Measurement of the reliability of pharmacy staff and simulated patient reports of non-prescription medicine requests in community pharmacies.

BACKGROUND: The use of simulated patients (SPs) in pharmacy practice research has become an established method to observe practice. The reliability of data reported using this method in comparison to pharmacy staff self-reported behaviour has yet to be ascertained. OBJECTIVE: To compare the inter-rater agreement of pharmacy staff and SP-reported data to researcher-reported data from audio recordings of SP encounters. METHODS: A dataset of 352 audio-recorded SP encounters was generated in March-October 2015 by 61 undergraduate pharmacy students completing SP visits to 36 community pharmacies in Sydney, Australia. Post-visit scores were recorded on data collection forms by SPs. Staff completed self-assessments on identical forms immediately after the encounter. Two-hundred-and-seventy visits were randomly selected as the sample for this study, where the researcher independently scored encounters via audio recordings. Inter-rater agreement was calculated through intra-class correlation (ICC) and weighted kappa analyses. RESULTS: Analysis of staff scores returned ICC values of 0.48 (95% CI:0.38-0.56; p < 0.001) for information gathering and 0.63 (95% CI:0.55-0.70; p < 0.001) for total score. Weighted kappa for information rating was 0.30 (95% CI:0.21-0.38; p < 0.001) and 0.43 (95% CI:0.34-0.51; p < 0.001) for overall outcome. ICC values for SPs were 0.91 (95% CI:0.88-0.93; p < 0.001) and 0.90 (95% CI:0.87-0.92; p < 0.001) for information gathering and total scores respectively. Weighted kappa values were 0.44 (95% CI:0.37-0.52; p < 0.001) for information rating and 0.63 (95% CI:0.55-0.70; p < 0.001) for overall outcome. CONCLUSION: Pharmacy staff self-reported their behaviour with a poor degree of reliability. Conversely, SPs had a high level of agreement with the researcher scoring from audio recordings. Disagreement for both groups of raters was most apparent in rating the information provided and overall appropriateness of outcome. Future research should investigate this discrepancy between staff-reported behaviour and actual behaviour and consider the implications of this discrepancy in the interpretation of self-reported data.

Three-year longitudinal cognitive functioning in patients recently diagnosed with bipolar disorder.

OBJECTIVE: The longitudinal course of neuropsychological functioning after the first manic episode in bipolar disorder is unknown. The present study evaluated cognitive change in bipolar disorder in the first 3 years after the initial manic episode. METHODS: Ninety-one newly diagnosed patients with bipolar disorder and 61 demographically similar healthy participants received a neuropsychological evaluation assessing multiple cognitive domains at baseline, 1-year, and 3-year time points. Patients also received clinical assessments including mood ratings at all time points. RESULTS: Patients showed deficits in all domains at baseline, but similar longitudinal trajectories across time relative to healthy participants in most cognitive domains. For processing speed, patients showed more gains than controls from baseline to 1 year, but these gains stabilized thereafter. Patients with alcohol/substance abuse showed an initial delay but subsequent recovery in executive functioning. Patients who discontinued antipsychotic treatment showed better cognitive outcomes in verbal memory. CONCLUSION: Appropriately treated patients with bipolar disorder showed favorable cognitive outcome in the first 3 years after experiencing an initial manic episode, arguing against cognitive neuroprogression at this stage of the illness. Discontinuation of antipsychotic treatment may be associated with better cognitive outcomes, but clarification of the role of antipsychotics on cognitive functioning requires further investigation.

Virus Genotype-Dependent Transcriptional Alterations in Lipid Metabolism and Inflammation Pathways in the Hepatitis C Virus-infected Liver.

Despite advances in antiviral therapy, molecular drivers of Hepatitis C Virus (HCV)-related liver disease remain poorly characterised. Chronic infection with HCV genotypes (1 and 3) differ in presentation of liver steatosis and virological response to therapies, both to interferon and direct acting antivirals. To understand what drives these clinically important differences, liver expression profiles of patients with HCV Genotype 1 or 3 infection (n = 26 and 33), alcoholic liver disease (n = 8), and no liver disease (n = 10) were analysed using transcriptome-wide microarrays. In progressive liver disease, HCV genotype was the major contributor to altered liver gene expression with 2151 genes differentially expressed >1.5-fold between HCV Genotype 1 and 3. In contrast, only 6 genes were altered between the HCV genotypes in advanced liver disease. Induction of lipogenic, lipolytic, and interferon stimulated gene pathways were enriched in Genotype 1 injury whilst a broad range of immune-associated pathways were associated with Genotype 3 injury. The results are consistent with greater lipid turnover in HCV Genotype 1 patients. Moreover, the lower activity in inflammatory pathways associated with HCV genotype 1 is consistent with relative resistance to interferon-based therapy. This data provides a molecular framework to explain the clinical manifestations of HCV-associated liver disease.

Methodological approaches to situational analysis in global mental health: a scoping review.

Global inequity in access to and availability of essential mental health services is well recognized. The mental health treatment gap is approximately 50% in all countries, with up to 90% of people in the lowest-income countries lacking access to required mental health services. Increased investment in global mental health (GMH) has increased innovation in mental health service delivery in LMICs. Situational analyses in areas where mental health services and systems are poorly developed and resourced are essential when planning for research and implementation, however, little guidance is available to inform methodological approaches to conducting these types of studies. This scoping review provides an analysis of methodological approaches to situational analysis in GMH, including an assessment of the extent to which situational analyses include equity in study designs. It is intended as a resource that identifies current gaps and areas for future development in GMH. Formative research, including situational analysis, is an essential first step in conducting robust implementation research, an essential area of study in GMH that will help to promote improved availability of, access to and reach of mental health services for people living with mental illness in low- and middle-income countries (LMICs). While strong leadership in this field exists, there remain significant opportunities for enhanced research representing different LMICs and regions.

Identification of common highly expressed genes of Salmonella Enteritidis by in silico prediction of gene expression and in vitro transcriptomic analysis.

Chickens are the reservoir host of Salmonella Enteritidis. Salmonella Enteritidis colonizes the gastro-intestinal tract of chickens and replicates within macrophages without causing clinically discernable illness. Persistence of S. Enteritidis in the hostile environments of intestinal tract and macrophages allows it to disseminate extra-intestinally to liver, spleen, and reproductive tract. Extra-intestinal dissemination into reproductive tract leads to contamination of internal contents of eggs, which is a major risk factor for human infection. Understanding the genes that contribute to S. Enteritidis persistence in the chicken host is central to elucidate the genetic basis of the unique pathobiology of this public health pathogen. The aim of this study was to identify a succinct set of genes associated with infection-relevant in vitro environments to provide a rational foundation for subsequent biologically-relevant research. We used in silico prediction of gene expression and RNA-seq technology to identify a core set of 73 S. Enteritidis genes that are consistently highly expressed in multiple S. Enteritidis strains cultured at avian physiologic temperature under conditions that represent intestinal and intracellular environments. These common highly expressed (CHX) genes encode proteins involved in bacterial metabolism, protein synthesis, cell-envelope biogenesis, stress response, and a few proteins with uncharacterized functions. Further studies are needed to dissect the contribution of these CHX genes to the pathobiology of S. Enteritidis in the avian host. Several of the CHX genes could serve as promising targets for studies towards the development of immunoprophylactic and novel therapeutic strategies to prevent colonization of chickens and their environment with S. Enteritidis.

Surgical management of a cat with hepatic arterioportal fistula.

A 9-month-old domestic short-haired cat presented with stunted growth and chronic gastrointestinal signs. Tachypnoea, a heart murmur and cranial abdominal bruit were detected on physical examination. Echocardiography revealed volume overload in all heart chambers. CT angiography identified an abnormal communication between the hepatic arterial circulation and the portal vein, along with multiple acquired shunts. The abnormal vascular communication was surgically ligated. Echocardiography documented improvement in cardiac parameters following surgery and the cat continues to have no clinical signs 39 months after surgery. This report describes successful surgical management of feline hepatic arterioportal fistula for the first time.

Cross-sectional study on emergency department management of sepsis.

INTRODUCTION: Emergency departments (EDs) play an important role in the early identification and management of sepsis. Little is known about local EDs' processes of care for sepsis, adoption of international recommendations, and the impact of the new Sepsis-3 definitions. METHODS: Structured telephone interviews based on the United Kingdom Sepsis Trust 'Exemplar Standards for the Emergency Management of Sepsis' were conducted from January to August 2017 with nominated representatives of all responding public hospital EDs in Hong Kong, followed by a review of hospital/departmental sepsis guidelines by the investigators. RESULTS: Sixteen of the 18 public EDs in Hong Kong participated in the study. Among various time-critical medical emergencies such as major trauma, sepsis was perceived by the interviewees to be the leading cause of in-hospital mortality and the second most important preventable cause of death. However, only seven EDs reported having departmental guidelines on sepsis care, with four adopting the Quick Sequential Organ Failure Assessment score or its modified versions. All responding EDs reported that antibiotics were stocked within their departments, and all EDs with sepsis guidelines mandated early intravenous antibiotic administration within 1 to 2 hours of detection. Reported major barriers to optimal sepsis care included lack of knowledge and experience, nursing human resources shortages, and difficulty identifying patients with sepsis in the ED setting. CONCLUSION: There are considerable variations in sepsis care among EDs in Hong Kong. More training, resources, and research efforts should be directed to early ED sepsis care, to improve patient outcomes.

Hyperbaric oxygen therapy: its use in medical emergencies and its development in Hong Kong.

Hyperbaric oxygen therapy is widely accepted as life-saving treatment for decompression illness. Yet its use in acute carbon monoxide poisoning has remained controversial because of inconsistent findings in clinical trials. Hyperbaric oxygen therapy has an adjunctive role in managing gas gangrene, necrotising soft-tissue infection, and crush injury, as supported by case series. Several cases have been reported in the literature detailing the use of hyperbaric oxygen therapy in patients with severe anaemia in whom blood transfusion is not possible. Today, use of hyperbaric oxygen therapy in Hong Kong is limited by low awareness among physicians and patients, a lack of service access, and inadequate hospital and critical care support for the existing non-hospital facility. The recent introduction of a hospital-based facility is expected to benefit more patients for whom hyperbaric oxygen therapy is appropriate. This article reviews the mechanistic basis of and emerging scientific evidence to support the use of hyperbaric oxygen therapy in a number of acute medical emergencies, as well as the past and future development of hyperbaric oxygen therapy in Hong Kong.

Soft X-Ray Second Harmonic Generation as an Interfacial Probe.

Nonlinear optical processes at soft x-ray wavelengths have remained largely unexplored due to the lack of available light sources with the requisite intensity and coherence. Here we report the observation of soft x-ray second harmonic generation near the carbon K edge (∼284 eV) in graphite thin films generated by high intensity, coherent soft x-ray pulses at the FERMI free electron laser. Our experimental results and accompanying first-principles theoretical analysis highlight the effect of resonant enhancement above the carbon K edge and show the technique to be interfacially sensitive in a centrosymmetric sample with second harmonic intensity arising primarily from the first atomic layer at the open surface. This technique and the associated theoretical framework demonstrate the ability to selectively probe interfaces, including those that are buried, with elemental specificity, providing a new tool for a range of scientific problems.

Quality of life in bipolar disorder: towards a dynamic understanding.

BACKGROUND: Although quality of life (QoL) is receiving increasing attention in bipolar disorder (BD) research and practice, little is known about its naturalistic trajectory. The dual aims of this study were to prospectively investigate: (a) the trajectory of QoL under guideline-driven treatment and (b) the dynamic relationship between mood symptoms and QoL. METHODS: In total, 362 patients with BD receiving guideline-driven treatment were prospectively followed at 3-month intervals for up to 5 years. Mental (Mental Component Score - MCS) and physical (Physical Component Score - PCS) QoL were measured using the self-report SF-36. Clinician-rated symptom data were recorded for mania and depression. Multilevel modelling was used to analyse MCS and PCS over time, QoL trajectories predicted by time-lagged symptoms, and symptom trajectories predicted by time-lagged QoL. RESULTS: MCS exhibited a positive trajectory, while PCS worsened over time. Investigation of temporal relationships between QoL and symptoms suggested bidirectional effects: earlier depressive symptoms were negatively associated with mental QoL, and earlier manic symptoms were negatively associated with physical QoL. Importantly, earlier MCS and PCS were both negatively associated with downstream symptoms of mania and depression. CONCLUSIONS: The present investigation illustrates real-world outcomes for QoL under guideline-driven BD treatment: improvements in mental QoL and decrements in physical QoL were observed. The data permitted investigation of dynamic interactions between QoL and symptoms, generating novel evidence for bidirectional effects and encouraging further research into this important interplay. Investigation of relevant time-varying covariates (e.g. medications) was beyond scope. Future research should investigate possible determinants of QoL and the interplay between symptoms and wellbeing/satisfaction-centric measures of QoL.

Clinical management of sepsis.

Sepsis is a common cause of hospital admission worldwide and contributes significantly to morbidity and mortality. The definition of sepsis has evolved from the 1991 American College of Chest Physicians/Society of Critical Care Medicine definition based on the criteria of systemic inflammatory response syndrome, to the 2016 Sepsis-3 definition that incorporates the Sequential Organ Failure Assessment score. The landmark trial on protocolised early goal-directed therapy was published in 2001, but three subsequent multicentre randomised controlled trials (ProCESS, ARISE, and ProMISe) in 2014-2015 did not confirm a survival benefit with protocolised care. Over the years, there has been considerable improvement in sepsis outcome and management that hinges on early detection; timely source control; prompt, appropriate, and correctly dosed antibiotics; aggressive fluid resuscitation; and shock reversal. These are all directed by repeated bedside assessment. This article summarises recent developments and landmark trials that should guide current sepsis management.

Diagnosis and body mass index effects on hippocampal volumes and neurochemistry in bipolar disorder.

We previously reported that higher body mass index (BMI) was associated with greater hippocampal glutamate+glutamine in people with bipolar disorder (BD), but not in non-BD healthy comparator subjects (HSs). In the current report, we extend these findings by examining the impact of BD diagnosis and BMI on hippocampal volumes and the concentrations of several additional neurochemicals in 57 early-stage BD patients and 31 HSs. Using 3-T magnetic resonance imaging and magnetic resonance spectroscopy, we measured bilateral hippocampal volumes and the hippocampal concentrations of four neurochemicals relevant to BD: N-acetylaspartate+N-acteylaspartylglutamate (tNAA), creatine+phosphocreatine (Cre), myoinositol (Ins) and glycerophosphocholine+phosphatidylcholine (Cho). We used multivariate factorial analysis of covariance to investigate the impact of diagnosis (patient vs HS) and BMI category (normal weight vs overweight/obese) on these variables. We found a main effect of diagnosis on hippocampal volumes, with patients having smaller hippocampi than HSs. There was no association between BMI and hippocampal volumes. We found diagnosis and BMI effects on hippocampal neurochemistry, with patients having lower Cre, Ins and Cho, and overweight/obese subjects having higher levels of these chemicals. In patient-only models that controlled for clinical and treatment variables, we detected an additional association between higher BMI and lower tNAA that was absent in HSs. To our knowledge, this was the first study to investigate the relative contributions of BD diagnosis and BMI to hippocampal volumes, and only the second to investigate their contributions to hippocampal chemistry. It provides further evidence that diagnosis and elevated BMI both impact limbic brain areas relevant to BD.

Lower cognitive functioning as a predictor of weight gain in bipolar disorder: a 12-month study.

OBJECTIVE: In cross-sectional studies, elevated body mass index (BMI) is associated with cognitive impairment in bipolar disorder (BD). We investigated the direction of this association by prospectively examining changes in BMI and cognition. METHOD: We measured BMI and performance in six cognitive domains over 12 months in 80 adolescent and young adult BD patients and 46 healthy comparison subjects (HS). Ninety-three percent of patients received pharmacotherapy and 84% were euthymic. We used repeated-measures ancova and longitudinal mixed models to investigate whether (i) higher BMI and increasing BMI over time predicted lower subsequent cognitive functioning, and (ii) lower cognitive functioning and changes in cognition predicted increasing BMI. RESULTS: Neither baseline BMI nor BMI change predicted lower cognitive functioning. Lower baseline scores in attention, verbal memory, working memory, and a composite measure of global cognition predicted increasing BMI in patients and HS. In patients, lower cognitive functioning remained associated with increasing BMI when clinical and treatment variables were adjusted for. Improvement in working memory predicted a smaller subsequent BMI increase in patients. CONCLUSION: Lower cognitive functioning in specific domains predicts increasing BMI in patients with BD and healthy young adults. Targeting cognition may be important for minimizing weight gain in BD.

Use of dual-phase contrast computed tomography for evaluation of the normal canine male genital tract.

OBJECTIVES: To evaluate the use of dual-phase contrast-enhanced computed tomography for the depiction of the features of the male genital tract, highlighting differences between entire and neutered dogs. METHODS: Computed tomography exams of 23 entire and 23 neutered male dogs with no history of urogenital disease were included in this retrospective study, with exams acquired pre-, 30 and 98·9 ±27·4 seconds after intravenous contrast administration. The genital structures were subjectively evaluated for visibility, contrast enhancement and enhancement pattern and differences between entire and neutered dogs were described. Objective measurements of attenuation and size of the prostatic tissue were acquired. RESULTS: The root, body and glans of the penis could be evaluated in all dogs and appeared larger in entire dogs, though objective measurements could not be reliably made because these structures are small and curved. There was contrast enhancement of the cavernous structures, most reliably in the bulb and corpus spongiosum and most frequently in entire dogs in the delayed post-contrast phase. In entire dogs, the small testicular vessels most commonly had a vermiform shape in the early post-contrast phase, and a homogeneous appearance in the delayed phase. Sternal recumbency with the coxofemoral joints extended improved visibility of the genital structures. CLINICAL SIGNIFICANCE: Dual-phase contrast-enhanced computed tomography is useful for depiction of the structures of the male genital tract, with the early phase especially highlighting the vascular and the delayed phase the cavernous structures.