Bioequivalence of a New Pediatric Paracetamol Oral Suspension Compared With a Marketed Formulation in Healthy Adults: A Randomized, Open-Label Study.

Background: A new oral paracetamol formulation with the same paracetamol quantity (24 mg/mL) as a marketed formulation but with finer active ingredient particle size and lower amounts of maltitol (5.85 g/dose in the test formulation vs 7.25 g/dose in the reference formulation) and sorbitol (2.4 g/dose vs 2.83 g/dose) was developed. Objective: Establish the bioequivalence of the new pediatric formulation (test treatment) compared with the marketed formulation (reference treatment). Methods: This Phase I, open-label trial assigned healthy adult volunteers to a single 42-mL (1 g para-cetamol) dose of test or reference treatment. Participants received both treatments in a randomized order separated by a 72-hour washout period. The primary endpoints were AUC0-tlast (AUC vs time curve from time 0 to last measurable sampling timepoint), Cmax, and tmax. Safety assessments included adverse event, clinical laboratory, and physical examination data. Results: Thirty-five participants were randomized and treated. The study population was 42.9% women (57.1% men) with a median age of 30 years; most participants were non-Hispanic White. Mean Cmax values were comparable between test and reference products, with a median tmax of 1.00 hour for both. The test/reference ratios (%) (90% CI) for AUC0-tlast and Cmax were 98.69% (96.46, 100.97) and 100.73% (95.63, 106.10), respectively. There were no adverse events or deaths. Conclusions: The new paracetamol formulation is bioequivalent to the marketed formulation.

Common Selfcare Indications of Pain Medications in Children.

Pain has a multifaceted impact on individuals worldwide, affecting their physical functioning, emotional well-being, and quality of life. Children (age < 18 years) have a high prevalence of conditions associated with pain, such as toothache, headache, earache, sore throat, and respiratory tract infections, many of which may be accompanied by fever. Globally, the pharmacologic treatment of pain in pediatric patients is limited largely to nonopioid analgesics, and dosing must account for differences in age, weight, metabolism, and risk of adverse effects. This narrative review summarizes the findings of a literature search on the pediatric indications, dosing approaches, dosing guidelines, and pharmacokinetics of paracetamol and ibuprofen, which are common pain medications available globally for self-care use in children. The review also discusses the risks and benefits associated with these agents. The current roles of paracetamol and ibuprofen in the symptomatic management of coronavirus disease 2019 (COVID-19) infection and in the management of post-COVID-19 immunization symptoms in children are also discussed. Therefore, while a very large amount of data over several decades is available for paracetamol and ibuprofen, an urgent need exists for well-designed studies of these medications for the management of pain and fever in pediatric patients with COVID-19 to ensure optimal relief with minimal toxicity.

Why paracetamol (acetaminophen) is a suitable first choice for treating mild to moderate acute pain in adults with liver, kidney or cardiovascular disease, gastrointestinal disorders, asthma, or who are older.

Acute pain is among the most common reasons that people consult primary care physicians, who must weigh benefits versus risks of analgesics use for each patient. Paracetamol (acetaminophen) is a first-choice analgesic for many adults with mild to moderate acute pain, is generally well tolerated at recommended doses (≤4 g/day) in healthy adults and may be preferable to non-steroidal anti-inflammatory drugs that are associated with undesirable gastrointestinal, renal, and cardiovascular effects. Although paracetamol is widely used, many patients and physicians still have questions about its suitability and dosing, especially for older people or adults with underlying comorbidities, for whom there are limited clinical data or evidence-based guidelines. Inappropriate use may increase the risks of both overdosing and inadequate analgesia. To address knowledge deficits and augment existing guidance in salient areas of uncertainty, we have researched, reviewed, and collated published evidence and expert opinion relevant to the acute use of paracetamol by adults with liver, kidney, or cardiovascular diseases, gastrointestinal disorders, asthma, or/and who are older. A concern is hepatotoxicity, but this is rare among adults who use paracetamol as directed, including people with cirrhotic liver disease. Putative epidemiologic associations of paracetamol use with kidney or cardiovascular disease, hypertension, gastrointestinal disorders, and asthma largely reflect confounding biases and are of doubtful relevance to short-term use (<14 days). Paracetamol is a suitable first-line analgesic for mild to moderate acute pain in many adults with liver, kidney or cardiovascular disease, gastrointestinal disorders, asthma, and/or who are older. No evidence supports routine dose reduction for older people. Rather, dosing for adults who are older and/or have decompensated cirrhosis, advanced kidney failure, or analgesic-induced asthma that is known to be cross-sensitive to paracetamol, should be individualized in consultation with their physician, who may recommend a lower effective dose appropriate to the circumstances.

To Determine the Diagnostic Accuracy of Diffusion-Weighted Imaging in the Diagnosis of Prostate Carcinoma Taking Histopathology As the Gold Standard.

Introduction Carcinoma of the prostate is the most common malignancy among males. Serum prostate-specific antigen (PSA) levels and digital rectal examination (DRE) are the initial investigations for the detection of prostate cancer. In recent years, some investigators have used color Doppler ultrasound and diffusion-weighted imaging (DWI) for the diagnosis of prostate cancer and avoided invasive and painful investigation, i.e., biopsy. The purpose of the study is to determine the validity of DWI in detecting prostatic cancer taking histopathology as the gold standard. Material and methods This cross-sectional study was conducted prospectively in the radiology department of a tertiary care hospital from January 1, 2019, to December 31, 2020. This study was approved by the Departmental Research Committee. A total of 272 male patients were included in our study who have elevated PSA levels (>4.0 ng/ml) with symptoms of hematuria and urinary retention. All included subjects were sent to the radiology department for DWI imaging. The DWI imaging was analyzed for prostate cancer and the results were correlated with histopathological diagnosis. Results The average age of patients was 50.28±9.93 years. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of DWI in the diagnoses of prostate cancer were 86.7%, 87.8%, 75.8%, 93.8%, and 87.5%, respectively. Conclusion DWI is an informative and non-invasive imaging modality with high diagnostic accuracy for the diagnosis of prostate carcinoma.

Social Entrepreneurship Orientation and Enterprise Fortune: An Intermediary Role of Social Performance.

Social entrepreneurship orientation (SEO) is a behavioral construct of social entrepreneurship (SE); therefore, we examined the influence of SEO of the organization on social and financial performance. A random sample of 810 employees was drawn from social enterprises of Pakistan during the COVID-19 pandemic. Although increasing research focuses on SE, the discipline continues to disintegrate, and this has led to appeals for a careful investigation of the associations of firms' SE. In the recent decade, "social entrepreneurship" has earned its importance as a segment of entrepreneurship. Instead of mixed activity, firms are more likely to engage in either for-profit or non-profit activities. The causes for and consequences of this conduct has been mainly studied using objective measures of SEO, social performance, and financial performance, with little attention paid to the subjective experiences of social enterprises. We rely on the theory of stakeholder and mixed structuring to postulate that social performance intermediates the SEO-financial performance relation. By assessing a sample of 810 employees from active enterprises, we discover that social performance mediates positively and partially between SEO and financial performance, and both direct and indirect paths are in the same direction and significant. Our findings exhibit that social performance variance explained 74% of the mediating role, and the remaining 26% of the effect is because of SEO. We consider the functions by which an SEO influences enterprise performance and delivers more prominent understanding into multiple spectrums of performance. We discuss the prospective suggestions of our research and foster an encouraging pathway for more enquiry on the SEO paradigm. The study adds contribution to the literature, which has not been testified before on hybrid firms. SEO is a newly defined construct and requires more prospective research. This research gives the researchers/scholars new directions to address related disciplines and further explore this domain.

Practical Challenges-Use of Paracetamol in Children and Youth Who are Overweight or Obese: A Narrative Review.

Worldwide, > 380 million children and adolescents are overweight or obese, including 41 million children aged < 5 years. Obesity can change the pharmacokinetic properties of drugs by altering their distribution, metabolism, and elimination. Thus, children who are overweight or obese are at increased risk for receiving inappropriate doses of commonly used drugs, which can result in treatment failure, adverse events, and/or drug toxicity. This review analyzes available data on paracetamol dosing for pain and fever in children and adolescents who are overweight or obese to identify gaps and challenges in optimal dosing strategies. Literature searches using Medline, Embase, and ClinicalTrials.gov were conducted to identify English-language articles reporting paracetamol pharmacokinetics, dosing practices, and guidelines in children and adolescents who are overweight or obese. Of 24 relevant studies identified, 20 were specific to overweight/obese individuals and 15 were specific to children and/or adolescents. Data on paracetamol pharmacokinetics in children and adolescents who are overweight or obese are lacking, and there is no high-quality evidence to guide paracetamol prescribing practices in these patients. Adult data have been extrapolated to pediatric populations; however, extrapolation does not address differences in paracetamol metabolism in adults versus children; the efficacy and safety effects of such differences are unknown. Given the growing worldwide prevalence of obesity in children and adolescents and the likelihood that paracetamol use in this population will increase accordingly, obesity-specific pediatric dosing guidelines for paracetamol are urgently needed. High-quality research is necessary to inform such guidelines.

Safety and efficacy of initial combination of linagliptin and metformin in patients with type 2 diabetes: A subgroup analysis of Indian patients from a randomized, double-blind, placebo-controlled study.

CONTEXT AND OBJECTIVES: The number of people with diabetes is increasing exponentially in India. Owing to a unique "Asian Indian Phenotype," Indians develop diabetes a decade earlier and have an earlier onset of complications than Western populations. Therefore, it is essential to evaluate more effective treatment strategies at an earlier stage of disease progression, such as initial combination therapy, in Indian patients. In this study, we evaluated the efficacy and safety of initial combination therapy with linagliptin plus metformin in comparison to linagliptin or metformin monotherapy in Indian patients with type 2 diabetes mellitus. METHODS: This is a subgroup analysis of Indian patients who participated in a Phase III, 24-week, double-blind, placebo-controlled, trial. Overall, 249 Indian patients were randomized to one of six treatment arms (Two free combination therapy arms: Linagliptin 2.5 mg twice daily [bid] + either low [500 mg, n = 36] or high [1000 mg, n = 44] dose metformin bid and four monotherapy arms: Linagliptin 5 mg once daily [qd, n = 40], metformin 500 mg [n = 49] or 1000 mg bid [n = 45], or placebo [n = 23]). RESULTS: The placebo-corrected mean change in glycated hemoglobin from baseline (8.9%) to week 24 was -1.83% for linagliptin + metformin 1000 mg bid; -1.46% for linagliptin + metformin 500 mg bid; -1.30% for metformin 1000 mg bid; -1.00% for metformin 500 mg bid; and -0.77% for linagliptin 5 mg qd. None of the patients in the combination therapy arms had hypoglycemia, whereas there was one event in the metformin 1000 mg bid arm. Rates of adverse event were similar across various treatments. CONCLUSIONS: In this subgroup analysis of Indian patients, initial combination therapy with linagliptin + metformin was more efficacious in improving glycemic control than the monotherapy arms, with a comparable tolerability profile. The results were comparable to the overall population.

Efficacy and safety of linagliptin as monotherapy or add-on treatment in Asian patients with suboptimal glycemic control: a pooled analysis.

AIMS: To evaluate the efficacy and safety of the dipeptidyl peptidase (DPP)-4 inhibitor linagliptin in Asian patients with type 2 diabetes mellitus (T2DM), a rapidly increasing population. METHODS: Data were pooled for Asian patients receiving linagliptin orally once daily, as monotherapy or added to existing oral antidiabetes therapies, in multinational randomized placebo-controlled clinical trials. Efficacy data were taken from four pivotal trials with 24-week durations to allow for robust efficacy assessment. Safety data were pooled from a wider group of 10 trials with varying durations to capture the largest possible incidence of adverse events (AEs). The primary efficacy endpoint was change from baseline to week 24 in HbA1c. AEs were analyzed descriptively. RESULTS: Mean baseline HbA1c (±SD) in this population was 8.2 ± 0.9%. Placebo-corrected mean change in HbA1c after 24 weeks was -0.79% (95% confidence interval [CI]: -0.92 to -0.67; p < 0.0001). Placebo-corrected mean change in fasting plasma glucose was -17.8 ± 2.4 mg/dL (95% CI: -22.6, -13.0; p < 0.0001). In a small subgroup, mean post-prandial glucose was reduced by a placebo-corrected -56.9 ± 14.0 mg/dL (95% CI: -85.2, -28.5). AEs occurred in 58.0% of linagliptin patients (serious AEs in 2.4%) and 58.2% of placebo patients (serious AEs in 3.0%). CONCLUSIONS: This study was limited by the post hoc nature of the analysis, and because the pooling did not differentiate between geographically distant Asian regions. Nonetheless, this analysis provides evidence that linagliptin was efficacious and well tolerated as monotherapy or added to other oral antidiabetes therapies in Asian patients with T2DM.

Azimuthal solitary surface wave in cylindrical tank.

This Brief Report is devoted to the study of the solitary surface wave rotating in the azimuthal direction, arising during water drainage from a cylindrical reservoir, when shallow flow conditions are reached. The linear dependence between the wave speed and its amplitude is shown to be similar to that expected from the classical Korteweg-de Vries equation.

Symmetrization of a polygonal hollow-core vortex through beat-wave resonance.

We report on the symmetrization phenomenon of a hollow-core vortex in shallow liquid conditions. This phenomenon accompanies the transition of m wave into (m+1) wave and involves a beat-wave resonance that mediates energy transfer between the background flow and the vortex core. It is shown that this beat wave has a frequency m/(m-1)times the frequency of the parent m wave.

Transition between Kelvin's equilibria.

A transition between Kelvin's equilibrium states is investigated. Using nonlinear theory, we have shown that the transition of polygonal patterns of the hollow vortex core from mode N=2 through N=4 occurs in two steps: quasiperiodicity and frequency locking. We have also shown that this transition can be modeled by a one-dimensional circle map. We extrapolate the present result and hypothesize that the transition between Kelvin's equilibria follows the same route and the ratios of locking frequencies form a Farey sum and staircase function against the control parameter, where the staircase corresponds to the rational frequency ratio, (N-1)/N.

Benign multicystic peritoneal mesothelioma associated with hydronephrosis and colovesical fistula formation: report of a case.

Mesotheliomas usually arise from the pleura and are malignant. We report an unusual case of benign peritoneal mesothelioma presenting in a 59-year-old woman. The disease resulted in bilateral hydronephrosis, colovesical fistula formation, recurrent small bowel obstruction and chronic abdominal pain. To date only a handful of cases have been reported and to the best of our knowledge, none has been so aggressive.

Valveless acoustic standing wave micropump for biomedical applications: a numerical study.

The operation principle of the valveless acoustic standing wave micropump is described. Time-variant flow structures through the planar diffuser-nozzle element of this micropump for different values of the divergence angle of the diffuser-nozzle element at excitation frequency of f = 20 kHz are numerically investigated. The variations of micropump flow rate, pressure loss coefficients of the nozzle and diffuser, and diffuser efficiency are shown as functions of theta. The higher micropump flow rate is found to be achieved at larger values of theta. However, increasing theta from 45. to 60. shows no significant increase in the net flow rate. The results also show that the maximum diffuser efficiency is achieved at theta = 45.