Drugs That Delay Wound Healing.

Drugs that delay wound healing.

Prescrire Int. 2013 Apr; 22(137): 94-8

Healing of surgical and traumatic wounds mainly involves the clotting process, inflammation, cell proliferation and tissue remodelling. Healing time depends on the depth of the wound. In order to identify drugs that can slow the healing process, we reviewed comparative clinical trials, epidemiological studies and detailed case reports, using the standard Prescrire methodology. Delayed healing of surgical or traumatic wounds is associated with persistent bleeding, increased wound seepage and, in some cases, failed wound closure. Delayed wound healing can have severe and sometimes life-threatening consequences, including deep-seated infection, prolonged hospitalisation, repeat surgery to join or rejoin the wound edges, and delayed functional recovery of a transplanted organ. Delayed healing may be due to failure of one or several steps in the healing process, caused by metabolic, cardiovascular, infectious, immunological or drug-related disorders. The principal drugs that can slow wound healing are cytotoxic antineoplastic and immunosuppressive agents, corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), and anticoagulants. In practice, when wound healing is delayed, it is best to keep in mind that a drug may be the cause, and to consider withdrawing any drug or drugs known to have this effect, in order to allow the wounds to heal. HubMed – drug


Ruxolitinib. Bone marrow fibrosis: theory versus practice.

Prescrire Int. 2013 Apr; 22(137): 93

Currently, the only curative treatment for bone marrow fibrosis is haematopoietic stem cell transplantation, but it is only feasible in a minority of patients. Ruxolitinib (Jakavi, Novartis) inhibits Janus kinases, enzymes necessary for haematopoiesis. Many cases of bone marrow fibrosis appear to be due to mutations that interfere with the expression of these kinases. Clinical assessment of ruxolitinib is based on a randomised placebo-controlled trial in 309 patients in whom conventional treatments had failed, and on a randomised, unblinded trial versus standard management in 219 patients. The patients enrolled in the placebo-controlled trial had a poor prognosis. Mortality appeared to be lower in the ruxolitinib arm after 24 and 51 weeks, but not in the trial versus standard management. Ruxolitinib had a short-lived symptomatic effect, but almost all patients enrolled in a non-comparative study discontinued ruxolitinib because of inadequate efficacy or adverse effects. Discontinuation often led to symptom rebound. The primary endpoint in these trials was the reduction in spleen volume, a surrogate outcome measure. Ruxolitinib was effective on this endpoint, but it is unclear whether reduction in spleen volume correlates with symptoms. Ruxolitinib aggravates haematological disorders associated with bone marrow fibrosis (anaemia, thrombocytopenia) and also causes neurological disorders (headache, dizziness, confusion). In practice, ruxolitinib appears to have an unfavourable harm-benefit balance in most patients. It is therefore better to avoid using this drug. Additional clinical trials are needed in patients for whom haematopoietic stem cell transplantation is not feasible, especially those with a large, expanding spleen. HubMed – drug


Bismuth + metronidazole + tetracycline. Why risk adding bismuth?

Prescrire Int. 2013 Apr; 22(137): 89-92

The standard treatment for peptic ulcer associated with Helicobacter pylori is a combination of omeprazole, amoxicillin and clarithromycin, which renders the bacterium undetectable in about 70% of cases. A fixed-dose combination of bismuth subcitrate potassium + metronidazole + tetracycline has been authorised in some European countries for use in this setting, combined with high-dose omeprazole. In a European trial with 440 patients, the 4-drug combination of omeprazole + bismuth subcitrate + metronidazole + tetracycline was significantly more active than the standard 3-drug regimen in terms of H. pylori eradication, as measured with the urea breath test (79.8% with bismuth, 55.4% without bismuth). In a North American trial with 275 patients the success rate was similar with the two treatments, again based on the urea breath test. There are no comparative trials of the 4-drug regimen in patients in whom standard treatment has failed. The main adverse effects of the 4-drug regimen observed in clinical trials were black stools, nausea, headache and dizziness. However, the trials were too small to detect infrequent but serious adverse effects such as bismuth encephalopathy. Safety during pregnancy is not known. Some patients included in clinical trials had detectable plasma bismuth concentrations. Omeprazole increases the absorption of bismuth subcitrate potassium. In practice, the 4-drug regimen combining omeprazole + bismuth subcitrate potassium + metronidazole + tetracycline is probably more effective than standard 3-drug therapy against H. pylori, at least in Europe, but this combination should be avoided due to uncertainties on the possible neurotoxicity of bismuth. Other antibiotic combinations are preferable, and there are too many questions surrounding the adverse effects of this combination for it to replace the standard 3-drug regimen in France. HubMed – drug


Effects of gabapentin on pain and opioid consumption after abdominal hysterectomy.

Pain Res Manag. 2013 Mar-Apr; 18(2): 94-6
Frouzanfard F, Fazel MR, Abolhasani A, Fakharian E, Mousavi G, Moravveji A

Postoperative pain is an important factor affecting anesthesia and surgery. The present study assessed the effects of 1200 mg gabapentin, an anticonvulsant drug that acts through voltage-dependent calcium channels, for the control of postoperative pain in patients undergoing abdominal hysterectomy. Fifty patients undergoing hysterectomy were enrolled in the present study. Subjects received either 1200 mg gabapentin or placebo 2 h before surgery. The amount of morphine consumption and level of postoperative pain at 2 h, 6 h, 12 h and 24 h after surgery were measured. There were no significant differences in age, duration of surgery and anesthesia, or body mass index between the two groups. The mean intensity of pain in the gabapentin group was significantly lower than in the placebo group. The mean amount of morphine used in the placebo group (5.2±2.8 mg) was significantly higher than in gabapentin group (1.2±0.29 mg; P=0.001). Nausea and vomiting in the placebo group was more common than in the gabapentin group (P=0.001). The time interval for initial ambulation after surgery was significantly shorter in the gabapentin group (12.24±2.18 h) compared with the placebo group (15±3.61 h; P=0.002). 1200 mg gabapentin reduced postoperative pain and the need for opioids, and enabled earlier ambulation of the patient. Significant side effects were not observed. HubMed – drug


Use and nonmedical use of prescription opioid analgesics in the general population of Canada and correlations with dispensing levels in 2009.

Pain Res Manag. 2013 Mar-Apr; 18(2): 69-74
Shield KD, Jones W, Rehm J, Fischer B

In Canada, harm from nonmedical prescription opioid analgesic (POA) use (NMPOU) has increased in recent years; however, there are limitations to the current estimates of NMPOU. The 2009 Canadian Alcohol and Drug Use Monitoring Survey presents an opportunity to produce more accurate estimates of NMPOU. To determine the prevalence of POA use, NMPOU and use of pain relievers to ‘get high’, and to assess correlations of these indicators with age, sex and provincial levels of dispensed POAs in Canada in 2009. Data regarding POA use were obtained from the 2009 Canadian Alcohol and Drug Use Monitoring Survey (n=13,032). The amount of POAs dispensed in standardized daily doses was obtained from a representative sample of 2700 retail pharmacies across Canada. Associations among POA use, age, sex and the amount of POAs dispensed were evaluated using regression models. Differences in POA use across provinces were assessed using the Wald test. In Canada in 2009, the prevalence of POA use was 19.2% (95% CI 18.0% to 20.5%), NMPOU was 4.8% (95% CI 4.1% to 5.5%) and the use of pain relievers to get high was 0.4% (95% CI 0.1% to 0.8%). NMPOU was significantly associated with age. The use of pain relievers to get high varied significantly across provinces, while POA use and NMPOU did not show significant variations. The amount of POAs dispensed per province was not significantly correlated with any type of POA use. These findings confirm high POA use and NMPOU across Canada. Research is required to identify determinants of NMPOU. HubMed – drug