Levonorgestrel intrauterine system versus medical therapy for menorrhagia

ABSTRACT: Menorrhagia is a common problem that interferes with a woman’s physical, emotional, and social life. Evidence to guide physicians for decision about therapy for heavy menstrual bleeding is lacking. One treatment option, the levonorgestrel-releasing intrauterine system (levonorgestrel-IUS), has been available in the United States since 2009. Updated meta-analyses comparing the levonorgestrel-IUS with nonhormonal and hormonal treatments showed that the levonorgestrel-IUS produced a greater reduction in menstrual blood loss at 3 to 12 months of follow-up. It is not clear whether these short-term benefits persist. Moreover, the rates of discontinuation of the levonorgestrel-IUS at 2 years are as high as 28%, and effects on bleeding-related quality of life are not known. This pragmatic, multicenter, randomized trial compared the effectiveness of the levonorgestrel-IUS with that of usual medical treatment among women with menorrhagia in a primary care setting. A total of 571 women with menorrhagia were randomized to treatment with levonorgestrel-IUS (n = 285) or usual medical treatment (n = 286). Usual treatment was tranexamic acid, mefenamic acid, combined estrogen-progestogen, or progesterone alone. The primary study outcome measure was the patient-reported score on the condition-specific Menorrhagia Multi-Attribute Scale (MMAS) assessed over a 2-year period. The MMAS scores range from 0 to 100, with lower scores indicating greater severity. Summary MMAS scores were assessed at 6, 12, and 24 months. Secondary outcome measures included general health-related quality of life, sexual-activity scores, and surgical intervention. There was a significant improvement in total MMAS scores from baseline to 6 months in both the levonorgestrel-IUS group and the usual-treatment group; the mean increase was 32.7 and 21.4 points, respectively; P < 0.001 for both comparisons. Over the 2-year follow-up, improvements were maintained in both groups but were significantly greater in the levonorgestrel-IUS group (mean between-group difference, 13.4 points; 95% confidence interval, 9.9–16.9; P < 0.001). Significantly greater improvements in all MMAS domains (practical difficulties, social life, psychological health, physical health, work and daily routine, and family life and relationships) occurred with the levonorgestrel-IUS than with the usual treatment (P < 0.001 with the use of a test for trend). This was also found for 7 of the 8 quality-of-life domains. At the 2-year end point, almost twice as many women were still using the levonorgestrel-IUS than were those receiving the usual medical treatment (64% vs 38%, P < 0.001). No significant between-group differences were noted in the rates of surgical intervention or sexual-activity scores as well as in the frequency of serious adverse events. These data show that levonorgestrel-IUS is more effective than usual medical treatment in improving the quality of life of women with menorrhagia in a primary care setting.

Should topical opioid analgesics be regarded as effective and safe when applied to chronic cutaneous lesions?

Objectives: The induction of analgesia for many chronic cutaneous lesions requires treatment with an opioid analgesic. In many patients suffering with these wounds such drugs are either contraindicated or shunned because of their association with death. There are now case reports involving over 100 patients with many different types of chronic superficial wounds, which suggest that the topical application of an opioid in a suitable gel leads to a significant reduction in the level of perceived pain. Key findings: Some work has been undertaken to elucidate the mechanisms by which such a reduction is achieved. To date there have been no proven deleterious effects of such an analgesic system upon wound healing. Although morphine is not absorbed through the intact epidermis, an open wound provides no such barrier and for large wounds drug absorption can be problematic. However, for most chronic cutaneous lesions, where data has been gathered, the blood levels of the drug applied ranges from undetectable to below that required for a systemic effect. Summary If proven, the use of opioids in this way would provide adequate analgesia for a collection of wounds, which are difficult to treat in patients who are often vulnerable. Proof of this concept is now urgently required. © 2011 Royal Pharmaceutical Society.

Pharmacology and the safe prescribing of drugs

Understanding the pharmacological principles and safe use of drugs is just as important in surgical practice as in any other medical specialty. With an ageing population with often multiple comorbidities and medications, as well as an expanding list of new pharmacological treatments, it is important that surgeons understand the implications of therapeutic drugs on their daily practice. The increasing emphasis on high quality and safe patient care demands that doctors are aware of preventable adverse drug reactions (ADRs) and interactions, try to minimize the potential for medication errors, and consider the benefits and harms of medicines in their patients. This chapter examines these aspects from the view of surgical practice and expands on the implications of some of the most common medical conditions and drug classes in the perioperative period. The therapeutic care of surgical patients is obvious in many circumstances – for example, antibacterial prophylaxis, thromboprophylaxis, and postoperative analgesia. However, the careful examination of other drug therapies is often critical not only to the sustained treatment of the associated medical conditions but to the perioperative outcomes of patients undergoing surgery. The benefit–harm balance of many therapies may be fundamentally altered by the stress of an operation in one direction or the other; this is not a decision that should wait until the anaesthetist arrives for a preoperative assessment or one that should be left to junior medical or nursing staff on the ward.