Drug Interaction Between Favipiravir and Warfarin: A Case Series.

Introduction: Initiating favipiravir in COVID-19 patients with long-term warfarin use can lead to increased INR. However, data on the onset and duration of the increasing INR are limited. Method: We reviewed patient charts to include COVID-19 adult patients who received favipiravir for at least 5 days and used warfarin at the same dose for at least 12 weeks. Data on demographics, comorbidities, other medical characteristics, international normalized ratio (INR), and signs of bleeding were collected. Result: Eight patients, with a mean age of 70.88 ± 8.49 years old, received the standard dose of favipiravir. The mean maximum INR (4.30 ± 1.26) was statistically different from the baseline INR (P = .00029) and the change was observed within 4.38 ± 1.99 days after initiating favipiravir. Warfarin was then discontinued without favipiravir discontinuation in most patients, allowing the INR to gradually decrease within 2 to 3 days. Conclusion: Concurrent use of favipiravir and warfarin led to INR prolongation within approximately 4 days. The effect of such interaction can be acute as the prolongation occurred within 1 day in 1 of the patients.

Efficacy and safety of bromelain: A systematic review and meta-analysis.

Background: Pineapple has an important role in ethnopharmacology and its enzyme, bromelain, has been extensively investigated for its medicinal properties. Aim: This systematic review and meta-analysis aimed to assess clinical evidence concerning the efficacy and safety of bromelain. Methods: A systematic search was conducted from conception to August 2022 using CINAHL Complete, MEDLINE, ScienceDirect, Scopus, and Thai Journal Online (TJO). The risk of bias was assessed using Risk of Bias 2 or ROBIN-I. A random-effect model with inverse variance weighting and DerSimonian and Laird method was used for meta-analysis. The heterogeneity was evaluated by I2 statistics. Results: We included 54 articles for qualitative summary and 39 articles for meta-analysis. The systematic review found that bromelain presented in serum with retained proteolytic activity after oral absorption. Bromelain may be effective against sinusitis but was not effective for cardiovascular diseases. Pain reduction from oral bromelain was slightly but significantly better than controls (mean difference in pain score = -0.27; 95% CI: -0.45, -0.08; n = 9; I2 = 29%). Adverse events included flatulence, nausea, and headache. Topical bromelain significantly reduced the time to complete debridement (mean difference in time = -6.89 days; 95% CI: -7.94, -5.83; n = 4; I2 = 2%). Adverse events may be irrelevant and include burning sensation, pain, fever, and sepsis. Conclusions: Moderate-quality studies demonstrated the potential of oral bromelain in pain control and topical bromelain in wound care. Major health risks were not reported during the treatment with bromelain.

Pharmacokinetic variability of phenobarbital: a systematic review of population pharmacokinetic analysis.

AIMS AND BACKGROUND: Population pharmacokinetics with Bayesian forecasting provides for an effective approach when individualized drug dosing, while phenobarbital is a narrow therapeutic index drug that requires therapeutic drug monitoring. To date, several population pharmacokinetic models have been developed for phenobarbital, these showing a number of significant predictors of phenobarbital clearance and volume of distribution. We have therefore conducted a systematic review to summarize how these predictors affect phenobarbital pharmacokinetics as well as their relationships with pharmacokinetic parameters. METHOD: A systematic search for studies of phenobarbital population pharmacokinetics that were carried out in humans and that employed a nonlinear mixed-effect approaches was made using the PubMed, Scopus, CINAHL Complete, and ScienceDirect databases. The search covered the period from these databases' inception to March 2020. RESULTS: Eighteen studies were included in this review, all of which used a one-compartment structure. The estimated phenobarbital clearance and volume of distribution ranged from 0.0034 to 0.0104 L/h/kg and 0.37 to 1.21 L/kg, respectively, with body weight, age, and concomitant antiepileptic drugs being the three most frequently identified predictors of clearance. Most models were validated through the use of an advanced internal approach. CONCLUSION: Phenobarbital clearance may be predicted from previously developed population pharmacokinetic models and their significant covariate-parameter relationships along with Bayesian forecasting. However, when applying these models in a target population, an external evaluation of these models using the target population is warranted, and it is recommended that future research be conducted to investigate the link between population pharmacokinetics and pharmacodynamics.

Predictive ability of published population pharmacokinetic models of valproic acid in Thai manic patients.

WHAT IS KNOWN AND OBJECTIVE: Population pharmacokinetic (PopPK) models of valproic acid (VPA) have been developed to aid individualized drug dosing, but most of these have been based on the treatment of epileptic patients and recent evidence shows that VPA clearance (CLVPA ) in manic patients differs from that in epileptic patients. In the light of this, the predictive ability of selected VPA PopPK models based on epileptic patients was assessed to determine whether they could be used with patients with mania. METHODS: VPA PopPK models that were based on the treatment of epileptic patients and developed using a non-linear mixed-effect approach with a one-compartment structure were selected and used to predict the VPA concentrations of a validation data set. The mean absolute prediction error (MAPE) and root mean square error (RMSE) were used to assess the accuracy and precision of the model. RESULTS: The validation data set consisted of 235 Thai manic patients with a mean age of 39.6 years and a mean weight of 62.8 kg. Five models were selected to predict VPA concentrations in patients suffering from mania, and these were labelled A, C, E, F and G. The results showed that all models sufficiently predicted VPA concentrations in patients with mania, and of the models studied, G provided the most accurate and precise predictions, with MAPE and RMSE of 23% and 29.75, respectively. WHAT IS NEW AND CONCLUSION: VPA PopPK models developed using patients with epilepsy can also be used for individualized dosing of patients with mania, but before implementation, the accuracy of these models' predictions should be assessed in the target population.

Association between polypharmacy and dementia - A systematic review and metaanalysis.

Objective: The association between polypharmacy and dementia is controversial. This systematic review and meta-analysis aims to summarize existing literature concerning the association between polypharmacy and dementia. Methods: A systematic literature review was performed by searching the EMBASE, PubMed, Scopus and International Pharmaceutical Abstract databases using terms related to polypharmacy and dementia. A meta-analysis was performed using random effect models. Results: Seven studies were included in this meta-analysis. The included studies were of medium to high quality with a potential for publication bias. A strong association between polypharmacy and dementia was found (pooled adjusted risk ratio (aRR) = 1.30 (95% CI: 1.16-1.46), I2 = 68%). Excessive polypharmacy was also strongly associated with dementia (pooled aRR = 1.52 (95% CI: 1.39-1.67), I2 = 24%). Conclusion: Pooled risk estimates from this meta-analysis showed that polypharmacy was associated with dementia. Although the causality of the relationship cannot be concluded from this analysis, the finding encourages the use of multidimensional assessment tools for dementia that includes the number of medications as a component.

A systematic review and meta-analysis of the association between vitamin A intake, serum vitamin A, and risk of liver cancer.

BACKGROUND: Previous evidence supports that vitamin A decreases the risk of several types of cancer. However, the association between vitamin A and liver cancer is inconclusive. AIM: This systematic review and meta-analysis summarizes the existing literature, discussing the association between vitamin A intake, serum vitamin A, and liver cancer in adult populations. METHODS: A systematic literature review was performed by searching the EMBASE, PubMed, Scopus and International Pharmaceutical Abstract databases using terms related to vitamin A (e.g. retinol, α-carotene, ß-carotene, and ß-cryptoxanthin) and hepatic cancer without applying any time restriction. A meta-analysis was performed using random effect models. RESULTS: The meta-analysis of five studies showed no association between serum retinol and liver cancer (pooled risk ratio = 1.90 (0.40-9.02); n = 5 studies, I2 = 92%). In addition, the systematic review of studies from 1955 to July 2017 found studies that indicated no association between the intake and serum level of α-carotene ( n = 2) and ß-cryptoxanthin ( n = 1) and the risk of liver cancer. Further, the associations between retinol intake ( n = 3), ß-carotene intake ( n = 3), or serum ß-carotene ( n = 3) and liver cancer were inconclusive. CONCLUSIONS: Current information on the association between vitamin A intake and liver cancer or serum vitamin A and liver cancer are limited. Most studies demonstrated no association between dietary vitamin A and the risk of liver cancer. However, the finding was based on a small number of studies with potential publication bias. Therefore, large observational studies should be conducted to confirm these associations.

Association between polypharmacy and death: A systematic review and meta-analysis.

OBJECTIVE: Polypharmacy has been linked to a myriad of adverse consequences, and escalating rates of polypharmacy present an emerging concern, particularly among older adults. This systematic review and meta-analysis summarizes the existing literature concerning the association between polypharmacy and mortality. DATA SOURCES: A systematic literature review was done by searching the EMBASE, PubMed, Scopus, and International Pharmaceutical Abstract databases to identify studies assessing the association between polypharmacy and death published until June 2016. STUDY SELECTION: Studies that investigated the association between polypharmacy and mortality were eligible for this systematic review and meta-analysis. DATA EXTRACTION: Data were extracted by the first and second authors independently using a data extraction form. Disagreement was resolved by consensus. A meta-analysis was performed using random effect models. Heterogeneity was assessed using the I2 statistic. RESULTS: Forty-seven studies were included in this meta-analysis. The underlying populations were heterogeneous (I2= 91.5%). When defined as a discrete variable, pooled risk estimates demonstrated a significant association between polypharmacy and death (pooled-adjusted odds ratio [aOR] 1.08 [95% CI 1.04-1.12]). When defined categorically, a dose-response relationship was observed across escalating thresholds for defining polypharmacy. Categorical thresholds for polypharmacy using values of 1-4 medications, 5 medications, and 6-9 medications were significantly associated with death (P <0.05; aOR 1.24 [1.10-1.39], aOR 1.31 [1.17, 1.47], and aOR 1.59 [1.36-1.87], respectively). Excessive polypharmacy (ie, the use of 10 or more medications) was also associated with death (aOR 1.96 [1.42-2.71]). CONCLUSIONS: Pooled risk estimates from this meta-analysis reveal that polypharmacy is associated with increased mortality risk, using both discrete and categorical definitions. The causality of this relationship remains unclear, but it emphasizes the need for approaches to health care delivery that achieve an optimal balance of risk and benefit in medication prescribing.

Communication between healthcare professionals and patients with hearing loss: A systematic review and meta-analysis.

PURPOSE: We aimed to systematically review and meta-analyze published evidence on modes of communication between healthcare professionals and patients with hearing loss. METHODS: MEDLINE/PubMed, Scopus, CINAHL, ScienceDirect, and Thai Journals Online Complete databases were searched. A meta-analysis was performed using a random-effects model. Data on the prevalence and types of communication between healthcare professionals and patients with any extent of hearing loss were extracted. RESULTS: Twenty studies were included. Using a hearing aid (pooled prevalence, 57.4%; 95% CI, 11.4%-103.4%, N = 3, I2 = 99.33) and gestures (pooled prevalence = 54.8%, 95%CI: 17.4% to 92.1%, N = 7, I2 = 99.68) were the most commonly reported modes of communication. Few healthcare professionals could use sign language, and limited access to qualified interpreters was common. CONCLUSION: Communication barriers exist. Qualified sign language interpreters and assistive technology should be used to improve communication.

Communication issues between pharmacists and d/Deaf people: a qualitative study in Thailand.

BACKGROUND: People who are d/Deaf face challenges when communicating with pharmacists, especially during medication counseling. AIM: This study aimed to explore and understand the perceptions and experiences of d/Deaf people regarding medication counseling by hospital pharmacists. METHOD: Five sets of semi-structured in-depth interviews (44 total) and one focus group were conducted among d/Deaf people, hospital pharmacists, and Thai sign language (TSL) interpreters. Data from d/Deaf people's perspectives were triangulated with data from pharmacists and TSL interpreters. RESULTS: Five themes emerged from the interview: (1) d/Deaf people believe that deafness is stigmatized, (2) d/Deaf people's needs during medication counseling, (3) skills for d/Deaf people to communicate with pharmacists, (4) values identified in d/Deaf people, 5) emotions related to medication counseling with pharmacists. Effort, trust, confidentiality, and privacy were values associated with counseling. d/Deaf people preferred communicating with pharmacists in TSL to communicating with pharmacists via TSL interpreters because of trust and confidentiality. They also preferred pharmacists with d/Deaf knowledge and skills. Moreover, d/Deaf people believed that deafness was stigmatized, so signing in nonprivate areas was embarrassing. When TSL was not used in communication, language, lipreading, and technology skills became important. With these non-TSL communications, d/Deaf people may not have understood the conversation. However, they may not have asked pharmacists because they felt Krengjai (the hesitancy to bother). CONCLUSION: Thai d/Deaf people have negative experiences during medication counseling. Skills and emotions can act as barriers to communication with pharmacists. TSL should be used to improve d/Deaf people's experiences during medication counseling.

Genetic alterations in myeloid sarcoma among acute myeloid leukemia patients: insights from 37 cohort studies and a meta-analysis.

Introduction: Variations in mutation rates among acute myeloid leukemia (AML) patients with myeloid sarcoma (MS) underscore the need for a thorough examination. This meta-analysis was conducted to fill the information gap concerning mutation frequencies in AML patients presenting with MS. Materials and methods: This study included retrospective and prospective cohorts. It examined genetic alterations in AML patients with and without MS across all age groups. The search strategy employed terms such as "acute myeloid leukemia," "extramedullary," "granulocytic sarcoma," "myeloid sarcoma," and "leukemic cutis" in the EMBASE, MEDLINE, and Scopus databases. Excluded from the study were reviews, case reports, and case series with fewer than 10 cases. Statistical analyses were performed with Review Manager 5.4 software. Results: The primary analysis incorporated data from 37 cohorts involving 5646 diagnosed AML patients and revealed a 17.42% incidence of MS. The most prevalent mutation among AML patients with MS was FLT3-ITD, with a pooled prevalence of 17.50% (95% CI 12.60% to 22.50%; I2 82.48%). The dominant fusion gene was RUNX1::RUNX1T1, displaying a pooled prevalence of 28.10% (95% CI 15.10% to 41.20%; I2 96.39%). In comparison, no significant intergroup differences were observed for NPM1, FLT3-ITD, KIT, and IDH2 mutations. Interestingly, the CEBPA mutation exhibited protective effects for MS patients, with an odds ratio of 0.51 (95% CI 0.32 to 0.81; I2 0%). Conversely, the NRAS mutation was associated with an increased risk of MS development, with an odds ratio of 5.07 (95% CI 1.87 to 13.73; I2 0%). Conclusion: This meta-analysis sheds light on the prevalence of genetic mutations in AML patients with MS, providing insights into the unique characteristics of the mutations and their frequencies. These discoveries are crucial in informing therapeutic and prognostic decisions for individuals with myeloid sarcoma.

The Association between Cardiovascular Risk Factors and Lichen Sclerosus: A Systematic Review and Meta-Analysis.

Background/Objective: Lichen sclerosus is a chronic inflammatory skin disease that affects people of all ages and sexes. Evidence of cardiovascular risk factors in lichen sclerosus has been continuously reported; however, the definitive association remains inconclusive. This meta-analysis aimed to summarize the association between cardiovascular risk factors and lichen sclerosus. Methods: Electronic databases, including MEDLINE and EMBASE, were systematically searched from inception to May 2024 to identify the literature reporting the association between cardiovascular risk factors and lichen sclerosus. A random-effects model was used for the meta-analysis. Results: We included 16 eligible studies: nine case-control studies, six retrospective cohort studies, and one cross-sectional study. A total of 432,457 participants were included. Lichen sclerosus was significantly associated with type 2 diabetes mellitus with an odds ratio of 2.07 (95% CI: 1.21-3.52). Although not statistically significant, a trend of increasing risk in hypertension, dyslipidemia, obesity, and metabolic syndrome was observed among lichen sclerosus patients, with odds ratios of 1.56 (95% CI: 0.90-2.70), 1.44 (95% CI: 0.94-2.23), 5.84 (95% CI: 0.37-92.27), and 1.36 (95% CI: 0.52-3.54), respectively. Conclusions: Lichen sclerosus was associated with diabetes mellitus and potentially correlated with hypertension, dyslipidemia, obesity, and metabolic syndrome. Population-based prospective observational studies are required to further elucidate these findings and assess the impact of these associations.

First-line immunosuppressive therapies for acquired hemophilia A: A 25-year cohort experience and network meta-analysis.

Acquired hemophilia A (AHA) presents a significant bleeding risk. Management involves bleeding control and immunosuppressive therapy (IST) to eliminate inhibitors. This study, encompassing a retrospective cohort of 76 newly diagnosed AHA patients (1997-2022), evaluated IST outcomes such as complete remission (CR), relapse, and mortality rates, alongside influencing factors. Supplementing these findings, a systematic review and network meta-analysis compared CR and relapse rates across ISTs, sourcing from Embase, Scopus, and ScienceDirect up to November 2023. In our cohort, demarcated by a 20 Bethesda-unit titer threshold, cyclophosphamide plus prednisolone (CP; n = 64) was the predominant initial IST. Lower inhibitor levels significantly correlated with higher CR rates (86.8 % vs 62.2 %; P = .014) and showed an odds ratio of 0.26 for CR (P = .021). Median relapse-free survival (RFS) extended to 37.13 months, significantly enhanced by CP (hazard ratio, 0.24; 95 % confidence interval, 0.10-0.60; P = .002). Our network meta-analysis, including 1476 CR and 636 relapse patients, indicated CP and rituximab-based ISTs significantly outperformed steroid monotherapy in terms of CR and lower relapse rates (risk differences of 0.15 and -0.13/-0.15, respectively; P < .05), without significant differences between CP and rituximab. Moreover, adding rituximab to the front-line treatment did not produce superior outcomes compared to the CP regimen alone, positioning CP as a viable first-line choice, particularly where rituximab is less accessible. The consideration of IST toxicity remains critical in treatment decisions.

Population pharmacokinetics of doxorubicin: A systematic review.

Because of the high interindividual pharmacokinetic variability, several population pharmacokinetic (PopPK) models of doxorubicin (DOX) were developed to characterize factors influencing such variability. However, significant predictors for DOX pharmacokinetics identified using PopPK models varied across studies. Thus, this review aims to summarize PopPK models of DOX and its metabolites (if any) as well as significant covariates influencing DOX (and its metabolites) pharmacokinetic variability. A systematic search from PubMed, CINAHL Complete, Science Direct, and SCOPUS databases identified 503 studies. Of these, 16 studies met the inclusion criteria and were included in this review. DOX pharmacokinetics was described with two- or three-compartment models. Most studies found a significant increase in DOX clearance with an increase in body surface area from the median value of 1.8 m2 . Moreover, this review identified that while a 10-year increase in patient age resulted in a decrease in DOX clearance in adults and the elderly, younger children had lower DOX clearance compared to older children. Further, low DOX exposure was observed in pregnant women, and thus dosage adjustment is required. Concerning model applicability, predictive performance assessment of these published models should be performed before implementing such models in clinical practice.

After morning, phew! A knowledge, attitudes, and practices survey related to emergency oral contraception in Thai pharmacists.

INTRODUCTION: Pharmacists' knowledge and attitude toward Emergency Oral Contraception (EOC) can affect users' access to EOCs, especially where EOCs are provided by pharmacists without the need for prescriptions. We conducted a Knowledge, Attitudes, and Practice (KAP) survey on Thai pharmacists to better understand KAP related to EOCs and the correlation among KAP components. METHODS: An in-depth interview, GoogleTrend search, and Pantip.com search were conducted. The findings, together with data from a previously published systematic review and meta-analysis, were used to develop KAP survey questions which were distributed online. Spearman's rank correlation coefficient and linear mixed model were used to investigate the correlation and association among KAP components. RESULTS: The in-depth interview with pharmacists showed that sex and unwanted pregnancy are very sensitive topics in Thailand. Sex and EOC education should be provided by parents and healthcare professionals at a young age. This agreed with opinions from Thai internet users that sex literacy was generally low and sex education was not provided adequately. From the total of 421 survey responses, Thai pharmacists had average knowledge, poor attitude, and average practice related to EOCs (median score = 51.02%, 21.81%, and 60.0%, respectively). The correlations between KAP in pharmacists were weak (ρ = 0.107-0.525, p < 0.02). Pharmacists who rated themselves as having higher scores in knowledge and attitude also rated themselves higher in the practice score. However, the total scores describing the knowledge of or attitude toward EOCs were not associated with EOC practice scores. CONCLUSIONS: In Thai pharmacists, self-rating KAP scores overestimated total KAP scores. The correlation among KAP components was weak. EOC knowledge and attitudes should be promoted, although this may not improve EOC practice in Thai pharmacists.

A multidisciplinary approach to verify and de-label of drug allergic histories in a university hospital in Thailand: a retrospective descriptive study.

BACKGROUND: Mislabeling of drug allergic histories causes avoidable negative impacts on patients and healthcare system. Although multidisciplinary adverse drug reaction (ADR) services to verify and de-label drug allergic histories have been operated in particular hospitals in Thailand, their performances have not been reported. This research aimed to examine the effectiveness of verification of drug allergic history and de-labeling (VD) services of the physician-led multidisciplinary ADR clinic. METHODS: This research was a retrospective descriptive study. Medical charts of patients with at least one drug allergic history who received VD services at the multidisciplinary clinic between January 2017 to December 2018, were reviewed. Data on the history of drug allergy, VD services, and results were analyzed and presented using descriptive statistics. RESULTS: Seventy patients' charts were reviewed, and 171 unconfirmed drug allergic histories were identified. 79.53% of the reported reactions involved skin and soft tissues. The most found adverse skin reactions were maculopapular rash, pruritic and erythematous rash, and angioedema. The remaining 20.47% were systemic reactions which included drug reaction with eosinophilia and systemic symptoms (DRESS), anaphylaxis, and nausea/vomiting was the most prevalent. Antituberculosis, beta-lactam antibiotics, and nonsteroidal anti-inflammatory drugs (NSAIDs) were the most reported suspected drugs. Drug allergic history reviewing by physicians or pharmacists could confirm and de-label for 3 and 20 reactions, respectively. Seven and one reactions were confirmed by enzyme-linked immunospot assay and patch test, respectively. The provocation tests with the suspected or alternative drug were conducted in 64 reactions. Twelve reactions were confirmed, and 45 reactions were de-labeled. Totally, 65/171 (38.01%) allergic histories were successfully de-labeled, 23/171 (13.45%) were confirmed, and 83/171 (48.53%) were inconclusive. CONCLUSIONS: More than half of drug allergic histories were successfully confirmed or de-labeled by the multidisciplinary ADR team. The collaborative activities of various healthcare professionals, consisting of physicians, nurse, and pharmacists as presented in the study were effective in VD services and should be implemented in other healthcare settings.

Phytochemicals and Antioxidant Activities of Red Oak, Red Coral and Butterhead.

Lactuca sativa L. is an economically important vegetable that contains numerous phytochemicals. This study aimed to determine the phytochemicals in three lettuce cultivars (red oak, red coral, and butterhead) and assess their total phenolics, total flavonoids and antioxidant activities. The dried leaves of each lettuce cultivar were macerated with hexane, ethyl acetate (EtOAc), and 95% ethanol (EtOH). Total phenolics, total flavonoids, and antioxidant activities from the three solvent extracts were measured. The phytochemical screening showed that the leaves from the three lettuce cultivars contained flavonoids, hydrolyzable tannins, coumarins, steroids, and phenolic compounds. While the EtOAc fraction of the red coral lettuce showed the highest total phenolic content (9.747 ± 0.021 mg gallic acid equivalent/g) and the hexane fraction of the butterhead lettuce contained the highest flavonoids (7.065 ± 0.005 mg quercetin equivalent/g). In the DPPH (2,2-diphenyl-1-picryl-hydrazyl-hydrate) assay, the EtOAc fraction of the red coral lettuce had the highest antioxidant capacity with an IC50 of 0.277 ± 0.006 mg/mL, whereas, in the ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)) assay, the 95% EtOH of the red coral lettuce had the highest antioxidant capacity with an IC50 of 0.300 ± 0.002 mg/mL. All three lettuce cultivars contained high levels of phenolic content and flavonoids, which are the source of antioxidant activities. These lettuce cultivars, especially the red coral lettuce, are a potential source of natural antioxidants. Further research on the application of natural antioxidants is required to investigate the therapeutic or the neutraceutical implication of the lettuce cultivars.

The development of an in-situ biopolymer-based floating gel for the oral delivery of metformin hydrochloride.

Diabetes remains a global public health threat because of its increasing prevalence and mortality, especially in people under the age of 25. Metformin hydrochloride (HCl), as recommended by American Diabetes Association in 2022, is the first-line therapy for type 2 diabetes in adults. Metformin has low oral bioavailability due to poor permeability. Therefore, by developing metformin HCl oral in situ gel, sustained delivery of metformin can be achieved, thus enhancing the absorption of the drug. Sodium alginate and pectin were used for formulating the system. Different adjuvant polymers, including HPMC K4M, HPMC K100 LV, PEG 4000, and SCMC were used as released-pattern-modifying agents. All formulations could afloat in 0.1 N HCl at the pH of 1.2 within a minute and stay afloat for over 8 h. The optimized formulation could be made from either sodium alginate (2%) and HPMC K4M (0.5%) or pectin (2%) and HPMC K4M (2%). The optimized formulations gradually released metformin HCl with a cumulative release of 80% within 8 h. We successfully developed floating in situ gels that can release metformin HCl sustainedly.

A systematic review and meta-analysis of the prevalence and association between levonorgestrel and ectopic pregnancy.

BACKGROUND: The use of levonorgestrel emergency oral contraceptives (EOCs) is one of the factors that may be associated with ectopic pregnancy. We aimed to investigate the incidence of ectopic pregnancy in EOC users and the association between EOCs and ectopic pregnancy. RESEARCH DESIGN AND METHODS: We searched for articles that provided the incidence of and the association between levonorgestrel EOCs and ectopic pregnancy in women of reproductive ages in CINAHL Complete, Medline, OpenDissertations, Scopus, Science Direct, and Thai Journal Online. The risk of bias was assessed by Risk Of Bias In Non-randomized Studies or Risk of Bias 2. A meta-analysis was conducted using the random-effects model. RESULTS: We retrieved 1839 nonredundant articles from the systematic search. The meta-analysis showed that the prevalence of ectopic pregnancy was not statistically different from zero (pooled prevalence estimate = 0.029%; 95%CI: -0.006, 0.065; N = 9; I2 = 0) and rare. In addition, levonorgestrel EOCs increased the risk of ectopic pregnancy (OR = 6.17; 95%CI: 3.78, 10.08; N = 5; I2 = 43%). CONCLUSIONS: Women with extrauterine or ectopic pregnancy had higher odds of using levonorgestrel emergency oral contraceptives than those with intrauterine pregnancy. However, the prevalence of ectopic pregnancy is rare.

Population Pharmacokinetics of Levetiracetam: A Systematic Review.

BACKGROUND: The use of levetiracetam (LEV) has been increasing, given its favorable pharmacokinetic profile. Numerous population pharmacokinetic studies for LEV have been conducted. However, there are some discrepancies regarding factors affecting its pharmacokinetic variability. Therefore, this systematic review aimed to summarize significant predictors for LEV pharmacokinetics as well as the need for dosage adjustments. METHODS: We performed a systematic search for population pharmacokinetic studies of LEV conducted using a nonlinear-mixed effect approach from PubMed, Scopus, CINAHL Complete, and Science Direct databases from their inception to March 2020. Information on study design, model methodologies, significant covariate-parameter relationships, and model evaluation was extracted. The quality of the reported studies was also assessed. RESULTS: A total of 16 studies were included in this review. Only two studies were conducted with a two-compartment model, while the rest were performed with a one-compartment structure. Bodyweight and creatinine clearance were the two most frequently identified covariates on LEV clearance (CLLEV). Additionally, postmenstrual age (PMA) or postnatal age (PNA) were significant predictors for CLLEV in neonates. Only three studies externally validated the models. Two studies conducted pharmacodynamic models for LEV with relatively small sample size. CONCLUSION: Significant predictors for LEV pharmacokinetics are highlighted in this review. For future research, a population pharmacokinetic-pharmacodynamic model using a larger sample size should be conducted. From a clinical perspective, the published models should be externally evaluated before clinical implementation.

Factors influencing decision making and antibiotic prescribing patterns for the treatment of carbapenem-resistant Enterobacteriaceae (CRE) among non-infectious physicians in Thailand: a qualitative study.

The treatment of carbapenem-resistant Enterobacteriaceae (CRE) is diverse in each region due to the difference in local resistant patterns of CRE. We aimed to explore how physicians in Thailand decide on selection options for treating CRE infections. In this study, 25 physicians who were not infectious disease (ID) specialists participated in this semi-structured in-depth interview. We found that they, in general, did not provide empiric antibiotics for the treatment of CRE. However, some patients, e.g., those with prior carbapenems exposure may have brought CRE to physicians' attention. ID specialists played critical roles in both empiric and specific CRE treatment. There were multiple scenarios when CRE management deviated from recommendations, especially when physicians perceived that the evidence that supported the recommendations was weak. Several supportive factors, challenges, and improvements were also suggested. In conclusion, ID specialists, adequate information, and consistent implementation of infectious control policy are crucial to the treatment and prevention of CRE infection.