Patterns of initial and first-intensifying antidiabetic drug utilization among patients with type 2 diabetes mellitus in Scotland, 2010-2020: A retrospective population-based cohort study.

AIM: To evaluate the utilization and prescribing patterns of antidiabetic drugs (ADDs) for patients with type 2 diabetes mellitus (T2DM) at treatment initiation and first intensification. METHODS: A retrospective cohort study was performed using linked routinely collected data of patients with T2DM who received ADDs between January 2010 and December 2020 in Scotland. The prescribing patterns were quantified using frequency/percentages, absolute/relative change, and trend tests. RESULTS: Overall, 145 909 new ADD users were identified, with approximately 91% (N = 132 382) of patients receiving a single ADD at first treatment initiation. Metformin was the most often prescribed monotherapy (N = 118 737, 89.69%). A total of 50 731 patients (39.40%) who were started on metformin (N = 46 730/118 737, 39.36%) or sulphonylurea (SU; N = 4001/10 029, 39.89%) monotherapy had their treatment intensified with one or more additional ADD. Most initial-metformin (45 963/46 730; 98.36%) and initial-SU users (3894/4001; 97.33%) who added further drugs were intensified with single ADDs. SUs (22 197/45 963; 48.29%) were the most common first-intensifying monotherapy after initial metformin use, but these were replaced by sodium-glucose cotransporter-2 (SGLT2) inhibitors in 2019 (SGLT2 inhibitors: 2039/6065, 33.62% vs. SUs: 1924/6065, 31.72%). Metformin was the most frequently added monotherapy to initial SU use (2924/3894, 75.09%). Although the majority of patients received a single ADD, the use of combination therapy significantly increased over time. Nevertheless, there was a significant increasing trend towards prescribing the newer ADD classes (SGLT2 inhibitors, dipeptidyl peptidase-4 inhibitors) as monotherapy or in combination compared with the older ones (SUs, insulin, thiazolidinediones) at both drug initiation and first intensification. CONCLUSIONS: An overall increasing trend in prescribing the newer ADD classes compared to older ADDs was observed. However, metformin remained the most commonly prescribed first-line ADD, while SGLT2 inhibitors replaced SUs as the most common add-on therapy to initial metformin use in 2019.

Live chicken egg embryos as an alternative in vivo tumour model for deep surface enhanced Raman spectroscopy.

Live chicken egg embryos offer new opportunities for evaluation and continuous monitoring of tumour growth for in vivo studies compared to traditional rodent models. Here, we report the first use of surface enhanced Raman scattering (SERS) mapping and surface enhanced spatially offset Raman scattering (SESORS) for the detection and localisation of targeted gold nanoparticles in live chicken egg embryos bearing a glioblastoma tumour.

Meta-analysis of factors associated with antidiabetic drug prescribing for type 2 diabetes mellitus.

BACKGROUND: There is a lack of consensus on prescribing alternatives to initial metformin therapy and intensification therapy for type 2 diabetes mellitus (T2DM) management. This review aimed to identify/quantify factors associated with prescribing of specific antidiabetic drug classes for T2DM. METHODS: Five databases (Medline/PubMed, Embase, Scopus, Web of Science) were searched using the synonyms of each concept (patients with T2DM, antidiabetic drugs and factors influencing prescribing) in both free text and Medical Subject Heading (MeSH) forms. Quantitative observational studies evaluating factors associated with antidiabetic prescribing of metformin, sulfonylurea, thiazolidinedione, Dipeptidyl-peptidase 4 inhibitors (DPP4-I), sodium glucose transporter 2 inhibitors (SGLT2-I), Glucagon-Like peptide receptor agonist (GLP1-RA) and insulin in outpatient settings and published from January 2009 to January 2021 were included. Quality assessment was performed using a Newcastle-Ottawa scale. The validation was done for 20% of identified studies. The pooled estimate was measured using a three-level random-effect meta-analysis model based on odds ratio [95% confidence interval]. Age, sex, body mass index (BMI), glycaemic control (HbA1c) and kidney-related problems were quantified. RESULTS: Of 2331 identified studies, 40 met the selection criteria. Of which, 36 and 31 studies included sex and age, respectively, while 20 studies examined baseline BMI, HbA1c and kidney-related problems. The majority of studies (77.5%, 31/40) were rated as good and despite that the overall heterogeneity for each studied factor was more than 75%, it is mostly related to within-study variance. Older age was significantly associated with higher sulfonylurea prescription (1.51 [1.29-1.76]), yet lower prescribing of metformin (0.70 [0.60-0.82]), SGLT2-I (0.57 [0.42-0.79]) and GLP1-RA (0.52 [0.40-0.69]); while higher baseline BMI showed opposite significant results (sulfonylurea: 0.76 [0.62-0.93], metformin: 1.22 [1.08-1.37], SGLT2-I: 1.88 [1.33-2.68], and GLP1-RA: 2.35 [1.54-3.59]). Both higher baseline HbA1c and having kidney-related problems were significantly associated with lower metformin prescription (0.74 [0.57-0.97], 0.39 [0.25-0.61]), but more insulin prescriptions (2.41 [1.87-3.10], 1.52 [1.10-2.10]). Also, DPP4-I prescriptions were higher for patients with kidney-related problems (1.37 [1.06-1.79]) yet lower among patients with higher HbA1c (0.82 [0.68-0.99]). Sex was significantly associated with GLP1-RA and thiazolidinedione prescribing (F:M; 1.38 [1.19-1.60] and 0.91 [0.84-0.98]). CONCLUSION: Several factors were identified as potential determinants of antidiabetic drug prescribing. The magnitude and significance of each factor differed by antidiabetic class. Patient's age and baseline BMI had the most significant association with the choice of four out of the seven studied antidiabetic drugs followed by the baseline HbA1c and kidney-related problems which had an impact on three studied antidiabetic drugs, whereas sex had the least impact on prescribing decision as it was associated with GLP1-RA and thiazolidinedione only.

Sepsis scoring systems and use of the Sepsis six care bundle in maternity hospitals.

BACKGROUND: This study aimed to assess the predictive power of three different Sepsis Scoring Systems (SSSs), namely maternity Systematic Inflammatory Response Syndrome (mSIRS), quick Sepsis-related Organ Failure Assessment (qSOFA) and Modified Early Warning System (MEWS) in identifying sepsis by comparing them with positive culture. This study also sought to evaluate compliance with using the Sepsis Six Care Bundle (SSCB) operated in an individual health board. METHODS: A retrospective cohort study was conducted in 3 maternity hospitals of a single Scottish health board that admitted 2690 pregnancies in a 12 weeks period in 2016. Data for study was obtained from medical notes, handheld and electronic health records for women who were prescribed antibiotics with a confirmed or suspected diagnosis of sepsis. Data on clinical parameters was used to classify women according to mSIRS, qSOFA and MEWS as having sepsis or not and this was compared to results of positive culture to obtain sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and area under Receiver Operating Characteristic curve (AUROC) along with their 95% confidence intervals. Data was also obtained on SSCB compliance. RESULTS: A total of 89 women were diagnosed with sepsis, of which 14 had missing data, leaving 75 for final analysis. Sensitivity, specificity, PPV, NPV and AUROC of mSIRS and MEWS were almost similar with AUROC of both being around 50%. Only 33 (37.1%) had identifiable sepsis six sticker displayed on medical notes and only 2 (2.2%) had all elements of SSCB delivered within the recommended one-hour post-diagnosis period. Blood culture and full blood count with other lab tests had been performed for most women (97%) followed by intravenous antibiotics and fluids (93.9%). CONCLUSIONS: mSIRS and MEWS were quite similar in detecting sepsis when compared to positive culture, with their ability to detect sepsis being close to chance. This underlines the need for creating a valid SSS with high sensitivity and specificity for clinical use in obstetric settings. Clinical use of SSCB was limited despite it being a health board policy, although there is considerable possibility of improvement following detailed audits and removal of barriers for implementing SSCB.

Antileishmanial efficacy and tolerability of combined treatment with non-ionic surfactant vesicle formulations of sodium stibogluconate and paromomycin in dogs.

Infection with Leishmania infantum causes the disease visceral leishmaniasis (VL), which is a serious clinical and veterinary problem. The drugs used to treat canine leishmaniasis (CanL) do not cause complete parasite clearance; they can be toxic, and emerging drug resistance in parasite populations limits their clinical utility. Therefore, in this study we have evaluated the toxicity and efficacy of joint treatment with a 1:1 mixture of sodium stibogluconate-NIV (SSG-NIV, 10 mg Sbv/day) and paromomycin-NIV (PMM-NIV, 10 mg PMM/kg/day), given intravenously daily for seven days from day 270 post-infection, to nine-month-old female beagle dogs (n = 6) experimentally infected with Leishmania infantum. Treatment significantly improved the clinical symptoms of VL infection in all the treated dogs, reduced parasite burdens in lymph nodes and bone marrow, and all symptomatic treated dogs, were asymptomatic at 90 days post-treatment. Treatment was associated with a progressive and significant decrease in specific IgG anti-Leishmania antibodies using parasite soluble antigen (p < 0.01) or rK39 (p < 0.01) as the target antigen. In addition, all dogs were classified as parasite negative based on Leishmania nested PCR and quantitative real time PCR tests and as well as an inability to culture of promastigote parasites from lymph nodes and bone marrow tissue samples taken at day 90 post-treatment. However, treatment did not cure the dogs as parasites were detected at 10 months post-treatment, indicating that a different dosing regimen is required to cause long term cure or prevent relapse.

Evaluating the appropriateness of carbapenem and piperacillin-tazobactam prescribing in a tertiary care hospital in Saudi Arabia.

BACKGROUND: Antimicrobial resistance (AMR) is presently considered an emergent major global public health concern and excessive and/or inappropriate use of broad-spectrum antimicrobials contribute to the development of AMR. OBJECTIVE: To evaluate the appropriateness of carbapenems and piperacillin-tazobactam use in a tertiary care hospital. METHODS: A retrospective, observational, cross-sectional, drug-utilization study was conducted. The study included all adult hospitalized patients who had received at least one dose of the antimicrobials during their admission for the period between 1 January 2016 and 31 December 2017. The appropriateness of antimicrobial therapy was evaluated according to the Infectious Diseases Society of America (IDSA) guidelines with the consideration of the institutional antibiogram. RESULTS: Overall, 2731 patients received 5005 courses with one of the antimicrobials, for a total of 5045.9 defined daily doses (DDD) of imipenem-cilastatin, 6492.3 of meropenem and 15,595 of piperacillin-tazobactam (4.93, 6.34 and 15.24 DDD/100 bed days, respectively). The mean age of the patients who received either antimicrobial was 55.5 ± 20.3 years, with a 14-day average length of hospital stay. About half (52%) of the prescriptions were written for patients treated in the medical ward. Pneumonia (26.6%) and sepsis (24.9%) were the most common indication for the initiation of antimicrobial therapy. Of the assessed prescriptions, only 2787 (56.5%) were prescribed appropriately, with 2142 (43.5%) deemed inappropriate. The three most common reasons for inappropriate prescription were: the spectrum of activity was too broad (44.6%), followed by antimicrobial use without culture request (32.4%), and failure of suitable antimicrobial de-escalation (19.9%). CONCLUSIONS: The study indicates that the overall rate of inappropriateness was high, emphasizing the need to develop initiatives to effectively improve broad-spectrum antimicrobial prescribing.

Stereoretentive Etherification of an α-Aryl-ß-amino Alcohol Using a Selective Aziridinium Ring Opening for the Synthesis of AZD7594.

A selective aziridinium ring-opening was used to etherify an α-aryl-ß-amino alcohol with stereochemical retention. This transformation was achieved in a biphasic system to address phenoxide solubility and the formation of a sulfonate ester impurity. The protecting group strategy was directed by a stability study of the activated α-aryl-ß-amino alcohol in this system. Process analytical techniques were used to establish reaction understanding, and mixing on large scale was modeled in silico. The process provided a selective and efficient method of preparing the nonsteroidal, inhaled selective glucocorticoid receptor modulator AZD7594.

Proof of concept studies for siRNA delivery by nonionic surfactant vesicles: in vitro and in vivo evaluation of protein knockdown.

RNA interference is an effective and naturally occurring post-transcriptional gene regulatory mechanism. This mechanism involves the degradation of a target messenger RNA (mRNA) through the introduction of short interfering RNA (siRNA) that is complementary to the target mRNA. The application of siRNA-based therapeutics is limited by the development of an effective delivery system, as naked siRNA is unstable and cannot penetrate the cell membrane. In this study, we investigated the use of cationic niosomes (CN) prepared by microfluidic mixing for siRNA delivery. In an in vitro model, these vesicles were able to deliver anti-luciferase siRNA and effectively suppress luciferase expression in B16-F10 mouse melanoma cells. More importantly, in an in vivo mouse model, intratumoral administration of CN-carrying anti-luciferase siRNA led to significant suppression of luciferase expression compared with naked siRNA. Thus, we have established a novel and effective system for the delivery of siRNA both in vitro and in vivo, which shows high potential for future application of gene therapeutics.

Optimizing carbapenem use through a national quality improvement programme.

Background: Concern about increasing carbapenem and piperacillin/tazobactam use led the Scottish Antimicrobial Prescribing Group (SAPG) to develop national guidance on optimal use of these agents, and to implement a quality improvement programme to assess the impact of guidance on practice. Objectives: To evaluate how SAPG guidance had been implemented by health boards, assess how this translated into clinical practice, and investigate clinicians' views and behaviours about prescribing carbapenems and alternative agents. Methods: Local implementation of SAPG guidance was assessed using an online survey. A bespoke point prevalence survey was used to evaluate prescribing. Clinicians' experience of using carbapenems and alternatives was examined through semi-structured interviews. National prescribing data were analysed to assess the impact of the programme. Results: There were greater local restrictions for carbapenems than for piperacillin/tazobactam. Laboratory result suppression was inconsistent between boards and carbapenem-sparing antibiotics were not widely available. Compliance with local guidelines was good for meropenem but lower for piperacillin/tazobactam. Indication for use was well documented but review/stop dates were poorly documented for both antibiotics. Decisions to prescribe a carbapenem were influenced by local guidelines and specialist advice. Many clinicians lacked confidence to de-escalate treatment. Use of both antibiotics decreased during the course of the programme. Conclusions: A multifaceted quality improvement programme was used to gather intelligence, promote behaviour change, and focus interventions on the use of carbapenems and piperacillin/tazobactam. Use of these antimicrobials decreased during the programme-a trend not seen elsewhere in Europe. The programme could be generalized to other antimicrobials.

Formulation of Nonionic Surfactant Vesicles (NISV) Prepared by Microfluidics for Therapeutic Delivery of siRNA into Cancer Cells.

Small interfering RNAs (siRNA) have a broad potential as therapeutic agents to reversibly silence any target gene of interest. The clinical application of siRNA requires the use of safe and effective delivery systems. In this study, we investigated the use of nonionic surfactant vesicles (NISV) for the delivery of siRNA. Different types of NISV formulations were synthesized by microfluidic mixing and then evaluated for their physiochemical properties and cytotoxicity. The ability of the NISV to carry and transfect siRNA targeting green fluorescent protein (GFP) into A549 that stably express GFP (copGFP-A549) was evaluated. Flow cytometry and Western blotting were used to study the GFP expression knockdown, and significant knockdown was observed as a result of siRNA delivery to the cells by NISV. This occurred in particular when using Tween 85, which was able to achieve more than 70% GFP knockdown. NISV were thus demonstrated to provide a promising and effective platform for therapeutic delivery of siRNA.

An association between socioeconomic deprivation and primary care antibiotic prescribing in Scotland.

OBJECTIVE: To evaluate the association between socioeconomic deprivation and antibiotic prescribing in Scotland. PATIENTS AND METHODS: Data for dispensed antibiotic prescriptions written by general practitioners were obtained for all Scottish National Health Service boards from 2010 to 2012. Deprivation was assessed linking dispensing events to the Scottish Index of Multiple Deprivation (SIMD) score for the patient's datazone (neighbourhood area). The relationship between the deprivation area and antibiotic use (items per 1000 persons per day) was stratified according to the patient's age and sex and the antibiotic class dispensed. A multivariate Poisson regression model was used to formally test the associations. RESULTS: Approximately 12 million prescription items during 2010-2012 were assessed. Patients in the most deprived SIMD quintile had an overall prescription rate that was 36.5% higher than those in the least deprived quintile. The effect of deprivation upon prescription rates was most pronounced for women aged 40-59 years, and for penicillins and metronidazole. CONCLUSIONS: Deprivation was found to have a consistent association with increased rates of antibiotic prescribing in Scotland, which may have significant implications for antimicrobial stewardship and public health campaigns.

Assessment of the antigen-specific antibody response induced by mucosal administration of a GnRH conjugate entrapped in lipid nanoparticles.

Vaccines administered parenterally have been developed against gonadotrophin-releasing hormone (GnRH) for anti-fertility and anti-cancer purposes. The aim of this study was to demonstrate whether mucosal delivery using GnRH immunogens entrapped in lipid nanoparticles (LNP) could induce anti-GnRH antibody titers. Immunogens consisting of KLH (keyhole limpet hemocyanin) conjugated to either GnRH-I or GnRH-III analogues were entrapped in LNP. Loaded non-ionic surfactant vesicles (NISVs) were administered subcutaneously, while nasal delivery was achieved using NISV in xanthan gum and oral delivery using NISV containing deoxycholate (bilosomes). NISV and bilosomes had similar properties: they were spherical, in the nanometre size range, with a slightly negative zeta potential and surface properties that changed with protein loading and inclusion of xanthan gum. Following immunization in female BALB/c mice, systemic antibody responses were similar for both GnRH-I and GnRH-III immunization. Only nasal delivery proved to be successful in terms of producing systemic and mucosal antibodies. FROM THE CLINICAL EDITOR: The main research question addressed in this study was whether mucosal delivery using gonadotrophin-releasing hormone immunogens entrapped in lipid nanoparticles could induce anti-GnRH antibody titers. Only nasal delivery proved to be successful in terms of producing systemic and mucosal antibodies with this approach.

Succinobucol-eluting stents increase neointimal thickening and peri-strut inflammation in a porcine coronary model.

OBJECTIVE: The aim of this study was to assess the efficacy of stent-based delivery of succinobucol alone and in combination with rapamycin in a porcine coronary model. BACKGROUND: Current drugs and polymers used to coat coronary stents remain suboptimal in terms of long term efficacy and safety. Succinobucol is a novel derivative of probucol with improved antioxidant and anti-inflammatory properties. METHODS: Polymer-free Yukon stents were coated with 1% succinobucol (SucES), 2% rapamycin (RES), or 1% succinobucol plus 2% rapamycin solutions (SucRES) and compared with a bare metal stent (BMS). RESULTS: The in vivo release profile of SucES indicated drug release up to 28 days (60% drug released at 7 days); 41 stents (BMS, n = 11; SucES, n =10; RES, n = 10; SucRES, n = 10) were implanted in the coronary arteries of 17 pigs. After 28 days, mean neointimal thickness was 0.31 ± 0.14 mm for BMS, 0.51 ± 0.14 mm for SucES, 0.19 ± 0.11 mm for RES, and 0.36 ± 0.17 mm for SucRES (P < 0.05 for SucES vs. BMS). SucES increased inflammation and fibrin deposition compared with BMS (P < 0.05), whereas RES reduced inflammation compared with BMS (P < 0.05). CONCLUSION: In this model, stent-based delivery of 1% succinobucol using a polymer-free stent platform increased neointimal formation and inflammation following coronary stenting.

Is additional oral phosphate supplementation for preterm infants necessary: an assessment of clinical audit.

UNLABELLED: Adequate phosphate intake is important for the prevention of metabolic bone disease in preterm infants. The European Society for Paediatric Gastroenterology, Hepatology and Nutrition recommends a daily phosphate intake of 184-230 mg/kg/day, which should be met by standard feed volumes of either commercially fortified breast milk or preterm formulae. We sought to investigate whether our local practise of providing supplemental oral phosphate for all infants born before 32 weeks' gestation continues to be necessary. Details of parenteral and milk feeding and both oral and parenteral phosphate supplementation from birth until 8 weeks of age were collected retrospectively from the case notes of 31 preterm infants. Routinely collected biochemical markers of bone mineral status were also recorded. Mean (SD) plasma phosphate concentration was higher when oral phosphate supplementation was given [2.10 (0.38) versus 1.92(0.50) mM/L without supplement (p < 0.001)]. A minimum average phosphate intake of 184 mg/kg/day was achieved by 47 and 77 % of babies in weeks 1 and 2, respectively, and by 84-100 % of infants from week 3. The percentage of plasma phosphate measurements below the minimum target of 1.8 mM/L was greater amongst unsupplemented babies (45 versus 18 %). CONCLUSION: A majority of infants <32 weeks' gestation did not achieve the recommended phosphate intake during the first week of life. Despite achieving the recommended phosphate intake from week 3, many infants did not have plasma phosphate concentrations within the accepted normal range. Additional oral supplementation may help to achieve blood phosphate concentrations within this target range.

Elderly Patient Involvement in the Decision-Making Process of Breast Cancer Management in Kuwait.

INTRODUCTION: Worldwide statistics highlight that around 40% of breast cancer cases occur in patients aged 65 years and above, with expectations that this will increase as the population gets older. Cancer management in elderly patients is still unclear and depends primarily on individual oncologist decisions. The literature suggests that elderly breast cancer patients receive less intensive chemotherapy than younger patients, which is mainly attributed to a lack of effective individualized assessment or age bias. The current study explored the impact of elderly patient involvement in the decision-making process of breast cancer management and less intensive treatment allocation in Kuwait. METHODS: In an observational exploratory populationbased study, 60 newly diagnosed breast cancer patients aged 60 years and above and candidates for chemotherapy were included. Patients were grouped based on the treating oncologists' decision to receive either intensive first-line chemotherapy (standard treatment) or less intensive/ other than first-line chemotherapy (non-standard treatment) according to standardized international guidelines recommendations. Patients' attitudes toward the recommended treatment (accept/ reject) were documented through a short semi-structured interview. The prevalence of patients' interference with the treatment was reported, and individual causes were investigated. RESULTS: Data showed that 58.8% and 41.2% of elderly patients were allocated for intensive and less intensive treatment, respectively. Overall, 15% of patients interfered with the treatment plan against their oncologists' recommendations even though they were allocated for less intensive treatment. Among those, 6.7% of patients rejected the recommended treatment, 3.3% delayed initiating treatment, and 5% received <3 cycles of chemotherapy but refused to continue cytotoxic treatment. None of the patients requested intensive treatment. This interference was mainly directed by cytotoxic treatment toxicity concerns and targeted treatment preference. CONCLUSION: In clinical practice, oncologists allocate selected breast cancer patients aged 60 years and above for less intensive cytotoxic treatment to enhance their tolerance; however, this was not always associated with patients' acceptance and compliance. Lack of awareness of targeted treatment indications and utilization directed 15% of patients to reject, delay, or refuse to continue the recommended cytotoxic treatment against their oncologists' recommendations.

Evaluation of RANO Criteria for the Assessment of Tumor Progression for Lower-Grade Gliomas.

PURPOSE: The Response Assessment in Neuro-Oncology (RANO) criteria for lower-grade gliomas (LGGs) define tumor progression as ≥25% change in the T2/FLAIR signal area based on an operator's discretion of the perpendicular diameter of the largest tumor cross-section. Potential sources of error include acquisition inconsistency of 2D slices, operator selection variabilities in both representative tumor cross-section and measurement line locations, and the inability to quantify infiltrative tumor margins and satellite lesions. Our goal was to assess the accuracy and reproducibility of RANO in LG. MATERIALS AND METHODS: A total of 651 FLAIR MRIs from 63 participants with LGGs were retrospectively analyzed by three blinded attending physicians and three blinded resident trainees using RANO criteria, 2D visual assessment, and computer-assisted 3D volumetric assessment. RESULTS: RANO product measurements had poor-to-moderate inter-operator reproducibility (r2 = 0.28-0.82; coefficient of variance (CV) = 44-110%; mean percent difference (diff) = 0.4-46.8%) and moderate-to-excellent intra-operator reproducibility (r2 = 0.71-0.88; CV = 31-58%; diff = 0.3-23.9%). When compared to 2D visual ground truth, the accuracy of RANO compared to previous and baseline scans was 66.7% and 65.1%, with an area under the ROC curve (AUC) of 0.67 and 0.66, respectively. When comparing to volumetric ground truth, the accuracy of RANO compared to previous and baseline scans was 21.0% and 56.5%, with an AUC of 0.39 and 0.55, respectively. The median time delay at diagnosis was greater for false negative cases than for false positive cases for the RANO assessment compared to previous (2.05 > 0.50 years, p = 0.003) and baseline scans (1.08 > 0.50 years, p = 0.02). CONCLUSION: RANO-based assessment of LGGs has moderate reproducibility and poor accuracy when compared to either visual or volumetric ground truths.

From libraries to candidate: the discovery of new ultra long-acting dibasic ß2-adrenoceptor agonists.

Libraries of dibasic compounds designed around the molecular scaffold of the DA(2)/ß(2) dual agonist sibenadet (Viozan™) have yielded a number of promising starting points that have been further optimised into novel potent and selective target molecules with required pharmacokinetic properties. From a shortlist, 31 was discovered as a novel, high potency, and highly efficacious ß(2)-agonist with high selectivity and a duration of action commensurable with once daily dosing.

Pharmaceutical care issues in lung cancer: can community pharmacists support patients receiving systemic anticancer therapy?

OBJECTIVES: Most patients receive systemic anticancer therapy (SACT) as day cases and toxicities, if they occur, are likely to appear first in primary care. Pharmaceutical care can be delivered by community pharmacists, but little is known about the epidemiology of SACT toxicities in the community and potential interventions to address these which raise the following questions: what are the typologies of SACT-associated toxicities experienced by community-based patients and what are the associated pharmaceutical care issues (PCIs)? The aim of this study was to identify toxicities and pharmaceutical care issues of patients prescribed SACT for lung cancer and understand the potential for community pharmacists to deliver aspects of cancer care including toxicity management. METHODS: Retrospective analysis of clinical records of patients prescribed oral and parenteral SACT in 2013-14, to describe patient characteristics; SACT toxicity; PCIs and episodes of unscheduled care. KEY FINDINGS: Twelve categories of toxicity and 13 categories of PCIs were identified from 50 patients. More PCIs were observed with oral SACT/oral-parenteral combinations than with parenteral regimens. The PCIs which could be managed by community pharmacists were mucositis; skin toxicity; gastrointestinal toxicity; reinforcing patient education and identification/prevention of drug interactions. CONCLUSIONS: Community pharmacists are ideally placed to provide pharmaceutical care to patients with lung cancer prescribed SACT. Cancer specialists in secondary care can signpost patients to community pharmacists for early management of low-grade SACT toxicity.

Exploring Physicians' Views, Perceptions and Experiences about Broad-Spectrum Antimicrobial Prescribing in a Tertiary Care Hospital Riyadh, Saudi Arabia: A Qualitative Approach.

Antimicrobial resistance (AMR) is a global public health threat associated with increased mortality, morbidity and costs. Inappropriate antimicrobial prescribing, particularly of broad-spectrums antimicrobials (BSAs), is considered a major factor behind growing AMR. The aim of this study was to explore physician perception and views about BSAs and factors that impact upon their BSAs prescribing decisions. Qualitative semistructured telephone interviews over an eleven-week period were conducted with physicians in a single tertiary care hospital in Riyadh, Saudi Arabia. Purposeful and snowball sampling techniques were adopted as sampling strategy. All interviews were audio recorded, transcribed verbatim, uploaded to NVivo® software and analysed following thematic analysis approach. Four major themes emerged: views on BSAs, factors influencing BSA prescribing and antimicrobial stewardship: practices and barriers and recommendations to improve appropriate BSA prescribing. Recommendations for the future include improving clinical knowledge, feedback on prescribing, multidisciplinary team decision-making and local guideline implementation. Identification of views and determinants of BSA prescribing can guide the design of a multifaceted intervention to support physicians and policymakers to improve antimicrobial prescribing practices.

Translational modifications to improve vaccine efficacy in an oral influenza vaccine.

Oral vaccination using protein antigens is complicated by the degradative effects of the inhospitable conditions in the gastrointestinal tract, such as low pH and digestive enzymes, nescessitating protection and effective delivery of the antigen. The bilosome is a lipid-based, vesicle delivery system incorporating bile salts, which is believed to protect the antigen from degradation, and has been shown to induce significant antibody responses when delivered orally with various vaccines. In translational research, from laboratory bench to industrial scale-up, it is necessary to optimise the manufacturing process in order to improve efficiency and simplify production, giving a more economical end-product. In this study we tested two simplified production methods (3-step and 1-step) along with two different storage methods (lyophilised and non-lyophilised), as well as looking at the effect of buffer pH. The formulations were assessed in a murine system for immunogenicity, alongside characterisation in terms of size and antigen entrapment, with the stability of these aspects assessed with respect to time. Both lyophilised and non-lyophilised 3-step formulations induced significant IgG1, IgG2a and IgA titres, with the lyophilised version showing stable size and antigen entrapment up to 9months.