Follow-Up Study of 17-ß Estradiol, Prolactin and Progesterone with the Kinetics and Prevalence of T. gondii Infection in Pregnant Women.

Toxoplasmosis is an infection caused by the parasite Toxoplasma gondii. One-third of the world's population has come into contact with this parasite. In Mexico, the prevalence is between 15% and 50% in the general population and 34.9% in women with high-risk pregnancies. In pregnancy, the highest incidence of infection occurs in the third trimester and fetal damage is inversely proportional to gestational age. Maternal hormones play a fundamental role in the immune response. There are very few studies, with controversial results, on the levels of increased hormones and their relationship to the kinetics of T. gondii infections during pregnancy. The aim was to determine the serum levels of 17-ß estradiol, prolactin, and progesterone, and their association with anti-T. gondii antibodies' kinetics in pregnancy. Fifty-two pregnant patients were studied. A questionnaire with sociodemographic and clinical aspects was used. Afterward, 10 mL of venous blood was collected by venipuncture every trimester. The concentrations of 17-ß estradiol, progesterone, and prolactin were measured, using the ELISA method. In addition, anti-Toxoplasma IgG and IgM antibodies were also determined in the first, second, and third trimester. The prevalence of anti-Toxoplasma IgG antibodies was 26.92% in the first and second trimester and 32.7% in the third trimester. In seropositive women, 17-ß estradiol increased in the second and third trimesters of pregnancy. Progesterone increased significantly p < 0.039 in the third trimester in these women, while prolactin increased in the second trimester with a statistical significance of p < 0.021. In addition, 17-ß estradiol, progesterone, and prolactin are associated with T. gondii infection during pregnancy. New studies are necessary to clarify the specific mechanisms of immune response related to these hormones during pregnancy.

A Rare Case of Biloma after Ascending Cholangitis and Endoscopic Retrograde Cholangiopancreatography.

Introduction: Biloma is an uncommon form of liver abscess composed of bile usually associated with procedures of the biliary tree and gallbladder. Cholangitis can be acute or chronic, can result in partial or complete obstruction of the flow of bile. The infection of the bile is so common, that positive blood cultures are highly characteristic. In the case of a suppurative cholangitis with signs of sepsis treatment alone with antibiotics is usually not sufficient to achieve medical remission. Multiple hepatic abscesses are often present, and the mortality approaches 100% unless prompt endoscopic or surgical relief of the obstruction and drainage of infected bile are carried out. Endoscopic retrograde cholangiopancreatography ERCP with endoscopic sphincterotomy is the preferred initial procedure for both establishing a definitive diagnosis and providing effective therapy. Case description: We present the case of a 69-year-old female patient with complex chronic comorbidities who presented with acute cholangitis initially managed with endoscopically inserted stent and later complicated by sepsis and biloma formation. The bile was drained, and it showed an infection with Candida spp. requiring antifungal therapy. Conclusions: The failure to perform sphincterotomy in patients with suppurative cholangitis can contribute to the backflow of bile and worse outcomes. LEARNING POINTS: Biloma formation is a rare complication of biliary duct procedures and diseases such as cholangitis. A prompt identification of signs of complications in patients with disease of the biliary ducts is key in preventing clinical deterioration.Sphincterotomy is vital in the management of ascending cholangitis, as it prevents backflow of bile into the intrahepatic biliary system.The presence of multiple comorbidities in complex cases can become an obstacle to optimal management and drainage of septic bile.

Optoelectronic Response to the Fluor Ion Bond on 4-(4,4,5,5-Tetramethyl-1,3,2-dioxoborolan-2-yl)benzaldehyde.

Boronate esters are a class of compounds containing a boron atom bonded to two oxygen atoms in an ester group, often being used as precursors in the synthesis of other materials. The characterization of the structure and properties of esters is usually carried out by UV-visible, infrared, and nuclear magnetic resonance (NMR) spectroscopic techniques. With the aim to better understand our experimental data, in this article, the density functional theory (DFT) is used to analyze the UV-visible and infrared spectra, as well as the isotropic shielding and chemical shifts of the hydrogen atoms 1H, carbon 13C and boron 11B in the compound 4-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)benzaldehyde. Furthermore, this study considers the change in its electronic and spectroscopic properties of this particular ester, when its boron atom is coordinated with a fluoride anion. The calculations were carried out using the LSDA and B3LYP functionals in Gaussian-16, and PBE in CASTEP. The results show that the B3LYP functional gives the best approximation to the experimental data. The formation of a coordinated covalent B-F bond highlights the remarkable sensitivity of the NMR chemical shifts of carbon, oxygen, and boron atoms and their surroundings. Furthermore, this bond also highlights the changes in the electron transitions bands n → π* and π → π* during the absorption and emission of a photon in the UV-vis, and in the stretching bands of the C=C bonds, and bending of BO2 in the infrared spectrum. This study not only contributes to the understanding of the properties of boronate esters but also provides important information on the interactions and responses optoelectronic of the compound when is bonded to a fluorine atom.

Characterization of a Trispecific PD-L1 Blocking Antibody That Exhibits EGFR-Conditional 4-1BB Agonist Activity.

Immune checkpoint blockade has changed the treatment paradigm for advanced solid tumors, but the overall response rates are still limited. The combination of checkpoint blockade with anti-4-1BB antibodies to stimulate tumor-infiltrating T cells has shown anti-tumor activity in human trials. However, the further clinical development of these antibodies has been hampered by significant off-tumor toxicities. Here, we generated an anti-4-1BB/EGFR/PD-L1 trispecific antibody consisting of a triple-targeting tandem trimerbody (TT) fused to an engineered silent Fc region. This antibody (IgTT-4E1-S) was designed to combine the blockade of the PD-L1/PD-1 axis with conditional 4-1BB costimulation specifically confined to the tumor microenvironment (TME). The antibody demonstrated simultaneous binding to purified EGFR, PD-L1, and 4-1BB in solution, effective blockade of the PD-L1/PD1 interaction, and potent 4-1BB-mediated costimulation, but only in the presence of EGFR-expressing cells. These results demonstrate the feasibility of IgTT-4E1-S specifically blocking the PD-L1/PD-1 axis and inducing EGFR-conditional 4-1BB agonist activity.

Characteristics and rates of infection by HIV in people receiving non-occupational post-exposure prophylaxis (nPEP) against HIV.

INTRODUCTION/OBJECTIVES: The use of non-occupational post-exposure prophylaxis (nPEP) emerges as a strategic intervention to reduce HIV infection risk following sexual encounters in our setting. Notwithstanding, there is a scarcity of contemporary data regarding adherence to this treatment, its effectiveness and tolerance. Our study aims to delve into these factors among individuals who have resorted to nPEP after high-risk sexual encounters. METHODS: We conducted a retrospective observational study of cases administered nPEP for HIV from 1 January 2018 to 31 December 2021 at a tertiary hospital in Madrid. The study included all adults over 18 years who sought care at the emergency department of the Fundación Jiménez Díaz Hospital following a risky sexual encounter and were subsequently recommended HIV nPEP treatment. RESULTS: 878 individuals received nPEP for HIV and underwent initial serological tests. Of these, 621 had comprehensive follow-ups. The prescribed regimen for all was raltegravir (RAL) 1200 mg combined with tenofovir/emtricitabine (TDF/FTC) 245/200 mg daily for 28 days. The study revealed a 1.1% rate (n=10) of previously undetected infection and a 0.16% (n=1) failure rate of nPEP. Regarding regimen tolerability, 5.6% (n=35) experienced symptoms linked to the treatment, yet none necessitated discontinuation of the regimen. On the contrary, six per cent (n=53) reported symptoms consistent with an STI during one of the medical visits; specifically, 4.4% had urethritis, and 1.6% had proctitis. CONCLUSION: nPEP with RAL/TDF/FTC demonstrates high efficacy and safety, contingent on proper adherence. There is an observed increase in STI prevalence in this cohort, with nearly half of the participants not engaging in appropriate follow-up after initiating nPEP.

Body Awareness as a Protective Factor against Suicidal Orientations in College Students.

In this study, binary logistic regression and linear regression analyses were used to examine the relationship between interoceptive body awareness and suicidal orientation among Colombian university students. Additionally, the bootstrap technique was employed to resample and estimate the distribution of the data. The results support the idea that greater interoceptive awareness may protect against suicidal orientation by improving emotional regulation. An inverse relationship was found between interoceptive awareness and suicidal ideation. These findings align with previous literature emphasizing the importance of body awareness for emotional well-being. Further longitudinal research is needed to explore this relationship more deeply.

Clinical Comparative Study of Shade Measurement Using Two Methods: Dental Guides and Spectrophotometry.

Tooth color is a determining factor in the fabrication of dental prostheses. The aim of the present study is to compare two measurement methods used in the field of dentistry: dental guides and spectrophotometry. A total of 2768 natural teeth were measured using the Vita Classical and Vita 3D-Master dental guides (Vita-Zahnfabrik, Bad Säckingen, Germany), as well as a Vita Easyshade Compact spectrophotometer (Vita-Zahnfabrik). The measurements were carried out by one operator under suitable illumination conditions at 5500 degrees Kelvin. The obtained results show that the measurements obtained with the Vita Classical dental guide classifies teeth into the A-B categories, while the spectrophotometer preferentially classifies teeth into the B-C categories. The correlation coefficients obtained with the dental guides ranged from -0.32 to -0.39 (p < 0.01), while those for the spectrophotometer ranged from -0.35 to -0.55 (p < 0.01). Therefore, we can conclude that the spectrophotometer is more reliable and reproducible in its measurements than the dental guides.

Mutual regulation of CD4+ T cells and intravascular fibrin in infections.

Innate myeloid cells especially neutrophils and their extracellular traps are known to promote intravascular coagulation and thrombosis formation in infections and various other conditions. Innate myeloid cell dependent fibrin formation can support systemic immunity while its dysregulation enhances the severity of infectious diseases. Less is known about the immune mechanisms preventing dysregulation of fibrin homeostasis in infection. During experimental systemic infections local fibrin deposits in the liver microcirculation cause rapid arrest of CD4+ T cells. Arrested T helper cells mostly represent Th17 cells that partially originate from the small intestine. Intravascular fibrin deposits activate mouse and human CD4+ T cells which can be mediated by direct fibrin - CD4+ T cell interactions. Activated CD4+ T cells suppress fibrin deposition and microvascular thrombosis by directly counteracting coagulation activation by neutrophils and classical monocytes. T cell activation, which is initially triggered by IL- 12p40- and MHC-II dependent mechanisms, enhances intravascular fibrinolysis via LFA-1. Moreover, CD4+ T cells disfavor the association of the fibrinolysis inhibitor TAFI with fibrin whereby fibrin deposition is increased by TAFI in the absence but not presence of T cells. In human infections thrombosis development is inversely related to microvascular levels of CD4+ T cells. Thus, fibrin promotes LFA-1 dependent T helper cell activation in infections which drives a negative feedback cycle that rapidly restricts intravascular fibrin and thrombosis development.

An international review of the characteristics of viral nucleic acid-amplification testing (NAT) reveals a trend towards the use of smaller pool sizes and individual donation NAT.

BACKGROUND AND OBJECTIVES: Nucleic acid-amplification testing (NAT) is used for screening blood donations/donors for blood-borne viruses. We reviewed global viral NAT characteristics and NAT-yield confirmatory testing used by blood operators. MATERIALS AND METHODS: NAT characteristics and NAT-yield confirmatory testing used during 2019 was surveyed internationally by the International Society of Blood Transfusion Working Party Transfusion-Transmitted Infectious Diseases. Reported characteristics are presented herein. RESULTS: NAT was mainly performed under government mandate. Human immunodeficiency virus (HIV), hepatitis C virus (HCV) and hepatitis B virus (HBV) NAT was performed on all donors and donation types, while selective testing was reported for West Nile virus, hepatitis E virus (HEV), and Zika virus. Individual donation NAT was used for HIV, HCV and HBV by ~50% of responders, while HEV was screened in mini-pools by 83% of responders performing HEV NAT. Confirmatory testing for NAT-yield samples was generally performed by NAT on a sample from the same donation or by NAT and serology on samples from the same donation and a follow-up sample. CONCLUSION: In the last decade, there has been a trend towards use of smaller pool sizes or individual donation NAT. We captured characteristics of NAT internationally in 2019 and provide insights into confirmatory testing approaches used for NAT-yields, potentially benefitting blood operators seeking to implement NAT.

Perception of Animal Abuse among Adolescents: Influence of Social and Demographic Factors.

Animal welfare is inherited in each society, shaped by the surrounding environment and upbringing of each individual. This influence becomes particularly significant during adolescence. Due to its cultural context, Spain is among the European Union nations with the highest number of cases of animal abuse. The Canary Islands, the scenario of this study, show the highest rates of intentional poisoning of wildlife and pets' abandonment. The aim of the present study was to explore the perception of animal welfare among adolescents, studying the influence of the main socio-demographic factors that may condition it. A validated questionnaire on animal abuse was used and distributed to adolescents aged 14-18 years in two public study centers. Animal abuse rates were correlated with socio-demographic variables. In total, 302 subjects answered the questionnaire. The perception of animal welfare was influenced by socio-demographic variables, gender being the most important. The demographic profile of the least responsive adolescent to animal abuse was a male engaged in sports, not owning a dog, and hailing from a family involved in hunting. Awareness should be raised at an early age, promoting artistic activities, encouraging contact with animals and sporting practices that do not generate a lack of empathy for animals.

Neutralizing IFN-γ autoantibodies are rare and pathogenic in HLA-DRB1*15:02 or 16:02 individuals.

BACKGROUNDWeakly virulent environmental mycobacteria (EM) can cause severe disease in HLA-DRB1*15:02 or 16:02 adults harboring neutralizing anti-IFN-γ autoantibodies (nAIGAs). The overall prevalence of nAIGAs in the general population is unknown, as are the penetrance of nAIGAs in HLA-DRB1*15:02 or 16:02 individuals and the proportion of patients with unexplained, adult-onset EM infections carrying nAIGAs.METHODSThis study analyzed the detection and neutralization of anti-IFN-γ autoantibodies (auto-Abs) from 8,430 healthy individuals of the general population, 257 HLA-DRB1*15:02 or 16:02 carriers, 1,063 patients with autoimmune disease, and 497 patients with unexplained severe disease due to EM.RESULTSWe found that anti-IFN-γ auto-Abs detected in 4,148 of 8,430 healthy individuals (49.2%) from the general population of an unknown HLA-DRB1 genotype were not neutralizing. Moreover, we did not find nAIGAs in 257 individuals carrying HLA-DRB1* 15:02 or 16:02. Additionally, nAIGAs were absent in 1,063 patients with an autoimmune disease. Finally, 7 of 497 patients (1.4%) with unexplained severe disease due to EM harbored nAIGAs.CONCLUSIONThese findings suggest that nAIGAs are isolated and that their penetrance in HLA-DRB1*15:02 or 16:02 individuals is low, implying that they may be triggered by rare germline or somatic variants. In contrast, the risk of mycobacterial disease in patients with nAIGAs is high, confirming that these nAIGAs are the cause of EM disease.FUNDINGThe Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH) (R01AI095983 and U19AIN1625568), the National Center for Advancing Translational Sciences (NCATS), the NIH Clinical and Translational Science Award (CTSA) program (UL1 TR001866), the French National Research Agency (ANR) under the "Investments for the Future" program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), ANR-GENMSMD (ANR-16-CE17-0005-01), ANR-MAFMACRO (ANR-22-CE92-0008), ANRSECTZ170784, the French Foundation for Medical Research (FRM) (EQU201903007798), the ANRS-COV05, ANR GENVIR (ANR-20-CE93-003), and ANR AI2D (ANR-22-CE15-0046) projects, the ANR-RHU program (ANR-21-RHUS-08-COVIFERON), the European Union's Horizon 2020 research and innovation program under grant agreement no. 824110 (EASI-genomics), the Square Foundation, Grandir - Fonds de solidarité pour l'enfance, the Fondation du Souffle, the SCOR Corporate Foundation for Science, the Battersea & Bowery Advisory Group, William E. Ford, General Atlantic's Chairman and Chief Executive Officer, Gabriel Caillaux, General Atlantic's Co-President, Managing Director, and Head of business in EMEA, and the General Atlantic Foundation, Institut National de la Santé et de la Recherche Médicale (INSERM) and of Paris Cité University. JR was supported by the INSERM PhD program for doctors of pharmacy (poste d'accueil INSERM). JR and TLV were supported by the Bettencourt-Schueller Foundation and the MD-PhD program of the Imagine Institute. MO was supported by the David Rockefeller Graduate Program, the Funai Foundation for Information Technology (FFIT), the Honjo International Scholarship Foundation (HISF), and the New York Hideyo Noguchi Memorial Society (HNMS).

Invasive Treatment Strategy in Adults With Frailty and Non-ST-Segment Elevation Myocardial Infarction: A Secondary Analysis of a Randomized Clinical Trial.

Importance: The MOSCA-FRAIL randomized clinical trial compared invasive and conservative treatment strategies in patients with frailty with non-ST-segment elevation myocardial infarction (NSTEMI). It showed no differences in the number of days alive and out of the hospital at 1 year. Objective: To assess the outcomes of the MOSCA-FRAIL trial during extended follow-up. Design, Setting, and Participants: The MOSCA-FRAIL randomized clinical trial was conducted at 13 hospitals in Spain between July 7, 2017, and January 9, 2021, and included 167 adults (aged ≥70 years) with frailty (Clinical Frailty Scale score ≥4) and NSTEMI. In this preplanned secondary analysis, follow-up was extended to January 31, 2023. Data analysis was performed from April 5 to 29, 2023, using the intention-to-treat principle. Interventions: Patients were randomized to a routine invasive (coronary angiography and revascularization if feasible [n = 84]) or a conservative (medical treatment with coronary angiography only if recurrent ischemia [n = 83]) strategy. Main outcomes and measures: The primary end point was the difference in restricted mean survival time (RMST). Secondary end points included readmissions for any cause, considering recurrent readmissions. Results: Among the 167 patients included in the analysis, the mean (SD) age was 86 (5) years; 79 (47.3%) were men and 88 (52.7%) were women. A total of 93 deaths and 367 readmissions accrued. The RMST for all-cause death over the entire follow-up was 3.13 (95% CI, 2.72-3.60) years in the invasive and 3.06 (95% CI, 2.84-3.32) years in the conservative treatment groups. The RMST analysis showed inconclusive differences in survival time (invasive minus conservative difference, 28 [95% CI, -188 to 230] days). Patients under invasive treatment tended to have shorter survival in the first year (-28 [95% CI, -63 to 7] days), which improved after the first year (192 [95% CI, 90-230] days). Kaplan-Meier mortality curves intersected, displaying higher mortality to 1 year in the invasive group that shifted to a late benefit (landmark analysis hazard ratio, 0.58 [95% CI, 0.33-0.99]; P = .045). Early harm was more evident in the subgroup with a Clinical Frailty Scale score greater than 4. No differences were found for the secondary end points. Conclusions and Relevance: In this extended follow-up of a randomized clinical trial of patients with frailty and NSTEMI, an invasive treatment strategy did not improve outcomes at a median follow-up of 1113 (IQR, 443-1441) days. However, a differential distribution of deaths was observed, with early harm followed by later benefit. The phenomenon of depletion of susceptible patients may be responsible for this behavior. Trial registration: ClinicalTrials.gov Identifier: NCT03208153.

Building community engagement with caregivers through online interaction and a salutogenic approach in a period of isolation.

Background: Informal caregivers are essential figures that deal with the effects of dependence in the elderly. However, they suffer from poorer health-related quality of life, particularly regarding mental health. Social support is crucial, but this was suspended or dramatically reduced during the Covid-19 pandemic. Salutogenesis theory explores the contributing factors for the promotion and maintenance of health. Considering all these, we offered caregivers the opportunity to join a participatory project aimed at creating communication spaces where they could share experiences, think together about potential solutions, and explore which salutogenic actions they used in their daily basis and how they had changed during Covid-19 restrictions. Methods: We used a qualitative methodology with a socio-constructivist and phenomenological approach and purposive sampling. We organized two focus groups consisting of online semi-structured discussions with seven participants in total. Conversations were videotaped and transcribed and we conducted content thematic analyses using the NVivo software. Results: Caregiving in our setting are primarily women with high levels of education that do not always feel comfortable with this load because it interferes with their personal and professional lives. The pandemic increased caregivers feelings of loneliness, resignation, and burden, directly affecting their mental health. Furthermore, the disappearance of prevention programs and the difficulties to access healthcare services produced negative consequences on the already fragile elderly and their family caregivers. Conclusion: The pandemic and its restrictions exacerbated the problematics affecting informal caregivers. Although these people are aware of their situation and have valued knowledge of how to improve their health, they cannot always put it into practice. We call policymakers to reframe interventions aimed at caregivers by introducing the voice of the community in the planning and to rethink the management of vulnerable people and their carers in other potential health crises.

Facial trauma in the major league baseball.

OBJECTIVE: The objectives of this study were to identify and describe significant facial trauma present in Major League Baseball (MLB) that resulted in players missing games or being placed in the injury reserve list. STUDY DESIGN: This was a retrospective cohort study. The predictor variables were the player's age, height, weight, body mass index, position, team conference, and if played games took place in playoffs season. The outcome variables were injury location (upper, middle, and lower facial third) and type of injury (soft tissue, fracture). Chi-square and logistic regression were computed to determine associations between predictor and outcome variables. RESULTS: A total of 109 players missed games due to facial injuries, and a total of 115 injuries were identified. Of the 115 injuries, none occurred in the upper facial third, 96 (83%) were in the middle third, and 19 (17%) in the lower third. Most fractures occurred in fielders (45%), and most soft tissue injuries in basemen (40%). CONCLUSIONS: Significant facial trauma in the MLB has risen in recent years. The player's height, conference, and playoff season were the most associated factors. Most injuries occurred in the periorbital area. A recommendation for the use of protection goggles can be made to prevent them.

An outsider on the Antarctic Peninsula: A new record of the non-native moth Plodia interpunctella (Lepidoptera: Pyralidae).

We report the first record of the microlepidopteran Plodia interpunctella beyond the South Shetland Islands at the Chilean Yelcho scientific station (64°52'33.1428″ S; 63°35'1.9572″ W), Doumer Island, close to the west coast of the Antarctic Peninsula. It is notable that P. interpunctella, a globally distributed stored product pest species, exhibits a remarkable capacity for prolonged viability within food storage facilities. The dual challenges of food transportation and storage in the context of Antarctica's challenging operational conditions may have facilitated P. interpunctella's initial arrival to the Antarctic region. Non-perishable food items, such as grains, flour and rice, provide practical options for the bulk food transportation and storage required in the long-term operation of Antarctic research stations. The presence of P. interpunctella in Antarctica, even if restricted to synanthropic environments within buildings, is a clear threat to Antarctic biodiversity, not only through being an invasive species itself but also as a potential vector for other non-native species (bacteria, acari, between others.), which could carry diseases to the native species.

Electroosmotic MHD ternary hybrid Jeffery nanofluid flow through a ciliated vertical channel with gyrotactic microorganisms: Entropy generation optimization.

In this study, the computational analysis of entropy generation optimization for synthetic cilia regulated ternary hybrid Jeffery nanofluid (Ag-Au-TiO2/PVA) flow through a peristaltic vertical channel with swimming motile Gyrotactic microorganisms is investigated. Understanding the intricate interaction of multiple physical phenomena in biomedical applications is essential for optimizing entropy generation and advancing microfluidic systems. The characteristics of nanofluid are explored for the electroosmotic MHD fluid flow in the presence of thermophoresis and Brownian motion, viscous dissipation, Ohmic heating and chemical reaction. Using the appropriate transformations, a set of ordinary differential equations are created from the governing partial differential equations. The resulting ODEs are numerically solved using the shooting technique using BVP5C in MATLAB after applying the long-wavelength and low Reynolds number approximation. The velocity, temperature, concentration, electroosmosis, and microorganism density profiles are analyzed graphically for different emerging parameters. Graphical investigation of engineering interest quantities like heat transfer rate, mass transfer rate, skin friction coefficient, and entropy generation optimization are also presented. It is observed that the rate of mass transfer increases for increasing thermophoretic parameter, while reverse effect is noted for Brownian motion parameter, Schmidt number, and chemical reaction number. The outcomes of present study can be pertinent in studying Cilia properties of respiratory tract, reproductive system, and brain ventricles.

Improving tuberculosis case detection through contact risk stratification by Xpert MTB/RIF Ultra and spatial parameters: Evaluation of an innovative active case finding strategy in Mozambique (Xpatial-TB).

Prompt diagnosis is critical for tuberculosis (TB) control, as it enables early treatment which in turn, reduces transmission and improves treatment outcomes. We investigated the impact on TB diagnosis of introducing Xpert Ultra as the frontline diagnostic test, combined with an innovative active-case finding (ACF) strategy (based on Xpert Ultra semi-quantitative results and spatial parameters), in a semi-rural district of Southern Mozambique. From January-December 2018 we recruited incident TB-cases (index cases, ICs) and their household contacts (HCs). Recruitment of close community contacts (CCs) depended on IC´s Xpert Ultra results, and the population density of their area. TB-contacts, either symptomatic or people living with HIV, were asked to provide a spot sputum for lab-testing. Trends on TB case notification were compared to the previous years and to those of two districts in the south of the Maputo province (control area), using an interrupted time series analysis with and without control (CITS/ITS). A total of 1010 TB ICs (37.1% laboratory-confirmed) were recruited; 3165 HCs and 4730 CCs were screened for TB. Eighty-nine additional TB cases were identified through the ACF intervention (52.8% laboratory-confirmed). The intervention increased by 8.2% all forms of TB cases detected in 2018. Xpert Ultra trace positive results accounted for a high proportion of laboratory confirmations in the ACF cohort (51.1% vs 13.7% of those passively diagnosed). The Number Needed to Screen to find a TB case differed widely among HCs (55) and CCs (153). During the intervention period, a reversal of the previous negative trend in lab-confirmed case notifications was observed in the district. However, the CITS model did not show any statistically significant difference compared to the control area. Paediatric population benefited the most from the ACF strategy and HCs screening seemed an effective intervention to find microbiological confirmed cases in early stages of the disease.

Patterns of multimorbidity in primary care electronic health records: A systematic review.

Background: Multimorbidity, the coexistence of multiple chronic conditions in an individual, is a complex phenomenon that is highly prevalent in primary care settings, particularly in older individuals. This systematic review summarises the current evidence on multimorbidity patterns identified in primary care electronic health record (EHR) data. Methods: Three databases were searched from inception to April 2022 to identify studies that derived original multimorbidity patterns from primary care EHR data. The quality of the included studies was assessed using a modified version of the Newcastle-Ottawa Quality Assessment Scale. Results: Sixteen studies were included in this systematic review, none of which was of low quality. Most studies were conducted in Spain, and only one study was conducted outside of Europe. The prevalence of multimorbidity (i.e. two or more conditions) ranged from 14.0% to 93.9%. The most common stratification variable in disease clustering models was sex, followed by age and calendar year. Despite significant heterogeneity in clustering methods and disease classification tools, consistent patterns of multimorbidity emerged. Mental health and cardiovascular patterns were identified in all studies, often in combination with diseases of other organ systems (e.g. neurological, endocrine). Discussion: These findings emphasise the frequent coexistence of physical and mental health conditions in primary care, and provide useful information for the development of targeted preventive and management strategies. Future research should explore mechanisms underlying multimorbidity patterns, prioritise methodological harmonisation to facilitate the comparability of findings, and promote the use of EHR data globally to enhance our understanding of multimorbidity in more diverse populations.