Risk Factors for Potential Drug-Drug Interactions in Patients on Chronic Peritoneal Dialysis.

INTRODUCTION: The prevalence of potential drug-drug interactions (pDDIs) is becoming a major safety concern, as it has been previously linked to a significant number of adverse drug events and could have serious consequences for patients, including death. This is especially relevant for patients with chronic renal failure, as they are particularly vulnerable to drug-drug interactions. The aim of this study was to evaluate the prevalence and associated factors of pDDIs in patients receiving chronic peritoneal dialysis. METHODS: An observational, cross-sectional study was conducted on consecutive peritoneal dialysis patients attending four tertiary care hospitals for regular monthly examination. The primary outcome was the number of pDDIs identified using Lexicomp. Potential predictors were determined using multiple linear regression. RESULTS: Total number of patients included in the study was 140. The results showed that pDDIs were highly prevalent, especially in patients who use antiarrhythmics (p = 0.001), have diabetes mellitus (p = 0.001), recently started peritoneal dialysis (p = 0.003), or have higher number of prescribed drugs (p < 0.001). Number of prescribed drugs (p < 0.001) remained a significant predictor of high-risk pDDIs in addition to the female gender (p = 0.043). CONCLUSION: Clinicians should be particularly cautious when prescribing multiple medications to high-risk patients, such as peritoneal dialysis patients, to mitigate the risk of drug-drug interactions and associated adverse health outcomes.

Nonpharmaceutical interventions reduce the incidence and mortality of COVID-19: A study based on the survey from the International COVID-19 Research Network (ICRN).

The recently emerged novel coronavirus, "severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)," caused a highly contagious disease called coronavirus disease 2019 (COVID-19). It has severely damaged the world's most developed countries and has turned into a major threat for low- and middle-income countries. Since its emergence in late 2019, medical interventions have been substantial, and most countries relied on public health measures collectively known as nonpharmaceutical interventions (NPIs). We aimed to centralize the accumulative knowledge of NPIs against COVID-19 for each country under one worldwide consortium. International COVID-19 Research Network collaborators developed a cross-sectional online survey to assess the implications of NPIs and sanitary supply on the incidence and mortality of COVID-19. The survey was conducted between January 1 and February 1, 2021, and participants from 92 countries/territories completed it. The association between NPIs, sanitation supplies, and incidence and mortality were examined by multivariate regression, with the log-transformed value of population as an offset value. The majority of countries/territories applied several preventive strategies, including social distancing (100.0%), quarantine (100.0%), isolation (98.9%), and school closure (97.8%). Individual-level preventive measures such as personal hygiene (100.0%) and wearing facial masks (94.6% at hospitals; 93.5% at mass transportation; 91.3% in mass gathering facilities) were also frequently applied. Quarantine at a designated place was negatively associated with incidence and mortality compared to home quarantine. Isolation at a designated place was also associated with reduced mortality compared to home isolation. Recommendations to use sanitizer for personal hygiene reduced incidence compared to the recommendation to use soap. Deprivation of masks was associated with increased incidence. Higher incidence and mortality were found in countries/territories with higher economic levels. Mask deprivation was pervasive regardless of economic level. NPIs against COVID-19 such as using sanitizer, quarantine, and isolation can decrease the incidence and mortality of COVID-19.

Factors affecting outcome in hospitalized patients treated according to recommendations from clinical pharmacologists.

OBJECTIVE: Although some of the positive effects of consulting a clinical pharmacologist when using complex treatment schedules have been demonstrated, the factors determining treatment outcomes are largely unknown. A main aim of this study was to identify and analyze the factors associated with the treatment outcomes in hospital patients in whom a therapeutic plan proposed by a clinical pharmacologist had been accepted and implemented. MATERIALS AND METHODS: The research was conducted as a retrospective cohort study on a random sample of 200 inpatients in the University Clinical Center Kragujevac, Serbia. The main outcome variables were i) in-hospital mortality, ii) inadequate clinical response to the therapy or pharmacological recommendations proposed by a clinical pharmacologist, iii) the total length of hospitalization, and iv) the length of hospitalization after consulting a clinical pharmacologist. The effect of putative predictors and confounders on the study outcomes were analyzed using multivariate regression models. RESULTS: Early integration of clinical pharmacologists in the course of patient treatment was associated with a reduction in the risk of a fatal outcome (OR = 1.146; 95% CI, 1.006 - 1.305; p = 0.040). Delay in consulting a clinical pharmacologist was associated with a longer overall length of patient hospitalization (B = 1.592; 95% CI, 1.100 - 2.084; p = 0.000). When the reasons for consulting a clinical pharmacologist involved the choice of drug or the occurrence of adverse drug reactions, the duration of hospitalization following the consultation was shorter by ~ 4 days (B = -4.337; 95% CI, -8.190 to -0.484; p = 0.028) and 12 days (B = -12.024; 95% CI, -19.108 to -4.940; p = 0.001), respectively. CONCLUSION: To achieve more favorable treatment outcomes in the case of difficult-to-treat hospital inpatients, clinical pharmacologists should be consulted early in the course of the disease, especially when the choice of drug is difficult, and the occurrence of adverse drug reactions is an important issue.

Hypovitaminosis D in infants: Evidence that increased intake of vitamin D reduces the incidence of allergic and respiratory disorders.

AIM: The study assessed the relationship between vitamin D status in infants and the presence of allergic and/or respiratory disorders. MATERIALS AND METHODS: The study cohort comprised 81 hospitalized infants presenting at the Pediatric Clinic, University Clinical Center Kragujevac, Serbia, between January 2011 and June 2016. RESULTS: The age of the infants ranged from 29 days to 12 months. All infants received prophylactic doses of vitamin D3 of 400 IU/daily until the end of the first year of life regardless of whether they are fed with adapted infant formula (n = 20) or breast milk (n = 37) or concurrently both (n = 24), up to the 5th month of life. The mean level of plasma 25(OH)D was 29.65 ng/mL. Hypovitaminosis D (mean serum level of 25(OH)D < 30 ng/mL) was found in n = 38 infants of which 6 presented with severe vitamin D deficiency (level below 10 ng/mL), 13 presented with vitamin D deficiency (level between 10 and 20 ng/mL) and 19 had vitamin D insufficiency (levels between 20 and 30 ng/mL). The median vitamin D serum level in infants with allergic disease (n = 16) was 32.35 ng/mL and in infants with respiratory disease (n = 65) 28.99 ng/mL. CONCLUSION: Daily vitamin D3 supplementation with 400 IU in infants until the end of the first year of life is too low to provide optimal defense against respiratory and/or allergic conditions.

Population Pharmacokinetic Modeling to Inform Sertraline Dosing Optimization in Patients with Depression.

Sertraline is one of the most prescribed antidepressants, but its pharmacokinetic (PK) properties are still not completely characterized. Using nonlinear mixed-effects modeling, we examined factors influencing sertraline PK variability in outpatients with major depressive disorder. Blood samples from 53 male and female adults treated with sertraline orally were collected at a steady state. Various demographic and clinical covariates were tested by stepwise regression procedure. We found that sertraline clearance is significantly influenced by serum concentrations of its main metabolite N-desmethylsertraline, whereas clearance of N-desmethylsertraline is affected by both creatinine clearance and drug daily dose. These results were confirmed by the reduction of points dispersion in goodness-of-fit plots for their predicted versus measured concentrations and with bootstrapping analyses. This finding can serve to inform sertraline dosing optimization, especially when changes in kidney function occur in treated individuals, to prevent adverse drug reactions and maximize therapeutic benefits.

Factors Associated with Potentially Inappropriate Prescribing in Patients on Peritoneal Dialysis.

INTRODUCTION: Inappropriate prescribing is common in patients with end-stage kidney disease, especially in those over 65 years of age. Our study aimed to reveal potentially inappropriate drug prescribing in patients on peritoneal dialysis (PD) and explore factors associated with this phenomenon. METHODS: The research was designed as an observational, cross-sectional study on a convenient sample of 145 consecutive patients with PD who attended the four tertiary-care hospitals in Serbia. The main outcome was the extent of inappropriate prescribing, as assessed by the medication appropriateness index, and potential predictors were tested by multiple linear regression. RESULTS: Inappropriate prescribing was a widespread phenomenon among patients on PD. The main factors that promote inappropriate prescribing in this subgroup of patients on kidney replacement therapy are comorbidities (p = 0.000), increased body weight (p = 0.022), a number of prescribed drugs (p = 0.000), and arterial hypertension on examination (p = 0.030). On the other hand, drinking alcohol and higher systolic blood pressure were associated with a lower inappropriate prescribing. CONCLUSION: In order to prevent the occurrence of inappropriate prescribing and its severe health or economic consequences, clinicians should pay special attention when prescribing new drugs to high-risk patients.

Predictors of Mortality in Early Neonatal Sepsis: A Single-Center Experience.

Background and Objectives: Early neonatal sepsis is associated with a significant mortality rate despite modern treatment strategies. Our aim was to identify risk factors contributing to the occurrence of death in newborns with early neonatal sepsis. Materials and Methods: We conducted a retrospective cross-sectional study that included newborns with early sepsis who received care in the intensive and semi-intensive care units at the Institute of Neonatology, Belgrade, Serbia. Newborns with early neonatal sepsis who died comprised the case group, whereas those who survived made up the control group. The diagnostic and therapeutic approach to the septic condition was carried out independently of this study, according to valid hospital protocols and current good practice guidelines. The influence of a large number of variables on the examined dichotomous outcome, as well as the mutual interaction of potential predictor variables, was examined by binary logistic regression. Results: The study included 133 pregnant women and 136 newborns with early neonatal sepsis, of which 51 (37.5%) died, while the remaining 85 newborns (62.5%) survived. Newborns who died had a statistically significantly lower birth weight compared to those who survived (882.8 ± 372.2 g vs. 1660.9 ± 721.1 g, p = 0.000). Additionally, compared to newborns who survived, among the deceased neonates there was a significantly higher proportion of extremely preterm newborns (74.5% vs. 22.4%, p = 0.000). The following risk factors for the occurrence of death in early neonatal sepsis were identified: low birth weight, sepsis caused by gram-negative bacteria, and the use of double-inotropic therapy and erythrocyte transfusion during the first week. Conclusions: Pediatricians should pay special attention to infants with early neonatal sepsis in whom any of the identified risk factors are present in order to prevent a fatal outcome.

The global case fatality rate of coronavirus disease 2019 by continents and national income: A meta-analysis.

The aim of this study is to provide a more accurate representation of COVID-19's case fatality rate (CFR) by performing meta-analyses by continents and income, and by comparing the result with pooled estimates. We used multiple worldwide data sources on COVID-19 for every country reporting COVID-19 cases. On the basis of data, we performed random and fixed meta-analyses for CFR of COVID-19 by continents and income according to each individual calendar date. CFR was estimated based on the different geographical regions and levels of income using three models: pooled estimates, fixed- and random-model. In Asia, all three types of CFR initially remained approximately between 2.0% and 3.0%. In the case of pooled estimates and the fixed model results, CFR increased to 4.0%, by then gradually decreasing, while in the case of random-model, CFR remained under 2.0%. Similarly, in Europe, initially, the two types of CFR peaked at 9.0% and 10.0%, respectively. The random-model results showed an increase near 5.0%. In high-income countries, pooled estimates and fixed-model showed gradually increasing trends with a final pooled estimates and random-model reached about 8.0% and 4.0%, respectively. In middle-income, the pooled estimates and fixed-model have gradually increased reaching up to 4.5%. in low-income countries, CFRs remained similar between 1.5% and 3.0%. Our study emphasizes that COVID-19 CFR is not a fixed or static value. Rather, it is a dynamic estimate that changes with time, population, socioeconomic factors, and the mitigatory efforts of individual countries.

Risk factors for potential drug-drug interactions in patients with pneumonia.

OBJECTIVE: The goal of our study was to discover and analyze possible risk factors for and possible protective factors against the occurrence of potential drug-drug interactions (pDDIs) in a hospitalized patient with community-acquired pneumonia. MATERIALS AND METHODS: The central outcome was the incidence of pDDIs in patients with community-acquired pneumonia checked by Lexicomp and Micromedex interaction checkers. RESULTS: The most severe pDDIs (Consider therapy modification D/Avoid combination X/Major/Contraindicated) were found in 19 (20%) and 54 (58%) patients, according to Lexicomp and Micromedex, respectively. Patients with community-acquired pneumonia who were older, smokers, and with more prescribed drugs by more than a few independent prescribers had a higher risk to experience pDDIs. Possible protective factors were longer length of hospitalization, transfer from the Emergency Department, antiarrhythmic drugs as well as an anticoagulant therapy. CONCLUSION: In conclusion, community-acquired pneumonia patients with the above-mentioned factors should have their treatment more deeply monitored for pDDIs.

The significant role of dietary intake of vitamin D in non-menopausal women health.

Optimal vitamin D status is very important for reflecting not only bone but overall woman's health. The aim of the study was to determine pharmacokinetic variability of 25-hydroxy vitamin D, to reveal and quantify the most significant factors that affect its variability in the population of healthy non-menopausal women using the population pharmacokinetic (PopPK) approach. The study population consisted of 74 healthy reproductive women aged from 35 to 50 years, without the use of any supplement. A population pharmacokinetics analysis was conducted using a nonlinear mixed-effects model software. A total of 35 factors were assessed: demographic, clinical, biochemical data and lifestyle factors. The average age and bodyweight of our participants were 40.11 ± 4.35 years 65.30 ± 6.80 kg, respectively. The observed mean serum concentration of 25-hydroxy vitamin D was 26.51 ± 13.49 ng/mL with a wide range of 6.97 to 59.89 ng/mL. Development final PopPK model of the clearance of 25-hydroxy vitamin D showed that only the average daily dose of vitamin D intake from food had a significant influence, with a magnitude of its effects of 0.00401. These results could help when individualizing vitamin D intake in the form of supplements, especially during the wintertime, in healthy reproductive women.

New instrument for measuring quality of life in patients with cervical cancer.

Our study aimed to develop and validate a reliable instrument that can measure the quality of life (QOL) of patients with cervical cancer living in a developing country, such as the Central Balkan country, Serbia. Our study was cross-sectional for assessing the reliability and validity of a questionnaire. Balkan questionnaire for QOL of patients with cervical cancer showed satisfactory reliability and temporal stability. When the investigators rated the questionnaire, Cronbach's alpha was 0.971 at the beginning, and one month later it was 0.967. When the questionnaire was rated by patients themselves, Cronbach's alpha was 0.972. The questionnaire should be considered as an addition to the existing armamentarium for measuring the quality of life in patients with cervical cancer.

Effects of Supplementation in Vitamin D3 Deficient or Insufficient Children with Allergic Diseases.

Background and Objectives: Although vitamin D insufficiency or deficiency is prevalent in children with allergic diseases, recommendations for supplementation dosing regimens are imprecise and variable in the literature, because clinical trials aiming to determine optimal doses were scarce in the past. This study aimed to investigate supplementation of vitamin D3 that may achieve therapeutically effective but not toxic serum levels in a subpopulation of children with allergic diseases and concomitant hypovitaminosis D. Materials and Methods: The retrospective, observational study with a cross-sectional design included 94 children suffering from allergic diseases and having vitamin D deficiency/insufficiency who were prescribed high-dose vitamin D3 supplementation by a pediatrician for at least 6 weeks and not more than 9 weeks. Serum levels of the major metabolite of vitamin D (25-(OH)D) were determined in all children twice: before and two weeks after the end of vitamin D3 supplementation. Results: An increase in serum level of the 25-(OH)D after supplementation was significant. However, if the subjects had higher serum levels of the 25-(OH)D before the supplementation, and if the supplementation lasted 8 instead of 6 weeks, the absolute increase in serum level of the 25-(OH)D was lower. Patients taking corticosteroids as inhalation or intranasally had a more intense effect of vitamin D3 supplementation, i.e., the absolute increase in levels of 25-(OH)D was higher than in patients not using such medication. Conclusions: Vitamin D deficiency and insufficiency in children with allergic diseases can be treated with maximal recommended doses of vitamin D3 for a short period of time, especially if they were prescribed with inhalation or intranasal corticosteroids.

Does the Severity of Obstructive Sleep Apnea Have an Independent Impact on Systemic Inflammation?

Background and Objectives: This paper aims to show whether obstructive sleep apnea (OSA) severity increases the level of systemic inflammation markers regardless of body mass index (BMI) and body composition. Materials and Methods: In total, 128 patients with OSA were included in the study. Examinees were divided into two groups: one with mild OSA (apnea-hypopnea index (AHI) < 15) and one with moderate and severe OSA (AHI ≥ 15). Nutritional status was assessed using body mass index, body composition by dual X-ray absorptiometry. Systemic inflammation was assessed on the basis of plasma concentrations of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and serum level of C-reactive protein (CRP). Results: We found elevated mean values of the evaluated systemic inflammation markers (CRP, TNF-α, IL-6) in a group with AHI ≥ 15, although there was no statistical significance. Our research found a significant positive correlation with BMI (r = 0.633, p < 0.001), as well as with body fat percentage (r = 0.450, p = 0.024) and serum CRP values. Significant correlation was found between the plasma IL-6 concentration and body fat percentage (FM%) (r = 0.579, p = 0.003) and lean body mass (r = -0.501, p = 0.013). Multivariate regression analysis did not show any independent predictor (parameters of OSA, nutritional status, body composition) of the systemic inflammation markers. Conclusions: Neither one tested parameter (nutritional status and body composition) of the severity of OSA was identified as an independent prognostic factor for the severity of systemic inflammation in patients with OSA.

Population pharmacokinetic analysis of bisoprolol in type 2 diabetic patients with hypertension.

PURPOSE: Given that it has been reported that type 2 diabetes mellitus may affect the pharmacokinetics of a large number of drugs and that there are still no published population pharmacokinetic (PopPK) analyses in routinely treated patients with hypertension and type 2 diabetes mellitus as comorbid condition, the aim of this study was to determine PK variability of bisoprolol in 70 Serbian patients using the PopPK approach. METHODS: PopPK analysis was conducted using a nonlinear mixed effects model (NONMEM), version 7.3.0 (Icon Development Solutions). In our patients, a total daily dose of bisoprolol ranged from 1.25 to 10 mg. The drug was administrated orally as a single daily dose or in two divided doses per day. RESULTS: A wide range of the drug concentrations were noted (1-103 ng/mL) in the population consisted of the adult patients with type 2 diabetes mellitus. From a total of 21 separately assessed covariates, our results indicated that only creatinine clearance could have a potential impact on the variability of the clearance of bisoprolol. CONCLUSION: Routine assessment of renal function should be carried out before the initiation of treatment with bisoprolol in order to individualize the dose and to prevent possible accumulation and adverse drug reactions.

Population Pharmacokinetic Analysis of Bisoprolol in Patients With Acute Coronary Syndrome.

To date, many questions about the extent and cause of pharmacokinetic (PK) variability of even the most widely studied and prescribed ß1-adrenergic receptor blockers, such as metoprolol and bisoprolol, remain unanswered. Given that there are still no published population pharmacokinetic (PopPK) analyses of bisoprolol in routinely treated patients with acute coronary syndrome (ACS), the aim of this study was to determine its PK variability in 71 Serbian patients with ACS. PopPK analysis was conducted using a nonlinear mixed-effects model (NONMEM), version 7.3.0 (Icon Development Solutions). In each patient, the same formulation of bisoprolol was administered once or twice daily at a total daily dose of 0.625-7.5 mg. We separately assessed the effects of 31 covariates on the PKs of bisoprolol, and our results indicated that only 2 covariates could have possible influence on the variability of the clearance of bisoprolol: the mean daily dose of the drug and smoking habits of patients. These findings suggest that possible autoinduction of drug metabolism by higher total daily doses and induction of cytochrome P450 isoform 3A4 (CYP3A4) by cigarette smoke in liver could be the potential causes of increased total clearance of bisoprolol in patients with ACS.

Effects of selective serotonin reuptake inhibitors on motility of isolated fallopian tube.

Selective serotonin reuptake inhibitors (SSRIs) affect the smooth muscle cells acting on voltage-dependent channels for Na+ , K+ and Ca2+ , but their action is tissue and species specific. The aim of our study was to investigate effects of selective serotonin reuptake inhibitors on motility of the isolated fallopian tubes. Isolated preparations of isthmus and ampoule were taken from fallopian tubes of 20 women during hysterectomy due to uterine fibroids and then tested for reactivity on increasing concentrations of selective serotonin reuptake inhibitors. Escitalopram (from 0.9 × 10-9  M/L to 1.4 × 10-6  M/L) produced concentration-dependent increase of spontaneous contractions of the isolated ampulla (EC50 = 1.20 ± 1.06 × 10-8  M/L, r = 0.580, P < 0.05) (F = 2.980, df1  = 6, df2  = 28, P < 0.05). Paroxetine (from 1.2 × 10-9  M/L to 5.1 × 10-5  M/L) produced concentration-dependent increase of spontaneous contractions of the isolated isthmus (EC50 = 7.01 ± 3.50 × 10-8  M/L, r = 0.500, P < 0.05) (F = 2.350, df1  = 9, df2  = 40, P < 0.05). The SSRIs differ among themselves in regard to their potential to affect motility of the fallopian tubes. Escitalopram and paroxetine have clear stimulating effect which may interfere with functioning of the fallopian tubes, and potentially impair fertility if taken by women in reproductive period of life. The other SSRIs tested in the study did not produce significant effect throughout the concentration range used in the experiments.

Antimicrobial susceptibility among urinary Escherichia coli isolates from female outpatients: age-related differences.

OBJECTIVES: Urinary tract infections (UTIs) are common problems in women, and important reason for visiting primary care physicians, resulting in substantial financial burden to community. The aim of this study was to determine the resistance rates of E. coli to commonly prescribed antimicrobial drugs for community-acquired UTIs in women and to establish the association between age and resistance to antibiotics among isolates of E. coli from urine. METHODS: The study was designed as a retrospective cross-sectional study during the 5-years period. It was conducted on a sample of urinary tract isolates of E. coli taken from women with community-acquired UTIs. After prevalence of E. coli resistance to antibiotics was established, the analysis of risk factors for emergence of resistance was conducted. RESULTS: There were 10,734 isolates of E. coli, comprising 70.62% of all samples analyzed. E. coli was the most frequently resistant to ampicillin (54.68%), followed by trimethoprim-sulphamethoxazole (37.46%), first and second generation cephalosporins (cephalexin and cefaclor) (29.53% both), and ciprofloxacin (23.80%). Less than 50% of E. coli isolates was sensitive to all three tested antibiotics, and nearly 13% acquired triple-resistance. Prevalence of isolates resistant to two or three agents was higher in the subgroup of women older than 65 years. CONCLUSIONS: Empirical choice of antimicrobial agent for community-acquired non-complicated UTIs in women should be individualized on the basis of the patient's age, prevalence of resistance in the local community, and compliance history of the patient.

Potentially inappropriate prescribing of drugs in elderly patients on chronic hemodialysis treatment
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PURPOSE: The aim of this study was to determine the prevalence of potentially inappropriate drug prescription (PIP) in older patients who were on chronic hemodialysis treatment and to explore the factors that lead to PIP. MATERIALS AND METHODS: The study was performed at the Department of Nephrology, Clinical Center Nis, Serbia. It included patients who were 65 years old and older who suffered from the end-stage of kidney failure and were treated by hemodialysis. Univariate and subsequent multivariate logistic regression was used to analyze risk factors for PIP or omission (PPO) according to the STOPP and START criteria. RESULTS: The study included 83 patients. According to the START criteria, PPO was found in 18 (22%) patients, and 32 (39%) patients experienced PIPs according to the STOPP criteria. The following factors were associated with PIP according to the START criteria: a number of comorbidities, reading the patient leaflet, and having the habit of drinking coffee. According to the STOPP criteria, polypharmacy was associated with PIP (OR = 1.287, p = 0.021): each additional drug increased the risk of potentially inadequate medications (PIM) by 28.7%. CONCLUSION: Adequate consideration of potential risk factors, as well as the implementation of valid criteria for assessment of PIP, are just some of the measures that would contribute to solving complex therapeutic problems and designing strategies for rational prescribing according to the individual characteristics of patients.
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Population pharmacokinetics of 25-hydroxy vitamin D in children with asthma
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OBJECTIVES: Asthma and vitamin D deficiency are widespread in the pediatric and adolescent population. The aim of this study was to develop a population pharmacokinetic (PPK) model and to evaluate the most important factors that can significantly affect clearance of 25-hydroxy vitamin D in asthmatic children using PPK analysis. MATERIALS AND METHODS: The study population included school children and adolescents from 7 to 18 years of age of both sexes. PPK analysis was performed by non-linear mixed-effects modeling (NONMEM), and 19 covariates were assessed. Goodness-of-fit plots, validation set and bootstrap analysis were conducted to confirm predictive performance of the final model. RESULTS: A total of 60 patients were included in the basic NONMEM data set for PPK modeling with a mean age of 10.2 years and body weight of 41.3 kg. The final pharmacokinetic model for the clearance of 25-hydroxy vitamin D included as covariates intake of vitamin D from foods (DD), hereditary predisposition to asthma (HPA) and the ratio of forced expiratory volume in first second and forced vital capacity (FEV1/FVC ratio). A validation set consisted of 14 separate patients with similar characteristics to the basic data set. The final model was confirmed by internal and external validation and also through goodness-of-fit plots. CONCLUSION: These results could be of help for individualization of vitamin D supplementation doses in this vulnerable population.
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A rating instrument for fear of hospitalisation.

AIMS AND OBJECTIVES: To develop and validate a reliable instrument that can measure fear of hospitalisation experienced by outpatients. BACKGROUND: After having a diagnosis established, some patients experience sense of fear, unpleasantness and embarrassment due to the possibility to be admitted to a hospital. Currently, there is no available instrument for measuring fear of hospitalisation. DESIGN: Cross-sectional study for assessing reliability and validity of a questionnaire. METHOD: The questionnaire with 17 items and answers according to the Likert scale was developed during two brainstorming sessions of the research team. Its reliability, validity and temporal stability were tested on the sample of 330 outpatients. The study was multicentric, involving patients from seven cities and three countries. RESULTS: Fear of hospitalisation scale showed satisfactory reliability, when rated both by the investigators (Cronbach's alpha .799) and by the patients themselves (Cronbach's alpha .760). It is temporally stable, and both divergent and convergent validity tests had good results. Factorial analysis revealed three domains: fear of being injured, trust to medical staff and fear of losing privacy or autonomy. CONCLUSIONS: This study developed new reliable and valid instrument for measuring fear of hospitalisation. RELEVANCE TO CLINICAL PRACTICE: Identification of patients with high level of fear of hospitalisation by this instrument should help clinicians to administer measures which may decrease fear and prevent avoidance of healthcare utilisation.