Systematic Review of Outcomes for Assessment of Medication Adherence Enhancing Interventions: An ISPOR Special Interest Group Report.

OBJECTIVES: The lack of universal guidance on outcome measures for evaluating medication adherence enhancing interventions (MAEIs) poses a challenge for assessing their effectiveness. This literature review aimed to provide a systematic overview of outcome measures currently used for the value assessment of MAEIs. METHODS: We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and searched MEDLINE, PsycINFO, Scopus, CINAHL, and Academic Search Complete for randomized and nonrandomized clinical trials, prospective cohort studies, model-based economic evaluations, and value frameworks published in English between January 2010 and September 2020. Two independent reviewers screened all titles and abstracts, followed by a full-text review. Due to the large number of relevant studies, data extraction was limited to articles published between January 2018 and September 2020. We collected data on the general characteristics of the study, the type of intervention, and the outcomes measured. RESULTS: We screened 14 685 records and identified 308 articles for data extraction. Behavioral interventions were the most common (n = 143), followed by educational interventions (n = 110) and mixed-method interventions (n = 73). Outcomes were clustered into 7 categories with medication adherence (n = 286) being the most frequently measured, followed by clinical outcomes (n = 155), health-related quality of life (n = 57), resource use (n = 43), patient satisfaction (n = 31), economic outcomes (n = 18), and other outcomes (n = 76). CONCLUSIONS: Various outcomes measures have been used to evaluate MAEIs, with only a small number of studies exploring economic and patient-reported outcomes. Future research is warranted to develop a consensus-based set of criteria for assessing MAEIs to facilitate the comparison of interventions and enable informed decision making.

Identification of Microbial Species and Analysis of Antimicrobial Resistance Patterns in Acute Cholangitis Patients with Malignant and Benign Biliary Obstructions: A Comparative Study.

Background and Objectives: Acute cholangitis (AC) is still lethal if not treated promptly and effectively. Biliary drainage, also known as source control, has been acknowledged as the backbone treatment for patients with AC; nonetheless, antimicrobial therapy allows these patients to undergo non-emergent drainage procedures. This retrospective study aims to observe the bacterial species involved in AC and analyze the antimicrobial resistance patterns. Materials and Methods: Data were collected for four years, comparing patients with benign and malignant bile duct obstruction as an etiology for AC. A total of 262 patients were included in the study, with 124 cases of malignant obstruction and 138 cases of benign obstruction. Results: Positive bile culture was obtained in 192 (73.3%) patients with AC, with a higher rate among the benign group compared with malignant etiologies (55.7%.vs 44.3%). There was no significant difference between the Tokyo severity scores in the two study groups, identifying 34.7% cases of malignant obstruction with Tokyo Grade 1 (TG1) and 43.5% cases of TG1 among patients with benign obstruction. Similarly, there were no significant differences between the number of bacteria types identified in bile, most of them being monobacterial infections (19% in the TG1 group, 17% in the TG2 group, and 10% in the TG3 group). The most commonly identified microorganism in blood and bile cultures among both study groups was E. coli (46.7%), followed by Klebsiella spp. (36.0%) and Pseudomonas spp. (8.0%). Regarding antimicrobial resistance, it was observed that significantly more patients with malignant bile duct obstruction had a higher percentage of bacterial resistance for cefepime (33.3% vs. 11.7%, p-value = 0.0003), ceftazidime (36.5% vs. 14.5%, p-value = 0.0006), meropenem (15.4% vs. 3.6%, p-value = 0.0047), and imipenem (20.2% vs. 2.6%, p-value < 0.0001). Conclusions: The positive rate of biliary cultures is higher among patients with benign biliary obstruction, while the malignant etiology correlates with increased resistance to cefepime, ceftazidime, meropenem, and imipenem.

Bevacizumab Treatment for Metastatic Colorectal Cancer in Real-World Clinical Practice.

Background and Objectives: Colorectal cancer (CRC) is a leading cause of cancer-related mortality and morbidity worldwide. Bevacizumab was approved for the treatment of metastatic colorectal cancer (mCRC) based on favorable benefit-risk assessments from randomized controlled trials, but evidence on its use in the real-world setting is limited. The aim of the current study is to evaluate the outcomes and safety profile of bevacizumab in mCRC in a real-world setting in Romania. Patients and Methods: This was an observational, retrospective, multicentric, cohort study conducted in Romania that included patients with mCRC treated with bevacizumab as part of routine clinical practice. Study endpoints were progression-free survival, overall survival, adverse events, and patterns of bevacizumab use. Results: A total of 554 patients were included in the study between January 2008 and December 2018. A total of 392 patients (71%) received bevacizumab in the first line and 162 patients (29%) in the second line. Bevacizumab was mostly combined with a capecitabine/oxaliplatin chemotherapy regimen (31.6%). The median PFS for patients treated with bevacizumab was 8.4 months (interquartile range [IQR], 4.7-15.1 months) in the first line and 6.6 months (IQR, 3.8-12.3 months) in the second line. The median OS was 17.7 months (IQR, 9.3-30.6 months) in the first line and 13.5 months (IQR, 6.7-25.2 months) in the second line. Primary tumor resection was associated with a longer PFS and OS. The safety profile of bevacizumab combined with chemotherapy was similar to other observational studies in mCRC. Conclusions: The safety profile of bevacizumab was generally as expected. Although the PFS was generally similar to that reported in other studies, the OS was shorter, probably due to the less frequent use of bevacizumab after disease progression and the baseline patient characteristics. Patients with mCRC treated with bevacizumab who underwent resection of the primary tumor had a higher OS compared to patients with an unresected primary tumor.

Insights into the Relationship between Pentraxin-3 and Cancer.

Although cancer can be cured if detected early and treated effectively, it is still a leading cause of death worldwide. Tumor development can be limited by an appropiate immune response, but it can be promoted by chronic extensive inflammation through metabolic dysregulation and angiogenesis. In the past decade, numerous efforts have been made in order to identify novel candidates with predictive values in cancer diagnostics. In line with this, researchers have investigated the involvement of pentraxin-3 (PTX-3) in cellular proliferation and immune escape in various types of cancers, although it has not been clearly elucidated. PTX-3 is a member of the long pentraxin subfamily which plays an important role in regulating inflammation, innate immunity response, angiogenesis, and tissue remodeling. Increased synthesis of inflammatory biomarkers and activation of different cellular mechanisms can induce PTX-3 expression in various types of cells (neutrophils, monocytes, lymphocytes, myeloid dendritic cells, fibroblasts, and epithelial cells). PTX-3 has both pro- and anti-tumor functions, thus dual functions in oncogenesis. This review elucidates the potential usefulness of PTX-3 as a serum biomarker in cancer. While future investigations are needed, PTX-3 is emerging as a promising tool for cancer's diagnosis and prognosis, and also treatment monitoring.

An Insight into Deficient Mismatch Repair Colorectal Cancer Screening in a Romanian Population-A Bi-Institutional Pilot Study.

Background and Objectives: Colorectal cancer (CRC) can be classified as mismatch-repair-deficient (dMMR) with high levels of microsatellite instability (MSI-H), or mismatch-repair-proficient (pMMR) and microsatellite stable (MSS). Approximately 15% of patients have microsatellite instability (MSI). MSI-H tumors are associated with a high mutation burden. Monoclonal antibodies that block immune checkpoints can induce long-term durable responses in some patients. Pembrolizumab is the first checkpoint inhibitor approved in the EU to treat dMMR-MSI-H metastatic CRC. Materials and Methods: Our study assesses the regional variability of MSI-H colorectal cancer tumors in Romania. Formalin-fixed, paraffin-embedded (FFPE) tissue blocks containing tumor samples from 90 patients diagnosed with colorectal cancer were collected from two tertiary referral Oncology Centers from Romania. Tissues were examined for the expression loss of MMR proteins (MLH1, PMS2, MSH2, MSH6) using immunohistochemistry or MSI status using polymerase chain reaction (PCR), respectively. Results: MSI-H was detected in 19 (21.1%) patients. MSI-H was located more in ascending colon (36.8% vs. 9.9%, p-value = 0.0039) and less in sigmoid (5.3% vs. 33.8%, p-value = 0.0136) than MSS patients. Most patients were stage II for MSI-H (42.1%) as well as for MSS (56.3%), with significant more G1 (40.9% vs. 15.8%, p-value = 0.0427) for MSS patients. Gender, N stage, and M stage were identified as significant prognostic factors in multivariate analysis. MSI status was not a statistically significant predictor neither in univariate analysis nor multivariate analysis. Conclusion: Considering the efficacy of PD-1 inhibitor in metastatic CRC with MSI-H or dMMR, and its recent approval in EU, it is increasingly important to understand the prevalence across tumor stage, histology, and demographics, since our study displayed higher regional MSI-H prevalence (21%) compared to the literature.

Methods for Measuring Multiple Medication Adherence: A Systematic Review-Report of the ISPOR Medication Adherence and Persistence Special Interest Group.

BACKGROUND: A broad literature base exists for measuring medication adherence to monotherapeutic regimens, but publications are less extensive for measuring adherence to multiple medications. OBJECTIVES: To identify and characterize the multiple medication adherence (MMA) methods used in the literature. METHODS: A literature search was conducted using PubMed, PsycINFO, the International Pharmaceutical Abstracts, the Cumulative Index to Nursing and Allied Health Literature and the Cochrane Library databases on methods used to measure MMA published between January 1973 and May 2015. A two-step screening process was used; all abstracts were screened by pairs of researchers independently, followed by a full-text review identifying the method for calculating MMA. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed to conduct this systematic review. For studies that met the eligibility criteria, general study and adherence-specific characteristics and the number and type of MMA measurement methods were summarized. RESULTS: The 147 studies that were included originated from 32 countries, in 13 disease states. Of these studies, 26 used proportion of days covered, 23 used medication possession ratio, and 72 used self-reported questionnaires (e.g., the Morisky Scale) to assess MMA. About 50% of the studies included more than one method for measuring MMA, and different variations of medication possession ratio and proportion of days covered were used for measuring MMA. CONCLUSIONS: There appears to be no standardized method to measure MMA. With an increasing prevalence of polypharmacy, more efforts should be directed toward constructing robust measures suitable to evaluate adherence to complex regimens. Future research to understand the validity and reliability of MMA measures and their effects on objective clinical outcomes is also needed.

Assessment of efficacy of dendritic cell therapy and viral therapy in high grade glioma clinical trials. A meta-analytic review.

In recent years, immunotherapy has raised the interest of many studies and provided different perspectives for the therapeutic management of high grade glioma. Our meta-analysis focused on the effectiveness of dendritic cell (DC) therapy and viral therapy (VT) in clinical trials. Fourteen eligible studies have been evaluated and the results suggest the improvement of both OS (HR = 0.65) (p < 0.0001) and PFS (HR = 0.59) (p = 0.01) for patients receiving DC therapy. The data for VT showed a slight improvement in terms of OS (HR = 0.81), while PFS was similar to the control arms (HR = 1.06) (p = 0.41).

Digging in real-word electronic database for assessing CDK 4/6 inhibitors adherence in breast cancer patients from Romania.

Introduction: It is imperative for patients to respect the prescribed treatments to achieve the anticipated clinical outcomes, including the outpatients receiving oral anti-cancer drugs such as selective cyclin-dependent kinase 4/6 inhibitors (CDK 4/6i). With the introduction of three CDK 4/6i drugs in the Romanian pharmaceutical market in 2018, our study aimed to evaluate medication adherence and the influencing factors among patients undergoing treatment with palbociclib, ribociclib, or abemaciclib for advanced or metastatic breast cancer. Methods: Medication adherence was assessed using the Proportion of Days Covered (PDC) method, and Spearman correlation analysis was conducted to explore the relationships between adherence, age, gender, and follow-up duration. Results: The study enrolled 330 breast cancer patients, with an average follow-up period of 14.6 ± 12.5 months for palbociclib, 10.6 ± 7.1 months for ribociclib, and 8.6 ± 6.4 months for abemaciclib-treated patients. A small proportion of patients demonstrated non-adherence: 12.8% for palbociclib, 14.6% for ribociclib, and 14.7% for abemaciclib. Among patients receiving palbociclib, there was no significant correlation between adherence, age (rho = 0.07, p = 0.35), or gender (rho = -0.144, p = 0.054). However, a significant correlation was found with the duration of follow-up (rho = -0.304, p < 0.0001). Similar results were observed for patients receiving ribociclib or abemaciclib. Most patients received combination therapy with letrozole (46%) and exemestane (13%) for palbociclib, letrozole (48%) and fulvestrant (19%) for ribociclib, and fulvestrant (39%) and letrozole (27%) for abemaciclib, Discussion: High adherence rates were observed among patients treated with CDK 4/6i drugs, with no significant differences noted among the three drugs in this class. However, the collected patient data was limited, lacking information on adverse reactions that could potentially lead to treatment discontinuation, as determined by the oncologist's decision not to prescribe. Consequently, a comprehensive understanding of all factors contributing to the low adherence levels is hindered.

The Effects of Arginine-Based Supplements on Fatigue Levels following COVID-19 Infection: A Prospective Study in Romania.

The purpose of this study was to examine the effects of two arginine-based supplements on the fatigue level of patients following the COVID-19 infection. This is a prospective study of the SARS-CoV-2-infected patients divided into two groups (according to family physicians' prescriptions, Group 1 of patients were treated with Astenor Energy® containing arginine aspartate, B6 vitamin, biotin and magnesium, and Group 2 of patients were treated with Astenor Forte® containing L-arginine and malic acid). The patients visited their family physicians from October 2021 to January 2022, complaining of physical and/or mental fatigue following the COVID-19 infection. We recorded 505 patients (146 patients in Group 1 and 359 patients in Group 2) and analyzed the fatigue level using the Fatigue Assessment Scale (FAS) through its total (FAS-T), mental (FAS-M) and physical (FAS-P) scores, at baseline and after three months of treatment. There was no difference between the two groups in terms of age (p = 0.265), but more men were included in Group 1 than in Group 2 (p = 0.001). The patients from Group 2 were significantly more likely to be treated at home than those included in Group 1 (89.7% vs. 65.1%, p < 0.0001) because of the lower severity of the COVID-19 infection (asymptomatic or mild: 82.5% vs. 48.7%, p < 0.0001). After 3 months of treatment, patients indicated no fatigue in the higher percentage compared to than at the baseline (68.7% vs. 27.7%), and the fatigue level significantly decreased both in Group 1 (median baseline 33.0 vs. follow-up 17.00, p < 0.0001) and Group 2 (median baseline 25.0 vs. follow-up 17.00, p < 0.0001). These findings suggest that supplements with L-arginine may be proposed as a remedy to restore physical and mental performance affected by the fatigue burden in people with COVID-19 or following the COVID-19 infection.

Digital technology for health shows disparities in cancer prevention between digital health technology users and the general population in Romania.

Introduction: Digital health services and technology are rapidly developing following the COVID-19 pandemic. This study aimed to reveal the differences between users of digital health technology (DHT) and the general population with regard to cancer prevention. Materials and Methods: This was an observational study on a conventional sample of 270 DHT users with completed data, performed in September 2021. Results: A significant difference was observed in the proportion of DHT users and the general population reporting the screening test results, which was 2-6 times higher in the DHT group. Digital technologies applied to the "self-care" model were more suitable for internet-literate populations. Discussion: Including digital technologies in a self-care model may be more suitable for internet-literate individuals. Thus, in a preventative health organizational framework, DHT should be integrated and used at the primary care level in the general population to improve disparities in the preventative health domain.

A Preclinical Systematic Review and Meta-Analysis of Behavior Testing in Mice Models of Ischemic Stroke.

Stroke remains one of the most important causes of death and disability. Preclinical research is a powerful tool for understanding the molecular and cellular response to stroke. However, a lack of standardization in animal evaluation does not always ensure reproducible results. In the present study, we wanted to identify the best strategy for evaluating animal behavior post-experimental stroke. As such, a meta-analysis was made, evaluating behavioral tests done on male C57BL/6 mice subjected to stroke or sham surgery. Overall, fifty-six studies were included. Our results suggest that different types of tests should be used depending on the post-stroke period one needs to analyze. In the hyper-acute, post-stroke period, the best quantifier will be animal examination scoring, as it is a fast and inexpensive way to identify differences between groups. When evaluating stoke mice in the acute phase, a mix of animal examination and motor tests that focus on movement asymmetry (foot-fault and cylinder testing) seem to have the best chance of picking up differences between groups. Complex tasks (the rotarod test and Morris water maze) should be used within the chronic phase to evaluate differences between the late-subacute and chronic phases.

Predicting mortality in patients with nonvariceal upper gastrointestinal bleeding using machine-learning.

Background: Non-endoscopic risk scores, Glasgow Blatchford (GBS) and admission Rockall (Rock), are limited by poor specificity. The aim of this study was to develop an Artificial Neural Network (ANN) for the non-endoscopic triage of nonvariceal upper gastrointestinal bleeding (NVUGIB), with mortality as a primary outcome. Methods: Four machine learning algorithms, namely, Linear Discriminant Analysis (LDA), Quadratic Discriminant Analysis (QDA), logistic regression (LR), K-Nearest Neighbor (K-NN), were performed with GBS, Rock, Beylor Bleeding score (BBS), AIM65, and T-score. Results: A total of 1,096 NVUGIB hospitalized in the Gastroenterology Department of the County Clinical Emergency Hospital of Craiova, Romania, randomly divided into training and testing groups, were included retrospectively in our study. The machine learning models were more accurate at identifying patients who met the endpoint of mortality than any of the existing risk scores. AIM65 was the most important score in the detection of whether a NVUGIB would die or not, whereas BBS had no influence on this. Also, the greater AIM65 and GBS, and the lower Rock and T-score, the higher mortality will be. Conclusion: The best accuracy was obtained by the hyperparameter-tuned K-NN classifier (98%), giving the highest precision and recall on the training and testing datasets among all developed models, showing that machine learning can accurately predict mortality in patients with NVUGIB.

Budget impact analysis of a bovine pericardial aortic bioprosthesis versus mechanical aortic valve replacement in adult patients with aortic stenosis in Romania.

AIMS: An analysis of the budget impact of using a bovine pericardial aortic bioprosthesis (BPAB) or a mechanical valve (MV) in aortic stenosis (AS) patients in Romania. MATERIALS AND METHODS: A decision-tree with a partitioned survival model was used to predict the financial outcomes of using either a BPAB (the Carpentier-Edwards Perimount Magna Ease Valve) or MV in aortic valve replacement (AVR) procedure over a 5-year period. The budget impact of various resource consumption including disabling strokes, reoperations, minor thromboembolic events, major bleeding, endocarditis, anticoagulation treatment and monitoring, and echocardiogram assessments were compared for both types of valves. One-way sensitivity analyses (OWSA) were conducted on the input costs and probabilities. RESULTS: The use of BPAB compared to MV approaches budget neutrality due to incremental savings year-on-year. The initial surgical procedure and reoperation costs for BPAB are offset by savings in acenocoumarol use, disabling strokes, major bleeding, minor thromboembolic events, and anticoagulation complications. The cost of the initial procedure per patient is 460 euros higher for a BPAB due to the higher valve acquisition cost, although this is partially offset by a shorter hospital stay. The OWSA shows that the total procedure costs, including the hospital stay, are the primary cost drivers in the model. LIMITATIONS: Results are limited by cost data aggregation in the DRG system, exclusion of costs for consumables and capital equipment use, possible underestimation of outpatient complication costs, age-related variations of event rates, and valve durability. CONCLUSIONS: Adopting BPAB as a treatment option for AS patients in Romania can lead to cost savings and long-term economic benefits. By mitigating procedure costs and increasing anticoagulation treatment costs, BPAB offers a budget-neutral option that can help healthcare providers, policymakers, and patients alike manage the growing burden of AS in Romania.

Outcomes in Patients Admitted for Upper Gastrointestinal Bleeding and COVID-19 Infection: A Study of Two Years of the Pandemic.

Upper gastrointestinal bleeding (UGIB) represents a major emergency, and patient management requires endoscopic assessment to ensure appropriate treatment. The impact of COVID-19 on patient mortality in UGIB may be related to the combination of respiratory failure and severe bleeding and indirectly to delayed admissions or a reduction in endoscopic procedures. METHODS: We conducted a retrospective study involving patients admitted between March 2020 and December 2021 with UGIB and confirmed. Our objective was to compare these types of patients with those negative for SARS-CoV-2 infection, as well as with a pre-pandemic group of patients admitted between May 2018 and December 2019. RESULTS: Thirty-nine patients (4.7%) with UGIB had an active COVID-19 infection. A higher mortality rate (58.97%) and a high risk of death (OR 9.04, p < 0.0001) were noted in the COVID-19 pandemic, mostly because of respiratory failure; endoscopy was not performed in half of the cases. Admissions for UGIB have decreased by 23.7% during the pandemic. CONCLUSIONS: COVID-19 infection in patients admitted for UGIB was associated with a higher mortality rate because of respiratory failure and possible delays in or contraindications of treatment.

CYP27B1 Enzyme in Psoriasis: A Preliminary Study of Immunohistochemical Observations.

Connections between vitamin D and psoriasis have been a matter of interest for the past decades, with its active metabolite, 1,25(OH)2 vitamin D, being valued for antiproliferative and immunomodulatory effects. However, none of vitamin D's actions could be possible without the CYP27B1 enzyme that bio-activates this metabolite of interest. In order to see if there is any link between the enzyme expression and the disease's particularities, we conducted a preliminary study that involved 11 skin biopsies of patients with mild (n = 4) or moderate to severe psoriasis (n = 7). The cell proliferation antigen Ki67 and the CD45RO+ marker were also assessed. Compared with healthy skin, in psoriasis, it is reported that the enzyme's expression seems to be more ubiquitous, but a clear correlation between the disease's severity and the CYP27B1 expression was, to our knowledge, lacking. We found that, in patients with very mild psoriasis, the enzyme expression was observed in the epidermal stratum basale in a similar manner as in healthy skin specimens. Contrary, for higher severity scores, a divergent result was observed, with the enzyme being either variably spread in the epidermal stratum spinosum or completely absent. Unlike malignant diseases, a significant connection between CYP27B1 and Ki67 (p = 0.313) or CYP27B1 and CD45RO+ (p = 0.657) does not seem to be relevant in psoriasis.

Association between Direct-Acting Agents Adherence and Health-Related Quality of Life of Patients with Hepatitis C.

This observational study included all patients undergoing HCV treatment with direct-acting antiviral (DAA)-based therapy between May 2020 and September 2023 at the Dolj County Hospital, Romania. The aim was to investigate adherence to DAAs among HCV patients and the effect of this treatment on their health-related quality of life (HRQoL). Chronic HCV-infected patients were prospectively evaluated at baseline (T0), before the beginning of treatment, and 12 weeks after completing DAAs treatment (T1). The HCV-AD10 questionnaire was used to measure DAAs adherence, and HRQoL was assessed with the 15D instrument. The 15D questionnaire was administered at two time points: T0 and T1, during which the Sustained Virologic Response (SVR) was also measured. The primary outcome was DAAs adherence, with secondary outcomes including quality of life (QoL), and sustained virologic response (SVR). DAAs based therapy was initiated for 368 patients, all of whom were health insured. HRQoL and psychological state of HCV patients clinically improved. The DAAs adherence was very good (mean±SD, 91.51±8.34), being influenced by age (younger patients were much adherent, rho=-0.112, p-value=0.031) and the severity of the disease (patients with more severe hepatitis were less adherent, rho=-0.167, p-value=0.001). DAAs had a significant effect on improving HRQoL of HCV patients, but did not influence medication adherence.

Evaluation of Pentraxin 3 and Serum Amyloid A in the Gingival Crevicular Fluid of Patients with Periodontal Disease and Obesity.

BACKGROUND: Pentraxin 3 (PTX3) is associated with periodontal tissue inflammation, a condition that precedes alveolar bone resorption. It is also elevated in obese tissues and is a useful biomarker of proinflammatory status. Serum amyloid A (SAA) is a proinflammatory and lipolytic adipokine. Adipocytes strongly express SAA, which suggests that it may have a significant role in the production of free fatty acids and local and systemic inflammation. MATERIALS AND METHODS: We statistically analyzed the gingival crevicular fluid (GCF) values of PTX3 and SAA in patients with periodontal disease, who were diagnosed with obesity, and compared them with the values of inflammatory markers from patients diagnosed with one of the diseases and with healthy patients. RESULTS: The patients with obesity and periodontitis had significantly higher levels of PTX3 and SAA than the patients diagnosed with either obesity or periodontitis. CONCLUSIONS: These two markers are involved in the association between the two pathologies, as evidenced by the correlations between these levels and some clinical parameters.

The Reduction of After-Hours and Weekend Effects in Upper Gastro-intestinal Bleeding Mortality During the COVID-19 Pandemic Compared to the Pre-Pandemic Period.

Background: In upper gastrointestinal bleeding (UGIB), admissions after normal working hours and during weekends may be associated with increased mortality. Aim: To assess the evolution of the after-hours and weekend effects during the COVID-19 pandemic as a result of progressive improved management despite management challenges during the pandemic. Methods: We performed an observational study of patients admitted for UGIB at a tertiary academic center between March 2020 and December 2021, compared to the corresponding timeframe before the pandemic. Admissions were assessed based on regular hours versus after-hours and weekdays versus weekends. We stratified patients based on demographic data, etiology, prognostic scores, the time between symptom onset and admission, as and between admission and endoscopy. The outcomes included mortality, rebleeding rate, the requirement for surgery and transfusion, and hospitalization days. Results: 802 cases were recorded during the pandemic, and 1006 cases before the pandemic. The overall mortality rate was 12.33%. Patients admitted after hours and during weekends had a higher mortality rate compared to those admitted during regular hours and weekdays (15.18% versus 10.22%, and 15.25% versus 11.16%), especially in cases of non-variceal bleeding. However, the difference in mortality rates was reduced by 2/3 during the pandemic, despite the challenges posed by COVID-19 infection. This suggests that there was an equalization effect of care in UGIB, regardless of the admission time. The differences observed in mortality rates for after-hours and weekend admissions seem to be primarily related to a higher proportion of patients who did not undergo endoscopy, while the proportion of severe cases remained similar. Blood requirements, hospital days, and rebleeding rate were similar between the two groups. Conclusion: Admissions during weekends and after-hours have been associated with increased mortality, particularly in cases of non-variceal bleeding. However, the impact of this association was significantly reduced during the pandemic.

C-Reactive Protein as a Marker of Inflammation in Children and Adolescents with Metabolic Syndrome: A Systematic Review and Meta-Analysis.

Metabolic syndrome (MetS) in the pediatric population has been reported in many studies to be associated with an inflammatory response. However, to our knowledge, there is no definitive conclusion in the form of a meta-analysis. The issue we aimed to address is whether C-reactive protein (CRP) is a trustworthy marker in detecting inflammation in children and adolescents with MetS. We systematically searched PubMed, MEDLINE, Cochrane Central Register of Controlled Trials, the ISI Web of Science, and SCOPUS until 31 June 2023 for studies involving children and adolescents with MetS where hsCRP or CRP were measured. After the screening process, we identified 24 full-text articles that compared 930 patients with MetS with either healthy (n = 3782) or obese (n = 1658) controls. The risk of bias in the included studies was assessed using the Begg's rank correlation test and Egger's regression test. Statistical analysis was carried out based on pooled mean differences (MDs) and an associated 95% CI. Data analysis showed that MetS is associated with higher levels of CRP than those in healthy controls (MD = 1.28, 95% CI: (0.49-2.08), p = 0.002) in obese patients (MD = 0.88, 95% CI: (0.38-1.39), p = 0.0006). However, conventional methods of CRP analysis were found to be more accurate in differentiating between children and adolescents with obesity and those with MetS, compared with hsCRP (MD = 0.60, 95% CI: (-0.08-1.28), p = 0.08). No risk of bias was assessed. In conclusion, CRP is a reliable inflammatory marker for differentiating pediatric patients with MetS from healthy ones. On the other hand, it did not prove to be very accurate in distinguishing between patients who had MetS and those who were obese. There should be more research performed in this field.