Risk factors predicting the need for intensive care unit admission within forty-eight hours of emergency department presentation: A case-control study.

BACKGROUND: Patients admitted from the emergency department to the wards, who progress to a critically unwell state, may require expeditious admission to the intensive care unit. It can be argued that earlier recognition of such patients, to facilitate prompt transfer to intensive care, could be linked to more favourable clinical outcomes. Nevertheless, this can be clinically challenging, and there are currently no established evidence-based methods for predicting the need for intensive care in the future. OBJECTIVES: We aimed to analyse the emergency department data to describe the characteristics of patients who required an intensive care admission within 48 h of presentation. Secondly, we planned to test the feasibility of using this data to identify the associated risk factors for developing a predictive model. METHODS: We designed a retrospective case-control study. Cases were patients admitted to intensive care within 48 h of their emergency department presentation. Controls were patients who did not need an intensive care admission. Groups were matched based on age, gender, admission calendar month, and diagnosis. To identify the associated variables, we used a conditional logistic regression model. RESULTS: Compared to controls, cases were more likely to be obese, and smokers and had a higher prevalence of cardiovascular (39 [35.1%] vs 20 [18%], p = 0.004) and respiratory diagnoses (45 [40.5%] vs 25 [22.5%], p = 0.004). They received more medical emergency team reviews (53 [47.8%] vs 24 [21.6%], p < 0.001), and more patients had an acute resuscitation plan (31 [27.9%] vs 15 [13.5%], p = 0.008). The predictive model showed that having acute resuscitation plans, cardiovascular and respiratory diagnoses, and receiving medical emergency team reviews were strongly associated with having an intensive care admission within 48 h of presentation. CONCLUSIONS: Our study used emergency department data to provide a detailed description of patients who had an intensive care unit admission within 48 h of their presentation. It demonstrated the feasibility of using such data to identify the associated risk factors to develop a predictive model.

Current management of fluid balance in critically ill patients with acute kidney injury: A scoping review.

Objective: The overall objective of this scoping review is to assess the extent of the literature related to the fluid management of critically ill patients with acute kidney injury (AKI). Introduction: AKI is common in critically ill patients where fluid therapy is a mainstay of treatment. An association between fluid balance (FB) and adverse patient-centred outcomes in critically ill patients with AKI regardless of severity has been demonstrated. The evidence for the prospective intervention of FB and its impact on outcomes is unknown. Inclusion criteria: All studies investigating FB in patients with AKI admitted to an intensive care unit were included. Literature not related to FB in the critically ill patient with AKI population was excluded. Methods: We searched MEDLINE, EMBASE, and CINAHL from January 1st, 2012, onwards. We included primary research studies, experimental and observational, recruiting adult participants admitted to an intensive care unit who had an AKI. We extracted data on study and patient characteristics, as well as FB, renal-based outcomes, and patient-centred outcomes. Two reviewers independently screened citations for eligible studies and performed data extraction. Results: Of the 13,767 studies reviewed, 22 met the inclusion criteria. Two studies examined manipulation of fluid input, 18 studies assessed enhancing fluid removal, and two studies applied a restrictive fluid protocol. Sixteen studies examined patients receiving renal replacement therapy, five studies included non-renal replacement therapy patients, and one study included both. Current evidence is broad with varied approaches to managing fluid input and fluid removal. The studies did not demonstrate a consensus approach for any aspect of the fluid management of critically ill patients. There was a limited application of a restrictive fluid protocol with no conclusions possible. Conclusions: The current body of evidence for the management of FB in critically ill patients with AKI is limited in nature. The current quality of evidence is unable to guide current clinical practice. The key outcome of this review is to highlight areas for future research.

Staphylococcus aureus Dormancy: Waiting for Insurgency.

Relapse infection usually results from resistance to the antibiotic, acquired genes, or persister cells. Persister cells are formed through mutation, reduced activity or metabolically inactive pathways induced by antibiotics, harassing conditions, low ATP, and malnutrition. These factors provide the ground for bacteria to grow slowly. Such a slow growth rate makes traditional antibiotics ineffective against persister cells. Staphylococcus aureus (S. aureus), in addition to this form, can be observed in Small Colony Variants (SCVs), L-forms, and dormant, all of which are characterized by at least one feature, i.e., slow growth. Despite their slow growth, they are metabolically active in terms of stringent SOS and cell wall stress responses. The stress response involves resistance against harassing conditions, and it survives until it is reactivated later. The present study aims to discuss the mechanisms of all persister cell formations, circumstances involved, gene mutation, and adoptable strategies against it.

Clinical testing panels for ALS: global distribution, consistency, and challenges.

Objective: In 2021, the Clinical Genome Resource (ClinGen) amyotrophic lateral sclerosis (ALS) spectrum disorders Gene Curation Expert Panel (GCEP) was established to evaluate the strength of evidence for genes previously reported to be associated with ALS. Through this endeavor, we will provide standardized guidance to laboratories on which genes should be included in clinical genetic testing panels for ALS. In this manuscript, we aimed to assess the heterogeneity in the current global landscape of clinical genetic testing for ALS. Methods: We reviewed the National Institutes of Health (NIH) Genetic Testing Registry (GTR) and members of the ALS GCEP to source frequently used testing panels and compare the genes included on the tests. Results: 14 clinical panels specific to ALS from 14 laboratories covered 4 to 54 genes. All panels report on ANG, SOD1, TARDBP, and VAPB; 50% included or offered the option of including C9orf72 hexanucleotide repeat expansion (HRE) analysis. Of the 91 genes included in at least one of the panels, 40 (44.0%) were included on only a single panel. We could not find a direct link to ALS in the literature for 14 (15.4%) included genes. Conclusions: The variability across the surveyed clinical genetic panels is concerning due to the possibility of reduced diagnostic yields in clinical practice and risk of a missed diagnoses for patients. Our results highlight the necessity for consensus regarding the appropriateness of gene inclusions in clinical genetic ALS tests to improve its application for patients living with ALS and their families.

Molecular mechanisms of Shigella effector proteins: a common pathogen among diarrheic pediatric population.

Different gastrointestinal pathogens cause diarrhea which is a very common problem in children aged under 5 years. Among bacterial pathogens, Shigella is one of the main causes of diarrhea among children, and it accounts for approximately 11% of all deaths among children aged under 5 years. The case-fatality rates for Shigella among the infants and children aged 1 to 4 years are 13.9% and 9.4%, respectively. Shigella uses unique effector proteins to modulate intracellular pathways. Shigella cannot invade epithelial cells on the apical site; therefore, it needs to pass epithelium through other cells rather than the epithelial cell. After passing epithelium, macrophage swallows Shigella, and the latter should prepare itself to exhibit at least two types of responses: (I) escaping phagocyte and (II) mediating invasion of and injury to the recurrent PMN. The presence of PMN and invitation to a greater degree resulted in gut membrane injuries and greater bacterial penetration. Infiltration of Shigella to the basolateral space mediates (A) cell attachment, (B) cell entry, (C) evasion of autophagy recognition, (D) vacuole formation and and vacuole rapture, (E) intracellular life, (F) Shiga toxin, and (G) immune response. In this review, an attempt is made to explain the role of each factor in Shigella infection.

A global overview of the most important zoonotic bacteria pathogens transmitted from Rattus norvegicus to humans in urban environments.

Zoonotic pathogens, comprising over 61% of all pathogenic microorganisms, can be transmitted from different animals to individuals in numerous ways either in the presence or the absence of a vector. Causing new emerging human infectious diseases, these pathogens could be categorized into 4 groups, bacteria, viruses, parasites, and fungi. Among the wide range of reservoirs for zoonotic pathogens, tremendous attention has been attracted to wild rats, due to their global distribution not only in urban environments but also in the sylvatic and agricultural surroundings. For the nonce, zoonotic bacteria transmitted via wild rats have turned into a global public health problem probably due to their ability to induce re-emerging diseases even after eradication and controlling management. Despite the importance of wild rats in spreading pathogens, little data are available about the bacterial diversity present in urban wild rat populations. In this review, we present a complete list of zoonotic bacterial pathogens isolated from wild rats in urban environments.

Staphylococcus aureus: Biofilm Formation and Strategies Against it.

Formation of Staphylococcus aureus biofilm causes significant infections in the human body. Biofilm forms through the aggregation of bacterial species and brings about many complications. It mediates drug resistance and persistence and facilitates the recurrence of infection at the end of antimicrobial therapy. Biofilm formation is completed in a series of steps, and any interference in these steps can disrupt its formation. Such interference may occur at any stage of biofilm production, including attachment, monolayer formation, and accumulation. Interfering agents can act as quorum sensing inhibitors and interfere in the functionality of quorum sensing receptors, attachment inhibitors, and affect cell hydrophobicity. Among these inhibiting strategies, attachment inhibitors could serve as the best agents against biofilm formation, because in case pathogens abort the attachment, the next stages of biofilm formation, e.g., accumulation and dispersion, will fail to materialize. Inhibition at this stage leads to suppression of virulence factors and invasion. One of the best knowing inhibitors is a chelator that collects metal, Fe+, Zn+, and magnesium critical for biofilm formation. These effective factors in the binding and formation of biofilm are investigated, and the coping strategy is discussed. This review examines the stages of biofilm formation and determines what factors interfere in the continuity of these steps. Finally, the inhibition strategies are investigated, reviewed, and discussed.

Hamstring graft diameter above 7 mm has a lower risk of failure following anterior cruciate ligament reconstruction.

PURPOSE: Multi-stranded hamstring-tendon autografts have been widely used for anterior cruciate ligament reconstruction (ACLR) surgeries. Recently, smaller diameter hamstring autografts have been linked with the risk of failure or graft rupture. However, there is limited evidence concerning the optimal diameter of the hamstring autografts for ACLR. The current systematic review and meta-analysis analysed the association of ACLR failure with the diameter of hamstring autografts. METHODS: A systematic search of three major scientific databases (Pubmed, EMBASE, and Cochrane library) was conducted to identify studies that presented ACLR failure-related outcomes with different diameters of hamstring autografts. The pooled data from the included studies were analysed to investigate the association between ACLR failure and the cut-off diameters of 6, 7, 8, and 9 mm. Subgroup analyses based on the level of evidence and follow-up duration were also performed at each cut-off diameter. RESULTS: Of the 2282 studies screened, 16 reported failure rates with hamstring autografts of different diameters, 15 of which were included in the meta-analysis. A graft diameter ≥ 7 mm was associated with significantly lower ACLR failure rates than a graft diameter < 7 mm (p = 0.005), based on pooled data of 19,799 cases. Age < 20 years and higher physical activity were associated with significantly higher ACLR failure rates. CONCLUSION: The current systematic review suggests that the hamstring graft diameter for ACLR should be more than 7 mm considering the significantly higher failure rates with graft diameters less than 7 mm. LEVEL OF EVIDENCE: Level IV.

Implementation of a pediatric early warning score tool in a pediatric oncology Ward in Palestine.

BACKGROUND: Pediatric Early Warning Scores (PEWS) are nurse-administered clinical assessment tools utilizing vital signs and patient signs and symptoms to screen for patients at risk for clinical deterioration.1-3 When utilizing a PEWS system, which consists of an escalation algorithm to alert physicians of high risk patients requiring a bedside evaluation and assessment, studies have demonstrated that PEWS systems can decrease pediatric intensive care (PICU) utilization, in-hospital cardiac arrests, and overall decreased mortality in high income settings. Yet, many hospital based settings in low and lower middle income countries (LMIC) lack systems in place for early identification of patients at risk for clinical deterioration. METHODS: A contextually adapted 16-h pediatric resuscitation program included training of a PEWS tool followed by implementation and integration of a PEWS system in a pediatric hematology/oncology ward in Beit Jala, Palestine. Four PDSA cycles were implemented post-implementation to improve uptake and scoring of PEWS which included PEWS tool integration into an existing electronic medical record (EMR), escalation algorithm and job aid implementation, data audits and ward feedback. RESULTS: Frequency of complete PEWS vital sign documentation reached a mean of 89.9%. The frequency and accuracy of PEWS scores steadily increased during the post-implementation period, consistently above 89% in both categories starting from data audit four and continuing thereafter. Accuracy of PEWS scoring was unable to be assessed during week 1 and 2 of data audits due to challenges with PEWS integration into the existing EMR (PDSA cycle 1) which were resolved by the 3rd week of data auditing (PDSA cycle 2). CONCLUSIONS: Implementation of a PEWS scoring tool in an LMIC pediatric oncology inpatient unit is feasible and can improve frequency of vital sign collection and generate accurate PEWS scores. CONTRIBUTION TO THE LITERATURE: This study demonstrates how to effectively implement a PEWS scoring tool into an LMIC clinical setting. This study demonstrates how to utilize a robust feedback mechanism to ensure a quality program uptake. This study demonstrates an effective international partnership model that other institutions may utilize for implementation science.

Estimated Direct Medical Cost of Osteoporosis in Saudi Arabia: A Single-Center Retrospective Cost Analysis.

Osteoporosis and its complications are a major health concern in Saudi Arabia, and the prevalence of osteoporosis is on the rise. The aim of this study was to estimate the direct healthcare cost for patients with osteoporosis. A retrospective study was carried out among adult patients with osteoporosis in a teaching hospital in Saudi Arabia. A bottom-up approach was conducted to estimate the healthcare resources used and the total direct medical cost for the treatment of osteoporosis and related fractures. The study included 511 osteoporosis patients, 93% of whom were female. The average (SD) age was 68.5 years (10.2). The total mean direct medical costs for patients without fractures were USD 975.77 per person per year (PPPY), and for those with osteoporotic fractures, the total direct costs were USD 9716.26 PPPY, of which 56% of the costs were attributable to surgery procedures. Prior to fractures, the main cost components were medication, representing 61%, and physician visits, representing 18%. The findings of this study indicated the economic impact of osteoporosis and related fractures. With the aging population in Saudi Arabia, the burden of disease could increase significantly, which highlights the need for effective prevention strategies to minimize the economic burden of osteoporosis.

A comprehensive review of bacterial osteomyelitis with emphasis on Staphylococcus aureus.

Osteomyelitis, a significant infection of bone tissue, gives rise to two main groups of infection: acute and chronic. These groups are further categorized in terms of the duration of infection. Usually, children and adults are more susceptible to acute and chronic infections, respectively. The aforementioned groups of osteomyelitis share almost 80% of the corresponding bacterial pathogens. Among all bacteria, Staphylococcus aureus (S. aureus) is a significant pathogen and is associated with a high range of osteomyelitis symptoms. S. aureus has many strategies for interacting with host cells including Small Colony Variant (SCV), biofilm formation, and toxin secretion. In addition, it induces an inflammatory response and causes host cell death by apoptosis and necrosis. However, any possible step to take in this respect is dependent on the conditions and host responses. In the absence of any immune responses and antibiotics, bacteria actively duplicate themselves; however, in the presence of phagocytic cell and harassing conditions, they turn into a SCV, remaining sustainable for a long time. SCV is characterized by notable advantages such as (a) intracellular life that mediates a dam against immune cells and (b) low ATP production that mediates resistance against antibiotics.

Responsiveness, Reliability, and Validity of Arabic Version of Oxford Knee Score for Total Knee Arthroplasty.

BACKGROUND: The Oxford Knee Score (OKS) is a reliable, valid, and sensitive assessment tool for individuals undergoing a total knee arthroplasty (TKA). The published psychometric assessment of the Arabic version of the OKS (OKS-Ar) is limited to male patients and has not been assessed for responsiveness following TKA. The aim of this study was to assess the reliability, validity, and responsiveness of the OKS-Ar in an inclusive population of patients undergoing TKA. METHODS: One hundred Arabic-speaking patients awaiting TKA were assessed with the OKS-Ar, the Arabic version of the Knee injury and Osteoarthritis Outcome Score (KOOS-Ar), and a visual analogue scale for pain (VAS-P) in order to assess the correlation between the OKS-Ar and the KOOS-Ar and VAS-P and determine the construct validity. Repeat assessments were completed 7 to 10 days after the first assessment and 6 months after TKA. RESULTS: Questionnaires were completed by 80 female and 20 male participants with a mean age of 62 ± 8 years. The test and retest median scores showed no significant difference from one another, with a strong Spearman correlation between the 2 measurements (rs = 0.94). Bland-Altman limits of agreement showed no significant bias. The Cronbach alpha was 0.85 indicating high internal consistency. There was no floor or ceiling effect before TKA, and the post-TKA ceiling effect was only 2%. The OKS-Ar pain component correlated strongly with the KOOS-Ar pain subscale (rs = 0.73). The OKS-Ar effect size was 3.09, which was larger than that of all of the KOOS subscales at 6 months after TKA. CONCLUSIONS: To our knowledge, this is the first study to assess reliability, validity, and responsiveness of the OKS-Ar after TKA. The validity and reliability results are similar to those found for both the original English-language OKS and the OKS translated into other languages. We believe that this is also the first study to assess OKS-Ar responsiveness after TKA and to show a large effect size. We found that the OKS-Ar is a feasible, valid, reliable, and sensitive measurement tool to assess pain and function in TKA-treated individuals whose main language is Arabic.

Molecular Mechanisms of Salmonella Effector Proteins: A Comprehensive Review.

Salmonella can be categorized into many serotypes, which are specific to known hosts or broadhosts. It makes no difference which one of the serotypes would penetrate the gastrointestinal tract because they all face similar obstacles such as mucus and microbiome. However, following their penetration, some species remain in the gastrointestinal tract; yet, others spread to another organ like gallbladder. Salmonella is required to alter the immune response to sustain its intracellular life. Changing the host response requires particular effector proteins and vehicles to translocate them. To this end, a categorized gene called Salmonella pathogenicity island (SPI) was developed; genes like Salmonella pathogenicity island encode aggressive or modulating proteins. Initially, Salmonella needs to be attached and stabilized via adhesin factor, without which no further steps can be taken. In this review, an attempt has been made to elaborate on each factor attached to the host cell or to modulating and aggressive proteins that evade immune systems. This review includes four sections: (A) attachment factors or T3SS- independent entrance, (B) effector proteins or T3SS-dependent entrance, (c) regulation of invasive genes, and (D) regulation of immune responses.

The Possible Role of Pathogenic and Non-Pathogenic Bacteria in Initiation and Exacerbation of Celiac Disease; A Comprehensive Review.

Celiac Disease (CD) is an immune-mediated enteropathy, generally of the proximal intestine, that occurs in genetically susceptible individuals triggered by the ingestion of gluten. The incidence and frequency of CD are increasing, and it is predicted that CD affects approximately 1% of the people worldwide. The common clinical manifestations of CD are divided in two sections, including classic and non-classic symptoms that can be created in childhood and adulthood. The relationship between pathogenic and non-pathogenic bacteria with CD is complex and multidirectional. In previous published studies, results demonstrated the triggering impact of bacteria, viruses, and parasites on initiation and development of Inflammatory Bowel Disease (IBD) and Irritable Bowel Syndrome (IBS). Different studies revealed the inducing effect of pathogenic and non-pathogenic bacteria on CD. However, increasing evidence proposes that some of these microorganisms can also play several positive roles in CD process. Although information of the pathogenesis of the CD is quickly expanding, the possible role of bacteria needs further examination. In conclusion, with respect to the possible correlation between different bacteria in CD, the current review-based study aims to discuss the possible relationship between CD and pathogenic and non-pathogenic bacteria and to show various and significant aspects of mechanisms involved in the CD process.

Phage therapy as a renewed therapeutic approach to mycobacterial infections: a comprehensive review.

Mycobacterial infections are considered to a serious challenge of medicine, and the emergence of MDR and XDR tuberculosis is a serious public health problem. Tuberculosis can cause high morbidity and mortality around the world, particularly in developing countries. The emergence of drug-resistant Mycobacterium infection following limited therapeutic technologies coupled with the serious worldwide tuberculosis epidemic has adversely affected control programs, thus necessitating the study of the role bacteriophages in the treatment of mycobacterial infection. Bacteriophages are viruses that are isolated from several ecological specimens and do not exert adverse effects on patients. Phage therapy can be considered as a significant alternative to antibiotics for treating MDR and XDR mycobacterial infections. The useful ability of bacteriophages to kill Mycobacterium spp has been explored by numerous research studies that have attempted to investigate the phage therapy as a novel therapeutic/diagnosis approach to mycobacterial infections. However, there are restricted data about phage therapy for treating mycobacterial infections. This review presents comprehensive data about phage therapy in the treatment of mycobacterial infection, specifically tuberculosis disease.

Are Viruses and Parasites Linked to Celiac Disease? A Question that Still has no Definite Answer.

Celiac Disease (CD) is a complex autoimmune enteropathy of the small intestine that commonly occurs in genetically predisposed individuals due to intake of gluten and related proteins. Gluten consumption, duration of breast-feeding, various infections, especially frequent intestinal infections, vaccinations and use of antibiotics can be linked to CD. It is predicted that it affects 1% of the global population and its incidence rate is increasing. Most of the people with the HLA-DQ2 or HLADQ8 are at a higher risk of developing this disease. The link between infections and autoimmune diseases has been very much considered in recent years. In several studies, we explained that pathogenic and non-pathogenic microorganisms might have multiple roles in initiation, exacerbation, and development of Irritable Bowel Syndrome (IBS) and Inflammatory Bowel Disease (IBD). In various studies, the relationship between infections caused by viruses, such as Epstein-Barr Virus (EBV), Rotavirus, Hepatitis C (HCV), Hepatitis B virus (HBV), Cytomegalovirus (CMV), and Influenza virus, and parasites including Giardia spp. and Toxoplasma gondii with CD has been raised. However, increasing evidence proposes that some of these microorganisms, especially helminths, can also have protective and even therapeutic roles in the CD process. Therefore, in order to determine the role of microorganisms in the process of this disease, we attempted to summarize the evidence suggesting the role of viral and parasitic agents in pathogenesis of CD.

Staphylococcus aureus versus neutrophil: Scrutiny of ancient combat.

Staphylococcus aureus (S.aureus) is a Gram-positive bacterium that causes many infections and diseases. This pathogen can cause many types of infections such as impetigo, toxic shock syndrome toxin (TSST1), pneumonia, endocarditis, and autoimmune diseases like lupus erythematosus and can infect other healthy individuals. In the pathogenic process, colonization is a main risk factor for invasive diseases. Various factors including the cell wall-associated factors and receptors of the epithelial cells facilitate adhesion and colonization of this pathogen. S. aureus has many enzymes, toxins, and strategies to evade from the immune system either by an enzyme that lyses cellular component or by hiding from the immune system via surface antigens like protein A and second immunoglobulin-binding protein (Sbi). The strategies of this bacterium can be divided into five groups: A: Inhibit neutrophil recruitment B: Inhibit phagocytosis C: Inhibit killing by ROS, D: Neutrophil killing, and E: Resistance to antimicrobial peptide. On the other hand, innate immune system via neutrophils, the most important polymorphonuclear leukocytes, fights against bacterial cells by neutrophil extracellular trap (NET). In this review, we try to explain the role of each factor in immune evasion.

Specification of Bacteriophage Isolated Against Clinical Methicillin-Resistant Staphylococcus Aureus.

OBJECTIVES: The emergence of resistant bacteria is being increasingly reported around the world, potentially threatening millions of lives. Amongst resistant bacteria, methicillin-resistant Staphylococcus aureus (MRSA) is the most challenging to treat. This is due to emergent MRSA strains and less effective traditional antibiotic therapies to Staphylococcal infections. The use of bacteriophages (phages) against MRSA is a new, potential alternate therapy. In this study, morphology, genetic and protein structure of lytic phages against MRSA have been analysed. METHODS: Isolation of livestock and sewage bacteriophages were performed using 0.4 µm membrane filters. Plaque assays were used to determine phage quantification by double layer agar method. Pure plaques were then amplified for further characterization. Sulfate-polyacrylamide gel electrophoresis and random amplification of polymorphic DNA were run for protein evaluation, and genotyping respectively. Transmission electron microscope was also used to detect the structure and taxonomic classification of phage visually. RESULTS: Head and tail morphology of bacteriophages against MRSA were identified by transmission electron microscopy and assigned to the Siphoviridae family and the Caudovirales order. CONCLUSION: Bacteriophages are the most abundant microorganism on Earth and coexist with the bacterial population. They can destroy bacterial cells successfully and effectively. They cannot enter mammalian cells which saves the eukaryotic cells from lytic phage activity. In conclusion, phage therapy may have many potential applications in microbiology and human medicine with no side effect on eukaryotic cells.

The impact of SIGN glaucoma guidelines on false-positive referrals from community optometrists in Central Scotland.

BACKGROUND: Since the introduction of National Institute for Health and Care Excellence glaucoma guidelines 2009, the number of referrals from community optometrists to hospital eye services has increased across the UK, resulting in increase in first visit discharge rates (FVDRs). AIM: To assess the impact of Scottish Intercollegiate Guidelines Network (SIGN) 144 on quality of referrals from community optometrists. METHODOLOGY: A retrospective study of patient records who attended as new adult glaucoma referrals to clinics in Princess Alexandra Eye Pavilion, Edinburgh, and in Greater Glasgow and Clyde, was carried out across October-November 2014 (group 1) and September-October 2016 (group 2), before and after the introduction of SIGN 144. The primary outcome of this study is FVDRs. A secondary outcome is the extent of compliance to referral recommendations by SIGN guidelines. RESULTS: Three hundred and twelve and 325 patients were included in groups 1 and 2, respectively. There was a significant decline in FVDRs between these two periods from 29.2% to 19.2%. (p=0.004) (OR 0.58 (95%CI 0.40 to 0.84)). Post-SIGN guidelines, 87% of referrals were compliant to SIGN referral criteria while 13% remained non-compliant. The main reasons for non-compliance were no repeatable visual field defects (42.0%) and referrals due to high intraocular pressure were either not repeated or not interpreted in the context of age and central corneal thickness (36.8%). CONCLUSION: Patients referred after the introduction of SIGN guidelines were 33.5% less likely to be discharged at the first visit. Although compliance to most recommendations in SIGN guidelines has improved, there is still a need to improve adherence to referral criteria.

Identification of Synergistic Interaction Between Cannabis-Derived Compounds for Cytotoxic Activity in Colorectal Cancer Cell Lines and Colon Polyps That Induces Apoptosis-Related Cell Death and Distinct Gene Expression.

Introduction: Colorectal cancer remains the third most common cancer diagnosis and fourth leading cause of cancer-related mortality worldwide. Purified cannabinoids have been reported to prevent proliferation, metastasis, and induce apoptosis in a variety of cancer cell types. However, the active compounds from Cannabis sativa flowers and their interactions remain elusive. Research Aim: This study was aimed to specify the cytotoxic effect of C. sativa-derived extracts on colon cancer cells and adenomatous polyps by identification of active compound(s) and characterization of their interaction. Materials and Methods: Ethanol extracts of C. sativa were analyzed by high-performance liquid chromatography and gas chromatograph/mass spectrometry and their cytotoxic activity was determined using alamarBlue-based assay (Resazurin) and tetrazolium dye-based assay (XTT) on cancer and normal colon cell lines and on dysplastic adenomatous polyp cells. Annexin V Assay and fluorescence-activated cell sorting (FACS) were used to determine apoptosis and cell cycle, and RNA sequencing was used to determine gene expression. Results: The unheated cannabis extracts (C2F), fraction 7 (F7), and fraction 3 (F3) had cytotoxic activity on colon cancer cells, but reduced activity on normal colon cell lines. Moreover, synergistic interaction was found between F7 and F3 and the latter contains mainly cannabigerolic acid. The F7 and F7+F3 cytotoxic activity involved cell apoptosis and cell cycle arrest in S or G0/G1 phases, respectively. RNA profiling identified 2283 differentially expressed genes in F7+F3 treatment, among them genes related to the Wnt signaling pathway and apoptosis-related genes. Moreover, F7, F3, and F7+F3 treatments induced cell death of polyp cells. Conclusions:C. sativa compounds interact synergistically for cytotoxic activity against colon cancer cells and induce cell cycle arrest, apoptotic cell death, and distinct gene expression. F3, F7, and F7+F3 are also active on adenomatous polyps, suggesting possible future therapeutic value.