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Let $$E$$ be a bounded subset of real line which contains its infimum and supremum. In this paper, we have defined the $$\phi -$$ transform and its inverse, where $$\phi $$ is a function from $$E$$ into $$(0,1]$$ . We will have shown that real-valued integrable functions on $$[a, b]$$ and real-valued continuous functions on $$E$$ can be approximated by this transformation with an arbitrary precision. [ABSTRACT FROM AUTHOR]

Plain Language Summary Title: What Psychiatrists Should Know About Prescribed Safer Opioid Supply., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: There is high inter-individual variability in clozapine metabolism due to genetic and non-genetic differences. Patient-specific factors such as smoking, inflammation indicated by elevated C-reactive protein (CRP), and certain concurrent medications have a significant influence on clozapine metabolism., Aim: To assess which patient-specific factors best explain variability in clozapine metabolism estimated by clozapine concentration to dose (C/D) ratios., Methods: A retrospective cohort analysis using electronic medical data was conducted on 172 inpatients at the BC Psychosis Program. Patients with normal renal and liver function were included if they were on clozapine and had at least one steady-state plasma concentration. The degree of influence of each factor on the variability of clozapine metabolism in the entire cohort and subgroups stratified by fluvoxamine use was evaluated using multiple linear regression analysis of C/D ratios., Results: Model fit testing showed that the entire cohort model accounts for 52.7% of C/D ratio variability, while the no fluvoxamine and fluvoxamine models accounted for 40.8% and 43.8%. In the entire cohort ( n = 172), fluvoxamine use explained the highest variance, and C/D ratios were higher by 30.6% on average. The second strongest predictor was elevated CRP > 10 mg/L, and C/D ratios were higher by 22.9% on average. Subsequently, obesity, nonsmoker status, and female sex explained a significant but modest proportion of variance. Among participants on fluvoxamine ( n = 58), only fluvoxamine dose was associated with an increase, and for every 25 mg increase in dose, C/D ratios increased by 5% on average., Conclusion: In a clinical population, this study replicated the relationship between reduced rate of clozapine metabolism and the use of fluvoxamine, elevated CRP, obesity, nonsmoking status, and female sex; and the magnitude of the effects were large enough to be clinically relevant., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: RR, AS, AR, NB, and KK have none to declare, AMB reports receiving research funding from Boehringer Ingelheim, RFW has received income from Canadian Agency for Drugs and Technologies in Health and Advisory Board Activities for HLS Therapeutics, CGS is a consultant to Clearmind Medicine, and CAB is founder and CEO of Sequence2Script Inc.

Model-informed precision dosing using virtual twins (MIPD-VTs) is an emerging strategy to predict target drug concentrations in clinical practice. Using a high virtualization MIPD-VT approach (Simcyp version 21), we predicted the steady-state clozapine concentration and clozapine dosage range to achieve a target concentration of 350 to 600 ng/mL in hospitalized patients with treatment-resistant schizophrenia (N = 11). We confirmed that high virtualization MIPD-VT can reasonably predict clozapine concentrations in individual patients with a coefficient of determination (R 2 ) ranging between 0.29 and 0.60. Importantly, our approach predicted the final dosage range to achieve the desired target clozapine concentrations in 73% of patients. In two thirds of patients treated with fluvoxamine augmentation, steady-state clozapine concentrations were overpredicted two to four-fold. This work supports the application of a high virtualization MIPD-VT approach to inform the titration of clozapine doses in clinical practice. However, refinement is required to improve the prediction of pharmacokinetic drug-drug interactions, particularly with fluvoxamine augmentation., (© 2024 The Authors. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Background: Preliminary evidence suggest clozapine is associated with more favorable impact on concurrent substance use disorder related outcomes in patients with concurrent schizophrenia spectrum disorders (SSD). At the same time, there is a dearth of evidence with regards to clozapine outcomes in the context of concurrent methamphetamine or amphetamine use disorder (MAUD)., Aims: To examine whether clozapine use decreases rate of methamphetamine or amphetamine (MA) relapses and increases the likelihood of maintaining abstinence from any MA use., Methods: A descriptive-analytic retrospective cohort study was conducted on individuals with SSD-MAUD in an inpatient provincial treatment and rehabilitation center for concurrent disorders. Antipsychotic exposure was categorized as "on clozapine" or "on other antipsychotic(s)." Data were collected using electronic health records. Logistic regression was used to examine association of clozapine treatment with likelihood of complete abstinence from MA use for the duration of antipsychotic exposure. Negative binomial regression was used to examine association of clozapine treatment with rate of MA relapses for the duration of antipsychotic exposure., Results: The majority of the 87 included patients were male. Ethnicity was diverse, with the largest groups self-identifying as Indigenous and European. Clozapine use was both associated with increased likelihood of maintaining abstinence from MA use (adjusted odds ratio (aOR) = 3.05, 95% confidence intervals (CI) = 1.15-8.1, p  = 0.025), and decreased rate of MA relapses (aRR = 0.45, 95% CI = 0.25-0.82, p  = 0.009) for the duration of antipsychotic exposure. Co-prescription of psychostimulants was associated with increased rate of MA relapses (aRR = 2.43, 95% CI = 1.16-5.10, p  = 0.019)., Conclusion(s): In this study, clozapine use compared with other antipsychotics in SSD was associated with improved outcomes related to severe concurrent MAUD. Co-prescription of psychostimulant medications was associated with a poor outcome., Competing Interests: Declaration of conflicting interestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: RR, LF, HM, NM, and SP have none to declare; MD reports receiving personal fees from Eisai Ltd, Otsuka, Winterlight Labs, and the Ontario Brain Institute; CAB is founder and CEO of Sequence2Script Inc.; WGH is a consultant to AbbVie, and Translational Life Sciences; and CGS is a consultant to Clearmind Medicine.

Background: Antipsychotic medications are the mainstay of treatment for schizophrenia and are associated with a reduction in psychiatric hospitalization and overall mortality. Some evidence suggest that antipsychotic medications might have a varying effect on the improvement of comorbid substance use disorders (SUDs), with clozapine showing more favorable outcomes., Aim: We systematically reviewed all available evidence on effects of clozapine on the improvement of SUDs other than nicotine., Methods: Electronic searches of MEDLINE, Embase, PsycINFO, and CINHAL were conducted up to March 1, 2022. Studies of any methodological design involving two concepts: (1) clozapine and (2) SUD terms (excluding nicotine) were included. For SUD outcomes with three or more comparative studies with available raw data meta-analysis was performed. SUD outcomes not meeting criteria for meta-analysis were described qualitatively. Risk of bias was examined using "Downs and Black," and "Q-Coh" instruments., Results: The majority of individuals in the included 31 studies were male and of European ancestry. Abstinence was the most common outcome. Most of the studies were of low-to-moderate quality, and none of the studies met all the quality criteria. Pooled findings from four observational studies in samples of patients with predominantly comorbid alcohol use disorder showed that clozapine treatment is associated with significantly higher odds of remaining abstinent. In addition clozapine was associated with decreased odds of psychiatric hospitalization in all but one observational study., Conclusions: Our systematic review and meta-analysis builds upon previous reviews, and it suggests the association of clozapine treatment with significantly higher odds of remaining abstinent from substance use and decreased likelihood of psychiatric hospitalization, compared with continuing treatment with other antipsychotic medications. Still, the validity of this association needs greater exploration and providing recommendations for the utility of clozapine in individuals without treatment-resistant psychosis and comorbid SUDs would be premature.

Interest in the use of parenteral ketamine has been increasing over the last 2 decades for the management of treatment-resistant depression (TRD). While intravenous (IV) ketamine has been the most common parenteral route of administration, subcutaneous (SC) and intramuscular options have been described. We developed a clinical treatment protocol for the use of repeated SC racemic ketamine (maximum six treatments, twice per week) in an inpatient psychiatric care setting with inclusion/exclusion criteria, dosing schedule, and description of treatment, assessment, and monitoring procedures. Results from the first 10 consecutive patients demonstrated the effectiveness of SC racemic ketamine in relieving symptoms of TRD as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) and Quick Inventory of Depressive Symptomatology, Self-Report (QIDS-SR 16 ). Response (≥50% reduction in scores from baseline to endpoint) was achieved in 8/10 cases on the MADRS and 6/10 on the QIDS-SR 16 . Remission was achieved in 8/10 (based on MADRS ≤10) and 5/10 (based on QIDS-SR 16 ≤6). Patients tolerated the treatments well with only transient blood pressure changes and dissociative side effects. Repeated SC ketamine treatments could be a safe, feasible, and effective alternative to IV ketamine infusions for patients with TRD., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Competing Interests: Competing interests: For activities not directly related to the case series reported here, Sukhpreet Poonia and Reza Rafizadeh have received payment for leading workshops on opioid-use disorder from the British Columbia Pharmacy Association; Ric Procyshyn has received royalties from the publisher of Clinical Handbook of Psychotropic Drugs, honoraria for advisory board service from Janssen, Lundbeck, and Otsuka, and honoraria for participation on speakers’ bureaus from Janssen, Lundbeck, Otsuka, and Eisai; and Randal White has received honoraria from HLS Therapeutics and the Canadian Agency for Drugs and Technology in Health. No other competing interests were declared.

Competing Interests: Competing interests: None declared.

Competing Interests: R.M. Procyshyn has received consulting fees or sat on paid advisory boards for Janssen, Lundbeck and Otsuka and is on the speakers bureau for Eisai, Janssen, Lundbeck and Otsuka. No other competing interests were declared.

Competing Interests: Competing interests: None declared.

Background: Breastfeeding is one of the most sensitive stages in the development of children, having many benefits for the mother and the child. The present study aimed to determine factors associated with breastfeeding intention and behavior in mothers living in Taft County, Iran., Methods: In this cross-sectional design, the statistical population consisted of 420 mothers with infants under 1 year of age living in Taft County of Yazd province, Iran. The research data were collected from health records of infants under one in health centers of the county as well as a researcher-made questionnaire including demographic information, knowledge and attitude towards breastfeeding, social support and perceived self-efficacy, and breastfeeding intention and behavior. Structural Equation Modeling (SEM) based on AMOS 18 were employed to analyze the relationship between research variables., Results: The mean age of mothers was 28.04 ± 6.49 year and the children were 10 ± 6 months. Half of the mothers (50.3%) had cesarean sections and more than half (55.8%) of the children were males. Mothers' attitude (β = 0.442; 95% CI: 0.284, 0.599), self-efficacy (β = 0.186; 95% CI: 0.047, 0.324) and perceived social support (β = 0.178; 95% CI: 0.035, 0.322) were respectively the strongest predictors of breastfeeding intention. Besides, the breastfeeding intention affected breastfeeding behavior with a high coefficient (0.857; 95% CI: 0.735, 0.979)., Conclusions: The study provided informative pathways on the association of maternal attitude, social support and self-efficacy with breast feeding behavior. These findings could be useful for designing health education and promotion programs about breast feeding among women.

Background: Antipsychotics have been approved for the treatment of certain psychiatric illnesses. However, these medications are also frequently used off label, and recent studies have suggested a concerning potential increase in the risk of death when used by elderly patients with dementia. Most of the available literature focusing on off-label use of antipsychotics comes from long-term care facilities; there is a lack of quantitative data for elderly patients in the acute care setting. This study was designed to examine this scenario and to identify potential quality improvement opportunities to minimize harm., Objectives: The primary objectives were to determine the prevalence of hospital-initiated off-label use of antipsychotics for elderly inpatients and to determine the plan for these drugs upon discharge. The secondary objectives included identifying the most common diagnosis and the most common agent used., Methods: A retrospective cohort study was performed with a convenience sample. Patients included in the analysis were elderly adults (≥ 65 years) who had been admitted to either of 2 medical units at a community hospital between September 1 and November 8, 2014. Descriptive statistics were used to examine prevalence patterns for the off-label use of antipsychotics., Results: A total of 250 patients were included in the analysis. Forty-five patients (18%, 95% confidence interval [CI] 13.7%-23.2%) received a hospital-initiated antipsychotic for off-label use during the admission. For 27 (60%, 95% CI 45.5%-73.0%) of these 45 patients, the off-label therapy was discontinued upon discharge or death, and for 13 (29%, 95% CI 17.7%-43.4%), the agent was continued upon discharge without a plan in place. The most frequent diagnosis was delirium, and the agent most frequently used was haloperidol., Conclusions: Off-label antipsychotic therapy was initiated for almost 1 in every 5 elderly patients receiving care in 2 medical units at a community hospital. These findings suggest a need to monitor and reassess the off-label use of these agents, especially at the time of discharge., Competing Interests: Competing interests: None declared.

Background: Symptomatic venous thromboembolism (VTE) occurs in about 1% of patients within 3 months after admission to a medical unit. Recent evidence for thromboprophylaxis in an unselected medical inpatient population has suggested only a modest net benefit. Consequently, guidelines recommend careful risk stratification to guide thromboprophylaxis., Objectives: To compare candidacy for thromboprophylaxis according to 4 risk stratification models: a regional preprinted order (PPO) set used in the study institution, the Padua Prediction Score, and the IMPROVE predictive and associative risk assessment models., Methods: A retrospective review of health records was undertaken for patients with no contraindication to pharmacologic thromboprophylaxis who were admitted to the internal medicine service of a teaching hospital between April and July 2013., Results: Of the 298 patients in the study cohort, 238 (80.0%) received pharmacologic thromboprophylaxis on admission, ordered according to the regional PPO. However, according to the Padua and the IMPROVE predictive risk assessment models, only 64 (21.5%) and 21 (7.0%) of the patients, respectively, were eligible for thromboprophylaxis at the time of admission. On the basis of risk factors identified during the subsequent hospital stay, 54 (18.1%) of the patients were eligible for thromboprophylaxis according to the IMPROVE associative model. Chance-corrected agreement between the PPO and the published risk assessment models was generally poor, with kappa coefficients of 0.109 for the PPO compared with the Padua Prediction Score and 0.013 for the PPO compared with the IMPROVE predictive model., Conclusions: These data suggest that quantitative models such as the Padua Prediction Score and the IMPROVE models identify more patients at low risk of venous thromboembolism than do in-hospital qualitative risk assessment models. Adoption of these guideline-based risk assessment models for predicting thromboembolic risk in medical inpatients could reduce the use of pharmacologic thromboprophylaxis from 80% to as low as 7%. Further external prognostic validation of risk assessment models and impact analysis studies may show improvements in safety and resource utilization.

Objective: To identify the vectors and reservoirs of cutaneous leishmaniasis in the endemic focus of Farashband, Fars Province, South of Iran., Methods: Sticky papers and Sherman trap were used for collection of sand flies and rodents, respectively. Polymerase chain reaction (PCR) of kDNA, ITS1-rDNA were used for identification of Leishmania parasite in sand flies as well as rodents., Results: Totally 2 010 sand flies were collected and the species of Phlebotomus papatasi Scopoli was the common specimen in outdoors and indoors places. PCR technique was employed on 130 females of Phlebotomus papatasi. One of them (0.76%) was positive to parasite Leishmania major (L. major) and one specimen (0.76%) was positive to Leishmania infantum. Microscopic investigation on blood smear of the animal reservoirs for amastigote parasites revealed 16 (44%) infected Tatera indica. Infection of them to L. major was confirmed by PCR against kDNA loci of the parasite., Conclusions: The results indicated that Phlebotomus papatasi was the dominant species circulating two species of parasites including L. major and Leishmania infantum among human and reservoirs. Furthermore, Tatera indica is the only main host reservoir for maintenance of the parasite source in the area., (Copyright © 2013 Asian Pacific Tropical Biomedical Magazine. Published by Elsevier B.V. All rights reserved.)

Objective: To determine the sand flies species responsible for most transmission of Leishmania major (L. major) to human, as well as to determine the main reservoir hosts of the disease., Methods: Sand flies were collected using sticky papers and mounted in Puri's medium for species identification. Rodents were trapped by live Sherman traps. Both sand flies and rodents were subjected to molecular methods for detection of leishmanial parasite., Results: Phlebotomus papatasi (P. papatasi) was the common species in outdoor and indoor resting places. Employing PCR technique only three specimens of 150 P. papatasi (2%) were found naturally infected by parasites with a band of 350 bp which is equal to the L. major parasite. Forty six rodents were captured by Sherman traps and identified. Microscopic investigation on blood smear of the animals for amastigote parasites revealed 1 (3.22%) infected Meriones libycus (M. libycus). Infection of this animal to L. major was confirmed by PCR against rDNA loci of the parasite., Conclusions: This is the first molecular report of parasite infection of both vector (P. papatasi) and reservoir (M. libycus) to L. major in the region. The results indicated that P. papatasi was the primary vector of the disease and circulating the parasite between human and reservoirs and M. libycus was the most important host reservoir for maintenance of the parasite source in the area., (Copyright © 2011 Hainan Medical College. Published by Elsevier B.V. All rights reserved.)