Use of lipid-lowering drugs in restricted health access settings: Results from the Trends in Drug Utilization During COVID-19 Pandemic in Turkey (PANDUTI-TR) study.

BACKGROUND: COVID-19 restrictions prompted changes in chronic disease management and lifestyle modifications, potentially altering cardiometabolic indicators and lipid-lowering pharmacotherapy patterns. We aimed to assess lipid-lowering drug (LLD) utilization trends during COVID-19 restrictions. METHODS: We obtained nationwide outpatient drug sales and prescribing data for 01.03.2018-31.12.2022 from IQVIA™ Turkey. We evaluated average monthly LLD consumption, their costs, and quarterly prescribing levels in three periods: "before restrictions" (BfR, 01.03.2018-31.03.2020), "during restrictions" (DuR, 01.04.2020-31.03.2022), and "after restrictions" (AfR, 01.04.2022-31.12.2022). Drug utilization was measured via "defined daily dose/1000 inhabitants/day" (DID) metric. RESULTS: LLD utilization increased from 25.4 ± 3.1 DID in BfR to 36.2 ± 6.8 DID in DuR (p < 0.001), and to 42.6 ± 5.3 DID in AfR (p < 0.001 vs. BfR). Statin consumption significantly rose from 22.0 ± 3.0 DID in BfR to 31.6 ± 6.3 DID in DuR (p < 0.001), and further to 37.6 ± 4.7 DID in AfR (p < 0.01 vs. DuR). High-intensity statin consumption elevated by 115.9% in AfR compared to baseline (p < 0.001). Prescribing of LLDs decreased from 12.5 ± 0.6 DID in BfR to 7.2 ± 1.2 DID in DuR (p < 0.001), later reached 13.6 ± 3.8 DID in AfR (p < 0.001 vs. DuR), with prescribing for ongoing users following similar trend. Expenditure on LLDs increased from €8.4 m ± 0.9 m in BfR to €11.4 m ± 2.0 m in DuR (p < 0.001) and to €12.8 m ± 1.9 m in AfR (p < 0.001 vs. BfR). CONCLUSIONS: This study revealed a surge in consumption of LLDs in Turkey following the onset of the COVID-19 pandemic. This rise might be related to practices facilitating drug access, in addition to potentially greater adherence, or the necessity for more intense pharmacotherapy due to elevated cardiovascular risk.

Favipiravir does not appear to be a major teratogen: Case series from Türkiye.

INTRODUCTION: Favipiravir has gained attention during the Coronavirus Disease-2019 pandemic due to its potential antiviral effect against Severe Acute Respiratory Syndrome Coronavirus-2. Favipiravir has been identified as a teratogen in animal studies, but there is limited human data. We aimed to evaluate the pregnancy outcomes of women exposed to favipiravir during the pandemic. MATERIAL AND METHODS: Pregnant women who were exposed to favipiravir and applied to Marmara University School of Medicine Medical Pharmacology Outpatient Clinic Teratology Information Service between December 2020-September 2021 are included in the study. The demographic information, medical and obstetric histories of patients were acquired during admission, the outcomes of the pregnancies and the characteristics of the infants were gathered by regular phone calls. The infants whose parents consented were evaluated by a pediatrician for general well-being and congenital anomalies. RESULTS: 22 pregnant women were included in this study. 81.8 % received the recommended favipiravir dose (8000 mg in 5 days), in the first trimester. Two patients were lost to follow-up, there was one elective termination and 19 live births. Congenital anomalies were found in 2 infants, one of whom had 9q34 duplication syndrome. Except for these, all newborns examined by the pediatrician were healthy. DISCUSSION: Within a limited case series, a subset of the infants exposed to favipiravir prenatally were followed up to 1 year of age. Two infants exhibited congenital malformations that cannot be directly linked to favipiravir due to confounding variables. Considering the limited data published, favipiravir does not appear to be a major teratogen.

Comparison of primary care prescriptions for old and very old hypertensive patients.

BACKGROUND: Elderly and very elderly individuals might be subject to different approaches for the treatment of hypertension. We aimed to compare drug utilization in hypertensive old patients and very old patients in primary care, along with the evaluation of potentially inappropriate drug prescribing. METHODS: In this cross-sectional study, we compared prescriptions of 65-79-year-old (old patient prescriptions [OPP], n = 433,988) vs. ≥80-year-old (very old patient prescriptions [VOPP], n = 134,079) with "essential hypertension" diagnosis, issued by 3:1 systematically-sampled primary care physicians (n = 1431) in Istanbul throughout 2016. Drug utilization patterns and distribution of antihypertensives based on drug class and combination status were evaluated. Frequency of potentially inappropriate drugs per Beers Criteria were identified and compared. RESULTS: Antihypertensive monotherapy practice was less common in OPP than VOPP (43.3% vs. 45.3%; p < 0.001). In both groups,the most commonly prescribed drugs were beta-blockers for monotherapy (37.4% vs. 33.1%, p < 0.001) and thiazide diuretics for combined therapy (69.8% vs. 67.4%, p < 0.001). Metoprolol was the most commonly prescribed antihypertensive both in OPP and VOPP (15.3% vs. 14.8%). Furosemide was ranked 10th in OPP and 3rd in VOPP (2.7% vs. 5.5%). Cardiovascular system drugs were the most commonly encountered potentially inappropriate medications in both groups (263.9 vs. 283.4 per 10,000 prescriptions, p = 0.004). Regarding antihypertensive drugs, 2.2% of those in OPP and 2.4% of those in VOPP were identified as potentially inappropriate (p = 0.002). DISCUSSION: Prescribing preferences to old and very old patients mostly showed slight differences. Almost half of prescriptions comprising antihypertensive monotherapy might imply hesitancy to prescribe combinations. Overuse of risky drugs such as furosemide in both groups, especially in the very elderly, requires more attention.

Supratherapeutic utilization of paracetamol versus ibuprofen among <12-year-old children in primary care in Istanbul.

BACKGROUND: Paracetamol and ibuprofen are the most preferred analgesics for pain and fever management in children. Prescribing of these drugs in supratherapeutic doses may predispose to their toxicity. We aimed to compare prescribing patterns and potential overdosing of paracetamol and ibuprofen in primary care for <12-year-old children. METHODS: We analysed paracetamol- and ibuprofen-containing prescriptions (PCPs, n = 173,575 and ICPs, n = 145,655) of 1- to 11-year-old children, issued by 3:1 systematically sampled primary care physicians (n = 1,431) in Istanbul during 2016. We compared drug use parameters and prescriptions surpassing daily and single-use dose limits for paracetamol and ibuprofen. RESULTS: We identified that 29.9% of PCPs and 20.8% of ICPs were generated for those aged 1-2 years. Concomitant analgesic use was higher in ICPs than in PCPs (15.1% vs. 12.8%). We found that 4.4% of PCPs and 3.1% of ICPs exceeded maximum daily dose limit of paracetamol and ibuprofen, respectively (P < 0.001). This was more common in girls (5.1% and 3.3%, respectively) and at 1 year of age in both groups (9.2% and 8.5%, respectively). Single-use supratherapeutic dosing was encountered in 16.5% of PCPs and 13.2% of ICPs (P < 0.001, pessimistic model) and in 8.6% of PCPs and 10.6% of ICPs (P < 0.001, optimistic model). CONCLUSIONS: Paracetamol and ibuprofen were generally used in primary care for similar clinical conditions with subtle differences. However, more pronounced in younger children and girls, potential overdosing seems to be more practiced for paracetamol than ibuprofen both in terms of maximal daily and single-use setting.

The association of chiral characteristic with drug withdrawal due to safety: A comparative analysis.

AIMS: Chirality of drugs might be associated with safety issues through pharmacokinetic or pharmacodynamic variations, interactions, or direct toxicological responses. We aimed to compare chiral status of the available drugs to that of drugs withdrawn due to adverse drug reactions (ADRs). METHODS: We searched the literature regarding withdrawn drugs due to safety-related issues (n = 391) to compare them with all available small-molecule drugs (n = 1633). We examined their chiral status and assigned as achiral compound, chiral mixture or pure enantiomer. We compared the mean survival (i.e., nonwithdrawal) time and withdrawal rates of drugs by their chirality, with further stratification by the launch year, ATC-1 (Anatomical Therapeutic Chemical) level and ADR. RESULTS: We identified higher withdrawal rate in achiral drugs (hazard ratio 2.1, 95% CI: 1.6-2.7) and chiral mixtures (hazard ratio 2.6, 95% CI: 1.9-3.5) compared to that in pure enantiomers. Pure enantiomers had the longest mean survival time (62.4 ± 0.8 years), followed by achiral drugs (55.4 ± 0.9 years, P < .01) and chiral mixtures (52.4 ± 1.4 years, P < .01). Pure enantiomers had higher survival rates than chiral mixtures if launched before 1941 (P = .02), in 1961-1980 (P < .001) or 1981-2000 (P < .001). Pure enantiomers had lower withdrawal rate (18.2%) vs. chiral mixtures (35.1%, P = .02) in nervous system drugs. Pure enantiomers had lower withdrawal rate than chiral mixtures in hepatotoxic (P < .01) and cardiovascular ADRs (P < .01). CONCLUSION: Our study showed lower likelihood of withdrawal for pure enantiomers compared to that in chiral mixtures and achiral drugs, which was more remarkable for those launched in certain time periods and several ADRs, including hepatotoxicity and cardiovascular toxicity.

Evaluation of health-related knowledge, attitudes, and behaviors of undergraduate students by cardiovascular risk factors.

AIM: To determine the presence of cardiovascular (CV) risk (CVR) factors in university students and evaluate how these factors are affected from the knowledge, attitudes, and habits of the individuals regarding healthy lifestyle. BACKGROUND: Starting from early ages, lifestyle habits such as lack of physical activity, unhealthy eating, and inappropriate drug use increase CV and metabolic risks of individuals. METHODS: In April-May 2018, sociodemographic characteristics of 770 undergraduate students, in addition to their knowledge, attitudes, and habits regarding their nutrition and physical activity status were obtained through face-to-face questionnaires. CVR factors were determined according to blood pressure, blood glucose, total cholesterol levels, and anthropometric measurements. Collected data were compared by CVR factor presence (CV[+] or CV[-]) in students. FINDINGS: The mean age of the participants was 22.3 ± 2.6 years. 59.6% were female and 71.5% were students of non-health sciences. In total, 274 individuals (35.9%) belonged to CV(+) group (mean risk number: 1.3 ± 0.5) with higher frequency in males (42.1% versus 31.6%, P < 0.05). The most common CVR factors were smoking (20.6%), high total cholesterol (7.5%), and hypertension/high blood pressure (6.0%). 15.5% of the participants regularly used at least one drug/non-pharmaceutical product. 11.3% complied the Mediterranean diet well. 21.9% of CV(+) stated consuming fast food at lunch compared to 14.3% of CV(-) (P < 0.05). 44.6% stated exercising below the CV-protective level. CONCLUSIONS: This study showed one-third of university students was at CVR, independent of their sociodemographic characteristics. Furthermore, the students appear to perform below expectations in terms of nutrition and physical activity. Extensive additional measures are needed to encourage young individuals for healthy nutritional and physical activity habits.

Evaluation of injectable metamizole utilization in children and adults in primary care.

OBJECTIVE: Use of injectable metamizole in the outpatient setting is controversial due to safety concerns. We aimed to compare injectable metamizole prescribing patterns for children and adults with further evaluation of nationwide metamizole consumption trend. MATERIALS AND METHODS: In this retrospective cross-sectional study, 100 injectable drug-containing prescriptions written in each month of 2010 in 32 provinces of Turkey were selected. Drug utilization patterns on injectable metamizole-containing prescriptions (n = 1,270) were analyzed and compared by "pediatric" and "adult" groups. Additionally, nationwide outpatient consumption data from 2010 to 2018 were obtained, and the utilization trend was examined. RESULTS: Children received 12.4% of injectable metamizole-containing prescriptions. Male predominance was observed in children (62.7%), as opposed to female predominance in adults (55.2%, p < 0.05). The most frequent diagnoses were "acute tonsillopharyngitis" and "acute bronchitis" in both groups. Single-diagnosis prescriptions constituted 79.1% of the pediatric group and 53.1% of the adult group (p < 0.05). Diagnoses, drugs, and injectable analgesics per prescription were significantly higher in adults (1.68 ± 0.86, 3.45 ± 0.90, and 1.06 ± 0.23, respectively) than in children (1.22 ± 0.43, 3.25 ± 0.88, and 1.00, respectively) (p < 0.05). The percentage of prescriptions containing injectable antibiotics was higher in children (83.6%) than in adults (64.9%). Outpatient injectable metamizole consumption showed a decreasing trend in 2010 - 2018. CONCLUSION: Despite recent downward trend, prescribing of injectable metamizole in primary care was considerably prevalent. This study, which highlights fundamental differences among metamizole utilization patterns in children and adults, addresses the inadequacy of rational use of the drug in terms of preferred indications and accompanying drugs.

Obestatin improves oxidative brain damage and memory dysfunction in rats induced with an epileptic seizure.

Obestatin was shown to alleviate renal, gastrointestinal and haemorrhage-induced brain injury in rats. In order to investigate the neuroprotective effects of obestatin on seizure-induced oxidative brain injury, an epileptic seizure was induced with a single intraperitoneal (i.p.) dose of pentylenetetrazole (PTZ, 45mg/kg) in male Wistar rats. Thirty minutes before the PTZ injection, rats were treated with either saline or obestatin (1µg/kg, i.p.). Seizure was video-taped and then evaluated by using Racine's scoring (0-5). For the assessment of memory function, passive-avoidance test was performed before seizure induction, which was repeated on the 3rd day of seizure. The rats were decapitated at the 24th or 72nd hour of seizures and brain tissues were obtained for histopathological examination and for measuring levels of malondialdehyde (MDA), glutathione (GSH), reactive oxygen radicals and myeloperoxidase (MPO) activity. Obestatin treatment reduced the average seizure score, decreased the occurrence and duration of generalized tonic-clonic seizures, presenting with a shorter latency to their onset. Increased lipid peroxidation and enhanced generation of oxygen-derived radicals detected at the post-seizure 72nd h were suppressed by the consecutive treatments of obestatin, but no changes were observed by the single obestatin treatment in the 24-h seizure group. Neuronal damage and increased GFAP immunoreactivity, observed in the hippocampal areas and cortex of PTZ-induced rats were alleviated in 3-day obestatin-treated PTZ group. PTZ-induced memory dysfunction was significantly improved in obestatin-treated PTZ group as compared to saline-treated rats. The present data indicate that obestatin ameliorated the severity of PTZ-induced seizures, improved memory dysfunction and reduced neuronal damage by limiting oxidative damage.