The relationship between wearable-derived sleep features and relapse in Major Depressive Disorder.

BACKGROUND: Changes in sleep and circadian function are leading candidate markers for the detection of relapse in Major Depressive Disorder (MDD). Consumer-grade wearable devices may enable remote and real-time examination of dynamic changes in sleep. Fitbit data from individuals with recurrent MDD were used to describe the longitudinal effects of sleep duration, quality, and regularity on subsequent depression relapse and severity. METHODS: Data were collected as part of a longitudinal observational mobile Health (mHealth) cohort study in people with recurrent MDD. Participants wore a Fitbit device and completed regular outcome assessments via email for a median follow-up of 541 days. We used multivariable regression models to test the effects of sleep features on depression outcomes. We considered respondents with at least one assessment of relapse (n = 218) or at least one assessment of depression severity (n = 393). RESULTS: Increased intra-individual variability in total sleep time, greater sleep fragmentation, lower sleep efficiency, and more variable sleep midpoints were associated with worse depression outcomes. Adjusted Population Attributable Fractions suggested that an intervention to increase sleep consistency in adults with MDD could reduce the population risk for depression relapse by up to 22 %. LIMITATIONS: Limitations include a potentially underpowered primary outcome due to the smaller number of relapses identified than expected. CONCLUSION: Our study demonstrates a role for consumer-grade activity trackers in estimating relapse risk and depression severity in people with recurrent MDD. Variability in sleep duration and midpoint may be useful targets for stratified interventions.

The usability of daytime and night-time heart rate dynamics as digital biomarkers of depression severity.

BACKGROUND: Alterations in heart rate (HR) may provide new information about physiological signatures of depression severity. This 2-year study in individuals with a history of recurrent major depressive disorder (MDD) explored the intra-individual variations in HR parameters and their relationship with depression severity. METHODS: Data from 510 participants (Number of observations of the HR parameters = 6666) were collected from three centres in the Netherlands, Spain, and the UK, as a part of the remote assessment of disease and relapse-MDD study. We analysed the relationship between depression severity, assessed every 2 weeks with the Patient Health Questionnaire-8, with HR parameters in the week before the assessment, such as HR features during all day, resting periods during the day and at night, and activity periods during the day evaluated with a wrist-worn Fitbit device. Linear mixed models were used with random intercepts for participants and countries. Covariates included in the models were age, sex, BMI, smoking and alcohol consumption, antidepressant use and co-morbidities with other medical health conditions. RESULTS: Decreases in HR variation during resting periods during the day were related with an increased severity of depression both in univariate and multivariate analyses. Mean HR during resting at night was higher in participants with more severe depressive symptoms. CONCLUSIONS: Our findings demonstrate that alterations in resting HR during all day and night are associated with depression severity. These findings may provide an early warning of worsening depression symptoms which could allow clinicians to take responsive treatment measures promptly.

Predictors of engagement with remote sensing technologies for symptom measurement in Major Depressive Disorder.

BACKGROUND: Remote sensing for the measurement and management of long-term conditions such as Major Depressive Disorder (MDD) is becoming more prevalent. User-engagement is essential to yield any benefits. We tested three hypotheses examining associations between clinical characteristics, perceptions of remote sensing, and objective user engagement metrics. METHODS: The Remote Assessment of Disease and Relapse - Major Depressive Disorder (RADAR-MDD) study is a multicentre longitudinal observational cohort study in people with recurrent MDD. Participants wore a FitBit and completed app-based assessments every two weeks for a median of 18 months. Multivariable random effects regression models pooling data across timepoints were used to examine associations between variables. RESULTS: A total of 547 participants (87.8% of the total sample) were included in the current analysis. Higher levels of anxiety were associated with lower levels of perceived technology ease of use; increased functional disability was associated with small differences in perceptions of technology usefulness and usability. Participants who reported higher system ease of use, usefulness, and acceptability subsequently completed more app-based questionnaires and tended to wear their FitBit activity tracker for longer. All effect sizes were small and unlikely to be of practical significance. LIMITATIONS: Symptoms of depression, anxiety, functional disability, and perceptions of system usability are measured at the same time. These therefore represent cross-sectional associations rather than predictions of future perceptions. CONCLUSIONS: These findings suggest that perceived usability and actual use of remote measurement technologies in people with MDD are robust across differences in severity of depression, anxiety, and functional impairment.

An observational study of the utility of continuous positive airway pressure ventilation for appropriate candidates in prehospital care in the Midwest region.

BACKGROUND: Emergency medical services (EMS) practitioners in Ireland have been recently licensed to use continuous positive airway pressure (CPAP) ventilation for patients with pulmonary oedema. Both the British Thoracic Society and the Canadian Medical Association advocate the use of CPAP in hospital for patients with severe exacerbations of pulmonary oedema. AIMS: The aim of this study was to identify prehospital patients in the Midwest, over a 6-month period, which could potentially benefit from CPAP if it were available in the National Ambulance Service. METHODS: Potential CPAP patients were identified in the Advanced Paramedic Clinical Activity Study (APCAS) database and then followed up in the receiving hospital emergency department (ED) and medical records. Prior to this study, Irish guidance for prehospital use of CPAP did not exist and therefore the database was interrogated using a Toronto EMS Medical Directive. Descriptive analysis was conducted in Microsoft Excel and SPSS. RESULTS: Emergency AS1 calls (999/112) were assessed (n = 1369) and 141 patients (10.3, 95 % confidence interval 8.9-12.1 %) were identified as potential candidates for prehospital CPAP. Further investigation of ED records for 63 potential candidates found 36.5 % (95 % confidence interval 26-49 %) met the Toronto EMS criteria for CPAP. CONCLUSIONS: This study suggests that a suitable patient cohort for CPAP exists in the prehospital environment and highlights the need for a prospective study of CPAP use on these patients.

ViEWS from the prehospital perspective: a comparison with a prehospital score to triage categorisation in the emergency department.

This aim of this observ estigate how the recently introduced National Early Warning Score (ViEWS) applied in the prehospital setting (Ph-ViEWS) compares with the Manchester Triage System (MTS) used in most Emergency Departments (ED) in Ireland. 386 patients fitted the inclusion criteria of which 272 (69%) had a complete set of values. Of 272 MTS 1 and 2 patients, only 114 (42%) had a Ph-ViEWS ⋝7. This study found that a substantial number of patients deemed urgent at the time of triage do not have elevated Ph-ViEWS.

Protein tyrosine phosphatase 1B negatively regulates S100A9-mediated lung damage during respiratory syncytial virus exacerbations.

Protein tyrosine phosphatase 1B (PTP1B) has anti-inflammatory potential but PTP1B responses are desensitized in the lung by prolonged cigarette smoke exposure. Here we investigate whether PTP1B expression affects lung disease severity during respiratory syncytial viral (RSV) exacerbations of chronic obstructive pulmonary disease (COPD). Ptp1b(-/-) mice infected with RSV exhibit exaggerated immune cell infiltration, damaged epithelial cell barriers, cytokine production, and increased apoptosis. Elevated expression of S100A9, a damage-associated molecular pattern molecule, was observed in the lungs of Ptp1b(-/-) mice during RSV infection. Utilizing a neutralizing anti-S100A9 IgG antibody, it was determined that extracellular S100A9 signaling significantly affects lung damage during RSV infection. Preexposure to cigarette smoke desensitized PTP1B activity that coincided with enhanced S100A9 secretion and inflammation in wild-type animals during RSV infection. S100A9 levels in human bronchoalveolar lavage fluid had an inverse relationship with lung function in healthy subjects, smokers, and COPD subjects. Fully differentiated human bronchial epithelial cells isolated from COPD donors cultured at the air liquid interface secreted more S100A9 than cells from healthy donors or smokers following RSV infection. Together, these findings show that reduced PTP1B responses contribute to disease symptoms in part by enhancing S100A9 expression during viral-associated COPD exacerbations.

Type-I interferons induce lung protease responses following respiratory syncytial virus infection via RIG-I-like receptors.

The role of proteases in viral infection of the lung is poorly understood. Thus, we examined matrix metalloproteinases (MMPs) and cathepsin proteases in respiratory syncytial virus (RSV)-infected mouse lungs. RSV-induced gene expression for MMPs -2, -3, -7, -8, -9, -10, -12, -13, -14, -16, -17, -19, -20, -25, -27, and -28 and cathepsins B, C, E, G, H, K, L1, S, W, and Z in the airways of Friend leukemia virus B sensitive strain mice. Increased proteases were present in the bronchoalveolar lavage fluid (BALF) and lung tissue during infection. Mitochondrial antiviral-signaling protein (MAVS) and TIR-domain-containing adapter-inducing interferon-ß-deficient mice were exposed to RSV. Mavs-deficient mice had significantly lower expression of airway MMP-2, -3, -7, -8, -9, -10, -12, -13, and -28 and cathepsins C, G, K, S, W, and Z. In lung epithelial cells, retinoic acid-inducible gene-1 (RIG-I) was identified as the major RIG-I-like receptor required for RSV-induced protease expression via MAVS. Overexpression of RIG-I or treatment with interferon-ß in these cells induced MMP and cathepsin gene and protein expression. The significance of RIG-1 protease induction was demonstrated by the fact that inhibiting proteases with batimastat, E64 or ribavirin prevented airway hyperresponsiveness and enhanced viral clearance in RSV-infected mice.

The Advanced Paramedic Clinical Activity Study (APCAS): an insight into the work of advanced paramedics in the mid-west of Ireland.

BACKGROUND: The Advanced Paramedic (AP) is a relatively recent role in Ireland and refers to a prehospital practitioner with Advanced Life Support (ALS) skills and training. The Advanced Paramedic Clinical Activity Study (APCAS) was initiated to provide an evaluation of the impact of the AP programme on patient care in Ireland. AIM: The aim of this study is to provide an insight into the clinical activity of APs over a 6-month period in the mid-west region of Ireland. METHODS: A prospective study was initiated whereby all ambulance calls dispatched by the regional Ambulance Control Centre were recorded by the attending AP, including calls received via the statutory 999/112 system. Participating APs were asked to complete a separate call log data sheet recording all demographic and clinical information for every call attended during the study period. RESULTS: A total of 17 APs participated and 1,969 ambulance calls were recorded in APCAS. The Mid-Western Regional Hospital, Limerick was the busiest receiving facility. Activity peaked at weekends and was lowest on Tuesdays. Crew response, on-scene times and transport times agree with previous reports. Most common emergencies include medical (12 %), cardiovascular (10%) and altered level of consciousness and seizures (10%). Least common calls include airway and ventilation and environmental emergencies (<1%). CONCLUSIONS: This study provides an insight into the work of APs in the mid-west region of Ireland. It would appear that despite the relative recency of the Irish AP programme, the findings of this study are in line with previous international studies.

The effect of behavioural risk factors on osteoporosis in Irish women.

BACKGROUND: Osteoporosis constitutes a major public health concern and its underlying pathogenesis is complex and multifactorial. Although hereditary factors strongly contribute to bone health, behavioural factors can modulate the genetically determined pattern of skeletal modelling and remodelling. AIM: The aim of this study was to investigate the effect(s) of behavioural risk factors on osteoporosis in Irish women. METHODS: Pre- and post-menopausal adult women (n = 189; 44 ± 15 years) participated in this cross-sectional study. Demographic, anthropometric and lifestyle data were collected during a single clinic visit. Dietary calcium intake and lifetime physical activity (PA) were assessed for each subject. Lumbar and femoral bone mineral density (BMD) was measured by dual energy X-ray absorptiometry (DXA). Multivariate analysis was used to determine the independent predictors of low BMD. RESULTS: Low BMD was present in 59% of subjects (42% pre- and 77% post-menopausal). Smoking was the strongest behavioural predictor of lumbar and femoral BMD. Age, height, family history, smoking, metabolic (MET) and mechanical (MECH) PA (lifetime) and weight (body mass) accounted for 39% of the variance in lumbar BMD. Age, height, family history, alcohol consumption, MET and MECH PA (lifetime) and weight accounted for 41% of the variance in femoral BMD. CONCLUSIONS: Prevalence of osteopenia and osteoporosis is high in Irish women and is associated with modifiable risk factors. A clearer focus should be paid to educate Irish women on preventative health behaviours for osteoporosis to curb the prevalence of this disease and the human and fiscal costs associated with it.

clinical risk factors for osteoporosis in Ireland and the UK: a comparison of FRAX and QFractureScores.

Recently two algorithms have become available to estimate the 10-year probability of fracture in patients suspected to have osteoporosis on the basis of clinical risk factors: the FRAX algorithm and QFractureScores algorithm (QFracture). The aim of this study was to compare the performance of these algorithms in a study of fracture patients and controls recruited from six centers in the United Kingdom and Ireland. A total of 246 postmenopausal women aged 50-85 years who had recently suffered a low-trauma fracture were enrolled and their characteristics were compared with 338 female controls who had never suffered a fracture. Femoral bone mineral density was measured by dual-energy X-ray absorptiometry, and fracture risk was calculated using the FRAX and QFracture algorithms. The FRAX algorithm yielded higher scores for fracture risk than the QFracture algorithm. Accordingly, the risk of major fracture in the overall study group was 9.5% for QFracture compared with 15.2% for FRAX. For hip fracture risk the values were 2.9% and 4.7%, respectively. The correlation between FRAX and QFracture was R = 0.803 for major fracture and R = 0.857 for hip fracture (P ≤ 0.0001). Both algorithms yielded high specificity but poor sensitivity for prediction of osteoporosis. We conclude that the FRAX and QFracture algorithms yield similar results in the estimation of fracture risk. Both of these tools could be of value in primary care to identify patients in the community at risk of osteoporosis and fragility fractures for further investigation and therapeutic intervention.

The bioactivity and ion release of titanium-containing glass polyalkenoate cements for medical applications.

The ion release profiles and bioactivity of a series of Ti containing glass polyalkenoate cements. Characterization revealed each material to be amorphous with a T(g) in the region of 650-660°C. The network connectivity decreased (1.83-1.35) with the addition of TiO(2) which was also evident with analysis by X-ray photoelectron spectroscopy. Ion release from cements were determined using atomic absorption spectroscopy for zinc (Zn(2+)), calcium (Ca(2+)), strontium (Sr(2+)), Silica (Si(4+)) and titanium (Ti(4+)). Ions such as Zn(2+) (0.1-2.0 mg/l), Ca(2+) (2.0-8.3 mg/l,) Sr(2+) (0.1-3.9 mg/l), and Si(4+) (14-90 mg/l) were tested over 1-30 days. No Ti(4+) release was detected. Simulated body fluid revealed a CaP surface layer on each cement while cell culture testing of cement liquid extracts with TW-Z (5 mol% TiO(2)) produced the highest cell viability (161%) after 30 days. Direct contact testing of discs resulted in a decrease in cell viability of the each cement tested.

A spectroscopic investigation into the setting and mechanical properties of titanium containing glass polyalkenoate cements.

Titanium (Ti) implants are extensively used in a number of biomedical and dental applications. This work introduces Ti into the glass phase of a zinc based glass polyalkenoate cement (GPC) and investigates changes in handling and mechanical properties considering two molecular weight polyacrylic acids (PAA), E9 and E11. Considering the handling properties, the working time (T (w)) increased from 50 s(E9), 32 s(E11) (BT 101, Ti-free) to 169 s(E9), 74 s(E11) with TW-Z (highest Ti content), respectively. The setting time (T (s)) increased from 76 s(E9), 47 s(E11) (BT 101) to 303 s(E9), 232 s(E11) with TW-Z, respectively. Ti was also found to have a significant increase on both compressive (sigma (c)) and biaxial flexural strength (sigma (f)), where sigma (c) increased from 36 MPa(E9), 56 MPa(E11) (BT 101) to 56 MPa(E9) and 70 MPa(E11) with TW-Z respectfully. sigma (f) also increased from 11 MPa(E9), 22 MPa(E11) (BT 101) to 22 MPa(E9) and 77 MPa(E11) with TW-Z, respectively. No increase in mechanical properties was evident with respect to maturation. Raman Spectroscopy was employed to investigate changes in glass structure and the setting of the cements with. This revealed increased glass network disruption with increasing TiO(2) content and matured cement setting with TW-Z as compared to the control BT 101. FT-IR was then employed to investigate any additional setting mechanism and changes with time. Spectroscopy determined that Ca(2+)/Sr(2+)PAA complexes are primarily responsible for the setting and mechanical strength with no changes occurring over time.

Mechanisms of HIV-associated lymphocyte apoptosis: 2010.

The inevitable decline of CD4T cells in untreated infection with the Human immunodeficiency virus (HIV) is due in large part to apoptosis, one type of programmed cell death. There is accumulating evidence that the accelerated apoptosis of CD4T cells in HIV infection is multifactorial, with direct viral cytotoxicity, signaling events triggered by viral proteins and aberrant immune activation adding to normal immune defense mechanisms to contribute to this phenomenon. Current antiviral treatment strategies generally lead to reduced apoptosis, but this approach may come at the cost of preserving latent viral reservoirs. It is the purpose of this review to provide an update on the current understanding of the role and mechanisms of accelerated apoptosis of T cells in the immunopathogenesis of HIV infection, and to highlight potential ways in which this seemingly deleterious process could be harnessed to not just control, but treat HIV infection.

Deficiency of cytomegalovirus (CMV)-specific CD8+ T cells in patients presenting with late-onset CMV disease several years after transplantation.

Cytomegalovirus (CMV) is a major cause of morbidity and mortality among transplant recipients. The routine use of anti-CMV prophylaxis has modified the epidemiology of post-transplant CMV infection by delaying the onset of clinical disease. While the majority of delayed-onset CMV disease still occurs during the first year after transplant, reports of late-onset CMV disease presenting many years after transplantation are increasing. Here, we describe 2 CMV-seropositive transplant recipients who presented with late-onset CMV disease at 8 and 11 years after transplantation. To determine whether CMV disease occurring at a very late period after transplantation is related to immune competence, we assessed global and CMV-specific cellular immunity by evaluating the activation capability of CD8+ T cells to a mitogenic stimulus and by quantitative and functional analysis (as assessed by intracellular cytokine production and degranulation) of CMV-specific CD8+ T cells. In both patients, we demonstrated the absence or marked deficiency of CMV-specific T-cell immunity despite CMV seropositivity, and in one patient, a partial defect in the immune response to phorbol myristate acetate and ionomycin suggesting impaired global immune competence. Hence, our data suggest that late-onset CMV disease occurring many years after transplantation remains related to defects in the immune competence of patients. Measurement of CMV-specific cellular immune competence may therefore provide an additional tool to screen for patients at high risk of developing late-onset CMV disease. The clinical utility of this assay, however, will need to be evaluated in larger prospective studies.

Raman spectroscopy of the human nail: a potential tool for evaluating bone health?

Dual X-ray absorptiometry (DEXA) is the current gold standard for the diagnosis of osteoporosis. However, patients can suffer osteoporotic fractures despite normal bone mineral density, partly because of unmeasured influences of both the protein and mineral phases of bone that are affected in osteoporosis. There is currently no clinically applicable method of evaluating the health of the protein phase. The proteins in human nail (keratin) and bone (collagen) require sulphation and disulphide bond (S-S) formation for structural integrity and disorders of either sulphur metabolism or cystathione beta-synthase can lead to structural abnormalities in these tissues. Raman protein spectra provide a method of non-invasive measurement of the degree of sulphation of structurally related proteins that may be indicative of bone health. Raman spectroscopy was used to evaluate the disulphide (S-S) content of fingernails. The nail samples came from from 169 women (84 pre- and 85 post-menopausal), of which 39 had a history of osteoporotic fracture. BMD was measured by DXA at the spine. Analyses included parametric and non-parametric tests, dependent on the distribution of the test variable. Mean disulphide content of the nail reduced with age and was slightly higher in pre-, compared to post-menopausal women (P = 0.187). Significantly lower disulphide content was observed in nails obtained from subjects with a history of fracture (P = 0.025). When either disulphide content or BMD was used as a predictor, the odds ratio of these two measures were found to be comparable predictors for fracture status. This suggests that measurements of change in the protein phase of structural proteins such as keratin in the human nail may be correlated with clinically relevant changes in bone proteins that are important in fracture risk.

Professional nursing roles. The reintegration of patient teaching.

This article stresses the critical nature of the education function of the nurse and suggests strategies for reintegrating teaching as a professional role. It is important that administrators value teaching and that staff development departments assist nurses in refining teaching skills.