To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure email@example.com
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
The first psychiatric intensive care unit (PICU) opened in the early 1970's in New York. This ward was designed to manage patient that did not respond to treatment in open psychiatric wards. There are about 15 PICUs in Sweden but the concept has not been specified by any public organs. In many county hospitals, both acute and intensive care units exists parallel.
Therefore, the aim of this study was to describe the core characteristics of PICU in Sweden and to describe the care activities provided for patients admitted to PICU.
Critical incident technique was used. In the study, eighteen caregivers at a PICU participated by completing a semi-structured questionnaire. Additional, in-depth interviews with three nurses and two assistant nurses also constitute the data.
Four categories were identified that characterise the core of PICU: the dramatic admission, protests and refusal of treatment, escalating behaviours and temporarily coercive measure. Care activities for PICU were also analysed and identified as controlling - establishing boundaries, protecting - warding off, supporting - giving intensive assistance and structuring the environment.
PICU were interpreted as a level of care as it is composed by limited structures and closeness in care.
To evaluate once-daily extended release quetiapine fumarate (quetiapine XR) as monotherapy (50, 150 and 300mg/day) (acute and maintenance treatment) or adjunct treatment (150 and 300mg/day) in patients with MDD.
Eight (7 acute, 1 maintenance) placebo-controlled studies were analysed. Primary endpoints: change from randomisation in Montgomery-Åsberg Depression Rating Scale (MADRS) scores (acute); time from randomisation to depressed event (maintenance). Statistical analyses: ANCOVA for difference between quetiapine XR and placebo in LSM change in MADRS total score from randomisation to study end (LOCF; acute); hazard ratio (HR) for time to recurrence of a depressed event (maintenance).
Figure 1 shows treatment differences (95% CIs) for primary efficacy variable for the seven acute studies. Four monotherapy studies (D1448C00001, D1448C00002, D1448C00003, D1448C00014) were significant in favour of quetiapine XR; Study D1448C00004 (monotherapy) was not. Studies D1448C00006 and D1448C00007 were significant in favour of adjunct quetiapine XR. Time from randomisation to depressed event (Study D1448C00005) significantly increased with quetiapine XR; HR (95% CI): 0.34(0.25, 0.46); p< 0.001; number of depressed events: 55, quetiapine XR; 132, placebo. Safety findings were consistent with the known tolerability profile of quetiapine.
Quetiapine XR consistently demonstrated antidepressant efficacy, with 6/7 acute studies positive in favour of quetiapine XR (monotherapy or adjunct). Quetiapine XR maintenance therapy significantly reduced risk of a depressed event, demonstrating relapse prevention. AstraZeneca funded
Evaluate the effects of once-daily extended release quetiapine fumarate (quetiapine XR) monotherapy in patients with major depressive disorder (MDD) according to disease severity.
Pooled data (quetiapine XR 50, 150 and 300mg/day doses combined) from four 6- or 8-week placebo-controlled quetiapine XR monotherapy studies (D1448C00001, D1448C00002, D1448C00003, D1448C00004) were analysed. Key inclusion criterion for all 4 studies: HAM-D total score ≥22. Primary endpoint: change from randomisation in Montgomery-Åsberg Depression Rating Scale (MADRS) total score. A post-hoc analysis assessed change from randomisation in MADRS total score and MADRS response (≥ 50% reduction in MADRS total score) at endpoint (Week 6 or Week 8) in 6 severity cohorts (defined by a MADRS total score at randomisation ≥24, ≥26, ≥28, ≥30, ≥32 or ≥34).
1752 patients (comprising the l’ all patients’ group) were evaluated (MADRS score ≥24 at randomisation, n=1601; ≥26, n=1467; ≥28, n=1269; ≥30, n=1038; ≥32, n=745; ≥34, n=500). Quetiapine XR significantly reduced mean MADRS total score at endpoint in lrsquo;all patients’ (p< 0.001 vs placebo) and in all 6 severity cohorts (≥24, ≥26, ≥28, ≥30 and ≥32, p< 0.001 vs placebo; ≥34, p< 0.01 vs placebo). MADRS response rates were significantly higher in the quetiapine XR group vs placebo in the ‘all patients’ group (p< 0.001 vs placebo) and in all 6 severity cohorts (≥24, ≥26, ≥28, ≥30 and ≥32, p< 0.001 vs placebo; ≥34, p=0.001 vs placebo).
Quetiapine XR monotherapy significantly improved depressive symptoms in patients with MDD irrespective of disease severity, including the most severe levels of depression.
Evaluate the effects of once-daily extended release quetiapine fumarate (quetiapine XR) monotherapy on sleep disturbance in patients with major depressive disorder (MDD).
Pooled data from four 6- or 8-week placebo-controlled quetiapine XR (50-300mg/day, administered in the evening) monotherapy studies (D1448C00001, D1448C00002, D1448C00003, D1448C00004) were analysed. Primary endpoint: change from randomisation in Montgomery-Åsberg Depression Rating Scale (MADRS) scores. Post-hoc analyses assessed changes in: MADRS item 4 (reduced sleep); Hamilton Rating Scale for Depression (HAM-D) items 4 (insomnia-early), 5 (insomnia-middle) and 6 (insomnia-late) and sleep disturbance factor (items 4+5+6); Pittsburgh Sleep Quality Index (PSQI) total and item scores. MADRS total score change was analysed for patients experiencing high (baseline HAM-D sleep disturbance factor score >=4) and low (baseline HAM-D sleep disturbance factor score < 4) sleep disturbance.
In total, 2,116 patients were randomised. At last assessment, quetiapine XR (all doses combined) significantly (p< 0.001) reduced MADRS item 4, HAM-D sleep disturbance factor and items 4, 5 and 6 and PSQI total scores from baseline versus placebo. Quetiapine XR significantly (p< 0.001) improved MADRS total score from baseline versus placebo at all time points in patients experiencing high sleep disturbance (n=865, quetiapine XR; n=514, placebo). Quetiapine XR improved MADRS total score versus placebo in patients with low sleep disturbance (n=252, quetiapine; n=121, placebo): difference significant at Weeks 2(p< 0.001), 4(p< 0.05) and 6(p< 0.05).
Quetiapine XR monotherapy improved symptoms of sleep disturbance in MDD and was effective against depressive symptoms in patients experiencing high and low sleep disturbance levels. AstraZeneca funded.
Data pertaining to changes in weight during long-term treatment with quetiapine (QTP) have been published previously (1).
Pooled data are presented from 26 short-term clinical studies (up to 12 weeks) of QTP or quetiapine extended-release (QTP XR)-as monotherapy or adjunct therapy-conducted by AstraZeneca up to November 2007. Studies were conducted in adult patients (18-65 years) across a number of psychiatric diagnoses. Variables were analyzed irrespective of fasting status with similar analyses planned in the fasting subset. LSM changes from baseline for the difference between QTP and placebo are presented.
Approximately 10000 patients were included in the analyses, 70% of whom were treated with QTP or QTP XR. Across the entire short-term dataset, the difference in LSM change in weight for QTP vs. placebo was 1.07 kg. Corresponding differences in glucose regulation parameters were 1.39 mg/dL for glucose and 0.04% units for HbA1C. the overall difference in total cholesterol was 5.48 mg/dL, with differences in HDL and LDL cholesterol of -0.62 mg/dL and 1.69 mg/dL. the difference in LSM change in triglycerides was 22.62 mg/dL.
Within the context of balancing potential risks against the acknowledged benefits of atypical antipsychotics, the degree and significance of variations in metabolic parameters is an area of continued interest. This analysis helps clinicians to better understand changes in important metabolic parameters across trials with QTP and QTP XR, and the size and uniqueness of the dataset permits further analyses within this important area.
Supported by funding from AstraZeneca Pharmaceuticals LP.
Investigate effects of adjunct extended release quetiapine fumarate (QTP-XR) on sleep disturbance and quality in patients with MDD and inadequate response to antidepressant (AD) therapy.
Data were pooled from two (D1448C00006/D1448C00007) 6-week, double-blind, randomised, placebo (placebo+AD)-controlled studies of adjunct QTP-XR (15 0 mg/day and 300 mg/day). Primary endpoint: MADRS total score change versus placebo+AD. Secondary endpoints (post hoc): change from randomisation in MADRS item 4 (reduced sleep), HAM-D items 4, 5 and 6 (early-, middle- and late-insomnia), sleep disturbance factor (HAM-D items 4+5+6) and sleep quality (PSQI global score). MADRS total score change in patients with baseline HAM-D sleep disturbance factor score > = 4 or < 4 (high and low sleep disturbance, respectively) was evaluated.
919 patients received adjunct QTP-XR: 150 mg/day (n = 309), 300 mg/day (n = 307), placebo+AD (n = 303). At Week 6, adjunct QTP-XR (both doses) reduced MADRS item 4, HAM-D sleep disturbance factor, HAM-D items 4, 5 and 6 and PSQI global scores from baseline versus placebo+AD (p < 0.001). In patients with baseline HAM-D>=4 (n = 226, 215 and 210, respectively) adjunct QTP-XR (both doses) improved (p< 0.01) MADRS total score versus placebo+AD from Week 1 onward. In patients with baseline HAM-D< 4 (n = 83, 92, 93, respectively) adjunct QTP-XR (both doses) improved (not statistically significantly) MADRS total score versus placebo+AD at Week 6.
Adjunct QTP-XR significantly restored sleep and improved sleep quality in patients with MDD and inadequate response to AD. Significant improvement in depressive symptoms was demonstrated with adjunct QTP-XR in patients with MDD and high baseline sleep disturbance. AstraZeneca funded.
To evaluate quetiapine XR as adjunct to ongoing antidepressant therapy in patients with MDD showing inadequate response to antidepressant treatment.
Data were analysed from two 6-week, multicentre, double-blind, randomised, placebo-controlled studies (D1448C00006; D1448C00007), prospectively designed to be pooled. Outpatients received adjunctive quetiapine XR 150mg/day (n=309), 300mg/day (n=307), placebo (n=303). Primary endpoint: change at Week 6 in MADRS total score. Other assessments included: MADRS individual item scores, HAM-A total scores, MADRS response and remission; AE reporting.
Quetiapine XR 150mg/day and 300mg/day (p< 0.001) reduced MADRS total scores versus placebo at Week 6 (-14.5, -14.8, -12.0) and Week 1 (-7.8, -7.3, -5.1). Subgroup analyses showed the therapeutic effect of quetiapine XR was neither limited to nor driven by factors such as gender or antidepressant class (SSRI/SNRI). Quetiapine XR demonstrated consistent improvements in individual MADRS items: 150mg/day and 300mg/day significantly improved 4/10 and 7/10 items at Week 6 versus placebo. At Week 6, MADRS response (≥50% decrease in total score) was 53.7% (p=0.063), 58.3% (p< 0.01) versus 46.2%; MADRS remission (total score ≤8) was 35.6% (p< 0.01), 36.5% (p< 0.001) versus 24.1% for quetiapine XR 150mg/day and 300mg/day and placebo, respectively. Quetiapine XR 150mg/day and 300mg/day improved HAM-A total scores versus placebo at Week 1 (-4.8 [p< 0.001], -4.2 [p< 0.01], -3.0) and Week 6 (-8.9 [p< 0.01], -9.1 [p< 0.001], -7.3). AEs (≥10%) were dry mouth, somnolence, sedation, dizziness, fatigue, constipation and headache with quetiapine XR.
In patients with MDD and an inadequate response to antidepressant therapy adjunctive quetiapine XR is effective and generally well tolerated.
This pooled analysis evaluated efficacy of adjunct quetiapine XR (QTP-XR) in subgroups of patients with anxious depression and lower levels of anxiety.
Pooled data from two 6-week, double-blind, randomised, placebo-controlled trials (D1448C00006/D1448C00007) in patients with inadequate response to antidepressants were analysed. Patients received adjunct QTP-XR (150 or 300 mg/day) or placebo+antidepressant (SSRI or SNRI). Using criteria defined in the STAR*D study, analyses conducted in patients with anxious depression or lower baseline anxiety levels (HAM-D anxiety/somatic factor score >/ = 7 and < 7, respectively) included LSM change at Week 6 in: MADRS total (primary endpoint), HAM-A and CGI-S total scores.
For patients with anxious depression (n = 697; 76% patients), adjunct QTP-XR 150mg/day (-14.44, p < 0.01) and 300 mg/day (-15.09, p < 0.001) significantly improved MADRS total scores versus placebo+antidepressant (-11.78) at Week 6, with significant improvement demonstrated from Week 1 onwards. Significant improvements were seen in HAM-A (QTP-XR 150 mg/day: -9.05, p < 0.01; 300 mg/day -9.43, p < 0.01) and CGI-S total scores (QTP-XR 150 mg/day: -1.60, p< 0.001; 300 mg/day -1.63, p < 0.001) versus placebo+antidepressant (-7.40, -1.22, respectively) at Week 6.
A smaller subgroup (n = 222; 24% patients) had lower baseline anxiety levels. At Week 1, adjunct QTP-XR (150 mg/day -9.09; p < 0.01; 300 mg/day -8.60; p < 0.05) significantly improved MADRS total score versus placebo+antidepressant (-5.93). At Week 6 there were no significant changes (QTP-XR 150 mg/day -14.49; p = 0.243; 300 mg/day -14.01; p = 0.388) versus placebo+antidepressant (-12.78).
For patients with anxious depression, adjunct QTP-XR (150 and 300 mg/day) was effective at reducing symptoms of anxiety and depression, with symptom improvement observed from Week 1 onwards. AstraZeneca funded.
Quetiapine extended release (XR) was developed to provide convenient, once-daily dosing and rapid dose escalation when compared to the immediate-release (IR) formulation.
To review preclinical and clinical study data on the efficacy and safety of quetiapine XR in bipolar depression and major depressive disorder (MDD).
Review of published studies and presentations at scientific congresses.
Quetiapine fumarate demonstrates a broad spectrum of efficacy in psychotic and mood disorders. In pharmacologic studies, quetiapine and its major active metabolite, norquetiapine, have actions on 5-HT2A receptors and D2 receptors, considered to explain efficacy in psychosis and mania. Norquetiapine, unlike quetiapine and other atypical antipsychotics at relevant doses, has affinity for the norepinephrine transporter in-vitro and demonstrates binding in-vivo, which may contribute to antidepressant efficacy. Quetiapine XR as monotherapy (300 mg/day) was significantly more effective than placebo in a study of patients with acute bipolar depression, with onset of effect as early as 1 week. In large, placebo-controlled studies, quetiapine XR as monotherapy (50-300 mg/day), or adjunct therapy (150-300 mg/day) to antidepressants, has demonstrated efficacy against depressive and comorbid symptoms in MDD, with rapid onset of effect. The safety profile of quetiapine XR in these studies was broadly consistent with quetiapine IR. Sedation intensity during initial dose escalation was significantly lower with quetiapine XR than IR in 1 study in patients with bipolar depression.
Quetiapine XR is effective in bipolar depression and MDD and has a safety profile consistent with quetiapine IR.
Psychiatric intensive care units (PICU) are rarely described since it is secluded from external insight. At the same time, it is highly intensive since staff and patients interact around the clock in the most acute phase of psychiatric illness. the PICUs admit patients who are considered extremely unmanageable within psychosis units or acute psychiatric wards, and who often demonstrate aggressive or other forms of severe behaviors.
This raises the question: What is going on in these units and what constitutes nursing care?
Spradley's 12-step ethnographic methodology was applied. Data was collected through more than 200 hours of field work on three PICUs including 16 hours of formal interviewing and numerous of informal interviews; data also consisted of writing memos and field notes. the field work aimed to understand the staff member's way of interact with the patients and what they did to care for these patients who was considered as unmanageable.
The findings presented here describe how and when nursing care is provided in PICUs. the findings are presented in relation to themes, as these emerged within the psychiatric intensive nursing care. Six themes emerged as frames for nursing care: providing surveillance, soothing, being present, trading information, maintaining security and reducing.
These themes are used to strike a balance between turbulence and stability and to achieve equilibrium. as the nursing care intervenes when turbulence emerges, the PICU becomes a sanctuary that offers tranquility, peace and rest.
Two 6-week, double-blind, placebo-controlled studies evaluated quetiapine XR (QTP-XR) adjunct to ongoing antidepressant therapy in patients with MDD and an inadequate response to prior antidepressant treatment (D1448C00006/D1448C00007).
Objective and aim:
A post hoc pooled analysis examined clinical and demographic characteristics as potential predictors of response to adjunct QTP-XR
Pooled MITT population (n = 616 QTP-XR [both doses]; n = 303 placebo) data were analysed from the two adjunct QTP-XR (150 or 300 mg/day) studies.
Effects of psychiatric history and baseline demographic and disease characteristics on efficacy were evaluated in subgroups based on Week 6 MADRS total score reduction: ≥50% reduction (responders: n = 345 QTP-XR, n = 140 placebo) versus < 50% (non-responders: n = 271 QTP-XR, n = 163 placebo); ≥75% reduction (responders: n = 175 QTP-XR, n = 60 placebo) versus < 25% (non-responders: n = 125 QTP-XR, n = 89 placebo).
Impact of baseline CGI-S score and number of episodes (0, 1, 2–3, 4–10, ≥10) over previous year and lifetime on Week 6 MADRS total score change was evaluated. Effect of baseline MADRS individual item (1–10) scores on Week 6 change in CGI-I score was evaluated.
No major differences between responders and non-responders to QTP-XR were observed for patient characteristics. there was no predictive association between baseline CGI-S score, number of depressive episodes, and baseline MADRS item scores and efficacy outcomes for adjunct QTP-XR.
This pooled analysis showed no major differences between responders and non-responders, and no suggestion of a predictive association between the parameters assessed and efficacy outcomes for adjunct QTP-XR. Further investigation including logistic regression may be required.
There is strong evidence that physical activity (PA) has an influence on physical performance in later life. Also, a small body size at birth has been associated with lower physical functioning in older age and both small and high birth weight have shown to be associated with lower leisure time physical activity. However, it is unknown whether size at birth modulates the association between PA and physical performance in old age. We examined 695 individuals from the Helsinki Birth Cohort Study born in Helsinki, Finland between 1934 and 1944. At a mean age of 70.7 years PA was objectively assessed with a multisensory activity monitor and physical performance with the Senior Fitness Test (SFT). Information on birth weight and gestational age was retrieved from hospital birth records. The study participants were divided in three birth weight groups, that is <3000 g, 3000–3499 g and ⩾3500 g. The volume of PA was significantly associated with the physical performance in all birth weight groups. However, the effect size of the association was large and significant only in men with a birth weight <3000 g (β 0.59; 95% confidence interval 0.37–0.81, P<0.001). Our study shows that the association between PA and physical performance is largest in men with low birth weight. Our results suggest that men with low birth weight might benefit most from engaging in PA in order to maintain a better physical performance.
This study aims to develop a typology of generic meeting places based on social contact and mixing of relevance for infectious disease transmission. Data were collected by means of a contact diary survey conducted on a representative sample of the Swedish population. The typology is derived from a cluster analysis accounting for four dimensions associated with transmission risk: visit propensity and its characteristics in terms of duration, number of other persons present and likelihood of physical contact. In the analysis, we also study demographic, socio-economic and geographical differences in the propensity of visiting meeting places. The typology identifies the family venue, the fixed activity site, the family vehicle, the trading plaza and the social network hub as generic meeting places. The meeting place typology represents a spatially explicit account of social contact and mixing relevant to infectious disease modelling, where the social context of the outbreak can be highlighted in light of the actual infectious disease.
The Universe is permeated by hot, turbulent, magnetized plasmas. Turbulent plasma is a major constituent of active galactic nuclei, supernova remnants, the intergalactic and interstellar medium, the solar corona, the solar wind and the Earth’s magnetosphere, just to mention a few examples. Energy dissipation of turbulent fluctuations plays a key role in plasma heating and energization, yet we still do not understand the underlying physical mechanisms involved. THOR is a mission designed to answer the questions of how turbulent plasma is heated and particles accelerated, how the dissipated energy is partitioned and how dissipation operates in different regimes of turbulence. THOR is a single-spacecraft mission with an orbit tuned to maximize data return from regions in near-Earth space – magnetosheath, shock, foreshock and pristine solar wind – featuring different kinds of turbulence. Here we summarize the THOR proposal submitted on 15 January 2015 to the ‘Call for a Medium-size mission opportunity in ESAs Science Programme for a launch in 2025 (M4)’. THOR has been selected by European Space Agency (ESA) for the study phase.
To evaluate a computer-assisted point-prevalence survey (CAPPS) for hospital-acquired infections (HAIs).
A 754-bed teaching hospital in the Netherlands.
For the internal validation of a CAPPS for HAIs, 2,526 patients were included. All patient records were retrospectively reviewed in depth by 2 infection control practitioners (ICPs) to determine which patients had suffered an HAI. Preventie van Ziekenhuisinfecties door Surveillance (PREZIES) criteria were used. Following this internal validation, 13 consecutive CAPPS were performed in a prospective study from January to March 2013 to determine weekly, monthly, and quarterly HAI point prevalence. Finally, a CAPPS was externally validated by PREZIES (Rijksinstituut voor Volksgezondheid en Milieu [RIVM], Bilthoven, Netherlands). In all evaluations, discrepancies were resolved by consensus.
In our series of CAPPS, 83% of the patients were automatically excluded from detailed review by the ICP. The sensitivity of the method was 91%. The time spent per hospital-wide CAPPS was ~3 hours. External validation showed a negative predictive value of 99.1% for CAPPS.
CAPPS proved to be a sensitive, accurate, and efficient method to determine serial weekly point-prevalence HAI rates in our hospital.
Major depressive disorder (MDD) is moderately heritable, however genome-wide association studies (GWAS) for MDD, as well as for related continuous outcomes, have not shown consistent results. Attempts to elucidate the genetic basis of MDD may be hindered by heterogeneity in diagnosis. The Center for Epidemiological Studies Depression (CES-D) scale provides a widely used tool for measuring depressive symptoms clustered in four different domains which can be combined together into a total score but also can be analysed as separate symptom domains.
We performed a meta-analysis of GWAS of the CES-D symptom clusters. We recruited 12 cohorts with the 20- or 10-item CES-D scale (32 528 persons).
One single nucleotide polymorphism (SNP), rs713224, located near the brain-expressed melatonin receptor (MTNR1A) gene, was associated with the somatic complaints domain of depression symptoms, with borderline genome-wide significance (pdiscovery = 3.82 × 10−8). The SNP was analysed in an additional five cohorts comprising the replication sample (6813 persons). However, the association was not consistent among the replication sample (pdiscovery+replication = 1.10 × 10−6) with evidence of heterogeneity.
Despite the effort to harmonize the phenotypes across cohorts and participants, our study is still underpowered to detect consistent association for depression, even by means of symptom classification. On the contrary, the SNP-based heritability and co-heritability estimation results suggest that a very minor part of the variation could be captured by GWAS, explaining the reason of sparse findings.
Workplaces are one of the most important regular meeting places in society. The aim of this study was to use simulation experiments to examine the impact of different workplace cultures on influenza dissemination during pandemics. The impact is investigated by experiments with defined social-mixing patterns at workplaces using semi-virtual models based on authentic sociodemographic and geographical data from a North European community (population 136 000). A simulated pandemic outbreak was found to affect 33% of the total population in the community with the reference academic-creative workplace culture; virus transmission at the workplace accounted for 10·6% of the cases. A model with a prevailing industrial-administrative workplace culture generated 11% lower incidence than the reference model, while the model with a self-employed workplace culture (also corresponding to a hypothetical scenario with all workplaces closed) produced 20% fewer cases. The model representing an academic-creative workplace culture with restricted workplace interaction generated 12% lower cumulative incidence compared to the reference model. The results display important theoretical associations between workplace social-mixing cultures and community-level incidence rates during influenza pandemics. Social interaction patterns at workplaces should be taken into consideration when analysing virus transmission patterns during influenza pandemics.