Diabetes insipidus. Current treatment recommendations.

Cranial diabetes insipidus (DI) arises when release of arginine vasopressin (AVP, antidiuretic hormone) in response to osmotic stimuli is inadequate. The correct diagnosis and management of cranial DI is particularly important when it arises as an acute complication of surgery, trauma or in subjects who lack thirst sensation. Desmopressin (1-desamino-8-D-arginine-vasopressin, DDAVP) provides an effective and convenient replacement therapy when given by the intranasal route. However, nasal administration is difficult for some patients, and in the future oral or transcutaneous desmopressin formulations may prove to be satisfactory alternatives. By contrast, treatments for nephrogenic DI, where there is failure of the antidiuretic response to endogenous or exogenous vasopressin, have been disappointing and water replacement remains the mainstay of therapy. An understanding of the physiology and pathophysiology of water homeostasis and correct interpretation of water balance and electrolyte data are essential for correct diagnosis and management of all cases of DI.     

Prevention of osteoporosis. Current recommendations.

Osteoporosis and its treatment have attracted much attention in recent years, especially since the widespread recognition of its association with the menopause. The resulting fractures are a cause of considerable morbidity and mortality in the elderly, and current costs of treating these patients has been estimated to be in excess of pounds 500 million per annum in the UK. As the causes of osteoporosis are now recognised the condition may be largely preventable, especially in women, and significant savings in health expenditure could be made if preventive methods are applied to those most at risk. The most well researched preventive treatment for osteoporosis is hormone replacement therapy (HRT) which offers additional benefits to those who choose it. Alternative methods currently under investigation for those who cannot or will not use HRT include those agents which inhibit the resorption of bone and those that stimulate the production of new bone. Treatment of established disease, i.e. attempts at increasing bone density in those with significant loss, is more difficult and methods so far investigated are not without risks and adverse effects. Furthermore, whether an increase in bone mineral density results in a reduced rate of fracture incidence has yet to be confirmed.     

Treatment of Wilms' tumour. Current recommendations.

Wilms' tumour (nephroblastoma, renal embryoma) is the fifth most common paediatric malignancy, arising from the embryonal tissue of kidneys and first formally described by Max Wilms in his classic 1899 monograph. Until the early part of this century, Wilms' tumour was associated with a less than 20% survival rate. The current survival rate exceeds 80%, primarily due to large multi-institutional trials such as the National Wilms' Tumor Study (NWTS). These studies have refined and defined the roles of surgery, chemotherapy, and radiation in treating Wilms' tumour, based on staging and histology. The dramatic improvement in the prognosis for children with Wilms' tumour, especially over the past 20 years, represents a landmark achievement in the history of paediatric oncology. Specific treatment recommendations are based on the current National Wilms' Tumor Study IV schema. Stages I and II favourable histology patients do not receive radiotherapy, but are treated postoperatively with 'pulsed' or 'conventional' dactinomycin and vincristine; stage III favourable histology requires postoperative abdominal radiotherapy followed by triple agent, 'conventional' or 'pulsed' chemotherapy (dactinomycin, doxorubicin and vincristine). Patients with stage IV favourable histology, stages II to IV anaplastic, clear cell or rhabdoid histology, are treated similarly with aggressive triple-agent chemotherapy, with the addition of radiotherapy to selected sites. Recurrent and adult Wilms' tumours have poor prognoses and are treated with aggressive surgery, radiotherapy and chemotherapy.     

Infective endocarditis. Current recommendations for prophylaxis

Antibiotic prophylaxis is indicated for any patient with a predisposing cardiac lesion who undergoes a procedure likely to produce bacteraemia with an organism having the propensity to cause bacterial endocarditis. Cardiac abnormalities have been ranked according to their approximate risk and it is known that the organisms most likely to cause endocarditis are viridans streptococci, Group D streptococci and staphylococci. The procedures likely to induce bacteraemia with each of these are, respectively, dental and upper respiratory with bleeding, urinary and gastrointestinal, and cardiac valve surgery. Antibiotic prophylaxis is impractical when bacteraemia cannot be anticipated and is unnecessary when it is due to organisms such as anaerobes and Gram-negative bacilli which rarely colonise the endocardium. A variety of prophylactic antibiotic regimens, directed against the common aetiological organisms, have been evaluated in animal models of infective endocarditis and it is on the basis of this kind of indirect evidence that several expert committees have made and regularly update their recommendations. Because infective endocarditis is an uncommon disease, a controlled clinical trial to prove the efficacy of prophylaxis would require the enrolment of a prohibitive number of patients. Consequently, there is room for differences of opinion over what constitutes optimum prophylaxis in any particular situation. This review examines the rationale for prophylaxis and compares and contrasts several authoritative recommendations, among which the trend in recent years has been towards simpler oral regimens.     

Drug therapy for nocturnal enuresis. Current treatment recommendations.

It is estimated that enuresis occurs in 5 to 7 million children in the United States. The treatment approach for enuresis is controversial, in large part due to a lack of consensus as to the exact cause of enuresis. Several factors either alone or together may contribute to this syndrome. In addition, there is strong evidence of a genetic component to enuresis. Pharmacotherapy continues to be the preferred treatment for both physicians and families. The most widely used drugs include antidepressants, anticholinergics, and desmopressin. The tricyclic antidepressant imipramine has been used extensively since the 1960s. The exact mechanism of action in enuresis is unknown although it appears to be related to the anticholinergic and antispasmodic effects of the drug. The most common adverse effects reported with imipramine include personality changes, insomnia, anorexia and anxiety. There has been renewed interest in antidiuretic treatment of enuresis. Researchers have found that enuretic children do not have the ability to reduce urine volume at night or concentrate the urine they produce during the night. Clinical trials with desmopressin administered by nasal inhalation report a marked reduction in enuretic episodes. Adverse effects were limited to nasal complaints, rhinitis, or epistaxis. Additional long term studies are needed to delineate desmopressin's role in therapy. Although the number of options for treatment of enuresis is expanding, criteria to predict patient response need to be defined.     

Current recommendations for the treatment of Lyme disease.

Lyme disease is a multisystem inflammatory disease caused by infection with Borrelia burgdorferi. Soon after the tick bite which transmits the infection, the pathognomonic skin rash erythema chronicum migrans occurs in 50 to 70% of patients, often with associated symptoms resembling a 'summer cold' or viral infection. Therapy for this stage of disease consists of 3 to 4 weeks of oral therapy. The agents currently used are: amoxicillin (500 mg 3 or 4 times daily) with or without probenecid 500 mg 3 times daily, doxycycline (100 mg twice daily), or tetracycline (500 mg 4 times daily). Longer duration therapy has never been evaluated and therefore is not currently indicated. Even patients with severe early manifestations of Lyme disease should be treated orally. Later features of Lyme disease include carditis and neurological disease, which can occur days to approximately 9 months after the onset of illness, and arthritis and neurological disease which can occur weeks to years after the onset of the illness. Treatment at this stage is with 2 to 3 weeks of intravenous antibiotics, currently cefotaxime (3 g every 12 hours), ceftriaxone (1 g every 12 hours or 2 g every day) and benzylpenicillin (14 g in divided doses). There is no evidence that longer duration therapy is indicated or more efficacious. The exception to this suggestion is the patient with isolated facial seventh cranial nerve palsy; if such a patient has no other signs or symptoms to suggest Lyme disease and has normal spinal fluid, oral therapy is usually sufficient, although some physicians will give concomitant corticosteroids to hasten the resolution of the palsy. Of major consequence to the practitioner and patient is the possibility that persistent symptoms (e.g. fibromyalgia) may be caused by a process which is no longer antibiotic-sensitive. Special care in the management of so-called 'chronic Lyme disease' is crucial lest the clinician prescribes prolonged or unending courses of antibiotics for such noninfectious problems.     

Current drug therapy recommendations for the treatment of endometriosis.

The principal symptoms and signs of endometriosis are tissue lesions and pelvic pain. These occur to varying degrees, with a chronic pattern and a tendency for deterioration with time. Patients with endometriosis often also have fertility problems, but the relationship between this and the signs and symptoms of the disease is inconsequent; the basic pathophysiology is not exactly known. Although an immunological defect resulting in an inflammatory reaction around discharged menstrual debris in the pelvic cavity has been shown, no treatments based on this process are available. Estrogen often plays an important role in the progression of lesions and pain. Therefore, the aim of treatment usually has been to downregulate the ovaries and/or given antiestrogenic drugs as an alternative to surgical removal. As complete downregulation of the ovaries and hypoestrogenaemia does not seem to be crucial, achievement of amenorrhoea seems to be sufficient. This means that women may continue to have circulating estrogen levels so that severe hypoestrogenic adverse effects such as bone demineralisation, dry vagina, psychiatric symptoms or anabolic/androgenic effects of gestagens can be avoided. However, as both symptoms and the dependence of hormones may vary between and within women, the treatment needs to be individualised. There are a number of available treatments for endometriosis on the market and it is important for the doctor to know how to reach the therapeutic window of these treatments for each woman. It is also important to inform the patient about the different possibilities so that the treatment with the least impact on her quality of life can be chosen. When the therapeutic window has been identified, the treatment may then either be continued for a long period of time or be repeated when needed.     

Prescribing antiepileptics for the elderly: differences between guideline recommendations and clinical practice

The incidence of epilepsy in patients aged >60 years is higher than in any other period of life. Yet, until recently, what was known about the treatment of older patients with epilepsy has been inferred from studies in younger patients. A growing body of clinical evidence focused exclusively on the elderly suggests that, while some issues are similar for older and younger adults, older patients with epilepsy may require even more attention regarding antiepileptic drug (AED) selection than younger patients. This article reviews published guidelines and recommendations to identify explicit recommendations for use of specific AEDs in the elderly, and assesses the extent to which those recommendations have been adopted in clinical practice.We found that while one systematically derived guideline stated that lamotrigine may be a good choice for older patients because of its favourable adverse effect profile, only clinical recommendations based on expert opinion explicitly identified AEDs that are more and less appropriate for use in the elderly. Examination of published studies describing recent AED-prescribing patterns suggests that clinical recommendations have been, at best, slowly adopted. This observation is exemplified by the fact that older patients newly diagnosed with epilepsy are still prescribed phenobarbital--a drug identified as suboptimal in 1985.In order to better understand the delay in adopting clinical recommendations, we examine these findings in light of diffusion of innovations theory, a theory that has been used to understand dissemination of other new medical technologies. According to this theory, while it is too early to suggest that use of second-generation AEDs in the elderly has been delayed, the continued use of phenobarbital in older patients newly diagnosed with epilepsy represents a serious delay in adoption of recent guidelines. Delays may be related to lack of knowledge by primary care clinicians and emergency room physicians (who frequently treat older patients with epilepsy), lack of 'opinion leaders' in primary care and perhaps general neurology, clinicians' focus on seizure control as the primary endpoint in treating patients with epilepsy, and difficulties in changing long-standing prescribing patterns.Research targeting barriers to more appropriate prescribing is needed to determine appropriate strategies for changing AED prescribing practices in the elderly.     

Current treatment recommendations for lupus nephritis

Renal disease is common in patients with systemic lupus erythematosus and may run an extremely variable course. Specific therapy is not necessary in patients with mild kidney involvement but a careful surveillance is needed to recognise possible transformations to more severe disease classifications or flare-ups. Vigorous treatment must be started early in patients with nephritic syndrome and/or active lesions at renal biopsy, i.e. glomerular cell proliferation, necrosis and inflammation. Corticosteroids remain the cornerstone for treating lupus nephritis. However, every attempt should be made to minimise their possible toxic effects. A short course of intravenous high-dose methylprednisolone followed by moderate doses of prednisone is a relatively nontoxic regimen which is generally effective in reversing the flare-ups of the disease. Once the activity is quenched the maintenance dosage of steroids should be reduced to the lowest possible dose, trying to switch the patient to an alternate-day regimen whenever possible. In patients with persisting activity the administration of a cytotoxic agent may obviate the need for protracted high-dose corticotherapy. Intermittent intravenous cyclophosphamide pulses may be considered in nonresponding patients. Other approaches, with cyclosporin, lymphoid irradiation, etc. although promising, are still preliminary. Although we are still far from an optimal treatment of lupus nephritis, the refined use of corticosteroid and cytotoxic agents and a careful monitoring of patients may allow excellent patient and kidney survival rates for 10 or more years.     

Current pharmacotherapeutic recommendations for acute pancreatitis

Disease severity in patients with acute pancreatitis varies from mild disease with minimal morbidity to severe disease in which a whole spectrum of local and systemic complications may occur. Infectious complications frequently arise, and pancreatic necrosis in particular is an important risk factor for mortality. Several strategies have been investigated to stop the progression of organ dysfunction, targeting different steps in the pathogenesis, but none of these have proved beneficial. In recent years, the widespread use of prophylactic antibiotics has also been in question, as one blinded study could not demonstrate an advantage. Better risk stratification methods should improve the design of future trials, so that only patients with a high probability of complications can be studied.     

Use of natural antimicrobials from a food safety perspective for control of Staphylococcus aureus

Staphylococcus aureus (S. aureus) is an important foodborne and environmental pathogen that can produce toxins in foods and cause infections in soft tissues. S. aureus that have developed resistance to the conventional antimicrobials are commonly called Methicillin-Resistant Staphylococcus aureus (MRSA) and Vancomycin-Resistant S. aureus (VRSA). Their prevalence is believed to be due to the widespread use of antibiotics. Therefore, natural antimicrobials are in urgent demand as alternatives to conventional antibiotics to treat S. aureus infections. In this review, natural antimicrobials from plant, animal and microbiological origins are discussed, including their mode of action and mechanisms of bacterial resistance, major components, chemical structure, effectiveness, synergistic effects and future prospects.     

Current anticoagulant safety

INTRODUCTION: Currently used anticoagulants such as unfractionated heparin, low-molecular-weight heparin and vitamin K antagonists, have several drawbacks, mostly related to safety. In this review, we will briefly discuss and compare the safety of anticoagulation therapy with 'old' and new agents. AREAS COVERED: Safety issues with anticoagulation therapy are mostly related to bleeding. The intensity of anticoagulation is related to the risk of bleeding and thus, for the efficacy not to be affected, must be maintained at the lower effective intensity. Several improvements have been made in the management of anticoagulation therapy; these include monitoring, pathology-based treatment schemes taking into account patient characteristics, patient education and the introduction of anticoagulation centers. Safety of novel anticoagulants is encouraging. EXPERT OPINION: Novel agents have the potential to compete with existing therapy for thromboprophylaxis, treatment and stroke prevention in atrial fibrillation. Promising results have emerged from trials comparing them with existing treatment. Not long from now we will see these new agents in the armamentarium of antithrombotic drugs.     

Current literature in. Pharmacoepidemiology and drug safety

In order to keep subscribers up‐to‐date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of pharmacoepidemiology and drug safety. Each bibliography is divided into 19 sections: 1 Books, Reviews & Symposia; 2 General; 3 Anti‐infective Agents; 4 Cardiovascular System Agents; 5 CNS Depressive Agents; 6 Non‐steroidal Anti‐inflammatory Agents; 7 CNS Agents; 8 Anti‐neoplastic Agents; 9 Haematological Agents; 10 Neuroregulator‐Blocking Agents; 11 Dermatological Agents; 12 Immunosuppressive Agents; 13 Autonomic Agents; 14 Respiratory System Agents; 15 Neuromuscular Agents; 16 Reproductive System Agents; 17 Gastrointestinal System Agents; 18 Anti‐inflammatory Agents ‐ Steroidal; 19 Others. Within each section, articles are listed in alphabetical order with respect to author. If, in the preceding period, no publications are located relevant to any one of these headings, that section will be omitted.