Showing papers in "International Journal of Clinical Practice in 2009"

Health benefits of physical activity in older patients: a review

Abstract: As the number of elderly persons in our country increases, more attention is being given to geriatric healthcare needs and successful ageing is becoming an important topic in medical literature. Concept of successful ageing is in first line on a preventive approach of care for older people. Promotion of regular physical activity is one of the main non-pharmaceutical measures proposed to older subjects as low rate of physical activity is frequently noticed in this age group. Moderate but regular physical activity is associated with a reduction in total mortality among older people, a positive effect on primary prevention of coronary heart disease and a significant benefit on the lipid profile. Improving body composition with a reduction in fat mass, reducing blood pressure and prevention of stroke, as well as type 2 diabetes, are also well established. Prevention of some cancers (especially that of breast and colon), increasing bone density and prevention of falls are also reported. Moreover, some longitudinal studies suggest that physical activity is linked to a reduced risk of developing dementia and Alzheimer's disease in particular.

Diagnosis of recurrent laryngeal nerve palsy after thyroidectomy: a systematic review.

Abstract: Summary Background: Recurrent laryngeal nerve palsy (RLNP) is a recognised possible complication after thyroid surgery. It may present with a variety of symptoms, such as voice change and respiratory symptoms. However, it may remain undetected and the true incidence may be under-reported. The aim of this study was to determine the reported incidence of temporary and permanent palsy after thyroid surgery using different vocal assessment methods. Methods: A Medline search was performed. A systematic review was undertaken which included 27 articles and 25,000 patients. Results: The average incidence of temporary RLNP after thyroid operations is 9.8% and the incidence of permanent RLNP is 2.3%. The RLNP rate varied according to the method of examining the larynx and ranged from 26% to 2.3%. Most of the reviewed studies recommend a follow-up period up to 1 year to assess and evaluate RLNP. Conclusion: Our study has identified that different methods are used to diagnose RNLP and that a wide variety of reported RLNP rates exist. We propose establishment of a ‘gold standard’ for assessing the voice after thyroidectomy to reduce reporting bias.

The relationship of mean platelet volume with the risk and prognosis of cardiovascular diseases.

Abstract: Summary Background: Mean platelet volume (MPV) is arousing increasing interest as a new independent cardiovascular risk factor. Aim: To provide a comprehensive review on the biological significance, the main determinants and the prognostic implications of MPV. Methods: A literature search was performed using key terms, such as ‘MPV’ or ‘mean platelet volume’, together with ‘stroke’, ‘myocardial infarction’ and ‘diabetes and ‘obesity’. Results: Large platelets are likely more reactive: elevated MPV values are associated with a shortened bleeding time and increased thromboxane B2 plasma levels. Thus, MPV could be considered an indicator of platelet function. Platelet size is mainly determined in the bone marrow during megakaryocytopoiesis, and subsequently does not substantially change. MPV is only partially regulated by thrombopoietin: in fact, growth factors and cytokines may also elicit the production of larger and more reactive platelets in the bone marrow, in the presence of conditions capable of increasing their concentrations, such as obesity, endothelial dysfunction and possibly myocardial and cerebral ischaemia. This phenomenon could play an important role in vascular diseases. In fact MPV is predictive of stroke, acute myocardial infarction (AMI) and restenosis of coronary angioplasty, is increased in the presence of obesity, diabetes mellitus, metabolic syndrome, AMI and stroke and has been shown to have a prognostic significance in patients with stroke and AMI. Conclusion: In assessing whole blood count, MPV should not be undervalued, as its increase should suggest a careful assessment of cardiovascular risk.

Understanding heterogeneity in meta-analysis: the role of meta-regression.

Abstract: Summary Background: Meta-regression has grown in popularity in recent years, paralleling the increasing numbers of systematic reviews and meta-analysis published in the biomedical literature. However, many clinicians and decision-makers may be unfamiliar with the underlying principles and assumptions made within meta-regression leading to incorrect interpretation of their results. Aims: This paper reviews the appropriate use and interpretation of meta-regression in the medical literature, including cautions and caveats to its use. Materials & Methods: A literature search of MEDLINE (OVID) from 1966-February 2009 was conducted to identify literature relevant to the topic of heterogeneity and/or meta-regression in systematic reviews and meta-analysis. Results: Meta-analysis, a statistical method of pooling data from studies included in a systematic review, is often compromised by heterogeneity of its results. This could include clinical, methodological or statistical heterogeneity. Meta-regression, said to be a merging of meta-analytic and linear regression principles, is a more sophisticated tool for exploring heterogeneity. It aims to discern whether a linear relationship exists between an outcome measure and on or more covariates. The associations found in a meta-regression should be considered hypothesis generating and not regarded as proof of causality. Conclusions: The current review will enable clinicians and healthcare decision-makers to appropriately interpret the results of meta-regression when used within the constructs of a systematic review, and be able to extend it to their clinical practice.

Saxagliptin added to a submaximal dose of sulphonylurea improves glycaemic control compared with uptitration of sulphonylurea in patients with type 2 diabetes: a randomised controlled trial

Abstract: Aims: Assess the efficacy and safety of saxagliptin added to a submaximal sulphonylurea dose vs. uptitration of sulphonylurea monotherapy in patients with type 2 diabetes and inadequate glycaemic control with sulphonylurea monotherapy.

Efficacy and safety of adding the dipeptidyl peptidase‐4 inhibitor alogliptin to metformin therapy in patients with type 2 diabetes inadequately controlled with metformin monotherapy: a multicentre, randomised, double‐blind, placebo‐controlled study

Abstract: Summary Aims: To evaluate the efficacy and safety of alogliptin, a new dipeptidyl peptidase-4 inhibitor, for 26 weeks at once-daily doses of 12.5 and 25 mg in combination with metformin in patients whose HbA1c levels were inadequately controlled on metformin alone. Methods and patients: Patients with type 2 diabetes and inadequate glycaemic control (HbA1c 7.0-10.0%) were randomised to continue a stable daily metformin dose regimen (≥ 1500 mg) plus the addition of placebo (n = 104) or alogliptin at once-daily doses of 12.5 (n = 213) or 25 mg (n = 210). HbA1c, insulin, proinsulin, C-peptide and fasting plasma glucose (FPG) concentrations were determined over a period of 26 weeks. Results: Alogliptin at either dose produced least squares mean (SE) decreases from baseline in HbA1c of −0.6 (0.1)% and in FPG of −17.0 (2.5) mg/dl [−1.0 (0.1) mmol/l], decreases that were significantly (p < 0.001) greater than those observed with placebo. The between treatment differences (alogliptin – placebo) in FPG reached statistical significance (p < 0.001) as early as week 1 and persisted for the duration of the study. Overall, adverse events (AEs) observed with alogliptin were not substantially different from those observed with placebo. This includes low event rates for gastrointestinal side effects and hypoglycaemic episodes. There was no dose-related pattern of AE reporting between alogliptin groups and few serious AEs were reported. Conclusion: Alogliptin is an effective and safe treatment for type 2 diabetes when added to metformin for patients not sufficiently controlled on metformin monotherapy.

Practical aspects of lifestyle modifications and behavioural interventions in the treatment of overactive bladder and urgency urinary incontinence

Abstract: Behavioural interventions are effective treatments for overactive bladder (OAB) and urgency urinary incontinence (UUI). They are in part aimed at improving symptoms with patient education on healthy bladder habits and lifestyle modifications, including the establishment of normal voiding intervals, elimination of bladder irritants from the diet, management of fluid intake, weight control, management of bowel regularity and smoking cessation. Behavioural interventions also include specific training techniques aimed at re-establishing normal voiding intervals and continence. Training techniques include bladder training, which includes a progressive voiding schedule together with relaxation and distraction for urgency suppression, and multicomponent behavioural training, which, in conjunction with pelvic floor muscle (PFM) exercises, includes PFM contraction to control urgency and increase the interval between voids. Guidelines for the conservative treatment of OAB and UUI have been published by several organisations and the physiological basis and evidence for the effectiveness of behavioural interventions, including lifestyle modifications, in the treatment of OAB and UUI have been described. However, many primary care clinicians may have a limited awareness of the evidence supporting the often straight-forward treatment recommendations and guidance for incorporating behavioural interventions into busy primary care practices, because most of this information has appeared in the specialty literature. The purpose of this review is to provide an overview of behavioural interventions for OAB and UUI that can be incorporated with minimal time and effort into the treatment armamentarium of all clinicians that care for patients with bladder problems. Practical supporting materials that will facilitate the use of these interventions in the clinic are included; these can be used to help patients understand lifestyle choices and voiding behaviours that may improve function in patients experiencing OAB symptoms and/or UUI as well as promote healthy bladder behaviours and perhaps even prevent future bladder problems. Interventions for stress urinary incontinence are beyond the scope of this review.

Lower quit rates among African American and Latino menthol cigarette smokers at a tobacco treatment clinic

Abstract: BACKGROUND: Lower rates of smoking cessation and higher rates of lung cancer in African American (AA) smokers may be linked to their preference for mentholated cigarettes. AIM: This study assessed the relationship between menthol smoking, race/ethnicity and smoking cessation among a diverse cohort of 1688 patients attending a specialist smoking cessation service. RESULTS: 46% of the patients smoked mentholated cigarettes, but significantly more AA (81%) and Latino (66%) patients than Whites (32%) smoked menthols. AA and Latino menthol smokers smoked significantly fewer cigarettes per day (CPD) than non-menthol smokers (15.7 vs. 20.3, for AA, and 17.0 vs. 22.1, for Latinos), with no differences among White menthol and non-menthol smokers. At 4-week follow up, AA, Latino and White non-menthol smokers had similar quit rates (54%, 50% and 50% respectively). In contrast, among menthol smokers, AAs and Latinos had lower quit rates (30% and 23% respectively) compared with Whites (43%, p < 0.001). AA and Latino menthol smokers had significantly lower odds of quitting [odds ratio (OR) = 0.34; 95% CI = 0.17, 0.69 for AA, and OR = 0.32; 95% CI = 0.16, 0.62 for Latinos] than their non-menthol counterparts. At 6-month follow up, a similar trend was observed for the race/ethnicity subgroups, with AA menthol smokers having half the odds of being abstinent compared with AA non-menthol smokers (OR = 0.48; 95% CI = 0.25, 0.9). CONCLUSIONS: Despite smoking fewer CPD, AA and Latino menthol smokers experience reduced success in quitting as compared with non-menthol smokers within the same ethnic/racial groups.

Barriers to insulin initiation and intensification and how to overcome them.

Abstract: Summary Aims: To review published evidence and clinical experience of the perceived barriers to insulin initiation and intensification and to develop solutions for patient management. Method: Literature review and workshop discussions. Results: Many patients with diabetes fail to achieve targets for glycaemic control because of inappropriate use of insulin. Patients and health care professionals face many potential barriers to insulin initiation and intensification in primary care. These can be categorised as low motivation, lack of familiarity or experience and time constraints. Conclusion: Solutions should be tailored to different health care settings. Strategies include improving education and training, providing prescribing aids and increasing the efficiency of collaborative working and communications.

Evidence-based guidelines for the use of biochemical markers of bone turnover in the selection and monitoring of bisphosphonate treatment in osteoporosis: a consensus document of the Belgian Bone Club.

Abstract: To review the clinical value of bone turnover markers (BTM), to initiate and/or monitor anti-resorptive treatment for osteoporosis compared with bone mineral density (BMD) and to evaluate suitable BTM and changes in BTM levels for significance of treatment efficiency. Consensus meeting generating guidelines for clinical practice after review and discussion of the randomised controlled trials or meta-analyses on the management of osteoporosis in postmenopausal women. Although the correlation between BMD and BTM is statistically significant, BTM cannot be used as predictive markers of BMD in an individual patient. Both are independent predictors of fracture risk, but BTM can only be used as an additional risk factor in the decision to treat. Current data do not support the use of BTM to select the optimal treatment. However, they can be used to monitor treatment efficiency before BMD changes can be evaluated. Early changes in BTM can be used to measure the clinical efficacy of an anti-resorptive treatment and to reinforce patient compliance. Determining a threshold of BTM reflecting an optimal long-term effect is not obvious. The objective should be the return to the premenopausal range and/or a decrease at least equal to the least significant change (30%). Preanalytical and analytical variability of BTM is an important limitation to their use. Serum C-terminal cross-linked telopeptide of type I collagen (CTX), procollagen 1 N terminal extension peptide and bone specific alkaline phosphatase (BSALP) appear to be the most suitable. Consensus regarding the use of BTM resulted in guidelines for clinical practice. BMD determines the indication to treat osteoporosis. BTM reflect treatment efficiency and can be used to motivate patients to persist with their medication.

Safety of Sildenafil Citrate: Review of 67 Double-Blind Placebo-Controlled Trials and the Postmarketing Safety Database

Abstract: Aim: To review special safety topics associated with sildenafil and to document the tolerability of 50- and 100-mg doses, overall and by age, in men with erectile dysfunction (ED).

Economic crises and mortality: a review of the literature

Abstract: Summary Background: Studies evaluating the association of economic variables with mortality have produced mixed findings. Objective: We sought to evaluate whether economic crises confer increase in mortality. Methods: We reviewed studies analysing mortality in the general population in periods of economic crisis compared with periods prior to or after the crisis, by searching PubMed, Scopus, Cochrane and the World Wide Web. Results: Eleven studies were included in this review; they referred to economic crises that occurred in Russia, South Korea, as well as South or Central American, African or European countries (5, 2, 2, 1 and 1 studies respectively). Periods of economic crises were associated with the increase in all-cause mortality in seven out of eight studies that reported specific relevant data and increase in cardiovascular mortality in six out of seven studies. Increase in mortality because of respiratory infections, chronic liver disease, suicides, homicides and mortality in infants was noted in association with economic crises in all 5, 4, 6, 5 and 3 studies, respectively, that reported specific relevant data. Mortality from transport accidents decreased with economic crises in five out of six studies. Conclusion: Economic crises in less affluent countries are accompanied with the increase in all-cause mortality, as well as mortality from most of the major specific causes. Further data are needed to establish the effect of economic crises on mortality in more affluent countries. We believe that the above-mentioned association could be attributed to increased psychosocial stress during such periods, among other factors. Public health authorities should be aware of this issue and consider appropriate preventive and control measures.

Observational studies: a review of study designs, challenges and strategies to reduce confounding.

Abstract: There are several methods in which one can assess the relationship between an intervention and an outcome. Randomized controlled trials (RCTs) are considered as the gold standard for evaluating interventions. However, for many questions of clinical importance, RCTs would be impractical or unethical. Clinicians must rely on observational studies for the best available evidence when RCTs are unavailable. This article provides an overview of observational research designs to facilitate the understanding and appraising of their validity and applicability in clinical practice. Major methodological issues of observational studies including selection bias and confounding are also discussed. In addition, strategies to minimize these problems in the design and analytical phases of a study are highlighted. Knowledge of the strengths, weaknesses and recent methodological advances in observational studies can assist clinicians to make informed decisions about whether a particular observational study would provide useful information to enhance patient care.

The mechanism and mitigation of niacin-induced flushing.

Abstract: SUMMARY Aims: To summarise the metabolic responses to niacin that can lead to flushing and to critically evaluate flushing mitigation research. Methods and results: This comprehensive review of the mechanism of action of niacin-induced flushing critically evaluates research regarding flushing mitigating formulations and agents. Niacin induces flushing through dermal Langerhans cells where the activation of G protein-coupled receptor 109A (GPR109A) increases arachidonic acid and prostaglandins, such as prostaglandin D2 (PGD2) and prostaglandin E2 (PGE2), subsequently activating prostaglandin D2 receptor (DP1), prostaglandin E2 receptor (EP2) and prostaglandin E receptor 4 (EP4) in capillaries and causing cutaneous vasodilatation. Controlling niacin absorption rates, inhibiting prostaglandin production, or blocking DP1 ,E P2 and EP4 receptors can inhibit flushing. Niacin extended-release (NER) formulations have reduced flushing incidence, duration and severity relative to crystalline immediate-release niacin with similar lipid efficacy. Non-steroidal anti-inflammatory drugs (NSAIDs), notably aspirin given 30 min before NER at bedtime, further reduce flushing. An antagonist to the DP1 receptor (laropiprant) combined with an ER niacin formulation can reduce flushing; however, significant residual flushing occurs with clinically-relevant dosages. Conclusions: Niacin is an attractive option for treating dyslipidemic patients, and tolerance to niacin-induced flushing develops rapidly. Healthcare professionals should particularly address flushing during niacin dose titration. Review Criteria Research regarding the mechanism of action of niacin and the formulations and agents used in the mitigation of flushing were systematically reviewed and summarised. PubMed was searched from 1960 to 2008 using the terms niacin, flushing, laropiprant, prostaglandins and aspirin. All hits were reviewed for inclusion of mechanism of action, and pertinent articles were included, excluding results which had been subsequently disproven.

Homocysteine, vitamin B12, folate and cognitive functions: a systematic and critical review of the literature.

Abstract: Elevated serum homocysteine, decreased folate and low vitamin B(12) serum levels are associated with poor cognitive function, cognitive decline and dementia. Despite evidence of an epidemiological association, randomised controlled trials did not provide any clear evidence so far that supplementation with vitamin B(12) and/or folate improves dementia or slows cognitive decline, even though it might normalise homocysteine levels. In this report, we review the current knowledge on the relationship between homocysteine, folate and vitamin B(12) levels and the way their disruption influences cognitive function in adults.

Dying in an acute hospital setting: the challenges and solutions.

Abstract: More than half of all UK deaths occur in hospital, yet evidence suggests that the quality of inpatient end of life care is suboptimal at best. Over half of all NHS complaints pertain to problems with care in the dying phase, particularly with regard to poor communication. This is a hugely topical area following the recent publication of the Department of Health's End of Life Care Strategy. With reference to current literature, we seek to investigate the challenges associated with providing 'a good death' in hospital and construct a framework of strategies for improvement; including communication skills training, use of integrated care pathways, advance planning, educational initiatives and the role of the palliative care team.

Pharmacokinetics of a novel transdermal rivastigmine patch for the treatment of Alzheimer’s disease: a review

Abstract: Background: Cholinesterase inhibitors have all been available in oral formulations, but a rivastigmine transdermal patch has now been developed and is approved in many countries worldwide for the treatment of mild-to-moderate Alzheimer’s disease (AD) (including the USA, Latin America, Europe and Asia).

High levels of anxiety and depression have a negative effect on quality of life of women with chronic pelvic pain.

Abstract: SUMMARY Background: Chronic pelvic pain (CPP) is a common and complex disease whose cause is often clinically inexplicable, with consequent difficulty in diagnosis and treatment Patients with CPP have high levels of anxiety and depression, with a consequent impairment of their quality of life Aims: The objective of this study was to determine the prevalence of anxiety and depression and their impact on the quality of life of women with CPP Materials and methods: A cross-sectional controlled study was conducted on 52 patients with CPP and 54 women without pain Depression and anxiety were evaluated by the Hospital Anxiety and Depression Scale, and quality of life was evaluated by the World Health Organization Quality of life Whoqol-bref questionnaire Data were analysed statistically by the Mann-Whitney U-test, the Fisher exact test, chi-square test and Spearman correlation test Results: The prevalence of anxiety was 73% and 37% in the CPP and control groups, respectively, and the prevalence of depression was 40% and 30% respectively Significant differences between groups were observed in the physical, psychological and social domains Patients with higher anxiety and depression scores present lower quality of life scores Discussion: The fact that DPC is a syndromic complex, many patients enter a chronic cycle of search for improvement of medical symptoms The constant presence of pain may be responsible for affective changes in dynamics, family, social and sexual Initially the person is facing the loss of a healthy body and active, to a state of dependence and limitations In this study, patients with higher scores of anxiety and depression scores had lower quality of life and patients with lower scores of anxiety and depression had scores of quality of life These results show that perhaps the depression and anxiety may be related to the negative impact on quality of life of these patients Conclusion: In view of this association, we emphasise the importance of a specific approach to the treatment of anxiety and depression together with clinical treatment to improve the quality of life of these patients What’s known Chronic pelvic pain is a common and complex syndrome of often unidentified cause, a fact that makes diagnosis and treatment more difficult Furthermore, the condition is frequently refractory to drug or surgical therapy CPP is an important topic with impact on the well-being of the patients, affecting their marital, social, professional and sexual life What’s new Chronic pelvic pain is directly related to depression and anxiety, altering the quality of life of affected patients However, no studies were found that would establish a correlation between the impact of anxiety and depression and the quality of life of patients with CPP On this basis, this study evaluated the prevalence of anxiety and depression and its impact on the quality of life of women with CPP

The therapeutic effect of balneotherapy: evaluation of the evidence from randomised controlled trials.

Abstract: Summary Study design: Systematic review. Summary of background data: There is widespread popular belief that balneotherapy is effective in the treatment of various ailments. Methods: We searched PubMed (1950–2006), Scopus and Cochrane library for randomised controlled trials (RCTs), examining the clinical effect of balneotherapy (both as a solitary approach and in the context of spa) on various diseases. Results: A total of 203 potentially relevant articles were identified. In all, 29 RCTs were further evaluated; 22 of them (75.8%) investigated the use of balneotherapy in rheumatological diseases and eight osteoarthritis, six fibromyalgia, four ankylosing spondylitis, four rheumatoid arthritis and three RCTs (10.3%) in other musculoskeletal system diseases (chronic low back pain). In addition, three relevant studies focused on psoriasis and one on Parkinson’s disease. A total of 1720 patients with rheumatological and other musculoskeletal diseases were evaluated in these studies. Balneotherapy did result in more pain improvement (statistically different) in patients with rheumatological diseases and chronic low back pain in comparison to the control group in 17 (68%) of the 25 RCTs examined. In the remaining eight studies, pain was improved in the balneotherapy treatment arm, but this improvement was statistically not different than that of the comparator treatment arm(s). This beneficial effect lasted for different periods of time: 10 days in one study, 2 weeks in one study, 3 weeks in one study, 12 weeks in 2 studies, 3 months in 11 studies, 16–20 weeks in one study, 24 weeks in three studies, 6 months in three studies, 40 weeks in one study and 1 year in one study. Conclusion: The available data suggest that balneotherapy may be truly associated with improvement in several rheumatological diseases. However, existing research is not sufficiently strong to draw firm conclusions.

Asenapine for schizophrenia and bipolar disorder: a review of the efficacy and safety profile for this newly approved sublingually absorbed second-generation antipsychotic.

Abstract: Summary Objective: To describe the efficacy and safety of asenapine for the treatment of schizophrenia and bipolar disorder. Data sources: The pivotal registration trials were accessed by querying http://www.pubmed.gov, http://www.fda.gov and http://www.clinicaltrials.govfor the search terms ‘asenapine’ or ‘ORG 5222’. Study selection: All available clinical reports of studies were identified, as well as preclinical animal and receptor affinity studies that describe potential mechanisms of action. Extensive documents available from the US Food and Drug Administration and Schering-Plough Corporation as posted on http://www.fda.gov provided much of this data. Product labelling also provided additional information. Data extraction: Descriptions of the principal results and calculation of number needed to treat (NNT) and number needed to harm (NNH) for relevant dichotomous outcomes were extracted from the study reports and synopses. Additional safety outcomes subject to NNH analysis were obtained from product labelling. Data synthesis: A sublingual formulation of asenapine has received regulatory approval for the acute treatment of schizophrenia and manic/mixed episodes of bipolar I disorder. Bioavailability is 35% when taken sublingually, but < 2% if ingested. Similar to other second-generation antipsychotics, asenapine’s binding profile includes 5-HT2A and D2 antagonism. Binding at the alpha-1 adrenergic and histamine H1 receptors predicts asenapine’s propensity to cause orthostasis and sedation in some patients. Efficacy in the treatment of acute schizophrenia is supported by 2 of 4 completed phase II/III randomised, placebo and active-controlled 6-week trials, principally at a dose of 5 mg bid. Responder analysis for one of the studies reveals a NNT of asenapine vs. placebo of six for response as defined by a minimum of a 20% decrease in the Positive and Negative Syndrome Scale total score from baseline, and a NNT of 8 for the threshold of a 30% decrease. Efficacy in the treatment of manic or mixed episodes of bipolar I disorder is supported by 2 of 2 completed phase III randomised, placebo and active-controlled 3-week trials and by a 9-week extension trial. The dose tested in the bipolar trials was 10 mg bid. Longer-term studies have been completed in patients with schizophrenia or bipolar disorder, but complete results have not yet been published. Asenapine has a relatively favourable tolerability profile. For the patients with schizophrenia, the NNH values for asenapine vs. placebo for commonly observed adverse reactions were 13 (95% CI 8–30) for akathisia (10 mg bid), 20 (95% CI 13–50) for oral hypoesthesia (5 mg bid) and 13 (95% CI 8–32) for somnolence (5 mg bid). For patients with bipolar disorder, the NNH values for asenapine 5–10 mg bid vs. placebo were 6 (95% CI 5–9) for somnolence, 13 (95% CI 9–25) for dizziness, 20 (95% CI 13–56) for extra-pyramidal symptoms (EPS) other than akathisia and 25 (95% CI 16–71) for increased weight. Asenapine is associated with a lower frequency for EPS than haloperidol. Asenapine has a mild effect on the ECG QT interval similar to that seen with quetiapine. Asenapine’s effect on prolactin is similar to that observed with olanzapine. Asenapine has a more favourable weight gain and metabolic profile compared with olanzapine. Conclusions: Asenapine sublingual tablets are a new option for the treatment of acute episodes of schizophrenia and for the treatment of acute manic or mixed episodes of bipolar I disorder. Although there is no evidence for asenapine’s efficacy to be superior to currently available agents, asenapine’s favourable weight and metabolic profile are of clinical interest. A caveat is that the data reviewed regarding asenapine are from its manufacturer. No independent studies of asenapine’s efficacy or safety are available. Obstacles to the use of asenapine are the recommendations for twice daily dosing and the need to avoid food or liquids for 10 min after administration. As asenapine’s bioavailability is very low if ingested, asenapine is unique among the antipsychotics, in that it needs to be swallowed to be covertly ‘cheeked’.

C-reactive protein as a predictor of disease in smokers and former smokers: a review

Abstract: BACKGROUND: Cigarette smoking is a classical and a major risk factor in the development of several diseases with an inflammatory component, including cardiovascular disease and chronic obstructive pulmonary disease. Improvements in assays for protein markers of inflammation have led to many studies on these factors and their roles in disease. AIMS: C-reactive protein (CRP) is one such marker and this review focuses on the evidence for using CRP as a diagnostic marker and how levels of this protein are modified according to the smoking status of the patient, both in terms of the current amount of cigarettes smoked and how CRP levels change following smoking cessation. CONCLUSIONS: Assay of CRP levels may be useful in monitoring disease progression and determining risk of future cardiovascular complications. However, as this marker is also an indicator of acute inflammation and challenges to the immune system, some caution must be exercised in interpreting the available data on CRP levels in patients with different chronic comorbidities.

In-hospital mortality and morbidity of elderly medical patients can be predicted at admission by the Modified Early Warning Score: a prospective study.

Abstract: Summary Objective: Although early warning scores were originally derived as bedside tools for alerting the medical staff, they may serve as decision rules for the admission of medical patients. We conducted this study to investigate the ability of the Modified Early Warning Score (MEWS) to identify a subset of patients at risk of deterioration, who might benefit from an increased level of attention. Design: Prospective, single centre, cohort study. Setting: A 64-bedded medical ward in a public, non-teaching Hospital in Italy. Patients: All patients consecutively admitted from 15th November 2005 to 9th June 2006. Interventions: On admission, the attending physician measured five physiological parameters (systolic blood pressure, pulse rate, respiratory rate, body temperature and level of consciousness) and calculated the MEWS. The main outcome measures were in-hospital mortality and a composite of mortality and transfer to a higher level of care. A secondary end-point was the length of stay for discharged patients. Measurements and results: In all, 1107 patients were admitted; 621 (56.1%) were women and 486 were men. Patients of female gender were also older (mean age 80.6 years) than men (mean age 77.1; p < 0.05). Of 1107, 995 patients (89.9%) were older than 64 years. A total of 966 patients were discharged, 102 deceased and 39 were transferred. In comparison with the lowest score, the risk of death was incremental among all the MEWS categories, as well as the risk of the combined outcome of death and transfer, and highly significant (risk of death, χ2 for trend 136.307; risk of death or transfer, χ2 for trend 105.762; p < 0.00001 for both). Patients with MEWS ≤ 4 were discharged after a mean stay of 8.3 days, and alive patients with MEWS of five or more were discharged after a mean stay of 9.4 days (p = ns). A patient with a MEWS of zero at admission has a very low probability to die or to be transferred because of clinical instability (OR 0.14, 95% CI: 0.08–0.24). Conclusions: We have confirmed that the MEWS, even when calculated once on admission, is a simple but highly useful tool to predict a worse in-hospital outcome.

Initiating insulin therapy with, or switching existing insulin therapy to, biphasic insulin aspart 30/70 (NovoMix® 30) in routine care: safety and effectiveness in patients with type 2 diabetes in the IMPROVE™ observational study

Abstract: Summary Aims: The IMPROVE™ observational study evaluated the safety profile and effectiveness of biphasic insulin aspart 30/70 (BIAsp 30) in patients with type 2 diabetes in routine practice in 11 countries. Methods: Patients who initiated insulin therapy with, or switched existing insulin therapy to, BIAsp 30 in routine care were eligible for this 26-week, non-interventional observational study. Data on adverse events, hypoglycaemia and glycaemic parameters were obtained from patients’ diaries and medical notes. Questionnaire-based patient treatment satisfaction was also measured. We report global results and, uniquely for a diabetes observational study, country-specific data. Results: A total of 52,419 patients were enrolled from three prestudy treatment groups: no pharmaceutical therapy (n = 8966, diabetes duration 2.0 years, baseline HbA1c 9.9%), oral antidiabetic drugs (OADs) only (n = 33,797, diabetes duration 7.4 years, baseline HbA1c 9.2%) and insulin ± OADs (n = 9568, diabetes duration 10.4 years, baseline HbA1c 9.3%). At final visit, HbA1c, fasting and postprandial blood glucose were significantly reduced from baseline in all subgroups (no pharmaceutical therapy: −3.1%, −5.9 and −9.0 mmol/l, respectively; OADs-only: −2.1%, −4.1 and −6.1 mmol/l; insulin ± OADs: −2.0%, −3.3 and −5.1 mmol/l). Major hypoglycaemia rates decreased in all subgroups; minor hypoglycaemia increased in the insulin-naive groups. There was no mean weight gain across subgroups. Across all countries, glycaemic parameters and major hypoglycaemia were reduced; weight increases were seen in some countries. Treatment satisfaction increased in all subgroups and countries following BIAsp 30 therapy. Conclusions: Initiating insulin with, or switching insulin therapy to, BIAsp 30 in routine care resulted in improved glycaemic control, reduced major hypoglycaemia and greater treatment satisfaction.

Paliperidone palmitate – review of the efficacy, safety and cost of a new second‐generation depot antipsychotic medication

Abstract: Summary Objective: To describe the efficacy, safety and cost of paliperidone palmitate, a depot antipsychotic medication recently approved for the treatment of schizophrenia. Data sources: A literature search was conducted by querying the websites http://www.pubmed.gov, http://www.fda.gov, http://www.accessdata.fda.gov/scripts/cder/drugsatfda and http://www.clinicaltrials.gov for the search term ‘paliperidone palmitate’. Cost information was obtained from the pharmaceutical vendor servicing a local state-operated psychiatric facility. Study selection: All available reports of studies were identified. Product labelling provided additional information. Data extraction: Descriptions of the principal results and calculation of the number needed to treat (NNT) and number needed to harm (NNH) for relevant dichotomous outcomes were extracted from the study reports and synopses. Additional safety outcomes subject to NNH analysis were obtained from product labelling. Data synthesis: Paliperidone palmitate is a newly available depot formulation of paliperidone (the 9-OH metabolite of risperidone). Upon injection into the deltoid or gluteal muscle, the release of the drug starts as early as day 1, reaches maximum plasma concentrations at 13 days and lasts for as long as 126 days. Maximum concentration following deltoid injection is approximately 28% higher compared with injection into the gluteal muscle, and thus paliperidone palmitate requires initiation by two initial deltoid injections spread 1 week apart to achieve therapeutic concentrations rapidly. Subsequent injections are at 4-week intervals. Acute efficacy was evidenced by four short-term double-blind, randomised, placebo-controlled, fixed-dose studies of acutely relapsed adult inpatients who met DSM-IV criteria for schizophrenia. NNT for a 30% or greater decrease in the Positive and Negative Syndrome Scale total score compared with placebo was consistently lower for the higher dose strengths of 156 and 234 mg, suggesting a therapeutic dose–response. Treatment with paliperidone palmitate at doses between 39 and 156 mg significantly delayed the time to recurrence of symptoms of schizophrenia after 24 weeks of maintained symptom stability. The NNT vs. placebo to avoid a recurrence of symptoms was 5 (95% CI 4–7). Overall, paliperidone palmitate was reasonably well tolerated, with low rates of extrapyramidal symptoms or body weight gain; however, these may be more common at higher doses. Injection site reactions occurred at a rate ranging from 4% to 10%, depending on the dose regimen, compared with 2% for the pooled placebo arms. The acquisition cost of a maintenance dose of paliperidone palmitate calculated on a per day basis is similar to that for risperidone microspheres, but about double the cost for oral paliperidone and approximately 19 times the cost of oral generic risperidone. Conclusions: Paliperidone palmitate is efficacious for the acute and maintenance treatment of schizophrenia and is reasonably well tolerated. It offers several advantages over other available second-generation depot antipsychotics: it comes in prefilled syringes in a number of different dosage strengths; it does not require refrigeration; it does not require supplementation with oral antipsychotics; it can be administered once monthly; it can be administered with a very small bore needle; the injection volume is small; the injection site can be either the deltoid or gluteal muscles; it does not require an additional precautionary observation period after the injection. For patients for whom oral risperidone or paliperidone is otherwise effective, paliperidone palmitate offers a guaranteed delivery system that enhances adherence. However, the high acquisition cost of paliperidone palmitate will likely be an important obstacle to its routine use.

Bipolar disorder and aggression

Abstract: Summary Aims: In clinical practice, overt aggressive behaviour is frequently observed in patients diagnosed with bipolar disorder. It can be dangerous and complicates patient care. Nevertheless, it has not been adequately studied as a phenomenon that is separate from other symptoms such as agitation. The aim of this review is to provide information on the prevalence, clinical context, and clinical management of aggression in patients with bipolar disorder. Methods: MEDLINE and PsycInfo data bases were searched for articles published between 1966 and November 2008 using the combination of key words ‘aggression’ or ‘violence’ with ‘bipolar disorder’. For the treatment searches, generic names of mood stabilisers and antipsychotics were used in combination with key words ‘bipolar disorder’ and ‘aggression’. No language constraint was applied. Articles dealing with children and adolescents were not included. Results: Acutely ill hospitalised bipolar patients have a higher risk for aggression than other inpatients. In a population survey, the prevalence of aggressive behaviour after age 15 years was 0.66% in persons without lifetime psychiatric disorder, but 25.34% in bipolar I disorder. Comorbidity with personality disorders and substance use disorders is frequent, and it elevates the risk of aggression in bipolar patients. Impulsive aggression appears to be the most frequent subtype observed in bipolar patients. Clinical management of aggression combines pharmacological and non-pharmacological approaches. Discussion: A major problem with the evidence is that aggression is frequently reported only as one of the items contributing to the total score on a scale or a subscale. This makes it impossible to ascertain specifically aggressive behaviour. Large controlled head-to-head randomised controlled studies comparing treatments for aggressive behaviour in bipolar disorder are not yet available. There is some evidence favouring divalproex, but it is not particularly strong .We do not know if there are any efficacy differences among antipsychotics for this indication.

Atherogenic forms of dyslipidaemia in women with polycystic ovary syndrome

Abstract: OBJECTIVE: Dyslipidaemia is very common in patients with polycystic ovary syndrome (PCOS) but, beyond plasma lipids, atherogenic lipoprotein (Lp) and apolipoprotein (apo) alterations are still ill defined. DESIGN: We measured concentrations of apoB, Lp(a) and small, dense low-density lipoprotein (LDL) in 42 patients with PCOS [age: 28 +/- 7 years, body mass index (BMI): 27 +/- 5 kg/m(2)] vs. 37 age- and BMI-matched healthy controls. METHODS: Elevated Lp(a) levels considered were those > 30 mg/dl while elevated apoB concentrations were those > 100 g/l. RESULTS: Polycystic ovary syndrome showed increased triglycerides levels (p = 0.0011) and lower high-density lipoprotein (HDL)-cholesterol concentrations (p = 0.0131) while total- and LDL cholesterol were similar. PCOS also showed smaller LDL size (p = 0.0005), higher levels of total small, dense LDL (p < 0.0001), higher concentrations of Lp(a), as considered as absolute values (p = 0.0143) and log-transformed (p = 0.0014), while no differences were found in apoB levels. Elevated Lp(a) concentrations were found in 24% of PCOS, while elevated apoB levels were relatively uncommon (14%). Spearman correlation analysis revealed that Lp(a) concentrations were weakly correlated only with HDL-cholesterol levels (r = -0.378, p = 0.0431). In addition, 36% of patients with PCOS with normal plasma lipid profile showed elevated levels of Lp(a), apoB or small, dense LDL. CONCLUSIONS: Atherogenic Lp abnormalities may be found in one-third of women with PCOS who have a normal lipid pattern. Future prospective studies are needed to test to which extent such atherogenic forms of dyslipidaemia may contribute to the increased cardiovascular risk in young women with PCOS.

Effects of flexible-dose fesoterodine on overactive bladder symptoms and treatment satisfaction: an open-label study.

Abstract: Aims: To evaluate the efficacy and tolerability of flexible-dose fesoterodine in subjects with overactive bladder (OAB) who were dissatisfied with previous tolterodine treatment.

Indirect comparisons of treatments based on systematic reviews of randomised controlled trials.

Abstract: SUMMARY Background: Randomised controlled trials are the most effective way to differentiate between the effects of competing interventions. However, head-to-head studies are unlikely to have been conducted for all competing interventions. Aim: Evaluation of different methodologies used to indirectly compare interventions based on meta analyses of randomised controlled trials. Methods: Systematic review of Cochrane Database of Systematic Reviews, Cochrane Methodology Register, EMBASE and MEDLINE for reports including meta analyses that contained an indirect comparison. Searching was completed in July 2007. No restriction was placed on language or year of publication. Results: Sixty-two papers identified contained indirect comparisons of treatments. Five different methodologies were employed: comparing point estimates (1 ⁄62); comparing 95% confidence intervals (26 ⁄62); performing statistical tests on summary estimates (8 ⁄62); indirect comparison using a single common comparator (20 ⁄62); and mixed treatment comparison (MTC) (7 ⁄62). The only methodologies that provide an estimate of the difference between the interventions under consideration and a measure of the uncertainty around that estimate are indirect comparison using a single common comparator and MTC. The MTC might have advantages over other approaches because it is not reliant on a single common comparator and can incorporate the results of direct and indirect comparisons into the analysis. Indirect comparisons require an underlying assumption of consistency of evidence. Utilising any of the methodologies when this assumption is not true can produce misleading results. Conclusions: Use of either indirect comparison using a common comparator or MTC provides estimates for use in decision making, with the preferred methodology being dependent on the available data. Review Criteria

Treating type 2 diabetes: how safe are current therapeutic agents?

Abstract: Sulphonylureas (SUs) and biguanides (metformin) are the current mainstays in the treatment of type 2 diabetes (T2DM) and represent the most commonly used oral hypoglycaemic agents (OHAs). In recent years, a variety of new OHAs have become available, including thiazolidinediones, glinides, alpha-glucosidase inhibitors, glucagon-like peptide-1 agonists, amylin analogues and dipeptidyl peptidase-IV inhibitors, providing physicians with a larger therapeutic catalogue than ever before. The traditional drugs metformin and SUs have an established safety profile through long-term use. However, long-term clinical trials and routine use are lacking for many of the new agents, and some potentially serious side effects have been reported with several of these compounds. Until adequate data is obtained, it is difficult to assess the risk-benefit ratio of these agents in relation to the traditional drugs. Until that becomes fully documented, it may be wise to start pharmacologic treatment of patients on an individual basis, weighing the benefits and costs of each medication. Thus, there remains a place for well-established drugs that have a proven safety record and are supported by years of clinical use for the treatment of T2DM.

The role of methadone in cancer pain treatment – a review

Abstract: Summary Background: Methadone is an opioid analgesic of step 3 of the World Health Organization (WHO) analgesic ladder. Aim and Methods: To outline pharmacodynamics, pharmacokinetics, drug interactions, equianalgesic dose ratio with other opioids, dosing rules, adverse effects and methadone clinical studies in patients with cancer pain. A review of relevant literature on methadone use in cancer pain was conducted. Results: Methadone is used in opioid rotation and administered to patients with cancer pain not responsive to morphine or other strong opioids when intractable opioid adverse effects appear. Methadone is considered as the first strong opioid analgesic and in patients with renal impairment. Methadone possesses different pharmacodynamics and pharmacokinetics in comparison to other opioids. The advantages of methadone include multimode analgesic activity, high oral and rectal bioavailability, long lasting analgesia, lack of active metabolites, excretion mainly with faeces, low cost and a weak immunosuppressive effect. The disadvantages include long and changeable plasma half-life, high bound to serum proteins, metabolism through P450 system, numerous drug interactions, lack of clear equianalgesic dose ratio to other opioids, QT interval prolongation, local reactions when administered subcutaneously. Conclusions: Methadone is an important opioid analgesic at step 3 of the WHO analgesic ladder. Future controlled studies may focus on establishment of methadone equianalgesic dose ratio with other opioids and its role as the first strong opioid in comparative studies with analgesia, adverse effects and quality of life taken into consideration.