Bisphosphonates for cancer patients: why, how, and when?

Bisphosphonates (BPs) are potent inhibitors of osteoclast-mediated bone resorption, and it is well accepted that tumor cells in bone, especially breast cancer and myeloma cells, can stimulate osteoclast formation and activity leading to the release of growth factors or cytokines, which will further stimulate cancer cells' growth and their secretion of osteolytic factors. BPs are now the standard treatment for cancer hypercalcemia, for which a dose of 90 mg of pamidronate or 1500 mg of clodronate is recommended; the former compound is more potent and has a longer lasting effect. Repeated pamidronate infusions exert clinically relevant analgesic effects in more than half of patients with metastatic bone pain. Recent data suggest that non-responding patients should perhaps be treated with higher doses. The optimal dose actually remains to be defined, especially as it is thought that it is probably a function of the disease stage. Regular pamidronate infusions can also achieve a partial objective response according to conventional UICC criteria and they can almost double the objective response rate to chemotherapy. Lifelong administration of oral clodronate to patients with breast cancer metastatic to bone reduces the frequency of morbid skeletal events by more than one-fourth. Two double-blind randomized placebo-controlled trials comparing monthly 90 mg pamidronate infusions to placebo infusions for 1-2 years in addition to hormone or chemotherapy in patients with at least one lytic bone metastasis have shown that the mean skeletal morbidity rate could be reduced by 30-40%. The results obtained with intravenous BPs are generally viewed as better than those obtained with oral clodronate. However, preference can be given to the oral route when BPs are started early in the process of metastatic bone disease in a patient receiving hormone therapy. According to the recently published ASCO guidelines, pamidronate 90 mg i.v. delivered over 2 h every 3-4 weeks can be recommended in patients with metastatic breast cancer who have imaging evidence of lytic destruction of bone and who are concurrently receiving systemic therapy with hormonal therapy or chemotherapy. Furthermore, the ASCO Panel considered it "reasonable" to start i.v. BPs in women with localized pain whose bone scans were abnormal and plain radiographs normal, but not when an abnormal bone scan is asymptomatic. The pertinence of these criteria is discussed below. Because BPs are providing supportive care, reducing the rate of skeletal morbidity but evidently not abolishing it, the criteria for stopping their administration have to be different from those used for classic antineoplastic drugs, and they should not be stopped when metastatic bone disease is progressing. However, criteria to determine whether and for how long an individual patient benefits from their administration are lacking. New biochemical markers of bone resorption might help identify those patients continuing to benefit from therapy. Even better results have been achieved in patients with multiple myeloma, and the general consensus is that BPs should be started as soon as the diagnosis of lytic disease is made in myeloma patients. On the other hand, data are scanty in prostate cancer, but large-scale trials with potent BPs are ongoing or planned in such patients. Similar results to those achieved with pamidronate have been obtained with monthly 6-mg infusions of the newer BP ibandronate in patients with breast cancer metastatic to bone. The tolerance of ibandronate could be better, and the drug has the potential to be administered as a 15- to 30-min infusion. Zoledronate can also be administered safely as a 15-min 4-mg infusion, and large scale phase III trials have just been completed. These newer BPs will simplify the current therapeutic schemes and improve the cost-effectiveness ratio; they also have the potential to improve the therapeutic efficacy, at least in patients with an aggressive osteolytic disease or when given as adjuvant therapy. For that matter, initial data with clodronate indicate that they have the potential to prevent the development of bone metastases, but the use of BPs in the adjuvant setting must still be viewed as experimental.     

Cryotherapy for Barrett's esophagus: Who, how, and why?

Cryotherapy is a noncontact ablation method that has long been used clinically in the treatment of a wide variety of malignant and premalignant diseases. The relative ease of use and unique mechanisms of cellular destruction make cryotherapy particularly attractive for the eradication of dysplastic Barrett's esophagus. Currently, liquid nitrogen and carbon dioxide are the most common cryogens used. Preliminary data with these agents have shown high efficacy in the reversal of dysplastic Barrett mucosa and excellent safety profiles. Intense investigation on cryotherapy ablation of Barrett's esophagus is ongoing.     

Ribavirin therapeutic drug monitoring: why,when and how?

Recent studies suggest the potential interest of ribavirin therapeutic drug monitoring to improve sustain virological response rate in hepatitis C virus‐infected patients. The present review details the pharmacokinetic properties of ribavirin, suggesting that it may be a good candidate for therapeutic drug monitoring, the different possible strategies and the analytical methods that could be employed.     

Patient monitoring during gastrointestinal endoscopy: why, when, and how?

Patient monitoring is intended to reduce the risk of sedation-related cardiopulmonary complications. Physiological monitoring and visual assessment by a qualified individual should be routine during endoscopic procedures. Additionally, ventilatory monitoring should be considered for high-risk patients and those receiving sedation with propofol.     

Raising an isolated low HDL-C level: why,how, and when?

Treating patients with isolated low high-density lipoprotein cholesterol (HDL-C) remains daunting. The decision to treat depends on the individual patient's overall risk for coronary heart disease (CHD). Strategies for raising HDL-C levels can include various lifestyle and drug therapies, which should be tailored to individual patients. While no current therapy is optimal, many can yield modest increases that translate into reduced risk for CHD events.     

Shared decision making and physical therapy: What,when, how,and why?

BackgroundShared decision making is a means of translating evidence into practice and facilitating patient-centred care by helping patients to become more active in the decision-making process. Shared decision making is a collaborative process that involves patients and clinicians making health-related decisions after discussing the available options; the benefits and harms of each option; and considering the patient's values, preferences, and personal circumstances.MethodsThis paper describes what shared decision making is, why it is important, when it is appropriate, and key elements. We report on physical therapists’ current use of and attitudes to shared decision making and explore factors that influence its uptake. Lastly, we examine what is needed to promote greater use of this approach.ResultsKey elements in the shared decision making process are: identifying the problem that requires a decision; providing an explanation of the health problem, including, where appropriate, the natural history of the condition; discussing the available options and the potential benefits and harms of each option; eliciting the patient's values, preferences, and expectations; and assisting the patient to weigh up the options to reach an informed decision. When applied in practice, shared decision making has been found to improve patient-clinician communication; improve patients’ accuracy of their expectations of intervention benefits and harms, involvement in decision-making, and feeling of being informed; and increase both patients’ and clinicians’ satisfaction with care.ConclusionDespite physical therapists’ enthusiasm for shared decision making, uptake of this approach has been slow. Multi-level strategies and behaviour change are required to encourage and support the sustainable incorporation of shared decision making in practice.     

Use of gloves in the community: why, when, which and how?

The use of gloves has become routine since the early 1980s. It is recognized that they have an important part to play in the protection of both staff and patient/clients in the prevention of cross-infection. However, as choices relating to glove usage have increased over the years, health-care staff need to adopt a risk assessment approach, considering why, when, which and how gloves should be used. This article outlines the different types of gloves available and when they should be used.     

The need for treatment against human parechoviruses: how, why and when?

Since 1999, human parechoviruses (HPeVs) have been classified as a separate group in the large and expanding family of Picornaviridae. In contrast to the well-established group of the human enteroviruses (HEVs), HPeVs have long been considered as irrelevant and have only been associated with mild disease manifestations in children. The identification of HPeV-3 in 2004 and its association with neonatal sepsis, refocused attention on this neglected group of viruses. Clinically HPeV infections may mimic HEV infections and are increasingly recognized as viral causes of sepsis-like illness and CNS infections in young children. Therapy is not available against HPeVs or HEVs. In this article, we will demonstrate that therapy against this group of picornaviruses is urgently needed and we will review the current knowledge of treatment options as well as the current developments in antiviral therapy against picornaviruses in the scope of treatment possibilities against HPeVs.     

Bariatric surgery for morbid obesity: why,who, when,how, where,and then what?

Bariatric surgery is not a cure, but it can take weight off and keep it off, improve most obesity-related conditions, reduce the risk of premature death, and improve quality of life. Given the interest in the procedure, primary care physicians need to understand the risks and benefits to help patients determine if this therapy is a good option, and they need to know the health changes that may occur after surgery when following these patients.     

Pharmacologic perfusion imaging. Who needs it and why?

Pharmacologic perfusion imaging is an excellent choice for patients who cannot undergo treadmill exercise stress testing. The use of pharmacologic imaging has proved valuable in all branches of medicine and surgery. Patients requiring cardiac evaluation before vascular or orthopedic surgery can now be examined quite completely; there are very few patients today who cannot be "stressed" adequately. Advances in this field are being made every day, and the accuracy of testing will improve further when such new technologies as positron-emission tomography are more widely available.     

Laparostomy: why and when?

This article is one of ten reviews selected from the Yearbook of Intensive Care and Emergency Medicine 2010 (Springer Verlag) and co-published as a series in Critical Care. Other articles in the series can be found online at . Further information about the Yearbook of Intensive Care and Emergency Medicine is available from .     

Molecular medicine: how, what, and when?

Integrating molecular medicine into clinical practice will create many challenges. But the existing genetic testing paradigm may not be the right model for introducing these new technologies.