Fever response to ibuprofen in viral and bacterial childhood infections.

OBJECTIVE: to compare the antipyretic effects of ibuprofen in febrile children with serious bacterial infections (SBI), and children with a presumed viral infection. METHODS: A prospective cross- sectional study was conducted in a pediatric Emergency department between October 2018 and March 2020 for children aged 3 months to 4 years with a rectal temperature ≥ 38.5 °C. Patients received 10 mg/kg of ibuprofen oral suspension. Rectal temperature was measured 60 and 120 min after administration. Laboratory and imaging evaluations were performed for each study participant in order to identify serious bacterial infection. RESULTS: Ninety patients were included, of which 18 were diagnosed with serious bacterial infections. There was no significant difference in age, fever at presentation and duration of fever between the groups. No significant difference was noted in body temperature reduction at 60 and 120 min after ibuprofen administration (1.09 ± 0.75 °C vs 0.89 ± 0.58 °C, mean difference -0.12 °C, 95% CI -0.54-0.15 °C; 1.85 ± 0.53 °C vs 1.78 ± 0.83 °C, mean difference - 0.07 °C, 95% CI -0.49-0.36 °C, in the SBI and non-SBI groups respectively). CONCLUSION: Fever response to Ibuprofen administration is not indicative of serious bacterial infections in children under 4 years of age. Larger prospective studies are required to define whether the lack of response to Ibuprofen has any impact on the management of febrile children.

Preparation of celecoxib tablet by hot melt extrusion technology and application of process analysis technology to discriminate solubilization effect.

The aim of this study was to prepare various types of solid dispersions (SDs) by the hot-melt extrusion technique. Next, process analytical technology (PAT) such as Fourier transform-infrared (FT-IR) and Raman and near infrared (NIR) spectroscopy were applied to determine the solubilization effect. The SDs and its tablets were prepared. Differential scanning calorimetry (DSC), X-ray diffraction (XRD), and scanning electron microscopy (SEM) were performed to determine the morphological and crystalline characteristics of the SDs. Additionally, PAT analyses were performed to identify the solubilization of the celecoxib. Dissolution testing was performed using the paddle method indicated in the US Pharmacopeia Apparatus II. Based on SEM, DSC, and XRD analysis, all SDs changed successfully from the crystalline to the amorphous form. However, FT-IR, Raman, and NIR analysis used in PAT showed that SDs were divided into two groups. New peaks formed as the amount of drug loading increased to >50% in the SD and the dissolution rates were lower than those of the marketed drug. Drug loading levels of ≤50% showed no new peak and exhibited strong solubilization effects. PAT tools can be used to discriminate between extrudates with poor (<50% drug release after 120 min) and desirable (>75% drug release after 120 min) dissolution performance.

2018 update of the EULAR recommendations for the management of hand osteoarthritis.

Since publication of the European League Against Rheumatism (EULAR) recommendations for management of hand osteoarthritis (OA) in 2007 new evidence has emerged. The aim was to update these recommendations. EULAR standardised operating procedures were followed. A systematic literature review was performed, collecting the evidence regarding all non-pharmacological, pharmacological and surgical treatment options for hand OA published to date. Based on the evidence and expert opinion from an international task force of 19 physicians, healthcare professionals and patients from 10 European countries formulated overarching principles and recommendations. Level of evidence, grade of recommendation and level of agreement were allocated to each statement. Five overarching principles and 10 recommendations were agreed on. The overarching principles cover treatment goals, information provision, individualisation of treatment, shared decision-making and the need to consider multidisciplinary and multimodal (non-pharmacological, pharmacological, surgical) treatment approaches. Recommendations 1-3 cover different non-pharmacological treatment options (education, assistive devices, exercises and orthoses). Recommendations 4-8 describe the role of different pharmacological treatments, including topical treatments (preferred over systemic treatments, topical non-steroidal anti-inflammatory drugs (NSAIDs) being first-line choice), oral analgesics (particularly NSAIDs to be considered for symptom relief for a limited duration), chondroitin sulfate (for symptom relief), intra-articular glucocorticoids (generally not recommended, consider for painful interphalangeal OA) and conventional/biological disease-modifying antirheumatic drugs (discouraged). Considerations for surgery are described in recommendation 9. The last recommendation relates to follow-up. The presented EULAR recommendations provide up-to-date guidance on the management of hand OA, based on expert opinion and research evidence.

Comparison the analgesic effect of magnesium sulphate and Ketorolac in the treatment of renal colic patients: Double-blind clinical trial study.

BACKGROUND: Ureter muscles contraction movements caused pain in renal colic. Magnesium sulphate could influence the pain by reducing acetylcholine in the nerve terminals. We have aimed to evaluate the analgesic effects of magnesium sulphate on acute renal colic pain. METHOD: In this double-blind clinical trial study, the patients with renal colic pain were randomly divided into 2 groups; Group I received an intravenous infusion of 30 mg of Ketorolac and normal saline as placebo, Group II 50 mg/kg magnesium sulphate 50%/100 ml normal plus 30 mg of Ketorolac. The pain severity of patients was assessed using the visual analog scale (VAS) at baseline, and 15 and 30 min after intervention. RESULTS: Baseline pain score and demographic characteristics did not significantly different between the groups. After 30 min the pain score significantly reduced in both groups. While, at 15 and 30 min, mean pain score did not show statistically significant differences. CONCLUSION: Our findings indicated that Magnesium sulphate did not influence renal colic pain relief.

ED treatment of migraine patients has changed.

STUDY OBJECTIVES: Numerous studies have shown benefits of nonnarcotic treatments for emergency department (ED) migraine patients. Our goal was to determine if ED treatment of migraine patients and the rate of return within 72 h have changed. METHODS: Design: Multi-hospital retrospective cohort. POPULATION: Consecutive ED patients from 1-1-1999 to 9-31-2014. PROTOCOL: For determining treatments, we examined charts at the beginning (1999-2000) and end (2014) of the time period. We combined similar medications into the following groups: parenteral narcotics, oral narcotics, antihistamines and dopamine receptor antagonists prochlorperazine/metoclopramide (DRA). We calculated the percent of migraine patients given each treatment in each time period. We identified those who returned to the same ED within 72 h, and calculated the difference in annual return rates between 1999-2000 and 2014. RESULTS: Of the 2,824,710 total visits, 8046 (0.28%) were for migraine. We reviewed 290 charts (147 in 1999-2000 and 143 in 2014) to determine migraine treatments. The use of IV fluids, DRA, ketorolac and dexamethasone increased from 1999-2000 to 2014, whereas narcotic use and discharge prescriptions for narcotics decreased. Of the 8046 migraine patients, 624 (8%) returned within 72 h. The return rate decreased from 1999-2000 to 2014 from 12% to 4% (difference = 8%, 95% CI 5%-11%). CONCLUSION: For ED migraine patients, the use of IV fluids, DRA, ketorolac and dexamethasone increased whereas the use of narcotics and discharge prescriptions for narcotics decreased. The return rates for migraines decreased. We speculate that the increased use of non-narcotic medications contributed to this decrease.

Self-Reported Pain Interference and Analgesic Characteristics in Rural Older Adults.

BACKGROUND: Pain impacts the lives of millions of community-dwelling older adults. An important characteristic of pain is "pain interference" which describes the influence of pain on function. A description of pain interference is limited in rural settings where the number of older adults is expected to increase, and health disparities exist. AIMS: The purpose of this study was to describe pain interference and analgesic medication use, highlighting those that may be potentially inappropriate in a sample of rural community-dwelling older adults. DESIGN: This secondary analysis was from a cross sectional study. SAMPLE AND SETTINGS: Data were analyzed from a sample of 138 rural community-dwelling older adults. METHODS: Statistical analyses were performed on demographics, health characteristics, pain interference, and potentially inappropriate analgesic medication data. RESULTS: Pain interference with work activity was reported by 76% of older adults overall, with 23% reporting moderate and 4% extreme interference, and 41% reported sleep difficulty due to pain. Higher pain interference was significantly associated with higher body mass index, more health providers, and the daily use of non-steroidal anti-inflammatory drugs (NSAIDs). Older women experienced more sleep difficulties due to pain. Over-the-counter analgesics were used most frequently by rural older adults to manage pain. Of most risk was the daily use of NSAIDs, in which only 30% used medications to protect the gastrointestinal system. CONCLUSIONS: Older adults in rural settings experience pain interference and participate in independent-medicating behaviors that may impact safety.

The effect of critical process parameters of the high pressure homogenization technique on the critical quality attributes of flurbiprofen nanosuspensions.

Flurbiprofen (FB) is an effective nonsteroidal anti-inflammatory and BCS class II drug and its poor solubility plays a critical role in limiting its bioavailability. Nanosuspensions can be defined as nanosized colloidal dispersions of drug particles stabilized with stabilizers. The solubility of poor soluble drugs can be increased thanks to their small size and large surface area. The aim of this study is to optimize FB nanosuspensions. The formulations were stabilized with Plantacare 2000® as a surfactant using a combination of High Speed Homogenization (HSH) and High Pressure Homogenization techniques (HPH). We also investigated the effects of the critical process parameters (CPPs) of these techniques (homogenization speed & time for HSH and homogenization pressure & cycle for HPH) on three critical quality attributes of nanosuspensions, being the particle size (PS), polydispersity index (PDI) and zeta potential (ZP). After the optimization of HSH, the macrosuspension was transferred to a high pressure homogenizer. After producing FB nanosuspensions by the HPH technique, seven processes which comprise different homogenization pressures, or combinations and different cycles, were applied. Due to the combination of HSH and HPH techniques and the optimization of CPPs, an optimum formulation for a dermal application was found using a 33 full factorial design with these process parameters, and characterization studies were also performed.

Pharmacological control of inflammation in wound healing.

Wound inflammation is a rapid and highly orchestrated process that significantly impacts the wound healing cascade. Consequent to injury, a series of events set off that include inflammatory, proliferation and maturation phases leading to wound closure and restoration of normal skin integrity. Stimuli causing stress to host immune system or induce inflammatory response include tissue damage and pathogenic microbial infection.Several evidences points towards the positive role of inflammation as it essential to fight against the attack of invading pathogens and to remove dead tissues from the site of injury. Besides its positive role, prolonged inflammation is injurious and may result in deregulated stages of the wound healing which may lead to excessive scarring. Achieving balance in inflammatory cascade is one of the challenging tasks for development of a wound healing drug. This review mainly focuses on the pharmacological control of inflammation by agents which critically balance the inflammatory cascade. However, none of the agent is available in the healthcare market which exclusively plays a role in wound repair. In this review we shall explore different factors or agents affecting inflammation in wound healing. This information might be helpful in designing and development new process, technologies or drugs for better management of wound care. In addition, understanding the effect of inflammation on the outcome of the healing process will serve as a significant milestone in the area of pathological tissue repair.

Dexibuprofen: Statistical assessment of drug release kinetics and investigative quality perspective.

Healthcare professionals including physicians and pharmacists have been trying since long to come across and work out regarding the issue of generic alternatives, which is highly affected by factors like therapeutic efficacy, cost effectiveness, aesthetic and elegant appearance and implementation of packaging number over the drug product. However, the community pharmacist professionals are also facing difficulty in making decision regarding selection and dispensing the most efficacious brand to the patients. In this regard, the initiation of recent approaches for the development of amenable drug products has led to evolve the concept of generating new avenues for achieving higher patient compliance. Hence, the objective of this study was to evaluate the quality attributes and make comparisons regarding different brands of Dexibuprofen available in market of Karachi, Pakistan. The study is based on evaluation of physical chemical parameters of five different brands. Moreover, a comparative dissolution profile of selected brands of Dexibuprofen was also performed by applying numerous approaches. DEX-1was selected as reference while DEX-2- DEX-5 was selected as test brands. Results of all the selected brands met all the compendial requirements. Interpretation of the entire aforementioned test was evaluated using model independent, model- dependent and one - way ANOVA. The work presented in this study has been designed to provide quality standard products easily accessible in Pakistani market.

Pharmaceutical and in vitro therapeutic equivalence studies of ketoprofen enteric coated 100 mg tablets.

The objective of this study was to assess the quality of six different brands of enteric coated Ketoprofen 100 mg tablets, KPB2 to KPB6 are available in commercial market of Karachi, Pakistan, while KPB1 was obtained from international source. We performed different physico-chemical assessments i.e. weight variation, diameter, hardness, friability, thickness, disintegration, content uniformity, assay and dissolution test. Results of all the investigations were found to be in adequate limits. Also pharmaceutical equivalence was determined by selecting different tests and assay assessment. Furthermore, in vitro therapeutic equivalence was also estimated at phosphate buffer pH 6.8 and 7.5. Results were evaluated by one way ANOVA, model independent and model dependent methods. ANOVA results showed that release behaviour were found to be similar as p values >0.05, also KPB 1 - KPB6 followed Weibull model at different dissolution media. Results indicated that innovator and brands not only passes the pharmaceutical equivalence assessment but also comply with the in vitro therapeutic equivalence.

Quality surveillance of immediate release aceclofenac tablets (100 mg) available in local market.

Aceclofenac is considered to be an effective drug that has been widely prescribed for multi-medical complaints globally. Owing to high demand many generic counterpart of aceclofenac tablets are now available in the commercial market. The aim of the present work is to evaluate and compare the quality attributes of various national/local brands of aceclofenac immediate release tablets (100mg) with the standard multi-national brand available in Pakistan. Physico-chemical evaluation was performed by determining the average tablet weight, thickness, hardness, disintegration time, percent dissolution and assay. Moreover, brands and reference formulation were exposed to multipoint dissolution. The in vitro drug release pattern was examined in various pH environment (1.2, 4.5 and 6.8) using USP dissolution apparatus 2 (paddle) at 50 rpm. The data was then analyzed by model dependent (Zero-order, first-order, Higuchi, Hixson-Crowell, Korsmeyer & Peppas, and Weibull model), pair wise procedure (f1 & f2) and one-way ANOVA methods. Results showed that the all aceclofenac brands and the reference tablets followed Weibull kinetics at pH 6.8. f1 & f2 were also found to be within the acceptable FDA limits. Furthermore, the values of One-way ANOVA also confirmed the absence of any significant difference among various aceclofenac brands.

National cross-sectional study of nonsteroidal anti-inflammatory drugs use highlights differences between parents and professionals and prompts safety concerns.

AIM: Controversy surrounding the safety of nonsteroidal anti-inflammatory drugs (NSAIDs) provides an opportunity to study parents' and healthcare professionals' differential use of over-the-counter drugs. METHODS: In this national cross-sectional study, general practitioners, paediatricians and pharmacists were asked to include up to five consecutive febrile paediatric patients aged 1 month to 12 years. Parents and healthcare professionals completed questionnaires about the current fever episode. We studied the differential use of NSAIDs by parents and healthcare professionals notably in three clinical conditions with various estimated risk of NSAIDs complications: varicella, gastroenteritis and pharyngitis. RESULTS: The 1534 healthcare professionals prescribed 15% of the 6596 children with an NSAID, but 32% of the parents gave their child an NSAID. Generally, NSAID use was associated with older children, higher temperatures, pain due to otitis and the absence of a rash or gastroenteritis. The differential use of NSAIDs by parents and professionals was greater in conditions with high than low estimated risks of NSAID complications, with odds ratios ranging from to 9.0 to 2.9, respectively. CONCLUSION: The differential use of NSAIDs by healthcare professionals and parents for clinical conditions with potential risks should prompt discussions about the safety of their over-the-counter status.

Application of quality by design (QbD) to formulation and processing of naproxen pellets by extrusion-spheronization.

The aim of this research was to apply quality by design (QbD) to the development of naproxen loaded core pellets which can be used as the potential core for colon-specific pellets. In the early stages of this study, prior knowledge and preliminary studies were systematically incorporated into the risk assessment using failure mode and effect analysis (FMEA) and fishbone diagram. Then Plackett-Burman design was used to screen eight potential high risk factors (spheronization speed, spheronization time, extrusion speed, drying method, CCMC-Na concentration, lactose concentration, water concentration and Tween 80 concentration) obtained from the above risk assessment. It was discovered that out of the eight potential high risk factors only three factors (spheronization speed, extrusion speed and CCMC-Na concentration) had significant effects on the quality of the pellets. This allowed the use of Box-Behnken design (BBD) to fully elucidate the relationship between the variables and critical quality attribute (CQA). Finally, the final control space was established within which the quality of the pellets can meet the requirement of colon-specific drug delivery system. This study demonstrated that naproxen loaded core pellets were successfully designed using QbD principle.

Quality evaluation and in vitro interaction studies between levofloxacin 250mg and diclofenac sodium 50mg tablets.

Fluoroquinolones are broad-spectrum antibiotics, work against Gram-positive and Gram-negative bacteria and are a clinically proven option for many resistant infections. Among fluoroquinolones Levofloxacin works best against acute sinusitis, inflammation of the lower airways, acute exacerbation of chronic bronchitis, community acquired pneumonia, complicated urinary tract infection including Pyelonephritis, chronic bacterial prostatitis and skin and soft tissue infection. Levofloxacin is a frequently prescribed antibacterial agent with Diclofenac Sodium for pain management in infectious conditions. The objective of the present work is to evaluate the level of interaction between Levofloxacin and Diclofenac Sodium. In this work market available brands of both drugs were also evaluated for quality.The physiochemical parameters like weight variation, thickness variation, and mechanical strength were determined. Similarly the percentage drug release and content uniformity test were also analyzed; the tested quality attributes were found within the recommended pharmacopeia ranges except brand L(6) that had high drug content 124.629±3.614 while brand L(4) and L(5) were not found similar in pH 1.2. When subjected to model dependent analysis Levofloxacin showed compliance with (first order, Higuchi, Hixson Crowell and Weibull) at pH (1.2, 4.5 and 6.8). However Diclofenac Sodium showed adherence with (first order, Hixson Crowell and Weibull) at pH (1.2, 4.5 and 6.8) but following Higuchi at pH 1.2 and 4.5 only. The interaction studies were also performed spectrophotometrically and simultaneous equation was used to estimate the percentage availability of both the drugs at pH 4.5, 6.8, FaSSGF and FaSSIF. The studies showed that the percent availability of Levofloxacin was increased significantly in FaSSIF i.e. 129.173±0.323 at 45 minutes in the presence of Diclofenac Sodium.

Determination of organic volatile impurities in nepafenac by GC method.

The methods for controlling volatile impurities, including reagent and starting material, in Nepafenac active pharmaceutical ingredient, are reported. The proposed methods were developed using gas chromatography (GC) and gas chromatography with headspace injection (GC-HS) and validated according to the requirements of the ICH (International Conference of Harmonization) validation guidelines Q2R1 and the guideline for residual solvents Q3C.

Evaluation of analgesic effect, joint function recovery and safety of meloxicam in knee osteoarthritis patients who receive total knee arthroplasty: A randomized, controlled, double-blind study.

ABSTRACT: Meloxicam is commonly administrated to control postoperative pain in orthopedic surgery, while its efficacy in total knee arthroplasty (TKA) is not clear. Therefore, this study aimed to explore the postoperative analgesic effect and tolerance of meloxicam in knee osteoarthritis (OA) patients undergoing TKA.Totally, 128 knee OA patients scheduled for TKA were enrolled in this randomized, controlled, double-blind study, then randomized into meloxicam group (N = 65) and control group (N = 63) as 1:1 ratio. Patients took meloxicam or placebo from 4 hours (h) to 72 h after TKA. Patients were followed up at 6 h, 12 h, day (D)1, D2, D3, D7, month (M)1, and M3.Pain visual analog scale score at rest was decreased in meloxicam group at 12 h, D1 and D3 compared to control group; pain visual analog scale score at flexion was reduced in meloxicam group at 6 h, 12 h, D1, D2, and D3 compared to control group. Additional and total consumption of patient-controlled analgesia were both attenuated in meloxicam group compared to control group. Furthermore, patient satisfaction score was higher on D1, D2, D3 in meloxicam group compared to control group. However, no difference of hospital for special surgery knee score score at M1 or M3 was found between the 2 groups. Moreover, the occurrence of adverse events was similar between the 2 groups.Meloxicam displays good effect on controlling postoperative pain and improving patient satisfaction, while does not affect long-term knee function recovery or safety profile in knee OA patients undergoing TKA.

Ibuprofen Better than Acetaminophen for Reducing Fever, Pain in Young Children.

According to this study: In children younger than age two, treatment with ibuprofen was associated with reduced fever and less pain within the first 24 hours compared with acetaminophen.The incidence of adverse events was low with both treatments.

2020 American College of Rheumatology Guideline for the Management of Gout.

OBJECTIVE: To provide guidance for the management of gout, including indications for and optimal use of urate-lowering therapy (ULT), treatment of gout flares, and lifestyle and other medication recommendations. METHODS: Fifty-seven population, intervention, comparator, and outcomes questions were developed, followed by a systematic literature review, including network meta-analyses with ratings of the available evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, and patient input. A group consensus process was used to compose the final recommendations and grade their strength as strong or conditional. RESULTS: Forty-two recommendations (including 16 strong recommendations) were generated. Strong recommendations included initiation of ULT for all patients with tophaceous gout, radiographic damage due to gout, or frequent gout flares; allopurinol as the preferred first-line ULT, including for those with moderate-to-severe chronic kidney disease (CKD; stage >3); using a low starting dose of allopurinol (≤100 mg/day, and lower in CKD) or febuxostat (<40 mg/day); and a treat-to-target management strategy with ULT dose titration guided by serial serum urate (SU) measurements, with an SU target of <6 mg/dl. When initiating ULT, concomitant antiinflammatory prophylaxis therapy for a duration of at least 3-6 months was strongly recommended. For management of gout flares, colchicine, nonsteroidal antiinflammatory drugs, or glucocorticoids (oral, intraarticular, or intramuscular) were strongly recommended. CONCLUSION: Using GRADE methodology and informed by a consensus process based on evidence from the current literature and patient preferences, this guideline provides direction for clinicians and patients making decisions on the management of gout.

Comparison of kidney-tonifying and blood-activating medicinal herbs vs NSAIDs in patients with knee osteoarthritis: A protocol for a systematic review and meta-analysis.

BACKGROUND: Knee osteoarthritis (KOA) is one of the most common chronic muscular diseases in old people. In recent years, people are more and more interested in the use of Chinese herbal medicine (CHM) in the treatment of KOA, such as kidney-tonifying and blood-activating medicinal herbs (KTBAMs) in the treatment of KOA. Many studies have confirmed that KTBAMs are effective in the treatment of KOA. However, it is still unknown whether KTBAMs and NSAIDs are more effective in the treatment of KOA. Therefore, we evaluated the efficacy and safety of KTBAMs and NSAIDs in the treatment of KOA. METHODS: Randomized controlled trials (RCTs) from online databases including PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure, Chinese Scientific Journal Database, Wanfang Data, and Chinese Biomedical Literature Database that compared the efficacy of KTBAMs and NSAIDs in the treatment of KOA were retrieved. The main outcomes included the evaluation of functional outcomes, pain and adverse effects. The Cochrane risk of bias (ROB) tool was used to assess methodological quality. RESULTS: The literature will provide a high-quality analysis of the current evidence supporting KTBAMs for KOA based on various comprehensive assessments including the total effective rate, visual analog scale scores, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Lequence scores, Knee Society Scale (KSS) scores, and adverse effects. CONCLUSION: This proposed systematic review will provide up-to-date evidence to assess the effect of KTBAMs in the treatment for patients with KOA. RESEARCH REGISTRY REGISTRATION NUMBER: : reviewregistry 783.