Repurposed Antiviral Drugs for Covid-19 - Interim WHO Solidarity Trial Results.

BACKGROUND: World Health Organization expert groups recommended mortality trials of four repurposed antiviral drugs - remdesivir, hydroxychloroquine, lopinavir, and interferon beta-1a - in patients hospitalized with coronavirus disease 2019 (Covid-19). METHODS: We randomly assigned inpatients with Covid-19 equally between one of the trial drug regimens that was locally available and open control (up to five options, four active and the local standard of care). The intention-to-treat primary analyses examined in-hospital mortality in the four pairwise comparisons of each trial drug and its control (drug available but patient assigned to the same care without that drug). Rate ratios for death were calculated with stratification according to age and status regarding mechanical ventilation at trial entry. RESULTS: At 405 hospitals in 30 countries, 11,330 adults underwent randomization; 2750 were assigned to receive remdesivir, 954 to hydroxychloroquine, 1411 to lopinavir (without interferon), 2063 to interferon (including 651 to interferon plus lopinavir), and 4088 to no trial drug. Adherence was 94 to 96% midway through treatment, with 2 to 6% crossover. In total, 1253 deaths were reported (median day of death, day 8; interquartile range, 4 to 14). The Kaplan-Meier 28-day mortality was 11.8% (39.0% if the patient was already receiving ventilation at randomization and 9.5% otherwise). Death occurred in 301 of 2743 patients receiving remdesivir and in 303 of 2708 receiving its control (rate ratio, 0.95; 95% confidence interval [CI], 0.81 to 1.11; P = 0.50), in 104 of 947 patients receiving hydroxychloroquine and in 84 of 906 receiving its control (rate ratio, 1.19; 95% CI, 0.89 to 1.59; P = 0.23), in 148 of 1399 patients receiving lopinavir and in 146 of 1372 receiving its control (rate ratio, 1.00; 95% CI, 0.79 to 1.25; P = 0.97), and in 243 of 2050 patients receiving interferon and in 216 of 2050 receiving its control (rate ratio, 1.16; 95% CI, 0.96 to 1.39; P = 0.11). No drug definitely reduced mortality, overall or in any subgroup, or reduced initiation of ventilation or hospitalization duration. CONCLUSIONS: These remdesivir, hydroxychloroquine, lopinavir, and interferon regimens had little or no effect on hospitalized patients with Covid-19, as indicated by overall mortality, initiation of ventilation, and duration of hospital stay. (Funded by the World Health Organization; ISRCTN Registry number, ISRCTN83971151; ClinicalTrials.gov number, NCT04315948.).

In vivo evaluation of the virucidal efficacy of chlorhexidine and povidone-iodine mouthwashes against salivary SARS-CoV-2. A randomized-controlled clinical trial.

OBJECTIVES: The oral cavity is potentially high-risk transmitter of COVID-19. Antimicrobial mouthrinses are used in many clinical preprocedural situations for decreasing the risk of cross-contamination in the dental setting. It is important to investigate the efficacy of mouthwash solutions against salivary SARS-CoV-2 in order to reduce the exposure of the dental team during dental procedures. AIMS: The aim of this in vivo study was to evaluate the efficacy of 2 preprocedural mouthrinses in the reduction of salivary SARS-CoV-2 viral load and to compare the results of the mouthwashes to a control group. MATERIALS AND METHODS: In this randomized-controlled clinical trial, studied group comprised laboratory-confirmed COVID-19 positive patients through nasopharyngeal swabs. Participants were divided into 3 groups. For 30 s, the control group mouthrinsed with distilled water, the Chlorhexidine group mouthrinsed with 0.2% Chlorhexidine and the Povidone-iodine group gargled with 1% Povidone-iodine. Saliva samples were collected before and 5 min after mouthwash. SARS-CoV-2 rRT-PCR was then performed for each sample. Evaluation of the efficacy was based on difference in cycle threshold (Ct) value. The analysis of data was carried out using GraphPad Prism version 5 for Windows. Kristal wullis and Paired t-test were used. A probability value of less than 0.05 was regarded as statistically significant. RESULTS: Sixty-one compliant participants (36 female and 25 male) with a mean age 45.3 ± 16.7 years-old were enrolled. A significant difference was noted between the delta Ct of distilled water wash and each of the 2 solutions Chlorhexidine 0.2% (P = .0024) and 1% Povidone-iodine (P = .012). No significant difference was found between the delta Ct of patients using Chlorhexidine 0.2% and 1% Povidone-iodine solutions (P = .24). A significant mean Ct value difference (P < .0001) between the paired samples in Chlorhexidine group (n = 27) and also in Povidone-iodine group (n = 25) (P < .0001) was found. In contrast, no significant difference (P = .566) existed before and after the experiment in the control group (n = 9). CONCLUSION: Chlorhexidine 0.2% and 1% Povidone-iodine oral solutions are effective preprocedural mouthwashes against salivary SARS-CoV-2 in dental treatments. Their use as a preventive strategy to reduce the spread of COVID-19 during dental practice should be considered.

Quality and safety measures in transfusion practice: The experience of eight southern/eastern Mediterranean countries.

BACKGROUND AND OBJECTIVES: Blood transfusion is inherently associated with risks, and little is known regarding the available quality and safety measures in developing countries. No studies or census has been carried out, and therefore, no data on this compelling issue are available. MATERIALS AND METHODS: Data emanating from eight Arabic eastern/southern Mediterranean countries who responded to five surveys were collected and tabulated. RESULTS: Asepsis during phlebotomy, screening for serological and immuno-haematological parameters and appropriate storage conditions are maintained across all countries. Variations in blood component processing exist. Universal leucoreduction is systematically applied in Lebanon. Nucleic acid testing is only performed in Egypt. Aphaeresis procedure, leucoreduction and quality control for blood components are virtually inexistent in Mauritania. Written donor questionnaire is absent in Algeria and Tunisia. Most donor deferral periods for infectious agents are inconsistent with international standards. CONCLUSION: Gaps in the processing and in the quality/safety measures applied to the manufacture of blood components are quite evident in most eastern/southern Mediterranean countries. The decision of establishing an effective collaboration network and an independent body - aside from WHO - composed of specialists that oversees all transfusion activities in these countries is certainly a crucial step towards ensuring an optimum level of blood safety.

Nano selenium ameliorates oxidative stress and inflammatory response associated with cypermethrin-induced neurotoxicity in rats.

Cypermethrin (CYP), a class II synthetic pyrethroid, is used to control household insects. CYP can cross the blood-brain barrier to exert neurotoxicity through changes in sodium ion channels. Selenium is an essential component of glutathione peroxidise enzyme; in addition, it shows a potential anti-inflammatory property. The present study aimed to investigate the neuroprotective role of Nano-Se on CYP-induced neurotoxicity. Twenty-four adult male Wister rats were randomly divided into three groups: a) control, b) CYP (1mg/kg) administered orally for 21 days, c) CYP (1mg/kg) administered orally for 21 days and Nano-Se (2.5 mg/kg) given once a day three times a week for three weeks). Locomotor activity was assessed using open field test then rats were sacrificed under anaesthesia, and their brains were dissected out and processed for biochemical and histopathological studies. Histological examination of CYP-treated rats demonstrated some degenerative changes; besides, CYP affected rat locomotor activity. CYP-treated rats showed increased levels of malondialdehyde (MDA), TNF-α and IL-1ß in addition to the reduction of glutathione (GSH) levels and gamma-Aminobutyric acid (GABA). Nano-Se restored normal behavioural function and significantly attenuated CYP-evoked degenerative changes. Nano-Se increased levels of GABA and glutathione; on the other hand, it significantly prevented the rise in the levels of MDA, TNF-α and IL-1ß. Therefore, Nano-Se demonstrated both anti-oxidant and anti-inflammatory potential. Nano-Se may be suggested to be a prospective candidate to ameliorate CYP-induced neurotoxicity.

The Lebanese Society for Infectious Diseases and Clinical Microbiology (LSIDCM) guidelines for adult community-acquired pneumonia (Cap) in Lebanon.

Adult community-acquired pneumonia (CAP) is a common cause of morbidity and mortality which is managed by different disciplines in a heterogeneous fashion. Development of consensus guidelines to standardize these wide variations in care has become a prime objective. The Lebanese Society of Infectious Diseases and Clinical Microbiology (LSIDCM) convened to set Lebanese national guidelines for the management of CAP since it is a major and a prevalent disease affecting the Lebanese population. These guidelines, besides being helpful in direct clinical practice, play a major role in establishing stewardship programs in hospitals in an effort to contain antimicrobial resistance on the national level. These guidelines are intended for primary care practitioners and emergency medicine physicians. They constitute an appropriate starting point for specialists' consultation being based on the available local epidemiological and resistance data. This document includes the following: 1/ Rationale and scope of the guidelines; 2/ Microbiology of CAP based on Lebanese data; 3/ Clinical presentation and diagnostic workup of CAP; 4/ Management and prevention strategies based on the IDSA/ATS Consensus Guidelines, 2007, and the ESCMID Guidelines, 2011, and tailored to the microbiological data in Lebanon; 5/ Comparison to regional guidelines. The recommendations made in this document were graded based on the strength of the evidence as in the 2007 IDSA/ATS Consensus Guidelines. Hopefully, these guidelines will be an important step towards standardization of CAP care in Lebanon and set the agenda for further research in this area.

Synthesis, Docking, and DFT Studies on Novel Schiff Base Sulfonamide Analogues as Selective COX-1 Inhibitors with Anti-Platelet Aggregation Activity.

Selective COX-1 inhibitors are preferential therapeutic targets for platelet aggregation and clotting responses. In this study, we examined the selective COX-1-inhibitory activities of four newly synthesized compounds, 10-13, along with their abilities to inhibit platelet aggregation against ADP and collagen. The target compounds 10-13 were synthesized using the conventional method, sonication, and microwave-assisted methods. Microanalytical and spectral data were utilized to elucidate the structures of the new compounds 10-13. Additionally, a spectral NMR experiment [NOESY] was conducted to emphasize the configuration around the double bond of the imine group C=N. The obtained results revealed no observed correlation between any of the neighboring protons, suggesting that the configuration at the C=N double bond is E. Biological results revealed that all the screened compounds 10-13 might serve as selective COX-1 inhibitors. They showed IC50 values ranging from 0.71 µM to 4.82 µM against COX-1 and IC50 values ranging from 9.26 µM to 15.24 µM against COX-2. Their COX-1 selectivity indices ranged between 2.87 and 18.69. These compounds show promise as promising anti-platelet aggregation agents. They effectively prevented platelet aggregation induced by ADP with IC50 values ranging from 0.11 µM to 0.37 µM, surpassing the standard aspirin with an IC50 value of 0.49 µM. Additionally, they inhibited the platelet aggregation induced by collagen with IC50 values ranging from 0.12 µM to 1.03 µM, demonstrating superior efficacy compared to aspirin, which has an IC50 value of 0.51 µM. In silico molecular modeling was performed for all the target compounds within the active sites of COX-1 and COX-2 to rationalize their selective inhibitory activities towards COX-1. It was found that the binding interactions of the designed compounds within the COX-1 active site had remained unaffected by the presence of celecoxib. Molecular modeling and DFT calculations using the B3LYP/6-31+G (d,p) level were performed to study the stability of E-forms with respect to Z-forms for the investigated compounds. A strong correlation was observed between the experimental observations and the quantum chemical descriptors.

Enhancing Pharmacokinetics and Pharmacodynamics of Rosuvastatin Calcium through the Development and Optimization of Fast-Dissolving Films.

Rosuvastatin (RSV) is a widely used cholesterol-lowering medication, but its limited bioavailability due to its susceptibility to stomach pH and extensive first-pass metabolism poses a significant challenge. A fast-dissolving film (FDF) formulation of RSV was developed, characterized, and compared to the conventional marketed tablet to address this issue. The formulation process involved optimizing the thickness, disintegration time, and folding durability. All formulations were assessed for in vitro disintegration, thickness, folding endurance, in vitro dissolution, weight, and content uniformity. The study's results revealed that the optimized RSV-FDF displayed a significantly faster time to maximum plasma concentration (tmax) of 2 h, compared to 4 h for the marketed tablet. The maximum plasma concentration (Cmax) for the RSV-FDF (1.540 µg/mL ± 0.044) was notably higher than that of the marketed tablet (0.940 µg/mL ± 0.017). Additionally, the pharmacodynamic assessment in male Wistar rats demonstrated that the optimized RSV-FDF exhibited an improved lipid profile, including reduced levels of low-density lipoproteins (LDLs), elevated high-density lipoproteins (HDLs), decreased triglycerides (TGs), and lower very-low-density lipoproteins (VLDLs) compared to the conventional tablet. These findings underscore the potential of RSV-FDFs as a promising alternative to enhance the bioavailability and therapeutic efficacy of rosuvastatin in treating dyslipidemia. The faster onset of action and improved lipid-lowering effects make RSV-FDFs an attractive option for patients requiring efficient cholesterol management.

A novel role of Nano selenium and sildenafil on streptozotocin-induced diabetic nephropathy in rats by modulation of inflammatory, oxidative, and apoptotic pathways.

AIMS: The present study aimed to investigate the effect of nano selenium, sildenafil, and their combination on inflammation, oxidative stress, and apoptosis in streptozotocin-induced diabetic nephropathy in rats. Herein, a new anti-inflammatory pathway for sildenafil as a high-mobility group box (HMGB1) inhibitor was proposed using the molecular docking technique. MATERIALS AND METHODS: Rats were divided into 7 groups: normal control, control nano selenium, control sildenafil, control diabetic, diabetic+ nano selenium, diabetic+ sildenafil, diabetic+ nano selenium+ sildenafil. The effects of drugs were evaluated by measuring serum urea, creatinine, lactate dehydrogenase (LDH), levels of tumor necrosis factor-alpha (TNF-α), Interleukin 1 beta (IL-1ß), HMGB1, receptor advanced glycation end product (RAGE), malondialdehyde (MDA), thioredoxin reductase (TrxR) by biochemical assays, nuclear factor-kappa b (NF-κB), toll-like receptor (TLR4) by immunohistochemistry, gene expressions of caspase 3 and monocyte chemoattractant protein (MCP-1) besides histopathological investigations of renal cells. KEY FINDINGS: Results showed beneficial effects of 8 weeks of treatment by nano selenium and sildenafil supported by improvement in kidney function, histopathological changes, and reduction in all of these parameters. These results supported molecular docking that indicated sildenafil had a high binding score and interactions with the HMGB1 receptor. SIGNIFICANCE: The current study demonstrated a renoprotective effect of nano­selenium and sildenafil by interfering at multiple pathways, especially the HMGB1/NF-κB signaling pathway.

Clinical and epidemiological characteristics of the first 150 patients with COVID-19 in Lebanon: a prospective descriptive study.

Background: Clinical features of confirmed COVID-19 cases cover a wide spectrum. Aims: To study the clinical, radiological and virological features of the first 150 patients with COVID-19 in Lebanon. Methods: Our university hospital was designated as the primary COVID-19 care centre in Lebanon. Between 21 February 2020, the date of the first confirmed case of COVID-19 in Lebanon, and 3 April 2020, our team treated 150 patients diagnosed with COVID-19. In this prospective descriptive study, we present our experience in treating these patients, specifically the diagnostic criteria, outcome, and demographic, clinical, radiological and biological characteristics. Results: Ninety-five (63.33%) of the patients were male and 55 (36.67%) were female. Most patients (58%) were aged > 50 years, and 8 (5.33%) were healthcare workers. Diagnosis was based on reverse transcription polymerase chain reaction, and patients were classified as mild, moderate or critical. Fifteen (10%) patients had a critical presentation and fever was the most prominent symptom at presentation. One hundred and thirty-eight (92%) patients underwent radiological evaluation. The most common laboratory findings were lymphocytopenia (34.38%), followed by neutropenia (28.13%), but leukocytosis was not prevalent (1.56%). Old age and comorbidity were significant indicators in patient risk stratification. Chest computed tomography was an invaluable method of diagnosis and management. Our radiological findings were consistent with the published literature. Conclusion: Our study underlines the variable presentation of COVID-19, the difference in severity, and the diverse methods of diagnosis. This suggests the need for a tailored approach, taking into consideration the wide spectrum of presentation.

The Effectiveness of COVID-19 Vaccines in Preventing Hospitalizations During the Delta Wave: A Patient-Population Study at a Major Referral Center.

Background and objective Coronavirus disease 2019 (COVID-19) has turned into a deadly global pandemic since its first discovery in Wuhan, China in December 2019. Safe and effective vaccines against COVID-19 have been introduced to the public and have been shown to reduce the severity of the disease and related mortality rates. COVID-19 vaccination was first introduced in Lebanon in mid-February 2021. In this study, we analyzed the effectiveness of vaccination against COVID-19-related hospitalization during the Delta wave at a major referral center in Lebanon. Methods This patient-population study was conducted on patients hospitalized with COVID-19 between July 1, 2021, and September 30, 2021, at the Rafik Hariri University Hospital (RHUH) in Beirut, Lebanon. Data were collected directly from the patients or from digitized records and included demographic characteristics (age, sex, and comorbidities), vaccination status, oxygen requirement, and outcomes. National vaccination data were collected from the daily bulletin provided by the Lebanese Ministry of Public Health. The data collected were analyzed using SPSS Statistics Version 19.0 (IBM Corp., Armonk, NY). Results A total of 289 patients were included in the study, of whom 90.3% were unvaccinated and 9.7% were vaccinated with at least one dose of a two-dose regimen. Only 4.5% of the 289 patients were fully vaccinated. Among those fully or partially vaccinated, the mean time from symptom onset to hospitalization was shorter but the hospital stay was longer compared to the unvaccinated group. The mortality rate was higher in the unvaccinated group (25.7%) compared to 14.3% among the vaccinated. The vaccine effectiveness compared to the national vaccination rate (22.5% in the population after the first and second dose) was 71.71% and 83.78% respectively. Conclusion The findings of this study highlight the fact that complete/partial vaccination against COVID-19 was highly protective against severe disease and hospitalization during the period with a predominance of the Delta variant in Lebanon.

International Multicenter Study Comparing Cancer to Non-Cancer Patients with COVID-19: Impact of Risk Factors and Treatment Modalities on Survivorship.

Background: In this international multicenter study we aimed to determine the independent risk factors associated with increased 30-day mortality and the impact of novel treatment modalities in a large group of cancer and non-cancer patients with COVID-19 from multiple countries. Methods: We retrospectively collected de-identified data on a cohort of cancer and non-cancer patients diagnosed with COVID-19 between January and November 2020, from 16 international centers. Results: We analyzed 3966 COVID-19 confirmed patients, 1115 cancer and 2851 non-cancer patients. Cancer patients were more likely to be pancytopenic, and have a smoking history, pulmonary disorders, hypertension, diabetes mellitus, and corticosteroid use in the preceding two weeks (p≤0.01). In addition, they were more likely to present with higher inflammatory biomarkers (D-dimer, ferritin and procalcitonin), but were less likely to present with clinical symptoms (p≤0.01). By multivariable logistic regression analysis, cancer was an independent risk factor for 30-day mortality (OR 1.46; 95% CI 1.03 to 2.07; p=0.035). Older age (≥65 years) was the strongest predictor of 30-day mortality in all patients (OR 4.55; 95% CI 3.34 to6.20; p< 0.0001). Remdesivir was the only therapeutic agent independently associated with decreased 30-day mortality (OR 0.58; CI 0.39-0.88; p=0.009). Among patients on low-flow oxygen at admission, patients who received remdesivir had a lower 30-day mortality rate than those who did not (5.9% vs 17.6%; p=0.03). Conclusions: Cancer is an independent risk factor for increased 30-day all-cause mortality from COVID-19. Remdesivir, particularly in patients receiving low-flow oxygen, can reduce 30-day all-cause mortality. Condensed Abstract: In this large multicenter worldwide study of 4015 patients with COVID-19 that included 1115 patients with cancer, we found that cancer is an independent risk factor for increased 30-day all-cause mortality. Remdesivir is a promising treatment modality to reduce 30-day all-cause mortality.

Economic Burden of Urinary Tract Infections From Antibiotic-Resistant Escherichia coli Among Hospitalized Adult Patients in Lebanon: A Prospective Cohort Study.

OBJECTIVES: The rising incidence of urinary tract infections (UTIs) attributable to Escherichia coli resistant isolates is becoming a serious public health concern. Although global rates of infection vary considerably by region, the growing prevalence of this uropathogen has been associated with a high economic burden and health strain. This study aims: (1) to estimate the differences in clinical and economic outcomes between 2 groups of adult hospitalized patients with UTIs from E. coli resistant and susceptible bacteria and (2) to investigate drivers of this cost from a payer's perspective. METHODS: A prospective multicenter cohort study was conducted in 10 hospitals in Lebanon. The cost analysis followed a bottom-up microcosting approach; a linear regression was constructed to evaluate the predictors of hospitalization costs and a Cox proportional hazards model was used to estimate the impact of resistance on length of stay (LOS) and in-hospital mortality. RESULTS: Out of 467 inpatients, 250 cases were because of resistant E. coli isolates. Results showed that patients with resistant uropathogens had 29% higher mean total hospitalization costs ($3429 vs $2651; P = .004), and an extended median LOS (6 days vs 5 days; P = .020) compared with susceptible cohorts. The selection of resistant bacteria and the Charlson comorbidity index predicted higher total hospitalization costs and in-hospital mortality. CONCLUSION: In an era of increased pressure for cost containment, this study showed the burden of treating UTIs resulting from resistant bacteria. The results can inform cost-effectiveness analyses that intend to evaluate the benefit of a national action plan aimed at decreasing the impact of antibiotic resistance.

Surveillance of antimicrobial resistance in low- and middle-income countries: a scattered picture.

Data on comprehensive population-based surveillance of antimicrobial resistance is lacking. In low- and middle-income countries, the challenges are high due to weak laboratory capacity, poor health systems governance, lack of health information systems, and limited resources. Developing countries struggle with political and social dilemma, and bear a high health and economic burden of communicable diseases. Available data are fragmented and lack representativeness which limits their use to advice health policy makers and orientate the efficient allocation of funding and financial resources on programs to mitigate resistance. Low-quality data means soaring rates of antimicrobial resistance and the inability to track and map the spread of resistance, detect early outbreaks, and set national health policy to tackle resistance. Here, we review the barriers and limitations of conducting effective antimicrobial resistance surveillance, and we highlight multiple incremental approaches that may offer opportunities to strengthen population-based surveillance if tailored to the context of each country.

Economic Burden of Urinary Tract Infections From Antibiotic-Resistant Escherichia coli Among Hospitalized Adult Patients in Lebanon: A Prospective Cohort Study.

OBJECTIVES: The rising incidence of urinary tract infections (UTIs) attributable to Escherichia coli resistant isolates is becoming a serious public health concern. Although global rates of infection vary considerably by region, the growing prevalence of this uropathogen has been associated with a high economic burden and health strain. This study aims: (1) to estimate the differences in clinical and economic outcomes between 2 groups of adult hospitalized patients with UTIs from E. coli resistant and susceptible bacteria and (2) to investigate drivers of this cost from a payer's perspective. METHODS: A prospective multicenter cohort study was conducted in 10 hospitals in Lebanon. The cost analysis followed a bottom-up microcosting approach; a linear regression was constructed to evaluate the predictors of hospitalization costs and a Cox proportional hazards model was used to estimate the impact of resistance on length of stay (LOS) and in-hospital mortality. RESULTS: Out of 467 inpatients, 250 cases were because of resistant E. coli isolates. Results showed that patients with resistant uropathogens had 29% higher mean total hospitalization costs ($3429 vs $2651; P = .004), and an extended median LOS (6 days vs 5 days; P = .020) compared with susceptible cohorts. The selection of resistant bacteria and the Charlson comorbidity index predicted higher total hospitalization costs and in-hospital mortality. CONCLUSION: In an era of increased pressure for cost containment, this study showed the burden of treating UTIs resulting from resistant bacteria. The results can inform cost-effectiveness analyses that intend to evaluate the benefit of a national action plan aimed at decreasing the impact of antibiotic resistance.

Prevalence of hepatitis B and anti-hepatitis C virus antibody among people who inject drugs in the Lebanese population.

BACKGROUND: People who inject drugs (PWIDs) are prone to a number of blood-borne viral infections. Hepatitis B virus (HBV) and hepatitis C virus (HCV) constitute an important public health concern in this high risk group. AIMS: We aimed to determine the prevalence of HBV and HCV antibody among PWIDs in Lebanon. METHODS: We conducted a prospective cross-sectional study between June 2015 and June 2016 on PWIDs recruited through Lebanese nongovernmental organizations in collaboration with the Lebanese Ministry of Public Health. The participants were tested for HBs antigen and HCV antibody using rapid test kits. The prevalence of each virus was then calculated. The correlation between both infections and other possible risk factors was also analysed. RESULTS: A total of 250 people were included in our study, of whom 98% were males. Mean age was 31.9 (standard deviation 8.7) years. The prevalence of HBsAg and anti-HCV among PWIDs was 1.2% and 15.6%, respectively. Older age, longer duration of drug use and lack of awareness were significantly correlated with a higher rate of HCV infection (P < 0.01). The high rate of needle sharing among our PWIDs significantly affected the prevalence of anti-HCVAb. CONCLUSION: PWIDs remain the subpopulation most affected with chronic HCV in Lebanon.

Safe management of bodies of deceased persons with suspected or confirmed COVID-19: a rapid systematic review.

INTRODUCTION: Proper strategies to minimise the risk of infection in individuals handling the bodies of deceased persons infected with 2019 novel coronavirus (2019-nCoV) are urgently needed. The objective of this study was to systematically review the literature to scope and assess the effects of specific strategies for the management of the bodies. METHODS: We searched five general, three Chinese and four coronavirus disease (COVID-19)-specific electronic databases. We searched registries of clinical trials, websites of governmental and other relevant organisations, reference lists of the included papers and relevant systematic reviews, and Epistemonikos for relevant systematic reviews. We included guidance documents providing practical advice on the handling of bodies of deceased persons with suspected or confirmed COVID-19. Then, we sought primary evidence of any study design reporting on the efficacy and safety of the identified strategies in coronaviruses. We included evidence relevant to contextual factors (ie, acceptability). A single reviewer extracted data using a pilot-tested form and graded the certainty of the evidence using the GRADE approach. A second reviewer verified the data and assessments. RESULTS: We identified one study proposing an uncommon strategy for autopsies for patients with severe acute respiratory syndrome. The study provided very low-certainty evidence that it reduced the risk of transmission. We identified 23 guidance documents providing practical advice on the steps of handling the bodies: preparation, packing, and others and advice related to both the handling of the dead bodies and the use of personal protective equipment by individuals handling them. We did not identify COVID-19 evidence relevant to any of these steps. CONCLUSION: While a substantive number of guidance documents propose specific strategies, we identified no study providing direct evidence for the effects of any of those strategies. While this review highlights major research gaps, it allows interested entities to build their own guidance.

Development of Betamethasone Dipropionate-Loaded Nanostructured Lipid Carriers for Topical and Transdermal Delivery.

INTRODUCTION: Betamethasone dipropionate is a highly effective corticosteroid anti-inflammatory. However, the main drawback of its topical use is the limited skin penetration into deeper skin layers. Also, its systemic use has shown many side effects. OBJECTIVE: The goal of this research was to formulate betamethasone dipropionate in nanostructured lipid carriers (NLC) formulae that contain oleic acid to aid its penetration to deeper skin layers and to aid absorption to local regions upon topical application. METHODS: NLC formulae were prepared by high shear homogenization then sonication. Formulae were characterized for their particle size, size distribution, electric potential, occlusion factor, entrapment efficiency, drug loading, transmission electron microscopy, in vitro drug release, and ex vivo skin penetration. Compatibility of ingredients with drug was tested using differential scanning calorimetry. Formulae were shown to have appropriate characteristics. NLC formulae were superior to traditional topical formulation in drug release. RESULTS: Upon testing ex vivo skin penetration, betamethasone dipropionate prepared in NLC formulae was shown to penetrate more efficiently into skin layers than when formulated as a traditional cream. NLC formulation that contained higher percentage of oleic acid showed higher penetration and higher amount of drug to pass through skin. CONCLUSION: In general, NLC with lower oleic acid percentage was shown to deliver betamethasone dipropionate more efficiently into deeper skin layers while that of a higher oleic acid percentage was shown to deliver the drug more efficiently into deeper skin layers and through the skin, transdermally.

Adenovirus Infection as a Cause of Fever of Unknown Origin and Allograft Dysfunction in a Kidney Transplant Recipient.

With the recent introduction of more potent modern immunosuppressive regimens in solid-organ transplant, new types of viral infections such as adenovirus are emerging as a potential cause for graft dysfunction and loss. We report a case of 41-year-old male patient with end-stage renal disease from recurrent kidney stones who underwent kidney transplant from a deceased 12-year-old female donor. He developed adenoviral infection with acute cystitis, microscopic hematuria, and necrotizing interstitial nephritis associated with graft dysfunction within the first month of the postoperative period. Diagnosis was made by graft biopsy that showed more than 60% necrosis with tubulointerstitial hemorrhage, thrombotic microangiopathy, and histologic features suggestive of viral infection with negative Cytomegalovirus and polyomavirus stains in the graft and elevated adenovirus PCR in the blood. Simultaneously, the patient had very low absolute total lymphocyte count of 70 cells/µL during which he received supratherapeutic tacrolimus at whole blood trough levels and mycophenolate mofetil. This prompted the tapering of immunosuppression and the discontinuation of all antimicrobial drugs. Within a 2-week period, the immune reconstitution was sufficient for the clearance of the infection and the subsequent gradual recovery of graft function.

Highlighting the gaps in quantifying the economic burden of surgical site infections associated with antimicrobial-resistant bacteria.

Antibiotics are the pillar of surgery from prophylaxis to treatment; any failure is potentially a leading cause for increased morbidity and mortality. Robust data on the burden of SSI especially those due to antimicrobial resistance (AMR) show variable rates between countries and geographical regions but accurate estimates of the incidence of surgical site infections (SSI) due to AMR and its related global economic impact are yet to be determined. Quantifying the burden of SSI treatment is an incentive to sensitize governments, healthcare systems, and the society to invest in quality improvement and sustainable development. However in the absence of a unified epidemiologically sound infection definition of SSI and a well-designed global surveillance system, the end result is a lack of accurate and reliable data that limits the comparability of estimates between countries and the possibility of tracking changes to inform healthcare professionals about the appropriateness of implemented infection prevention and control strategies. This review aims to highlight the reported gaps in surveillance methods, epidemiologic data, and evidence-based SSI prevention practices and in the methodologies undertaken for the evaluation of the economic burden of SSI associated with AMR bacteria. If efforts to tackle this problem are taken in isolation without a global alliance and data is still lacking generalizability and comparability, we may see the future as a race between the global research efforts for the advancement in surgery and the global alarming reports of the increased incidence of antimicrobial-resistant pathogens threatening to undermine any achievement.

Effect of carbapenem resistance on outcomes of bloodstream infection caused by Enterobacteriaceae in low-income and middle-income countries (PANORAMA): a multinational prospective cohort study.

BACKGROUND: Low-income and middle-income countries (LMICs) are under-represented in reports on the burden of antimicrobial resistance. We aimed to quantify the clinical effect of carbapenem resistance on mortality and length of hospital stay among inpatients in LMICs with a bloodstream infection due to Enterobacteriaceae. METHODS: The PANORAMA study was a multinational prospective cohort study at tertiary hospitals in Bangladesh, Colombia, Egypt, Ghana, India, Lebanon, Nepal, Nigeria, Pakistan, and Vietnam, recruiting consecutively diagnosed patients with carbapenem-susceptible Enterobacteriaceae (CSE) and carbapenem-resistant Entero-bacteriaceae (CRE) bloodstream infections. We excluded patients who had previously been enrolled in the study and those not treated with curative intent at the time of bloodstream infection onset. There were no age restrictions. Central laboratories in India and the UK did confirmatory testing and molecular characterisation, including strain typing. We applied proportional subdistribution hazard models with inverse probability weighting to estimate the effect of carbapenem resistance on probability of discharge alive and in-hospital death, and multistate modelling for excess length of stay in hospital. All patients were included in the analysis. FINDINGS: Between Aug 1, 2014, and June 30, 2015, we recruited 297 patients from 16 sites in ten countries: 174 with CSE bloodstream infection and 123 with CRE bloodstream infection. Median age was 46 years (IQR 15-61). Crude mortality was 20% (35 of 174 patients) for patients with CSE bloodstream infection and 35% (43 of 123 patients) for patients with CRE bloodstream infection. Carbapenem resistance was associated with an increased length of hospital stay (3·7 days, 95% CI 0·3-6·9), increased probability of in-hospital mortality (adjusted subdistribution hazard ratio 1·75, 95% CI 1·04-2·94), and decreased probability of discharge alive (0·61, 0·45-0·83). Multilocus sequence typing showed various clades, with marginal overlap between strains in the CRE and CSE clades. INTERPRETATION: Carbapenem resistance is associated with increased length of hospital stay and mortality in patients with bloodstream infections in LMICs. These data will inform global estimates of the burden of antimicrobial resistance and reinforce the need for better strategies to prevent, diagnose, and treat CRE infections in LMICs. FUNDING: bioMérieux.