Effectiveness of diclofenac versus paracetamol in knee osteoarthritis: a randomised controlled trial in primary care

Background

The effectiveness of diclofenac versus paracetamol in primary care patients with pain caused by knee osteoarthritis is unclear.

Aim

To assess the effectiveness of diclofenac compared with paracetamol over a period of 2, 4, and 12 weeks in patients with knee osteoarthritis.

Design and setting

Randomised controlled trial in general practice.

Method

There were 104 patients included in the study, they were aged ≥45 years consulting their GP with knee pain caused by knee osteoarthritis. Patients were randomly allocated to diclofenac (n = 52) or paracetamol (n = 52) for at least 2 weeks. Primary outcomes were daily knee pain severity, and knee pain and function measured with the Knee Injury and Osteoarthritis Outcome Score (KOOS).

Results

Over a period of 2- and 4-weeks follow-up, no significant difference in daily knee pain was found between the patient groups: estimated differences of 0.5 (95% CI = −0.2 to 1.3) and −0.2 (95% CI = −1.0 to 0.7), respectively. Over the 12-weeks follow-up, no significant differences were found between both groups for KOOS pain: estimated difference of −2.8 (95% CI = −10.7 to 5.1) and KOOS function of −2.7 (−10.6 to 5.0).

Conclusion

Over a period of 2- and 4-weeks follow-up no significant difference in daily measured knee pain severity was found between primary care patients with knee osteoarthritis taking paracetamol or diclofenac. Also, over a period of 12-weeks follow-up no significant differences were found regarding KOOS pain and KOOS function between both groups. Patients more frequently reported minor adverse events after taking diclofenac (64%) than paracetamol (46%).     

Pharmacological approach to acute pancreatitis

The aim of the present review is to summarize the current knowledge regarding pharmacological prevention and treatment of acute pancreatitis （AP） based on experimental animal models and clinical trials. Somatostatin （SS） and octreotide inhibit the exocrine production of pancreatic enzymes and may be useful as prophylaxis against Post Endoscopic retrograde cholangiopancreatography Pancreatitis （PEP）. The protease inhibitor Gabexate mesilate （GM） is used routinely as treatment to AP in some countries, but randomized clinical trials and a meta-analysis do not support this practice. Nitroglycerin （NGL） is a nitrogen oxide （NO） donor, which relaxes the sphincter of Oddi. Studies show conflicting results when applied prior to ERCP and a large multicenter randomized study is warranted. Steroids administered as prophylaxis against PEP has been validated without effect in several randomized trials. The non-steroidal anti-inflammatory drugs （NSAID） indomethacin and diclofenac have in randomized studies showed potential as prophylaxis against PEP. Interleukin 10 （IL-10） is a cytokine with anti-inflammatory properties but two trials testing IL-10 as prophylaxis to PEP have returned conflicting results. Antibodies against tumor necrosis factor-alpha （TNF-α） have a potential as rescue therapy but no clinical trials are currently being conducted. The antibiotics beta- lactams and quinolones reduce mortality when necrosis is present in pancreas and may also reduce incidence of infected necrosis. Evidence based pharmacological treatment of AP is limited and studies on the effect of potent anti-inflammatory drugs are warranted.     

Gastrointestinal safety and tolerability of oral non-aspirin over-the-counter analgesics

Over-the-counter (OTC) analgesics are routinely used worldwide for self-management of various painful conditions. Despite this, there has been little in-depth review of the safety of non-aspirin analgesics at OTC doses. This paper reviews the available literature on the gastrointestinal (GI) and hepatic safety of non-aspirin OTC analgesics, including nonsteroidal anti-inflammatory drugs (NSAIDs; ibuprofen, ketoprofen, diclofenac, and naproxen) and acetaminophen; safety in overdose is also reviewed. Each non-aspirin OTC analgesic has a distinct adverse event (AE) profile, with GI AE rates for OTC dosing in one study ranging from 37% for diclofenac to 7.2% for ibuprofen and 7.6% for acetaminophen; GI effects accounted for 75% of total AEs in the study. Across all studies reviewed here, the risk of serious GI toxicity, including upper GI bleeding and peptic ulcers, was low at OTC doses. By contrast, while both NSAIDs and acetaminophen may be associated with hepatotoxicity and acute liver failure (ALF), the risks associated with acetaminophen are somewhat higher and better documented. Reports of NSAID-associated hepatotoxicity rarely make distinctions by dose, making the risk at OTC doses difficult to assess. Liver injury due to acetaminophen, however, can occur at doses < 4000 mg. Case reports of NSAID-associated overdose are rare, while acetaminophen-containing drugs are a leading cause of overdose and are implicated in up to 97% of ALFs leading to transplant involving overdose. OTC analgesics are effective for self-management of pain; however, they are associated with a low but important rate of GI and hepatic events, as well as a risk of intentional and non-intentional overdose. Given the widespread use of this class of drugs, it is important for healthcare professionals to be mindful of their patients’ use of OTC analgesics.     

双氯芬酸钠水分离联合转核技术在超声乳化术中的应用

目的：研究双氯芬酸钠水分离联合转核技术对预防白内障超声乳化术后后发性白内障的影响。

方法：将2013-01/2014-12在我院接受白内障超声乳化术的80例86眼患者纳入研究,随机分为两组,观察组患者接受双氯芬酸钠水分离联合转核操作,对照组患者接受平衡液水分离。比较两组患者的后发性白内障程度、视力水平和角膜内皮细胞计数。

结果：(1)后发性白内障程度：观察组患者的后发性白内障程度优于对照组(Z=6.982,P<0.05);(2)视力水平：术后1、2、3、4wk时,观察组的患眼视力水平均高于对照组(0.37±0.07 vs 0.23±0.04,0.68±0.09 vs 0.35±0.05,0.77±0.09 vs 0.48±0.06,0.91±0.12 vs 0.68±0.08; F=6.583, 8.983,7.182,5.492; P<0.05);(3)角膜内皮细胞计数：术后1、2、3、4wk时,观察组与对照组角膜内皮细胞计数比较,差异无统计学意义(F=1.841,1.003,0.077,0.390; P>0.05)。

结论：双氯芬酸钠水分离联合转核技术能有效降低后发性白内障发生率,且眼内使用较为安全。     

Delivery and Biodistribution of Traceable Polymeric Micellar Diclofenac in the Rat

The nonsteroidal anti-inflammatory drugs elevate cardiovascular risk, perhaps, due to their accumulation in the heart and kidneys. We designed nanodelivery systems for cardiotoxic diclofenac to reduce its presence in these organs. Diclofenac ethyl ester (DFEE) was encapsulated in traceable micelles based on poly(ethylene oxide)-b-poly(ε-caprolactone) (DFEE-PCL-TM) or poly(ethylene oxide)-b-poly(α-benzyl carboxylate-ε-caprolactone) (DFEE-PBCL-TM). Diclofenac pharmacokinetics and tissue distribution were studied after intravenous (iv) and intraperitoneal administration of the nanoformulations and compared with those after iv doses of free diclofenac (n = 3-6/group). The average diameters for DFEE-PBCL-TM and DFEE-PCL-TM were 37.2 ± 0.06 and 45.1 ± 0.06 nm, respectively. Drug concentration dropped below the assay sensitivity after free drug administration in 6 h, but persisted for 24 h following DFEE-PBCL-TM (2.3 ± 1.4 μg/mL) and DFEE-PCL-TM (1.9 ± 0.6 μg/mL) iv administration. The diclofenac heart:blood and kidney:blood ratios were 5- to 12-fold lower with the nanoformulations than with free diclofenac. Near-infrared fluorescence measurements in tissues suggested exposure patterns to nanocarriers parallel with those achieved for delivered diclofenac by nanoformulations. Administration of DFEE-PCL-TM by iv or intraperitoneal injection, resulted in comparable pharmacokinetics and 6 h postdose near-infrared fluorescence in the heart, kidneys, liver, and spleen. When compared to each other, DFEE-PBCL-TM showed significantly lower diclofenac levels in the heart compared to DFEE-PCL-TM (0.3 ± 0.03 vs. 0.5 ± 0.1 μg/g). Developed nanoformulations of diclofenac prolonged diclofenac circulation and reduced its presence in the heart and kidneys, strongly suggesting cardiac-safe delivery vehicles for diclofenac.     

抗风湿类中成药及保健品中非法添加双氯芬酸钠的快速筛查方法研究

目的建立抗风湿类中成药和保健品中非法添加双氯芬酸钠的快速筛查方法。方法采用一种化学方法进行快速筛查,同时建立高效液相色谱法测定含量,并用高效液相色谱-二极管阵列检测器和超高效液相色谱-串联三重四级杆质谱联用仪对样品进行确证。结果 50批样品中共检出15批阳性样品,漏检率为0,误检率为0,正确率为100%,阳性样品含量分别在7⁴0 mg/粒。结论本快筛方法灵敏度高,专属性强,操作简便快捷,环保安全,经济适用,适用于基层单位的快速筛查。     

Albumin‐binding of diclofenac and the effect of a site II inhibitor in the aqueous humor of cataract patients with the instillation of diclofenac

Diclofenac instillation has been used widely in cataract surgery to prevent postoperative inflammation. Since diclofenac binds strongly to albumin in the circulation, it does not have a sufficient effect on patients in whom diclofenac binds strongly to albumin in the aqueous humor. A decrease in diclofenac binding and an increase in free diclofenac levels are necessary in these patients. The binding of diclofenac to albumin was investigated in the aqueous humor. In a diclofenac binding assay with albumin in the aqueous humor of individual patients, diclofenac was extracted from aliquots of the aqueous humor, and its total levels were measured using ultra high performance liquid chromatography (UHPLC). Free diclofenac levels were measured using ultrafiltration and UHPLC. The albumin‐binding fraction of diclofenac was 0.8 or higher in the aqueous humor of some patients. Ibuprofen significantly inhibited diclofenac binding to site II of albumin in mimic aqueous humor, but not in pooled aqueous humor. This difference may have been due to the weak binding of diclofenac to site II in the pooled aqueous humor. Flurbiprofen was used instead of diclofenac. Flurbiprofen has been shown to bind more strongly than diclofenac to the same site of albumin. Thus, the inhibitory effect of ibuprofen on the binding of flurbiprofen to albumin was investigated in pooled aqueous humor. The results indicated that ibuprofen significantly inhibited the flurbiprofen binding. An effective diclofenac administration method may be established for clinical application by the instillation of an appropriate inhibitor of binding to the albumin site II. Copyright © 2014 John Wiley & Sons, Ltd.     

HPLC法测定复方愈酚麻黄糖浆中四种成分的含量

目的建立测定复方愈酚麻黄糖浆中盐酸麻黄碱、愈创甘油醚、马来酸氯苯那敏、双氯芬酸含量的HPLC方法。方法采用Insteril ODS-3C18色谱柱,梯度洗脱,流速：1．0mL·min^-1,柱温：30℃,检测波长：257nm。结果盐酸麻黄碱、愈创甘油醚、马来酸氯苯那敏、双氯芬酸分别在0．4018～6．4287μg（r=0．9999）、3．1836～50．9379μg（r=0．9999）、0．1610～2．5762μg（r=1．0000）、0．1485～2．3759μg（r=0．9999）范围内线性关系良好,平均回收率分别为99．589／6（RSD=0．39％）、99．58％（RSD=0．30％）、99．36％（RSD=0．29％）、99．40％（RSD=0．46％）（n=9）。结论本方法经方法学验证可用于复方愈酚麻黄糖浆中盐酸麻黄碱、愈创甘油醚、马来酸氯苯那敏、双氯芬酸的含量检测。     

Preparation,characterization, and antibacterial activity of diclofenac-loaded chitosan nanoparticles

Emerging antibiotic resistance necessitates the development of new therapeutic approaches. Many studies have reported the antimicrobial activity of diclofenac sodium (DIC) and chitosan nanoparticles (CNPs). Hence, this study aimed to prepare non-antibiotic DIC-loaded CNPs (DIC.CNPs) and characterize their in vitro antibacterial activity. DIC.CNPs were prepared from low and high molecular weight (LMW and HMW, respectively) chitosan using an ionic gelation method. Prepared NPs were characterized, and their antibacterial activity against gram-positive Staphylococcus aureus and Bacillus subtilis was evaluated using the agar diffusion and broth dilution methods. The particle size, polydispersity index (PDI), and encapsulation efficiency of the formulated DIC.CNPs increased with increasing MW of chitosan. The prepared NPs showed a narrow size distribution with low PDI values (0.18 and 0.24) and encapsulation efficiency (29.3% and 31.1%) for LMW.DIC.CNPs and HMW.DIC.CNPs, respectively. The in vitro release profile of DIC from the DIC.CNPs was biphasic with a burst release followed by slow release and was influenced by the MW of chitosan. DIC.CNPs exhibited significantly higher antibacterial activity against S. aureus (minimum inhibitory concentration [MIC₉₀] _LMW.DIC.CNPs?=?35?µg/mL and MIC_{90 HMW.DIC.CNPs}?=?18?µg/mL) and B. subtilis (MIC_{90 LMW.DIC.CNPs}?=?17.5?µg/mL and MIC_{90 HMW.DIC.CNPs}?=?9?µg/mL) than DIC alone did (MIC_{90 DIC}?=?250 and 50?µg/mL against S. aureus and B. subtilis, respectively). The antibacterial activity was influenced by pH and the MW of chitosan. Collectively, these results may suggest the potential usefulness of DIC.CNPs as non-antibiotic antibacterial agent necessitating further future studies to asses the stability of DIC.CNPs prepared.