Effective treatment of urethritis. A practical guide.

Most cases of urethritis can be readily treated using recommended regimens. The most important causes of urethritis are Chlamydia trachomatis and Neisseria gonorrhoeae, and initial treatment is directed at them. Optimal management requires obtaining a thorough sexual history, evaluation for objective clinical and laboratory evidence of infection, antimicrobial therapy directed towards the major aetiologies, and evaluation and treatment of sexual partners. Treatment of gonorrhoea requires a single-dose regimen active against N. gonorrhoeae, plus a regimen active against C. trachomatis and nongonococcal urethritis. The usually recommended treatment for N. gonorrhoeae is a single dose of ceftriaxone 250mg intramuscularly, but there are many alternatives, including oral ones. Only in very restricted geographical areas and under restricted situations are penicillins still reliable against N. gonorrhoeae. Recommended optimal treatment of C. trachomatis or nongonococcal urethritis currently requires 7 days' treatment with a tetracycline. Some guidelines now propose ofloxacin 300 mg orally twice daily for 7 days as an equivalent alternative, and there are very promising data with a single dose therapy with azithromycin, a long-acting macrolide antimicrobial. Using recommended regimens, microbiological failure is infrequent in compliant patients. Recurrent urethritis is, however, frequent. For patients who receive recommended treatment and do well, no follow-up cultures are needed. Patients with persistent or recurrent symptoms require careful re-evaluation of the patient, documentation of urethritis, and retreatment with antimicrobial agents a second time if urethritis is documented by positive cultures or increased numbers of polymorphonuclear leucocytes in urethral secretions.(ABSTRACT TRUNCATED AT 250 WORDS)     

A practical guide to the treatment of complicated skin and soft tissue infections

Complicated skin and soft tissue infections (SSTIs) remain a common reason for hospitalisation. Optimal management of complicated SSTIs begins with a physical examination, and obtaining the complete social and medical history of the patient. Empirical intravenous antibacterial therapy is guided by expected pathogens, patient factors and diagnostic procedure reports, such as the Gram-stained smear of discharge or exudates. The majority of community-acquired SSTIs are caused by Staphylococcus aureus and beta-haemolytic streptococci. On the basis of recent surveillance data, 80-90% of these pathogens remain susceptible to cefazolin or oxacillin. Consequently, a first generation cephalosporin or an antistaphylococcal penicillin remains the first line empirical therapy for community-acquired skin and soft tissue infections. Vancomycin may be an appropriate alternative when vancomycin-resistant S. aureus is highly suspected on the basis of patient history and co-morbid conditions. With the global emergence and spread of macrolide-resistant S. aureus and beta-haemolytic streptococci, clindamycin rather than a macrolide is the recommended agent for empirical antibacterial therapy of community-acquired SSTIs in penicillin-allergic patients. Nosocomial complicated SSTIs are predominantly caused by S. aureus, Pseudomonas aeruginosa, Enterococcus spp., Escherichia coli and other Enterobacteriaceae. Piperacillin/tazobactam with or without vancomycin is the preferred agent for empirical treatment depending on local resistance statistics. The newer fluoroquinolones may have a role in the treatment of complicated SSTIs, especially in penicillin-allergic patients. More clinical studies are needed before a formal recommendation can be made. Many of the newer antimicrobial agents such as the carbapenems, oxazolidinones and streptogramins have been shown to be effective for the treatment of complicated SSTIs. However, because of their proven activity against highly resistant organisms including methicillin-resistant S. aureus and vancomycin-resistant enterococci (oxazolidinones and streptogramins), and Gram-negative bacilli producing extended spectrum beta-lactamases (carbapenems), these antibacterials should be reserved for life-threatening situations and/or when resistant pathogens are suspected. Complicated skin and soft tissue infections are often associated with exudates, ulcerations, fluid collections or abscesses. Adequate debridement of devitalized tissues and drainage of abscesses and fluid collections in addition to systemic antibacterial therapy is an integral part of appropriate management.     

A practical guide to the management of oesophageal varices

Bleeding oesophageal varices are a frequent and sometimes fatal complication of portal hypertension. Prompt resuscitation and arrest of haemorrhage are the immediate short term priorities. Vasoactive therapy to reduce portal pressure is administered on presentation. Early endoscopy is necessary to make a definitive diagnosis and initiate appropriate therapy; usually emergency sclerotherapy or banding. After the acute bleeding episode, follow-up therapy is instituted either to obliterate the varices by sclerotherapy or banding, or to chronically lower portal pressure and hence reduce the risk of bleeding pharmacologically; a combination of both strategies may be also used. Active surveillance of those at risk of developing varices is advocated. Long term beta-blocker therapy has been demonstrated to be effective in both the primary prevention of variceal haemorrhage and the prevention of rebleeding in those who have already bled. Despite a multitude of therapeutic regimes and ongoing clinical trials, mortality from this condition remains disappointingly high.     

Community-acquired pneumonia in the elderly: a practical guide to treatment

The incidence of community-acquired pneumonia (CAP), an infectious disease, sharply increases among the elderly and the main risk factor for CAP in this age group is chronic comorbidity. The use of the term CAP in the elderly population should be reserved for pneumonia acquired outside of the nursing home setting, since nursing home-acquired pneumonia differs from CAP in terms of its aetiology and clinical manifestations. The main aetiology for CAP is Streptococcus pneumoniae, but atypical pathogens also play an important role as causative agents. The clinical presentations of CAP in the elderly can be different from those in younger patients, and therefore it is important to be aware of and familiar with these differences to avoid unnecessary delays in reaching the correct diagnosis. Imaging is essential to diagnose CAP and to assess its severity. Clinical and laboratory indices can be used to identify elderly patients with CAP who are at low risk for mortality and who can be treated as outpatients. The decision not to hospitalise elderly patients with CAP is contingent on a good clinical condition and the existence of home support systems. The aetiology of CAP cannot be determined on the basis of clinical manifestations, imaging or routine laboratory test results, and the initial antibiotic therapy for elderly patients with CAP should be empirical, based on accepted guidelines. In the light of developments in recent years, elderly patients with CAP, except those who are severely ill, can be treated empirically with once-daily antibiotic monotherapy in the initial phase, using a third-generation fluoroquinolone preparation, such as sparfloxacin, levofloxacin or moxifloxacin, or a new macrolide such as clarithromycin, azithromycin or dirithromycin. In addition to antibiotic therapy, it is critically important to identify and treat the physiological disturbances that accompany CAP as well as decompensation of chronic comorbid conditions. As soon as the patient's condition permits, oral antibiotic therapy should replace intravenous therapy and early discharge from the hospital should be considered. Since influenza and pneumococcus immunisation can reduce morbidity and mortality from CAP, it is important to implement regular immunisation programmes in the primary care setting.     

Secondary prevention of stroke: a practical guide to drug treatment

Stroke is a disease of the elderly and, as a result of the expected demographic changes in many industrialised countries, its incidence is likely to increase in the future. A first-ever stroke significantly increases the likelihood of further events; thus, secondary prevention is of major importance. Only a minority of recurrent strokes can be prevented by surgical or other invasive methods, meaning that most secondary preventive measures involve drug treatment, which has become increasingly sophisticated in recent years. Ischaemic stroke constitutes the vast majority of all strokes; effective secondary prevention depends on a variety of factors, of which the correct classification in terms of subtypes and aetiological mechanisms is a pivotal prerequisite, as is the assessment of the patient's cardiovascular risk profile. In addition to the evaluation of pathomechanisms, stratification of subtypes of brain infarction is mainly based on morphology seen with brain imaging techniques, which provides additional evidence for the presumed cause of the stroke. Inhibitors of platelet function and anticoagulants are the two major groups of antithrombotic drugs used for the secondary prevention of stroke. Antiplatelet agents are still indicated in the majority of patients after ischaemic stroke, especially if an arterial origin is presumed. In addition to aspirin (acetylsalicylic acid), the position of which as the first-line antiplatelet drug is increasingly being questioned, other compounds with antiplatelet activity have been developed and have proven effective in secondary stroke prevention, including ticlopidine, clopidogrel and dipyridamole. Anticoagulants are principally indicated after cardioembolic ischaemic stroke; however, their inherent bleeding risks render their use in many cases rather difficult, in particular for elderly patients. Patient compliance with the recommended treatment is of major importance, given the somewhat limited efficacy of antithrombotic agents in stroke prevention. Since 'real world' experience does not match the circumstances under which clinical trials are conducted, this article will also deal with problems not covered by specific studies, such as risk stratification for anticoagulant treatment and how to proceed in cases of unknown stroke aetiology. The management of major cardiovascular risk factors is the other mainstay of secondary stroke prevention. Recent evidence indicates that antihypertensive treatment may be as effective as antithrombotic drugs for secondary prevention of stroke. This still needs to be proven for the treatment of other cardiovascular risk factors, such as diabetes mellitus and hypercholesterolemia. Nevertheless, the results of recent studies investigating the effect of HMG-CoA reductase inhibitors ('statins') on cardiovascular events strongly suggest a stroke-preventive effect.     

Risk factors in geriatric drug prescribing. A practical guide to avoiding problems

Although the use of medication has helped to cure and control disease, it has also led to serious iatrogenic illness. Toxicity is most common and severe in the elderly. Confusion, falls, depression, sedation, deterioration of function, and urinary incontinence and retention are frequently the manifestation of that toxicity. Normal ageing places older patients at risk because of changes in metabolism, distribution, and excretion of drugs, and sensitivity to drug effects is often greater in the elderly. Disease and the interactions of other drugs can increase the incidence and severity of side effects. Certain drugs should be avoided in the elderly. Those that are long acting and require hepatic metabolism, those with strong anticholinergic properties, and those that are highly sedating tend to cause the most problems. In every case, physicians must weigh the potential benefit of prescribing against the potential risk.     

A practical guide to the management of hypertension in renal transplant recipients

Hypertension as well as hypotension can be harmful to a newly transplanted renal allograft. Elevated blood pressure is also a major risk factor for cardiovascular death, which is a frequent occurrence despite successful renal transplantation. Renal artery stenosis, immunosuppressive drugs, chronic rejection, retained native kidneys, and excessive extracellular fluid volume may all contribute to post-transplant hypertension. Antihypertensive agents are widely used in the management of post-transplant hypertension. Careful clinical judgement and knowledge of the pharmacology, pharmacodynamics, pharmacokinetics, adverse drug reaction profiles, potential contraindications, and drug-drug interactions of antihypertensive agents are important when therapy with antihypertensive drugs is initiated in renal transplant recipients. Since blood pressure elevation in any individual is determined by a large number of hormonal and neuronal systems, the effect of antihypertensive agents on the allograft should be considered a critical factor in the management of hypertension in renal transplant recipients. Most renal transplant recipients have other risk factors for premature cardiovascular death such as diabetes mellitus, hypercholesterolemia, insulin resistance, obesity, left ventricular hypertrophy and ischaemic heart disease. Initial antihypertensive therapy should be tailored individually according to the patient's risk factors. A realistic therapeutic goal for blood pressure management in the initial post-operative state is a systolic blood pressure <160 mm Hg and a diastolic blood pressure <90 mm Hg with lower pressure targets becoming applicable late post-transplantation.     

A practical guide to pharmaceutical polymorph screening & selection

Prevalence and importance of polymorphism occurring in pharmaceutical compounds are well recognized. It is of great importance to prepare and select the right form from the beginning during drug discovery and development. This review introduces the basic concepts of “What is polymorphism?”, addresses a fundamental question of “Why do polymorphs form?”, and provides practical guidelines of “How to prepare polymorphs?” “How to evaluate the relative thermodynamic stability between polymorphs?”, and “How to analyze polymorphs?”. Moreover, case studies of pharmaceutically important polymorphs are provided.     

A practical guide to antimicrobial management of complicated urinary tract infection

Complicated urinary tract infection occurs in the setting of a functionally or structurally abnormal genitourinary tract. Many different abnormalities may lead to a designation of complicated urinary tract infection, and these abnormalities will have different influences on the frequency of infection and likelihood of relapse or reinfection. The microbiology of complicated urinary tract infection is characterised by a greater variety of organisms and increased likelihood of antimicrobial resistance compared with acute uncomplicated urinary tract infection. Appropriate management requires a urine specimen for culture prior to institution of antimicrobial therapy, and ensuring that the underlying abnormality is fully characterised to determine whether it can be corrected. A wide variety of antimicrobial agents are effective for treatment, and are usually given for 7 to 14 days. If the underlying abnormality can be corrected, subsequent infections may be prevented. However, if the underlying abnormality cannot be corrected a high recurrence rate of infection, approaching 50% by 4 to 6 weeks, is expected. Further study of complicated urinary tract infection is necessary, including determination of when asymptomatic bacteriuria warrants treatment, and exploration of nonantimicrobial approaches to management.     

Use of oral rehydration therapy in acute watery diarrhoea. A practical guide.

Various foods and fluids have been used in traditional treatments for diarrhoeal illnesses in infants and children for centuries. During the last 2 decades, however, with the advent of an improved scientific understanding of oral rehydration, effective treatment of dehydrating diarrhoea has been improved, expanded and simplified. The appropriate use of oral rehydration solutions depends on an appreciation of the physiological mechanisms of diarrhoeal illness. Since dehydrating diarrhoea is such a common cause of morbidity and mortality, and because oral rehydration therapy is inexpensive, effective and adaptable, it has become a powerful intervention for improvement in health care for all ages. Newer formulations using starches, cereals and/or amino acids promise to make oral rehydration therapy even more efficacious and acceptable. Nearly all developing countries now have active national diarrhoeal control programmes which facilitate rehydration therapy as the first treatment of diarrhoea while discouraging the use of other diarrhoea medicines (e.g. kaolin and pectin, antispasmodics, etc.). Industrialised countries are also increasingly using oral rather than intravenous fluids. For most patients with lesser degrees of dehydration (up to about 8%) or no detectable dehydration, oral rehydration therapy is the only form of hydration needed. The 'standard' oral replacement solution recommended by the World Health Organization has the advantage of wide experience, demonstrated safety and effectiveness and wide availability. However, rehydration is only part of the management of diarrhoea, and nutritional management (including electrolytes and glucose, alternative substrates to glucose, inclusion of starches and proteins in the solution if possible, etc.) must also be integrated into programmes for diarrhoea control.     

Narcolepsy in children: a practical guide to its diagnosis, treatment and follow-up

Narcolepsy is a neurological syndrome characterised by daytime somnolence and cataplexy which often begins in childhood. Failing to recognise the condition may lead to mislabelling a child as lazy or depressed. The diagnostic criteria for narcolepsy vary with age. In children 8 years and older a Multiple Sleep Latency Test with an average latency of less than 8 minutes, and 2 or more sleep onset REM episodes supports the diagnosis. Human leucocyte antigen (HLA) marker DQbeta1 -0602 has been associated with narcolepsy. The current evidence supports the hypothesis that transmission of narcolepsy is multifactorial. with at least two genes, one of which is non-HLA related. The goal of all therapeutic approaches in narcolepsy is to control the narcoleptic symptoms and allow the patient to continue to fully participate in personal and academic activities. This usually requires a combination of behavioural therapy along with medication. Medications for patients with excessive sleepiness are usually stimulants, including amphetamines. However, a novel wake promoting agent, modafinil, is now available. Cataplexy can be controlled by medications with noradrenergic reuptake-blocking properties, such as clomipramine and fluoxetine, through their active metabolites. Increased awareness of narcolepsy is important to allow earlier diagnosis. Research on the effects different medications have, specifically on children with narcolepsy, has been very limited.     

A practical guide for calculating indirect costs of disease

There may be some discussion about whether indirect costs should be taken into account at all in an economic appraisal, but there is certainly considerable debate about the proper way of estimating these costs. This reviews offers a practical guide for quantifying and valuing these indirect costs of disease, both at an aggregated level of general cost of illness studies, and in an economic appraisal of specific healthcare programmes. Two methods of calculating these costs are considered: the traditional human capital approach, and the more recently developed friction cost method. The former method estimates the potential value of lost production as a result of disease, whereas the latter method intends to derive more realistic estimates of indirect costs, taking into account the degree of scarcity of labour in the economy. All necessary steps in the estimation procedure and the data required at various points will be described and discussed in detail.     

The use of visualization as a means of integrating the spiritual dimension into treatment: A practical guide

A recognition of the importance of the spiritual dimension in recovery is evident among many substance abuse practitioners, particularly those with strong ties to 12-Step programs. This paper describes visualization techniques derived from Jungian principles, as a practical means for the recovery-oriented psychotherapist to foster a spiritual connection. They are also useful in work on the psychological and interpersonal issues that emerge as the client establishes abstinence and progresses from there. This approach does not require allegiance to any specific religious beliefs, but allows the client to build on an inner experience as a way to develop resources in recovery.     

A clinical guide to antipsychotic drugs.

Antipsychotic medications have altered the treatment of psychosis. The effect of typical agents is presumed to be associated with dopamine D2-receptor blockade. Response to these drugs can be evaluated by measuring target symptoms. Behavioural symptoms are generally first to respond, followed by affective symptoms, and then symptoms of disturbed cognition and perception. Predictors of response include age of onset, premorbid function, family history, cognitive function, ventricle size, and levels of homovanillic acid. As all conventional antipsychotic medications of comparable dose are generally of equivalent efficacy (with the exception of clozapine), choice is based on past response and the patient's tolerance of adverse effects. When antipsychotic agents are administered in the short term to control agitated dangerous behaviour, they can be given intramuscularly and augmented with benzodiazepines. For the ongoing treatment of psychosis, haloperidol 5 mg/day, or its equivalent, is usually sufficient. Continuation of treatment after an acute episode may be decided on the basis of chronicity of the psychotic illness. Relapse rates are higher when patients do not continue to receive medication. Lower maintenance doses may result in higher relapse rates but fewer adverse effects. Long-acting intramuscular depot preparations may be used to aid compliance in long term therapy. Adverse reactions correlate with potency. High potency drugs (i.e. those with greater D2 postsynaptic receptor affinity) are generally associated with extrapyramidal symptoms, including acute dystonic reactions, akathisia, tardive dyskinesia and Parkinsonism. Neuroleptic malignant syndrome is associated with all neuroleptic drugs. Low potency agents may cause orthostatic hypotension, sedation and anticholinergic effects. Clozapine has been shown to be effective in 30 to 40% of patients resistant to previous treatment. It does not cause extrapyramidal symptoms, but does have side effects similar to those of low potency agents and may cause agranulocytosis; it is therefore reserved for those patients who have not responded to therapy with 2 other agents. Several other atypical drugs are currently being investigated.