Quality Improvement Within a Mental Health Setting: Alcohol Detoxification.

Aims We describe a clinical audit on alcohol detoxification, using NICE guidelines as a comparable standard. NICE guidelines recommend completing a thorough alcohol history, documentation of a physical examination including screening for Wernicke's encephalopathy, monitoring of vital signs and liver investigations. Breath alcohol level and standardised assessment of withdrawal should be completed in addition to documentation of chlordiazepoxide and thiamine prescriptions. The reported mental health service completed the first cycle of the audit as part of a large-scale, international audit on alcohol detoxification by the Prescribing Observatory for Mental Health, UK (POMH-UK). Two additional audit cycles were completed within the service to ensure continuous quality improvement and clinical effectiveness. Methods Retrospective chart reviews were performed for admissions within pre-defined 6-month periods. Inclusion criteria: ICD-10 F10 diagnosis; prescription of alcohol detoxification schedule. Results This mental health service demonstrated greater compliance with the NICE standards in comparison to other services in the POMH-UK audit. The second-cycle audit showed increased compliance in most areas compared to the initial results. The third-cycle audit focused on two specific areas that required improvement to optimise quality improvement - Breath Alcohol Level and Clinical Institute of Withdrawal Assessment, documentation of which improved from 79% to 85% and 39% to 91% respectively in the final audit cycle. Conclusion The results of this audit indicate that adherence to defined clinical standards within this mental health service exceeds that of the benchmark POMH-UK data. The effectiveness of electronic patient records in improving adherence to set clinical standards, specifically in relation to documentation of clinical parameters is evident. The report also confirms continued improved results with each audit cycle within the service.

Variability in sleep disturbance, physical activity and quality of life by level of depressive symptoms in women with Type 2 diabetes.

AIMS: To examine (1) the prevalence of depressive symptoms in women with Type 2 diabetes, (2) the associations between depressive symptoms and the following dependent variables: sleep disturbance; physical activity; physical health-related; and global quality of life, and (3) the potential moderating effects of antidepressants and optimism on the relationship between depressive symptoms and dependent variables. METHODS: Participants in the Women's Health Initiative who had Type 2 diabetes and data on depressive symptoms (N=8895) were included in the analyses. In multivariable linear regression models controlling for sociodemographic, medical and psychosocial covariates, we examined the main effect of depressive symptoms, as well as the interactions between depressive symptoms and antidepressant use, and between depressive symptoms and optimism, on sleep disturbance, physical activity, physical health-related quality of life; and global quality of life. RESULTS: In all, 16% of women with Type 2 diabetes reported elevated depressive symptoms. In multivariable analyses, women with depressive symptoms had greater sleep disturbance (P<0.0001) and lower global quality of life (P<.0001). We found evidence of significant statistical interaction in the models for quality-of-life outcomes: the increased risk of poor physical health-related quality of life associated with antidepressant use was stronger in women without vs with depressive symptoms, and the association between greater optimism and higher global quality of life was stronger in women with vs without depressive symptoms. CONCLUSIONS: To improve health behaviours and quality of life in women with Type 2 diabetes, sociodemographic and medical characteristics may identify at-risk populations, while psychosocial factors including depression and optimism may be important targets for non-pharmacological intervention.

Spectroscopic evidence for negative electronic compressibility in a quasi-three-dimensional spin-orbit correlated metal.

Negative compressibility is a sign of thermodynamic instability of open or non-equilibrium systems. In quantum materials consisting of multiple mutually coupled subsystems, the compressibility of one subsystem can be negative if it is countered by positive compressibility of the others. Manifestations of this effect have so far been limited to low-dimensional dilute electron systems. Here, we present evidence from angle-resolved photoemission spectroscopy (ARPES) for negative electronic compressibility (NEC) in the quasi-three-dimensional (3D) spin-orbit correlated metal (Sr1-xLax)3Ir2O7. Increased electron filling accompanies an anomalous decrease of the chemical potential, as indicated by the overall movement of the deep valence bands. Such anomaly, suggestive of NEC, is shown to be primarily driven by the lowering in energy of the conduction band as the correlated bandgap reduces. Our finding points to a distinct pathway towards an uncharted territory of NEC featuring bulk correlated metals with unique potential for applications in low-power nanoelectronics and novel metamaterials.

Hot electron plasmon-protected solar cell.

A solar cell based on a hot electron plasmon protection effect is proposed and made plausible by simulations, non-local modeling of the response, and quantum mechanical calculations. In this cell, a thin-film, plasmonic metamaterial structure acts as both an efficient photon absorber in the visible frequency range and a plasmonic resonator in the IR range, the latter of which absorbs and protects against phonon emission the free energy of the hot electrons in an adjacent semiconductor junction. We show that in this structure, electron-plasmon scattering is much more efficient than electron-phonon scattering in cooling-off hot electrons, and the plasmon-stored energy is recoverable as an additional cell voltage. The proposed structure could become a prototype of a new generation of high efficiency solar cells.

Nanoscope based on nanowaveguides.

The far field spatial resolution of conventional optical lenses is of the order of the wavelength of light, due to loss in the far field of evanescent, near electromagnetic field components. We show that subwavelength details can be restored in the far field with an array of divergent nanowaveguides, which map the discretized, subwavelength image of an object into a magnified image observable with a conventional optical microscope. We demonstrate in simulations that metallic nanowires, nanocoaxes, and nanogrooves can be used as such nanowaveguides. Thus, an optical microscope capable of subwavelength resolution - a nanoscope - can be produced, with possible applications in a variety of fields where nanoscale optical imaging is of value.

Prevalence of depression in patients referred with snoring and obstructive sleep apnoea.

BACKGROUND AND AIMS: Depression and obstructive sleep apnoea are two common entities, with common symptoms that make identification of either condition difficult. Our aim was to examine, within a group of patients referred with snoring and obstructive sleep apnoea, (i) the prevalence of depression with the 14-question Hospital Anxiety and Depression Scale (HADS), (ii) the correlation between the two lead depression symptoms from the Mini-International Neuropsychiatric Interview (MINI) and HADS, and (iii) the relationship between depression symptoms with physiological markers of OSA. METHODS: An observational study of depression questionnaires in patients referred because of snoring to a sleep clinic within university-affiliated public teaching hospital. RESULTS: Ninety-seven per cent of 240 patients approached responded, and 32% had a positive HADS (score >16/42). The HADS and MINI significantly correlated (r = 0.736, P < 0.001). Fifty-three per cent had either doctor-diagnosed depression (28%) and/or a positive HADS or MINI (25%). HADS correlated with the degree of sleepiness (r = 0.252, P < 0.0001) and inversely with hypoxaemia (r=-0.231, P < 0.0003) but not with the frequency of apnoeas and hypopnoeas (r = 0.116, P > 0.05). CONCLUSION: Depending on classification, 32-53% of patients with snoring had depressive symptoms or were on treatment, which is significantly greater than the Australian average of 21%. A simplified depression questionnaire was validated. Severity of depression correlated with sleepiness and hypoxaemia but not with severity of sleep apnoea.

Effect of (Neo)adjuvant zoledronic acid on disease-free and overall survival in clinical stage II/III breast cancer.

BACKGROUND: Despite neoadjuvant/adjuvant chemotherapy, women with resectable stage II/III breast cancer (BC) have high risk of recurrent disease. Recent data suggest that zoledronic acid (ZOL) therapy concurrent with adjuvant treatments may improve cancer-related outcomes in patients with BC. METHODS: Disease-free survival (DFS; secondary end point) and overall survival (OS; tertiary end point) were evaluated in 119 women with stage II/III BC randomised to intravenous ZOL 4 mg every 3 weeks for 1 year or no ZOL (control) starting with the first chemotherapy cycle. RESULTS: At 61.9 months' median follow-up, there was no significant difference in recurrence or survival between study arms. However, time to recurrence or death (DFS) was significantly different between subgroups defined by oestrogen receptor (ER) status (interaction P=0.010 for DFS and 0.025 for OS). Hazard ratios (HRs) for disease recurrence and death were significantly less among patients with ER-negative (ER(-)) tumours who received ZOL vs no ZOL (DFS: HR=0.361, 95% confidence interval (CI) 0.148, 0.880; OS: HR=0.375, 95% CI 0.143, 0.985). CONCLUSION: ZOL administered with chemotherapy may improve DFS and OS in a subset of BC patients with ER(-) tumours. This study was not powered to compare subgroups of patients; thus, these findings should be considered hypothesis generating.

Phase II trial of temsirolimus in patients with metastatic breast cancer.

Preclinical models suggested that activating mutations of the PIK3CA gene are associated with sensitivity to inhibitors of the mammalian target of rapamycin (mTOR). In breast cancers, PIK3CA mutations are associated with estrogen receptor (ER) positivity. We therefore performed an open-label single arm phase II study of the rapamycin analog, temsirolimus, at a dose of 25 mg weekly, in women with pretreated breast cancers that were positive for ER, PR, or HER2. Archived formalin-fixed paraffin embedded tumor was collected for immunohistochemical evaluation of components of the PI3K/Akt/mTOR pathway and PIK3CA mutation analysis. Thirty-one patients were enrolled. There were no major objective responses; however, three patients had stable disease for over 24 weeks. Twenty-three tumor samples were available for mutational analysis. There were five tumors with PIK3CA mutations; no association was found between prolonged stable disease and PIK3CA mutation or any immunohistochemical marker. There was a trend toward improved progression free survival (PFS) for patients with positive nuclear staining for phospho-Akt308. One patient remains on study four and a half years after starting therapy; her tumor did not have a PIK3CA mutation. We conclude that single agent temsirolimus has minimal activity in a population of women with heavily pretreated breast cancer. We found no evidence that either absence of immunohistochemical staining for PTEN or mutations in the hotspot domains of PIK3CA in the primary tumor were associated with clinical benefit.

Maternal smoking and alcohol consumption during pregnancy as risk factors for sudden infant death.

A population based case control study was conducted to examine alcohol consumption and maternal smoking during pregnancy and the risk of SIDS in an Irish population. Each SIDS case (n = 287) was compared with control infants (n = 832) matched for date and place of birth for infants born from 1994 to 2001. Conditional logistic regression was used to investigate differences between Cases and Controls establishing Odds Ratio's (OR) and 95% Confidence Intervals (CI). Mothers who smoked were 3 times more likely to have a SIDS Case, and a dose response effect was apparent, with mothers smoking 1-10 cigarettes/day OR 2.93 (CI 1.50-5.71), and those smoking > 10 cigarettes/day OR 4.36 (CI 2.50-7.61). More Case mothers consumed alcohol during pregnancy than Control mothers and, within drinkers, the amount of alcohol consumed was also greater (p < 0.05). A dose response with frequency of drinking was apparent. The adjusted odds ratio for those consuming alcohol in all three trimesters was 3.59 (CI:1.40-9.20). Both of these risk factors are modifiable and need to be incorporated into antenatal education from a SIDS point of view.

Suppression of crosstalk in multielectrode arrays with local shielding.

Electrical crosstalk can constrain the performance of multielectrode arrays in electro- and neurophysiology, in terms of both stimulation and recording. This is especially so at high electrode density, desirable for spatiotemporal mapping of bioelectrical signals from multiple cells. Channel interference due to crosstalk is currently only partially addressed, via continuous interleaved sampling or post-data acquisition spike sorting. Here, we show that a locally-shielded electrode architecture significantly suppresses crosstalk, and enables multi-site recording at high electrode density without the need for spike sorting. Arrays of shielded electrodes, prepared by micro- and nanofabrication techniques in a vertically-oriented coaxial geometry, demonstrate at least a 400 times improvement in spatial density over the unshielded case.

Tachycardia in adults with cystic fibrosis is associated with normal autonomic function.

BACKGROUND: Whether autonomic dysfunction contributes to tachycardia in cystic fibrosis (CF) is unknown. METHODS: Heart rate variability (HRV) was assessed to determine high frequency power and the low/high frequency power ratio (HF, LF/HF) as markers of vagal and sympathovagal balance, respectively, under spontaneous and controlled breathing (15 breaths per minute (bpm)) conditions in 17 CF and 17 healthy control subjects. RESULTS: Under spontaneously breathing conditions, the CF group was tachycardic (75.4 ± 11.2 vs 60.2 ± 9.0 br/min P < 0.001) and tachypnoeic (22.6 ± 5.8 vs 13.6 ± 4.1 br/min, P= 0.001) compared with controls. No significant difference in HRV was observed between groups during spontaneous or controlled breathing. Coexistent diabetes mellitus and ß(2) agonist use were not associated with altered autonomic control. During controlled breathing, the CF group showed a negative correlation between forced expiratory volume in 1 s (FEV(1)) % predicted and HF power (P= 0.013, r=-0.59) and a positive correlation between FEV(1) % predicted and LF/HF ratio (P= 0.002, r= 0.69) suggesting an exaggerated normal vagal response. CONCLUSION: CF patients have normal autonomic function.

Cardiovascular mortality and morbidity in chronic obstructive pulmonary disease: the impact of bronchodilator treatment.

Chronic obstructive pulmonary disease (COPD) is a substantial health burden. Cardiovascular disease (CVD), the leading cause of death, frequently coexists with COPD, an effect attributed to high individual disease prevalences and shared risk factors. It has long been recognized that COPD, whether stable or during acute exacerbations, is associated with an excess of cardiac arrhythmias. Bronchodilator medications have been implicated in the excess CVD seen in COPD, either as an intrinsic medication effect or related to side-effects. Despite the theory behind increased pro-arrhythmic effects in COPD, the reported results of trials investigating this for inhaled formulations at therapeutic doses are few. Methodological flaws, retrospective analysis and inadequate adjustment for concomitant medications, including short-acting 'relief' bronchodilators and non-respiratory medications with known arrhythmia propensity, mar many of these studies. For most bronchodilators at therapeutic levels in stable COPD, we can be reassured of their safety from current studies. The exception to this is ipratropium bromide, where the current data indicate an association with increased cardiovascular adverse effects. Moreover, there is no proven benefit from combining short-acting beta-agonists with short-acting anticholinergics at high doses in the acute setting, and although this practice is widespread, it is associated with increased cardiovascular risk.

Towards spectrally selective catastrophic response.

We study the large-amplitude response of classical molecules to electromagnetic radiation, showing the universality of the transition from linear to nonlinear response and breakup at sufficiently large amplitudes. We demonstrate that a range of models, from the simple harmonic oscillator to the successful Peyrard-Bishop-Dauxois type models of DNA, which include realistic effects of the environment (including damping and dephasing due to thermal fluctuations), lead to characteristic universal behavior: formation of domains of dissociation in driving force amplitude-frequency space, characterized by the presence of local boundary minima. We demonstrate that by simply following the progression of the resonance maxima in this space, while gradually increasing intensity of the radiation, one must necessarily arrive at one of these minima, i.e., a point where the ultrahigh spectral selectivity is retained. We show that this universal property, applicable to other oscillatory systems, is a consequence of the fact that these models belong to the fold catastrophe universality class of Thom's catastrophe theory. This in turn implies that for most biostructures, including DNA, high spectral sensitivity near the onset of the denaturation processes can be expected. Such spectrally selective molecular denaturation could find important applications in biology and medicine.

Hemoglobins in sheep: multiple differences in amino acid sequences of three beta-chains and possible origins.

Among the three adult sheep hemoglobins (A, B, and C), two (A and B) are reportedly products of alleles. The beta-chains of A and B differ by at least seven scattered amino acid residues whereas the beta-sequence of C differs from A by at least 16 residues and from B by at least 21 residues. These changes suggest that the origin of C-beta antedated the divergence of A and B. Five shared differences between A-beta and C-beta with respect to B-beta can be interpreted as the result of selective advantage in favor of B. A complex of additional mechanisms has possibly been involved in maintaining the A-B- C porymorphism.

Human chorionic gonadotropin: its possible role in maternal lymphocyte suppression.

Human chorionic gonadotropin completely inhibits the response of lymphocytes to phytohemagglutinin. The effect is both reversible and noncytotoxic. These observations support the theory that the fetus is accepted because human chorionic gonadotropin represents trophoblastic surface antigen and blocks the action of maternal lymphocytes.

The six-minute walk test: a useful metric for the cardiopulmonary patient.

Measurement of exercise capacity is an integral element in assessment of patients with cardiopulmonary disease. The 6-min walk test (6MWT) provides information regarding functional capacity, response to therapy and prognosis across a range of chronic cardiopulmonary conditions. A distance less than 350 m is associated with increased mortality in chronic obstructive pulmonary disease, chronic heart failure and pulmonary arterial hypertension. Desaturation during a 6MWT is an important prognostic indicator for patients with interstitial lung disease. The 6MWT is sensitive to commonly used therapies in chronic obstructive pulmonary disease such as pulmonary rehabilitation, oxygen, long-term use of inhaled corticosteroids and lung volume reduction surgery. However, it appears less reliable to detect changes in clinical status associated with medical therapies for heart failure. A change in walking distance of more than 50 m is clinically significant in most disease states. When interpreting the results of a 6MWT, consideration should be given to choice of predictive values and the methods by which the test was carried out.

An extended core nanocoax pillar architecture for enhanced molecular detection.

Biosensors that incorporate nanomaterials and nanofabrication techniques enable molecular detection of chemical and biological macromolecules with a high degree of specificity and ultrasensitivity. Here, we present a novel fabrication process that yields a nanostructure capable of detecting biological macromolecules. The extended core nanocoax (ECC) structure builds on a previously reported nanocoaxial-based sensor. The fabrication of the device incorporates an extended inner pillar, with controllable extension above the annulus and into the surrounding solution. This new design eliminates structural constraints inherent in the original nanocoax architecture. We also provide results demonstrating improvement in biosensing capability. Specifically, we show the capability of the new architecture to detect the B subunit of the Vibrio cholerae toxin at improved sensitivity (100 pg/ml) in comparison to optical enzyme-linked immunosorbant assay (1 ng/ml) and previously reported coaxial nanostructures (2 ng/ml).

Obesity and the lung: 2. Obesity and sleep-disordered breathing.

As the prevalence of obesity increases in both the developed and the developing world, the respiratory consequences are often underappreciated. This review discusses the presentation, pathogenesis, diagnosis and management of the obstructive sleep apnoea, overlap and obesity hypoventilation syndromes. Patients with these conditions will commonly present to respiratory physicians, and recognition and effective treatment have important benefits in terms of patient quality of life and reduction in healthcare utilisation. Measures to curb the obesity epidemic are urgently required.

Randomised placebo controlled trial of non-invasive ventilation for hypercapnia in cystic fibrosis.

BACKGROUND: The clinical benefits of domiciliary non-invasive positive pressure ventilation (NIV) have not been established in cystic fibrosis (CF). We studied the effects of nocturnal NIV on quality of life (QoL), functional and physiological outcomes in CF subjects with awake hypercapnia (arterial carbon dioxide pressure PaCO2>45 mm Hg). METHODS: In a randomised, placebo controlled, crossover study, eight subjects with CF, mean (SD) age 37 (8) years, body mass index 21.1 (2.6) kg/m2, forced expiratory volume in 1 s 35 (8)% predicted and PaCO2 52 (4) mm Hg received 6 weeks of nocturnal (1) air (placebo), (2) oxygen and (3) NIV. The primary outcome measures were CF specific QoL, daytime sleepiness and exertional dyspnoea. Secondary outcome measures were awake and asleep gas exchange, sleep architecture, lung function and peak exercise capacity. RESULTS: Compared with air, NIV improved the chest symptom score in the CF QoL Questionnaire (mean difference 10; 95% CI 5 to 16; p = 0.002) and the transitional dyspnoea index score (mean difference 3.1; 95% CI 1.2-5.0; p = 0.01). It reduced maximum nocturnal pressure of transcutaneous CO2 (PtcCO2 mean difference -17 mm Hg; 95% CI -7 to -28 mm Hg; p = 0.005) and increased exercise performance on the Modified Shuttle Test (mean difference 83 m; 95% CI 21 to 144 m; p = 0.02). NIV did not improve sleep architecture, lung function or awake PaCO2. CONCLUSION: 6 weeks of nocturnal NIV improves chest symptoms, exertional dyspnoea, nocturnal hypoventilation and peak exercise capacity in adult patients with stable CF with awake hypercapnia. Further studies are required to determine whether or not NIV can improve survival.