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Terms modified by Individual Patients Selected AbstractsSensitivity to sulphonylureas in patients with hepatocyte nuclear factor-1, gene mutations: evidence for pharmacogenetics in diabetesDIABETIC MEDICINE, Issue 7 2000E. R. Pearson SUMMARY Introduction Maturity-onset diabetes of the young (MODY) is characterized by autosomal dominantly inherited, early-onset, non-insulin-dependent diabetes. Mutations in the hepatocyte nuclear factor (HNF)-1, gene are the commonest cause of MODY. Individual patients with HNF-1, mutations have been reported as being unusually sensitive to the hypoglycaemic effects of sulphonylurea therapy. We report three patients, attending a single clinic, with HNF-1, mutations that show marked hypersensitivity to sulphonylureas. Case reports In cases 1 and 2 there were marked changes in HbA1c on cessation (4.4% and 5.8%, respectively) and reintroduction (5.0% and 2.6%) of sulphonylureas. Case 3 had severe hypoglycaemic symptoms on the introduction of sulphonylureas despite poor glycaemic control and was shown with a test dose of 2.5 mg glibenclamide to have symptomatic hypoglycaemia (blood glucose 2 mmol/l) after 4 h despite eating. Conclusions HNF-1, MODY diabetic subjects are more sensitive to sulphonylureas than Type 2 diabetic subjects and this is seen in different families, with different mutations and may continue up to 13 years from diagnosis. This is an example of pharmacogenetics, with the underlying aetiological genetic defect altering the pharmacological response to treatment. The present cases suggest that in HNF-1, MODY patients: (i) sulphonylureas can dramatically improve glycaemic control and should be considered as initial treatment for patients with poor glycaemic control on an appropriate diet; (ii) hypoglycaemia may complicate the introduction of sulphonylureas and therefore very low doses of short acting sulphonylureas should be used initially; and (iii) cessation of sulphonylureas should be undertaken cautiously as there may be marked deterioration in glycaemic control. Keywords, genetics, HNF-1,, MODY, pharmacogenetics, sulphonylurea sensitivity [source] Changes of psychiatric parameters and their relationships by oral isotretinoin in acne patientsTHE JOURNAL OF DERMATOLOGY, Issue 5 2009Bong Jin HAHM ABSTRACT Oral isotretinoin is a highly effective agent for the treatment of moderate to severe acne, but ever since oral isotretinoin was introduced as a modality for acne, the relationship between oral isotretinoin therapy and psychiatric problems, especially depression, has been controversial. The purposes of this study were to know the acute effects of oral isotretinoin therapy on psychiatric symptoms and to investigate the relationships among them, which have not been reported in the published work. This cohort study included 38 acne patients who started oral isotretinoin therapy. Individual patients were examined before administering oral isotretinoin and 2 and 8 weeks after commencement. Acne severity was graded using the Leeds revised acne grading system. Acute psychiatric effects of oral isotretinoin were assessed using a questionnaire authorized by two psychiatrists. This questionnaire included assessments of acne-related quality of life (Assessment of the Psychological and Social Effects of Acne [APSEA]), depression (Beck's depression inventory [BDI]), anxiety (Beck's anxiety inventory [BAI]) and psychopathology (Symptomchecklist-90-revised [SCL-90-R]). Acne grading and APSEA showed similar change patterns. Both improved after 8 weeks of oral isotretinoin treatment. On the other hand, the severity of depression decreased after 2 weeks of treatment. A significant correlation was found between BDI and APSEA, but no correlation was found between BDI and acne grade. These results indicate that oral isotretinoin therapy alleviates depressive symptoms. Improvements in depression are directly related to acne-related life quality improvements rather than to improvement in acne grade. [source] RANDOMIZED, CONTROLLED STUDY COMPARING SITZ-BATH AND NO-SITZ-BATH TREATMENTS IN PATIENTS WITH ACUTE ANAL FISSURESANZ JOURNAL OF SURGERY, Issue 8 2006Pravin J. Gupta Background: To determine the efficacy and safety of sitz baths in the management of acute anal fissures. Methods: Individual patients were randomized to either receive sitz baths or no sitz baths for 4 weeks in addition to oral psyllium husk. Patients were asked to soak their hips and buttocks in a tub containing plain lukewarm water for 10 min, once after defecation in the morning and again at bedtime. Each week, the patients were called to assess pain scores and healing of fissures, whereas the level of satisfaction was recorded at the end of 4 weeks. Main outcome measures were validated pain scores and levels of satisfaction. Results: Fifty-eight subjects were recruited for this study. In all, 52 of them completed the trial (27 in the sitz bath group and 25 in the control group). Although the pain score was lesser in the sitz bath group than in the control group, it failed to reach statistical significance. There were no significant differences in fissure healing between the two groups over the 4-week study period. However, patients in the sitz bath group reported better satisfaction levels than the control group (P < 0.01). Although no serious adverse effects were observed, two patients from sitz bath group developed perianal skin rash. Conclusion: This study suggests that sitz baths improve patient satisfaction in acute anal fissures. However, the healing and overall pain relief was not significant enough to attract attention. It was also found to be associated with adverse effects in few patients. [source] The effect of therapeutic glucocorticoids on the adrenal response in a randomized controlled trial in patients with rheumatoid arthritis,ARTHRITIS & RHEUMATISM, Issue 5 2006John R. Kirwan Objective To measure the effect of low-dose systemic glucocorticoid treatment on the adrenal response to adrenocorticotropic hormone (ACTH) in patients with rheumatoid arthritis (RA). Methods Patients with RA who took part in a randomized double-blind placebo-controlled trial of budesonide (3 mg/day and 9 mg/day) and prednisolone (7.5 mg/day) underwent a short (60-minute) test with injection of ACTH (tetracosactide hexaacetate) at baseline and the day after completing the 3-month treatment program. Plasma cortisol measurements at baseline and 3 months were compared within and between the treatment groups. Individual patients were classified as normal responders to ACTH or as abnormal responders if changes were >2 SD below the pretreatment value in the entire group of study patients. Results Short tests with ACTH injection were performed on 139 patients before beginning the study medication and on 134 patients after cessation of the medication. There were no changes in the placebo group. Mean plasma cortisol levels following treatment were reduced in all active treatment groups. In addition, mean values were significantly reduced for the 30-minute and 60-minute responses to ACTH. The maximum reduction (35%) occurred in the prednisolone group at 60 minutes. Following treatment, 34% of patients taking budesonide 9 mg and 46% of those taking prednisolone 7.5 mg failed to reach the normal maximum cortisol response to ACTH. Four patients failed to achieve the normal percentage increase in cortisol levels, but only 1 patient failed to meet both criteria. Conclusion Low doses of a glucocorticoid resulted in depression of baseline and ACTH-stimulated cortisol levels after 12 weeks of therapy. Although the responsiveness of the hypothalamic,pituitary,adrenal axis in individual patients generally remained within the normal range, these changes should be investigated further. [source] Asthma medication , persistence with adrenergics, steroids and combination products over a 5-year periodJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 5 2009D. Haupt RPh Summary Background:, Many patients with asthma underuse steroids for inhalation. This has been identified as a main cause of therapy failure and of excess health care utilization. Objective:, To elucidate the medication persistence of patients using asthma drugs, how patients combine the drugs over time and whether medication persistence was influenced by patients switching to combination products. Methods:, Individual patients' drug acquisition data were obtained from a pharmacy record database for the period 2000,2004. A patient was considered to have satisfactory medication possession ratio (MPR) if the medication supplies covered ,80% of the prescribed treatment. Drug use profiles were constructed as graphs for each patient, showing the date of each refill and the time period covered by the dispensed drugs. From the graphs the combination of drugs, the continuity of the therapy over time and the MPR for each patient could be determined. Results:, Of 1812 patients with asthma drugs in the database, 815 fulfilled the inclusion criteria. The percentage of patients with satisfactory MPR was low (11,27%), but significantly higher among patients using combination products than among those using steroids. For patients who switched from adrenergics plus steroids in two inhalers to combination products in one inhaler, the number of patients with satisfactory MPR was significantly increased. Conclusion:, Satisfactory MPR was low for all types of asthma drugs. More patients had satisfactory MPR with combination products in one inhaler than with adrenergics and steroids in two separate inhalers. Asthma drug-delivery is important and combination products of the two ingredients could therefore improve asthma therapy. [source] Surge Capacity for Healthcare Systems: A Conceptual FrameworkACADEMIC EMERGENCY MEDICINE, Issue 11 2006Amy Kaji MD This report reflects the proceedings of a breakout session, "Surge Capacity: Defining Concepts," at the 2006 Academic Emergency Medicine Consensus Conference, "Science of Surge Capacity." Although there are several general descriptions of surge capacity in the literature, there is no universally accepted standard definition specifying the various components. Thus, the objectives of this breakout session were to better delineate the components of surge capacity and to outline the key considerations when planning for surge capacity. Participants were from diverse backgrounds and included academic and community emergency physicians, economists, hospital administrators, and experts in mathematical modeling. Three essential components of surge capacity were identified: staff, stuff, and structure. The focus on enhancing surge capacity during a catastrophic event will be to increase patient-care capacity, rather than on increasing things, such as beds and medical supplies. Although there are similarities between daily surge and disaster surge, during a disaster, the goal shifts from the day-to-day operational focus on optimizing outcomes for the individual patient to optimizing those for a population. Other key considerations in defining surge capacity include psychosocial behavioral issues, convergent volunteerism, the need for special expertise and supplies, development of a standard of care appropriate for a specific situation, and standardization of a universal metric for surge capacity. [source] Psychiatric services for people with severe mental illness across western Europe: what can be generalized from current knowledge about differences in provision, costs and outcomes of mental health care?ACTA PSYCHIATRICA SCANDINAVICA, Issue 2006T. Becker Objective:, To report recent findings regarding differences in the provision, cost and outcomes of mental health care in Europe, and to examine to what extent these studies can provide a basis for improvement of mental health services and use of findings across countries. Method:, Findings from a number of studies describing mental health care in different European countries and comparing provision of care across countries are reported. Results:, The development of systems of mental health care in western Europe is characterized by a common trend towards deinstitutionalization, less in-patient treatment and improvement of community services. Variability between national mental healthcare systems is still substantial. At the individual patient level the variability of psychiatric service systems results in different patterns of service use and service costs. However, these differences are not reflected in outcome differences in a coherent way. Conclusion:, It is conceivable that the principal targets of mental healthcare reform can be achieved along several pathways taking into account economic, political and sociocultural variation between countries. Differences between mental healthcare systems appear to affect service provision and costs. However, the impact of such differences on patient outcomes may be less marked. The empirical evidence is limited and further studies are required. [source] Self-monitoring of blood glucose in type-2 diabetes: what is the evidence?DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 6 2007Grace McGeoch Abstract Background There is a controversy about self-monitoring of blood glucose (SMBG) in patients with type 2 diabetes who are not using insulin. Randomized trials are limited in duration, size, and validity. Methods Systematic search for randomized trials and observational studies published since 1990. For inclusion studies had to report on SMBG in type 2 diabetes managed with oral hypoglycaemic agents and/or diet alone, HbA1c or clinical outcome, have at least 50 patients and be of at least 6 months' duration. Results Three randomized trials with 1000 patients were included, though all had interventions differing in the amount of education on SMBG, and in the population studied. The two larger studies had statistically significantly lower HbA1c levels with SMBG. Thirteen observational studies had information on over 60 000 patients. Smaller studies had lower initial HbA1c and showed no association between SMBG and laboratory or clinical improvement. Larger studies tended to have higher initial HbA1c and did show an association between SMBG and laboratory or clinical improvement. Overall, improvement in glycaemic control with SMBG tended to be seen in studies with initial HbA1c above 8%. Conclusions It is likely that SMBG is beneficial in some circumstances, for example as an educational tool, for patients with type 2 diabetes not using insulin who have poor glycaemic control. More information is needed at the level of the individual patient, rather than group means, and about timing and frequency of monitoring, response to those results, what constitutes effective patient education, and long-term clinical outcomes. Copyright © 2007 John Wiley & Sons, Ltd. [source] Suicide, suicidality and suicide prevention in affective disordersACTA PSYCHIATRICA SCANDINAVICA, Issue 2003H. J. Möller Objective:, It is well known that functional psychiatric disorders are one of the main causes of suicidal behaviour. This paper discusses the epidemiology and risk factors of suicidal behaviour in affective disorders and goes on to describe the treatment and prevention of such suicidal behaviour. Method:, A narrative overview of relevant epidemiological and drug studies. Results:, About 60,70% of patients with acute depression experience suicidal ideas. There is a high incidence of suicide (10,15%) in depressive patients. Psychopharmacological treatment with antidepressants and/or mood stabilizers is the most successful approach to avoid the risk of suicidal behaviour. In addition, psychotherapeutic and psychosocial interventions are of importance. Conclusion:, Suicidal behaviour and suicide must be considered when treating patients with affective disorders. The complex causation of suicidality has to be borne in mind when considering methods of suicide prevention. In order to obtain the best results, psychosocial, psychotherapeutic and psychopharmacological approaches should be combined, depending on the risk factors of each individual patient. [source] Heel ulcers don't heal in diabetes.DIABETIC MEDICINE, Issue 9 2005Or do they? Abstract Aim To obtain information on outcome of heel ulcers in diabetes. Methods Data were recorded prospectively on all patients with heel ulcers who were referred to a specialist multidisciplinary clinic between 1 January 2000 and 30 November 2003. Outcomes were assessed on 31 March 2004. Results There were 157 heel ulcers in the patients referred in the period. Three ulcers were excluded from analysis because of associated osteomyelitis. Of 154 remaining ulcers (121 limbs; 97 patients, 55 male; mean age 68.5 ± 12.8 sd years), 101 (65.6%) healed after a median (range) 200 (24,1225) days. Of 53 non-healed ulcers, 11 (7.1% of 154) were resolved by major amputation, 30 (19.5% of 154) were unhealed at time of patient's death, and 12 (7.8% of 154) remained unhealed. Ulcers healed in 59 of 97 affected patients (60.8%). Twenty-six patients (26.8% of 97) died during the period, of whom 20 died with ulcers unhealed. Worse outcomes were observed in larger ulcers (P = 0.001, Mann,Whitney U -test = 1883.5) and limbs with clinical evidence of peripheral arterial disease (P = 0.001, Mann,Whitney U -test = 1163.00). Backward step-wise logistic regression analysis showed 70.1% of healing could be predicted from these two baseline characteristics. Conclusions The common perception that ,heel ulcers don't heal' is not reflected in clinical practice. Outcome is generally favourable even in a population often affected by serious comorbidity and with limited life expectancy. These data can be used to help define management plans, as well as a basis for counselling of the individual patient. [source] ENDOSCOPIC MANAGEMENT OF BILIARY STRICTURESDIGESTIVE ENDOSCOPY, Issue 2004Yoshitsugu Kubota ABSTRACT Endoscopic stenting, due to being less invasive, is feasible for most patients with biliary strictures; however, presumed efficacy should be balanced against the procedure-related morbidities for an individual patient. Self-expandable metallic stents have a longer patency, but are not retrievable. Therefore, the use of self-expandable metallic stents should be limited to those with unequivocal findings of unresectable malignancy. Plastic stents are indicated for strictures due to benign etiologies and equivocal malignancy. Endoscopic stenting for hilar biliary stricture is challenging. Bilateral hepatic drainage seems ideal but is often demanding to achieve with endoscopic technique, and contrast injection into undrained segments may pose a substantial risk for cholangitis and aggravate prognosis. Therefore, the extent of drainage should be balanced against the procedure-related complications. Preoperative magnetic resonance cholangiopancreatography may help determine feasibility of bilateral drainage or an ,intended and selective drainage' with a single stent and might obviate the possible morbidities. [source] Current management of esophageal perforation: 20 years experienceDISEASES OF THE ESOPHAGUS, Issue 4 2009A. Eroglu SUMMARY Esophageal perforations are surgical emergencies associated with high morbidity and mortality rates. No single strategy has been sufficient to deal with the majority of situations. We aim to postulate a therapeutic algorithm for this complication based on 20 years of experience and also on data from published literature. We performed a retrospective clinical review of 44 patients treated for esophageal perforation at our hospital between January 1989 and May 2008. We reviewed the characteristics of these patients, including age, gender, accompanying diseases, etiology of perforation, diagnosis, location, time interval between perforation and diagnosis, treatment of the perforation, morbidity, hospital mortality, and duration of hospitalization. Perforation occurred in the cervical esophagus in 14 patients (31.8%), thoracic esophagus in 18 patients (40.9%), and abdominal esophagus in 12 patients (27.3%). Management of the esophageal perforation included primary closure in 23 patients (52.3%), resection in 7 patients (15.9%), and nonsurgical therapy in 14 patients (31.8%). In the surgically treated group, the mortality rate was 3 of 30 patients (10%), and 2 of 14 patients (14.3%) in the conservatively managed group. Four of the 14 nonsurgical patients were inserted with covered self-expandable stents. The specific treatment of an esophageal perforation should be selected according to each individual patient. To date, the most effective treatment would appear to be operative management. With improvements in endoscopic procedures, the morbidity and mortality rates of esophageal perforations are significantly decreased. We suggest that minimally invasive techniques for the repair of esophageal perforations will be very important in the future treatment of this condition. [source] Brief alcohol intervention,where to from here?ADDICTION, Issue 6 2010Challenges remain for research, practice ABSTRACT Brief intervention (BI) is intended as an early intervention for non-treatment-seeking, non-alcohol-dependent, hazardous and harmful drinkers. This text provides a brief summary of key BI research findings from the last three decades and discusses a number of knowledge gaps that need to be addressed. Five areas are described: patient intervention efficacy and effectiveness; barriers to BI implementation by health professionals; individual-level factors that impact on BI implementation; organization-level factors that impact on BI implementation; and society-level factors that impact on BI implementation. BI research has focused largely upon the individual patient and health professional levels, with the main focus upon primary health care research, and studies are lacking in other settings. However, research must, to a larger degree, take into account the organizational and wider context in which BI occurs, as well as interaction between factors at different levels, in order to advance the understanding of how wider implementation of BI can be achieved in various settings and how different population groups can be reached. It is also important to expand BI research beyond its current parameters to investigate more ambitious long-term educational programmes and new organizational models. More widespread implementation of BI will require many different interventions (efforts, actions, initiatives, etc.) at different interlinked levels, from implementation interventions targeting individual health professionals' knowledge, skills, attitudes and behaviours concerning alcohol issues, BI and behaviour change counselling to efforts at the organizational and societal levels that influence the conditions for delivering BI as part of routine health care. [source] Multivariate Neuropsychological Prediction of Seizure Lateralization in Temporal Epilepsy Surgical CasesEPILEPSIA, Issue 8 2007Therese A. Keary Summary:,Purpose: Neuropsychological assessment can be of assistance in determining seizure lateralization in cases where EEG and MRI findings do not provide clear lateralizing data. While several studies have examined the lateralizing value of individual neuropsychological measures, clinicians are still in need of a statistically sound method that permits the incorporation of multiple neuropsychological variables to predict seizure lateralization in the individual patient. Method: The present study investigated the lateralizing value of several commonly used neuropsychological measures in a large sample of patients (n = 217) who eventually underwent surgical resection to treat their epilepsy. Side of surgery was used to operationally define seizure lateralization. A comparison of the relative utility of a multivariate versus univariate approach to predict seizure lateralization was conducted in temporal epilepsy cases. Results: The results provide evidence for the incremental validity of neuropsychological measures, other than memory and IQ tests, in the prediction of seizure lateralization in patients with medically intractable epilepsy. These data indicate that a multivariate approach increases the accuracy of prediction of seizure lateralization for temporal lobe epilepsy cases. Conclusion: This study supports the use of a multivariate approach using neuropsychological measures to predict seizure lateralization in temporal epilepsy surgical candidates. Regression formulas are provided to enhance the clinical utility of these findings. [source] Involvement of the human thalamus in relational and non-relational memoryEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2008Eleonore Soei Abstract Damage to the human thalamus has been associated with selective anterograde recognition memory impairments. Recently, recognition memory has been subdivided into relational and non-relational memory. The aim of the present study was to assess the potentially differential involvement of the human thalamus in relational and non-relational memory. Ten patients with focal ischemic thalamic lesions were compared to individualized control groups of healthy subjects matched to each individual patient on age and IQ. Six patients showed poorer relational memory than their respective control samples. None of the 10 patients showed a significant deficit on the non-relational memory task. These observations suggest an involvement of the thalamus in relational memory, and are discussed in terms of disruption of mediotemporal-thalamic and thalamic-fronto-striatal circuits. [source] New Generation of Multifunctional Nanoparticles for Cancer Imaging and TherapyADVANCED FUNCTIONAL MATERIALS, Issue 10 2009Kyeongsoon Park Abstract Advances in nanotechnology have contributed to the development of novel nanoparticles that enable the tumor-specific delivery of imaging probes and therapeutic agents in cancer imaging and therapy. Nanobiotechnology combines nanotechnology with molecular imaging, which has led to the generation of new multifunctional nanoparticles for cancer imaging and therapy. Multifunctional nanoparticles hold great promise for the future of cancer treatment because they can detect the early onset of cancer in each individual patient and deliver suitable therapeutic agents to enhance therapeutic efficacy. The combination of tumor-targeted imaging and therapy in an all-in-one system provides a useful multimodal approach in the battle against cancer. Novel multifunctional nanoparticles thus offer a new avenue in the application of personalized medicine in the near future. Herein, new trends and the significance of novel multifunctional nanoparticles in cancer imaging and therapy are reviewed. [source] The role of prophylaxis in bleeding disordersHAEMOPHILIA, Issue 2010E. BERNTORP Summary., The rationale for long-term prophylaxis in more severe forms of von Willebrand's disease (VWD) is obvious, as mucosal bleeding and haemophilia-like joint bleeds resulting in chronic morbidity may occur. However, the experience with prophylactic treatment in this group is scanty. An international VWD Prophylaxis Network (VWD PN) was established in 2006. The VWD PN will investigate prophylaxis with retrospective and prospective studies. Eighteen centres in Europe and North America are recruiting patients and an additional 40 centres are preparing for or evaluating participation. In the absence of randomized prospective studies for most rare bleeding disorders, guidelines for prophylaxis are a subject of controversy. In situations where there is a strong family history of bleeding, long-term prophylaxis is administered in selected cases. Short intervals of prophylaxis can also be given before some surgeries or during pregnancy. The benefits of prophylaxis must be balanced by the risk of side effects. Therefore, it is essential to delineate its management in a specialized comprehensive care environment. In haemophilia, decades of clinical experience and numerous retrospective and, recently, prospective studies clearly demonstrate that prophylactic treatment is superior to on-demand treatment, regardless of whether the outcome is the number of joint- or life-threatening bleeds, arthropathy evaluated by X-ray or MRI, or quality of life measured by generic or haemophilia-specific instruments. Optimal prophylactic treatment should be started early in life (primary prophylaxis) but various options exist for the dose and dose interval. These depend on the objective of treatment in the individual patient, which, in turn, is dependent on resources in the health care system. [source] In vivo recovery of factor VIII and factor IX: intra- and interindividual variance in a clinical settingHAEMOPHILIA, Issue 1 2007S. BJÖRKMAN Summary., In vivo recovery (IVR) is traditionally used as a parameter to characterize the pharmacokinetic properties of coagulation factors. It has also been suggested that dosing of factor VIII (FVIII) and factor IX (FIX) can be adjusted according to the need of the individual patient, based on an individually determined IVR value. This approach, however, requires that the individual IVR value is more reliably representative for the patient than the mean value in the population, i.e. that there is less variance within than between the individuals. The aim of this investigation was to compare intra- and interindividual variance in IVR (as U dL,1 per U kg,1) for FVIII and plasma-derived FIX in a cohort of non-bleeding patients with haemophilia. The data were collected retrospectively from six clinical studies, yielding 297 IVR determinations in 50 patients with haemophilia A and 93 determinations in 13 patients with haemophilia B. For FVIII, the mean variance within patients exceeded the between-patient variance. Thus, an individually determined IVR value is apparently no more informative than an average, or population, value for the dosing of FVIII. There was no apparent relationship between IVR and age of the patient (1.5,67 years). For FIX, the mean variance within patients was lower than the between-patient variance, and there was a significant positive relationship between IVR and age (13,69 years). From these data, it seems probable that using an individual IVR confers little advantage in comparison to using an age-specific population mean value. Dose tailoring of coagulation factor treatment has been applied successfully after determination of the entire single-dose curve of FVIII:C or FIX:C in the patient and calculation of the relevant pharmacokinetic parameters. However, the findings presented here do not support the assumption that dosing of FVIII or FIX can be individualized on the basis of a clinically determined IVR value. [source] Use of pharmacokinetics in the coagulation factor treatment of patients with haemophiliaHAEMOPHILIA, Issue 6 2005A. D. Shapiro Summary., Dosing decisions for replacement coagulation factors in patients with haemophilia should be made on an individual patient basis, with the required dose dependent on factors including the clinical situation, the severity of the factor deficiency, and the location and extent of bleeding. Moreover, there is considerable variability in the pharmacokinetics of coagulation products that needs to be considered; in particular, with both factor (F) IX and FVIII products, there is considerable inter-patient variability in in vivo recovery and terminal half-life values. In the present report, we provide a practical guide to calculating and applying pharmacokinetic parameters relevant to the optimal dosing of coagulation products. We discuss the conduct of a pharmacokinetic study in an individual patient, how to calculate pharmacokinetic values from raw data and clinical situations where an individual pharmacokinetic study is helpful. We highlight the importance of considering an individual pharmacokinetic study in all patients starting a new coagulation product. [source] A critical appraisal of prognostic and predictive factors for common lung cancersHISTOPATHOLOGY, Issue 7 2006F B J M Thunnissen The outlook for patients with lung cancer remains poor despite advances in the understanding of the pathology and biology of this disease. To optimize treatment protocols prognostic data are essential. The current era with molecular research on mRNA expression analysis and proteomics will lead to a plethora of new molecular markers, which are likely to be correlated, at least in part, with each other and with disease activity, progression and survival. However, although the number of prognostic factors analysed in published systematic reviews on lung cancer is large, the scope of these factors in individual studies is often narrow. In daily practice prognostic factors other than general TNM staging are not implemented. To assess the efficacy of new prognostic factors for the management of individual patients with non-small cell lung cancer, studies with clinically relevant modelling are required. In this review arguments are provided to use a model combining radiological and histopathological growth rate, histopathological diagnosis and molecular characteristics as markers for metastatic capacity, tumour volume doubling time and expected response to targeted therapy. This may reveal time-related predictive information useful for treatment guidance of the individual patient. [source] The role of genotype-specific human papillomavirus detection in diagnosing residual cervical intraepithelial neoplasiaINTERNATIONAL JOURNAL OF CANCER, Issue 2 2002Ruud LM Bekkers Abstract We assessed prospectively whether residual cervical intraepithelial neoplasia (CIN) after treatment for high-grade CIN can be predicted by genotype-specific high-risk HPV (HR-HPV) detection in follow-up cervical scrapes. A broad spectrum, highly sensitive SPF10 -LiPA-PCR HPV detection technique was used on cervical scrapes before large loop excision of the transformation zone (LLETZ), on the LLETZ biopsy and on follow-up scrapes of 90 patients treated for high-grade CIN. HR-HPV was detected in the biopsies of 93% (n = 84) of the patients and in the follow-up scrapes of 48% (n = 43) of the patients. In 12 patients, genotype-specific HR-HPV persistence was detected in both follow-up scrapes. In 10 patients, residual CIN was detected. In 5 of these patients (including all patients with residual CIN 3), the follow-up scrapes showed genotype-specific HR-HPV persistence. In 2 patients, a different HR-HPV was detected, and 3 patients had HR-HPV-negative follow-up scrapes. Conventional cytologic follow-up was abnormal in 13 patients including all 10 patients with residual CIN. The negative predictive value (NPV) of HR-HPV detection on follow-up scrapes was high (94%). Repeat detection of genotype-specific HR-HPV showed a lower sensitivity and NPV than repeat detection of any HR-HPV, but its specificity was higher. Repeat conventional cytologic follow-up showed the highest sensitivity and NPV. In conclusion, the presence of HR-HPV in cervical scrapes after LLETZ for high-grade CIN is a risk factor for the presence of residual CIN. HR-HPV genotype-specific persistence is specifically present in patients with residual CIN 3. However, HR-HPV detection cannot predict or exclude the presence of residual CIN in the individual patient and additional procedures remain necessary. © 2002 Wiley-Liss, Inc. [source] Incidence of In-Hospital Falls in Geriatric Patients Before and After the Introduction of an Interdisciplinary Team,Based Fall-Prevention InterventionJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 12 2007Wolfgang Von Renteln-Kruse MD Falls are among the most common unwanted events in older hospital inpatients, but evidence of effective prevention is still limited compared with that in the community and in long-term care facilities. This article describes a prevention program and its effects on the incidence of falls in geriatric hospital wards. It was a prospective cohort study with historical control including all 4,272 patients (mean age 80, 69% female) before and 2,982 (mean age 81, 69% female) after introduction of the intervention. The intervention included fall-risk assessment on admission and reassessment after a fall; risk alert; additional supervision and assistance with the patients' transfer and use of the toilet; provision of an information leaflet; individual patient and caregiver counseling; encouragement of appropriate use of eyeglasses, hearing aids, footwear, and mobility devices; and staff education. Measurements included standardized fall-incidence reporting, activity of daily living and mobility status, number of falls and injurious falls, and number of patients who fell. Before the intervention was introduced, 893 falls were recorded. After the intervention was implemented, only 468 falls were recorded (incidence rate ratio (IRR)=0.82, 95% confidence interval (CI)=0.73,0.92), 240 versus 129 total injurious falls (IRR=0.84, 95% CI=0.67,1.04), 10 versus nine falls with fracture (IRR=1.40, 95% CI=0.51,3.85) and 611 versus 330 fallers. The relative risk of falling was significantly reduced (0.77, 95% CI=0.68,0.88). A structured multifactorial intervention reduced the incidence of falls, but not injurious falls, in a hospital ward setting with existing geriatric multidisciplinary care. Improvement of functional competence and mobility may be relevant to fall prevention in older hospital inpatients. [source] Resistant Pathogens in Urinary Tract InfectionsJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 2002Lindsay E. Nicolle MD Antimicrobial susceptibility of bacteria causing urinary tract infection (UTI) has evolved over several decades as antimicrobial exposure has repeatedly been followed by emergence of resistance. Older populations in the community, long-term care facilities, or acute care facilities have an increased prevalence of resistant bacteria isolated from UTI. Resistant isolates are more frequent in long-term care populations than the community. Resistant isolates include common uropathogens, such as Escherichia coli or Proteus mirabilis, and organisms with higher levels of intrinsic resistance, such as Pseudomonas aeruginosa or Providencia stuartii. Isolation of resistant organisms is consistently associated with prior antimicrobial exposure and higher functional impairment. The increased likelihood of resistant bacteria makes it essential that a urine specimen for culture and susceptibility testing be obtained before instituting antimicrobial therapy. Therapy for the individual patient must be balanced with the possibility that antimicrobial use will promote further resistance. Antimicrobial therapy should be avoided unless there is a clear clinical indication. In particular, asymptomatic bacteriuria should not be treated with antimicrobials. Where symptoms are mild or equivocal, urine culture results should be obtained before initiating therapy. This permits selection of specific therapy for the infecting organism and avoids empiric, usually broad-spectrum, therapy. Where empirical therapy is necessary, prior infecting organisms should be isolated, and recent antimicrobial therapy, as well as regional or facility susceptibility patterns, should be considered in antimicrobial choice. Where empirical therapy is used, it should be reassessed 48 to 72 hours after initiation, once pretherapy cultures are available. [source] Residual Lifetime Risk of Fractures in Women and Men,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 6 2007Nguyen D Nguyen Abstract In a sample of 1358 women and 858 men, ,60 yr of age who have been followed-up for up to 15 yr, it was estimated that the mortality-adjusted residual lifetime risk of fracture was 44% for women and 25% for men. Among those with BMD T-scores , ,2.5, the risks increased to 65% in women and 42% in men. Introduction: Risk assessment of osteoporotic fracture is shifting from relative risk to an absolute risk approach. Whereas BMD is a primary predictor of fracture risk, there has been no estimate of mortality-adjusted lifetime risk of fracture by BMD level. The aim of the study was to estimate the residual lifetime risk of fracture (RLRF) in elderly men and women. Materials and Methods: Data from 1358 women and 858 men ,60 yr of age as of 1989 of white background from the Dubbo Osteoporosis Epidemiology Study were analyzed. The participants have been followed for up to 15 yr. During the follow-up period, incidence of low-trauma, nonpathological fractures, confirmed by X-ray and personal interview, were recorded. Incidence of mortality was also recorded. BMD at the femoral neck was measured by DXA (GE-LUNAR) at baseline. Residual lifetime risk of fracture from the age of 60 was estimated by the survival analysis taking into account the competing risk of death. Results: After adjusting for competing risk of death, the RLRF for women and men from age 60 was 44% (95% CI, 40,48) and 25% (95% CI, 19,31), respectively. For individuals with osteoporosis (BMD T-scores , ,2.5), the mortality-adjusted lifetime risk of any fracture was 65% (95% CI, 58,73) for women and 42% (95% CI, 24,71) for men. For the entire cohort, the lifetime risk of hip fracture was 8.5% (95% CI, 6,11%) for women and 4% (95% CI, 1.3,5.4%) for men; risk of symptomatic vertebral fracture was 18% (95% CI, 15,21%) for women and 11% (95% CI, 7,14%) for men. Conclusions: These estimates provide a means to communicate the absolute risk of fracture to an individual patient and can help promote the identification and targeting of high-risk individuals for intervention. [source] Management of Bone Loss After Organ Transplantation,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 12 2004Adi Cohen Organ transplant recipients experience rapid bone loss and high fracture rates, particularly during the early post-transplant period. Early rapid bone loss occurs in the setting of uncoupled bone turnover with increased bone resorption and decreased bone formation. Because there are no clinical factors that reliably predict post-transplant bone loss and fractures in the individual patient, all transplant recipients should be considered candidates for early preventive therapy for osteoporosis. Long-term transplant recipients with densitometric osteoporosis and/or fractures should also receive treatment. Although active metabolites of vitamin D and bisphosphonates have both shown efficacy, data from clinical trials suggest that bisphosphonates are the safest and most consistently effective agents for the prevention and treatment of post-transplantation osteoporosis in adults. Kidney transplant recipients represent a special population, and more research is needed to delineate the risks and benefits of treating bone disease in these patients. [source] Vignettes in Osteoporosis: A Road Map to Successful Therapeutics,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 1 2004Clifford J Rosen Abstract The diagnosis and management of osteoporosis have become increasingly more complex as new drugs enter the marketplace and meta-analyses of randomized trials with "other" agents become more prolific. We describe five common clinical scenarios encountered in the practice of osteoporosis medicine and various road maps that could lead to successful therapy. Introduction: The diagnosis and treatment of osteoporosis have changed dramatically in the last decade. Advances in diagnostic technologies and a range of newer treatment options have provided the clinician with a wide array of choices for treating this chronic disease. Despite the issuance of several "guidelines" and practice recommendations, there still remains confusion among clinicians about basic approaches to the management of osteoporosis. This paper should be used as a case-based approach to define optimal therapeutic choices. Materials and Methods: Five representative cases were selected from two very large clinical practices (Bangor, ME; Pittsburgh, PA). Diagnostic modalities and treatment options used in these cases were selected on an evidence-based analysis of respective clinical trials. Subsequent to narrative choices by two metabolic bone disease specialists (SG and CR), calculation of future fracture risk and selection of potential alternative therapeutic regimens were reviewed and critiqued by an epidemiologist (DB). Results: A narrative about each case and possible management choices for each of the five cases are presented with references to justify selection of the various therapeutic options. Alternatives are considered and discussed based on literature and references through July 2003. The disposition of the individual patient is noted at the end of each case. Conclusions: A case-based approach to the management of osteoporosis provides a useful interface between guidelines, evidence-based meta-analyses, and clinical practice dilemmas. [source] Long-Term Variability of Markers of Bone Turnover in Postmenopausal Women and Implications for Their Clinical Use: The OFELY Study,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 10 2003Patrick Garnero Abstract Bone marker variability has raised concern for its use in individual patients. Serum osteocalcin (formation) and CTX (resorption) were measured every year for 4 years in 268 postmenopausal women. Seventy percent to 80% of women classified as having high bone turnover at baseline were similarly classified by the same methods 4 years later. Introduction: High bone marker levels are a risk factor for osteoporosis in postmenopausal women, but variability of measurements has raised doubts about their clinical use in an individual patient. Methods: We studied 268 untreated postmenopausal women (50,81 years of age) belonging to a population-based prospective cohort. We collected fasting morning blood samples every year for 4 years to measure serum intact osteocalcin (OC) and serum C-terminal cross-linked telopeptide of type I collagen (CTX) as bone formation and resorption markers, respectively. Results: Serum OC and CTX remained stable during follow-up (+1.2%/year, p = 0.003 and ,0.13%/year, p = 0.70 for OC and S-CTX, respectively). At baseline, women were classified as having low (tertile 1), intermediate (tertile 2), or high (tertile 3) bone turnover. Agreement of classification between baseline and 4-year measurements was moderate (, [95% CI]: 0.51 [0.43,0.59] and 0.52 [0.44,0.60] for OC and S-CTX, respectively). Less than 10% of women in tertile 1 or 3 of either marker at baseline were found in the opposite tertile 4 years later. When the two markers were combined, only 2% of women at high turnover at baseline,defined as OC and/or S-CTX in tertile 3,were classified at low turnover 4 years later. Among women classified at high bone turnover at baseline (tertile 3), 70,80 % were also found at high turnover 4 years later. Among women in tertile 2, only 51% and 43% for OC and CTX, respectively, remained in the same tertile at the second measurement. Conclusions: Serum levels of bone formation and resorption markers are stable over 4 years in postmenopausal women, on average. The majority of women classified as having high bone turnover were similarly classified by the same methods 4 years later. However, 20,30 % of these women at risk for fracture would be incorrectly classified, suggesting that further investigation would be required to reduce the number of patients who would be treated unnecessarily if the decision was made on bone marker measurement. For women with intermediate levels, classification may be improved by a second measurement or by combining two markers. [source] Patients undergoing total hip arthroplasty: a perioperative pain experienceJOURNAL OF CLINICAL NURSING, Issue 4 2006Margareta Warrén Stomberg PhD Aim., The aim was to evaluate patient's perioperative pain experience after total hip replacement and patients' satisfaction with pain management. Background., Total hip arthroplasty is a common surgical procedure intended to reduce pain and return patients to better function. Realistic expectations about total hip arthroplasty is important for optimal postoperative recovery and the information must be adapted to fit the individual patient. Methods., A descriptive design was used comparing patients outcome data. Pitman's test was used for statistical analyses. Adult patients (n = 112) undergoing surgical hip replacement procedures answered a 17-item questionnaire on the fourth postoperative day. The questionnaire included given alternatives and visual analogue scales (0,100 mm) for the pain assessment. Result., The patients' postoperative pain experience after hip replacement surgery was in average low, 33·1 mm on a 100 mm visual analogue scale. Patient's pain experience was reported to be highest on the first postoperative day for most of the patients. The preoperative pain experience tends to be higher than the postoperative pain experience. Older patients reported less average pain level postoperatively. Satisfaction with pain management was high. Conclusion., The pain experience tends to be higher preoperatively than postoperatively. Patients who reported a higher pain experience postoperatively reported that their pain experience was significant higher than preoperative expected. Relevance to practice., It is important for the postoperative outcome measure that the patients have a realistic expectation of pain experiences after total hip arthroplasty. The nurse is one of the staff members responsible for information to the individual patient. [source] Direct versus Indirect Veneer Restorations for Intrinsic Dental StainsJOURNAL OF ESTHETIC AND RESTORATIVE DENTISTRY, Issue 2 2006Article first published online: 25 APR 200 abstract Objective:, The purpose of this study was to examine the effectiveness of indirect and direct veneer restorations, particularly with regard to longevity and patient satisfaction. Materials and Methods:, This study evaluated the literature on randomized clinical trials comparing direct and indirect veneers on anterior teeth. The search strategy involved Medline and other databases and was followed by contacting authors to determine whether any additional published or unpublished studies were available. Relevant studies were assessed for factors such as quality of randomization, outcome assessment, and completeness of recall evaluation. Data from the studies were extracted by three independent reviewers using special forms. Authors were contacted for clarification and missing data. Study details such as dates, demographics of the sample, and outcomes were recorded. Results:, The electronic searches identified 29 clinical trials and 1 systematic review. Six of those were screened as potentially relevant to the review, but following a more detailed screening, only one study (Meijering and colleagues, 1998) met all of the inclusion criteria. In the 2-year recall of that study, the overall survival rates were 94% for porcelain, 90% for indirect composite, and 74% for direct composite veneers. The survival rate was higher when the incisal edge was reduced. Patient satisfaction rates were 93% for porcelain, 82% for indirect composite, and 67% for direct composite. Conclusion:, Very little reliable evidence compares the effectiveness of indirect versus indirect veneers. For an individual patient, the choice between the two options should take into account patient preference and the clinician's experience. [source] Integrating evidence into clinical practice: an alternative to evidence-based approachesJOURNAL OF EVALUATION IN CLINICAL PRACTICE, Issue 3 2006Mark R. Tonelli MD MA Abstract Evidence-based medicine (EBM) has thus far failed to adequately account for the appropriate incorporation of other potential warrants for medical decision making into clinical practice. In particular, EBM has struggled with the value and integration of other kinds of medical knowledge, such as those derived from clinical experience or based on pathophysiologic rationale. The general priority given to empirical evidence derived from clinical research in all EBM approaches is not epistemically tenable. A casuistic alternative to EBM approaches recognizes that five distinct topics, 1) empirical evidence, 2) experiential evidence, 3) pathophysiologic rationale, 4) patient goals and values, and 5) system features are potentially relevant to any clinical decision. No single topic has a general priority over any other and the relative importance of a topic will depend upon the circumstances of the particular case. The skilled clinician must weigh these potentially conflicting evidentiary and non-evidentiary warrants for action, employing both practical and theoretical reasoning, in order to arrive at the best choice for an individual patient. [source] |