Prescription Patterns of Antidepressants: The Effect of the Black Box Warning among Pediatric Patients

Introduction: Our aim was to investigate the prescription patterns of antidepressant in the southern Israel during the years 2000 to 2005, before and after the FDA black box warning issued regarding the prescription of antidepressants in children. Patients and methods: A cross sectional study. Data regarding prescription of anti-depressant drugs was examined retrospectively. All information was obtained from the computerized databases of the Clalit Health care services, southern county. Data was analyzed by using descriptive statistics, and analytical statistics. Multi-variate analysis was performed when applicable.Results: When comparing the prescription rate of fluoxetine and fluvoxamine versus other SSRI’s included in the health agencies warnings during the years mentioned, there was a gradual increase in the percentage of the other SSRI’s until 2003 from 12.2% in 2000 to 64.2% in 2003 and then a reversal of this trend from 51.9% in 2004 to 47.8% in 2005.Discussion and conclusions: This study shows that the CSM advice has not had a significant effect in reversing the rising prevalence of antidepressant prescribed to children and adolescents in primary care. It has however changed the choice of antidepressant medication chosen within the group of SSRI’s

Inference from gated first-passage times

First-passage times provide invaluable insight into fundamental properties of stochastic processes. Yet, various forms of gating mask first-passage times and differentiate them from actual detection times. For instance, imperfect conditions may intermittently gate our ability to observe a system of interest, such that exact first-passage instances might be missed. In other cases, e.g., certain chemical reactions, direct observation of the molecules involved is virtually impossible, but the reaction event itself can be detected. However, this instance need not coincide with the first collision time since some molecular encounters are infertile and hence gated. Motivated by the challenge posed by such real-life situations we develop a universal -- model-free -- framework for the inference of first-passage times from the detection times of gated first-passage processes. In addition, when the underlying laws of motions are known, our framework also provides a way to infer physically meaningful parameters, e.g. diffusion coefficients. Finally, we show how to infer the gating rates themselves via the hitherto overlooked short-time regime of the measured detection times. The robustness of our approach and its insensitivity to underlying details are illustrated in several settings of physical relevance

Runtime Distributions and Criteria for Restarts

Randomized algorithms sometimes employ a restart strategy. After a certain number of steps, the current computation is aborted and restarted with a new, independent random seed. In some cases, this results in an improved overall expected runtime. This work introduces properties of the underlying runtime distribution which determine whether restarts are advantageous. The most commonly used probability distributions admit the use of a scale and a location parameter. Location parameters shift the density function to the right, while scale parameters affect the spread of the distribution. It is shown that for all distributions scale parameters do not influence the usefulness of restarts and that location parameters only have a limited influence. This result simplifies the analysis of the usefulness of restarts. The most important runtime probability distributions are the log-normal, the Weibull, and the Pareto distribution. In this work, these distributions are analyzed for the usefulness of restarts. Secondly, a condition for the optimal restart time (if it exists) is provided. The log-normal, the Weibull, and the generalized Pareto distribution are analyzed in this respect. Moreover, it is shown that the optimal restart time is also not influenced by scale parameters and that the influence of location parameters is only linear

Defining localities of inadequate treatment for childhood asthma: A GIS approach

BACKGROUND: The use of Geographic Information Systems (GIS) has great potential for the management of chronic disease and the analysis of clinical and administrative health care data. Asthma is a chronic disease associated with substantial morbidity, mortality, and health care use. Epidemiologic data from all over the world show an increasing prevalence of asthma morbidity and mortality despite the availability of effective treatment. These facts led to the emergence of strategies developed to improve the quality of asthma care. THE OBJECTIVE: To develop an efficient tool for quality assurance and chronic disease management using a Geographic Information System (GIS). GEOGRAPHIC LOCATION: The southern region of Israel. January 1998 – October 2000. DATABASES: Administrative claims data of the largest HMO in Israel: drug dispensing registry, demographic data, Emergency Room visits, and hospitalization data bases. METHODS: We created a list of six markers for inadequate pharmaceutical treatment of childhood asthma from the Israeli clinical guidelines. We used this list to search the drug dispensing registry to identify asthmatic children who received inadequate treatment and to assess their health care utilization and bad outcomes: emergency room visits and hospitalizations. Using GIS we created thematic maps on which we located the clinics with a high percentage of children for whom the treatment provided was not in adherence with the clinical guidelines. RESULTS: 81% of the children were found to have at least one marker for inadequate treatment; 17.5% were found to have more than one marker. Children with markers were found to have statistically significant higher rates of Emergency Room visits, hospitalizations and longer length of stay in hospital compared with children without markers. The maps show in a robust way which clinics provided treatment not in accord with the clinical guidelines. Those clinics have high rates of Emergency Room visits, hospitalizations and length of stay. CONCLUSION: Integration of clinical guidelines, administrative data and GIS can create an efficient interface between administrative and clinical information. This tool can be used for allocating sites for quality assurance interventions

The Antidepressant and Anxiolytic Effects of Cannabinoids in Chronic Unpredictable Stress: A Preclinical Systematic Review and Meta-Analysis

Neuroscience research presents contradictory evidence in support of both the protective and destructive effects of cannabinoids in depression. Therefore, this systematic review and meta-analysis summarizes the existing preclinical literature on the effects of cannabinoid administration in the chronic unpredictable stress model of depression in order to evaluate the effects of cannabinoids and identify gaps in the literature. After protocol registration (PROSPERO #CRD42020219986), we systematically searched Scopus, Embase, Psychology & Behavioral Sciences Collection, APA PsychINFO, PubMed, CINAHL Complete, and ProQuest Dissertations & Theses Global from the earliest record of the databases, February 1964, to November 2020 for articles that met inclusion criteria (e.g., rodent subjects and administration of a cannabinoid. A total of 26 articles were included representing a sample size estimate of 1132 rodents with the majority of articles administering daily intraperitoneal injections during chronic unpredictable stress. These articles were evaluated using a modified SYRCLE\u27s risk-of-bias tool. For each continuous behavioral measure, the standardized mean difference was calculated between cannabinoid and vehicle groups in rodents subjected to chronic unpredictable stress. The effects of cannabinoids on depressive-like behavior was evaluated using a multilevel mixed-effects model with effect size weights nested within control groups. Cannabinoid administration moderately improved the pooled negative effects of chronic unpredictable stress on anhedonia, learned helplessness, novelty suppressed feeding, time in the anxiogenic context, and entries into the anxiogenic context. Although the interpretations are limited, these findings suggest that with further investigation, cannabinoids may be a viable long-term treatment for stress-related psychopathologies such as depression

Mean first-passage time of surface-mediated diffusion in spherical domains

We present an exact calculation of the mean first-passage time to a target on the surface of a 2D or 3D spherical domain, for a molecule alternating phases of surface diffusion on the domain boundary and phases of bulk diffusion. The presented approach is based on an integral equation which can be solved analytically. Numerically validated approximation schemes, which provide more tractable expressions of the mean first-passage time are also proposed. In the framework of this minimal model of surface-mediated reactions, we show analytically that the mean reaction time can be minimized as a function of the desorption rate from the surface.Comment: to appear in J. Stat. Phy

Financial Incentive Increases CPAP Acceptance in Patients from Low Socioeconomic Background

OBJECTIVE: We explored whether financial incentives have a role in patients' decisions to accept (purchase) a continuous positive airway pressure (CPAP) device in a healthcare system that requires cost sharing. DESIGN: Longitudinal interventional study. PATIENTS: The group receiving financial incentive (n = 137, 50.8±10.6 years, apnea/hypopnea index (AHI) 38.7±19.9 events/hr) and the control group (n = 121, 50.9±10.3 years, AHI 39.9±22) underwent attendant titration and a two-week adaptation to CPAP. Patients in the control group had a co-payment of $330-660; the financial incentive group paid a subsidized price of$55. RESULTS: CPAP acceptance was 43% greater (p = 0.02) in the financial incentive group. CPAP acceptance among the low socioeconomic strata (n = 113) (adjusting for age, gender, BMI, tobacco smoking) was enhanced by financial incentive (OR, 95% CI) (3.43, 1.09-10.85), age (1.1, 1.03-1.17), AHI (>30 vs. <30) (4.87, 1.56-15.2), and by family/friends who had positive experience with CPAP (4.29, 1.05-17.51). Among average/high-income patients (n = 145) CPAP acceptance was affected by AHI (>30 vs. <30) (3.16, 1.14-8.75), living with a partner (8.82, 1.03-75.8) but not by the financial incentive. At one-year follow-up CPAP adherence was similar in the financial incentive and control groups, 35% and 39%, respectively (p = 0.82). Adherence rate was sensitive to education (+yr) (1.28, 1.06-1.55) and AHI (>30 vs. <30) (5.25, 1.34-18.5). CONCLUSIONS: Minimizing cost sharing reduces a barrier for CPAP acceptance among low socioeconomic status patients. Thus, financial incentive should be applied as a policy to encourage CPAP treatment, especially among low socioeconomic strata patients

Absence of CD34 on Murine Skeletal Muscle Satellite Cells Marks a Reversible State of Activation during Acute Injury

Background: Skeletal muscle satellite cells are myogenic progenitors that reside on myofiber surface beneath the basal lamina. In recent years satellite cells have been identified and isolated based on their expression of CD34, a sialomucin surface receptor traditionally used as a marker of hematopoietic stem cells. Interestingly, a minority of satellite cells lacking CD34 has been described. Methodology/Principal Findings: In order to elucidate the relationship between CD34+ and CD34- satellite cells we utilized fluorescence-activated cell sorting (FACS) to isolate each population for molecular analysis, culture and transplantation studies. Here we show that unless used in combination with a7 integrin, CD34 alone is inadequate for purifying satellite cells. Furthermore, the absence of CD34 marks a reversible state of activation dependent on muscle injury. Conclusions/Significance: Following acute injury CD34- cells become the major myogenic population whereas the percentage of CD34+ cells remains constant. In turn activated CD34- cells can reverse their activation to maintain the pool of CD34+ reserve cells. Such activation switching and maintenance of reserve pool suggests the satellite cell compartment is tightly regulated during muscle regeneration

Overexpression of UV-DAMAGED DNA BINDING PROTEIN 1 links plant development and phytonutrient accumulation in high pigment-1 tomato

Fruits of tomato plants carrying the high pigment-1 mutations hp-1 and hp-1w are characterized by an increased number of plastids coupled with enhanced levels of functional metabolites. Unfortunately, hp-1 mutant plants are also typified by light-dependent retardation in seedling and whole-plant growth and development, which limits their cultivation. These mutations were mapped to the gene encoding UV-DAMAGED DNA BINDING PROTEIN 1 (DDB1) and, recently, fruit-specific RNA interference studies have demonstrated an increased number of plastids and enhanced carotenoid accumulation in the transgenic tomato fruits. However, whole-plant overexpression of DDB1, required to substantiate its effects on seedling and plant development and to couple them with fruit phenotypes, has heretofore been unsuccessful. In this study, five transgenic lines constitutively overexpressing normal DDB1 in hp-1 mutant plants were analysed. Eleven-day-old seedlings, representing these lines, displayed up to ∼73- and ∼221-fold overexpression of the gene in hypocotyls and cotyledons, respectively. This overexpression resulted in statistically significant reversion to the non-mutant developmental phenotypes, including more than a full quantitative reversion. This reversion of phenotypes was generally accompanied by correlated responses in chlorophyll accumulation and altered expression of selected light signalling genes: PHYTOCHROME A, CRYPTOCHROME 1, ELONGATED HYPOCOTYL 5, and the gene encoding CHLOROPHYLL A/B-BINDING PROTEIN 4. Cumulatively, these results provide the missing link between DDB1 and its effects on tomato plant development