COVIDENCE, and performed the data extraction and the risk of bias assessment. Discrepancies were resolved by consensus. Registered on PROSPERO (CRD42021234185). RESULTS: We retrieved 6757 records and 12 COVID-19 pregnancy registries from the search strategy; 38 clinical and non-clinical studies (involving 2,398,855 pregnant persons and 56 pregnant animals) were included. Most studies (89%) were conducted in high-income countries and were cohort studies (57%). Most studies (76%) compared vaccine exposures with no exposure during the three trimesters of pregnancy. The most frequent exposure was to AS03 adjuvant, in the context of A/H1N1 pandemic influenza vaccines, (n = 24) and aluminum-based adjuvants (n = 11). Only one study reported exposure to messenger RNA in lipid nanoparticles COVID-19 vaccines. Except for one preliminary report about A/H1N1 influenza vaccination (adjuvant AS03), corrected by the authors in a more thorough analysis, all studies concluded that there were no safety concerns. CONCLUSION: This rapid review found no evidence of pregnancy-associated safety concerns of COVID-19 vaccines or of their components or platforms when used in other vaccines. However, the need for further data on several vaccine platforms and components is warranted, given their novelty. Our findings support current WHO guidelines recommending that pregnant persons may consider receiving COVID-19 vaccines, particularly if they are at high risk of exposure or have comorbidities that enhance the risk of severe disease.

Utilization of biologic disease-modifying anti-rheumatic drugs in patients with rheumatoid arthritis and cancer.

INTRODUCTION: Biologic disease-modifying anti-rheumatic drugs (bDMARDs) interfere with the immune system and could theoretically increase risk of malignancies. However, recent evidence has not substantiated such concerns and physicians are less reluctant in treating patients with underlying cancer with such bDMARDs. We aimed to understand the current utilization patterns of bDMARDs for the treatment of rheumatoid arthritis (RA) in cancer patients. METHODS: We performed a retrospective cohort study of patients with prevalent RA and cancer initially seen at MD Anderson Cancer Center between 2002 and 2014. A cohort of cancer patients was identified from the tumor registry, and patients with RA were identified through ICD-9 codes, followed by review of electronic medical records. We included patients 18 years and older, with a cancer diagnosis, and a diagnosis of RA by a rheumatologist. Patients were followed until 2016. RESULTS: We identified 431 patients with RA and cancer that met our inclusion criteria. Overall, 111 (26%) received bDMARDs after their cancer diagnosis; of these, 60 (54%) had received bDMARDs prior to their cancer diagnosis and continued to receive this therapy following their diagnosis. Thirteen (22%) switched to a different bDMARD, and the rest continued to receive the same agent after their cancer diagnosis. Of all patients on a bDMARD, 91 (82%) received tumor necrosis factor inhibitors (TNFi). CONCLUSIONS: The treatment landscape of patients with a history of cancer and RA is changing. Future studies evaluating the safety of bDMARDs in patients with a recent history of cancer or with active cancer are needed. Part of the data of this project was presented as a poster at the 2016 American College of Rheumatology annual meeting. Zamora NV, Siddhanamatha H, Barbo A, Tayar J, Lin H, Suarez-Almazor M. Utilization of Biologic Therapy in Patients with Rheumatoid Arthritis and Cancer [abstract].Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/utilization-of-biologic-therapy-in-patients-with-rheumatoid-arthritis-and-cancer/. Accessed September 30, 2019. Key Points • One in four patients with RA and concomitant cancer received bDMARDs, including TNFi, after their cancer diagnosis, at our institution. • Half of the patients with RA and cancer who received bDMARDs had initiated therapy prior to the cancer diagnosis, continuing thereafter.