Investigation and optimum design of the generalized second-order phase-locked loop

In this dissertation, a second-order phase-locked loop (PLL) in which the loop filter contains complex zeros is investigated in both its linear and nonlinear modes of operation; prior designs used a filter containing a simple zero on the negative real axis. This generalized second-order PLL had been heretofore essentially unexplored. The basic characteristics of the generalized second-order PLL operating in the linear mode including the open and closed-loop responses and the corresponding root locus were generated and compared against those of the conventional second-order PLL. As in the conventional case, the generalized second-order PLL is found to be unconditionally stable. The closed-loop response of the generalized second-order PLL indicates a noise bandwidth which is theoretically infinite, thus making the predetection filter critical to the performance of this PLL. Such is not the case in the conventional PLL. A method is presented for achieving an optimum design for the generalized second-order PLL for a number of useful modulation types including a single-channel FM speech signal, FDM-FM and FDM-PM. This optimum design is in terms of threshold performance and theoretically predicts that superior performance is possible over the conventional second-order PLL. Using the Continuous System Modeling Program (CSMP), a nonlinear model of the generalized second-order PLL was simulated for the test-tone modulation case, both in the absence of noise and with the signal corrupted by bandpass additive Gaussian noise. In addition, preliminary simulation results were obtained for the case of a single-channel FM speech signal. Using simulation techniques, a measure of the mean-square phase error at threshold for the generalized second-order PLL was obtained. This parameter is useful in the optimum design procedure. Additional insight into the operation of the generalized second-order PLL was obtained through investigation of its acquisition and tracking behavior. This was accomplished using phase plane techniques to study the nonlinear differential equation which governs the loop operation. The results indicate that two distinct types of behavior are theoretically possible depending upon the loop parameters. In one case the behavior is not unlike that of the conventional second-order PLL. In the second case, however, additional singularities are introduced into the phase plane and the behavior is seen to change markedly

Ethical Considerations for Global Pediatric Cardiac Surgical Assistance Programs

Global health initiatives have expanded over the last 25 years and are no longer based solely on improving public health issues like clean water and childhood vaccination programs. Global healthcare assistance has grown into programs that provide specialty services and education today. Cardiovascular diseases are causing more deaths today in low and middle-income countries today as infectious diseases cease to be the number one cause of mortality in many of these countries. Growth in cardiovascular assistance has been substantial during the last 25 years and especially in the area of pediatric cardiac care. We discuss the ethical issues that can be found when visitors assist countries with different cultural values. The success of program development depends on navigating the ethical issues such that all stakeholders are satisfied with the project and the end result. The foundation of program development should be based upon medical ethics that are sensitive to cultural differences so that a capable sustainable program is developed upon completion

Impact of anxiety symptoms on outcomes of depression: an observational study in Asian patients

OBJECTIVE: To investigate the impact of anxiety symptoms on depression outcomes in Asian patients with major depressive disorder (MDD) (n=714). METHODS: The 17-item Hamilton Depression Scale (HAMD-17), overall severity, somatic symptoms, and quality of life (QOL) (EuroQOL Questionnaire-5 Dimensions [EQ-5D]) were assessed at baseline and 3 months. Anxiety was measured using items 10 and 11 from the HAMD-17. Linear, tobit, and logistic multiple regression models analyzed the impact of anxiety symptoms on outcomes. Baseline anxiety was related to age and the presence of pain symptoms at baseline. RESULTS: Regression models showed that a higher level of anxiety was associated with a lower frequency of remission and lower QOL at 3 months. Patients with lower baseline anxiety symptoms had higher remission rates (odds ratio for each point of anxiety symptoms, 0.829 [95% confidence interval [CI]: 0.723-0.951]). Patients with higher levels of baseline anxiety had a lower QOL at 3 months (a decrease in EQ-5D tariff score for each point of anxiety symptoms, 0.023 [95% CI: 0.045-0.001]). CONCLUSION: In conclusion, the presence of anxiety symptoms negatively impacts the outcomes of depression

Sex differences in the course of schizophrenia across diverse regions of the world

This study explores sex differences in the outcomes of patients with schizophrenia (clinical/functional remission and recovery) across diverse regions of the world (Northern Europe, Southern Europe, Central and Eastern Europe, Latin America, East Asia, and North Africa and the Middle East). Data (n=16,380 for this post hoc analysis) were taken from the World-Schizophrenia Health Outcomes Study. In most regions, females had a later age at first service contact for schizophrenia, a lower level of overall/negative symptom severity, lower rates of alcohol/substance abuse and paid employment, and higher percentages of having a spouse/partner and independent living. Overall, females had slightly higher rates of clinical remission (58.0% vs 51.8%), functional remission (22.8% vs 16.0%), and recovery (16.5% vs 16.0%) at 36 months (P<0.001 for all). This pattern was consistently observed in Southern Europe and Northern Europe even after controlling for baseline sex differences, but not in other regions. In Central and Eastern Europe, rates of clinical remission were higher in females at 36 months, but those of functional remission and recovery were similar between males and females. The opposite was observed for Latin America. In East Asia, sex differences were rarely observed for these outcomes. Finally, in North Africa and the Middle East, sex differences in these outcomes were pronounced only in regression analyses. These regional variations shed light on the importance of psychosocial and cultural factors and their effects on sex in the prognosis of schizophrenia

Predictors of remission in the treatment of major depressive disorder: real-world evidence from a 6-month prospective observational study

BACKGROUND: This study examined potential predictors of remission among patients treated for major depressive disorder (MDD) in a naturalistic clinical setting, mostly in the Middle East, East Asia, and Mexico. METHODS: Data for this post hoc analysis were taken from a 6-month prospective, noninterventional, observational study that involved 1,549 MDD patients without sexual dysfunction at baseline in 12 countries worldwide. Depression severity was measured using the Clinical Global Impression of Severity and the 16-item Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR16). Depression-related pain was measured using the pain-related items of the Somatic Symptom Inventory. Remission was defined as a QIDS-SR16 score ≤5. Generalized estimating equation regression models were used to examine baseline factors associated with remission during follow-up. RESULTS: Being from East Asia (odds ratio [OR] 0.48 versus Mexico; P<0.001), a higher level of depression severity at baseline (OR 0.77, P=0.003, for Clinical Global Impression of Severity; OR 0.92, P<0.001, for QIDS-SR16), more previous MDD episodes (OR 0.92, P=0.007), previous treatments/therapies for depression (OR 0.78, P=0.030), and having any significant psychiatric and medical comorbidity at baseline (OR 0.60, P<0.001) were negatively associated with remission, whereas being male (OR 1.29, P=0.026) and treatment with duloxetine (OR 2.38 versus selective serotonin reuptake inhibitors, P<0.001) were positively associated with remission. However, the association between Somatic Symptom Inventory pain scores and remission no longer appeared to be significant in this multiple regression (P=0.580), (P=0.008 in descriptive statistics), although it remained significant in a subgroup of patients treated with selective serotonin reuptake inhibitors (OR 0.97, P=0.023), but not in those treated with duloxetine (P=0.182). CONCLUSION: These findings are largely consistent with previous reports from the USA and Europe. They also highlight the potential mediating role of treatment with duloxetine on the negative relationship between depression-related pain and outcomes of depression

Impact of Negative Symptoms on Quality of Life in Patients with Schizophrenia

Objectives: The present study analyses the impact and influence of negative symptoms on quality of life (QoL). Methods: The W-SOHO study is a three year follow-up study on the outpatient care of schizophrenia that included 17,384 patients from 37 countries. Patients were recruited in W-SOHO by their treating psychiatrists when starting or changing antipsychotic medication. Evaluation was conducted during the normal course of care and was scheduled every six months after the baseline visit. The Clinical Global Impressions Severity Scale - Schizophrenia version (CGI-SCH) was used to assess symptom severity across overall, positive, negative, depressive and cognitive subdomains. Quality of life (QoL) was assessed using the EuroQOL 5-D questionnaire. Pearson correlation coefficients (PCC) were used to analyze the relationship between continuous variables. A mixed model with repeated measures (MMRM) was used to analyze the factors associated with quality of life during follow-up. Results: Quality of life at baseline was more highly correlated with negative symptoms than with positive symptoms (PCC -0.25 for positive symptoms and -0.29 for negative symptoms; p<0.001). Improvement in negative symptoms was highly correlated to improvement in QoL (PCC 0.33; p<0.0001). The regression model analysing the influence of both positive and negative symptoms on QoL at baseline was confirmative and showed a greater beta coefficient (higher influence) for negative symptoms compared with positive symptoms [(3.9 (se 0.14) versus 2.9 (se 0.13)]. Another model found that patients with greater negative symptoms at baseline experienced lower improvement in QoL (beta coefficient -0.81; se 0.11; p<0.001). Conclusions: In patients with schizophrenia negative symptoms seem to have a larger influence onself-perceived QoL than positive symptoms. Improvement in negative symptoms is highly associated with improvements in QoL

Recovery in patients with major depressive disorder (MDD): results of a 6-month, multinational, observational study

Abstract Not all individuals treated for major depressive disorder (MDD) achieve recovery. This observational study examined the recovery rates in MDD patients and the patient characteristics associated with achieving recovery in a naturalistic clinical setting. Recovery was defined as having both clinical and functional remission. Data for this post hoc analysis were taken from a 24-week prospective, observational study that involved 1,549 MDD patients. Clinical remission was assessed using the 16-item Quick Inventory of Depressive Symptomatology Self-Report and functional remission through the Sheehan Disability Scale and no days of reduced productivity in the previous week. Generalized estimating equation regression models were used to examine the baseline factors associated with recovery during follow-up. Clinical and functional remission was achieved in 70.6% and 56.1% of the MDD patients, respectively. MDD patients who achieved recovery (52.1%) were significantly less likely to have impaired levels of functioning, concurrent medical or psychiatric conditions, low levels of education, or nonadherence to therapy at follow-up. The level of functioning during the index episode seems to be a better predictor of recovery than symptom severity. Therefore, the level of functioning should be considered while determining recovery from depression

Patient characteristics associated with treatment initiation among paediatric patients with Attention-Deficit/Hyperactivity Disorder symptoms in a naturalistic setting in Central Europe and East Asia

BACKGROUND: Cultural views of Attention-Deficit/Hyperactivity Disorder (ADHD), differing healthcare systems and funding mechanisms, and the availability of mental health services can greatly influence the perceptions, diagnosis, and treatment of ADHD. There is, however, lack of information about treatment practice and the treatment decision-making process for ADHD, particularly in non-Western countries. Our study compared characteristics of paediatric patients newly diagnosed with ADHD symptoms who did and who did not initiate treatment, and also examined whether any differences varied by region in Central Europe and East Asia. METHODS: Data were taken from a 1-year prospective, observational study that included 1,068 paediatric patients newly diagnosed with ADHD symptoms. Clinical severity was measured using the Clinical Global Impression-ADHD-Severity (CGI-ADHD-S) scale and the Child Symptom Inventory-4 (CSI-4) checklist. Logistic regression was used to explore patient characteristics associated with treatment initiation (pharmacotherapy and/or psychotherapy) at baseline for each region. RESULTS: A total of 74.3% of patients initiated treatment at baseline (78.3% in Central Europe and 69.9% in East Asia). Of these, 48.8% started with both pharmacotherapy and psychotherapy in Central Europe, and only 17.1% did so in East Asia. The level of clinical severity was highest in the combination treatment group in Central Europe, but was highest in the psychotherapy only group in East Asia. In East Asia, treatment initiation was associated with being older, being male, and having a higher CGI-ADHD-S score. In Central Europe, treatment initiation was associated with parental psychological distress, having a higher CSI-4 score, and not being involved in bullying. CONCLUSIONS: Although factors associated with treatment initiation differed to some extent between Central Europe and East Asia, clinical severity appeared to be one of the most important determinants of treatment initiation in both regions. However, the choice between pharmacotherapy and psychotherapy, either alone or in combination, varied substantially across the regions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12888-014-0304-x) contains supplementary material, which is available to authorized users

Predictors and consequences of adherence to the treatment of pediatric patients with attention-deficit/hyperactivity disorder in Central Europe and East Asia.

PURPOSE: To assess baseline predictors and consequences of medication non-adherence in the treatment of pediatric patients with attention-deficit/hyperactivity disorder (ADHD) from Central Europe and East Asia. PATIENTS AND METHODS: Data for this post-hoc analysis were taken from a 1-year prospective, observational study that included a total of 1,068 newly-diagnosed pediatric patients with ADHD symptoms from Central Europe and East Asia. Medication adherence during the week prior to each visit was assessed by treating physicians using a 5-point Likert scale, and then dichotomized into either adherent or non-adherent. Clinical severity was measured by the Clinical Global Impressions-ADHD-Severity (CGI-ADHD) scale and the Child Symptom Inventory-4 (CSI-4) Checklist. Health-Related Quality of Life (HRQoL) was measured using the Child Health and Illness Profile-Child Edition (CHIP-CE). Regression analyses were used to assess baseline predictors of overall adherence during follow-up, and the impact of time-varying adherence on subsequent outcomes: response (defined as a decrease of at least 1 point in CGI), changes in CGI-ADHD, CSI-4, and the five dimensions of CHIP-CE. RESULTS: Of the 860 patients analyzed, 64.5% (71.6% in Central Europe and 55.5% in East Asia) were rated as adherent and 35.5% as non-adherent during follow-up. Being from East Asia was found to be a strong predictor of non-adherence. In East Asia, a family history of ADHD and parental emotional distress were associated with non-adherence, while having no other children living at home was associated with non-adherence in Central Europe as well as in the overall sample. Non-adherence was associated with poorer response and less improvement on CGI-ADHD and CSI-4, but not on CHIP-CE. CONCLUSION: Non-adherence to medication is common in the treatment of ADHD, particularly in East Asia. Non-adherence was associated with poorer response and less improvement in clinical severity. A limitation of this study is that medication adherence was assessed by the treating clinician using a single item question

Comparison of clinical outcomes with orodispersible versus standard oral olanzapine tablets in nonadherent patients with schizophrenia or bipolar disorder

Abstract PURPOSE: Medication nonadherence is common in the treatment of patients with severe mental illness and is a frequent cause of relapse. Different formulations have been developed in an effort to improve medication adherence. The aim of this study was to explore whether there are differential clinical outcomes between two different formulations of olanzapine (orodispersible tablets [ODTs] vs standard oral tablets [SOT]) for the treatment of nonadherent patients with schizophrenia or bipolar disorder. METHODS: Data for this analysis were from an observational study conducted in Europe (N=903). Adult schizophrenia and bipolar disorder patients in outpatient settings who initiated or changed to either olanzapine ODT or SOT according to physician decision within the last 45 days were eligible for enrollment. The follow-up period was 1 year. Of the 903 participants, 266 nonadherent patients (Medication Adherence Rating Scale score 0-4 at baseline) were included in the analysis. Clinical outcomes of interest were: 1) hospitalization and 2) relapse identified by the participating psychiatrist or hospitalization. An adjusted logistic regression model was fitted. RESULTS: Patients taking ODT had more severe illness at baseline (P<0.001) as assessed with the Clinical Global Impression with mean (standard deviation [SD]) scores of ODT 4.63 (1.03) and SOT 4 (1.16). In the regression models adjusted for potential confounders, patients taking ODT had significantly lower odds for hospitalization (odds ratio =0.355; 95% confidence interval =0.13-0.974) and relapse or hospitalization (odds ratio =0.368; 95% confidence interval =0.183-0.739), respectively. CONCLUSION: Nonadherent patients with schizophrenia or bipolar disorder treated with the orodispersible formulation were less likely to be hospitalized or suffer relapse compared to those patients taking the standard oral coated tablets