In silico study to explore the mechanism of Toxoplasma-induced inflammation and target therapy based on sero and salivary Toxoplasma.

We aimed to assess salivary and seroprevalence of Toxoplasma immunoglobulins in risky populations and evaluate drug docking targeting TgERP. A cross-sectional study was conducted in Alexandria University hospitals' outpatient clinics. 192 participants were enrolled from September 2022 to November 2023. Anti-Toxoplasma IgG and IgM were determined in serum and saliva by ELISA. An in-Silico study examined TgERP's protein-protein interactions (PPIs) with pro-inflammatory cytokine receptors, anti-inflammatory cytokine, cell cycle progression regulatory proteins, a proliferation marker, and nuclear envelope integrity-related protein Lamin B1. Our findings revealed that anti-T. gondii IgG were detected in serum (66.1%) and saliva (54.7%), with 2.1% of both samples were positive for IgM. Salivary IgG had 75.59% sensitivity, 86.15% specificity, 91.40% PPV, 64.40% NPP, 79.17% accuracy and fair agreement with serum IgG. On the other hand, the sensitivity, specificity, PPV, NPV, and accuracy in detecting salivary IgM were 75.0%, 99.47%, 75.0%, 99.47%, and 98.96%. AUC 0.859 indicates good discriminatory power. Examined synthetic drugs and natural products can target specific amino acids residues of TgERP that lie at the same binding interface with LB1 and Ki67, subsequently, hindering their interaction. Hence, salivary samples can be a promising diagnostic approach. The studied drugs can counteract the pro-inflammatory action of TgERP.

A comparison of antimicrobial regimen outcomes and antibiogram development in microbial keratitis: a prospective cohort study in Alexandria, Egypt.

INTRODUCTION: Antimicrobial resistance in microbial keratitis has not been previously explored in Alexandria. We aim to recommend effective therapies through identification of etiological agents, determination of antimicrobial susceptibilities, and comparing outcomes of empiric topical antimicrobials. METHODS: In this 2022 prospective cohort conducted in Alexandria Main University Hospital cornea clinic, antimicrobial susceptibilities of isolated microorganisms from corneal scrapings were detected and antibiograms were developed. Bacterial (BK), fungal (FK), or mixed fungal/bacterial keratitis (MFBK) patients on empiric regimens were compared for ulcer healing, time-to-epithelialization, best-corrected visual acuity, interventions, and complications. RESULTS: The prevalent microorganisms in 93 positive-cultures were coagulase-negative staphylococci (CoNS, 30.1%), Pseudomonas aeruginosa (14%), and Aspergillus spp. (12.9%). CoNS were susceptible to vancomycin (VAN, 100%) and moxifloxacin (MOX, 90.9%). Gram-negative bacteria showed more susceptibility to gatifloxacin (90.9%) than MOX (57.1%), and to gentamicin (GEN, 44.4%) than ceftazidime (CAZ, 11.8%). Methicillin-resistance reached 23.9% among Gram-positive bacteria. Fungi exhibited 10% resistance to voriconazole (VRC). Percentages of healed ulcers in 49 BK patients using GEN + VAN, CAZ + VAN and MOX were 85.7%, 44.4%, and 64.5%, respectively (p = 0.259). Their median time-to-epithelialization reached 21, 30, and 30 days, respectively (log-rank p = 0.020). In 51 FK patients, more ulcers (88.9%) healed with natamycin (NT) + VRC combination compared to VRC (39.1%) or NT (52.6%) (p = 0.036). Their median time-to-epithelialization was 65, 60, and 22 days, respectively (log-rank p < 0.001). The VRC group required more interventions (60.9%) than NT + VRC-treated group (11.1%) (p = 0.018). In 23 MFBK patients, none healed using NT + CAZ + VAN, while 50% healed using VRC + CAZ + VAN (p = 0.052). Regimens had comparable visual outcomes and complications. CONCLUSION: Based on the higher detected susceptibility, we recommend empiric MOX in suspected Gram-positive BK, gatifloxacin in Gram-negative BK, and GEN + VAN in severe BK. Due to better outcomes, we recommend NT + VRC in severe FK. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT05655689. Registered December 19, 2022- Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT05655689?cond=NCT05655689.&draw=2&rank=1.

Effect of medication therapy management services on medication-burden quality of life in hemodialysis patients.

BACKGROUND: Hemodialysis (HD) patients commonly receive polypharmacy leading to increased likelihood of drug related problems (DRPs) and poor quality of life. Medication Therapy Management (MTM) services discover and resolve DRPs and may specifically improve Medication-burden Quality of life (MBQoL) in HD patients. We aimed to assess the effect of MTM services on DRPs and MBQoL among HD patients. METHODS: A prospective pre-post study was conducted on 104 patients in an HD unit in Alexandria, Egypt. MBQoL was assessed at baseline and after three months of MTM sessions, using the Arabic, validated version of the Patient Reported Outcomes Measure of Pharmaceutical Therapy (PROMPT) questionnaire. Cohen's d test and multiple linear regression were used to assess the effect size of MTM and the factors affecting MBQoL, respectively. DRPs, adverse events and adherence were also monitored. RESULTS: MBQoL improved significantly after the implementation of MTM (Cohen's d=0.88, p < 0.01) with the largest effect size in the "medicine information and relation with healthcare providers" domain. DRPs decreased significantly after MTM implementation (11.97 ± 4.65 versus 7.63 ± 3.85 per patient, p<0.001). The mean adverse events per patient were also reduced (9.69 ± 4.12 versus 6.56 ± 3.77, p < 0.001). CONCLUSION: Applying MTM services presents an opportunity to improve care for HD patients by improving MBQoL, decreasing DRPs and adverse events.

Catastrophic Costs among Tuberculosis-Affected Households in Egypt: Magnitude, Cost Drivers, and Coping Strategies.

Despite national programs covering the cost of treatment for tuberculosis (TB) in many countries, TB patients still face substantial costs. The end TB strategy, set by the World Health Organization (WHO), calls for "zero" TB households to be affected by catastrophic payments by 2025. This study aimed to measure the catastrophic healthcare payments among TB patients in Egypt, to determine its cost drivers and determinants and to describe the coping strategies. The study utilized an Arabic-validated version of the TB cost tool developed by the WHO for estimating catastrophic healthcare expenditure using the cluster-based sample survey with stratification in seven administrative regions in Alexandria. TB payments were considered catastrophic if the total cost exceeded 20% of the household's annual income. A total of 276 patients were interviewed: 76.4% were males, 50.0% were in the age group 18-35, and 8.3% had multidrug-resistant TB. Using the human capital approach, 17.0% of households encountered catastrophic costs compared to 59.1% when using the output approach. The cost calculation was carried out using the Egyptian pound converted to the United States dollars based on 2021 currency values. Total TB cost was United States dollars (USD) 280.28 ± 29.9 with a total direct cost of USD 103 ± 10.9 and a total indirect cost of USD 194.15 ± 25.5. The direct medical cost was the main cost driver in the pre-diagnosis period (USD 150.23 ± 26.89 pre diagnosis compared to USD 77.25 ± 9.91 post diagnosis, p = 0.013). The indirect costs (costs due to lost productivity) were the main cost driver in the post-diagnosis period (USD 4.68 ± 1.18 pre diagnosis compared to USD 192.84 ± 25.32 post diagnosis, p < 0.001). The households drew on multiple financial strategies to cope with TB costs where 66.7% borrowed and 25.4% sold household property. About two-thirds lost their jobs and another two-thirds lowered their food intake. Being female, delay in diagnosis and being in the intensive phase were significant predictors of catastrophic payment. Catastrophic costs were high among TB households in Alexandria and showed wide variation according to the method used for indirect cost estimation. The main cost driver before diagnosis was the direct medical costs, while it was the indirect costs, post diagnosis.

A Meta-Analysis on the Safety and Immunogenicity of Covid-19 Vaccines.

OBJECTIVE: The presented meta-analysis (MA) aims at identifying the vaccine safety and immunogenicity in published trials about SARS-CoV-2 vaccines. METHODS: All relevant publications were systematically searched and collected from different databases (Embase, Scopus, EBSCO, MEDLINE central/PubMed, Science Direct, Cochrane Central Register for Clinical Trials (CENTRAL), Clinical Trials.gov, WHO International Clinical Trials Registry Platform (ICTRP), COVID Trial, COVID Inato, Web of Science, ProQuest Thesis, ProQuest Coronavirus Database, SAGE Thesis, Google Scholar, Research Square, and Medxriv) up to January 10, 2021. The pooled vaccine safety and immunogenicity following vaccination in phase 1 and 2 vaccine clinical trials, as well as their 95% confidence intervals (CI), were estimated using the random-effects model. RESULTS: The predefined inclusion criteria were met in 22 out of 8592 articles. The proportion of anti-severe acute respiratory distress coronavirus 2 (SARS-CoV-2) antibody responses after 7 days among 72 vaccinated persons included in 1 study was 81% (95% CI: 70-89), after 14 days among 888 vaccinated persons included in 6 studies was 80% (95% CI: 58-92), after 28 days among 1589 vaccinated persons included in 6 studies was 63% (95% CI: 59-67), after 42 days among 478 vaccinated persons included in 5 studies was 93% (95% CI: 80-98), and after 56 days among 432 vaccinated persons included in 2 studies was 93% (95% CI: 83-97). Meta regression explains more than 80% of this heterogeneity, where the main predictors were; the inactivated vaccine type (ß = 2.027, P = 0.0007), measurement of antibodies at week 1 (ß = -4.327, P < 0.0001) and at week 3 of the first dose (ß = -2.02, P = 0.0025). Furthermore, the pooled proportion adverse effects 7 days after vaccination was 0.01 (0.08-0.14) for fever, headache 0.23 (0.19-0.27), fatigue 0.10 (0.07-0.13), and 0.18 (0.14-0.23) for muscle pain. CONCLUSION: Immunogenicity following vaccination ranged from 63% to 93% depending on the time at which the antibody levels were measured.

Efficacy and Effectiveness of SARS-CoV-2 Vaccines: A Systematic Review and Meta-Analysis.

The coronavirus disease 2019 (COVID-19) pandemic has threatened global health and prompted the need for mass vaccination. We aimed to assess the efficacy and effectiveness of COVID-19 vaccines to prevent mortality and reduce the risk of developing severe disease after the 1st and 2nd doses. From conception to 28 June 2021, we searched PubMed, Cochrane, EBSCO, Scopus, ProQuest, Web of Science, WHO-ICTRP, and Google Scholar. We included both observational and randomized controlled trials. The pooled vaccine efficacy and effectiveness following vaccination, as well as their 95 percent confidence intervals (CI), were estimated using the random-effects model. In total, 22 of the 21,567 screened articles were eligible for quantitative analysis. Mortality 7 and 14 days after full vaccination decreased significantly among the vaccinated group compared to the unvaccinated group (OR = 0.10, ([95% CI, 0.04-0.27], I2 = 54%) and (OR = 0.46, [95% CI, 0.35-0.61], I2 = 0%), respectively. The probability of having severe disease one or two weeks after 2nd dose decreased significantly (OR = 0.29 [95% CI, 0.19-0.46], I2 = 25%) and (OR = 0.08 [95% CI, 0.03-0.25], I2 = 74%), respectively. The incidence of infection any time after the 1st and 2nd doses diminished significantly (OR = 0.14 [95% CI, 0.07-0.4], I2 = 100%) and (OR = 0.179 [95% CI, 0.15-0.19], I2 = 98%), respectively. Also, incidence of infection one week after 2nd dose decreased significantly, (OR = 0.04, [95% CI (0.01-0.2], I2 = 100%). After meta-regression, the type of vaccine and country were the main predictors of outcome [non-mRNA type, ß = 2.99, p = 0.0001; country UK, ß = -0.75, p = 0.038; country USA, ß = 0.8, p = 0.02]. This study showed that most vaccines have comparable effectiveness, and it is purported that mass vaccination may help to end this pandemic.

A Community Pharmacy-Based Intervention in the Matrix of Type 2 Diabetes Mellitus Outcomes (CPBI-T2DM): A Cluster Randomized Controlled Trial.

INTRODUCTION: Egypt has the ninth highest diabetes mellitus (DM) prevalence in the world. There is a growing interest in community involvement in DM management. AIM OF THE STUDY: The aim of the study was to evaluate the tailored diabetes care model (DCM) implementation in Alexandria governorate by community pharmacy-based intervention (CPBI) from a clinical, humanistic, and economic aspect. METHODS: This is a 6-month period cross-over cluster randomized control trial conducted in Alexandria. Ten clusters owing 10 community pharmacies (CPs) recruited 100 health insurance-deprived T2DM patients with >7% HbA1c in 6-months. The study was divided into 2 phases (3 months for each period) with a 1-month washout period in between. After CPs training on DCM, the interventional group received pictorial training for 45 minutes in first visit, and 15 minutes in weekly visits, whereas the control group patients received the usual care (UC). At baseline and end of each phase (3 months), patients had clinical and physical activity assessments, filled all forms of study questionnaire (knowledge, self-management, satisfaction, and adherence) and did all laboratory investigations (Fasting Blood Glucose [FBG]), HbA1c, protein-creatinine clearance (PCR), creatine clearance (GFR), and lipid profile. RESULTS: There was no significant difference in the basal systolic and diastolic blood pressure between patients in the CBPI and UC groups, but the CBPI had significantly decreased the mean SBP and DBP by (P = .008, .040, respectively). Also, significant waist circumference and BMI reductions (-5.82 cm and -1.86 kg/m2, P = .001) were observed in the CBPI. The CBPI patients achieved a greater reduction in FBG and HbA1C than the UC patients (102 mg/dL and 1.9%, respectively P < .001). Also, significant reductions in total cholesterol, LDL, and triglyceride (-6.4, -15.4, and -6.3 mg/dL respectively, P = .001) were achieved in the CBPI group. No significant differences were found in HDL, GFR, and PCR. Moreover, significant improvements of behavior, score of knowledge, self-management, satisfaction, and adherence were observed in CBPI patients. After multivariate analysis, HbA1C readings were significantly influenced by baseline HbA1C and eating habits. The cost saving for CPBI was -1581 LE per 1% HbA1c reduction. CONCLUSION: This is the first study in Egypt that illustrated the positive impact of pictorial DCM delivered by CPBI collaborative care on clinical, humanistic, laboratory, and economic outcomes to local T2DM patients.

Evaluation of Praziquantel Effectivenss After Decades of Prolonged Use in an Endemic Area in Egypt.

PURPOSE: Praziquantel (PZQ) is the preferred drug for schistomiasis treatment because of its safety. As PZQ is used for mass drug administration (MDA) in schistosomiasis endemic areas, the effectiveness of the drug, used solely for decades, should be continuously monitored to detect drug resistance. We aimed to assess the effectiveness of PZQ to cure Schistosoma mansoni infection and to reduce the intensity of infection in an endemic area by estimating the cure rate (CR), egg reduction rate (ERR), and comparing these estimates to the levels recommended by the World Health Organization (WHO). METHODS: A total of 342 children aged 5-15 years living in Kafr-El-Sheikh were screened for S. mansoni infection. Stool samples were examined microscopically using Kato-Katz (KK) technique. Among the screened children, 106 children had S. mansoni ova in stool, 100 of them received the first dose of PZQ (40 mg/kg). Four weeks later, 96 of 100 children received the second dose of PZQ. Stool samples, collected 4 weeks after each dose of PZQ, were examined using KK. The effectiveness of PZQ was assessed based on ERR and CR. RESULTS: CR after the first dose of PZQ was 66.7%, increased to 79.12% after second dose (X2 = 3.05, P = 0.08). Median egg count before treatment was 30.00 (6.00-744), that significantly decreased after two doses of PZQ to 0.00 (0.00-221.33) (Z = 8.29, P = 0.001). Children aged 10-15 years showed higher CR (91.3%) than those aged 5-9 years (OR = 5.25, CI 1.58-17.40). CONCLUSIONS: PZQ is still an effective agent against S. mansoni in endemic areas, achieving a high CR and ERR with predominantly low intensity of infection. Age is a main predictor of response to PZQ.

Improving Timeliness of Internal Medicine Consults in the Emergency Department: A Quality Improvement Initiative.

INTRODUCTION: Emergency department (ED) wait time is an important health system quality indicator. Prolonged consult to decision time (CTDT), the time it takes to reach a disposition decision after receiving a specialty consultation request, can contribute to increased overall length of stay in the ED. OBJECTIVE: To identify delays in the consultation process for general internal medicine (GIM) and trial interventions to reduce CTDT. METHODS: The study was conducted at a large tertiary teaching hospital with GIM inpatient wards at two campuses. Four interventions were trialed over sequential Plan-Do-Study-Act cycles: (1) process mapping, (2) resident education sessions, (3) audit and feedback of CTDT, and (4) adding a swing shift during peak consult volume. MEASUREMENTS: The primary outcome measures were mean CTDT for patients admitted to GIM and the proportion of admitted patients with CTDT of less than 3 hours. RESULTS: Mean CTDT decreased from 4.61 hours before intervention to 4.18 hours after intervention (p < .0001). The proportion of GIM patients with CTDT less than 3 hours increased from 25% to 33% (p < .0001). CONCLUSIONS: The interventions trialed led to a sustained reduction in CTDT over a 12-month period and demonstrated the effectiveness of education in influencing physician performance.