Compartmental modeling for pandemic data analysis: The gap between statistics and models.

A scrutiny analysis of the COVID-19 data is required to get insights into effective strategies for pandemic control. However, there is a gap between official data and methods used to assess the effectiveness of the potential measures, which was partly addressed in an editorial-letter-type discussion on the impact of the COVID-19 passport in Lithuania. The therein-applied descriptive statistics method provides only limited evidence, while detailed analysis requires more sensitive and reliable methods. In this regard, this paper advocates a maximum likelihood compartmental modeling approach, which provides the flexibility to raise various hypotheses about infection, recovery, and mortality dynamics and to find the most likely answers given the data. Our paper is based on COVID-19 deaths, which are more reliable and essential than infection cases. It should also be noted that officially collected data are unsuitable for in-depth analyses, including compartmental modeling, as they do not capture important information. Overall, this paper does not aim to solve the underlying problems completely but rather stimulate a discussion.

Over-Prescription of the Imidazoline Receptor Agonists: Evidence for Restriction of the Therapeutic Indication.

BACKGROUND: Major antihypertensive drug classes (but not Imidazoline Receptor Agonists) have been demonstrated to reduce cardiovascular morbidity and mortality. In 2017, Latvia and Lithuania had the highest cardiovascular mortality among the Eastern, Central, Northern, and Western Member States of the European Union (EU). Cardiovascular mortality in Estonia is much lower than in Lithuania and Latvia. OBJECTIVE: To evaluate the consumption of Imidazoline Receptor Agonists in the Baltic States and its potential implications. MATERIALS AND METHODS: The study included data on the sales of Imidazoline Receptor Agonists in Lithuania, Latvia, and Estonia; the marketing authorization databases of the competent authorities; the guidelines on the treatment of hypertension, and the reimbursement conditions. RESULTS: The study showed a very high consumption of the Imidazoline Receptor Agonists in Lithuania and Latvia. From 2016 to 2019, the average consumption of Imidazoline Receptor Agonists in Lithuania was 15.5 times higher than in Estonia; in Latvia, it was 8.9 times higher than in Estonia. The guidelines recommend the use of the Imidazoline Receptors Agonists as one of the last options in hypertension therapy, but the marketing authorizations do not restrict their line of therapy. CONCLUSIONS: Consumption of IRAs in Lithuania and Latvia is very high. The authorized use of the IRAs in the EU Member States is not in line with the guidelines on the management of arterial hypertension and therefore patients might be deprived of therapies that reduce the cardiovascular risk. The drug regulatory authorities of the EU should review the data on the safety and efficacy of the IRAs and restrict their therapeutic indications if necessary.

Off-Label Use of Antipsychotic Agents in Dementia: Evidence for the Revision of the Reimbursement Policy.

BACKGROUND: Harmonized requirements apply for the marketing authorization of medicinal products in the EU Member States. On the contrary, the national legislations on the drug reimbursement are not harmonized. The aim of this study was to find out if they are robust enough to ensure high standards of public health protection with focus on the symptomatic treatment of dementia in the elderly. METHODS: A computerized search of authorized therapeutic indications of haloperidol and trihexyphenidyl in the national databases of 8 EU member states and an analysis of the national legislation on reimbursement policies in Lithuania and Latvia was performed. RESULTS: There is a discrepancy in the decisions on the marketing authorization vs the reimbursement in Lithuania and Latvia (reimbursement of haloperidol and trihexyphenidyl for the off-label treatment of dementia). CONCLUSIONS: National legislation on the drug reimbursement in Lithuania and Latvia does not provide safeguards for public health at the same level as the marketing authorization does. Absence of a revision of former decisions in the light of new evidence is a critical weakness of the drug reimbursement in Lithuania and Latvia. Reimbursement for the off-label indications may pose a risk to public health.

Cisplatin increases urinary sodium excretion in rats: gender-related differences.

OBJECTIVE. There are well-documented reports of cisplatin-associated hyponatremia in the literature, but there are no data on gender-dependent differences. The aim of the present study was to define characteristics of 24-hour urinary sodium excretion in young adult Wistar rats of both genders and to evaluate the gender-related effect of cisplatin. MATERIALS AND METHODS. Twelve control Wistar rats (6 males and 6 females) and 12 cisplatin-treated Wistar rats (6 males and 6 females) after a single and repeated injection of cisplatin (once a day for 3 days) at a dose of 2.5 mg/kg body weight into the caudal vein were examined. The experiment was carried out by measuring 24-h urinary sodium, potassium, chloride, magnesium, creatinine excretion and pH in the urine of age-matched male and female rats. RESULTS. The 24-h urinary sodium excretion, sodium/chloride ratio, and diuresis showed no gender-related differences in control rats. After a single administration of 2.5 mg/kg cisplatin, 24-h urinary sodium excretion was not significantly higher in cisplatin-treated rats than in gender-matched controls. After repeated cisplatin administration, 24-h urinary sodium excretion was significantly higher in cisplatin-treated male rats as compared to matched controls (P<0.05). No such effect was found in cisplatin-treated female rats. CONCLUSION. The study data show that cisplatin enhances urinary sodium excretion in male but not in female rats. The mechanism of such a gender-related effect is not yet clear. Further investigations are necessary to elucidate the mechanism of this pharmacological effect of cisplatin.

Analysis of antidepressant prescribing tendencies in Lithuania in 2003-2004.

Depression is one of the leading causes of disability worldwide, affecting 121 million people in whole world. In many developed countries, the number of prescriptions for antidepressants increased steeply during the 1990s. The objective of the present study was to evaluate the antidepressant prescribing patterns in all regions of Lithuania during 2003-2004, to analyze the use within different antidepressant groups, and to examine trends in age- and gender-specific antidepressant use. Antidepressants were classified into three groups according to Anatomic Therapeutic Chemical (ATC) Classification specifying the defined daily doses. The results of our study show an increase in the use of reimbursed antidepressants except tricyclic in 2004 when compared to 2003. Increase in the use of selective serotonin reuptake inhibitors and other nontricyclic antidepressants is probably related to their better tolerability, improved risk-benefit ratio, and less toxicity in overdose. There was no increase in the percentage of consumed selective serotonin reuptake inhibitors in elderly patients when compared with younger ones, despite elderly patients are most likely to benefit from reduced sedation, less antimuscarinic and less cardiac toxicity of selective serotonin reuptake inhibitors. The prevalence of the antidepressant use is the highest among middle-aged people (40-59 years), while the young (under 20) and elderly (older than 70) patients receive mostly selective serotonin reuptake inhibitors. Additional studies should be carried out in order to assess drug-prescribing patterns in accordance with the guidelines of depression treatment in Lithuania considering diagnosis, dosage, and duration of treatment.

[Breastfeeding and medications]. / Zindymas ir medikamentai.

Breastfeeding is the most healthful method of feeding neonates and infants. In 2001 about 98% of new mothers in Lithuania started breastfeeding their neonates. One-third of nursing women (34%) discontinued breastfeeding at the time when infant reached the age of 3 months. About 56% of women breastfed their infants longer than 4 months. Only 3-6% of nursing women discontinued breastfeeding after the fourth month. Discontinuation of breastfeeding in 21-23% of all cases was directly or indirectly associated with use of medications. Such data suggest that there is a lack of information often leading physicians to advise mothers to discontinue breastfeeding because of medication use. The aim of this article was to survey the situation about classification of drugs used during breastfeeding and factors influencing drug transfer into milk in order to give more information for physician concerning the use of medication during breastfeeding. In this review, a short description of main pharmacokinetic characteristics, influencing drug transfer into milk; information on the classification of drugs used during breastfeeding; some considerations on drug safety and possible adverse effects of medications on breastfed infant; the list of drugs preferred for nursing women are presented.

[Antipsychotic agents and pharmacotherapy of psychoses]. / Antipsichoziniai vaistai ir psichoziu farmakoterapija.

Antipsychotic drugs have been used clinically for approximately 50 years. Reserpine and chlorpromazine were first drugs found be useful in schizophrenia. The term "antipsychotic" is used to describe a group of drugs that has been used mainly for treating of schizophrenia, but also is effective in some other psychoses and agitated states. The dopamine hypothesis is the most fully developed of several hypothesis and is the basis for rational drug therapy. However, the dopamine hypothesis is far from complete. Typical antipsychotic drugs have a wide spectrum of central nervous system, autonomic and endocrine effects. The most recently introduced antipsychotics are at least as potent in inhibiting 5-HT receptors as they are in inhibiting D receptors. A rational choice of antipsychotic drugs may be based on differences between chemical structures and pharmacological differences. No basis exists for choosing drugs for the use against selected target symptoms, as there is no evidence of specificity in their effects.