Appropriateness of aspirin prescribing for primary and secondary prevention of cardiovascular disease in type 2 diabetes in different care settings.

BACKGROUND: Type 2 diabetes is associated with an increased cardiovascular risk. Use of aspirin has been shown to be of benefit for secondary prevention of cardiovascular disease in patients with type 2 diabetes; benefits in primary prevention have not been clearly proven. AIMS: This study aims to (a) determine if aspirin is prescribed appropriately in type 2 diabetes for primary or secondary prevention of cardiovascular disease (CVD) and (b) evaluate whether there are differences in aspirin prescribing according to where people receive their care. DESIGN: Cross-sectional study METHODS: The medical records of individuals with type 2 diabetes aged over 18 years and attending Elmwood Primary Care Centre and Cork University Hospital Diabetes outpatient clinics (n = 400) between February and August 2017 were reviewed. RESULTS: There were 90 individuals exclusively attending primary care and 310 persons attending shared care. Overall, 49.0% (n = 196) of those were prescribed aspirin, of whom 42.3% were using it for secondary prevention. Aspirin was used significantly more in people attending shared care (p < 0.001). About 10.8% of individuals with diabetes and CVD attending shared care met guidelines for, but were not prescribed aspirin. CONCLUSION: A significant number of people with type 2 diabetes who should have been prescribed aspirin for secondary prevention were not receiving it at the time of study assessment. In contrast, a substantial proportion who did not meet criteria for aspirin use was prescribed it for primary prevention.

Successfully implementing a national electronic health record: a rapid umbrella review.

AIM: To summarize the findings from literature reviews with a view to identifying and exploring the key factors which impact on the success of an EHR implementation across different healthcare contexts. INTRODUCTION: Despite the widely recognised benefits of electronic health records (EHRs), their full potential has not always been achieved, often as a consequence of the implementation process. As more countries launch national EHR programmes, it is critical that the most up-to-date and relevant international learnings are shared with key stakeholders. METHODS: A rapid umbrella review was undertaken in collaboration with a multidisciplinary panel of knowledge-users and experts from Ireland. A comprehensive literature review was completed (2019) across several search engines (PubMed, CINAHL, Scopus, Embase, Web of Science, IEEE Xplore, ACM Digital Library, ProQuest, Cochrane) and Gray literature. Identified studies (n = 5,040) were subject to eligibility criterion and identified barriers and facilitators were analysed, reviewed, discussed and interpreted by the expert panel. RESULTS: Twenty-seven literature reviews were identified which captured the key organizational, human and technological factors for a successful EHR implementation according to various stakeholders across different settings. Although the size, type and culture of the healthcare setting impacted on the organizational factors, each was deemed important for EHR success; Governance, leadership and culture, End-user involvement, Training, Support, Resourcing, and Workflows. As well as organizational differences, individual end-users have varying Skills and characteristics, Perceived benefits and incentives, and Perceived changes to the health ecosystem which were also critical to success. Finally, the success of the EHR technology depended on Usability, Interoperability, Adaptability, Infrastructure, Regulation, standards and policies, and Testing. CONCLUSION: Fifteen inter-linked organizational, human and technological factors emerged as important for successful EHR implementations across primary, secondary and long-term care settings. In determining how to employ these factors, the local context, individual end-users and advancing technology must also be considered.

Inferolateral T wave inversion in athletes: phenotype-genotype correlation.

AIMS: Significant T wave inversion in young asymptomatic athletes is rare but poses a significant clinical challenge. Pre-participation sports screening programs identify such subjects. Clinical concern that such ECG changes represent an occult cardiomyopathy or forme fruste hypertrophic cardiomyopathy leads to diagnostic and therapeutic dilemma. We sought to genotype a cohort of such subjects with a normal cardiac phenotype identified in our unit over a 3-year period. METHODS: Ten athletes were referred from external screening. All exhibited deep T wave inversion inferolaterally. All had negative family history for sudden death and had a normal phenotype. A panel of 133 cardiac genes were screened. RESULTS: Ten male subjects with mean age of 39 years were screened. Seven had no evidence of mutations. Three subjects demonstrated variants of uncertain significance in 5 different genes: alpha-2-actinin (ACTN2), myopalladin (MYPN), the calcium channel genes CACNA1C and TRPM4 and potassium channel gene KCNQ1. The variants found have not been described in cardiomyopathies or channelopathies. At 3-year follow-up, one patient had undergone detraining, and his ECG showed complete resolution of all T wave changes. He did not have any demonstrated variants. CONCLUSIONS: The absence of mutations in target genes and heterogeneous sequence variations identified in this study suggest that inferolateral T wave inversion in athletes without a phenotype may potentially represent a benign repolarization syndrome related to athletic adaptation. This was the first study to assess a phenotype-genotype correlation in this population. Further genetic studies need to be undertaken in this area.

An analysis of the effects of using Zolpidem and an innovative multimodal interdisciplinary team approach in prolonged disorders of consciousness (PDOC).

Zolpidem has been used with mixed effects in patients presenting with Prolonged Disorders of Consciousness (PDOC). This single case report describes an interdisciplinary team (IDT) protocol combined with Zolpidem 10 mg in a single case of a patient in PDOC. 'Emily', a 44-year-old lady was admitted to a rehabilitation unit in Ireland one year post onset of subarachnoid haemorrhage. Standardized assessments diagnosed her as being in a minimally conscious state (MCS). An IDT protocol was devised to stimulate and record responses to sensory and pharmacological stimuli. The protocol was applied pre and post administration of Zolpidem 10 mg. Across standardized measures of awareness, improved results post-Zolpidem were recorded. Spontaneous, appropriate verbalization was the most significant change observed 30 min after administration of Zolpidem 10 mg. This ceased after approximately 2 h with Emily reverting to a non-verbal state. The combined effect of Zolpidem and the IDT protocol applied over an eight-week period resulted in durable functional and communicative gains for Emily, inferring neuro-plasticity. This report highlights the impact of a combined approach of intensive IDT intervention in conjunction with Zolpidem. The use of Zolpidem with this patient population warrants further investigation.

Sleep and fatigue after TBI.

BACKGROUND: Whilst post traumatic brain injury fatigue (PTBIF) and sleep disturbance are common sequelae following brain injury, underlying mechanisms, and the potential for targeted interventions remain unclear. OBJECTIVE: To present a review of recent studies exploring the epidemiology of PTBIF and sleep disturbance, the relationship and neuropsychological correlates of these issues, potential approaches to intervention, and implications for neurorehabilitation. METHODS: A review of relevant literature was undertaken, with a focus on PTBIF relating to sleep disturbance, the neuropsychological correlates of these issues and implications for neurorehabilitation. This paper does not set out to provide a systematic review. RESULTS: Multidimensional approaches to assessment and treatment of sleep disturbance and PTBIF are required. CONCLUSIONS: There is a need for more robust findings in determining the complex nature of relationships between PTBIF, sleep disturbance, and correlates. Longitudinal prospective data is required to increase our understanding of the nature and course of PTBIF and sleep disturbance post TBI. Large scale clinical trials are required in evaluating the potential benefits of interventions.

Bioluminescence as an ecological factor during high Arctic polar night.

Bioluminescence commonly influences pelagic trophic interactions at mesopelagic depths. Here we characterize a vertical gradient in structure of a generally low species diversity bioluminescent community at shallower epipelagic depths during the polar night period in a high Arctic fjord with in situ bathyphotometric sampling. Bioluminescence potential of the community increased with depth to a peak at 80 m. Community composition changed over this range, with an ecotone at 20-40 m where a dinoflagellate-dominated community transitioned to dominance by the copepod Metridia longa. Coincident at this depth was bioluminescence exceeding atmospheric light in the ambient pelagic photon budget, which we term the bioluminescence compensation depth. Collectively, we show a winter bioluminescent community in the high Arctic with vertical structure linked to attenuation of atmospheric light, which has the potential to influence pelagic ecology during the light-limited polar night.

Cardiac arrest in an 18-year-old man caused by anomalous right coronary artery origin.

An 18-year-old man presented to hospital following an out of hospital ventricular fibrillation cardiac arrest, with successful resuscitation at the scene. The incident happened during a competitive football match in which the man was playing. In the course of an extensive work up, a CT coronary angiogram demonstrated an anomalous right coronary artery (RCA) origin in the left coronary sinus. The RCA followed an initial intramural and subsequent interarterial course between the ascending aorta and pulmonary artery trunk. Cardiac MRI showed a small subendocardial area of delayed gadolinium enhancement in the inferoseptal wall, consistent with a small infarct. Treatment involved elective coronary artery bypass of the RCA with a right internal mammary artery graft. The patient made a full recovery. An implantable cardioverter-defibrillator was not inserted and he was advised not to return to competitive sports.

Phase I/II Study of Metastatic Melanoma Patients Treated with Nivolumab Who Had Progressed after Ipilimumab.

The checkpoint inhibitor nivolumab is active in patients with metastatic melanoma who have failed ipilimumab. In this phase I/II study, we assessed nivolumab's safety in 92 ipilimumab-refractory patients with unresectable stage III or IV melanoma, including those who experienced grade 3-4 drug-related toxicity to ipilimumab. We report long-term survival, response duration, and biomarkers in these patients after nivolumab treatment (3 mg/kg) every 2 weeks for 24 weeks, then every 12 weeks for up to 2 years, with or without a multipeptide vaccine. The response rate for ipilimumab-refractory patients was 30% (95% CI, 21%-41%). The median duration of response was 14.6 months, median progression-free survival was 5.3 months, and median overall survival was 20.6 months, when patients were followed up for a median of 16 months. One- and 2-year survival rates were 68.4% and 31.2%, respectively. Ipilimumab-naïve and ipilimumab-refractory patients showed no significant difference in survival. The 21 patients with prior grade 3-4 toxicity to ipilimumab that was managed with steroids tolerated nivolumab well, with 62% (95% CI, 38%-82%) having complete or partial responses or stabilized disease at 24 weeks. High numbers of myeloid-derived suppressor cells (MDSC) were associated with poor survival. Thus, survival and long-term safety were excellent in ipilimumab-refractory patients treated with nivolumab. Prior grade 3-4 immune-related adverse effects from ipilimumab were not indicative of nivolumab toxicities, and patients had a high overall rate of remission or stability at 24 weeks. Prospectively evaluating MDSC numbers before treatment could help assess the expected benefit of nivolumab.

Nivolumab in Resected and Unresectable Metastatic Melanoma: Characteristics of Immune-Related Adverse Events and Association with Outcomes.

PURPOSE: Retrospective analysis of irAEs in melanoma patients treated with nivolumab. EXPERIMENTAL DESIGN: Data were pooled from 148 patients (33 resected, 115 unresectable) treated with nivolumab plus peptide vaccine or nivolumab alone every 2 weeks for 12 weeks. Patients with stable disease or regression received an additional 12-week cycle, then nivolumab alone every 12 weeks for up to 2 additional years. Frequency, grade, and characteristics of immune-related adverse events (irAE) were analyzed. A 12-week landmark survival analysis using a multivariate time-dependent Cox proportional hazard model assessed difference in overall survival (OS) in the presence or absence of irAEs. RESULTS: IrAEs of any grade were observed in 68.2% of patients (101 of 148). Grade III/IV irAEs were infrequent: 3 (2%) had grade III rash, 2 (1.35%) had asymptomatic grade III elevation in amylase/lipase, and 2 (1.35%) had grade III colitis. A statistically significant OS difference was noted among patients with any grade of irAE versus those without (P ≤ 0.001), and OS benefit was noted in patients who reported three or more irAE events (P ≤ 0.001). Subset analyses showed statistically significant OS differences with rash [P = 0.001; HR, 0.423; 95% confidence interval (CI), 0.243-0.735] and vitiligo (P = 0.012; HR, 0.184; 95% CI, 0.036-0.94). Rash and vitiligo also correlated with statistically significant OS differences in patients with metastatic disease (P = 0.004 and P = 0.028, respectively). No significant survival differences were seen with other irAEs (endocrinopathies, colitis, or pneumonitis). CONCLUSIONS: Cutaneous irAEs are associated with improved survival in melanoma patients treated with nivolumab, and clinical benefit should be validated in larger prospective analyses.

Distribution of Agrobacterium vitis in Grapevines and Its Relevance to Pathogen Elimination.

Agrobacterium vitis, the cause of crown gall disease on grapevine, survives internally in vines and can be spread in cuttings for propagation. The possibility of generating pathogen-free vines through tissue culture makes it essential to understand the distribution of the pathogen in grapevines. A highly sensitive magnetic capture hybridization procedure along with real-time polymerase chain reaction were used to measure the distribution of tumorigenic A. vitis in dormant canes and green shoots of grapevines. Tumorigenic A. vitis was distributed from the basal to apical nodal and internodal tissues of canes as well as in nonlignified green shoots. In experiments conducted in 2013, A. vitis was detected in up to 17% of shoot tips and 52% of meristems of greenhouse-grown plants initiated from known A. vitis-contaminated cuttings. A lower frequency of detection was observed from surface-disinfected shoot tips (7%) as compared with nondisinfected tips (37%), suggesting epiphytic survival on green tissues. In 2014, vines propagated from cuttings collected from crown gall-infected vines from a different vineyard yielded lower incidences of A. vitis from shoot tips, and the bacterium was not detected in meristems. Tumorigenic A. vitis was also detected in cuttings of wild grapevines (Vitis riparia) that were collected both adjacent to and far removed from commercial vineyards.

Is Ambient Light during the High Arctic Polar Night Sufficient to Act as a Visual Cue for Zooplankton?

The light regime is an ecologically important factor in pelagic habitats, influencing a range of biological processes. However, the availability and importance of light to these processes in high Arctic zooplankton communities during periods of 'complete' darkness (polar night) are poorly studied. Here we characterized the ambient light regime throughout the diel cycle during the high Arctic polar night, and ask whether visual systems of Arctic zooplankton can detect the low levels of irradiance available at this time. To this end, light measurements with a purpose-built irradiance sensor and coupled all-sky digital photographs were used to characterize diel skylight irradiance patterns over 24 hours at 79°N in January 2014 and 2015. Subsequent skylight spectral irradiance and in-water optical property measurements were used to model the underwater light field as a function of depth, which was then weighted by the electrophysiologically determined visual spectral sensitivity of a dominant high Arctic zooplankter, Thysanoessa inermis. Irradiance in air ranged between 1-1.5 x 10-5 µmol photons m-2 s-1 (400-700 nm) in clear weather conditions at noon and with the moon below the horizon, hence values reflect only solar illumination. Radiative transfer modelling generated underwater light fields with peak transmission at blue-green wavelengths, with a 465 nm transmission maximum in shallow water shifting to 485 nm with depth. To the eye of a zooplankter, light from the surface to 75 m exhibits a maximum at 485 nm, with longer wavelengths (>600 nm) being of little visual significance. Our data are the first quantitative characterisation, including absolute intensities, spectral composition and photoperiod of biologically relevant solar ambient light in the high Arctic during the polar night, and indicate that some species of Arctic zooplankton are able to detect and utilize ambient light down to 20-30m depth during the Arctic polar night.