Flavocoxid is as effective as naproxen for managing the signs and symptoms of osteoarthritis of the knee in humans: a short-term randomized,double-blind pilot study

Flavocoxid (Limbrel), a proprietary mixture of flavonoid molecules (baicalin and catechin), was tested against a traditional nonsteroidal anti-inflammatory drug, naproxen, for the management of the signs and symptoms of moderate osteoarthritis (OA) in humans. Discomfort and global disease activity were used as the primary end points, and safety assessments were also taken for both treatments as a secondary endpoint. In this double-blind study, 103 subjects were randomly assigned to receive either flavocoxid [500 mg twice daily (BID)] or naproxen (500 mg BID) in a 1-month onset of action trial. Outcome measures included the short Western Ontario and McMaster University Osteoarthritis Index, subject Visual Analogue Scale for discomfort and global response, and investigator Visual Analogue Scale for global response and fecal occult blood. Both flavocoxid and naproxen showed significant reduction in the signs and symptoms of knee OA (P ≤ .001). There were no statistically detectable differences between the flavocoxid and naproxen groups with respect to any of the outcome variables. Similarly, there were no statistically detectable differences between the groups with respect to any adverse event, although there was a trend toward a higher incidence of edema and nonspecific musculoskeletal discomfort in the naproxen group. In this short-term pilot study, flavocoxid was as effective as naproxen in controlling the signs and symptoms of OA of the knee and would present a safe and effective option for those individuals on traditional nonsteroidal anti-inflammatory drugs or cyclooxygenase-2 inhibitors. A low incidence of adverse events was reported for both groups.     

Complete response, as determined by prostate-specific antigen level, to chlormadinone acetate withdrawal persisting longer than 2 years in patients with advanced prostate cancer: Two case reports

Antiandrogen withdrawal syndrome (AWS) is a well-established phenomenon in prostate cancer. However, responses to AWS are usually of limited duration, and a complete response (CR) is extremely rare. We present two patients who exhibited a chemical CR for more than 2 years after the discontinuation of steroidal antiandrogen chlormadinone acetate use. Whether patients who respond to antiandrogen withdrawal include a group of patients with a better prognosis remains uncertain. However, considering that the usual survival period of patients with hormone-resistant prostate cancer is approximately 12 months, both of the patients reported here, who are present in excellent physical condition, exhibiting an improved quality of life, and attending their hospital as outpatients, obviously acquired a prolonged survival because of AWS.     

Short-term niflumic-acid-induced acute renal failure in children

Several reports emphasize the adverse effects of non-steroidalanti-inflammatory drugs (NSAIDs) on renal function. We haveobserved over the last 10 years seven cases of acute renal failure(ARF) due to immune interstitial nephritis in children. A recommendedoral or rectal dose of niflumic acid was prescribed for ear-nose-throatdisorders, Length of exposure was 1–5 days. Clinical symptoms (oedema, oliguria or anuria) appeared between3 and 6 days. Three patients had previously received the drug.Hypersensitivity signs (fever, skin rash, eosinophilia, and/orincreased IgE) were present in all cases, leukocyturia in fivecases, and haematuria in six cases. Renal biopsy showed interstitiallesions with lymphocyte, eosinophil, and plasma cell infiltrateswithout tubular cell necrosis. Glomeruli were normal on light-microscopy,except in one patient. Electron-microscopy showed extensivepodocyte fusion in two patients, who had clinical and laboratoryevidence of nephrotic syndrome (NS). ARF rapidly disappeared after NSAID withdrawal, except in twopatients whose renal failure was irreversible despite methylprednisolonebolus. ARF is very rare in children treated with niflumic acid.When ARF occurs, different pathophysiological mechanisms areinvolved but the most common is immunological.     

Effects of two antiandrogen treatments on hirsutism and insulin sensitivity in women with polycystic ovary syndrome

Thirty-two women with polycystic ovary syndrome (PCOS) wereallocated to two antiandrogen treatment regimens; 28 women completedthe trial. Twenty women were treated with ethinyloestradioland cyproterone acetate (EO-CA) cyclically for 6 months andeight women were treated with the gonadotrophin releasing hormone(GnRH) analogue, goserelin for 6 months. Effects on hirsutism,insulin sensitivity (estimated by glucose clamp technique),blood lipids and hormones were measured. Women treated withEO-CA showed a reduction in hirsutism (P <0.05), and decreasedserum androgen concentrations (P <0.001) as well as reducedinsulin sensitivity (P <0.05). In women treated with goserelin,serum androgen concentrations also decreased (P <0.001),but there was no significant reduction of hirsutism. This group,however, showed an improved insulin sensitivity (P <0.05)despite an unchanged body mass index. Bone mineral density wasunaltered in both treatment groups. The reduction in androgenconcentrations caused by EO-CA was not paralleled by increasedinsulin sensitivity, most probably due to the effect of ethinyloestradiolper se. In contrast, the reduction in androgen concentrationsby goserelin was accompanied by an improved insulin sensitivity.     

Tryptase and histamine release during aspirin-induced respiratory reactions

The involvement of mast cells in the pathogenesis of aspirin (ASA)-induced respiratory reactions was investigated by measuring serum levels of tryptase, a neutral protease that is a specific marker of mast cell activation. ASA challenges were performed in 17 ASA-sensitive patients with asthma and rhinosinusitis, and tryptase and histamine levels were measured in their venous blood samples. In three subjects who experienced moderate to severe respiratory reactions extending to the skin and/or gastrointestinal tract, marked elevations of tryptase levels in postreaction serum samples (peak levels, 51.9 and 40.0 ng/ml) were discovered in two of these three subjects, and a small elevation of tryptase occurred in the serum of the third subject (3.1 ng/ml peak). Plasma histamine levels in postreaction samples were significantly elevated over baseline values in all three subjects (delta mean plasma histamine, 238 pg/ml versus 56 pg/ml for the remaining 14 subjects; p less than 0.04). In the remaining 14 subjects, who experienced similar respiratory reactions without extrapulmonary symptoms during aspirin challenge, changes in tryptase and histamine levels were not observed.     

Risk of Gastrointestinal Bleeding With Extended Use of Nonsteroidal Anti-Inflammatory Drug Analgesia After Joint Arthroplasty

BackgroundChronic nonsteroidal anti-inflammatory drug (NSAID) use is associated with gastrointestinal bleeding via inhibition of endogenous mucosal protection and platelet aggregation. This study aimed to determine whether extended NSAIDs after joint arthroplasty is associated with increased risk of gastrointestinal bleeding.MethodsThis was a retrospective study examining 28,794 adults who underwent joint arthroplasty by one of 50 surgeons from 2016 to 2018. Episodes of gastrointestinal bleeding within 90 days postoperatively were identified prospectively. Postoperative medications were reported directly by patients with electronic questionnaires. The primary analysis was performed using binary logistic regression.ResultsA total of 74 (0.26%) episodes of gastrointestinal bleeding occurred within 90 days (median 8 days) postoperatively. Of 5086 patients with complete data included in the primary analysis, 59.6% had used NSAIDs with median duration of 2 weeks (interquartile range, 0-6 weeks). Patients with gastrointestinal bleeding were significantly older (71.3 vs 67.0 years), required longer hospitalizations (2.1 vs 1.5 days), and more commonly had a history of peptic ulcers (10.8% vs 0.9%). However, there was no positive association between NSAID use and gastrointestinal bleeding. In fact, the odds of gastrointestinal bleeding were lower in patients taking NSAIDs. Gastrointestinal bleeding was associated with anticoagulants, antiplatelet agents, and, to a lesser extent, aspirin.ConclusionNSAIDs were not associated with gastrointestinal bleeding and may be prescribed safely for a majority of patients after joint arthroplasty. The greatest odds of gastrointestinal bleeding occurred in patients with peptic ulcer disease and those who received antiplatelet and anticoagulation agents. Increasing age and bilateral surgery were also associated with gastrointestinal bleeding.Level of EvidenceLevel III.