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.

Assessing effects of tamoxifen on tolerance, dependence, and glutamate and glutamine levels in frontal cortex and hippocampus in chronic morphine treatment.

Tamoxifen has been shown to reduce glutamate release from presynaptic glutamatergic nerves and reverse tolerance to morphine-induced respiratory depression. Changes in glutamatergic neurotransmission in the central nervous system contribute to morphine tolerance, dependence, and withdrawal. This study, therefore, evaluated effects of tamoxifen on development of analgesic tolerance and dependence, and brain glutamate and glutamine levels in chronic morphine administration. Mice implanted with placebo or morphine pellets were injected with tamoxifen (0.6-2 mg/kg) or vehicle twice daily for 3 days. Nociceptive response was evaluated in the hot plate and tail immersion tests, 4, 48 and 72 h post-implant, and following a challenge dose of morphine (10 mg/kg). Withdrawal signs were determined after naloxone (1 mg/kg) administration. Morphine increased nociceptive threshold which declined over time. At 72 h, acute morphine elicited tolerance to the analgesic effect in the hot plate test in vehicle or tamoxifen administered animals. In the tail immersion test, however, tolerance to morphine analgesia was observed in tamoxifen, but not vehicle, co-administration. Tamoxifen did not reduce withdrawal signs. In contrast to previous reports, glutamate and glutamine levels in the hippocampus and frontal cortex did not change in the morphine-vehicle group. Confirming previous findings, tamoxifen (2 mg/kg) decreased glutamate and glutamine concentrations in the hippocampus in animals with placebo pellets. Both doses of tamoxifen significantly changed glutamate and/or glutamine concentrations in both regions in morphine pellet implanted animals. These results suggest that tamoxifen has no effect on dependence but may facilitate tolerance development to the antinociception, possibly mediated at the spinal level, in chronic morphine administration.

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.

Evaluation of Stress Response in Middle-Aged Male Diabetic Hypertensive Patients.

CONTEXT: Stress triggers a cascade of reactions that alter the organism's dynamic steady state. There is a scarcity of interventional studies that show cortisol variability upon stress over time in groups of patients with chronic noncommunicable diseases and comorbidities. OBJECTIVE: We aimed to examine salivary cortisol changes in the cognitive stress response of patients with hypertension and diabetes mellitus (HT&DM) and patients with hypertension (HT) and to determine differences between them. METHODS: The study was conducted using a stress test of solving an arithmetic task in 62 patients with HT&DM and HT who were being treated in the outpatient clinic of the Medical Pharmacology and Clinical Pharmacology Department in Istanbul University, Istanbul Medical Faculty Hospital. RESULTS: There was no statistically significant difference between the HT&DM and HT groups for systolic blood pressure (SBP) and diastolic blood pressure (DBP) values (P = .331 and P = .058). When measured by repeated ANOVA, salivary cortisol level [F (1.842, 60) = 8.771, P < .0001], SBP [F (2.185, 60) = 12.080, P < .0001], DBP [F (2.793, 60) = 6.043, P = .001], and heart rate [F (2.073, 60) = 13.259, P < .0001] were statistically significant for the main effect (time), while the effect of the group × time interaction factor was statistically not significant (P = .773; P = .751; P = .713 and P = .506, respectively). CONCLUSION: The arithmetic problem-solving task used with the HT&DM and HT patients was useful as an acute stress test in the laboratory environment. There was no statistically significant difference for group × time interaction factor between the HT&DM and HT groups; however, the salivary cortisol and BP values increased significantly after acute stress within each group.

Evaluation of Risk Factors Associated With Antihypertensive Treatment Success Employing Data Mining Techniques.

OBJECTIVE: This study aimed to evaluate the effects of potential risk factors on antihypertensive treatment success. METHODS: Patients with hypertension who were treated with antihypertensive medications were included in this study. Data from the last visit were analyzed retrospectively for each patient. To evaluate the predictive models for antihypertensive treatment success, data mining algorithms (logistic regression, decision tree, random forest, and artificial neural network) using 5-fold cross-validation were applied. Additionally, study parameters between patients with controlled and uncontrolled hypertension were statistically compared and multiple regression analyses were conducted for secondary endpoints. RESULTS: The data of 592 patients were included in the analysis. The overall blood pressure control rate was 44%. The performance of random forest algorithm (accuracy = 97.46%, precision = 97.08%, F1 score = 97.04%) was slightly higher than other data mining algorithms including logistic regression (accuracy = 87.31%, precision = 86.21%, F1 score = 85.74%), decision tree (accuracy = 76.94%, precision = 70.64%, F1 score = 76.54%), and artificial neural network (accuracy = 86.47%, precision = 83.85%, F1 score = 84.86%). The top 5 important categorical variables (predictive correlation value) contributed the most to the prediction of antihypertensive treatment success were use of calcium channel blocker (-0.18), number of antihypertensive medications (0.18), female gender (0.10), alcohol use (-0.09) and attendance at regular follow up visits (0.09), respectively. The top 5 numerical variables contributed the most to the prediction of antihypertensive treatment success were blood urea nitrogen (-0.12), glucose (-0.12), hemoglobin A1c (-0.12), uric acid (-0.09) and creatinine (-0.07), respectively. According to the decision tree model; age, gender, regular attendance at follow-up visits, and diabetes status were identified as the most critical patterns for stratifying the patients. CONCLUSION: Data mining algorithms have the potential to produce predictive models for screening the antihypertensive treatment success. Further research on larger populations and longitudinal datasets are required to improve the models.

Efficacy of topical dexamethasone eye drops in preventing ocular inflammation and cystoid macular edema following uncomplicated cataract surgery with or without injection of a single dose perioperative subtenon triamcinolone acetonide.

PURPOSE: To evaluate the efficacy and safety of topical dexamethasone (DEX) eye drops in combination with a single perioperative subtenon triamcinolone acetonide (sTA) injection versus conventional topical DEX eye drops in the prevention of ocular inflammation and cystoid macular edema following cataract surgery. MATERIALS AND METHODS: Medical records of 245 eyes of 245 patients who underwent uncomplicated cataract surgery were analyzed in this retrospective controlled clinical study. Topical DEX eye drops were administered to 128 eyes routinely postoperatively, and 117 eyes were given a single dose of sTA (40 mg/ml) together with topical DEX eye drops for postoperative care. Postoperative topical antibiotic prophylaxis was applied to all eyes. The primary outcomes were anterior chamber (AC) cells and flare, central macular thickness (CMT), best corrected visual acuity (BCVA), and intraocular pressure (IOP) measurements on day 7, day 30, day 90, and day 180 following surgery. RESULTS: Although CMT increased in the DEX group, no increment was observed in the DEX + sTA treated group for all follow-up periods (on day 7 (+1.3 ± 18.6 and -8.7 ± 21.9 µm, p = 0.038), on day 30 (+20.5 ± 58.4 and -4.1 ± 25.2 µm, p = 0.009), on day 90 (+7.2 ± 19.9 and -5.7 ± 30.6 µm, p = 0.029), and on day 180 (+8.2 ± 22.6 and -6.4 ± 32.9 µm, p = 0.032)). There was no significant difference in terms of AC cells and flare between the two groups during the entire follow-up period (p > 0.05). Significant improvement in BCVA was observed in the DEX + sTA group at day 30 (p = 0.008). IOP differences were comparable, and both groups had high ocular tolerance. There were no severe adverse effects recorded. CONCLUSIONS: Topical DEX eye drops in combination with single dose perioperative injection of sTA have robust efficacy in preventing ocular inflammation and the development of cystoid macular edema following uncomplicated cataract surgery.

Long term results of three anti-vascular endothelial growth factor agents in pachychoroid neovasculopathy.

PURPOSE: To assess morphological changes and visual results in eyes with pachychoroid neovasculopathy (PNV) that underwent different intravitreal anti-vascular endothelial growth factor (VEGF) agents. MATERIALS AND METHODS: This is a retrospective, observational, comparative study that included 76 PNV eyes in 76 patients that were allocated to three groups according to the monotherapy injection procedure, as follows: the intravitreal bevacizumab (IVB) group, intravitreal ranibizumab (IVR) group, and intravitreal aflibercept (IVA) group. Central macular thickness (CMT), best-corrected visual acuity (BCVA), and subfoveal choroidal thickness (SFCT) were measured at baseline, after treatment 1st month, 3rd month, 6th month, and 12th month, and at the final post-treatment examination. RESULTS: Mean age of the patients was 57.31 ± 5.91 years (range: 34-67 years). The mean duration of follow-up was 31.50 ± 12.91 months (range: 13-60 months). The IVB group included 30 eyes, the IVR group included 22 eyes, and the IVA group included 24 eyes. There weren't any significant differences in BCVA changes between the groups at any post-baseline measurement time point. Although CMT did not change significantly in the IVB group from baseline to the final follow-up visit (baseline: 376.33 ± 86.31 µm; final visit: 340.80 ± 122.70 µm) (p = 0.172), CMT did change significantly in the IVA group (baseline: 383.41 ± 131.83 µm; final visit: 297.33 ± 103.81 µm) (p = 0.029) and IVR group (baseline: 379.18 ± 97.93 µm; final visit: 335.72 ± 111.45 µm) (p = 0.041). SFCT decreased significantly in the IVR and IVA groups (p = 0.015 and p < 0.001, respectively). The mean number of injections was 12.06 ± 4.72 (range: 6-20) in the IVB group, 11.81 ± 3.31(range: 7-17) in the IVR group, and 7.16 ± 3.15 (range: 4-13) in the IVA group (p = 0.004). CONCLUSION: All three anti-VEGFs were effective in terms of visual results in patients with PNV. Patients treated with IVA required fewer injections than those treated with IVB or IVR. Furthermore, IVR and IVA treatment significantly decreased SFCT, whereas IVB did not.

Early Effects of Low Molecular Weight Heparin Therapy with Soft-Mist Inhaler for COVID-19-Induced Hypoxemia: A Phase IIb Trial.

In COVID-19-induced acute respiratory distress syndrome, the lungs are incapable of filling with sufficient air, leading to hypoxemia that results in high mortality among hospitalized patients. In clinical trials, low-molecular-weight heparin was administered via a specially designed soft-mist inhaler device in an investigator initiated, single-center, open-label, phase-IIb clinical trial. Patients with evidently worse clinical presentations were classed as the "Device Group"; 40 patients were given low-molecular-weight heparin via a soft mist inhaler at a dose of 4000 IU per administration, twice a day. The Control Group, also made up of 40 patients, received the standard therapy. The predetermined severity of hypoxemia and the peripheral oxygen saturation of patients were measured on the 1st and 10th days of treatment. The improvement was particularly striking in cases of severe hypoxemia. In the 10-day treatment, low-molecular-weight heparin was shown to significantly improve breathing capability when delivered via a soft-mist inhaler.

Percutaneous cholecystostomy: A curative treatment modality forelderly and high ASA score acute cholecystitis patients.

BACKGROUND: Acute cholecystitis (AC) is a common emergency seen by general surgeons. Optimal treatment is laparoscopic cholecystectomy (LC); however, in cases where surgery cannot be performed due to high risk of morbidity and mortality, such as in elderly patients with comorbid diseases, other treatment modalities may be used. Percutaneous cholecystostomy (PC) is one alternative method to treat AC. PC can be used to provide drainage of the gall bladder and control infection. Subsequently, interval cholecystectomy can be performed when there are better conditions. Presently described is experience and results with PC in high risk, elderly patients with AC. METHODS: Medical records of all consecutive patients who underwent PC between January 2011 and January 2014 were identified. Tokyo Guidelines were used for definitive diagnosis and severity assessment of AC. Senior surgeon elected to perform PC based on higher risk-benefit ratio due to comorbidity, age, or duration of symptoms. All PC procedures were performed by the same interventional radiologist under local anesthesia with ultrasonographic guidance. RESULTS: Total of 40 PC procedures were performed during the study period. Of those, 22 (55%) were male and 18 were (45%) were female, with median age of 70.5 years (range: 52-87 years). All of the patients had American Society of Anesthesiologists classification of either 3 or 4. Success rate of PC was 100% with complication rate of 2.5% (n=1). One patient was operated on shortly after PC procedure due to bile peritonitis complication. PC drains were kept in place for 6 weeks. Total of 16 patients (40%) had surgery following removal of PC drain. In 3 (18.8%) cases, conversion from LC was required. Remaining 23 (57.5%) patients did not have subsequent operation after drain removal. No disease recurrence was observed in follow-up. CONCLUSION: When elderly patients present in emergency setting with AC and LC cannot be performed due to comorbid disease or poor general condition, PC can be performed safely. After removal of PC drain, LC may be performed with acceptable conversion rate of 18.8%.