The effects of aging and frailty on inpatient glycemic control by continuous glucose monitoring in patients with type 2 diabetes.

BACKGROUND: Older adults with diabetes in the hospital are generally managed similarly to younger adults, however, it is unknown if the degree of frailty can affect glucose control among hospitalized patients. METHODS: We examined glycemic parameters derived from continuous glucose monitoring (CGM) in older adults with type 2 diabetes and frailty who were hospitalized in non-acute settings. Data was pooled from 3 prospective studies using CGM including 97 patients wearing Libre CGM sensors and 166 patients wearing Dexcom G6 CGM. Glycemic parameters (time in range (TIR) 70-180; time below range (TBR) <70 and 54 mg/dl) by CGM were compared between 103 older adults ≥60 years and 168 younger adults <60 years. Frailty was assessed using validated laboratory and vital signs frailty index FI-LAB (n = 85), and its effect on hypoglycemia risk was studied. RESULTS: Older adults, as compared to younger adults, had significantly lower admission HbA1c (8.76% ± 1.82 vs. 10.25% ± 2.29, p < 0.001), blood glucose (203.89 ± 88.65 vs. 247.86 ± 124.17 mg/dl, p = 0.003), mean daily BG (173.9 ± 41.3 vs. 183.6 ± 45.0 mg/dl, p = 0.07) and higher percent TIR 70-180 mg/dl (59.0 ± 25.6% vs. 51.0 ± 26.1%, p = 0.02) during hospital stay. There was no difference in hypoglycemia occurrence between older and younger adults. Higher FI-LAB score was associated with higher % CGM < 70 mg/dl (0.204) and % CGM < 54 mg/dl (0.217). CONCLUSION: Older adults with type 2 diabetes have better glycemic control prior to admission and during hospital stay compared to younger adults. Frailty is associated with longer presence of hypoglycemia in non-acute hospital settings.

Assessment of Newer Radiation Dose Reduction Techniques During Coronary Angiography.

Aims To evaluate the impact of Allura Clarity technology on radiation exposure in patients undergoing diagnostic coronary angiography. Methods A retrospective analysis was undertaken of invasive coronary angiograms performed by a single experienced operator in Cork University Hospital (CUH) (Allura Xper FD10 angiography system). In order to reduce operator variability, we also analysed cases performed by the same operator in the Bon Secours Hospital Cork (BSHC) (Allura Clarity FD10 angiography system). Cases were selected consecutively, having excluded those involving percutaneous coronary intervention, graft studies, aortography, ventriculography, right heart studies or fractional flow reserve studies. Results A total of 178 patients were included, equally distributed between the CUH arm (n=89) and the BSHC arm (n=89). Cohorts were very well matched in terms of age, gender, Body Mass Index, and procedural approach. The median radiation dose in CUH was a Dose Area Product (DAP) of 10,460 mGy.cm2 vs. median DAP of 12,795 mGy.cm2 in BSHC (p=0.148). The median fluoroscopy time in CUH was 2.25mins vs. median fluoroscopy time of 2.17mins in BSHC (p=0.675). Conclusion The use of the Allura Clarity system for diagnostic coronary angiography did not result in a significant difference in radiation dose or fluoroscopy time when compared to the reference Allura Xper system. Further research is needed to investigate the benefit of this new image noise reduction technology in diagnostic coronary angiography.

Factors Influencing Ambulance Usage in Acute Coronary Syndrome.

Aims The aims of this study are to identify the proportion of ACS patients using an ambulance to transport to hospital and to explore the factors influencing mode of transport. Methods A retrospective, observational cohort design was utilised in this study. Data concerning cases of ACS in a university hospital over a 9-year period was obtained from the Coronary Heart Attack Ireland Register. Descriptive statistics were used to detail demographic and clinical data, as well as to establish the proportion of ambulance usage among ACS patients. Chi-square and t-tests were used to differentiate between groups at baseline. Factors influencing mode of transport were analysed by binary logistic regression. Results 4,229 cases were obtained. Exclusion and inclusion criteria were applied, leaving 1,964 cases for overall analysis. 533 (27%) patients directly used an ambulance, 1,098 (56%) patients presented initially to their GP while 333 (17%) went directly to A&E. Logistic regression showed that age, clinical factors, smoking status and diagnosis each had a statistically significant effect on ambulance usage. Conclusions Ambulance services are underutilised by ACS patients, despite clear benefits of their use. Several factors impacted patients' mode of transport. Knowledge of these is essential in guiding future awareness campaigns to promote ambulance usage in ACS.

Identifying Risks for Persistent Postconcussive Symptoms in a Pediatric Emergency Department: An Examination of a Clinical Risk Score.

OBJECTIVE: External examination of a clinical risk score to predict persistent postconcussive symptoms (PPCS) in a pediatric emergency department (ED). METHODS: Prospective cohort study of 5- to 18-year-old patients diagnosed with an acute concussion. Risk factors were collected at diagnosis and participants (n = 85) were followed to determine PPCS 30 days postinjury. Univariate logistic regression analyses were completed to examine associations of risk factors with PPCS. RESULTS: Headache and total clinical risk score were associated with increased odds of PPCS in the univariate analyses, OR 3.37 (95% CI 1.02, 11.10) and OR 1.25 (95% CI 1.02, 1.52), respectively. Additionally, teenage age group, history of prolonged concussions, and risk group trended toward association with PPCS, OR 4.79 (95% CI 0.93, 24.7), OR 3.41 (95% CI 0.88, 13.20), and OR 2.23 (95% CI 0.88, 5.66), respectively. CONCLUSION: Our study supports the use of multiple variables of a clinical risk score to assist with ED risk stratification for pediatric patients at risk for PPCS.

Exposure to discrimination and subsequent changes in self-rated health: prospective evidence from the UK's Life Opportunities Survey.

OBJECTIVES: We sought to estimate risk of poor self-rated health (SRH) following exposure to disability-related and other forms of overt discrimination in a cohort of working age adults. STUDY DESIGN: The study design is a population-based cohort survey. METHODS: Secondary analysis of data collected in Waves 1 and 2 of the UK's Life Opportunities Survey which at Wave 2 involved the participation of 12,789 working age adults. Adjusted prevalence rate ratios were used to estimate the impact of exposure to disability and non-disability discrimination on two measures of SRH at Wave 2, controlling for SRH status at Wave 1. RESULTS: Exposure to disability discrimination in the previous year was reported by 3.9% of working age British adults. Other forms of discrimination were reported less frequently (age: 3.7%, ethnicity: 2.5%, gender: 1.6%, religion: 0.8%, sexual orientation: 0.4%). In all analyses, there were stronger associations between exposure to disability discrimination and poor SRH at Wave 2 when compared with exposure to other forms of discrimination. CONCLUSIONS: Disability discrimination represents a violation of human rights. It is also likely to be a major contributor to the health inequities experienced by working age adults with disability.

The BeSMART (Best Supportive Management for Adults Referred with Tonsillopharyngitis) multicentre observational study.

Introduction Tonsillopharyngitis is the most common ear, nose and throat emergency admission, with 80,000 episodes recorded in England in 2015-2016. Despite this, there is a paucity of evidence addressing the supportive management of tonsillopharyngitis in inpatients. The aim of this retrospective multicentre observational study was to consider the Best Supportive Management for Adults Referred with Tonsillopharyngitis (BeSMART) in the inpatient setting, and to establish any associations between practice and outcomes. Methods Seven hospitals in North West England and North East Scotland participated in the study. Overall, 236 adult patients admitted with tonsillopharyngitis were included. The main outcome measures were interval to return to soft diet, length of stay (LOS), pain scores and readmissions. Results Women were more likely to seek professional help before presenting to secondary care (p=0.04). Patients admitted at the weekend were more likely to have a shorter LOS (p=0.03). There was no relationship between day of admission and seniority or specialty of the doctor initially seen. Prescription of corticosteroid, analgesia and a higher initial intravenous fluid infusion rate were not related to a shorter LOS. Conclusions This study is the first to yield valuable insights into the inpatient management of tonsillopharyngitis. This work represents part of an ongoing project to establish the evidence for common medical interventions for sore throat. Patient and professional surveys as well as a prospective interventional study are planned for the future.

A dynamic relationship between mucosal T helper type 17 and regulatory T-cell populations in nasopharynx evolves with age and associates with the clearance of pneumococcal carriage in humans.

Pneumococcal carriage is common in young children, which may account for the high incidence of disease in this age group. Host factors determining the clearance of carriage in humans remain unclear. We aimed to study the relationships between T helper type 17 (Th17) and Foxp3(+) regulatory T (Treg) cells in nasopharynx-associated lymphoid tissue (NALT) and carriage in children and adults. Frequencies of Th17 and Treg cells in NALT were analysed by flow cytometry in association with age and pneumococcal carriage status. Cytokine responses following pneumococcal stimulation were analysed by cytometric beads array. The frequencies of Th17 and Treg cells in NALT were inversely correlated (R -0.60). Whereas Treg cell frequency decreased with age (R -0.63), both Th17 and the Th17: Treg ratio increased with age (R 0.62 and R 0.64, respectively). Also, the Th17: Treg ratio was higher in carriage-negative than in carriage-positive children (p <0.01). Pneumococcal stimulation of tonsillar cells increased both Th17 and Treg cell numbers, but the Th17: Treg ratio and pattern of cytokine responses differed between carriage-negative and carriage-positive children. The former showed markedly higher Th17: Treg and interleukin-17A: interleukin-10 ratios than in the latter (p <0.01). Pneumococcal stimulation also induces Th17, although the capacity of this Th17 differentiation from naive T cells of young children was low, but increased with age. We demonstrated a dynamic relationship between Th17 and Treg cells in human nasopharynx that evolves with age. The balance between Th17 and Treg cells in NALT appears to be a major host factor closely associated with the clearance of Streptococcus pneumoniae from the nasopharynx.

A critical role of T follicular helper cells in human mucosal anti-influenza response that can be enhanced by immunological adjuvant CpG-DNA.

T Follicular helper cells (TFH) are considered critical for B cell antibody response, and recent efforts have focused on promoting TFH in order to enhance vaccine efficacy. We studied the frequency and function of TFH in nasopharynx-associated lymphoid tissues (NALT) from children and adults, and its role in anti-influenza antibody response following stimulation by a live-attenuated influenza vaccine (LAIV) or an inactivated seasonal virus antigen (sH1N1). We further studied whether CpG-DNA promotes TFH and by which enhances anti-influenza response. We showed NALT from children aged 1.5-10 years contained abundant TFH, suggesting efficient priming of TFH during early childhood. Stimulation by LAIV induced a marked increase in TFH that correlated with a strong production of anti-hemagglutinin (HA) IgA/IgG/IgM antibodies in tonsillar cells. Stimulation by the inactivated sH1N1 antigen induced a small increase in TFH which was markedly enhanced by CpG-DNA, accompanied by enhanced anti-HA antibody responses. In B cell co-culture experiment, anti-HA responses were only seen in the presence of TFH, and addition of plasmacytoid dendritic cell to TFH-B cell co-culture enhanced the TFH-mediated antibody production following CpG-DNA and sH1N1 antigen stimulation. Induction of TFH differentiation from naïve T cells was also shown following the stimulation. Our results support a critical role of TFH in human mucosal anti-influenza antibody response. Use of an adjuvant such as CpG-DNA that has the capacity to promote TFH by which to enhance antigen-induced antibody responses in NALT tissue may have important implications for future vaccination strategies against respiratory pathogens.

Vitamin D and incident urinary incontinence in older adults.

BACKGROUND/OBJECTIVES: The aim of this study is to determine whether vitamin D status is associated with incident urinary incontinence (UI) among community-dwelling older adults. SUBJECTS/METHODS: The University of Alabama at Birmingham Study of Aging is a prospective cohort study of community-dwelling Medicare enrollees. Standardized assessment of UI was conducted using the validated Incontinence Severity Index. The analysis of 25-hydroxyvitamin D [25(OH)D] levels was performed on stored baseline sera. UI was assessed every 6-12 months for up to 42 months. The analyses included multivariable logistic regression and Cox proportional hazard models. RESULTS: Of 350 participants (175 male, 147 black, mean age 73.6±5.8), 54% (189/350) were vitamin D deficient (25(OH)D <20 ng/ml) and 25% (87/350) were vitamin D insufficient (25(OH)D: 20 ng/ml to <30 ng/ml). Among the 187 subjects with no UI at baseline, 57% (107/187) were vitamin D deficient and 24% (45/187) were vitamin D insufficient. A total of 175 of the 187 subjects had follow-up evaluation for incident UI over 42 months, and incident UI occurred in 37% (65/175). After adjustment, cumulative incident UI at 42 months was associated with baseline vitamin D insufficiency (P=0.03) and demonstrated a trend association with deficiency (P=0.07). There was no association between baseline vitamin D status and the time to incident UI. CONCLUSIONS: These preliminary results support an association between vitamin D and incident UI in community-dwelling older adults. Future studies may target specific at-risk groups, such as men with BPH or women with pelvic floor disorders for evaluation of the impact of vitamin D supplementation on urinary symptoms.

Perceptions of safety and exposure to violence in public places among working age adults with disabilities or long-term health conditions in the UK: cross sectional study.

OBJECTIVES: To examine perceptions of safety and exposure to violence in public places among working age adults with and without disabilities in the UK and to assess the extent to which any between-group differences may be moderated by gender and socio-economic situation. STUDY DESIGN: Cross-sectional study. METHODS: Secondary analysis of data collected in Wave 3 (2011-13) of Understanding Society. Data were extracted on a subsample of 5069 respondents aged 16 to 64 years (28% of whom had a disability/long-term health condition) who were administered a questionnaire module addressing experiences of harassment. Between-group comparisons were made on four self-reported indicators of safety. RESULTS: Respondents with disabilities/long-term health conditions were significantly more likely to have been attacked (adjusted OR 2.30, 95%CI 1.17-4.50, P < 0.05), insulted (adjusted OR 1.48, 95%CI 1.16-1.90, P < 0.01) and to feel unsafe in public places (adjusted OR 1.32, 95%CI 1.16-1.56, P < 0.01) over the previous 12 months. There were no statistically significant differences between groups with regard to self-reported avoidance of public places. These associations were moderated by both gender and poverty status, with the increased risk of exposure to violence among people with disabilities being greater for both women and people living in poverty. CONCLUSIONS: The data add further support to the growing evidence base suggesting that people with a disability/long-term health condition are at significantly increased risk of exposure to interpersonal violence, particularly if they are living in poverty or are women. As such, there is a clear need to develop interventions that are targeted to the particular circumstances and needs of these high risk groups.

Can you die from obstructive sleep apnoea syndrome (OSAS)?

Studies suggest an independent association between Obstructive Sleep Apnoea Syndrome (OSAS) and cardiovascular death. The purpose of our study is to examine doctors' awareness of this association and to determine whether this correlates with recording of OSAS on death certificates. We contacted the Central Statistics Office (CSO) and obtained relevant mention of OSAS on death certificates. We surveyed doctors on their view of OSAS-related deaths, CSO data from 2008-2011 reveal two deaths with OSAS documented as a direct cause and 52 deaths with OSAS as a contributory cause. Seventy-five doctors' surveyed (41%) believe OSAS can be a direct cause of death and 177 (96%) believe OSAS can be an indirect cause of death. Only 22 (12%) had putdown OSAS as a cause of death. OSAS is seldom recorded on death certificates. This is at odds with epidemiological forecasts and contrary to an opinion poll from a selection of doctors.

Chronic kidney disease and obesity in Ireland: comparison of self-reported coronary artery disease in population study with clinic attendees.

Obesity is a growing issue in Ireland. The link between obesity, CKD and CAD has not previously been described in the Irish population. The prevalence of obesity and CKD was compared across 3 groups: population based estimates with self-reported CAD, population based estimates without self-reported CAD (SLAN-07) and a random selection of cardiology outpatients with CAD. The SLAN-07 is a representative survey of 1207 randomly selected participants ≥ 45 years. Validated methods measured parameters including waist circumference, blood pressure and markers of renal function specifically glomerular filtration rate (eGFR) and albumin: creatinine ratio. The Cardiology clinic surveyed a random selection of 126 participants ≥ 45 years with CAD. Similar parameters were measured using the validated methods utilised in SLAN-07 study. Prevalence of obesity and renal disease was significantly higher in both CAD groups. At population level, risk factors were modelled using logistic regression to compare odds of participants with self-reported CAD with those without. Age, hypertension, obesity, elevated waist circumference, renal disease and diabetes are significantly associated with existing CAD. Obesity and CKD are more frequent in patients with CAD. Routine evaluation is essential to facilitate more intensive management of these risk factors.

Repeated morphine treatment alters cannabinoid modulation of GABAergic synaptic transmission within the rat periaqueductal grey.

BACKGROUND AND PURPOSE: Cannabinoids and opioids produce antinociception by modulating GABAergic synaptic transmission in a descending analgesic pathway from the midbrain periaqueductal grey (PAG). While chronic opioid treatment produces opioid tolerance, it has recently been shown to enhance cannabinoid-induced antinociception within the PAG. This study examined the effect of repeated opioid treatment on opioid and cannabinoid presynaptic modulation of GABAergic synaptic transmission in PAG. EXPERIMENTAL APPROACH: Midbrain PAG slices were prepared from untreated rats, and rats that had undergone repeated morphine or saline pretreatment. Whole-cell voltage-clamp recordings were made from neurons within the ventrolateral PAG. KEY RESULTS: In slices from untreated animals, the cannabinoid receptor agonist WIN55212 and the µ receptor agonist DAMGO inhibited electrically evoked GABAA receptor-mediated inhibitory postsynaptic currents (IPSCs) IPSCs in PAG neurons, with IC50 s of 30 and 100 nM respectively. The inhibition of evoked IPSCs produced by WIN55212 (30 nM) and DAMGO (100 nM) was similar in PAG neurons from morphine- and saline-treated animals. The cannabinoid CB1 receptor antagonist AM251 increased the frequency of spontaneous miniature IPSCs in PAG neurons from repeated morphine-, but not saline-treated animals. DAMGO inhibition of evoked IPSCs was enhanced in the presence of AM251 in morphine-, but not saline-treated animals. CONCLUSIONS AND IMPLICATIONS: These results indicate that the efficiency of agonist-induced inhibition of GABAergic synaptic transmission is enhanced by morphine treatment, although this is dampened by endocannabinoid-mediated tonic inhibition. Thus, endocannabinoid modulation of synaptic transmission could provide an alternative analgesic approach in a morphine-tolerant state. LINKED ARTICLES: This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2.

Retrospective costing of warfarin.

In Ireland, there are four anticoagulants available for prescribing to patients with atrial fibrillation for stroke prevention. A key feature of the three most recent anticoagulants is that monitoring is redundant. Despite this, there is continued prescribing of the incumbent anticoagulant, warfarin, which requires monitoring. Lack of information regarding the cost of monitoring, and the extra burden it places on health budgets and patients, motivated this costing study. Using micro costing, the costs of warfarin treatment (including monitoring) was disaggregated and isolated from both the patients' and health care provider's perspectives in a Cork hospital. Costs to the health care provider per patient per clinic visited were 21.57 Euros. Patient costs incurred per patient per clinic were 48.50 Euros. Thus, the total costs per patient per visit were 70.07 Euros. This result reveals that while the pharmaceutical cost of warfarin is low; it is not an inexpensive therapy when monitoring costs are considered.

An examination of calibration intervals required for accurately tracking blood pressure using pulse transit time algorithms.

Pulse transit time (PTT) is defined as the time it takes the blood pressure (BP) wave to propagate from the heart to a specified point on the body. After an initial BP measurement, PTT can track BP over short periods of time. This paper evaluates two PTT algorithms: Chen's and Poon's algorithm; two of the most cited works in the area. The criteria for evaluating them were: which was capable of best tracking changes in BP and which provided the longest time between subsequent BP measurements. These establish the suitability of the PTT method for practical applications, which has not been examined previously. Accuracy was evaluated using the Association of Advancement of Medical Instrumentation (AAMI) and the British Hypertension Society's (BHS) standards. Results show that Chen's algorithm is dependent on its lookup table at short intervals but remains accurate using a 6-min calibration interval, with r=0.96 and r(2)=0.98. Poon's algorithm fails when using a 2-min calibration interval, but is more capable of reflecting changes in BP. The short calibration interval and accuracy limit the usefulness of calculating BP using PTT. Therefore, neither of the algorithms can be recommended because of their shortcomings when estimating BP.

Spinal actions of ω-conotoxins, CVID, MVIIA and related peptides in a rat neuropathic pain model.

BACKGROUND AND PURPOSE: Antagonists of the N-type voltage gated calcium channel (VGCC), Cav 2.2, have a potentially important role in the treatment of chronic neuropathic pain. ω-conotoxins, such MVIIA and CVID are effective in neuropathic pain models. CVID is reported to have a greater therapeutic index than MVIIA in neuropathic pain models, and it has been suggested that this is due to faster reversibility of binding, but it is not known whether this can be improved further. EXPERIMENTAL APPROACH: We examined the potency of CVID, MVIIA and two intermediate hybrids ([K10R]CVID and [R10K]MVIIA) to reverse signs of neuropathic pain in a rat nerve ligation model in parallel with production of side effects. We also examined the potency and reversibility to inhibit primary afferent synaptic neurotransmission in rat spinal cord slices. KEY RESULTS: All ω-conotoxins produced dose-dependent reduction in mechanical allodynia. They also produced side effects on the rotarod test and in a visual side-effect score. CVID displayed a marginally better therapeutic index than MVIIA. The hybrids had a lesser effect in the rotarod test than either of their parent peptides. Finally, the conotoxins all presynaptically inhibited excitatory synaptic neurotransmission into the dorsal horn and displayed recovery that was largely dependent upon the magnitude of inhibition and not the conotoxin type. CONCLUSIONS AND IMPLICATIONS: These findings indicate that CVID provides only a marginal improvement over MVIIA in a preclinical model of neuropathic pain, which appears to be unrelated to reversibility from binding. Hybrids of these conotoxins might provide viable alternative treatments.

Human oncoprotein MDM2 activates the Akt signaling pathway through an interaction with the repressor element-1 silencing transcription factor conferring a survival advantage to cancer cells.

The current paradigm states that the Akt signaling pathway phosphorylates the human oncoprotein mouse double minute 2 (MDM2), leading to its nuclear translocation and degradation of the tumor suppressor p53. Here we report a novel Akt signaling pathway elicited by MDM2. Upregulation of endogenous MDM2 promotes, whereas its downregulation diminishes, Akt phosphorylation irrespective of p53 status. MDM2 requires phosphatidylinositol (PI)3-kinase activity for enhancing Akt phosphorylation and upregulates this activity by repressing transcription of the regulatory subunit p85 of PI3-kinase. MDM2 interacts with the repressor element-1 silencing transcription factor (REST), a tumor suppressor that functions by downregulating PI3-kinase activity and Akt phosphorylation, prevents localization of REST on the p85 promoter and represses p85 expression. The deletion mutant of MDM2 capable of upregulating Akt phosphorylation represses p85 expression and interferes with localization of REST on the p85 promoter, whereas the deletion mutant of MDM2 that does not increase Akt phosphorylation cannot perform these functions. Silencing of REST abrogates the ability of MDM2 to upregulate Akt phosphorylation and downregulate p85 expression, implicating the ability of MDM2 to interact with REST in its ability to inhibit p85 expression and activate Akt phosphorylation. Inhibition of MDM2-mediated Akt phosphorylation with an Akt-phosphorylation-specific inhibitor abrogates its ability to improve cell survival. Consistently, the Akt phosphorylation function of MDM2 was required for its ability to improve cell survival after treatment with a chemotherapeutic drug. Our report not only unravels a novel signaling pathway that contributes to cell survival but also implicates a p53-independent transcription regulatory function of MDM2 in Akt signaling.

Hairy polyp of the oropharynx in association with a first branchial arch sinus.

OBJECTIVES: Hairy polyps are rare, congenital malformations of the oropharynx and nasopharynx. To date, approximately 145 cases have been reported. However, the histogenesis of these lesions remains unclear. CASE REPORT: We report the case of a 2-day-old neonate presenting with a hairy polyp attached to the left palate, who re-presented aged 16 months with a discharging first branchial arch sinus. CONCLUSION: We propose this case as supporting evidence for the theory that hairy polyps are a malformation of the first branchial arch system.