Assessment of patient perceptions of counselling on oral antineoplastic agents by a dedicated cancer services pharmacist in an outpatient cancer clinic.

BACKGROUND: Oral antineoplastic agents have caused a paradigm shift in cancer treatment, however, they produce many unique challenges. Although oral antineoplastics can have complex administration regimes, low adherence rates and high possibilities of drug-drug interactions, they are administered unsupervised at home. Cancer services pharmacists have the required skillsets to improve patient outcomes associated with oral antineoplastic treatment by increasing patient health literacy, improving concordance and optimising administration protocols. AIM: To evaluate patients' perceptions, experiences and overall satisfaction with dedicated clinical pharmacist consultations in patients treated with oral antineoplastic agents at a major public hospital. METHOD: In this retrospective cross-sectional study at a quaternary hospital in Western Australia, data were collected by a paper questionnaire (mailed in March 2022) to a random sample of 191 patients initiated on oral antineoplastic drugs between January 2021 and February 2022. Demographics, prescribed antineoplastic drug/s, cancer type data were collected including using 5-point Likert scale questions assess patients' overall satisfaction with the clinical pharmacist consultations. RESULTS: The questionnaire response rate was 27.7% (52/188) (mean age 63.2 years; 57.5% female). Most patients (42/52; 80.8%) were satisfied with pharmacist consultations, trusted the pharmacist's advice (45/52; 86.5%), considered that the pharmacist improved their understanding of how to manage side effects (43/52; 82.7%) and they provided an important service in outpatient care (45/52; 86.5%). CONCLUSION: Overall, patients reported positive perceptions, experiences, and satisfaction with the cancer services pharmacist counselling services during their oral antineoplastic treatment.

The use of psychotropic medications in autistic individuals (21 years and younger) in Western Australia: A preliminary investigation.

LAY ABSTRACT: Prescriptions and use of medications to treat mental health conditions in young autistic populations are inconsistent worldwide. This makes it hard to compare findings from international studies to the Australian autistic population, where there are limited relevant studies. Apart from risperidone, there are no other medications specified for direct use in autistic persons. This study aims to gain initial broad understanding of the use of medications, commonly prescribed for mental health conditions, specifically by autistics under the age of 21 years. We analysed data that were previously collected as part of the Western Australian Autism Biological Registry between 2011 and 2015 which amounted to 239 surveys completed on young persons with diagnosed autism. The questionnaires included information on co-occurring conditions, current or previous use of medications and reasons for use of the medications. Only one-quarter of the participants in this study reported using at least one mental health-related medication in their lifetime. The most reported medications were stimulants, antidepressants and antiepileptics. The reasons for using medication included managing attention deficit hyperactivity disorder, challenging behaviours, seizures, sleep difficulties and symptoms of anxiety and depression. The number of individuals reporting medication use in this study was lower compared to other developed countries. Nevertheless, these medications should be monitored due to limited understanding of their use to manage co-occurring symptoms in young autistic persons. The findings highlight the importance of ongoing research to better understand mental health-related medications and inform best practice.

The New Normal: Delayed Peak SARS-CoV-2 Viral Loads Relative to Symptom Onset and Implications for COVID-19 Testing Programs.

BACKGROUND: Early in the coronavirus disease 2019 (COVID-19) pandemic, peak viral loads coincided with symptom onset. We hypothesized that in a highly immune population, symptom onset might occur earlier in infection, coinciding with lower viral loads. METHODS: We assessed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A viral loads relative to symptom duration in symptomatic adults (≥16 years) presenting for testing in Georgia (4/2022-4/2023; Omicron variant predominant). Participants provided symptom duration and recent testing history. Nasal swabs were tested by Xpert Xpress SARS-CoV-2/Flu/RSV assay and cycle threshold (Ct) values recorded. Nucleoprotein concentrations in SARS-CoV-2 polymerase chain reaction (PCR)-positive samples were measured by single molecule array. To estimate hypothetical antigen rapid diagnostic test (Ag RDT) sensitivity on each day after symptom onset, percentages of individuals with Ct value ≤30 or ≤25 were calculated. RESULTS: Of 348 newly-diagnosed SARS-CoV-2 PCR-positive individuals (65.5% women, median 39.2 years), 317/348 (91.1%) had a history of vaccination, natural infection, or both. By both Ct value and antigen concentration measurements, median viral loads rose from the day of symptom onset and peaked on the fourth/fifth day. Ag RDT sensitivity estimates were 30.0%-60.0% on the first day, 59.2%-74.8% on the third day, and 80.0%-93.3% on the fourth day of symptoms.In 74 influenza A PCR-positive individuals (55.4% women; median 35.0 years), median influenza viral loads peaked on the second day of symptoms. CONCLUSIONS: In a highly immune adult population, median SARS-CoV-2 viral loads peaked around the fourth day of symptoms. Influenza A viral loads peaked soon after symptom onset. These findings have implications for ongoing use of Ag RDTs for COVID-19 and influenza.

Use of oral nutritional supplements in irradiated patients with head and neck cancer.

OBJECTIVES: Malnutrition is common among patients with head and neck cancer (HNC) and associated with poorer outcomes. Oral nutritional supplements (ONS) are often prescribed, with concerns raised about their cariogenicity. This study examined ONS use and caries experience in patients with HNC 12 months post-diagnosis. METHODS: Fifty-four patients with HNC referred for pre-radiotherapy dental assessment were recruited. Data collected included: age, gender, residential postcode, smoking, alcohol use, HNC characteristics, dental history, oral hygiene habits, dietary advice and ONS use. Data was collected at diagnosis, during radiotherapy and 6 weeks, three, six- and 12-months post-treatment completion. RESULTS: Fifty-one subjects completed the study. 76.5% of the participants used ONS for an average of 13.8 weeks. Caries developed in 22.9% of ONS users and 11.1% of non-users (p = 0.6585). The mean overall duration of ONS use was 18.7 weeks for the caries group and 8.5 weeks for the caries-free group (p = 0.1507). Lack of collaboration and disconnection was noted between dietary advice given by dieticians and dentists. CONCLUSIONS: ONS use is common among patients with HNC. Larger studies are needed to establish the reasons for caries development and impacts of ONS use on oral health. Importance of multidisciplinary management of malnutrition is highlighted.

Standardization and Comparison of Emergency Use Authorized COVID-19 Assays and Testing Laboratories.

Motivation: The motivation for this work was the need to establish a predefined cutoff based on genome copies per ml (GE/ml) rather than Ct, which can vary depending on the laboratory and assay used. A GE/ml-based threshold was necessary to define what constituted 'low positives" for samples that were included in data sets submitted to the FDA for emergency use approval for SARS-CoV-2 antigen tests. Summary: SARS-CoV-2, the causal agent of the global COVID-19 pandemic, made its appearance at the end of 2019 and is still circulating in the population. The pandemic led to an urgent need for fast, reliable, and widely available testing. After December 2020, the emergence of new variants of SARS-CoV-2 led to additional challenges since new and existing tests had to detect variants to the same extent as the original Wuhan strain. When an antigen-based test is submitted to the Food and Drug Administration (FDA) for Emergency Use Authorization (EUA) consideration it is benchmarked against PCR comparator assays, which yield cycle threshold (CT) data as an indirect indicator of viral load - the lower the CT, the higher the viral load of the sample and the higher the CT, the lower the viral load. The FDA mandates that 10-20% of clinical samples used to evaluate the antigen test have to be low positive. Low positive, as defined by the FDA, are clinical samples in which the CT of the SARS-CoV-2 target gene is within 3 CT of the mean CT value of the approved comparator test's Limit of Detection (LOD). While all comparator tests are PCR-based, the results from different PCR assays used are not uniform. Results vary depending on assay platform, target gene, LOD and laboratory methodology. The emergence and dominance of the Omicron variant further challenged this approach as the fraction of low positive clinical samples dramatically increased as compared to earlier SARS-CoV-2 variants. This led to 20-40% of clinical samples having high CT values and therefore assays vying for an EUA were failing to achieve the 80% Percent Positive Agreement (PPA) threshold required. Here we describe the methods and statistical analyses used to establish a predefined cutoff, based on genome copies per ml (GE/ml) to classify samples as low positive (less than the cutoff GE/ml) or high positive (greater than the cutoff GE/mL). CT 30 for the E gene target using Cobas® SARS-CoV-2-FluA/B platform performed at TriCore Reference Laboratories, and this low positive cutoff value was used for two EUA authorizations. Using droplet digital PCR and methods described here, a value 49,447.72 was determined as the GE/ml equivalent for the low positive cutoff. The CT cutoff corresponding to 49447.72 GE/ml was determined across other platforms and laboratories. The methodology and statistical analysis described here can now be used for standardization of all comparators used for FDA submissions with a goal towards establishing uniform criteria for EUA authorization.

Sensitivity of rapid antigen tests against SARS-CoV-2 Omicron and Delta variants.

Rapid antigen tests (RATs) have become an invaluable tool for combating the COVID-19 pandemic. However, concerns have been raised regarding the ability of existing RATs to effectively detect emerging SARS-CoV-2 variants. We compared the performance of 10 commercially available, emergency use authorized RATs against the Delta and Omicron SARS-CoV-2 variants using both individual patient and serially diluted pooled clinical samples. The RATs exhibited lower sensitivity for Omicron samples when using PCR cycle threshold (CT) value (a rough proxy for RNA concentration) as the comparator. Interestingly, however, they exhibited similar sensitivity for Omicron and Delta samples when using quantitative antigen concentration as the comparator. We further found that the Omicron samples had lower ratios of antigen to RNA, which offers a potential explanation for the apparent lower sensitivity of RATs for that variant when using C T value as a reference. Our findings underscore the complexity in assessing RAT performance against emerging variants and highlight the need for ongoing evaluation in the face of changing population immunity and virus evolution.

Prevalence of SARS-CoV-2 in hemoglobinopathies is modified by age and race.

Prior literature has established a positive association between sickle cell disease and risk of contracting SARS-CoV-2. Data from a cross-sectional study evaluating COVID-19 testing devices (n = 10,567) was used to examine the association between underlying health conditions and SARS-CoV-2 infection in an urban metropolis in the southern United States. Firth's logistic regression was used to fit the model predicting SARS-CoV-2 positivity using vaccine status and different medical conditions commonly associated with COVID-19. Another model using the same method was built using SARS-CoV-2 positivity as the outcome and hemoglobinopathy presence, age (<16 Years vs. ≥16 Years), race/ethnicity and comorbidities, including hemoglobinopathy, as the factors. Our first model showed a significant association between hemoglobinopathy and SARS-CoV-2 infection (OR: 2.28, 95 % CI: (1.17,4.35), P = 0.016). However, in the second model, this association was not maintained (OR: 1.35, 95 % CI: (0.72,2.50), P = 0.344). We conclude that the association between SARS-CoV-2 positivity and presence of hemoglobinopathies like sickle cell disease is confounded by race, age, and comorbidity status. Our results illuminate previous findings by identifying underlying clinical/demographic factors that confound the reported association between hemoglobinopathies and SARS-CoV-2. These findings demonstrate how social determinants of health may influence disease manifestations more than genetics alone.

The New Normal: Delayed Peak SARS-CoV-2 Viral Loads Relative to Symptom Onset and Implications for COVID-19 Testing Programs.

Background: Early in the COVID-19 pandemic, peak viral loads coincided with symptom onset. We hypothesized that in a highly immune population, symptom onset might occur earlier in infection, coinciding with lower viral loads. Methods: We assessed SARS-CoV-2 and influenza A viral loads relative to symptom duration in recently-tested adults. Symptomatic participants ≥16y presenting to testing sites in Georgia (4/2022-4/2023; Omicron variant predominant) provided symptom duration. Nasal swab samples were tested by the Xpert Xpress SARS-CoV-2/Flu/RSV assay and Ct values recorded. Nucleoprotein concentrations in SARS-CoV-2 PCR-positive samples were measured by Single Molecule Array. To estimate hypothetical antigen rapid diagnostic test (Ag RDT) sensitivity on each day after symptom onset, percentages of individuals with Ct value ≤30 or ≤25 were calculated. Results: Of 621 SARS-CoV-2 PCR-positive individuals (64.1% women, median 40.9y), 556/621 (89.5%) had a history of vaccination, natural infection, or both. By both Ct value and antigen concentration measurements, median viral loads rose from the day of symptom onset and peaked on the fourth day. Ag RDT sensitivity estimates were 35.7-71.4% on the first day, 63.9-78.7% on the third day, and 78.6-90.6% on the fourth day of symptoms.In 74 influenza A PCR-positive individuals (55.4% women; median 35.0y), median influenza viral loads peaked on the second day of symptoms. Conclusions: In a highly immune adult population, median SARS-CoV-2 viral loads peaked on the fourth day of symptoms. Influenza A viral loads peaked soon after symptom onset. These findings have implications for ongoing use of Ag RDTs for COVID-19 and influenza. Key Points: In a highly immune adult population, median SARS-CoV-2 viral loads by cycle threshold and antigen measurements peaked on the fourth day of symptoms, with implications for testing practice. In contrast, viral loads for influenza A peaked soon after symptom onset.

Sensitivity of Rapid Antigen Tests Against SARS-CoV-2 Omicron and Delta Variants.

Rapid Antigen Tests (RAT) have become an invaluable tool for combating the COVID-19 pandemic. However, concerns have been raised regarding the ability of existing RATs to effectively detect emerging SARS-CoV-2 variants. We compared the performance of eight commercially available, emergency use authorized RATs against the Delta and Omicron SARS-CoV-2 variants using individual patient and serially diluted pooled clinical samples. The RATs exhibited lower sensitivity for Omicron samples when using PCR Cycle threshold (C T ) value (a proxy for RNA concentration) as the comparator. Interestingly, however, they exhibited similar sensitivity for Omicron and Delta samples when using quantitative antigen concentration as the comparator. We further found that the Omicron samples had lower ratios of antigen to RNA, which offers a potential explanation for the apparent lower sensitivity of RATs for that variant when using C T value as a reference. Our findings underscore the complexity in assessing RAT performance against emerging variants and highlight the need for ongoing evaluation in the face of changing population immunity and virus evolution.

Changes in quality of life over time in patients diagnosed with oral leukoplakia: A prospective longitudinal study.

BACKGROUND: Oral leukoplakia (OL) is one of the most prevalent oral potentially malignant disorders (OPMD). Although there is emerging evidence that quality of life (QoL) is impaired in subjects with OL; studies to date are based on single and heterogenous point-in-time assessments. The aim of this study was to ascertain if QoL scores change over time in individuals diagnosed with OL. METHODS: Forty-one individuals with OL were administered the Short Generic Health Questionnaire (SF-12) and the discipline-specific Oral Potentially Malignant Disorder Questionnaire (OPMDQ) at four points in time: at the time of clinical diagnosis, at the post-biopsy review (confirmed diagnosis), and at 3- and 6-month follow-up appointments. Responses were compared between the four time points. RESULTS: No significant differences were observed in the SF-12 questionnaire scores over time. However, a general improvement in the participants' life quality was evident over the 6-month period under investigation in the domains of psychological and social well-being (p = 0.0027) and effect of treatment on daily life (p = 0.0317) as well as in the total score (p = 0.0005) of the OPMDQ. Age, gender, medical status, tobacco/alcohol use, lesion site, size, the presence of dysplasia and treatment did not impact QoL scores over time. CONCLUSIONS: QoL scores of OL subjects may improve with time. Our results suggest that studies examining QoL in individuals with OL should be controlled for time at which the participants are surveyed.

Healthcare services use by patients with heart failure in Australia: Findings from the SHAPE study.

BACKGROUND AND OBJECTIVES: General practitioners (GPs) play a central role in healthcare, serving as the first point of contact, making appropriate referrals and coordinating care for chronic conditions such as heart failure (HF). We sought to determine healthcare use by people with HF in primary care. METHOD: In this Study of Heart failure in the Australian Primary carE setting (SHAPE), we analysed records of 1.93 million adult patients who attended a total of 43 practices between 1 July 2013 and 30 June 2018. We identified and examined the data of 20,219 patients with HF to describe the frequency of visits and use of Medicare Benefits Schedule items. RESULTS: Patients with HF saw GPs 14.4 times per annum on average; 59.5% had a General Practice Management Plan (GPMP), 2.9% of GPMPs were reviewed annually or more frequently, and 46.8% of patients had been referred to a cardiologist. A total of 3761 had coexisting anxiety or depression, and of these 37.1% had a mental health plan. DISCUSSION: Patients with HF visit their GP frequently, with many not reaching guideline therapy nor referred to cardiologists. Low use of care planning and reviews presents an opportunity for GPs to improve care.

Cross-sectional Census Survey of Patients With Cancer who Received a Pharmacist Consultation in a Pharmacist Led Anti-cancer Clinic.

Pharmacists have a critical consulting role in patients undergoing oral antineoplastic drug therapy to ensure harm minimisation. Studies exploring the benefits of pharmacists in this role are limited. This study evaluated patient perceptions, experiences and overall satisfaction with clinical pharmacist consultations in patients treated with oral antineoplastic drugs. Data on 160 patients initiated on oral antineoplastic drugs between January 2019 and February 2021 were collected retrospectively from an outpatient Comprehensive Cancer Centre of a quaternary hospital in Western Australia (demographics, cancer type, oral antineoplastic drugs prescribed). In addition, patients were mailed a hard copy questionnaire in March 2021 to assess their satisfaction with pharmacist consultations in the pharmacist clinic, using a 5-point Likert scale. The statements included perceptions of the patient's understanding, medication adherence, experiences and overall satisfaction with the clinical pharmacist consultation. There were 76 (47.5%) completed questionnaires returned (52.6% female; average age was 63.2 ± 13.9 years). The majority of patients were satisfied with the service offered by the clinical pharmacist (73/76; 96.1%), perceived that clinical pharmacists provided an important service in outpatient cancer care (71/76; 93.4%) and improved their understanding of the use of oral antineoplastic drugs and side-effect management (48/74; 64.9%). Patients' perceived understanding of their medication regimen and additional health services available improved after pharmacist counselling. The patients also reported overall satisfaction with the service provided by the clinical pharmacist and found it beneficial to their care. The study supports the expanding role of the clinical pharmacist in an outpatient cancer centre.

Implementation factor mapping of a pilot study of point-of-care C-reactive protein testing for respiratory tract infections in community pharmacy.

Background: Explicit consideration of implementation factors in community pharmacy service development may facilitate widespread implementation and sustainability. Objectives: This study involved mapping the methodology for the pilot study of point-of-care C-reactive protein (CRP) testing to support pharmacists' management of respiratory tract infections in Western Australian pharmacies against an implementation factor framework, focussing on the resources and training program provided to participating pharmacy staff. Methods: Phase 1 involved post hoc mapping of the pilot study methodology against the framework previously described by Garcia-Cardenas et al.; phase 2 was an a priori evaluation of the resources and training program, involving pre-training, post-training, and post-pilot questionnaires administered to pharmacists and pharmacy assistants/interns. A mixed model analysis compared pharmacists' responses at the three time points. Results: Employment of comprehensive strategies to optimise service feasibility and sustainability was demonstrated across the five domains of 'professional service', 'pharmacy staff', 'pharmacy', 'local environment' and 'system'; further consideration of 'consumer' or 'patient' factors is needed to address issues such as patient refusal. Study pharmacists (n = 10) and pharmacy assistants/interns (n = 5) reported high levels of satisfaction with the training (100% 'good'/'excellent'). Pharmacists reported significantly improved attitudes towards, confidence in, and knowledge about CRP testing and service provision from pre- to post-training (p < 0.05). Positive perceptions were maintained at the post-pilot time point. Conclusions: Post hoc mapping of implementation factors highlighted potential strengths and deficiencies of the current service model. Systematic, prospective mapping, coupled with strategies to explicitly emphasise the patient perspective, may have value in optimising service implementation or modifying future service delivery models.

Construct validity, reliability, and responsiveness of the Wrist Position Sense Test for use in children with hemiplegic cerebral palsy.

INTRODUCTION: We investigate the construct validity, test re-test reliability, and responsiveness of the Wrist Position Sense Test (WPST) for children with hemiplegic cerebral palsy (CP). METHODS: Twenty-eight children with spastic hemiplegic CP [mean age 10.8 years; SD 2.4 years] and 39 typically developing (TD) children [mean age 11 years; SD 2.9 years] participated in a cross-sectional study to investigate construct validity and association with an upper limb activity measure, the Box and Block Test (BBT). Twenty-two TD children were tested at a second time-point to examine reliability. Test responsiveness was determined by random allocation of 17 children with CP to a treatment (n = 10) or control (n = 7) group with assessments completed at four time-points. RESULTS: Significantly greater differences were observed in mean error of indicated wrist position (p < 0.01) in children with CP at baseline (M = 21.6°, SD = 21.6°) than in TD children (M = 12.8°, SD = 11.0°). Larger WPST errors were associated with poorer performance on the BBT (p < 0.01) indicating a substantial association, and there were no consistent differences between time-points indicating test re-test reliability within a TD population. The WPST demonstrated responsiveness to intervention with a statistically significant reduction in mean error following treatment (p < 0.001), not seen in the control group (p = 0.28). CONCLUSION: The WPST demonstrated construct validity in this preliminary study. Scores were associated with an upper limb activity measure, and scores changed significantly following somatosensory training. These findings support further research and future psychometric investigation of the WPST in children with CP. KEY POINTS FOR OCCUPATIONAL THERAPY: This study provides psychometric knowledge about the WPST tool The WPST shows promise as a discriminative measure with preliminary evidence of responsiveness and intra-rater reliability Until further testing, the WPST can be used cautiously in future research studies to measure wrist position sense.

Alpha-synucleinopathy reduces NMNAT3 protein levels and neurite formation that can be rescued by targeting the NAD+ pathway.

Parkinson's disease is characterized by the deposition of α-synuclein, which leads to synaptic dysfunction, the loss of neuronal connections and ultimately progressive neurodegeneration. Despite extensive research into Parkinson's disease pathogenesis, the mechanisms underlying α-synuclein-mediated synaptopathy have remained elusive. Several lines of evidence suggest that altered nicotinamide adenine dinucleotide (NAD+) metabolism might be causally related to synucleinopathies, including Parkinson's disease. NAD+ metabolism is central to the maintenance of synaptic structure and function. Its synthesis is mediated by nicotinamide mononucleotide adenylyltransferases (NMNATs), but their role in Parkinson's disease is not known. Here we report significantly decreased levels of NMNAT3 protein in the caudate nucleus of patients who have died with Parkinson's disease, which inversely correlated with the amount of monomeric α-synuclein. The detected alterations were specific and significant as the expression levels of NMNAT1, NMNAT2 and sterile alpha and TIR motif containing 1 (SARM1) were not significantly different in Parkinson's disease patients compared to controls. To test the functional significance of these findings, we ectopically expressed wild-type α-synuclein in retinoic acid-differentiated dopaminergic SH-SY5Y cells that resulted in decreased levels of NMNAT3 protein plus a neurite pathology, which could be rescued by FK866, an inhibitor of nicotinamide phosphoribosyltransferase that acts as a key enzyme in the regulation of NAD+ synthesis. Our results establish, for the first time, NMNAT3 alterations in Parkinson's disease and demonstrate in human cells that this phenotype together with neurite pathology is causally related to α-synucleinopathy. These findings identify alterations in the NAD+ biosynthetic pathway as a pathogenic mechanism underlying α-synuclein-mediated synaptopathy.

Coronary computed tomographic angiography derived findings and risk score improves the allocation of lipid lowering therapy compared to clinical score.

ABSTRACT: The initiation of therapy for atherosclerotic cardiovascular disease (ASVCD) is currently guided by cohort-based risk scores. Coronary computed tomographic angiography (CCTA) offers more personalised risk assessments to optimise therapy allocation. This study investigates the utility of CCTA determined coronary stenosis (both obstructive and non-obstructive plaque) to guide allocation of lipid lowering therapy. A retrospective analysis of 450 patients with CCTA performed for the assessment of chest pain at a single centre was conducted. Baseline characteristics, investigations, treatments and clinical outcomes were recorded. The allocation of lipid lowering therapy was evaluated with three models, cohort-based risk score (pooled cohort equation), a previously validated CCTA based clinical risk score (pooled cohort equation and CCTA findings) and CCTA alone (without clinical characteristics). The reclassification analysis included 266 patients. Compared to the cohort-based risk score, CCTA based clinical risk score in total reassigned 23% of patients. CCTA alone compared to the CCTA based clinical risk score correctly reassigned 23% and incorrectly reassigned 10%. When comparing the performance of CCTA alone against the cohort-based risk score, both the additive NRI of 25.8 (95% CI 4.12-37.56) and absolute NRI of 13.2 (95% CI 5.88-19.77) was significant. Revascularisation was required in 3% with a low cohort-based risk, but no patients with low risk as per CCTA alone or CCTA based clinical risk score required revascularisation The use of a CCTA based clinical risk score or CCTA alone compared to cohort-based risk scores can improve the allocation of lipid lowering therapy.

Point-of-care C-reactive protein testing service for respiratory tract infections in community pharmacy: a qualitative study of service uptake and experience of pharmacists.

Background Targeted interventions in community pharmacies, such as point-of-care C-reactive protein testing, could reduce inappropriate antimicrobial consumption in patients presenting with symptoms of respiratory tract infections, although data regarding Australian pharmacists' perspectives on its provision are limited. Aim To explore pharmacists' experiences and perspectives of point-of-care C-reactive protein testing, including barriers and facilitators, influencing service provision and uptake. Method A point-of-care C-reactive protein testing service for patients presenting with respiratory tract infection symptoms was trialled in five purposively selected community pharmacies in metropolitan Western Australia. Two pharmacists from each pharmacy participated in one-to-one semi-structured telephone interviews, regarding pharmacist demographics, pharmacy characteristics, experience with the point-of-care C-reactive protein service and training/resources. Interviews were audio-recorded and transcribed. Data were imported into NVivo for thematic analysis. Results Interview durations ranged from 28.2 to 60.2 min (mean: 50.7 ± 10.2 min). Of the five themes which emerged, participants reported the point-of-care C-reactive protein testing was simple, fast, reliable and accurate, assisted their clinical decision-making and contributed to antimicrobial stewardship. A major factor facilitating service provision and uptake by consumers was the accessibility and credibility of pharmacists. Barriers included time constraints and heavy documentation. Participants believed there was a public demand for the service. Conclusion Given the global antimicrobial resistance crisis, pharmacists have an important role in minimising the inappropriate use of antimicrobials. The point-of-care C-reactive protein service was readily accepted by the public when offered. However, ensuring efficient service delivery and adequate remuneration are essential for its successful implementation.

Proton pump inhibitors are associated with incident type 2 diabetes mellitus in a prospective population-based cohort study.

AIM: To investigate the association between proton pump inhibitors (PPIs) and risk of incident diabetes in a follow-up study and to investigate its potential mechanisms. METHODS: A total of 9531 individuals without type 2 diabetes (T2DM) at baseline were included from the Rotterdam Study, a prospective population-based cohort of 14 926 individuals aged 45 years or older. During the study period (1 April 1997 to 1 January 2012) all incident cases of T2DM were enrolled. We used multivariable linear regression analysis to investigate the associations of baseline PPI use and various serum biomarkers (eg, serum magnesium, insulin-like growth factor 1) which might modify the association. Thereafter, we excluded prevalent PPI users and performed a Cox proportional hazard regression analysis to explore the time-varying effect of incident PPI use on T2DM during follow-up. RESULTS: Baseline use of a PPI was associated with increased serum levels of fasting insulin (0.091 pmoL/L, 95% confidence interval [CI] 0.049, 0.133), homeostasis model assessment-insulin resistance (0.100, 95% CI 0.056, 0.145) and C-reactive protein (0.29 mg/L, 95% CI 0.198, 0.384), but decreased levels of magnesium (-0.009 mmol/L, 95% CI -0.014, -0.004) and IGF-1 (-0.805 nmoL/L, 95% CI -1.015, -0.595). After adjustment for risk factors such as physical activity and body mass index/waist-to-hip ratio, current use of PPI was associated with an increased risk of incident T2DM (hazard ratio [HR] 1.69, 95% CI 1.36-2.10). The effect was dose-dependent with the highest risk (HR 1.88, 95% CI 1.29-2.75) in those on more than one defined daily dose. CONCLUSION: New users of PPIs during follow-up had a significantly higher dose-dependent risk of incident diabetes. We suggest vigilance regarding their potential adverse effect on glucose homeostasis.

Nicotinamide N-Methyltransferase: An Emerging Protagonist in Cancer Macro(r)evolution.

Nicotinamide N-methyltransferase (NNMT) has progressed from being considered merely a Phase II metabolic enzyme to one with a central role in cell function and energy metabolism. Over the last three decades, a significant body of evidence has accumulated which clearly demonstrates a central role for NNMT in cancer survival, metastasis, and drug resistance. In this review, we discuss the evidence supporting a role for NNMT in the progression of the cancer phenotype and how it achieves this by driving the activity of pro-oncogenic NAD+-consuming enzymes. We also describe how increased NNMT activity supports the Warburg effect and how it promotes oncogenic changes in gene expression. We discuss the regulation of NNMT activity in cancer cells by both post-translational modification of the enzyme and transcription factor binding to the NNMT gene, and describe for the first time three long non-coding RNAs which may play a role in the regulation of NNMT transcription. We complete the review by discussing the development of novel anti-cancer therapeutics which target NNMT and provide insight into how NNMT-based therapies may be best employed clinically.