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 We aimed to compare chiral status of the available drugs to that of drugs withdrawn due to adverse drug reactions (ADRs). METHODS: We searched the literature regarding withdrawn drugs due to safety-related issues (n = 391) to compare them with all available small-molecule drugs (n = 1633).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.

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.

Association of arbitrary prescribing behavior to costly drug expenditures: a pharmacoeconomic study in primary care.

BACKGROUND: We aimed to examine the cost-related prescribing performance of primary care physicians who had a higher versus lower tendency of arbitrary prescribing. METHODS: In this cross-sectional study, we evaluated the prescriptions of primary care physicians in Istanbul, collected with 3:1 systematic sampling. We determined higher versus lower arbitrary prescribing by the physician's degree of writing the solo diagnosis of "Z00- General examination without diagnosis/complaint": those for whom such prescriptions constituted >5% were classified as Group A and those with them at <0.5% as Group B. We compared these two groups by the total and disease-specific drug costs per prescription they produced for 10 frequently encountered indications. RESULTS: The median cost of disease-specific medication for all diagnoses in Group A and Group B, except anemia, was equal. In upper respiratory tract infections (URTIs), hypertension, anemia, diabetes, and conjunctivitis, the mean prescription costs of Group A were significantly higher than those of Group B (P < .001, P < .001, P = .009, P = .007, and P < .001, respectively), whereas disease-specific drug costs per prescription were similar (P > .05 in all diagnoses). In myalgia, Group A had lower cost per prescription (P < .001) and higher analgesic costs per prescription (P < .001) compared to those in Group B. We found significantly higher disease-specific drug cost share in Group B for URTIs (antibiotic), gastroesophageal reflux disease (gastric acid-suppressant), hypertension (antihypertensive), anemia (iron preparations), diabetes (antidiabetic), depression (antidepressant), and conjunctivitis (corticosteroid) than those in Group A (P < .001 for each). CONCLUSIONS: Our study showed that physicians who had a higher tendency of prescribing for no clear indication are also more likely to produce costly prescriptions.

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.

Utilization trend of gastric acid-suppressing agents in relation to analgesics.

BACKGROUND: Controversies exist about excessive use of gastric acid-suppressing agents or lack of adequate indications, especially when co-prescribed with analgesics for gastroprotection. We aimed to analyze the nationwide trend of gastric acid-suppressing agents and analgesics. METHODS: We obtained nationwide consumption data of analgesics (nonsteroidal anti-inflammatory drugs [NSAIDs], opioids, others) and gastric acid-suppressing agents (proton pump inhibitors [PPI] and histamine-2 receptor antagonists [H2RAs]) between years of 2014-2018 from IQVIA Turkey. Drug utilization was measured by defined daily dose (DDD)/1000 inhabitants/day (DID) unit. Drug sales data were further used to test the correlation of PPIs and H2RAs to analgesics. RESULTS: During the study period, analgesic utilization increased from 65.7 to 67.4 DID. NSAIDs constituted 82.7%-84.9% of all analgesic utilization. The consumption of NSAIDs increased by 3.1%, and the most commonly consumed analgesic was diclofenac (18.5 ± 1.5 DID), constituting 25.4%-29.0% of all analgesics. PPI utilization was found to regularly raise from 52.1 DID in 2014 to 72.0 DID in 2018 with an overall increment of 38.2%. Use of H2RAs was found to increase from 11.4 DID in 2014 to 14.0 DID in 2018. The physician visit-adjusted utilization of both antirheumatic NSAIDs and non-antirheumatic analgesics showed significantly moderate-strong positive correlations with PPIs (r: 0.63, 0.48-0.76 and r: 0.63, 0.47-0.75, respectively) and H2RAs (r: 0.61, 0.44-0.73 and r: 0.57, 0.41-0.71, respectively). CONCLUSION: The utilization trend exhibited a dramatic increase of the gastric acid-suppressing agents -more pronounced for PPIs, with a modest increase in analgesics. Excessive utilization of PPIs does not seem to imply a tendency toward only NSAID-related gastroprotection.

Knowledge, opinions and attitudes of primary care physicians about generic drugs: a cross-sectional study.

BACKGROUND: Generic drug (GD) use is affected by many factors, including physicians' approach. OBJECTIVE: This study aimed to investigate the knowledge, opinions and attitudes of primary care physicians (PCPs) about GDs and potentially associated factors. METHODS: An adequately representative sample (n = 354) of PCPs was determined via stratified and simple random sample selection method in this descriptive, cross-sectional study. The research data were collected through a face-to-face 40-item survey, where the knowledge, opinions and attitudes about GDs were questioned. The prescribing percentage of GDs overall was also examined. RESULTS: The survey was completed by 305 PCPs (mean age: 49.2 ± 7.9 years; 57.4% male). The rate of correct responses about GDs was 67.6% for basic knowledge and 46.6% for the development process. The percentages of PCPs who declared that GDs were 'less efficacious', 'of lower quality' and 'less safe' than original drugs were 65.2%, 53.4% and 35.4%, respectively. More than half (60.3%) of the PCPs declared not to pay attention to whether the drug is generic while prescribing. It was observed that, as the knowledge level of the physicians increased, negative opinions and prescribing attitudes regarding the effectiveness, quality and safety of the GDs decreased. The rate of GD prescribing (51.6%) in Izmir was lower than the rest of the country (54.6%; P < 0.001). CONCLUSION: This study shows that the knowledge of PCPs about GDs is generally inadequate, which reflects negatively on their opinions and attitudes regarding the use of GDs. Educational activities can help establish awareness that GDs can be used without doubt of their effectiveness, quality and safety.

Generic drug prescribing in primary care: A nationwide analysis.

INTRODUCTION: Dissemination of generic drug (GD) use could provide significant savings on drug expenditures and contribute to the long-term sustainability of healthcare. We aimed to exhibit the nationwide trend of GD use in primary care and investigate potentially relevant drug and patient factors. METHODS: Prescriptions written by primary care physicians in Turkey between 2013 and 2016 were analysed using the National Prescribing Information System. We determined the ratio of GD prescriptions with all prescriptions in terms of quantity and cost. In addition, we analysed the use of GD in terms of demographic characteristics of the patients, the most frequently prescribed preparations and frequent indications. RESULTS: In the 4-year period, we identified 518,335,821 prescriptions, those with at least one GD constituted 54.0% (n = 786,972,813) with a total cost-share of 36.9%-37.8%. GD use was the highest in 2016 (54.4%) and lowest in 2014 (53.6%). GD prescribing was higher in women than men every year (P < .001 for each), with the highest difference in 2016 as 54.7% vs 54.0%. GD utilisation decreased as the age group increased, which was 64.0%-64.5% in <18-year-old group and 46.0%-47.1% in ≥75-year-old group. Among the top ten encountered indications, the highest and lowest GD prescribing was detected in acute tonsillitis (68.1%) and hypertension (33.9%). Metformin had the highest percentage of GD prescribing (96.1%-97.7%), whereas esomeprazole showed the lowest GD prescribing (4.5%-14.8%) among the most frequently used preparations in primary care. CONCLUSION: This study shows a modest upward trend of GD utilisation in primary care, though its share appears to be lower than expected. GD use revealed a consistent reduction towards older age groups. GDs were more likely to be prescribed for acute conditions, particularly infectious diseases.

Utilization of biotechnological drugs in rare diseases requiring the use of off-label drugs in children in Turkey

Background/aim: Pediatric patients, especially those with rare diseases, represent a population that has a high tendency towards off- label drug use (OLDU) and needs a more careful practice of pharmacotherapy than in adults. We aimed to investigate biotechnological drug use in children with rare diseases requiring OLDU. Materials and methods: This retrospective study examined all single-diagnosed OLDU applications (n = 5792) for 4992 children (<18- year) in Turkey. Applications of rare diseases were selected, and their descriptive characteristics were examined, including demographic features of patients, biotechnological drug utilization status, and disease categories. The off-label statuses of the drugs at the end of 2020 were also examined. Results: In total, 77.7% (n = 4501) of OLDU applications were made for rare diseases. Biotechnological drug use was higher in rare disease applications than in nonrare diseases (37.9% vs. 19.2%, respectively; p < 0.0001). Canakinumab was the top applied biotechnological drug (73.2%). Compared to that in small-molecule drugs, the mean age of patients was higher in biotechnological drug-containing applications (8.1 ± 5.3 vs. 9.7 ± 4.9, respectively; p < 0.0001). Biotechnological drug use was higher in nonneoplastic rare diseases (40.3%) than in neoplastic rare diseases (26.4%), (p < 0.0001). At the end of 2020, the approval status of the off-label indications covered in 2016 was significantly higher for rare (24.4%) vs. nonrare (5.2%, p < 0.0001) diseases and for biotechnological (32.3%) vs. small- molecule (13.9%, p < 0.0001) drugs. In total, 87.7% of the drugs would have to be still used in the off-label setting at the end of 2020. Conclusion: It was seen that more than three-quarters of the pediatric OLDU applications are for rare diseases, and the need for biotechnological OLDU in this group is almost 2-fold of small-molecule drug use. While further projected findings imply a higher approval tendency for rare diseases and biotechnological drugs, there seems to be more room for improvement for pediatric drug use.

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.

Baseline characteristics predicting clinical outcomes and serious adverse events in middle-aged hypertensive women: a subanalysis of the SPRINT in women aged <65 years

Background/aim: The predictability of clinical outcomes in hypertension in specific patient groups, especially underrepresented populations is the key to rational treatment. This study aimed to investigate the impact of baseline characteristics of <65-year-old hypertensive women with an increased risk of cardiovascular events, managed with standard- or intensive-approach, on their clinical outcomes and serious adverse events (SAEs). Materials and methods: Baseline characteristics of <65-year-old hypertensive women (n = 1247) in SPRINT, a multicenter randomized trial to compare standard and intensive antihypertensive treatment, were analyzed with Cox-regression method to determine potential predictors of the clinical outcomes and SAEs. The primary outcome was the composite of myocardial infarction (MI), non-MI acute coronary syndrome, stroke, heart failure, or cardiovascular death. Results: The primary outcome occurred in 3.1% and SAEs in 27.6% of the population. The treatment groups were similar in terms of the primary outcome, SAEs, or their individual components. The primary outcome occurred significantly more in current smokers vs. nonsmokers (HR: 2.85, 95% CI: 1.34­6.09). The subjects who were on aspirin in the intensive-group were significantly more likely to develop the primary outcome (HR: 3.17, 95% CI: 1.23-8.19) and MI (HR: 10.15, 95% CI: 1.19-86.88) compared with those not using aspirin. The risk of overall SAEs was significantly higher in blacks vs. nonblacks (HR: 1.27, 95% CI: 1.01-1.58), in current-smokers vs. nonsmokers (HR: 1.59, 95% CI: 1.23-2.05), and those with vs. without chronic kidney disease (CKD), (HR: 1.38, 95% CI: 1.08-1.77). The likelihood of SAEs significantly increased with age (HR: 1.04, 95% CI: 1.01-1.07). Conclusion: Smoking, aspirin, CKD, black race, and age seemed as important baseline characteristics in follow-up of <65-year-old hypertensive women, also depending on therapeutic strategy. Clinicians are expected to consider these critical parameters for effective antihypertensive management that promotes better outcomes in this middle-aged female population.

Relative risk of tuberculosis in patients with rheumatic diseases managed with anti-tumour necrosis factor-alpha therapy: A nationwide cohort study.

WHAT IS KNOWN AND OBJECTIVE: Anti-tumour necrosis factor-alpha (anti-TNF-α) therapy is known to raise the risk of granulomatous infections, leading to development of risk management strategies at national or global level. This study aimed to determine the relative risk (RR) of tuberculosis (TB) due to anti-TNF-α usage in patients with rheumatologic diseases (RDs) in a nationwide basis. METHOD: This retrospective cohort study included patients with rheumatoid arthritis (RA), ankylosing spondylitis, juvenile idiopathic arthritis or psoriatic arthritis (PsA) that treated with or without anti-TNF-α agents, as registered in the national prescription information system between years 2013 and 2015. Two-year RR of TB after anti-TNF-α therapy initiation was calculated in this RD population, including main subgroups. RESULTS AND DISCUSSION: The study cohort included 413 500 RD patients, where anti-TNF-α(+) arm (n = 2117) had mean age of 41.9 ± 13.4 years and male distribution of 54.3%. Four patients among anti-TNF-α users developed TB compared to 128 patients in anti-TNF-α-naïve group (189 vs 31 cases per 100 000 patients, respectively), yielding a 2-year RR of 6.07 (95% CI, 2.25-16.42) with an attributable risk of 0.16%. These RRs (95% CI), which were particularly pronounced, were 5.39 (1.69-7.17) in men, 6.12 (2.26-16.55) in adults, and 5.70 (1.41-23.08) in RA and 13.46 (1.58-114.40) in PsA patients. There was no difference between the anti-TNF-α users who developed and undeveloped TB regarding drug utilization characteristics, except significantly less immunosuppressive drug exposure in TB patients. WHAT IS NEW AND CONCLUSION: This study is the first prescription-based nationwide study to suggest an elevated RR of TB in a comparably younger population with a broad spectrum of RDs managed with any approved anti-TNF-α drug in Turkey.

Assessment of the association between drug disposal practices and drug use and storage behaviors.

OBJECTIVE: Keeping unnecessary drugs at home is a situation showing both causes and consequences of irrational use of medicine. This study aimed to evaluate the approaches of a company's employees regarding drug storage, use, and disposal. METHOD: This online-based descriptive study was held in a multi-centered private-sector company in a voluntary basis. The survey assessing participants' drug handling and storage behaviors was answered by 1121 employees from across eight provinces of Turkey in 2016. Main outcome measures were storage and disposal of unused/unwanted drugs at home in a rational way. RESULTS: The percentage of participants who declared that they keep unused/unwanted drugs at home was 28.0%. About one-third of participants disposed their unused/unwanted drugs via the "garbage, sink, toilet, etc.". Participants ≥30 years old and living with <4 household members significantly tended to bring their unused/unwanted drugs to the company's drug-box. Nearly half of all participants (46.5%) stated a recent change in their disposal behavior. The vast majority of participants (94.6%) who previously took drugs back to the company's drug-box stated that they either had, or would, help their contacts adopt such behaviors. These participants were also significantly less likely to dispose of drugs inappropriately, practice self-medication, be unaware of expired drugs at home, or fail to store drugs according to the labelling. CONCLUSION: While our findings showed that a substantial number of participants still had unused drugs at home and disposed of them inappropriately, it is understood that they started to exhibit more favorable behaviors in recent years.

Variation of antibiotic consumption and its correlated factors in Turkey.

BACKGROUND: Presentation of antibiotic utilization data by reliable and comparable analyses constitutes an important way of ensuring rational use of antibiotics. This study aimed to evaluate antibiotic consumption (AC) of Turkey by each city/region and to investigate any association of such consumption with socio-economic factors. METHOD: For 81 provinces and 12 regions in Turkey, AC data from IMS (Intercontinental Medical Statistics) in 2011 was analyzed in accordance with "ATC/DDD, DID" (Anatomical Therapeutic Chemical/Defined Daily Doses, DID = DDD/1000 inhabitants/day) methodology supported by World Health Organization. Association between provincial AC rates and socio-economic development index (SEDI)-2011 and between regional AC rates and some health indicators were analyzed. RESULTS: While provincial AC data of Turkey was detected to vary between 17.2 and 55.2 DID (Hakkari and Usak, respectively), regional AC ranged from 28.4 to 48.9 DID (Middle Eastern Anatolia and Western Anatolia, respectively). Mostly consumed antibiotic group among all regions were beta-lactamase inhibitor/penicillin combinations (range: 9.9-17.6 DID). SEDI and AC of each city showed positive correlation (rho = 0.683, p < 0.001). While regional AC was positively associated with percentage of 14-year-old population (p = 0.002) and pharmacist density (p < 0.001), it was negatively associated with physician density (p = 0.038). CONCLUSION: It is remarkable that Turkey, at both provincial and regional levels, exhibits important variations in AC, which is proportional to socio-economic status. Besides, the consumption is found to be closely associated with recognized critical factors of access to healthcare. These findings are expected to provide important insights to the activities promoting rational use of antibiotics.

Rational use of medicine in dentistry: do dentists prescribe antibiotics in appropriate indications?

PURPOSE: There are concerns regarding appropriate use of antibiotics in dentistry practice. Data on dental antibiotic prescribing patterns by dentists is relatively limited. This nationwide study aimed to examine dentists' antibiotic prescriptions in a diagnosis-based manner in Turkey. METHODS: This retrospective study on utilization of systemic antibiotics for dental problems was based on the national health data of the dentists obtained from Prescription Information System between January 2013 and August 2015. Only those prescriptions containing single diagnosis and at least one systemic antibiotic were included in the study. Antibiotic prescribing was compared by diagnoses and expertise of dentists. RESULTS: A total of 9,293,410 antibiotics were detected in 9,214,956 prescriptions that contained "single diagnosis and at least one antibiotic." The number of antibiotics per prescription was 1.01. "Periapical abscess without sinus" (28.1%), "dental examination" (20.7%), and "dental caries" (16.2%) were the three most common indications in which antibiotics were prescribed by dentists. While only 3.4% of antibiotics were prescribed upon the single and appropriate "cellulitis and abscess of mouth" diagnosis, the remaining 96.6% was prescribed for irrational/uncertain indications. Consistent in all diagnoses, "amoxicillin + enzyme inhibitor" (58.6%) was the mainly prescribed antibiotic. Analysis of the most preferred "amoxicillin + enzyme inhibitor" prescriptions by expertise of dentists showed significantly much higher prescription rates among Group A specialists and Group B specialists (67.0 and 67.8%, respectively) than those in unidentified dental practitioners (58.2%, p < 0.0001). CONCLUSIONS: This study showed that dentists prescribed antibiotics in an arbitrary and mostly unnecessary manner. In general, their antibiotic choices for examined diagnoses could be regarded as irrational. These results indicate the urgent need for improvement of rational antibiotic prescribing habits of dentists.

Drug utilization studies in Turkiye: A systematic review.

OBJECTIVE: Drug utilization studies (DUS) provide a framework for drug utilization at the national or targeted population level and important information on unmet medical needs, particularly in assessing the rationality of drug use. We aimed to systematically review DUS conducted in Turkiye. METHODS: We examined 162 DUS with an accessible full-text, published as "research articles" and conducted in Turkiye between 2000 and 2021 using medical records and prescription data. We included English or Turkish papers with English abstracts. We examined the scientific characteristics of the publications, source of the data, place/time of collection, research designs, and studied drug groups. RESULTS: We found that 79.6% of articles were in English, 45.1% were listed in SCI/SCIE, and 63.0% were on the WOS platform with 3.5 (interquartile range: 1-15) citations. The mean study period and publication time were 2.9±3.1 and 2.9±2.1 years, respectively. The highest number of studies (17.9%) were published in 2021 and (26.5%) were conducted nationwide. We identified that 93.8% of the studies had retrospective design, 67.8% were conducted in secondary/tertiary health-care institutions, and 54.9% used direct hospital data. We detected that 68.5% of the studies were conducted on the general population, 19.1% on adults, 12.4% on children, and 44.4% were antibiotic oriented. CONCLUSION: Our study showed that a significant portion of the DUS, the trend of which has gained momentum in recent years, was antibiotic focused and conducted with a retrospective design from hospital-based data collected on the general patient population. This situation points to the necessity of expanding the existing DUS range by effectively using the new advantages provided by medical record databases and conducting more DUS that can provide critical clues for specific patients and drug groups.

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.

Good versus poor prescribers: the comparison of prescribing competencies in primary care.

AIM: To compare the competencies of primary care physicians (PCPs) with poor and good prescribing performance in frequently encountered indications. BACKGROUND: Primary care centers are one of the mostly visited health facilities by the population for different health issues. METHODS: In this cross-sectional study, we analyzed 6 125 487 prescriptions generated by 1431 PCPs which were selected by systematic sampling in 2016 in Istanbul. We defined PCPs as poor prescriber (n = 227) or good prescriber (n = 210) in terms of their prescribing performance per WHO/INRUD criteria. We compared solo diagnosis prescriptions of these two groups in 'percentage of prescriptions in compliance with clinical guidelines' and also rational prescribing indicators. FINDINGS: Poor prescribers and good prescribers significantly differed in each of the prescribing indicators for their all solo diagnosis prescriptions. Hypertension had the highest difference of the average cost per encounter (Δ = 284.2%) between poor prescribers (US$43.99 ± 63.05) and good prescribers (US$11.45 ± 45.0), whereas headache had the highest difference between the groups in the percentage encounters with an antibiotic (14.9% vs. 1.5%). Detailed analysis of the prescribing performances showed significantly higher values of each WHO/INRUD indicators for all examined diagnoses. We found significantly higher percentages of guideline-compliant drugs in good prescribers compared to that in poor prescribers in hypertension (40.8% vs 34.8%), tonsillopharyngitis (57.9% vs 50.7%), and acute sinusitis (46.4% vs 43.6%). CONCLUSION: This study shows that the prescribing performances of PCPs are not rational enough in terms of drug selection and prescription content. Furthermore, even the physicians who have good prescribing practice appear as not satisfactorily rational in compliance with current pharmacotherapy competencies.

Comparison of pediatric antibiotic prescribing practice between low and high prescribers for children in primary care.

BACKGROUND: Antibiotic prescribing is more prevalent in children. Many factors influence this practice, including the burden of outpatient visits. We aimed to compare antibiotic prescribing for children by low prescribers (LP) and high prescribers (HP) in primary care. METHODS: We analyzed pediatric prescriptions in primary care in Istanbul. Among the physicians randomly selected by systematic sampling, those generating ≥1 pediatric prescription/day (n=1218) were defined as LP or HP when they belonged to the lowest (n=305) or highest (n=304) quartile of prescribing, respectively. The antibiotic prescribing characteristics of these groups were compared. RESULTS: We identified that 38.5% of the prescriptions written by physicians included antibiotics, significantly higher in HPs (38.8%) than in LPs (37.2%), (p=0.04). Among antibiotic-containing prescriptions, the mean number of drugs and boxes and the percentage of prescriptions containing injectable drugs/antibiotics were significantly higher in HPs compared to that in LPs. We detected that co-amoxiclav was the most frequently prescribed antibiotic in the LP and HP groups (61.1% and 48.3%, respectively). Stratification of antibiotics by their spectra showed that 11.2% were narrow, 79.8% were broad and 0.5% were ultra-broad-spectrum drugs. LPs were significantly more likely to prescribe broad-spectrum antibiotics (82.5%) than do HPs (78.9%,p < 0.001). CONCLUSIONS: Antibiotic prescribing remains excessive in pediatric primary care, slightly more marked in HPs. While HPs also tend to prescribe a higher number of overall and injectable drugs/antibiotics, broad-spectrum anti-biotherapy seems to be more practiced by LPs surprisingly. Both physician groups appeared to prefer either narrow- or broad-spectrum drugs without paying enough attention to their pharmacodynamic properties.

Evaluation of the pregnant women's approaches regarding drug utilization.

OBJECTIVE: Drug utilization habits of the pregnant are a critical aspect of rational use of the medicine (RUM). This study aimed to analyze the RUM related attitudes and the behaviors of women during their pregnancies. METHODS: The data were collected between May 2016-October 2016 by conducting surveys to 71 pregnant women admitted to the private and governmental hospitals in five districts of Northern Cyprus. The sociodemographic characteristics of the pregnant as well as their attitudes and behaviors concerning drug use were evaluated. RESULTS: The mean age and the gestational week of the patients was 29.7±4.3 years and 25.7±11.2 weeks, respectively. Planned pregnancies constituted 71.8% of all. The percentage of patients with an unplanned pregnancies who were using drugs at the time of the survey (25.0%) was lower than that in those with planned pregnancies (49.0%, p<0.05). Almost two-thirds (66.2%) of the women were exposed to a drug during pregnancy, mostly for "vitamin/mineral prophylaxis" (38.3%) and agents controlling nausea/vomiting (19.1%). Two out of eleven women (18.2%) were using folic acid when they learned about their pregnancy. One of the drugs used for the chronic disorder in the third trimester was acetylsalicylic acid (11.1%), a category D drug in this setting. Most of the patients stated that they frequently read the instructions (60.9%), "often" paying attention to side effects (56.5%). Considering some of the habits related to drug use, 8.7% and 10.9% of pregnant women declared that they sometimes "did not follow the instructions" and "dosage/duration of the drug usage", respectively. Seven patients (15.2%) declared that they did not consider side effects on the medication guide while more than half (56.5%) did it "often". Near one in five (19.6%) of the pregnant women stated that they hesitated about the drug usage due to teratogenicity risks. CONCLUSION: Our study highlights the drug utilization attitudes and behaviors of pregnant women during pregnancy in Northern Cyprus, indicating several shortcomings, including insufficient prenatal folic acid use, occasional use of risky drugs, and unsatisfactory medication guide handling. Available findings underline the necessity of education not only for patients but also for healthcare providers to disseminate RUM in pregnancy.