Combined Intervention Strategy Research Articles

Real-world performance of point-of-care vs. standard-of-care HIV viral load testing in western Kenya: Secondary analysis of Opt4Kids and Opt4Mamas studies.

Routine HIV viral load testing is important for evaluating HIV treatment outcomes, but conventional viral load testing has many barriers including expensive laboratory equipment and lengthy results return times to patients. A point-of-care viral load testing technology, such as GeneXpert HIV-1 quantification assay, could reduce these barriers by decreasing cost and turnaround time, however real-world performance is limited. We conducted a secondary analysis using 900 samples collected from participants in two studies to examine the performance of GeneXpert as point-of-care viral load compared to standard-of-care testing (which was conducted with two centralized laboratories using traditional HIV-1 RNA PCR quantification assays). The two studies, Opt4Kids (n = 704 participants) and Opt4Mamas (n = 820 participants), were conducted in western Kenya from 2019-2021 to evaluate the effectiveness of a combined intervention strategy, which included point-of-care viral load testing. Paired viral load results were compared using four different thresholds for virological non-suppression, namely ≥50, ≥200, ≥400, ≥1000 copies/ml. At a threshold of ≥1000 copies/mL, paired samples collected on the same day: demonstrated sensitivities of 90.0% (95% confidence interval [CI] 68.3, 98.8) and 66.7% (9.4, 99.2), specificities of 98.4% (95.5, 99.7) and 100% (96.5, 100), and percent agreements of 97.7% (94.6, 99.2) and 99.1% (95.0, 100) in Opt4Kids and Opt4Mamas studies, respectively. When lower viral load thresholds were used and the paired samples were collected an increasing number of days apart, sensitivity, specificity, and percent agreement generally decreased. While specificity and percent agreement were uniformly high, sensitivity was lower than expected. Non-specificity of the standard of care testing may have been responsible for the sensitivity values. Nonetheless, our results demonstrate that GeneXpert may be used reliably to monitor HIV treatment in low- and middle- income countries to attain UNAID's 95-95-95 HIV goals.

A combined intervention strategy to increase linkage to and retention in substance use treatment for individuals accessing hospital-based services: study protocol

BackgroundIn 2020, New Mexico had the highest alcohol related death and the 11th highest drug overdose rate in the U.S. Towards the long-term goal of addressing this public health problem, we are implementing and evaluating an multi-level intervention designed to identify adults at risk of substance use disorder (SUD) and encourage linkage to and retention in treatment. The first level includes equipping the ED and medical inpatient units of a safety-net hospital with a method to screen individuals at risk of a SUD. The second level includes Seeking Safety (SS), a trauma-specific treatment for PTSD and SUD; and pharmacotherapy for SUD. Motivational Interviewing (MI) is used throughout both levels. Using the SPIRIT guidelines and checklist, this study protocol describes the multi-level intervention and the methodology we are using to assess feasibility and effectiveness.MethodsWe are using a Type 1 hybrid implementation design with a non-randomized approach (ISRCTN registration # ISRCTN33100750). We aim to enroll 110 adults (≧18) who screen positive for unhealthy use of alcohol, prescription medications (used nonmedically) and/or illicit drugs. Peer support workers are responsible for screening, using MI to increase engagement in screening and treatment and delivery of SS. Pharmacotherapy is provided by addiction clinical specialists. Treatment is provided post hospital discharge via telehealth to increase access to care. Participants are identified through (1) review of electronic health records for individuals with a chief or secondary complaint or mental health condition relating to alcohol and/or other drug use, (2) referrals from clinical staff and (3) screening in the ED and medical inpatient units. Feasibility is being measured through process data. Effectiveness will be determined by changes in two primary outcomes: (i) PTSD symptom severity; and (ii) substance use.DiscussionOur study will expand on research related to the implementation of treatment strategies for patients presenting at EDs and admitted to medical inpatients units wherein there is a significant window of opportunity to link patients with follow-up behavioral and clinical services for alcohol and/or drug misuse. The challenges associated with implementation and strategies that have been helpful to address these challenges will further inform the field.

Effectiveness of combining prevention psychological interventions with interventions that address the social determinants of mental health in low and middle-income countries: protocol of a systematic review and meta-analysis

IntroductionCommon mental health conditions (CMHCs), including depression, anxiety and post-traumatic stress disorder (PTSD), are highly prevalent in low and middle-income countries (LMICs). Preventive strategies combining psychological interventions with interventions addressing...

Towards reducing diagnostic delay in endometriosis in primary care: a qualitative study.

Due to a heterogeneity of symptoms, a lack of an adequate diagnostic test, and a lack of awareness, diagnostic delay in endometriosis in primary care on average amounts to 35 months. To determine which interventions are most feasible to reduce time to diagnosis in primary care, focusing on GPs' preferences, the intervention's content, design, and implementation. We conducted a qualitative study by performing focus groups with GPs and GP trainees between July and October 2021. Data collection was continued until saturation was obtained. Focus groups were transcribed and openly encoded. Themes were formulated by three independent researchers. Divided over five focus groups 22 GPs and 13 GP trainees participated. Three themes were formulated: increasing awareness, combined intervention, and reaching unaware GPs. Suggestions for a combined intervention strategy were adaptation of guidelines, a diagnostic support tool, and compulsory education. To reach unaware GPs, participants felt that education should be offered in regional networks and education for GP trainees should be mandatory. A guideline on menstrual symptoms should be considered and the term endometriosis should be added to the differential diagnosis paragraphs of existing guidelines. A diagnostic support tool should be linked to a guideline and consist of a flowchart with steps starting with the first presentation of symptoms leading to the diagnosis of endometriosis. According to GPs, a combined intervention strategy consisting of an adapted guideline, a diagnostic support tool, and education might be successful interventions in reducing diagnostic delay in endometriosis.

Combined intervention strategy for reversing iron-deficiency anaemia and deficiency in psychomotor development in chronic malnutrition.

Background: chronic iron-deficiency anaemia in children has a negative impact on neuronal and cognitive development. Despite current knowledge on this subject, in Bolivia iron intake along the psychomotor development stimulation as part of a comprehensive rehabilitation process for children with severe chronic malnutrition is not yet used. Objective: to evaluate the effect of a neurorestorative diet, consisting of iron supplements and other micronutrients, along with psychomotor stimulation in preschool children with chronic malnutrition, iron-deficiency anaemia and severe psychomotor delay. Patients and methods: twenty-four children between 1 and 56 months of age admitted to the integral nutritional recovery centre (INRC), Paediatric Hospital of Cochabamba, Bolivia were included. A strategy of intervention was applied consisting of nutritional replenishment through the administration of elaborated meals prepared from local foods with high heme and non-heme iron concentration, added with vegetables plus the administration of micronutrient´s supplementation and the psychomotor stimulation. Anthropometric indices, psychomotor and biochemical parameters were measured at four times points, during the hospitalisation period. Results: at the beginning, the anthropometric and psychomotor parameters were decreased (between -2 and -3 z score and below 50 % respectively). Combined strategy intervention with iron and other micronutrients together photons produced significant changes between the evaluated time points, both in anthropometric and psychomotor parameters, although these changes were less than expected. Conclusions: the combined strategy used in this study allowed recovery from the anaemia and minimal growth due to the low birth weight or chronic malnutrition. However, the intervention was insufficient to achieve a complete recovery.

Mapping brucellosis risk in Kenya and its implications for control strategies in sub-Saharan Africa

In Sub-Saharan Africa (SSA), effective brucellosis control is limited, in part, by the lack of long-term commitments by governments to control the disease and the absence of reliable national human and livestock population-based data to inform policies. Therefore, we conducted a study to establish the national prevalence and develop a risk map for Brucella spp. in cattle to contribute to plans to eliminate the disease in Kenya by the year 2040. We randomly generated 268 geolocations and distributed them across Kenya, proportionate to the area of each of the five agroecological zones and the associated cattle population. Cattle herds closest to each selected geolocation were identified for sampling. Up to 25 cattle were sampled per geolocation and a semi-structured questionnaire was administered to their owners. We tested 6,593 cattle samples for Brucella immunoglobulin G (IgG) antibodies using an Enzyme-linked immunosorbent assay (ELISA). We assessed potential risk factors and performed spatial analyses and prevalence mapping using approximate Bayesian inference implemented via the integrated nested Laplace approximation (INLA) method. The national Brucella spp. prevalence was 6.8% (95% CI: 6.2–7.4%). Exposure levels varied significantly between agro-ecological zones, with a high of 8.5% in the very arid zone with the lowest agricultural potential relative to a low of 0.0% in the agro-alpine zone with the highest agricultural potential. Additionally, seroprevalence increased with herd size, and the odds of seropositivity were significantly higher for females and adult animals than for males or calves. Similarly, animals with a history of abortion, or with multiple reproductive syndromes had higher seropositivity than those without. At the herd level, the risk of Brucella spp. transmission was higher in larger herds, and herds with a history of reproductive problems such as abortion, giving birth to weak calves, or having swollen testes. Geographic localities with high Brucella seroprevalence occurred in northern, eastern, and southern regions of Kenya all primarily characterized by semi-arid or arid agro-ecological zones dominated by livestock pastoralism interspersed with vast areas with mixed livestock-wildlife systems. The large spatial extent of our survey provides compelling evidence for the widespread geographical distribution of brucellosis risk across Kenya in a manner easily understandable for policymakers. Our findings can provide a basis for risk-stratified pilot studies aiming to investigate the cost-effectiveness and efficacy of singular and combined preventive intervention strategies that seek to inform Kenya’s Brucellosis Control Policy.

Probiotic and Muscadine Grape Extract Interventions Shift the Gut Microbiome and Improve Metabolic Parameters in Female C57BL/6 Mice.

Obesity and Western-like diet consumption leads to gut microbiome dysbiosis, which is associated with the development of cardio-metabolic diseases and poor health outcomes. The objective of this study was to reduce Western diet-mediated gut microbial dysbiosis, metabolic dysfunction, and systemic inflammation through the administration of a novel combined intervention strategy (oral probiotic bacteria supplements and muscadine grape extract (MGE)). To do so, adult female C57BL/6 mice were fed a low-fat control or Western-style diet and sub-grouped into diet alone, probiotic intervention, antibiotic treatments, MGE supplementation, a combination of MGE and probiotics, or MGE and antibiotics for 13 weeks. Mouse body weight, visceral adipose tissue (VAT), liver, and mammary glands (MG) were weighed at the end of the study. Fecal 16S rRNA sequencing was performed to determine gut bacterial microbiome populations. Collagen, macrophage, and monocyte chemoattractant protein-1 (MCP-1) in the VAT and MG tissue were examined by immunohistochemistry. Adipocyte diameter was measured in VAT. Immunohistochemistry of intestinal segments was used to examine villi length, muscularis thickness, and goblet cell numbers. We show that dietary interventions in Western diet-fed mice modulated % body weight gain, visceral adiposity, MG weight, gut microbial populations, and inflammation. Intervention strategies in both diets effectively reduced VAT and MG fibrosis, VAT and MG macrophages, adipocyte diameter, and VAT and MG MCP-1. Interventions also improved intestinal health parameters. In conclusion, dietary intervention with MGE and probiotics modulates several microbial, inflammatory, and metabolic factors reducing poor health outcomes associated with Western diet intake.

Protocol for the PATHOME study: a cohort study on urban societal development and the ecology of enteric disease transmission among infants, domestic animals and the environment

IntroductionGlobal morbidity from enteric infections and diarrhoea remains high in children in low-income and middle-income countries, despite significant investment over recent decades in health systems and water and sanitation infrastructure....

EE19 Cost-Effectiveness Analysis of Nonpharmaceutical Interventions Combined with Inactivated Vaccination and Oral Medicine in China

Various interventions were used to control the COVID-19 pandemic and protect population health, including vaccination, medication and nonpharmaceutical interventions (NPIs). This study aims to examine the cost-effectiveness of different combinations of NPIs (including social distancing, mask wearing, tracing-testing-isolation, mass testing, and lockdown), oral medicine (Paxlovid), and vaccination (including two-dose and three-dose vaccination) under the Delta and Omicron pandemic in China. We constructed a Markov model using a SIRI structure with a one-week cycle length over one-year time horizon to estimate the cost-effectiveness of different combinations in China from societal perspective. Effectiveness of interventions, disease transition probabilities and costs were from published data, quality-adjusted life years (QALYs) gained and incremental cost-effectiveness ratios (ICER) and net monetary benefits were calculated for one-year time horizon. One-way and probabilistic sensitivity analyses were performed to test the robustness of the model. Scenario analysis was developed to examine different situations under the Omicron pandemic. Under the Delta pandemic, implementing the combination of social distancing, mask wearing, mass testing and three-dose vaccination was the optimal strategy, with cost at $11165635.33 and utility of 94309.94 QALYs, and had 60% probability of being cost-effective compared with other strategies. Three-dose vaccination combinations were better than two-dose combinations. Under the Omicron pandemic, antigen testing was better than nucleic testing by avoiding cross infections; second, adding Paxlovid or lockdown to the combined intervention strategies could increase limited health outcomes at huge cost and thus were not cost-effective; last, encouraging patients to stay at home can save societal costs compared with concentrated quarantine at hospitals. Three-dose vaccination and self-quarantine of asymptomatic and mild cases can save total costs. Under the Omicron pandemic outbreak, antigen testing is a better way to control the pandemic, and adding Paxlovid or lockdown to intervention combinations is not cost-effective.

Analysis of the effect of art design combined with drug therapy on college students’ depression

BackgroundWith the increasing social employment pressure, the psychological pressure of college students in their daily study and life is also increasing. Because students’ physical and mental growth is not sound, it is difficult for them to carry out targeted self-intervention and adjustment against psychological pressure, which leads to long-term accumulation of negative psychology and eventually forms depressive symptoms. In recent years, the number of depression patients in colleges and universities has been increasing. It is necessary to form a daily treatment strategy system that is in line with students’ psychological characteristics.Subjects and Methods90 students diagnosed with depression were selected and divided into three groups. The first group was a single drug intervention group, which only used the common form of depression drug intervention. The second group was a single art design appreciation intervention, which used professional art design and appreciation psychological intervention strategies to intervene students’ depression. The third group is the design appreciation and drug combined intervention group. The students in this group participated in professional art design and appreciation psychological intervention while taking antidepressant drug treatment. The study collected the depression psychological status of the three groups of patients before and after treatment, and used the collected data for quantitative analysis.ResultsThe research results showed that before the start of treatment, the Self-Rating Depression (SDS) scores of the three groups of students with depression were 63.21 points in the single drug intervention group, 64.32 points in the single art design appreciation intervention group and 63.54 points in the art design appreciation and drug combined intervention group. It showed that the levels of depression symptoms of the three groups of students before the intervention were similar. After intervention, the SDS score of the single drug intervention group decreased to 45.22 points, the SDS score of the single art design appreciation intervention group decreased to 46.51 points, and the SDS score of art design appreciation and drug combined intervention decreased to 40.13 points. It can be seen that the intervention effect of art design appreciation and drug intervention is the most obvious. Compared with the other two methods, this method is more conducive to the depression intervention for students.ConclusionsFrom the comparison of the patients’ condition in the single drug intervention group, the single art design appreciation intervention group, and the art design appreciation and drug combination intervention group before and after the intervention, it can be seen that the art design appreciation and drug combination intervention strategy designed by the research is more conducive to forming a better intervention effect in the student group, helping them to establish a psychological reaction mechanism in life with antidepressant drugs and reduce the severity of self-depression.Table 1.Group intervention effectGroupNumber of group membersSDS score before treatmentSDS score after treatmentSingle drug intervention3063.2145.22Single art design appreciation intervention3064.3246.51Art design appreciation and drug joint intervention3063.5440.13

Modeling the spread dynamics of multiple-variant coronavirus disease under public health interventions: A general framework

The COVID-19 pandemic was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is a single-stranded positive-stranded RNA virus with a high multi-directional mutation rate. Many new variants even have an immune-evading property, which means that some individuals with antibodies against one variant can be reinfected by other variants. As a result, the realistic is still suffering from new waves of COVID-19 by its new variants. How to control the transmission or even eradicate the COVID-19 pandemic remains a critical issue for the whole world. This work presents an epidemiological framework for mimicking the multi-directional mutation process of SARS-CoV-2 and the epidemic spread of COVID-19 under realistic scenarios considering multiple variants. The proposed framework is used to evaluate single and combined public health interventions, which include non-pharmaceutical interventions, pharmaceutical interventions, and vaccine interventions under the existence of multi-directional mutations of SARS-CoV-2. The results suggest that several combined intervention strategies give optimal results and are feasible, requiring only moderate levels of individual interventions. Furthermore, the results indicate that even if the mutation rate of SARS-CoV-2 decreased 100 times, the pandemic would still not be eradicated without appropriate public health interventions.

Is voluntary male medical circumcision still cost-effective in the setting of antiretroviral therapy scaleup in sub-Saharan Africa?

Voluntary medical male circumcision (VMMC) has been part of the combined biomedical HIV prevention intervention strategies since January, 2007, when WHO/UNAIDS recommended it as one of the strategies to reduce HIV acquisition in sub-Saharan Africa.1 Since then WHO estimates that, between 2008 and 2020, more than 26·8 million VMMC procedures have been carried out in 15 priority countries in sub-Saharan Africa.2 However, during the same period, there has been a massive increase to 25·7 million people living with HIV, with 16·3 million on antiretroviral therapy (ART).

Mathematical Modelling of Combined Intervention Strategies for the Management and Control of Plasma Glucose of a Diabetes Mellitus Patient: A System Dynamic Modelling Approach

With the rapid increase of diabetes mellitus cases in the world, management and control of the disease has become a complex and highly dynamic process. This challenge requires a multifaceted approach to manage and control the complications associated with the hyperglycaemia or hypoglycaemia conditions. This paper presents a mathematical model for determining the influence of combined intervention strategies in the management and control for the plasma glucose of the type II diabetes. System dynamics (SD) techniques were used in modelling the sub-compartments of biological systems of an Identifiable Patient (IP). The system dynamic model developed gave an illustration on how typical glucose-insulin dynamics occur at different intervention strategies involving varying amounts of carbohydrates taken, intensity of physical exercises, stress levels and the amount of exogenous insulin administered. The model was conceptualized within a semi-closed loop system representing the patient ecosystem by extending the Bergman Minimal Model. Stochastic differential equations (SDE) were used to capture the non-linear, continuous time varying interactions of the measurements associated with plasma glucose-insulin dynamics. The estimated results from the model showed combined intervention strategies of reduced amounts of carbohydrates intake, reduced stress levels and varying moderately high-to-low exercise intensity at a constant unit of exogenous insulin produced good plasma glucose levels control.

Perceived stress, resilience, and stress coping in patients with drug resistant epilepsy and functional dissociative seizures

PurposeDepression and anxiety are psychiatric disorders related to chronic stress, commonly found in patients with drug-resistant epilepsy (DRE) and functional dissociative seizures (FDS). The present study compares the levels of perceived stress, resilience, and the styles of stress coping among patients with DRE (n=60), FDS (n=28), and controls (n=31). MethodsWe performed a cross-sectional study. All patients underwent Video Electroencephalography to confirm the diagnosis and completed the psychiatric assessment (SCID I and II of DSM IV) supported by several instruments validated in Spanish. ResultsFDS scored higher in perceived stress (p = 0.004) with lower levels of resilience compared to controls (p = 0.01). Stress coping subscales show higher scores in negative self-focus and hostility in patients with FDS compared to controls (p=0.003). Similarly, DRE patients scored higher in perceived stress (p = 0.001), and presented lower levels of resilience (p = 0.004) with higher levels of hostility compared to controls (p=0.02). However, no significant differences were found between FDS and DRE on stress coping variables. Anxiety scores and depression rates were higher in the FDS group compared to DRE (p=0.008) and higher in DRE compared to controls (p<0.05). A positive correlation between depression and perceived stress was found (r = 0.6, p=0.0001). ConclusionsOur results delineate a more detailed picture of the psychological profile of this population, emphasizing the importance of stress factors in patients with FDS and DRE. Combined intervention strategies which enhance stress coping may be appropriate to direct treatment and psychotherapy.

Impact of collaborative physician-pharmacist stewardship strategies on prophylactic antibiotic practices: a quasi-experimental study

BackgroundAn effective use of surgical antibiotic prophylaxis (SAP) appears essential to prevent the development of infections linked to surgery while inappropriate and excessive prescriptions of prophylactic antibiotics increase the risk of adverse effects, bacterial resistance and Clostridium difficile infections. In this study, we aimed to analyze SAP practices in an acute secondary hospital in Belgium during the years 2016–2021 in order to evaluate the impacts of combined stewardship interventions, implemented thanks to a physician-pharmacist collaboration.MethodsA quasi-experimental study on SAP practices was conducted during 5 years (2016–2021) in a Belgian University Hospital. We first performed a retrospective observational transversal study on a baseline group (2016.1–2016.4). Then, we constituted a group of patients (2017.1–2017.4) to test a combined intervention strategy of stewardship which integrated the central role of a pharmacist in antibiotic stewardship team and in the pre-operative delivery of nominative kits of antibiotics adapted to patient factors. After this test, we collected patient data (2018.1–2018.4) to evaluate the sustained effects of stewardship interventions. Furthermore, we evaluated SAP practices (2019.1–2019.4) after the diffusion of a computerized decision support system. Finally, we analyzed SAP practices in the context of the COVID-19 pandemic (2020.1–2020.4 and 2021.1–2021.4). The groups were compared from year to year in terms of compliance to institutional guidelines, as evaluated from seven criteria (χ2 test).ResultsIn total, 760 surgical interventions were recorded. The observational study within the baseline group showed that true penicillin allergy, certain types of surgery and certain practitioners were associated with non-compliance (p < 0.05). Compared with the baseline group, the compliance was significantly increased in the test group for all seven criteria assessed (p < 0.05). However, the effects were not fully sustained after discontinuation of the active interventions. Following the diffusion of the computerized decision support system, the compliance to guidelines was not significantly improved. Finally, the COVID-19 pandemic did not appear to affect the practices in terms of compliance to guidelines.ConclusionsThis study shows that optimization of SAP practices is achievable within a proactive multidisciplinary approach including real-time pharmaceutical interventions in the operating area and in the care units practicing SAP.

The CombinADO study to assess the impact of a combination intervention strategy on viral suppression, antiretroviral therapy adherence, and retention in HIV care among adolescents and young people living with HIV: protocol for a cluster-randomized controlled trial

BackgroundAdolescents and youth living with HIV (AYAHIV) have worse HIV outcomes than other age groups, particularly in sub-Saharan Africa (SSA). AYAHIV in SSA face formidable health system, interpersonal- and individual-level barriers to retention in HIV care, uptake of ART, and achievement of viral suppression (VS), underscoring an urgent need for multi-component interventions to address these challenges. This cluster-randomized control trial (cRCT) aims to evaluate the effectiveness and monitor implementation of a community-informed multi-component intervention (“CombinADO strategy”) addressing individual-, facility-, and community-level factors to improve health outcomes for AYAHIV.MethodsThis trial will be conducted in 12 clinics in Nampula Province, Northern Mozambique. All clinics will implement an optimized standard of care (control) including (1) billboards/posters and radio shows, (2) healthcare worker (HCW) training, (3) one-stop adolescent and youth-friendly services, (4) information/motivation walls, (5) pill containers, and (6) tools to be used by HCW during clinical visits. The CombinADO strategy (intervention) will be superadded to control conditions at 6 randomly selected clinics. It will include five additional components: (1) peer support, (2) informational/motivational video, (3) support groups for AYAHIV caregivers, (4) AYAHIV support groups, and (5) mental health screening and linkage to adolescent-focused mental health support. The study conditions will be in place for 12 months; all AYAHIV (ages 10–24 years, on ART) seeking care in the participating sites will be exposed to either the control or intervention condition based on the clinic they attend. The primary outcome is VS (viral load < 50 copies/mL) at 12 months among AYAHIV attending participating clinics. Secondary outcomes include ART adherence (self-reported and TDF levels) and retention in care (engagement in the preceding 90 days). Uptake, feasibility, acceptability, and fidelity of the CombinADO strategy during implementation will be measured. Trial outcomes will be assessed in AYAHIV, caregivers, healthcare workers, and key informants. Statistical analyses will be conducted and reported in line with CONSORT guidelines for cRCTs.DiscussionThe CombinADO study will provide evidence on effectiveness and inform implementation of a novel community-informed multi-component intervention to improve retention, adherence, and VS among AYAHIV. If found effective, results will strengthen the rationale for scale up in SSA.Trial registrationClinicalTrials.gov NCT04930367. Registered on 18 June 2021

A newly intervention strategy in preeclampsia: Targeting PD-1/Tim-3 signaling pathways to modulate the polarization of decidual macrophages.

Programmed cell death-1 (PD-1) and T-cell immunoglobulin mucin-3 (Tim-3) are important immune checkpoint receptors that prevent an overreacted maternal immune response to fetal antigens during pregnancy. Disruption of complex immune regulation mechanisms is associated with adverse pregnancy outcomes, including preeclampsia (PE). Our recent study showed that the Tim-3 pathway was involved in the regulation of decidual macrophage polarization. Decidual macrophages polarized to the M1 phenotype may impair uterine vessel remodeling during placentation, accounting for the occurrence of PE. Co-blockade of the PD-1/Tim-3 pathway was shown to successfully control tumor growth in preclinical cancer models. However, the effects of activating both PD-1 and Tim-3 pathways as a combined intervention strategy in PE are never reported. Herein, we observed the skew of decidual macrophage polarization toward the M1 phenotype in patients with PE and lipopolysaccharide (LPS)-induced PE-like rat model. Moreover, we found that the activation of PD-1/Tim-3 pathway by using PD-L1 and Gal-9 fusion proteins could alleviate the manifestation of the LPS-induced PE-like rats and protect their offspring. Compared with the single intervention, the combination of PD-L1and Gal-9 fusion proteins exhibited obvious advantages in the relief of PE-like symptoms, trophoblast invasion, and fetal vascular development, indicating a synergistic effect of the activated PD-1/Tim-3 pathway. The in vitro study also revealed that the combined intervention using PD-L1 and Gal-9 fusion proteins inhibited the LPS-induced M1macrophage polarization via the synergic activation of the ERK/GSK3β/β-catenin signaling pathway. Together, our findings provide the first evidence that simultaneous activation of PD-1/Tim-3signaling pathways may have an optimal protective effect and serve as a new potential target for PE intervention.

Predicting the impact of control strategies on the tuberculosis burden in South and North Korea using a mathematical model

BackgroundAmong high-income countries, South Korea has a considerable tuberculosis (TB) burden; North Korea has one of the highest TB burdens in the world. Predicting the impact of control strategies on...

Airborne infection risks of SARS-CoV-2 in U.S. schools and impacts of different intervention strategies

The potential airborne transmission of SARS-CoV-2 has triggered concerns as schools continue to reopen and resume in-person instruction during the current COVID-19 pandemic. It is critical to understand the risks of airborne SARS-CoV-2 transmission under different epidemiological scenarios and operation strategies for schools to make informed decisions to mitigate infection risk. Through scenario-based analysis, this study estimates the airborne infection risk of SARS-CoV-2 in 111,485 U.S. public and private schools and evaluates the impacts of different intervention strategies, including increased ventilation, air filtration, and hybrid learning. Schools in more than 90% of counties exhibit infection risk of higher than 1%, indicating the significance of implementing intervention strategies. Among the considered strategies, air filtration is found to be most effective: the school average infection risk when applying MERV 13 is over 30% less than the risk levels correlating with the use of increased ventilation and hybrid learning strategies, respectively. For most schools, it is necessary to adopt combined intervention strategies to ensure the infection risk below 1%. The results provide insights into airborne infection risk in schools under various scenarios and may guide schools and policymakers in developing effective operations strategies to maintain environmental health.

Combined Drug Interventions and its Efficacy in the Reduction of COVID-19 Burden : A Within-Host Modeling Study with reference to HCQ and BCG Vaccination

The COVID-19 pandemic has resulted in more 176 million cases and around 3.82 million deaths worldwide. Different drug interventions acting at multiple stages of the pathogenesis of COVID-19 can substantially reduce infection-induced mortality. The current within-host mathematical modeling studies deals with the optimal combined drug intervention strategy and its efficacy in reducing the burden of COVID-19. The drug interventions considered here include Hydroxychloroquine (HCQ), the first BCG vaccine dose, and a booster dose of BCG administered at a later stage. In this work, we consider two scenarios involving the administration of these interventions. The findings of these studies include the following: the average infected cell count and viral load decreased the most when both the HCQ and BCG interventions were applied together in both scenarios. On the other hand, the average susceptible cell count decreased the best when HCQ alone was administered in both these scenarios. From the comparative effectiveness study it was observed that the basic reproduction number and viral count decreased the best when HCQ and BCG booster interventions were applied together, reinstating the fact obtained earlier in the optimal control setting. These findings may help physicians with decision making in the treatment of life-threatening COVID-19 pneumonia. This study involving different drug interventions is first of its kind. © Research India Publications.