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Selected AbstractsTreatment-emergent behavioural side effects with selective serotonin re-uptake inhibitors in adults with learning disabilitiesHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 2 2001A. B. Biswas Abstract Selective serotonin re-uptake inhibitors are widely used for the treatment of depression suffered by adults with learning disabilities. However, the presentation, time of onset and prevalence of treatment emergent symptoms, have not been extensively studied in adults with learning disabilities. The aim of this study was to determine these aspects of treatment. The study design involved retrospective analysis of case notes of all adults with learning disabilities treated with either fluoxetine or paroxetine for depression. During 31% of treatment episodes, patients suffered treatment emergent symptoms during treatment with either selective serotonin re-uptake inhibitor (SSRI). These symptoms subsided on discontinuation of the SSRI. The common emergent symptoms in this group were elevated mood (39%), decreased sleep (35%), hyperactivity (30%), overtalkativeness (26%), agitation (24%) and aggression (37%). In 20% symptoms developed within 1 month and in 67% within 7 months of starting treatment with a SSRI. There were no significant differences noted in the frequency and nature of treatment emergent symptoms between fluoxetine and paroxetine. Few guidelines, if any, exist for initiating and continuing antidepressant treatment for therapeutic or prophylactic use in this patient population. Close monitoring of efficacy and tolerability, including treatment emergent psychiatric symptoms is warranted. Copyright © 2001 John Wiley & Sons, Ltd. [source] Treatment of recurrent hepatitis B infection in liver transplant recipientsLIVER TRANSPLANTATION, Issue 10B 2002Norah A. Terrault MD 1Therapeutic decisions are guided by a patient's clinical status (severity of disease and presence of comorbidities) and previous drug-exposure history. 2Lamivudine is safe and effective in liver transplant recipients with recurrent hepatitis B virus (HBV) infection caused by wild-type virus or failure of hepatitis B immunoglobulin therapy. Lamivudine resistance, developing in approximately 25% after 12 months of therapy, is its main limitation. 3Famciclovir is safe in liver transplant recipients; however, virological and clinical responses are less consistent than with lamivudine. Thus, lamivudine is favored over famciclovir as first-line therapy in transplant recipients with no previous exposure to nucleoside analogues. 4Although limited in availability, adefovir dipivoxil appears safe and effective in treating liver transplant recipients with lamivudine-resistant HBV disease. Close monitoring of renal function is recommended, with dose adjustment in patients with reduced creatinine clearances. 5Limited data suggest that intravenous ganciclovir, tenofovir disoproxil fumarate, and interferon alfa may be useful as rescue therapies for patients with lamivudine- or famciclovir-resistant HBV disease. 6Antiviral therapy with two or more suitable agents may minimize the chance for viral resistance; therefore, future therapeutic strategies likely will use combination therapy in the long-term management of recurrent HBV disease. [source] Guidelines for the optimization of microsurgery in atherosclerotic patientsMICROSURGERY, Issue 5 2006F.A.C.S., Hung-Chi Chen M.D. We review the pathogenesis of atherosclerosis and the issues that must be taken into consideration when performing microsurgery in atherosclerotic patients. Atherosclerosis is a systemic disease, and may affect the success of microsurgery. Atherosclerotic patients have a tendency toward thrombosis, because the nature of the arteries is changed. Such patients are usually old and have additional medical problems. To increase the success rate of microsurgery in atherosclerotic patients, special precautions should be considered. Patients must be evaluated properly for the suitability of microsurgery. The microsurgical technique requires a meticulous approach, and various technical tricks can be used to avoid thrombosis. Recipient-vessel selection, anastomotic technique, and the use of vein grafts are all important issues. Prophylactic anticoagulation is recommended in severely atherosclerotic patients. Close monitoring of the patient and flap is necessary after the operation, as with routine microvascular free-tissue transfers. We conclude that atherosclerosis is not a contraindication for microsurgery. If the microsurgeon knows how to deal with the difficulties in atherosclerotic patients, microsurgery can be performed safely. © 2006 Wiley-Liss, Inc. Microsurgery, 2006. [source] Associated factors of rehospitalization among schizophrenic patientsPSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 6 2003YURIKO SUZUKI md Abstract, The purpose of the present study was to identify the associated factors of rehospitalization in schizophrenic patients. A case-control study was conducted. The cases consisted of rehospitalized patients (n = 67) and controls selected from the outpatients who were matched by age, gender, and the period after the last discharge (n = 62). In the multiple logistic regression analysis, no clinic visits in the second month prior to entry, the number of clinic visits in the previous month, and junior high school graduation as education level were significantly (P < 0.01) associated with rehospitalization after controlling their present function as assessed by the Global Assessment of Functioning. Close monitoring of clinic visits and outreach service appear to be important in preventing rehospitalization of schizophrenic patients. These identified modifiable factors suggest further needs for development and implementation of integrated mental health services in the community. [source] Deterioration in cord blood gas status during the second stage of labour is more rapid in the second twin than in the first twinBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 6 2004Tak-Yeung Leung Objective To compare in twin pregnancy the rate of deterioration in umbilical blood gas status during the second stage of labour, and to investigate whether the duration of the first twin's delivery has any effect on the blood gas status of the second twin. Design A retrospective study. Setting Department of Obstetrics and Gynaecology in a university teaching hospital. Population Twin pregnancies with both of the twins delivered by normal cephalic vaginal mode, at or beyond 34 weeks of gestation, over a period of seven years. Twins with any maternal or fetal complications including discordant growth, intrauterine growth restriction, intrauterine death, fetal malformations, fetal distress, pre-eclampsia and diabetes were excluded. Methods The first twins' second stage was defined as from the start of maternal pushing to his/her delivery, while the second twins' second stage started after the delivery of the first twin and ended by his/her delivery. The total duration of the second stage was the sum of the above two intervals. The correlations between the first twins' umbilical cord blood gas parameters and the duration of their own second stage, the second twins' umbilical cord blood gas parameters and the duration of their own second stage, as well as that of the total second stage, were studied. Main outcome measures The changes of umbilical arterial pH of each twin with the duration of the corresponding second stage of labour, and the difference among them. Results A total of 51 cases were reviewed. The median gestation at delivery was 37 weeks. The median duration of first twins' second stage was 10 minutes (range 1,75) while that of the second twins' was 10 minutes (range 3,26). The first twins' second stage was inversely correlated with their arterial pH, venous pH and base excess [BE] (P < 0.01). Both the second twins' second stage and the total second stage were inversely correlated with both of their arterial and venous pH and BE (P < 0.01). However, further multiple regression analysis suggested that the correlation of the total second stage with the second twins' cord blood parameters could be solely explained by their own second stage. The rate of reduction in the second twins' arterial pH was 4.95 × 10,3 per minute, and was significantly faster than that of the first twins', which was 1.55 × 10,3 per minute (P < 0.05). Conclusions During normal vaginal delivery, the umbilical cord blood gas status of both the first and the second twins deteriorated with the duration of their corresponding second stages, but the effects are greater in the latter. Furthermore, the duration of the first twins' second stage does not affect the blood gas status of the second twins'. These observations support the postulation of a diminished uteroplacental exchange function after the delivery of the first twin. Close monitoring and expeditious delivery of the second twins are important. [source] Causes of death in sickle cell disease: an autopsy studyBRITISH JOURNAL OF HAEMATOLOGY, Issue 2 2003Elizabeth A. Manci Summary. More precise analysis of causes of death is needed to focus research efforts and improve morbidity and mortality in sickle cell disease. In this study, the morphological evidence of the cause of death was studied in 306 autopsies of sickle cell disease, which were accrued between 1929 and 1996. The most common cause of death for all sickle variants and for all age groups was infection (33,48%). The terminal infection was heralded by upper respiratory tract syndromes in 72·6% and by gastroenteritis in 13·7%. The most frequent portal of entry in children was the respiratory tract but, in adults, a site of severe chronic organ injury. Other causes of death included stroke 9·8%, therapy complications 7·0%, splenic sequestration 6·6%, pulmonary emboli/thrombi 4·9%, renal failure 4·1%, pulmonary hypertension 2·9%, hepatic failure 0·8%, massive haemolysis/red cell aplasia 0·4% and left ventricular failure 0·4%. Death was frequently sudden and unexpected (40·8%) or occurred within 24 h after presentation (28·4%), and was usually associated with acute events (63·3%). This study shows that the first 24 h after presentation for medical care is an especially perilous time for patients with sickle cell disease and an acute event. Close monitoring and prompt aggressive treatment are warranted. [source] Phase 1 pharmacokinetic and drug-interaction study of dasatinib in patients with advanced solid tumorsCANCER, Issue 6 2010Faye M. Johnson MD Abstract BACKGROUND: The recently developed the Src and Abelson (Abl) kinase inhibitor dasatinib has antitumor effects in epithelial and mesenchymal tumors. Preclinical data have indicated that dasatinib is metabolized primarily through cytochrome P450 3A4 (CYP3A4) and may cause QT prolongation. In light of its improved tolerability, the authors were interested in the safety of a once-daily dasatinib regimen. METHODS: The authors conducted a phase 1 trial of dasatinib in 29 patients with advanced solid tumors. Segment 1 of the trial was short term and sequential and was designed to determine whether the coadministration of the potent CYP3A4 inhibitor ketoconazole had an effect on the pharmacokinetics of dasatinib. Segment 2 was designed to evaluate the safety of dasatinib as dosing was increased. QT intervals were monitored closely in both segments. Efficacy was assessed in Segment 2 using both positron emission tomography and computed tomography. RESULTS: Hematologic toxicities were markedly less than those observed in patients with leukemia, whereas nonhematologic toxicities were similar. The authors determined that the maximum recommended dose was 180 mg once daily based on the incidence of pleural effusion. Coadministration of ketoconazole led to a marked increase in dasatinib exposure, which was correlated with an increase in corrected QT (QTc) values of approximately 6 msec. No adverse cardiac events were observed. CONCLUSIONS: The dose-limiting toxic effect for dasatinib was pleural effusion. The pharmacokinetic and cardiac studies indicated that coadministration of dasatinib with potent CYP3A4 inhibitors or agents that prolong the QTc interval should be avoided if possible. Close monitoring for toxicity and dose reduction should be considered if the coadministration of such agents cannot be avoided. Cancer 2010. © 2010 American Cancer Society. [source] Making the case for objective performance metrics in newborn screening by tandem mass spectrometryDEVELOPMENTAL DISABILITIES RESEARCH REVIEW, Issue 4 2006Piero Rinaldo Abstract The expansion of newborn screening programs to include multiplex testing by tandem mass spectrometry requires understanding and close monitoring of performance metrics. This is not done consistently because of lack of defined targets, and interlaboratory comparison is almost nonexistent. Between July 2004 and April 2006 (N = 176,185 cases), the overall performance metrics of the Minnesota program, limited to MS/MS testing, were as follows: detection rate 1:1,816, positive predictive value 37% (54% in 2006 till date), and false positive rate 0.09%. The repeat rate and the proportion of cases with abnormal findings actually been reported are new metrics proposed here as an objective mean to express the overall noise in a program, where noise is defined as the total number of abnormal results obtained using a given set of cut-off values. On the basis of our experience, we propose the following targets as evidence of adequate analytical and postanalytical performance: detection rate 1:3,000 or higher, positive predictive value >20%, and false positive rate <0.3%. © 2006 Wiley-Liss, Inc. MRDD Research Reviews 2006;12:255,261. [source] Selenium Deficiency Associated with Cardiomyopathy: A Complication of the Ketogenic DietEPILEPSIA, Issue 4 2003A. G. Christina Bergqvist Summary: ,Purpose: The ketogenic diet (KD) is an efficacious treatment for intractable epilepsy, associated with infrequent side effects. The KD is known to be deficient in most vitamins and minerals and may be deficient in trace minerals. We report biochemical selenium deficiency in nine patients on the KD, including one who developed cardiomyopathy. Methods: A whole-blood selenium level was obtained on the symptomatic patient after noting the patient's poor appearance on physical examination. Children already treated and children beginning the KD were then evaluated prospectively for selenium status by measuring whole-blood or serum selenium as part of routine laboratory evaluation every 3 months. Results: The index case had no detectable whole-blood selenium. Cardiac physical examination and ECG were normal, but the echocardiogram revealed cardiomyopathy. Thirty-nine additional children had the selenium status evaluated. Eight had selenium levels below the normal range (six initially, and two developed low selenium levels on serial testing). They were referred for cardiology evaluations, which were normal. Selenium supplementation improved levels in all children. Low levels were seen in some children after only a few months of treatment. Conclusions: The nutrient adequacy of the currently used KD has not been fully evaluated. The nutrient content of KD with usual supplements may not meet Recommended Dietary Allowances (RDA) for selenium and may not provide other trace minerals in adequate amounts. At our center, selenium deficiency was found in 20% of the patients evaluated. Screening for selenium deficiency is suggested if the patient KD regimen does not meet ,75% of the RDA or if the child is symptomatic. Nutrient supplementation should provide adequate trace elements for children treated with the KD. The KD requires close monitoring of the overall nutritional status. [source] Covance's global mentoring initiative develops people through exceptional partnershipsGLOBAL BUSINESS AND ORGANIZATIONAL EXCELLENCE, Issue 1 2006Miriam Darmstadter The global mentoring program at Covance plays a dual role as a diversity initiative and a resource-efficient developmental tool, providing a powerful developmental experience that enriches worklife for all participants. After studying successful programs in leading companies, the Covance team crafted a program that includes selection criteria and a careful matching process, training and tools for mentoring pairs, ongoing support, and close monitoring and evaluation. The company has also tackled the challenges of long-distance mentoring relationships to make the program more accessible to its global workforce. As the program continues to grow and receive rave reviews, the Covance team continues to refine it for even greater effectiveness. © 2006 Wiley Periodicals, Inc. [source] Perceived job stress of women workers in diverse manufacturing industriesHUMAN FACTORS AND ERGONOMICS IN MANUFACTURING & SERVICE INDUSTRIES, Issue 3 2005Jinky Leilanie Lu An investigation of the impact of organizational factors on perceived job stress among women workers in the IT-dominated garment and electronics industries in the Philippines was undertaken. The sample included 23 establishments with 630 women respondents. Questionnaires, walk-through surveys of the industries, and interviews were done. The workplace factors included the content of the job, the nature of tasks, job autonomy, hazard exposure, and management and supervisory styles. Chi-square analysis showed that there were interactions among the organizational factors (P = 0.05 and 0.10). These factors included the need for better quality and new products; tasks requiring intense concentration; exposure to radiation, chemical, noise, and vapor hazards; standing for prolonged periods of time; and highly monitored, repetitious work. Workers experienced job stress (P = .05) when they were subjected to low job autonomy, poor work quality, close monitoring, and hazardous work pressure. © 2005 Wiley Periodicals, Inc. Hum Factors Man 15: 275,291, 2005. [source] Growth after intestinal resection for Crohn's disease in children, adolescents, and young adultsINFLAMMATORY BOWEL DISEASES, Issue 4 2000Timothy A. Sentongo Abstract Objective: Growth before and after intestinal resection for Crohn's disease (CD) was examined in a group of children, adolescents, and young adults. Methods: Retrospective chart review of patients who had intestinal resections as clinical management of complications of CD between 1985 and 1996. Pre- and postoperative measurements of weight and height were reviewed. Z-scores were computed for weight-forage (WAZ), height-for-age (HAZ), and weight-for-height (WHZ). Two tailed t tests were used to compare postoperative growth patterns. Significance was defined as p < 0.05. Results: Twenty-five subjects (8 females, mean age 16.2 ± 2.8 years with one operation, and 3 males, mean age 15.7 years with multiple operations) were identified. There were significant improvements in the postoperative growth patterns of subjects who had one operation: HAZ (-1.28 ± 1.45 versus ,0.98 ± 1.37, p = 0.041), WAZ (-1.35 ± 1.02 versus ,0.74 ± 0.93, p = 0.0006) and WHZ (-0.64 ± 0.95 versus ,0.23 ± 0.81, p = 0.036). Furthermore, the magnitude of postoperative weight gain directly correlated with the age at CD diagnosis, R2 = 0.16, p = 0.046. Trends towards improved postoperative WAZ (-0.83 versus ,0.49) and HAZ (-0.47 versus ,0.27) were also observed in the three subjects who had multiple operations. Conclusion: The pattern of weight and height growth was improved after intestinal resection for CD. Nonetheless, close monitoring of postoperative growth is necessary especially in children diagnosed with CD at a young age. [source] Acute generalized exanthematous pustulosis mimicking toxic epidermal necrolysisINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 7 2001Arnon D. Cohen MD A 91-year-old patient presented with a nonfebrile, pruritic, widespread eruption that appeared 10 days after starting therapy with cefuroxime tablets, 1000 mg/day, due to stasis dermatitis with secondary infection. The patient was also treated with paracetamol tablets, 500,1000 mg/day, 10 days before the onset of the eruption. Previous diseases included congestive heart disease, hyperglycemia, and ectropion. There was no personal or family history of psoriasis. Additional medications, taken for more than 2 years at the time of the eruption, included indomethacin, captopril, hydrochlorothiazide, isosorbide-5-mononitrate tablets, and a combination drug Laxative®. Examination revealed widespread erythema involving 95% of the total body surface area, with numerous 1,2 mm nonfollicular pustules (Fig. 1). There was no predilection to the body folds. Within 24 h of hospitalization, during intravenous therapy with cefuroxime, the patient's condition worsened and bullae containing clear fluid appeared. Nikolsky's sign was positive on erythematous skin, and eventually skin detachment involved 41% of the total body surface area (Fig. 2). There were no target or target-like lesions and there was no involvement of the mucous membranes. Figure 1. Numerous, 1,2 mm, nonfollicular pustules, with confluence (viewed in the lower left part of the photograph), on erythematous skin Figure 2. Widespread skin detachment An early biopsy from a pustule revealed subcorneal and intraepidermal spongiform pustules, papillary edema, perivascular mononuclear infiltrate with a few eosinophils in the dermis, and leukocytoclastic vasculitis. A later biopsy showed similar findings with no evidence of full-thickness epidermal necrosis or necrotic keratinocytes. Direct immune fluorescence (DIF) taken from erythematous skin was negative. Laboratory studies showed the following results: sedimentation rate, 80 mm/h; white blood cell count, 26,200/mm3 with 87% polymorphonuclears and 1.8% eosinophils; hemoglobin, 13.0 g/dL; albumin, 2.8 g/dL (normal, 3.5,5.5 g/dL); other blood chemistry tests were normal. Immunologic studies for rheumatoid factor, antinuclear antibodies, antismooth muscle antibodies, antiparietal cell antibodies, antimitochondrial antibodies, C3, and C4 were normal or negative. Serology for venereal disease research laboratory (VDRL) test, Epstein,Barr virus, cytomegalovirus, hepatitis B virus, hepatitis C virus, human immunodeficiency virus, and antistreptolysin titer was negative. Chest X-ray was normal. Blood cultures were negative. Swab cultures taken from the pustules revealed Staphylococcus aureus as well as coagulase-negative Staphylococcus. All systemic drugs, including intravenous cefuroxime, were withdrawn with close monitoring for signs of heart failure or infection. Topical therapy consisted of application of wet dressings. Within 10 days, the eruption resolved with re-epithelialization of the erosions and the appearance of widespread post-pustular desquamation (Fig. 3) Figure 3. Post-pustular desquamation on the trunk [source] Unusual hypersensitivity to warfarin in a critically ill patientJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 5 2004H. Konishi PhD Summary A patient was admitted to the intensive care unit because of respiratory failure, and warfarin therapy was started at 2 mg/day for the treatment of pulmonary embolism, together with other medications. Despite the low dosage of warfarin, international normalized ratio (INR) was markedly elevated from 1·15 to 11·28 for only 4 days, and bleeding symptoms concurrently developed. Vitamin K2 was infused along with discontinuation of warfarin. One day later, the INR was found to have decreased, and bleeding was also improved. An objective causality assessment indicated a probable relationship between clotting abnormality and warfarin administration, although the degree of elevation of the INR was unusual in the light of the daily warfarin dose and duration of its exposure. Based on the clinical status of the patient, it was suspected that several conditions contributed to the abnormal hypersensitivity to warfarin. Contributory factors probably included pharmacokinetic interactions with co-administrated drugs, vitamin K deficiency caused by decreased dietary intake, reduced gut bacterial production, impaired intestinal absorption and hepatic synthetic capacity, and increased consumption of clotting factors. In view of our experience in the present case, it should be stressed that close monitoring of coagulation capacity is necessary in critically ill patients in order to avoid fatal haemorrhage after initiating warfarin therapy regardless of the dosage. [source] Effect of Piperine, a Major Component of Black Pepper, on the Intestinal Absorption of Fexofenadine and Its Implication on Food,Drug InteractionJOURNAL OF FOOD SCIENCE, Issue 3 2010Ming-Ji Jin ABSTRACT:, The present study aimed to investigate the effect of piperine, a major component of black pepper, on the oral exposure of fexofenadine in rats. Pharmacokinetic parameters of fexofenadine were determined in rats following an oral (10 mg/kg) or intravenous (5 mg/kg) administration of fexofenadine in the presence and absence of piperine (10 or 20 mg/kg, given orally). Compared to the control group given fexofenadine alone, the combined use of piperine increased the oral exposure (AUC) of fexofenadine by 180% to 190% while there was no significant change in,Cmax and,T1/2 of fexofenadine in rats. The bioavailability of fexofenadine was increased by approximately 2-folds via the concomitant use of piperine. Furthermore,,Tmax tends to be increased which might be attributed to the delayed gastric emptying in the presence of piperine. In contrast, piperine did not alter the intravenous pharmacokinetics of fexofenadine, implying that piperine may increase mainly the gastrointestinal absorption of fexofenadine rather than reducing hepatic extraction. In conclusion, piperine significantly enhanced the oral exposure of fexofenadine in rats likely by the inhibition of P-glycoprotein-mediated cellular efflux during the intestinal absorption, suggesting that the combined use of piperine or piperine-containing diet with fexofenadine may require close monitoring for potential drug,diet interactions. [source] SLE, atherosclerosis and cardiovascular diseaseJOURNAL OF INTERNAL MEDICINE, Issue 6 2005J. FROSTEGÅRD Abstract. Atherosclerosis is an inflammatory disease and the major cause of cardiovascular disease (CVD) in general. Atherosclerotic plaques are characterized by the presence of activated immune competent cells, but antigens and underlying mechanisms causing this immune activation are not well defined. During recent years and with improved treatment of acute disease manifestations, it has become clear that the risk of CVD is very high in a prototypic autoimmune disease, systemic lupus erythematosus (SLE). SLE-related CVD and atherosclerosis are important clinical problems but may in addition also shed light on how immune reactions are related to premature atherosclerosis and atherothrombosis. A combination of traditional and nontraditional risk factors, including dyslipidaemia (and to a varying degree hypertension, diabetes and smoking), inflammation, antiphospholipid antibodies (aPL) and lipid oxidation are related to CVD in SLE. Premature atherosclerosis in some form leading to atherothrombosis is likely to be a major underlying mechanism, though distinctive features if any, of SLE-related atherosclerosis when compared with ,normal' atherosclerosis are not clear. One interesting possibility is that factors such as inflammation or aPL make atherosclerotic lesions in autoimmune disease more prone to rupture than in ,normal' atherosclerosis. Whether premature atherosclerosis is a general feature of SLE or only affects a subgroup of patients remains to be demonstrated. Treatment of SLE patients should also include a close monitoring of traditional risk factors for CVD. In addition, attention should also be paid to nontraditional risk factors such as inflammation and SLE-related factors such as aPL. Hopefully novel therapeutic principles will be developed that target the causes of the inflammation and immune reactions present in atherosclerotic lesions. [source] Occult hepatitis B infection in patients infected with HIV: Report of two cases of hepatitis B reactivation and prevalence in a hospital cohortJOURNAL OF MEDICAL VIROLOGY, Issue 2 2010B. Bloquel Abstract Patients co-infected with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) are particularly at risk of hepatitis B reactivation. Two cases of patients infected with HIV with isolated anti-HBc antibodies who had experienced an HBV reactivation are described. In the two cases HBV reactivation occurred after withdrawal of anti-retroviral treatment with anti-HBV activity from the patients' highly active antiretroviral therapy (HAART), in accordance with HIV genotypic resistance profiles. Consequently, plasma samples from 383 patients infected with HIV were tested to assess the prevalence of occult HBV infection in the Infectious Diseases Department Unit of Nancy Hospital by investigating serological patterns and HBV replication. Forty-five percent (172/383) of patients had had previous contact with HBV. Isolated anti-HBc antibodies were observed in 48 patients (48/383, 12%) and, among these, 2 were HBV-DNA positive. Since 75% (288/383) of the patients were treated with HAART, including at least one drug active against HBV, occult HBV infection was perhaps unrecognized. In cases of HIV infection, all patients should be screened for HBV infection and the knowledge of HBV status as well as the monitoring of HBV viral load are essential in preventing HBV reactivation. Consideration should be given to the continuation of drugs with anti-HBV activity in co-infected patients receiving HAART, as cessation of therapy is associated with a risk of HBV reactivation. At least, close monitoring of the HBV viral load is warranted in such situations. J. Med. Virol. 82:206,212, 2010. © 2009 Wiley-Liss, Inc. [source] Acute suicidality after commencing atomoxetineJOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 10 2008Georgia Armat Paxton Abstract: An 11 year old boy developed acute agitation and suicidal ideation after commencing atomoxetine shortly after it was approved for use in Australia. The clinical features were similar to reactions described in response to selective serotonin reuptake inhibitors. The case highlights the importance of close monitoring when starting newly registered medications. An increased risk of suicidal thinking was subsequently identified for this drug leading to a Food and Drug Administration alert and a boxed warning in September 2005, however there are still no other published case reports of acute suicidality. [source] Effects of non-steroidal anti-inflammatory drugs on the pharmacokinetics and elimination of aciclovir in ratsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 3 2005Hye-Sun Gwak This study aims to investigate the effect of commonly used non-steroidal anti-inflammatory drugs (NSAIDs) on the pharmacokinetics and the renal elimination of aciclovir in rats. Pharmacokinetic parameters were determined following an intravenous administration of aciclovir (5 mg kg,1) to rats in the presence and absence of ketoprofen or naproxen (25 mg kg,1). Compared with the control (given aciclovir alone), pre-treatment with ketoprofen or naproxen 30 min before aciclovir administration significantly altered the pharmacokinetics of aciclovir. Renal clearance of aciclovir was reduced by approximately two fold in the presence of ketoprofen or naproxen. Consequently, the systemic exposure (AUC) to aciclovir in the rats pre-treated with ketoprofen or naproxen was significantly (P < 0.05) higher than that from the control group given aciclovir alone. Furthermore, the mean terminal plasma half-life of aciclovir was enhanced by 4,5 fold by pre-treatment with ketoprofen or naproxen. These results suggest that NSAIDs, such as ketoprofen and naproxen, are effective in altering the pharmacokinetics of aciclovir by inhibiting the organic anion transporter-mediated tubular secretion of aciclovir. Therefore, concomitant use of ketoprofen or naproxen with aciclovir should require close monitoring for clinical consequence of potential drug interaction. [source] Bacterial infection and neutropenia during peginterferon plus ribavirin combination therapy in patients with chronic hepatitis C with and without baseline neutropenia in clinical practiceALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 9 2009J.-F. YANG Summary Background, Peginterferon-,,based therapy frequently leads to neutropenia. It remains unclear whether neutropenia is associated with bacterial infection in chronic hepatitis C (CHC). Aim, To evaluate the risk of bacterial infection and neutropenia in patients with CHC treated with peginterferon-,/ribavirin. Methods, In all, 207 patients with CHC with (group A, n = 30) and without (group B, n = 177) baseline neutropenia were treated with peginterferon-,/ribavirin. Results, Group A had significantly higher rates of moderate (<750 cells/,L) and severe (<500 cells/,L) neutropenia than group B (70.0% and 26.7% vs. 20.3% and 8.5% respectively, both P < 0.0001). The sustained virological response rate was similar between patients with and without neutropenia, at baseline or during treatment. Bacterial infection occurred in 4.3% of patients. Group A and patients with lower baseline neutrophil counts had substantially higher rates of bacterial infection. Patients with cirrhosis had significantly higher rates of infection during combination therapy than those without cirrhosis (15%, 3 of 20 vs. 3.2%, 6 of 187, P = 0.045). Nadir neutrophil counts were not correlated to infection episodes. Conclusions, Bacterial infection during peginterferon-based therapy for CHC was associated with comorbidity of cirrhosis, but not with neutropenia, whether at baseline or during treatment. Neutropenic CHC patients might be treated safely with close monitoring. [source] How to diagnose and treat hepatitis B virus antiviral drug resistance in the liver transplant settingLIVER TRANSPLANTATION, Issue S2 2008Anna S. F. Lok Key Points 1Hepatitis B virus variants with antiviral drug,resistant mutations and/or hepatitis B immune globulin,resistant mutations are the main cause of hepatitis B virus reinfections post,liver transplant. 2Early diagnosis of antiviral drug resistance and prompt initiation of rescue therapy are important in preventing hepatitis flares and hepatic decompensation. 3Virologic breakthrough is the first indication of antiviral drug resistance. 4Genotypic resistance testing should be performed when possible to avoid unnecessary modification of treatment in patients who do not have confirmed antiviral drug resistance and to permit appropriate selection of rescue therapy in those who have confirmed antiviral drug resistance. 5Choice of rescue therapy requires knowledge of the past history of hepatitis B virus treatments and virologic response to those treatments, patterns of mutations detected at the time of virologic breakthrough, and in vitro cross-resistance data. 6Occurrence of antiviral drug resistance can be reduced by the use of the most potent nucleos(t)ide analogue(s) with the highest genetic barrier to resistance, emphasis of medication compliance, and close monitoring of virologic response. Liver Transpl 14:S8,S14, 2008. © 2008 AASLD. [source] Experience of Methadone Therapy in 100 Consecutive Chronic Pain Patients in a Multidisciplinary Pain CenterPAIN MEDICINE, Issue 7 2008FRCPC, Philip Peng MBBS ABSTRACT Objective., The objective of the study was to describe the experience of methadone use in 100 consecutive chronic pain patients managed in a single multidisciplinary center. Design., A chart review of chronic pain patients on methadone therapy initiated at the Wasser Pain Management Center from January 2001 to June 2004. Setting, Patients, and Intervention., Outpatients receiving methadone for chronic pain management in a tertiary multidisciplinary pain center. Outcome Measure., Effects on pain relief and function, conversion ratio from other opioids, side effects, and disposition were reviewed. Results., Charts of 100 methadone patients (age 45 ± 11 years old; M/F: 3/7; duration of pain 129 ± 110 months) managed by five physicians and one nurse were reviewed. The main reason for the initiation of methadone therapy was opioid rotation (72%). The average oral morphine equivalent dose was 77 mg/day before methadone therapy, and the methadone dose after initial stabilization was 42 mg with no consistent conversion ratio observed. The mean duration of methadone therapy was 11 months. Most of the patients (91%) were taking concomitant adjuvant analgesics or psychotropic agents, mostly antidepressants and anticonvulsants. The average Numeric Verbal Rating Score before and after methadone treatment was 7.2 ± 1.7 and 5.2 ± 2.5 (P < 0.0001). Thirty-five patients discontinued their methadone treatment mainly because of side effects, ineffectiveness, or both. Conclusion., From our experience, methadone is an effective alternative to conventional opioids for chronic pain management when used by experienced clinicians in a setting that allows for close monitoring and careful dose initiation and adjustment. [source] Results of living donor liver transplantation in five children with congenital cardiac malformations requiring cardiac surgeryPEDIATRIC TRANSPLANTATION, Issue 8 2006Jose Pablo Garbanzo Abstract:, In the pediatric population, the concomitant presentation of end-stage liver disease and congenital cardiac malformation occurs rarely. Determining the surgical priority in these cases is a challenge due to the presence of hemodynamic alterations that increase surgical risks. We examined five cases that received living-donor liver transplantation. In four patients that had congenital heart disease with a left to right shunt, two had cardiac surgery first, one had both heart and liver surgery simultaneously, and one underwent liver transplantation first. Both of the patients that received heart surgery before liver transplantation needed emergency liver transplantation because of post-operative liver failure. All five patients had a good outcome. Meticulous surgery, close monitoring, and adequate volume management, in addition to tailoring management decisions to the patient's specific condition, make it possible to correct both the liver and the heart abnormalities with satisfactory results. [source] Use of albumin in three French university hospitals: is prescription monitoring still useful in 2004?,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 1 2007Vincent Pradel MD Abstract Purpose Use of albumin (indications and quantities involved) has not been assessed in France since major changes occurred after the publication of Cochrane group meta-analysis. The objectives of this study were to measure the repartition of albumin indications in three French university hospitals in 2004 and to assess the feasibility and usefulness to implement a prescription-monitoring program. Methods Exhaustive record of albumin prescription during 2 months in three French university hospitals of Marseille. Inclusion of all patients with a first prescription of albumin between 15 March 2004 and 15 May 2004. Indication, formulation and quantity prescribed were recorded for each prescription. Results One hundred and eighty-seven patients received a total of 426 prescriptions for a total quantity of 21,094 g of albumin during the study. The first indications were hypoalbuminemia (33% of total quantity), plasmapheresis (30.2%) and ascites or hepatorenal syndrome (13.7%). Fifty per cent of total quantity was used by 14 patients (7.5% of included patients). Conclusions Most of albumin consumption in our study is concentrated on recognized indications or indications without alternative to albumin. The different levels of analysis (number of patient treated, number of prescription and quantities used) must be taken into account when analyzing medications such as albumin. Only a marginal proportion of consumption is expected to be saved with close monitoring of indications. Copyright © 2006 John Wiley & Sons, Ltd. [source] Extremum-seeking control of retention for a microparticulate systemTHE CANADIAN JOURNAL OF CHEMICAL ENGINEERING, Issue 5 2008Audrey Favache Abstract The operation of a paper machine relies on the close monitoring and control of several integrated units to ensure a high quality paper with the required specifications. In this paper, the retention control system in the wet-end of a paper machine is considered. The control objective is to maximize the retention of fines and fibres in the paper sheet to prevent the accumulation of micro particles in the water system. We present an adaptive extremum-seeking scheme for the optimization and control of retention in the wet-end of a paper machine. An adaptive learning technique is introduced to construct an algorithm that drives the system to the optimal retention value. Lyapunov's stability theory is used in the design of the extremum-seeking controller structure and the development of the parameter learning laws. The performance of the technique is illustrated via simulations based on a first-principles dynamic model developed previously for a micro-particulate system. Le bon fonctionnement d'une machine à papier repose sur le suivi et le contrôle étroits de plusieurs unités intégrées afin d'assurer une haute qualité de papier ayant les spécifications requises. Dans cet article, on considère le système de contrôle de rétention dans la partie humide d'une machine à papier. L'objectif du contrôle est de maximiser la rétention des fines et des fibres dans la feuille de papier afin de prévenir l'accumulation de micro-particules dans le système d'eau. On présente un schéma de recherche adaptatif des extrêmes pour l'optimisation et le contrôle de la rétention dans la partie humide d'une machine à papier. Une technique d'apprentissage adaptative est introduite pour construire un algorithme qui amène le système à une valeur de rétention optimale. La théorie de stabilité de Lyapunov est utilisée dans la conception de la structure des contrôleurs de recherche des extrêmes et l'élaboration de lois d'apprentissage des paramètres. La performance de la technique est illustrée par des simulations basées sur un modèle dynamique fondamental mis au point antérieurement pour un système de micro-particules. [source] Osteonecrosis of the Mandible or Maxilla Associated with the use of New Generation BisphosphonatesTHE LARYNGOSCOPE, Issue 1 2006Matthew C. Farrugia DO Objective: The use of bisphosphonates is well established for the treatment of patients with metastatic bone disease, osteoporosis, and Paget's disease. Osteonecrosis of the mandible or maxilla associated with the use of bisphosphonates is a newly described entity never before discussed in the otolaryngology literature. In this paper, we review a series of patients diagnosed with osteonecrosis, all treated with new generation bisphosphonates. Our objective is to inform and educate others, particularly otolaryngologists/head and neck surgeons, about this drug induced entity, a condition that should be recognized early to avoid potential devastating consequences. Study Design: Retrospective chart review of a series of patients from a tertiary referral center. Methods: Pathology reports of specimens submitted from either the mandible or maxilla were reviewed from the previous 12 months. Any patient diagnosed with osteonecrosis without evidence of metastatic disease at that site was included; those with a previous history of radiation therapy were excluded. Each patient's medical history and profile were reviewed. Results: Twenty-three patients were identified with osteonecrosis of the mandible or maxilla. All of these were associated with the use of new generation bisphosphonates: zolendronate (Zometa, Novartis), pamidronate (Aredia, Novartis), and alendronate (Fosamax, Merck). Eighteen patients with known bone metastases had been treated with the intravenous form, whereas five patients with either osteoporosis or Paget's disease were using oral therapy. Patients typically presented with a nonhealing lesion, often times the result of previous dental intervention. Although the majority of these patients were treated with conservative surgical debridement, we present a case requiring a near total maxillectomy. Conclusions: Drug induced osteonecrosis of the mandible or maxilla has been recently recognized as a sequelae of treatment with the new generation of bisphosphonates. Most patients can be treated with conservative surgical debridement and cessation of bisphosphonate therapy, whereas a few may require radical surgical intervention. Other recommendations include regimented prophylactic care with an assessment of dental status before the administration of bisphosphonates, avoidance of dental procedures, and close monitoring of oral hygiene. [source] Recombinant human relaxin in the treatment of systemic sclerosis with diffuse cutaneous involvement: A randomized, double-blind, placebo-controlled trial,ARTHRITIS & RHEUMATISM, Issue 4 2009Dinesh Khanna Objective A phase II randomized controlled trial of recombinant human relaxin suggested that a dosage of 25 ,g/kg/day was safe and clinically effective in improving skin disease and reducing functional disability in scleroderma (systemic sclerosis; SSc). We undertook a large randomized, double-blind, placebo-controlled clinical trial to compare placebo with 10 ,g/kg/day and 25 ,g/kg/day recombinant human relaxin, given for 24 weeks in patients with stable, diffuse, moderate-to-severe SSc. Methods Men and women ages 18,70 years with diffuse cutaneous SSc (dcSSc) were administered recombinant human relaxin (10 ,g/kg/day or 25 ,g/kg/day) or placebo for 24 weeks as a continuous subcutaneous infusion. There was a followup safety visit at week 28. Results The primary outcome measure, the modified Rodnan skin thickness score, was similar among the 3 groups at baseline and at weeks 4, 12, and 24. Secondary outcomes such as functional disability were similar in all 3 groups, while the forced vital capacity decreased significantly in the relaxin groups. The discontinuation of both doses of relaxin at week 24 led to statistically significant declines in creatinine clearance and serious renal adverse events (defined as doubling of serum creatinine, renal crisis, or grade 3 or 4 essential hypertension) in 7 patients who had received relaxin therapy but in none who had received placebo. Conclusion Recombinant relaxin was not significantly better than placebo in improving the total skin score or pulmonary function or in reducing functional disability in patients with dcSSc. In addition, relaxin was associated with serious renal adverse events, the majority of which occurred after stopping the infusion. If relaxin is used therapeutically for any conditions other than scleroderma, close monitoring of blood pressure and renal function must be performed. [source] Using 20-gauge percutaneous peripheral catheters to reliably collect serial 4-mL blood samples from conscious dogsAUSTRALIAN VETERINARY JOURNAL, Issue 6 2010KF Elliott Objective To determine the reliability of collecting serial 4-mL blood samples over 13 h using a 20-gauge, cephalic catheter in conscious dogs. Design Prospective, observational study. Animals Twelve (6 males, 6 females) healthy, neutered, lean dogs. Procedure Percutaneous placement of a 20-gauge, 1.1 × 30 mm intravenous over-the-needle catheter into the cephalic vein was performed in each dog on three occasions. Catheter patency was maintained by intermittent flushing with 0.9% saline and 1 IU/mL heparinised saline solutions. Blood samples (4 mL) were obtained at 10 time-points over 13 h, with close monitoring of the dogs and the indwelling catheters. Blood volume, resistance on aspirating blood sample (minimal or marked resistance) and the methods used to improve blood flow were recorded. Results A high proportion (93%) of blood sample collections achieved the required 4-mL volume, and the remaining samples were greater than 1.5 mL. Of the 358 collections via the cephalic catheter, 311 (87%) were obtained with ,minimal resistance'. The remaining collections had ,marked resistance' (n=47) and were associated with a loose catheter in 11% (5/47) and of unknown cause in 89% (42/47). After ,marked resistance' had been encountered and the catheter was flushed with saline and heparin solutions, subsequent sampling with ,minimal resistance' was frequently possible from the same catheter. Conclusion Use of a percutaneous, 20-gauge intravenous cephalic catheter allowed reliable serial collection of 4-mL blood samples over 13 h in conscious dogs. [source] Maternal complications and pregnancy outcome in women with mechanical prosthetic heart valves treated with enoxaparinBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 12 2009C McLintock Objective, To determine maternal and fetal outcomes in women with mechanical heart valves managed with therapeutic dose enoxaparin during pregnancy. Design, Retrospective audit. Setting, Hospital-based high-risk antenatal clinics. Population, Pregnant women with mechanical heart valves attending high-risk antenatal clinics, treated with enoxaparin (1 mg/kg twice daily) during pregnancy. Methods, Women with mechanical heart valves treated with enoxaparin at any stage during pregnancy (1997,2008) identified using a database of women with mechanical heart valves attending the high-risk clinics and a prospective database of women prescribed enoxaparin for any indication during pregnancy. Main outcome measures, Maternal outcomes included thromboembolic and haemorrhagic complications. Pregnancy and fetal outcomes included miscarriage, stillbirth, baby death and live birth, small-for-gestational-age infants, warfarin embryopathy and warfarin-related fetal loss. Results, Thirty-one women underwent 47 pregnancies. In 34 pregnancies (72.3%), anticoagulation was with predominantly enoxaparin and 13 (27.7%) pregnancies women received mainly warfarin, with enoxaparin given in the first trimester and/or peri-delivery. Seven (14.9%) thrombotic complications occurred, of which five (10.6%) were associated with enoxaparin treatment. Non-compliance or sub-therapeutic anti-Xa levels contributed in each case. Antenatal and postpartum haemorrhagic complications occurred in eight (17%) and 15 (32%) pregnancies respectively. Of 35 pregnancies continuing after 20 weeks' gestation, 96% (22/23) of women taking predominantly enoxaparin had a surviving infant compared with 75% (9/12) in women taking primarily warfarin. Four perinatal deaths occurred, three attributable to warfarin. Conclusions, Compliance with therapeutic dose enoxaparin and aspirin during pregnancy in women with mechanical heart valves is associated with a low risk of valve thrombosis and good fetal outcomes, but close monitoring is essential. [source] Devolution and Disability Equality Legislation: The Implementation of Part 4 of the Disability Discrimination Act 1995 in England and ScotlandBRITISH JOURNAL OF SPECIAL EDUCATION, Issue 2 2003Sheila Riddell Part 4 of the Disability Discrimination Act 1995 (as amended) came into force in September 2002. The Act covers Great Britain but, in relation to schools, is implemented through different special educational needs legislation in England and Scotland. This article by Sheila Riddell, Professor of Social Policy (Disability Studies) at Glasgow University and Director of the Strathclyde Centre for Disability Research, explores the key differences in these legal frameworks, and discusses their implications for delivering consistent anti-discrimination policies north and south of the border. Professor Riddell argues that there is a need for close monitoring of the implementation of Part 4 of the DDA in English and Scottish schools. If major differences in implementation of the legislation emerge over time, there may be a need to consider the case for devolving responsibility for equal opportunities to the Holyrood Parliament or amending national education legislation to make it more consistent. This article will be of interest to anyone concerned with the implementation of Part 4 of the Disability Discrimination Act in England and Scotland. [source] | |||||||||||||||||||||||||||||||