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Non-communicable diseases (NCDs) including obesity, diabetes, and allergy are chronic, multi-factorial conditions that are affected by both genetic and environmental factors. Over the last decade, the microbiome has emerged as a possible contributor to the pathogenesis of NCDs. Microbiome profiles were altered in patients with NCDs, and shift in microbial communities was associated with improvement in these health conditions. Since the genetic component of these diseases cannot be altered, the ability to manipulate the microbiome holds great promise for design of novel therapies in the prevention and treatment of NCDs. Together, the Developmental Origins of Health and Disease concept and the microbial hypothesis propose that early life exposure to environmental stimuli will alter the development and composition of the human microbiome, resulting in health consequences. Recent studies indicated that the environment we are exposed to in early life is instrumental in shaping robust immune development, possibly through modulation of the human microbiome (skin, airway, and gut). Despite much research into human microbiome, the origin of their constituent microbiota remains unclear. Dust (also known as particulate matter) is a key determinant of poor air quality in the modern urban environment. It is ubiquitous and serves as a major source and reservoir of microbial communities that modulates the human microbiome, contributing to health and disease. There are evidence that reported significant associations between environmental dust and NCDs. In this review, we will focus on the impact of dust exposure in shaping the human microbiome and its possible contribution to the development of NCDs.
Novel IoT market solutions and research promise IoT modules that do not require programming or electrical setup, yet shop floor personnel need to face problem solving activities to create technical solutions. This paper introduces the Karakuri card deck and presents a case study composed of four workshop sessions in four manufacturing settings, where shop floor personnel tested the cards as a means of ideating and presenting conceptual IoT solutions in the form of diagrams. The results indicate the validity of the proposed conceptual solutions and suggest prototyping as a next step.
This article draws inspiration from two concepts, which initially appear to be at odds with each other. The first refers to the impact that plastics use has had on the environment and human health, while the second explores the prevalence and continued increase in the use of plastic materials. The manufacturing of plastic packaging will be reviewed to identify appropriate intervention. This article focuses on the future development of PET packaging in South Africa, exploring current literature and legislation which aid in the holistic development of the plastic packaging value chain.
A testbed was developed aiming to contribute to further knowledge on what is required from a VR application in order to be useful for planning of assembly tasks. In a pilot study the testbed was tested on students. The focus of the study was to explore the users’ behaviour, and to gain a better understanding of their experience using VR. The students experienced a gap between the real world and VR, which confirms theories that VR is not a copy or twin of an object or environment.
Substance abuse is clearly associated with criminal recidivism among offenders with and without mental disorder. Treatment for substance abuse correlates with lower rates of re-offending among participants in outpatient-based as well as institution-based substance abuse treatment programs. However, for offenders with mental disorder, research on the possible preventive effect of substance abuse treatment on criminal recidivism is sparse. This paper reports from on an ongoing naturalistic and prospective interview study on the relationship between post-release outpatient substance abuse treatment and re-offending.
The Stockholm county sample comprises 246 offenders of both genders subjected to a forensic psychiatric assessment, who screened positive for substance abuse problems. Eighty-five percent (n=210) agreed to participate in the study. Baseline data and follow-up interview data, collected immediately on release from incarceration (prison/forensic hospital) and 6 and 12 months later, include self-reported substance abuse, treatment involvement and criminality. By February 2010, data will be available from the first follow-up for 150 participants, from the second follow-up for 80 individuals and from the third follow-up for 10 subjects.
Results and conclusions
The focus of the presentation will be recidivism comparisons between substance abuse treatment utilizers and those who decline treatment. Data on ongoing levels of substance abuse, mental health problems and offending will serve as dependent variables. Additional analyses will present perceived benefit from and reasons for accepting or rejecting treatment.
Substance abuse is associated with criminal recidivism. Substance abuse treatment has been found to correlate negatively with re-offending among treatment utilizers. However, for offenders with mental health problems and substance abuse, research on how substance abuse treatment affects re-offending is sparse.
The study aimed to examine the relationship between self-reported outpatient-based substance abuse treatment and self-reported a) re-offending, b) substance use and c) psychiatric problems among offenders with mental health and substance use problems.
Data were gathered from a naturalistic follow-up study with 208 participants, subjected to a court-ordered psychiatric assessment. This analysis covers 91 individuals who were followed-up after an average study period of 17 months. Among these, 68% had been sentenced to institutional imprisonment or forensic psychiatric care.
Offences, substance use and psychiatric problems declined between baseline and follow-up. However, the reduction was not associated with self-reported treatment utilization. Among participants who were sentenced to non-institutional corrections, more individuals had utilized outpatient-based treatment compared to individuals who were sentenced to imprisonment or forensic psychiatric care.
A definitive conclusion about the effect of treatment is difficult to draw. For instance, self-reported data may not reflect actual treatment consumption. However, one interpretation is that participants naturally recovered over time. Institutional correction might also have resulted in positive outcomes equivalent to outpatient-based treatment.
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.
Escitalopram is considered to be more effective than citalopram and to have less side effects. Previous studies have found that common cardiac manifestations of escitalopram overdose are QT prolongation and bradycardia. Some case reports inform about bradycardia without ECG abnormalities with therapeutic doses of escitalopram.
We report of a 29-year-old female patient diagnosed with major depression, hospitalized for 2 weeks. She had no history of any treatment with antidepressive drugs. After administration of 5 mg/day escitalopram the patient's blood pressure and pulse rate were mildly reduced and we observed presyncopal episodes daily. After 1 week of treatment the dose of escitalopram was raised to 10 mg/day and she complained about dizziness. In this case we found that presyncopal episodes lasted longer and both hypotension and bradycardia increased. These symptoms disappeared within 24 hours after escitalopram treatment was discontinuated. Results from routine laboratory tests, ECG, EEG, brain CT were normal. No other farmacologic causes were supposed to induce the above mentioned vegetativ symptoms.
Bradycardia and hypotonia have been previously reported with citalopram, but there are only a few case reports about these side effects induced by a therapeutic dose of escitalopram. Both central and - by directly inhibiting the entry of Ca into vascular smooth muscles resulting in vasodilatation - periferial effects of escitalopram are supposed to be responsible for these rare phenomena. This case report supports the importance of monitoring heart rate and blood pressure when escitalopram treatment is introduced, especially in cases of previously untreated depressive patients.
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.
The ConstaTRE study was designed to compare long-term relapse in stable patients treated with risperidone long-acting injectable (RLAI) or the oral atypical antipsychotic quetiapine.
This was a randomized, open-label, prospective, active-controlled, multicenter, 2-year trial in symptomatically stable patients with schizophrenia or related disorder who were switched from stable treatment with oral risperidone, olanzapine, or oral conventional antipsychotic to RLAI or quetiapine. Primary efficacy measure was time-to-relapse. Positive and Negative Syndrome Scale (PANSS) scores and safety (adverse events [AEs] and Extrapyramidal Symptom Rating Scale [ESRS]) evaluations were reported.
710 patients were randomized (n=355 per group), with 666 patients (n=329 RLAI and n=337 quetiapine) being evaluable. Mean doses were 32.8±8.0 mg every-two-weeks for RLAI and 396.8±141.9 mg/day for quetiapine. Kaplan-Meier analysis indicated a significantly longer relapse-free period with RLAI treatment (log rank: p< 0.0001). Relapse occurred in 16.5% of RLAI and 31.3% of quetiapine patients. Mean duration of treatment was 483.8±277.8 and 400.7±290.6 days for RLAI and quetiapine, respectively. Total PANSS scores improved significantly from baseline to endpoint for the RLAI-treated group (p< 0.001). the endpoint difference favors RLAI over quetiapine (p< 0.001). Treatment-emergent AEs were similar between groups. ESRS total scores decreased for both groups. Possibly prolactin-related AEs occurred more often with RLAI than quetiapine (4.6% versus 1.5%, respectively). Somnolence was reported less often with RLAI than quetiapine (1.8% versus 11.3%, respectively).
Time-to-relapse was significantly longer and relapse rates were significantly lower for RLAI compared with quetiapine. both treatments were well tolerated.
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 report the functional recovery results from an open-label, randomized-controlled, relapse prevention trial (ConstaTRE) in stable patients with schizophrenia or schizoaffective disorder treated with risperidone long-acting injectable (RLAI) or the oral atypical antipsychotic quetiapine.
Clinically stable adults with schizophrenia or schizoaffective disorder previously treated with oral risperidone, olanzapine, or oral conventional antipsychotics were randomized to treatment with either RLAI (25 mg every-two-weeks) or quetiapine (300-400 mg/day) for 24 months. Functional recovery was assessed using the Social and Occupational Functioning Assessment Scale (SOFAS) and two quality-of-life (QoL) measures (Short -Form 12 [SF-12] and Schizophrenia Quality-of-Life Scale Revision 4 [SQLS-R4]).
710 subjects were randomized to treatment with RLAI or quetiapine (n=355 patients/group). Baseline demographics were similar between treatment groups. Relapse occurred in 16.5% RLAI and 31.3% quetiapine patients. A total of 105 RLAI and 107 quetiapine patients dropped out of the study for other reasons than relapse, most commonly due to withdrawal of consent. A significant improvement in SOFAS, SF-12, and SQLS-R4 scores was observed from baseline to month-24 with both RLAI and quetiapine. at months 6, 12, and endpoint, SOFAS had significantly increased more for RLAI than quetiapine (p< 0.05).
Among stable patients with schizophrenia or schizoaffective disorder, the likelihood of functional recovery appears to be higher in those switching to RLAI. Improvement in functional status and QoL from baseline was observed with both RLAI and quetiapine.
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.