Summary Chronic insomnia is the most common sleep disorder among adults and is associated with a wide range of negative outcomes. This article reviews the economic consequences of the disorder and ...the cost effectiveness of insomnia treatments. First, the total costs of insomnia are reviewed; in aggregate these costs exceed $100 billion USD per year, with the majority being spent on indirect costs such as poorer workplace performance, increased health care utilization, and increased accident risk. Next, the deleterious impact of insomnia on quality of life and the impact of treatment on quality of life are briefly considered. Finally, ten published studies evaluating the cost effectiveness of both pharmacological and behavioral treatments for insomnia are reviewed in detail. A significant majority of studies reviewed found that the cost of treating primary and comorbid insomnia is less than the cost of not treating it. Treatments were generally found to be cost-effective using commonly employed standards, with treatment costs being recouped within 6–12 mo.
Retrospective studies have shown that statins decrease the rate and severity of exacerbations, the rate of hospitalization, and mortality in chronic obstructive pulmonary disease (COPD). We ...prospectively studied the efficacy of simvastatin in preventing exacerbations in a large, multicenter, randomized trial.
We designed the Prospective Randomized Placebo-Controlled Trial of Simvastatin in the Prevention of COPD Exacerbations (STATCOPE) as a randomized, controlled trial of simvastatin (at a daily dose of 40 mg) versus placebo, with annual exacerbation rates as the primary outcome. Patients were eligible if they were 40 to 80 years of age, had COPD (defined by a forced expiratory volume in 1 second FEV1 of less than 80% and a ratio of FEV1 to forced vital capacity of less than 70%), and had a smoking history of 10 or more pack-years, were receiving supplemental oxygen or treatment with glucocorticoids or antibiotic agents, or had had an emergency department visit or hospitalization for COPD within the past year. Patients with diabetes or cardiovascular disease and those who were taking statins or who required statins on the basis of Adult Treatment Panel III criteria were excluded. Participants were treated from 12 to 36 months at 45 centers.
A total of 885 participants with COPD were enrolled for approximately 641 days; 44% of the patients were women. The patients had a mean (±SD) age of 62.2±8.4 years, an FEV1 that was 41.6±17.7% of the predicted value, and a smoking history of 50.6±27.4 pack-years. At the time of study closeout, the low-density lipoprotein cholesterol levels were lower in the simvastatin-treated patients than in those who received placebo. The mean number of exacerbations per person-year was similar in the simvastatin and placebo groups: 1.36±1.61 exacerbations and 1.39±1.73 exacerbations, respectively (P=0.54). The median number of days to the first exacerbation was also similar: 223 days (95% confidence interval CI, 195 to 275) and 231 days (95% CI, 193 to 303), respectively (P=0.34). The number of nonfatal serious adverse events per person-year was similar, as well: 0.63 events with simvastatin and 0.62 events with placebo. There were 30 deaths in the placebo group and 28 in the simvastatin group (P=0.89).
Simvastatin at a daily dose of 40 mg did not affect exacerbation rates or the time to a first exacerbation in patients with COPD who were at high risk for exacerbations. (Funded by the National Heart, Lung, and Blood Institute and the Canadian Institutes of Health Research; STATCOPE ClinicalTrials.gov number, NCT01061671.).
Abstract
Study Objectives
To examine the impact of untreated insomnia on health care utilization (HCU) among a nationally representative sample of Medicare beneficiaries.
Methods
Our data source was ...a random 5% sample of Medicare administrative data for years 2006–2013. Insomnia was operationalized as the presence of at least one claim containing an insomnia-related diagnosis in any given year based on International Classification of Disease, Version 9, Clinical Modification codes or at least one prescription fill for an insomnia-related medication in Part D prescription drug files in each year. We compared HCU in the year prior to insomnia diagnosis to HCU among to non-sleep disordered controls during the same period.
Results
A total of 151 668 beneficiaries were found to have insomnia. Compared to controls (n = 333 038), beneficiaries with insomnia had higher rates of HCU across all point of service locations. Rates of HCU were highest for inpatient care (rate ratio RR 1.61; 95% confidence interval CI 1.59, 1.64) and lowest for prescription fills (RR 1.17; 95% CI 1.16, 1.17). Similarly, compared to controls, beneficiaries with insomnia demonstrated $63,607 (95% CI $60,532, $66,685) higher all-cause costs, which were driven primarily by inpatient care ($60,900; 95% CI $56,609, $65,191). Emergency department ($1,492; 95% CI $1,387, $1,596) and prescription costs ($486; 95% CI $454, $518) were also elevated among cases relative to controls.
Conclusions
In this randomly selected and nationally representative sample of older Medicare beneficiaries and compared to non-sleep disordered controls, individuals with untreated insomnia demonstrated increased HCU and costs across all points of service.
Recent epidemiologic studies have demonstrated that Tourette syndrome (TS) and chronic tic disorder (CT) are more common than previously recognized. However, few population-based studies have ...examined the prevalence of co-occurring neuropsychiatric conditions such as obsessive-compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD). We evaluated the prevalence of TS, CT, and their overlap with OCD and ADHD in the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort.
A total of 6,768 children were evaluated using longitudinal data from mother-completed questionnaires.
DSM-IV-TR diagnoses of TS and CT were derived using three levels of diagnostic stringency (Narrow, Intermediate, and Broad). Validity of the case definitions was assessed by comparing gender ratios and rates of co-occurring OCD and ADHD using heterogeneity analyses.
Age 13 prevalence rates for TS (0.3% for Narrow; 0.7% for Intermediate) and CT (0.5% for Narrow; 1.1% for Intermediate) were consistent with rates from other population-based studies. Rates of co-occurring OCD and ADHD were higher in TS and CT Narrow and Intermediate groups compared with controls but lower than has been previously reported. Only 8.2% of TS Intermediate cases had both OCD and ADHD; 69% of TS Intermediate cases did not have either co-occurring OCD or ADHD.
This study suggests that co-occurring OCD and ADHD is markedly lower in TS cases derived from population-based samples than has been reported in clinically ascertained TS cases. Further examination of the range of co-occurring neuropsychiatric disorders in population-based TS samples may shed new perspective on the underlying shared pathophysiology of these three neurodevelopmental conditions.
The class Frizzled of G protein-coupled receptors (GPCRs), consisting of ten Frizzled (FZD
) paralogs and Smoothened, remains one of the most enigmatic GPCR families. This class mediates signaling ...predominantly through Disheveled (DVL) or heterotrimeric G proteins. However, the mechanisms underlying pathway selection are elusive. Here we employ a structure-driven mutagenesis approach in combination with an extensive panel of functional signaling readouts to investigate the importance of conserved state-stabilizing residues in FZD
for signal specification. Similar data were obtained for FZD
and FZD
suggesting that our findings can be extrapolated to other members of the FZD family. Comparative molecular dynamics simulations of wild type and selected FZD
mutants further support the concept that distinct conformational changes in FZDs specify the signal outcome. In conclusion, we find that FZD
and FZDs in general prefer coupling to DVL rather than heterotrimeric G proteins and that distinct active state micro-switches in the receptor are essential for pathway selection arguing for conformational changes in the receptor protein defining transducer selectivity.
Acute exacerbations adversely affect patients with chronic obstructive pulmonary disease (COPD). Macrolide antibiotics benefit patients with a variety of inflammatory airway diseases.
We performed a ...randomized trial to determine whether azithromycin decreased the frequency of exacerbations in participants with COPD who had an increased risk of exacerbations but no hearing impairment, resting tachycardia, or apparent risk of prolongation of the corrected QT interval.
A total of 1577 subjects were screened; 1142 (72%) were randomly assigned to receive azithromycin, at a dose of 250 mg daily (570 participants), or placebo (572 participants) for 1 year in addition to their usual care. The rate of 1-year follow-up was 89% in the azithromycin group and 90% in the placebo group. The median time to the first exacerbation was 266 days (95% confidence interval CI, 227 to 313) among participants receiving azithromycin, as compared with 174 days (95% CI, 143 to 215) among participants receiving placebo (P<0.001). The frequency of exacerbations was 1.48 exacerbations per patient-year in the azithromycin group, as compared with 1.83 per patient-year in the placebo group (P=0.01), and the hazard ratio for having an acute exacerbation of COPD per patient-year in the azithromycin group was 0.73 (95% CI, 0.63 to 0.84; P<0.001). The scores on the St. George's Respiratory Questionnaire (on a scale of 0 to 100, with lower scores indicating better functioning) improved more in the azithromycin group than in the placebo group (a mean ±SD decrease of 2.8±12.8 vs. 0.6±11.4, P=0.004); the percentage of participants with more than the minimal clinically important difference of -4 units was 43% in the azithromycin group, as compared with 36% in the placebo group (P=0.03). Hearing decrements were more common in the azithromycin group than in the placebo group (25% vs. 20%, P=0.04).
Among selected subjects with COPD, azithromycin taken daily for 1 year, when added to usual treatment, decreased the frequency of exacerbations and improved quality of life but caused hearing decrements in a small percentage of subjects. Although this intervention could change microbial resistance patterns, the effect of this change is not known. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00325897.).
Frizzleds act as dynamic pharmacological entities Schulte, Gunnar; Scharf, Magdalena M.; Bous, Julien ...
Trends in pharmacological sciences (Regular ed.),
05/2024, Letnik:
45, Številka:
5
Journal Article
Recenzirano
Odprti dostop
The initiation of Wingless/Int1 (WNT) signaling is governed by the formation of higher-order complexes termed WNT signalosomes.WNT stimulation of the Frizzled family of transmembrane receptors (FZDs) ...induces dynamic conformational rearrangements in the receptor molecule reminiscent of what we know from other G protein-coupled receptors (GPCRs).The recent identification of conserved molecular switches and dynamic interaction networks in FZDs underlines the requirements of protein dynamics for FZD activation.Protein dynamics and an understanding of the details of FZD activation lay the foundations for targeting FZDs pharmacologically.The concept of the WNT signalosome and FZD dynamics must be merged to fully grasp FZD activation mechanisms and WNT signal initiation.
The Frizzled family of transmembrane receptors (FZD1–10) belongs to the class F of G protein-coupled receptors (GPCRs). FZDs bind to and are activated by Wingless/Int1 (WNT) proteins. The WNT/FZD signaling system regulates crucial aspects of developmental biology and stem-cell regulation. Dysregulation of WNT/FZD communication can lead to developmental defects and diseases such as cancer and fibrosis. Recent insight into the activation mechanisms of FZDs has underlined that protein dynamics and conserved microswitches are essential for FZD-mediated information flow and build the basis for targeting these receptors pharmacologically. In this review, we summarize recent advances in our understanding of FZD activation, and how novel concepts merge and collide with existing dogmas in the field.
The Frizzled family of transmembrane receptors (FZD1–10) belongs to the class F of G protein-coupled receptors (GPCRs). FZDs bind to and are activated by Wingless/Int1 (WNT) proteins. The WNT/FZD signaling system regulates crucial aspects of developmental biology and stem-cell regulation. Dysregulation of WNT/FZD communication can lead to developmental defects and diseases such as cancer and fibrosis. Recent insight into the activation mechanisms of FZDs has underlined that protein dynamics and conserved microswitches are essential for FZD-mediated information flow and build the basis for targeting these receptors pharmacologically. In this review, we summarize recent advances in our understanding of FZD activation, and how novel concepts merge and collide with existing dogmas in the field.
The genetics of Tourette syndrome: A review O'Rourke, Julia A; Scharf, Jeremiah M; Yu, Dongmei ...
Journal of psychosomatic research,
12/2009, Letnik:
67, Številka:
6
Journal Article
Recenzirano
Odprti dostop
Abstract Objectives This article summarizes and evaluates recent advances in the genetics of Gilles de la Tourette syndrome (GTS). Methods This is a review of recent literature focusing on (1) the ...genetic etiology of GTS; (2) common genetic components of GTS, attention deficit hyperactivity disorder (ADHD), and obsessive compulsive disorder (OCD); (3) recent linkage studies of GTS; (4) chromosomal translocations in GTS; and (5) candidate gene studies. Results Family, twin, and segregation studies provide strong evidence for the genetic nature of GTS. GTS is a heterogeneous disorder with complex inheritance patterns and phenotypic manifestations. Family studies of GTS and OCD indicate that an early-onset form of OCD is likely to share common genetic factors with GTS. While there apparently is an etiological relationship between GTS and ADHD, it appears that the common form of ADHD does not share genetic factors with GTS. The largest genome wide linkage study to date observed evidence for linkage on chromosome 2p23.2 ( P =3.8×10−5 ). No causative candidate genes have been identified, and recent studies suggest that the newly identified candidate gene SLITRK1 is not a significant risk gene for the majority of individuals with GTS. Conclusion The genetics of GTS are complex and not well understood. The Genome Wide Association Study (GWAS) design can hopefully overcome the limitations of linkage and candidate gene studies. However, large-scale collaborations are needed to provide enough power to utilize the GWAS design for discovery of causative mutations. Knowledge of susceptibility mutations and biological pathways involved should eventually lead to new treatment paradigms for GTS.
Recent studies described association between chronic obstructive pulmonary disease (COPD) and increased risk of cardiovascular diseases (CVD). In their analysis none of these studies accounted for ...sociodemographic factors, health behaviors, and patient comorbidities simultaneously.
To study whether COPD diagnosis is an independent risk factor for CVD.
Subjects aged 40 years and older (N = 18,342) from the sample adult file of the 2002 National Health Interview Survey (NHIS) were included in the analysis. Chi-squared tests and odds ratios (OR) were utilized to compare the data. Multiple logistic regression was employed to analyze the association between COPD and CVD with simultaneous control for sociodemographic factors (age, gender, race, marital status, education, income), health behaviors (tobacco use, alcohol consumption, physical activity), and patient comorbidities (diabetes, hypertension, high cholesterol, and obesity). The analysis employed NHIS sampling weights to generate data representative of the entire US population.
The COPD population had increased prevalence of CVD (56.5% vs 25.6%; P < 0.0001). Adjusted logistic regression showed that COPD patients (N = 958) were at higher risk of having coronary heart disease (OR = 2.0, 95% CI: 1.5-2.5), angina (OR = 2.1, 95% CI: 1.6-2.7), myocardial infarction (OR = 2.2, 95% CI: 1.7-2.8), stroke (OR = 1.5, 95% CI: 1.1-2.1), congestive heart failure (OR = 3.9, 95% CI: 2.8-5.5), poor circulation in lower extremities (OR = 2.5, 95% CI: 2.0-3.0), and arrhythmia (OR = 2.4, 95% CI: 2.0-2.8). Overall, the presence of COPD increased the odds of having CVD by a factor of 2.7 (95% CI: 2.3-3.2).
These findings support the conclusion that COPD is an independent risk factor for CVD.
PDF
