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Discontinuation
Kinds of Discontinuation Terms modified by Discontinuation Selected AbstractsPrognostic Factors Affecting Long-Term Retention of Topiramate in Patients with Chronic EpilepsyEPILEPSIA, Issue 3 2000S. D. Lhatoo Summary: Purpose: To determine the long-term retention rate of topiramate (TPM) therapy in patients with chronic epilepsy and to identify the relevant prognostic factors that influence retention. Methods: All patients with chronic epilepsy (n = 393) prescribed TPM between October 1, 1995, and December 31, 1998, at a tertiary referral centre for epilepsy were analysed. The retention rate for TPM was calculated by using Kaplan-Meier survival analysis, and the prognostic factors influencing retention were analysed by using Cox regression. Results: Of patients prescribed TPM, 30% continued taking the drug beyond 3 years. Discontinuation was mainly due to adverse events and lack of efficacy. Use of more than one new concurrent antiepileptic drug (AED) and lower maximal daily doses were more likely to result in treatment discontinuation due to adverse events. Older age at onset of epilepsy, a history of having previously taken more than one new AED [lamotrigine (LTG), gabapentin (GBP), or vigabatrin (VGB)], and lower maximal daily doses were more likely to lead to discontinuation due to lack of efficacy. Conclusions: A third of patients with chronic epilepsy started on TPM therapy will continue on treatment for >3 years. Absence of learning disabilities, late age at onset of seizures, previous use of more than one new AED, two or more concurrent AED use, and low maximal daily doses of TPM are more likely to result in discontinuation of medication. These factors should be taken into account when considering the use of TPM for the treatment of chronic epilepsy. [source] A cost-effectiveness analysis of caspofungin vs. liposomal amphotericin B for treatment of suspected fungal infections in the UKEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 6 2007Karin Bruynesteyn Abstract Objective:, To evaluate the cost-effectiveness of caspofungin vs. liposomal amphotericin B in the treatment of suspected fungal infections in the UK. Methods:, The cost-effectiveness of caspofungin vs. liposomal amphotericin B was evaluated using a decision-tree model. The decision tree was populated using both data and clinical definitions from published clinical studies. Model outcomes included success in terms of resolution of fever, baseline infection, absence of breakthrough infection, survival and quality adjusted life years (QALYs) saved. Discontinuation due to nephrotoxicity or other adverse events were included in the model. Efficacy and safety data were based on additional analyses of a randomised, double blind, multinational trial of caspofungin compared with liposomal amphotericin B. Information on life expectancy, quality of life, medical resource consumption and costs were obtained from peer-reviewed published data. Results:, The caspofungin mean total treatment cost was £9762 (95% uncertainty interval 6955,12 577), which was £2033 (,2489; 6779) less than liposomal amphotericin B. Treatment with caspofungin resulted in 0.40 (,0.12; 0.94) additional QALYs saved in comparison with liposomal amphotericin B. Probabilistic sensitivity analysis found a 95% probability of the incremental cost per QALY saved being within the generally accepted threshold for cost-effectiveness (£30 000). Additional analyses with varying dose of caspofungin and liposomal amphotericin B confirmed these findings. Conclusion:, Given the underlying assumptions, caspofungin is cost-effective compared with liposomal amphotericin B in the treatment of suspected fungal infections in the UK. [source] Effect of intravenous immunoglobulin on cerebellar ataxia and neuropathic pain associated with celiac diseaseEUROPEAN JOURNAL OF NEUROLOGY, Issue 12 2008N. Souayah Background:, Cerebellar syndrome and small fiber neuropathy may complicate celiac disease (CD) and may be resistant to a strict gluten-free diet. Methods:, Case series. Results:, We report three patients with biopsy-proven CD who developed cerebellar ataxia and neuropathic pain despite strict adherence to a gluten-free diet. A small fiber neuropathy was suggested by skin biopsy findings in two patients. All patients' symptoms, including small fiber neuropathy symptoms, responded to treatment with intravenous immunoglobulin (IVIG). Discontinuation of IVIG in two patients resulted in worsened ataxia that reversed after resumption of IVIG. Conclusion:, Intravenous immunoglobulin may be effective in treating cerebellar ataxia and small fiber neuropathy associated with CD, suggesting an immune pathogenesis. Further prospective, controlled studies are necessary to determine the long-term response to IVIG or other immunomodulation therapy. [source] Discontinuation of prophylactic therapy in severe haemophilia: incidence and effects on outcomeHAEMOPHILIA, Issue 6 2001K. Fischer A cohort study was performed to assess adherence to early prophylactic therapy and its effects on outcome in 49 patients with severe haemophilia born 1970,1980. Median age at start of prophylaxis was 5.5 years. The majority (69%) of patients interrupted prophylactic treatment one or more times of their own accord (median total interruption 2.2 years). Patients who discontinued prophylaxis at any point tended to have more arthropathy as measured by the Pettersson scale (median 8 points versus 4 points). One-third of these patients interrupted prophylaxis for longer periods and had permanently stopped taking prophylaxis at a mean age of 20.1 years (mean ± SD duration 4.1 ± 4 years) and consequently experienced 5.4 ± 3.4) joint bleeds per year. This subgroup could be identified by a predictive score based on age at start of prophylaxis, weekly dose of prophylaxis, and joint bleed frequency on prophylaxis. In conclusion, while on prophylaxis, more than two-thirds of patients with severe haemophilia try to discontinue treatment, resulting in slightly more arthropathy. One-third of these patients permanently discontinue prophylaxis in adulthood, while maintaining a low number of joint bleeds. [source] Preemptive lamivudine therapy based on HBV DNA level in HBsAg-positive kidney allograft recipientsHEPATOLOGY, Issue 5 2002Tak Mao Chan Hepatitis B surface antigen (HBsAg)-positive kidney transplant recipients have increased liver-related mortality. The impact of lamivudine treatment on patient survival, the optimal time to start treatment, and the feasibility of discontinuing treatment have not been determined. This study examined these issues with a novel management protocol. Serum hepatitis B virus (HBV) DNA levels were measured serially in HBsAg-positive kidney transplant recipients, and lamivudine was administered preemptively to patients with increasing HBV DNA levels with or without elevation of aminotransferase levels. Outcomes of patients who underwent transplantation before or after institution of this preemptive management strategy (in January 1996) were compared. Eleven de novo patients (91.7%) who underwent transplantation between 1996 and 2000 and 15 existing patients (39.5%) who underwent transplantation between 1983 and 1995 received preemptive lamivudine therapy for 32.6 ± 13.3 months. The treatment criteria were met by de novo patients at 8.4 ± 6.2 months (range, 1-18 months) after transplantation. Suppression of HBV DNA and normalization of aminotransferase levels were achieved in all treated patients, and 21.4% had hepatitis B e antigen (HBeAg) seroconversion. The survival of preemptively managed de novo transplant patients was similar to that of HBsAg-negative controls, whereas HBsAg-positive patients who underwent transplantation before January 1996 had inferior survival (relative risk of death, 9.7 [P < .001]; relative risk of liver-related mortality, 68.0 [P < .0001]). Eleven patients (40.7%) developed lamivudine resistance. Discontinuation of lamivudine was attempted in 12 low-risk patients after stabilization and was successful in 5 (41.7%). In conclusion, preemptive lamivudine therapy based on serial HBV DNA levels and clinical monitoring improved the survival of HBsAg-positive renal allograft recipients. Treatment can be discontinued safely in selected patients after stabilization to minimize the selection of drug-resistant HBV mutants. [source] Long-term follow-up of nevirapine-treated patients in a single-centre cohortHIV MEDICINE, Issue 8 2009M Colafigli Objectives We reviewed the safety and efficacy of nevirapine (NVP)-based therapy in all patients initiating NVP-containing combined antiretroviral therapy [cART (,3 drugs)] in our clinic since 1994. Methods Patient characteristics and laboratory values from the start of the NVP-based cART regimen to the last available follow-up or to NVP discontinuation were retrieved from an observational database. Results Five hundred and seventy-three patients were treated with NVP-based cART for a median of 18.4 (range 0.1,128.8) months. The 1-year cumulative estimated probability of discontinuing NVP-containing regimens for toxicity was 0.203. Only 1.9% developed a grade 3 alanine aminotransferase (ALT) elevation. Significant increases in high-density lipoprotein cholesterol were observed up to month 12 except in treatment-naļve patients, where the increase was limited to 3 months. Discontinuation because of cutaneous reaction was predicted independently by female gender [Hazard Ratio (HR) 3.21, P<0.001] and Centers for Disease Control class C (HR 0.50, P=0.012). Discontinuation because of liver toxicity was predicted independently by anti-hepatitis C virus positivity (HR 3.84, P<0.001). In patients starting NVP-containing cART with undetectable viral loads, the 5-year estimated probability of viral load >400 HIV-1 RNA copies/mL was 0.34. Conclusions Long-term follow-up with an NVP-containing cART showed a low rate of discontinuation caused by liver toxicity and the maintenance of virological suppression in patients switched with undetectable viral loads. [source] Recovery of Trabecular and Cortical Bone Turnover After Discontinuation of Risedronate and Alendronate Therapy in Ovariectomized RatsJOURNAL OF BONE AND MINERAL RESEARCH, Issue 10 2008Robyn K Fuchs Abstract Alendronate (ALN) and risedronate (RIS) are bisphosphonates effective in reducing bone loss and fractures associated with postmenopausal osteoporosis. However, it is uncertain how long it takes bone turnover to be re-established after treatment withdrawal, and whether this differs between the two drugs. The objective of this study was to determine the time required to re-establish normal bone turnover after the discontinuation of ALN and RIS treatment in an animal model of estrogen-deficiency osteoporosis. Two hundred ten, 6-mo-old female Sprague-Dawley rats were ovariectomized and 6 wk later were randomized into baseline controls (n = 10) and four treatment groups (n = 50/group): vehicle-treated controls (CON; 0.3 ml sterile water), ALN (2.4 ,g/kg), low-dose RIS (RIS low; 1.2 ,g/kg), and high-dose RIS (RIS high; 2.4 ,g/kg). Treatments were administered 3 times/wk by subcutaneous injection. Baseline controls were killed at the initiation of treatment. Other groups were treated for 8 wk, and subgroups (n = 10/ treatment group) were killed 0, 4, 8, 12, and 16 wk after treatment was withdrawn. Static and dynamic histological analyses were performed for cortical (tibial diaphysis) and trabecular (proximal tibia and L4 vertebrae) bone. DXA and mechanical testing was performed on the L5 vertebra. After 8 wk of treatment, trabecular bone turnover rates were significantly suppressed in all drug-treated animals. Trabecular bone formation rate (BFR/BS) remained significantly lower than vehicle in bisphosphonate-treated animals through 12 wk. Sixteen weeks after treatment withdrawal, trabecular BFR/BS in the proximal tibia was re-established in animals treated with RIS but not in animals treated with ALN compared with controls. BMD of the fifth lumbar vertebra remained significantly higher than controls 16 wk after treatment withdrawal in ALN-treated animals but not in RIS-treated animals. Despite reductions in BMD and increases in bone turnover, ultimate force of the fifth lumbar vertebra remained significantly higher in all drug-treated animals through 16 wk after withdrawal. [source] Sustained Nonvertebral Fragility Fracture Risk Reduction After Discontinuation of Teriparatide TreatmentJOURNAL OF BONE AND MINERAL RESEARCH, Issue 9 2005Richard Prince Abstract A follow-up in 1262 women was conducted after the discontinuation of teriparatide. The hazard ratio for combined teriparatide group (20 and 40 ,g) for the 50-month period after baseline was 0.57 (p = 0.002), suggesting a sustained effect in reducing the risk of nonvertebral fragility fracture. Introduction: Treatment with teriparatide {rhPTH(1-34)} 20 and 40 ,g once-daily subcutaneous dosing significantly reduced the risk of nonvertebral fragility fractures over a median exposure of 19 months. Materials and Methods: All participants in the Fracture Prevention Trial were invited to participate in a follow-up study. Prior treatment assignments were revealed, and patients were able to receive osteoporosis treatments without restriction. Results: Approximately 60% of the 1262 patients received an osteoporosis treatment at some time during follow-up, with greater use in the former placebo group than in the combined former teriparatide group (p < 0.05). The hazard ratios for nonvertebral fragility fractures in each teriparatide group relative to placebo were statistically significant for the 50-month period including treatment and follow-up (p < 0.03). In the follow-up period, the hazard ratio was significantly different between the 40 ,g and combined groups versus placebo but not for the 20 ,g group versus placebo. However, the 20 and 40 ,g groups were not different from each other. Kaplan-Meier analysis of time to fracture showed that the fracture incidence in the former placebo and teriparatide groups diverged during the 50-month period including teriparatide treatment and follow-up (p = 0.009). Total hip and femoral neck BMD decreased in teriparatide-treated patients who had no follow-up treatment; BMD remained stable or further increased in patients who received a bisphosphonate after teriparatide treatment. Conclusions: While the study design is observational, the results support a sustained effect of teriparatide in reducing the risk of nonvertebral fragility fractures up to 30 months after discontinuation of treatment. [source] Discontinuation of penicillamine in the absence of alternative orphan drugs (trientine,zinc): a case of decompensated liver cirrhosis in Wilson's diseaseJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 1 2007C. C. Ping MPharm Summary Objectives:, To report a case of early-decompensated liver cirrhosis secondary to discontinuation of penicillamine therapy in a patient with Wilson's disease. Case summary:, A 33-year-old Chinese female patient was diagnosed with Wilson's disease, for which penicillamine 250 mg p.o. once daily was prescribed. However, the patient developed intolerance and penicillamine was discontinued without alternative treatment. Five months later, she developed decompensated liver cirrhosis with hepatic encephalopathy. Eventually, the patient died because of the complications of sepsis and decompensated liver failure. Discussion:, Chelating agent is the mainstay of treatment in Wilson's disease, which is an inherited disorder of hepatic copper metabolism. Therapy must be instituted and continued for life once diagnosis is confirmed. Interruption of therapy can be fatal or cause irreversible relapse. Penicillamine given orally is the chelating agent of first choice. However, its unfavourable side-effects profile leads to discontinuation of therapy in 20,30% of patients. In most case reports, cessation of penicillamine without replacement treatment causes rapid progression to fulminant hepatitis, which is fatal unless liver transplantation is performed. Conclusion:, In this, we highlight a case of discontinuation of penicillamine in a patient with Wilson's disease without substitution with alternative regimen. This was caused by unavailability of the alternative agents such as trientine in our country. Consequently, the patient progressed to decompensated liver cirrhosis with encephalopathy and eventually passed-away within 5 months. One recent study supports a combination of trientine and zinc in treating patient with decompensated liver cirrhosis. This combination is capable of reversing liver failure and prevents the need of liver transplantation. Both trientine and zinc are not registered in Malaysia. Therefore, liver transplantation was probably the only treatment option for this patient. Hence, non-availability of orphan drugs in clinical practice is certainly a subject of serious concern. Systems for better management of patients with rare diseases need to be instituted by all the institutions concerned. [source] The Frequency Of Arterial Hypertension Versus Orthostatic Hypotension In Diabetic PatientsJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 3 2000C Ionescu-Tīrgoviste Aim: The aim of this study was to assess the relationship between supine high blood pressure and orthostatic hypotension both in Type 1 (T1DM) and Type 2 (T2DM) diabetic patients. Patients and Methods: Our study included 321 T2DM patients (153 M/168 F; mean age 62.3 (14.2 yr; duration of disease 12.1 (7.6 yr) and 116 T1DM patients (65 M/51 F; mean age 39.7 (9.2 yr; duration of diabetes 11.9 (8.1 yr). Patients with orthostatic hypotension were divided into 3 groups: A , without symptoms; B , mild/moderate symptoms (short and tolerable dizziness when standing); C , severe symptoms (persistent and disabling dizziness or even fainting in upright position). Results: Arterial hypertension was registered in 67.6% of T2DM patients (217 from 321 cases) and in 50.0% of T1DM patients (58 from 116 cases). Orthostatic hypotension (defined as a decrease in systolic blood pressure (30 mm Hg)) was encountered in 64.5% in T2DM patients (207 out of 321 cases) and in 60.3% of T1DM patients (70 out of 116 cases). From 207 T2DM patients with orthostatic hypotension, 105 were in Group A (50.7%), 89 in Group B (42.99%) and 13 in Group C (6.28%), while from 70 T1DM patients with orthostatic hypotension 14 were in Group A (20.0%), 51 in Group B (72.8%) and 5 in Group C (7.14%). An association of supine arterial hypertension with orthostatic hypotension was registered in 96 (29.9%) T2DM patients (68 of them receiving antihypertensive treatment) and in 25 (21.5%) T1DM patients (19 of which were on antihypertensive treatment). From the 18 patients with severe orthostatic hypotension (13 T2DM and 5 T1DM), supine arterial hypertension was registered in 5 cases (3 T2DM and 2 T1DM). In 4 of these 5 cases, patients were receiving antihypertensive treatment. Discontinuation of this treatment led to a decrease in the intensity of clinical signs of orthostatic hypotension in 4 out of 5 cases. An improvement of clinical symptoms of orthostatic hypotension was recorded in about 1/3 of hypertensive patients after discontinuation or just lowering of the dose of antihypertensive drugs (26 out of 87 cases). Conclusion: An association between hypertension and orthostatic hypotension is frequent both in T1DM and in T2DM, rising in difficulties for treatment. The treatment of hypertension in diabetic patients should take into account the possible orthostatic hypotension induced by some of the antihypertensive drugs. [source] Review article: success and failure of nucleoside and nucleotide analogues in chronic hepatitis BALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2007W. F. LEEMANS SUMMARY Background, Strong suppression of viral replication and normalization of alanine aminotransferase is feasible with nucleos(t)ide analogues. It is estimated viral replication and liver inflammation can be controlled in 90% of patients with chronic hepatitis B with the current available treatments. Aim, To review the studies currently available on the management of chronic hepatitis B with nucleos(t)ide analogues. Results, Although very potent, nucleos(t)ide analogues are not effective in every patient. Some factors are known to influence treatment outcome, but many host and viral factors are still unknown. Stopping rules have to be defined to assess treatment efficacy in an early stage and change the regimen. Discontinuation of nucleos(t)ide analogues is often followed by reactivation of HBV. Data on the risk factors for relapse are necessary in order to decide if treatment can be safely discontinued. Another major drawback of nucleos(t)ide analogues is the emergence of resistance. The efficacy of compounds for the treatment of mutant virus and the impact of cross-resistance is largely unknown. The use of combination therapy to prevent resistance looks promising, but has to be proven. Conclusions, HBV has become a treatable disease, however much research is needed to optimize treatment for individual patients and treatment failures. [source] The relationship between dosing of alosetron and discontinuation patterns reported by patients participating in a follow-up programmeALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2007P. TENNIS Summary Background Alosetron was reintroduced for treatment of irritable bowel syndrome with a risk management programme in November 2002. Recommended starting dosage was 1 mg/day for 4 weeks. If symptoms remained uncontrolled, dosage could be changed to 2 mg/day. Aim To describe alosetron dosages and associated patient characteristics from the Lotronex follow-up survey programme. Methods Patients reported dosages of alosetron at start and regular follow-up intervals. Analyses were limited to patients with the potential to have at least 1 year of follow-up (enrolled between 9 December 2002 and 31 December 2003). Results At baseline, 75% of 2817 respondents reported starting on 1 mg/day, 17% on 2 mg/day and 8% on other doses. Adherence to recommended starting dosage did not vary by status at end of follow-up, previous alosetron experience or age. At last reported dose, 50% of respondents were using 1 mg/day; 29% were using 2 mg/day. Discontinuation was not related to baseline doses. Longer times to discontinuation were associated with previous use, symptoms for more than 6 months and dose change throughout follow-up. Conclusions High adherence to recommended dosing at baseline and follow-up suggests that the risk management programme is encouraging safe use of alosetron, including adherence to dosing recommendations. [source] Change in editorial policy from January 2010: Discontinuation of the Spectral Assignments and Reference Data and Notes categories, and introduction of the new category MRC LettersMAGNETIC RESONANCE IN CHEMISTRY, Issue 10 2009James Keeler Editor in Chief Cambridge, July 200 [source] Long-term efficacy of botulinum toxin A in treatment of various movement disorders over a 10-year periodMOVEMENT DISORDERS, Issue 6 2002G-Y.R. Hsiung MD Abstract Although botulinum toxin A (BTX) has been licensed in Canada for treatment of various movement disorders since 1990, few clinical studies regarding its long-term efficacy and side effects have been reported. We conducted a retrospective analysis of 235 patients who received BTX from our movement disorders clinic over a 10-year period (January 1990 to December 1999). A total of 2,616 treatment cycles (multiple injections) were administered to 235 patients with cervical dystonia (CD), hemifacial spasm (HS), blepharospasm (BP), and other movement disorders. Substantial benefit at 5 years was seen in most patients (90% in BP, 88% in HS, 63% in CD, 100% in jaw closing and lower limb dystonia, and 56% in writer's cramp). Benefit was maintained for up to 10 years in CD, HS, and BP data, with a 75.8% benefit reported. Twenty-eight percent of patients discontinued treatment during the follow-up period due to a variety of reasons. Of these, 9.1% of patients developed primary resistance, and 7.5% of patients secondary resistance. Adverse effects, mostly minor, developed in 27% of patients at any one time, occurring over 4.5% of treatment cycles. These were most frequently reported in blepharospasm (22 of 36 patients in 40 cycles), followed by hemifacial spasm (21 of 70 patients in 46 cycles), and cervical dystonia (17 of 106 in 28 cycles). Only 1.3% of patients discontinued therapy due intolerable adverse effects. The results show that BTX is a safe and effective treatment of various types of movement disorders, and most side effects are well tolerated. Discontinuation for any reason was also low after 5 years. Efficacy was maintained after long periods of treatment with high degree of patient satisfaction. © 2002 Movement Disorder Society [source] Persistence with cholinesterase inhibitor therapy in a population-based cohort of patients with Alzheimer's diseasePHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 7 2010Joseph E. Amuah PhD Abstract Purpose To estimate the risk (and determinants) of discontinuing cholinesterase inhibitors (ChEIs) in a population-based sample of Alzheimer's disease (AD) patients. Methods This is a retrospective cohort study based on linked de-identified administrative health data from the province of Saskatchewan, Canada. The cohort included all AD patients receiving a ChEI prescription during the first year of provincial coverage (2000,2001). Persistence was defined as no gap of 60+ days between depletion and subsequent refill of a ChEI prescription. Kaplan-Meier analysis was used to estimate the risk of discontinuation over 40 months. Cox regression with time-varying covariates was used to assess risk factors for ChEI discontinuation. Results The sample included 1080 patients (64% female, average age 80,±,7 years). Baseline mean (SD) Mini-Mental State Examination (MMSE) and Functional Activities Questionnaire (FAQ) scores were 20.8 (4.4) and 17.5 (7.7), respectively. Over 40 months, 84% discontinued therapy. The 1-year risk of discontinuation was 66.4% (95%CI 63.5,69.3%). Discontinuation was significantly more likely for females (adjusted HR 1.34, 95%CI 1.16,1.55) and among those with lower MMSE scores (2.52, 2.01,3.17 if <15), not receiving social assistance (1.25, 1.07,1.45), and paying at least 65% of total prescription costs (1.51, 1.30,1.74). It was significantly less likely for patients with frequent physician visits (0.78, 0.66,0.93, for 7,19 vs. <7 visits), higher Chronic Disease Scores (0.74, 0.61,0.89, for 7+ vs. <4), and FAQ scores of 9+ (0.82, 0.69,0.99). Conclusion The likelihood of discontinuing ChEI therapy was high in this real-world sample of AD patients. Significant predictors included clinical, socioeconomic, and practice factors. Copyright © 2010 John Wiley & Sons, Ltd. [source] Latest news and product developmentsPRESCRIBER, Issue 3 2007Article first published online: 14 MAR 200 PPIs and hip fracture Treatment with a PPI may increase the risk of hip fracture, with longer use associated with higher risk according to a study in UK patients (J Am Med Assoc 2006;297:2947-53). The case control study compared use of PPIs by 13 556 patients with hip fracture and 135 386 controls in the UK General Practice Research Database. Use of a PPI for more than one year was associated with an increase of 44 per cent in the odds of hip fracture. The risk was higher for longer- term use (59 per cent after four years) and at higher doses (more than doubled with long-term high doses). The mechanism for this possible effect may be impaired calcium absorption associated with hypochlorhydria and reduced bone resorption. CHD NSF Statin prescribing has increased by 30 per cent every year since the publication of the Coronary Heart Disease NSF, the Department of Health says. The estimated number of lives saved attributable to statins had risen to 9700 in 2005. The proportion of patients with acute MI who were given thrombolysis within 30 minutes of admission has increased to 83 per cent. Flu jabs cut pneumonia deaths A US study suggests that flu vaccine protects against death during the flu season in patients admitted with community-acquired pneumonia (Arch Intern Med 2007;167:53-9). Nineteen per cent of patients admitted with pneumonia during the winters of 1999-2003 were known to have been vaccinated against flu. Their risk of death during their hospital stay was 70 per cent lower than that of nonvaccinated individuals. After adjustment for antipneumococcal vaccination and comorbidity, the odds of death were still 39 per cent lower. Model to predict admissions The King's Fund, together with New York University and Health Dialog, has published a model that predicts the risk of emergency hospital admission (see www.kingsfund.org.uk). The model is intended for use by PCTs and draws on data from secondary and primary care to define clinical profiles, allowing patients whose condition is deteriorating to be identified before they need admission. Problem drinking The National Treatment Agency for Substance Misuse (NTA), a special authority within the NHS, has published a critical appraisal of the evidence for various treatments for alcohol problems (www.nta.nhs.uk). The 212-page document estimates that over seven million hazardous or harmful drinkers may benefit from brief interventions by any health workers, and over one million dependent drinkers may benefit from specialist intervention. It concludes that cognitive behavioural approaches to specialist treatment are most effective and that treatment probably accounts for about one-third of improvements made in problem drinking. of patients remained on the same treatment after one year, falling to half at two years and about 40 per cent at three years. Treatment was more frequently stopped for lack of efficacy than for adverse effects. Stopping anti-TNFs Discontinuation of treatment with anti-TNF agents is more common in clinical practice than in clinical trial populations, a French study has found (J Rheumatol 2006;33:2372-5). The retrospective analysis of a single centre's experience of treating 770 patients with etanercept (Enbrel), infliximab (Remicade) or adalimumab (Humira) found that fewer than two-thirds of patients remained on the same treatment after one year, falling to half at two years and about 40 per cent at three years. Treatment was more frequently stopped for lack of efficacy than for adverse effects. There were no statistically significant differences between the three agents but there was a trend for infliximab to be least well tolerated. Generic statin savings The Department of Health has estimated that prescribing simvastatin and pravastatin generically would save £85 million per year. Its analysis of the ,Better care, better value' indicators (see www.productivity.nhs.uk) shows that statin prescribing has increased by 150 per cent in the past five years, with costs totalling £600 million in 2005. The Department says that if every PCT prescribed pravastatin and simvastatin by generic name in only 69 per cent of cases ,the level achieved by the top quarter of trusts ,the savings would be over £85 million a year. Herceptin reporting Press reports of a two-year trial of trastuzumab (Herceptin) were generally accurate in reporting its effectiveness but few reported an increased risk of adverse effects, according to the NHS National Library for Health (www.library.nhs.uk). The Herceptin Adjuvant (HERA) trial (Lancet 2007;369:29-36) found that, after an average follow-up of two years, 3 per cent of women treated with trastuzumab died compared with 5 per cent of controls; estimated three-year survival rates were 92.4 and 89.7 per cent respectively. All four press articles reported these findings accurately, but only two mentioned the increased risk of adverse effects. Updated guidance on CDs The Department of Health has published updated guidance on the strengthened governance requirements for managing controlled drugs, taking into account new regulations that came into force on 1 January (seewww.dh.gov.uk/asset Root/04/14/16/67/04141667.pdf). Statin adherence lowers MI mortality Patients with acute myocar- dial infarction (MI) who take their statins as prescribed are significantly more likely to survive for two to three years than those with low adherence (J Am Med Assoc 2007;297: 177-86). The four-year observational study of 31 455 patients with acute MI found that, compared with those who had taken at least 80 per cent of prescribed daily doses, the risk of death in those with less than 40 per cent adherence was 25 per cent greater over 2.4 years. For individuals with intermediate adherence (40-79 per cent), the risk was 12 per cent greater. Both differences were statistically significant after adjustment for potential confounding factors. The authors believe their finding is explained by differences in adherence rather than healthier behaviour because the excess risk of low adherence was less marked with beta-blockers and not significant for calcium-channel blockers. Improving community medicines management Mental health trusts need to improve medicines management by their community teams and improve information sharing with GPs, the Healthcare Commission has found (www.healthcare commission.org.uk). Its national report revealed limited evidence of pharmacist involvement in community mental health teams, even though 90 per cent of patients were cared for in the community. Only 11 per cent of assertive outreach patients had the tests necessary to ensure safe use of their medicines. Medication reviews found that 46 per cent of patients in mental health trusts and 12 per cent of those in acute trusts were not taking their medication appropriately. The Commission also reported that acute trusts received a complete drug history from GPs for fewer than half of audited patients when they were admitted to hospital, and only 30 per cent of PCTs reported that GPs received adequate information on patients' medicines on discharge. Copyright © 2007 Wiley Interface Ltd [source] Proceedings of the 20th Annual Conference of the Japanese Association for Adolescent Psychotherapy, 16 November 2002, Tokyo, JapanPSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 5 2003Article first published online: 28 AUG 200 Inpatient treatment of obsessive,compulsive disorder in a child and adolescent psychiatry ward M. USAMI National Center of Neurology and Psychiatry, Kohnodai Hospital, Chiba, Japan This is a case report of a 13-year-old-boy (2nd grade in junior high school). His father had poor communication; his mother was a very fragile woman. The boy had been overprotected by his parents, as long as he responded to their expectations. He did not have any other siblings. He played well with his friends since he was young, and did not have problems until the 1st term (from April to July) of 1st grade in junior high school. However, in September he started to have difficulties going well with his friends, and going to school. He spent most of his time in his room, and began to repeat checking and hand-washing frequently. Even at midnight, he forced his mother to touch the shutter from outside of the house for many times. He also ritually repeated to touch his mother's body, after he licked his hands, for over an hour. He became violent, when his parents tried to stop him. In April, year X, his parents visited our hospital for the first time. From then, his mother could not tolerate her son's coerciveness any longer. His father explained to the boy that ,your mother has been hospitalized', and she started to live in the next room to the boy's without making any noise. After 3 months he noticed that his mother was not hospitalized, and he got very excited. He was admitted to our hospital with his family and relatives, in October, year X. At the initial stage of hospitalization he showed distrust and doubt towards the therapist and hospital. He had little communication with other boys and did not express his feelings. Therefore, there was a period of time where he seemed to wonder whether he could trust the treatment staff or not. During his interviews with his therapist he repeated only ,I'm okay' and did not show much emotional communication. For the boy, exposing himself was equivalent to showing his vulnerability and incompleteness. Therefore, the therapist considered that he was trying to denying his feelings to avoid this. The therapist set goals for considering his own feelings positively and expressing them appropriately. Also, the therapist carried out behavioral restrictions towards him. He hardly had any emotional communication with the staff, and his peer relationship in the ward was superficial. Therefore, he gradually had difficulty spending his time at the end of December On the following day in which he and the therapist decided to return to his house for the first time, he went out of the ward a few days before without permission. From thereon it was possible for him to share feelings such as hostility and aggression, dependence and kindness with the therapist. The therapist changed his role from an invasive one to a more protective one. Then, his unsociability gradually faded. He also developed good peer relationships with other boys in the ward and began to express himself feeling appropriately. He was also able to establish appropriate relations with his parents at home, and friends of his neighborhood began to have normal peer relationships again. During childhood and adolescence, boys with obsessive,compulsive disorder are known to have features such as poor insight and often involving their mothers. We would like to present this case, through our understanding of dynamic psychiatry throughout his hospitalization, and also on the other therapies that were performed. Psychotherapy with a graduate student that discontinued after only three sessions: Was it enough for this client? N. KATSUKI Sophia University, Tokyo, Japan Introduction: Before and after the psychotherapy, SWT was administrated in this case. Comparing these two drawings, the therapist was provided with some ideas of what kind of internal change had taken place inside this client. Referring to the changes observed, we would like to review the purposes and the ways of the psychotherapy, as well as the adequacy of the limited number of the sessions (vis-a-vis result attained.) Also we will discuss later if any other effective ways could be available within the capacities of the consulting system/the clinic in the university. Case: Ms. S Age 24 years. Problems/appeal: (i) awkwardness in the relationship with the laboratory colleagues; (ii) symptoms of sweating, vomiting and quivering; and (iii) anxiety regarding continuing study and job hunting. Diagnosis: > c/o PTSD. Psychotherapeutic setting: At the therapy room in the clinic, placed at the university, 50 min-session; once a week; paralleled with the medical treatment. Process: (1) Since she was expelled from the study team in the previous year, it has become extremely difficult for her to attend the laboratory (lab) due to the aforementioned symptoms. She had a feeling of being neglected by the others. When the therapist suggested that she compose her mental confusions in the past by attending the therapy room, she seemed to be looking forward to it, although she said that she could remember only a few. (2) She reported that she overdosed on sedatives, as she could not stop irritating. She was getting tough with her family, also she slashed the mattress of her bed with a knife for many times. She complained that people neither understood nor appreciated her properly. and she said that she wanted revenge on the leader of the lab by punishing him one way or other. (3) Looking back the previous session, she said ,I had been mentally mixed up at that time, but I feel that now I can handle myself, as I stopped the medication after consulting the psychiatrist. According to what she said, when she disclosed the occurrences in the lab to her mother, she felt to be understood properly by her mother and felt so relieved. and she also reported that she had been sewing up the mattress which she slashed before, without any reason. She added, " although I don't even know what it means, I feel that this work is so meaningful to me, somehow". Finally, she told that she had already made her mind to cope with the situation by herself from now on, although it might result in a flinch from the real solution. Situations being the above, the session was closed. Swt: By the remarkable changes observed between the two drawings, the meanings of this psychotherapy and its closure to the client would be contemplated. Question of how school counselors should deal with separation attendant on students' graduation: On a case in which the separation was not worked through C. ASAHARA Sophia University, Tokyo, Japan Although time limited relationship is one of the important characteristics in school counseling, the question of separation attendant on it has not been much discussed based on specific cases. This study focuses on the question of separation through looking at a particular case, in which the separation was not worked through, and halfway relationship continued even after the student's graduation and the counselor's resignation. I was a part time school counselor at a junior high school in Tokyo. The client was a 14-year-old female student, who could not go to her classroom, and spent a few hours in a sick bay when she came to school. She was in the final grade and there was only half a year left before graduation when we first met, and we started to see each other within a very loose structure. As her personality was hyper-vigilant and defensive, it took almost 2 months before I could feel that she was nearer. Her graduation was the first occasion of separation. On that occasion, I found that there had been a discrepancy between our expectations; while I took it for granted that our relationship would end with the graduation, she expected to see me even after she graduated, and she actually came up to see me once in a while during the next year. A year later, we faced another occasion of separation, that was my resignation. Although I worried about her, all I have done for her was to hand a leaflet of a counseling office, where I work as a part time counselor. Again I could not refer to her feelings or show any concrete directions such as making a fixed arrangement. After an occasional correspondence for the next 10 months (about 2 years after her graduation), she contacted me at the counseling office asking for a constant counseling. Why could I not deal with both occasions? and how did that affect the client thereafter? There were two occasions of separation. At the time of the client's graduation, I seemed to be enmeshed in the way of separation that is peculiar to the school setting. In general in therapeutic relationship, mourning work between counselor and client is regarded as being quite important. At school, however, separation attendant on graduation is usually taken for granted and mourning work for any personal relationship tends to be neglected. Graduation ceremony is a big event but it is not about mourning over one's personal relationships but separation from school. That may be why I did not appreciate how the client counted on our relationship. At the time of my resignation I was too worried about working through a change from very loose structure which is peculiar to the school setting to a usual therapeutic structure (fees are charged, and time, place are fixed). That is why I did nothing but give her a leaflet. In this way, we never talked about her complex feelings such as sadness or loneliness, which she was supposed to experience on separation. Looking at the aforementioned process from the client's viewpoint, it can be easily imagined that she could not accept the fact of separation just because she graduated. and later, she was forced to be in double-bind situation, in which she was accepted superficially (handed a leaflet), while no concrete possibility was proposed concerning our relationship (she could never see me unless she tries to contact me.) As a result, she was left alone and at a loss whether she could count on me or not. The halfway situation or her suspense was reflected in her letter, in which she appeared to be just chatting at first sight, but between the lines there was something more implying her sufferings. Above discussion suggests that in some case, we should not neglect the mourning work even in a school setting. To whom or how it is done is the next theme we should explore and discuss in the future. For now, we should at least be conscious about the question of separation in school setting. Study of the process of psychotherapy with intervals for months M. TERASHIMA Bunkyo Gakuin University, Tokyo, Japan This is a report on the process of psychotherapy of an adolescent girl who showed manic and depressive state. At the time of a depressed state, she could not go to a college and withdrew into home, and the severe regressive situation was shown. Her therapy began at the age of 20 and she wanted to know what her problem was. The process of treatment went on for 4 years but she stopped coming to sessions for several months because of failure of the therapist. She repeated the same thing twice. After going through these intervals the client began to remember and started to talk about her childhood , suffering abusive force from her father, with vivid impressions. They once were hard for her to accept, but she began to establish the consistent figure of herself from past to present. In this case, it could be thought that the intervals of the sessions had a certain role, with which the client controlled the structure of treatment, instead of an attack against the therapist. Her object relation, which is going to control an object offensively, was reflected in these phenomena. That is, it can be said that the ambivalence about dependency , difficult to depend but desirous of the object , was expressed. Discontinuation of the sessions was the product of the compromise formation brought about the ambivalence of the client, and while continuing to receive this ambivalence in the treatment, the client started to realize discontinuance of her memories and then advanced integration of her self-image. For the young client with conflict to dependence such as her, an interval does not destroy the process of treatment but in some cases it could be considered as a therapeutic element. In the intervals the client could assimilate the matter by herself, that acquired by the sessions. Psychotherapy for a schizoid woman who presented eccentric speech and behaviour M. OGASAWARA Osaka University Graduate School of Medicine, Osaka, Japan Case presentation: A case of a 27-year-old woman at the beginning of therapy. Life history: She had been having a wish for death since she was in kindergarten and she had been feeling strong resistance to do the same as others after school attendance. She had a history of ablutomania from the age of 10,15, but the symptom disappeared naturally. and she said that she had been eliminated from groups that she tried to enter. After graduating a junior college, she changed jobs several times without getting a full-time position. Present history: Scolded by her boy friend for her coming home too late one day, she showed confusion such as excitement, self-injury or terror. She consulted a psychiatrist in a certain general hospital, but she presented there eccentric behaviours such as tense facial expression, stiffness of her whole body, or involuntary movement of limbs. and because she felt on bad terms with the psychiatrist and she had come to cause convulsion attacks in the examination room, she was introduced to our hospital. Every session of this psychotherapy was held once a week and for approximately 60 min at a time. Treatment process: She sometimes presented various eccentric attitudes, for example overturning to the floor with screaming (1), going down on her knees when entrance at the door (5), entering with a knife in her mouth and hitting the wall suddenly (7), stiffening herself just outside the door without entering the examination room (9), taking out a knife abruptly and putting it on her neck (40), exclaiming with convulsion responding to every talk from the therapist (41), or stiffening her face and biting herself in the right forearm suddenly (52). She also repeated self-injuries or convulsion attacks outside of the examination room in the early period of the therapy. Throughout the therapy she showed hypersensitivity for interpersonal relations, anxiety about dependence, terror for self-assertion, and avoidance for confrontation to her emotional problems. Two years and 6 months have passed since the beginning of this therapy. She ceased self-injury approximately 1 year and 6 months before and her sense of obscure terror has been gradually reduced to some extent. Discussion: Her non-verbal wariness and aggression to the therapist made the sessions full of tension and the therapist felt a sense of heaviness every time. In contrast, she could not express aggression verbally to the therapist, and when the therapist tried to identify her aggression she denied it. Her anxiety, that she will be thoroughly counterattacked to self-disintegration if she shows aggression to other persons, seems to be so immeasurably strong that she is compelled to deny her own aggression. Interpretations and confrontations by the therapist make her protective, and occasionally she shows stronger resistance in the shape of denial of her problems or conversion symptoms (astasia, aphonia, or involuntary movements) but she never expresses verbal aggression to the therapist. and the therapist feels much difficulty to share sympathy with her, and she expresses distrust against sympathetic approach of the therapist. However, her obvious disturbance that she expresses when she feels the therapist is not sympathetic shows her desire for sympathy. Thus, because she has both strong distrust and desire for sympathy, she is in a porcupine dilemma, which is characteristic of schizoid patients as to whether to lengthen or to shorten the distance between herself and the therapist. This attitude seems to have been derived from experience she might have had during her babyhood and childhood that she felt terror to be counterattacked and deserted when she showed irritation to her mother. In fact, existence of severe problems of the relationship between herself and her mother in her babyhood and childhood can be guessed from her statement. Although she has been repeating experiences to be excluded from other people, she shows no attitude to construct interpersonal relationship actively. On the contrary, by regarding herself to be a victim or devaluating other persons she externalizes responsibility that she herself should assume essentially. The reason must be that her disintegration anxiety is evoked if she recognizes that she herself has problems; that is, that negative things exist inside of her. Therefore, she seems to be inhibited to get depressive position and obliged to remain mainly in a paranoid,schizoid position. As for the pathological level, she seems to have borderline personality organization because of frequent use of mechanisms to externalize fantastically her inner responsibility. For her high ability to avoid confronting her emotional problems making the most of her verbal ability, every intervention of the therapist is invalidated. So, it seems very difficult for her to recognize her own problems through verbal interpretations or confrontation by the therapist, for the present. In general, it is impossible to confront self problems without containing negative emotions inside of the self, but her ability seemed to be insufficient. So, to point out her problems is considered to be very likely to result in her confusion caused by persecution anxiety. Although the therapy may attain the stage on which verbal interpretation and confrontation work better some day, the therapist is compelled to aim at promoting her ability to hold negative emotion inside of herself for the time being. For the purpose, the therapist is required to endure the situation in which she brings emotion that makes the therapist feel negative counter-transference and her process to experience that the therapeutic relation itself would not collapse by holding negative emotion. On supportive psychotherapy with a male adolescent Y. TERASHIMA Kitasato University Health Care Center, Kanagawa, Japan Adolescent cases sometimes show dramatic improvements as a consequence of psychotherapy. The author describes how psychotherapy can support an adolescent and how theraputic achievements can be made. Two and a half years of treatment sessions with a male adolescent patient are presented. The patient was a 19-year-old man, living with his family. He had 5 years of experience living abroad with his family and he was a preparatory school student when he came to a mental clinic for help. He was suffering from not being able to sleep well, from difficulties concerning keeping his attention on one thing, and from fear of going to distant places. He could barely leave his room, and imagined the consequence of overdosing or jumping out of a window. He claimed that his life was doomed because his family moved from a town that was familiar to him. At the first phase of psychotherapy that lasted for approximately 1 year, the patient seldom responded to the therapist. The patient was basically silent. He told the therapist that the town he lives in now feels cold or that he wants to become a writer. However, these comments were made without any kind of explanation and the therapist felt it very difficult to understand what the patient was trying to say. The sessions continued on a regular basis. However, the therapist felt very useless and fatigued. Problems with the patient and his family were also present at this phase of psychotherapy. He felt unpleasant at home and felt it was useless to expect anything from his parents. These feelings were naturally transferred to the therapist and were interpreted. However, interpretation seemed to make no changes in the forms of the patient's transference. The second phase of psychotherapy began suddenly. The patient kept saying that he did not know what to talk about. However, after a brief comment made by the therapist on the author of the book he was reading, the patient told the therapist that it was unexpected that the therapist knew anything of his favorite writer. After this almost first interaction between the patient and the therapist, the patient started to show dramatic changes. The patient started to bring his favorite rock CDs to sessions where they were played and the patient and the therapist both made comments on how they felt about the music. He also started asking questions concerning the therapist. It seemed that the patient finally started to want to know the therapist. He started communicating. The patient was sometimes silent but that did not last long. The therapist no longer felt so useless and emotional interaction, which never took place in the first phase, now became dominant. The third phase happened rapidly and lasted for approximately 10 months. Conversations on music, art, literature and movies were made possible and the therapist seldom felt difficulties on following the patient's line of thought. He started to go to schools and it was difficult at first but he started adjusting to the environment of his new part-time jobs. By the end of the school year, he was qualified for the entrance to a prestigious university. The patient's problems had vanished except for some sleeping difficulties, and he did not wish to continue the psychotherapy sessions. The therapist's departure from the clinic added to this and the therapy was terminated. The patient at first reminded the therapist of severe psychological disturbances but the patient showed remarkable progress. Three points can be considered to have played important roles in the therapy presented. The first and the most important is the interpretation by behavior. The patient showed strong parental transference to the therapist and this led the therapist to feel useless and to feel fatigue. Content analysis and here-and-now analysis seemed to have played only a small part in the therapy. However, the therapist tried to keep in contact with the patient, although not so elegant, but tried to show that the therapist may not be useless. This was done by maintaining the framework of the therapy and by consulting the parents when it was considered necessary. Second point is the role that the therapist intentionally took as a model or target of introjection. With the help of behavioral interpretation that showed the therapist and others that it may not be useless, the patient started to introject what seemed to be useful to his well being. It can be considered that this role took some part in the patient going out and to adjust to the new environment. Last, fortune of mach must be considered. The patient and the therapist had much in common. It was very fortunate that the therapist knew anything about the patient's favorite writer. The therapist had some experience abroad when he was young. Although it is a matter of luck that the two had things in common, it can be said that the congeniality between the patient and the therapist played an important role in the successful termination of the therapy. From the physical complaint to the verbal appeal of A's recovery process to regain her self-confidence C. ITOKAWA and S. KAZUKAWA Toyama Mental Health Center, Toyama, Japan This is one of the cases at Toyama Mental Health Center about a client here, we will henceforth refer to her simply as ,A'. A was a second grade high school student. We worked with her until her high school graduation using our center's full functions; counseling, medical examination and the course for autogenic training (AT). She started her counseling by telling us that the reason for her frequent absences from school began because of stomach pains when she was under a lot of stress for 2 years of junior high school, from 2nd grade to 3rd grade. Due to a lack of self confidence and a constant fear of the people around her, she was unable to use the transportation. She would spend a large amount of time at the school infirmary because she suffered from self-diagnosed hypochondriac symptoms such as nausea, diarrhea and a palpitation. She continued that she might not be able to have the self-confidence to sit still to consult me on her feelings in one of our sessions. A therapist advised her to take the psychiatric examination and the use of AT and she actually saw the medical doctor. In counseling (sessions), she eventually started to talk about the abuse that started just after her entering of junior high school; she approached the school nurse but was unable to tell her own parents because she did not trust them. In doing so, she lost the rest of her confidence, affecting the way she looked at herself and thought of how others did. At school she behaved cheerfully and teachers often accused her of idleness as they regarded this girl's absences along with her brightly dyed hair and heavy make-up as her negligent laziness. I, as her therapist, contacted some of the school's staff and let them know of her situation in detail. As the scolding from the teachers decreased, we recognized the improvement of her situation. In order to recover from the missed academic exposure due to her long absence, she started to study by herself. In a couple of months her physical condition improved gradually, saying ,These days I have been doing well by myself, haven't I?' and one year later, her improved mental condition enabled her to go up to Tokyo for a concert and furthermore even to enjoy a short part-time job. She continued the session and the medical examination dually (in tangent) including the consultation about disbelief to the teachers, grade promotion, relationships between friends and physical conditions. Her story concentrated on the fact that she had not grown up with sufficiently warm and compassionate treatment and she could not gain any mental refuge in neither her family nor her school, or even her friends. Her prospects for the future had changed from the short-ranged one with no difficulty to the ambitious challenge: she aimed to try for her favorite major and hoped to go out of her prefecture. But she almost had to give up her own plan because the school forced her to change her course as they recommended. (because of the school's opposition with her own choice). So without the trust of the teachers combined with her low self-esteem she almost gave up her hopes and with them her forward momentum. In this situation as the therapist, I showed her great compassion and discussed the anger towards the school authorities, while encouraging this girl by persuading her that she should have enough self-confidence by herself. Through such sessions, she was sure that if she continued studying to improve her own academic ability by herself she could recognize the true meaning of striving forward. and eventually, she received her parents' support who had seemed to be indifferent to her. At last she could pass the university's entrance exams for the school that she had yearned to attend. That girl ,A' visited our center 1 month later to show us her vivid face. I saw a bright smile on her face. It was shining so brightly. [source] Incidence, Risk Factors and Clinical Consequences of Neutropenia Following Kidney Transplantation: A Retrospective StudyAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2009L. Zafrani Neutropenic episodes in kidney transplant patients are poorly characterized. In this retrospective study, neutropenia was experienced by 112/395 patients (28%) during the first year posttransplant. The only factor found to be significantly associated with the occurrence of neutropenia was combined tacrolimus-mycophenolate therapy (p < 0.001). Neutropenic patients experienced more bacterial infections (43% vs. 32%, p = 0.04). Grade of neutropenia correlated with the global risk of infection. Discontinuation of mycophenolic acid (MPA) due to neutropenia was associated with an increased incidence of acute rejection (odds ratios per day 1.11, 95% confidence intervals 1.02,1.22) but not with reduced renal function at 1 year. The time from onset of neutropenia to MPA discontinuation correlated with the duration of neutropenia. Granulocyte colony-stimulating factor (G-CSF) administration was safe and effective in severely neutropenic kidney graft recipients, with absolute neutrophil count >1000/,L achieved in a mean of 1.5±0.5 days. Neutropenia is an important and frequent laboratory finding that may exert a significant influence on outcomes in kidney transplantation. As well as leading to an increased incidence of infection, it is associated with a higher rate of allograft rejection if MPA is discontinued for >6 days (p = 0.02). G-CSF accelerates recovery of neutropenia and may be a good therapeutic alternative for severely neutropenic patients. [source] Withdrawal of antiepileptic drugs after neocortical epilepsy surgeryANNALS OF NEUROLOGY, Issue 2 2010Kyung-Il Park MD Objective This study investigated the prevalence of successful antiepileptic drug withdrawal and identified predictors of seizure recurrence after antiepileptic drug reduction following resectional operation for intractable neocortical epilepsy. Methods We retrospectively assessed 223 patients (100 with neocortical temporal lobe epilepsy, 69 with frontal lobe epilepsy, 23 with parietal lobe epilepsy, 25 with occipital lobe epilepsy, and 6 with multifocal epilepsy) who underwent surgery. The mean period of observation was 84.4 months (range, 24,152 months) after surgery and 72.6 months (range, 12,138 months) after initial reduction. Clinical characteristics, magnetic resonance imaging, and surgical parameters were evaluated for their potential to predict recurrence associated with antiepileptic drug withdrawal. Results Antiepileptic drug reduction was attempted in 147 patients (65.9%), 78 (53.1%) of whom had seizure recurrence after initial reduction. Discontinuation was achieved in 73 patients (32.7%), and 59 (80.8%) of these remained seizure free until final assessment. Multivariate analysis revealed that early drug tapering, normal magnetic resonance imaging results, seizure before reduction, and longer epilepsy duration were associated with recurrence. Finally, 27.4% of patients were seizure free without drugs, and 26.9% were seizure free with drugs. Compared with preoperative status, the number of antiepileptic drugs needed decreased in 50.7% of patients, did not change in 19.3%, and increased in 30.0% after surgery. Interpretation The complete-cure rate of intractable neocortical epilepsy by resectional surgery was 27.4%. When patients undertake early tapering, and have normal magnetic resonance imaging results, seizure before reduction, and longer disease duration, further withdrawal should be done cautiously because of the high risk of relapse. ANN NEUROL 2010;67:230,238 [source] Suppression of skin and kidney disease by inhibition of spleen tyrosine kinase in lupus-prone miceARTHRITIS & RHEUMATISM, Issue 7 2010Guo-Min Deng Objective Spleen tyrosine kinase (Syk) is involved in membrane-mediated signaling in various cells, including immune cells. It is overexpressed in T cells from patients with systemic lupus erythematosus (SLE), and its inhibition has been shown to improve T cell function as well as to improve disease manifestations in (NZB × NZW)F1 lupus-prone mice and in patients with rheumatoid arthritis. While clinical trials examining Syk inhibition in patients with SLE are being considered, the aim of our experiments was to determine whether the therapeutic effects of Syk inhibition extend to other strains of lupus-prone mice and whether they result in improvement in skin disease and modification of established disease. Methods Female MRL/lpr or BAK/BAX mice were studied. Starting either at age 4 weeks (before disease) or at age 16 weeks (after established disease) and continuing for up to 16 weeks, mice were fed chow containing the Syk inhibitor R788 or control chow. Results We found that inhibition of Syk in MRL/lpr and BAK/BAX mice prevented the development of skin disease and significantly reduced established skin disease. Similarly, Syk inhibition reduced the size of the spleen and lymph nodes, suppressed the development of renal disease, and suppressed established renal disease. Discontinuation of treatment resulted in extended suppression of skin disease for at least 8 weeks and suppression of renal disease for 4 weeks. Conclusion Syk inhibition suppresses the development of lupus skin and kidney disease in lupus-prone mice, suppresses established disease in lupus-prone mice, and may represent a valuable treatment for patients with SLE. [source] Etanercept combined with methotrexate for high-need psoriasisBRITISH JOURNAL OF DERMATOLOGY, Issue 2 2008R.J.B. Driessen Summary Background, For some high-need psoriatic patients, the efficacy of etanercept monotherapy is insufficient. In these cases it might be indicated to combine etanercept with other conventional treatments. Objectives, To provide daily practice safety and efficacy data for etanercept and methotrexate combination therapy. Methods, Data were extracted from an existing database, which contains prospective safety and efficacy data of all patients who were treated with etanercept in clinical practice. A case was defined as a patient using etanercept and methotrexate simultaneously for an indefinite period during follow-up. For all cases, baseline data, Psoriasis Area and Severity Index (PASI) scores, adverse events and laboratory values were investigated. Furthermore, the influence of introduction and discontinuation of methotrexate on these parameters was analysed. Results, Fourteen patients with simultaneous use of etanercept and methotrexate were selected. In six patients, methotrexate was introduced after etanercept to avoid further psoriasis deterioration, which resulted in an improvement of psoriasis in four of these patients. Eight patients were on methotrexate therapy before start of etanercept. Discontinuation of methotrexate in six of these patients resulted in a decrease in PASI improvement in five patients. Etanercept combined with methotrexate was well tolerated, and only mild adverse events were reported. No clinically significant changes in laboratory parameters occurred. Conclusions, Results show that combining etanercept with methotrexate is reasonable when efficacy of etanercept monotherapy is insufficient, or when rapid deterioration of psoriasis after abrupt discontinuation of methotrexate is expected. Laboratory values and adverse events were not different from what would have been expected when using methotrexate alone. [source] Cushing's syndrome due to pharmacological interaction in a cystic fibrosis patientACTA PAEDIATRICA, Issue 9 2002KM Main Treatment of allergic bronchopulmonary aspergillosis with itraconazole is becoming more widespread in chronic lung diseases. A considerable number of patients is concomitantly treated with topical or systemic glucocorticoids for anti-inflammatory effect. As azole compounds inhibit cytochrome P450 enzymes such as CYP3A isoforms, they may compromise the metabolic clearance of glucocorticoids, thereby causing serious adverse effects. A patient with cystic fibrosis is reported who developed iatrogenic Cushing's syndrome after long-term treatment with daily doses of 800 mg itraconazole and 1600 ,g budesonide. The patient experienced symptoms of striae, moon-face, increased facial hair growth, mood swings, headaches, weight gain, irregular menstruation despite oral contraceptives and increasing insulin requirement for diabetes mellitus. Endocrine investigations revealed total suppression of spontaneous and stimulated plasma cortisol and adrenocorticotropin. Discontinuation of both drugs led to an improvement in clinical symptoms and recovery of the pituitary-adrenal axis after 3 mo. Conclusion: This observation suggests that the metabolic clearance of budesonide was compromised by itraconazole's inhibition of cytochrome P450 enzymes, especially the CYP3A isoforms, causing an elevation in systemic budesonide concentration. This provoked a complete suppression of the endogenous adrenal function, as well as iatrogenic Cushing's syndrome. Patients on combination therapy of itraconazole and budesonide inhalation should be monitored regularly for adrenal insufficiency. This may be the first indicator of increased systemic exogenous steroid concentration, before clinical signs of Cushing's syndrome emerge. [source] Comparison of fesoterodine and tolterodine extended release for the treatment of overactive bladder: a head-to-head placebo-controlled trialBJU INTERNATIONAL, Issue 1 2010Sender Herschorn Study Type , Therapy (RCT) Level of Evidence 1b OBJECTIVE To compare the efficacy and tolerability of fesoterodine 8 mg with tolterodine extended-release (ER) 4 mg and placebo in a randomized clinical trial of patients with an overactive bladder (OAB). PATIENTS AND METHODS In this 12-week double-blind, double-dummy, placebo-controlled, randomized clinical trial, eligible patients reported OAB symptoms for ,3 months and recorded ,8 voids and ,1 urgency urinary incontinence (UUI) episode per 24 h in 3-day bladder diaries at baseline. Patients were randomized in a 2:2:1 ratio to fesoterodine (4 mg for 1 week then 8 mg for 11 weeks); tolterodine ER 4 mg; or placebo (with sham dose escalation for tolterodine ER and placebo). Endpoints were changes from baseline to week 12 in UUI episodes (primary endpoint), total and nocturnal voids, urgency episodes, severe urgency episodes, and frequency-urgency sum per 24 h; mean voided volume per void (MVV); and the OAB questionnaire (OAB-q), Patient Perception of Bladder Condition (PPBC), and Urgency Perception Scale (UPS). Safety and tolerability were assessed and summarized over the 12-week study period. RESULTS Fesoterodine (636 patients) significantly improved UUI episodes at week 12 (primary endpoint) compared with tolterodine ER (641 patients; P = 0.017) and placebo (313 patients; P < 0.001). Fesoterodine also produced significantly greater improvements than tolterodine ER in MVV (P = 0.005). Fesoterodine significantly improved all diary endpoints compared with placebo (P < 0.001), except for nocturnal voids (P = 0.327). Tolterodine ER significantly improved all diary endpoints vs placebo (P < 0.001), except for nocturnal voids (P = 0.506) and MVV (P = 0.103). Diary dry rates (the proportion of patients reporting no UUI episodes at endpoint among those with one or more UUI episodes at baseline) were significantly higher with fesoterodine (64%) than with tolterodine ER (57%; P = 0.015) and placebo (45%; P < 0.001). Improvements in PPBC, UPS and OAB-q scale and domain scores at week 12 were all significantly better with fesoterodine than placebo (all P < 0.001) and tolterodine ER (all P < 0.05) except for the OAB-q Sleep domain vs tolterodine ER (P = 0.081). Dry mouth and constipation rates were 28% and 5% in the fesoterodine group, 16% and 4% in the tolterodine ER group, and 6% and 3% with placebo, respectively. Discontinuations due to treatment-emergent adverse events were 6%, 4% and 2% in the fesoterodine, tolterodine ER, and placebo groups, respectively. CONCLUSION In patients with OAB, fesoterodine 8 mg showed superior efficacy over tolterodine ER 4 mg and placebo in reducing UUI episodes (primary endpoint) and in improving most patient-reported outcome measures. Both active treatments were well tolerated. [source] A 6-month follow-up study of 1048 patients diagnosed with an occupational skin diseaseCONTACT DERMATITIS, Issue 5 2009Tarja Mälkönen Background: Occupational skin diseases (OSDs) often have considerable medical and occupational consequences. Previous data on prognostic factors have been derived from studies with fairly small sample sizes. Objectives: To determine the medical and occupational outcome in 1048 patients diagnosed with OSD at the Finnish Institute of Occupational Health and to identify the prognostic risk factors for the continuation of OSD. Methods: Patients examined in 1994,2001 filled out a follow-up questionnaire 6 months after the diagnosis. Data on atopy, contact allergies, and occupation were analysed. Results: Six months after the diagnosis the skin disease had healed in 27% of the patients. The OSD had cleared up in 17% of those with no changes at work, and in 34% of those who had changed their job/occupation. The best clearing had occurred in the patients with contact urticaria (35%), whereas the healing of allergic (27%) and irritant (23%) contact dermatitis was similar. The risk factors for continuing occupational contact dermatitis (OCD) were no changes in work, age > 45 years, food-related occupations, respiratory atopy, and male sex. Conclusions: The healing of OSD was associated with discontinuation of the causative exposure. A change in work and the presence of easily avoidable work-related allergies were associated with a good prognosis. [source] Responses of the bronchial and pulmonary circulations to short-term nitric oxide inhalation before and after endotoxaemia in the pigACTA PHYSIOLOGICA, Issue 1 2002R. J. M. Middelveld ABSTRACT The physiological responses of the bronchial circulation to acute lung injury and endotoxin shock are largely unexplored territory. This study was carried out to study the responsiveness of the bronchial circulation to nitric oxide (NO) inhalation before and after endotoxaemia, in comparison with the pulmonary circulation, as well as to study changes in bronchial blood flow during endotoxaemia. Six anaesthetized pigs (pre-treated with the cortisol-synthesis inhibitor metyrapone) received an infusion of 10 µg/kg endotoxin during 2 h. Absolute bronchial blood flow was measured via an ultrasonic flow probe around the bronchial artery. The pigs received increasing doses of inhaled NO over 5 min each (0, 0.2, 2 and 20 ppm) before and after 4 h of endotoxaemia. The increase in bronchial vascular conductance during 5 min of inhalation of 20 ppm NO before endotoxin shock was significantly higher (area under curve (AUC) 474.2 ± 84.5% change) than after endotoxin shock (AUC 118.2 ± 40.4%, P < 0.05 Mann,Whitney U -test). The reduction of the pulmonary arterial pressure by 20 ppm NO was not different. A short rebound effect of the pulmonary arterial pressure occurred after discontinuation of inhaled NO before endotoxaemia (AUC values above baseline 54.4 ± 19.7% change), and was virtually abolished after endotoxaemia (AUC 6.1 ± 4.0%, P = 0.052, Mann,Whitney U -test). Our results indicate that the responsiveness of the bronchial circulation to inhalation of increasing doses of inhaled NO during endotoxin shock clearly differ from the responsiveness of the pulmonary circulation. The reduced responsiveness of the bronchial circulation is probably related to decreased driving pressure for the bronchial blood flow. The absence of the short rebound effect on pulmonary arterial pressure (PAP) after induction of shock could be related to maximum constriction of the pulmonary vessels at 4 h. [source] Efficacy and safety of duloxetine in the treatment of generalized anxiety disorder: a flexible-dose, progressive-titration, placebo-controlled trialDEPRESSION AND ANXIETY, Issue 3 2008Moira Rynn M.D. Abstract Generalized anxiety disorder (GAD), a prevalent and chronic illness, is associated with dysregulation in both serotonergic and noradrenergic neurotransmission. Our study examined the efficacy, safety, and tolerability of duloxetine hydrochloride, a dual reuptake inhibitor of serotonin and norepinephrine, for short-term treatment of adults with GAD. In a 10-week, double-blind, progressive-titration, flexible-dose trial, 327 adult outpatients with a DSM-IV,defined GAD diagnosis were randomized to duloxetine 60,120,mg (DLX, N=168) or placebo (PLA, N=159) treatment. The primary efficacy measure was mean change from baseline to endpoint in Hamilton Anxiety Scale (HAMA) total score. Secondary outcome measures included response rate (HAMA total score reduction ,50% from baseline), Clinician Global Impression,Improvement (CGI-I) scores, and Sheehan Disability Scale (SDS) scores. Patients who received duloxetine treatment demonstrated significantly greater improvement in HAMA total scores (P=.02); a higher response rate (P=.03), and greater improvement (P=.04) than patients who received placebo. Duloxetine-treated patients were also significantly more improved than placebo-treated patients on SDS global functional (P<.01) and work, social, and family/home impairment scores (P<.05). The rate of discontinuation due to adverse events (AEs) was higher for the duloxetine group compared with the placebo group (P=.002). The AEs most frequently associated with duloxetine were nausea, dizziness, and somnolence. Duloxetine was an efficacious, safe, and well-tolerated treatment that resulted in clinically significant improvements in symptom severity and functioning for patients with GAD. Depression and Anxiety 0:1,8, 2007. © 2007 Wiley-Liss, Inc. [source] Open trial of nefazodone among Hispanics with major depression: Efficacy, tolerability, and adherence issuesDEPRESSION AND ANXIETY, Issue 3 2001J. Arturo Sįnchez-Lacay M.D., M.P.H. Abstract The efficacy and tolerability of nefazodone in the treatment of major depression among Spanish-monolingual Hispanics was examined and compared to historical controls among English-speaking, predominantly non-Hispanic subjects. Fifty monolingual Hispanic outpatients with major depression and a HAM-D17 score ,18 were treated with nefazodone in a flexible-dose 8-week open-label protocol. Sixty-three percent of the intent-to-treat (ITT) sample with ,1 efficacy visit were considered responders according to CGI-I criteria, falling within the range of response rates (58,69%) reported in six prior nefazodone trials with non-Hispanic subjects. Significant improvement was found for the ITT and completer samples in HAM-D17, HAM-D28, and SCL-90 scores and in two measures of psychosocial functioning. Endpoint mean dose in the ITT sample was 379 mg/day (SD=170), also within the range of previous trials (321,472mg/day). Adverse effects were not elevated, with only dry mouth (8%) reported by >6% of subjects. However, 42% of the sample dropped out of treatment before study termination, usually because of side effects or due to family or work difficulties, a higher rate than previously reported for nefazodone (21,33%). This open trial finds nefazodone to be an efficacious treatment for major depression among monolingual Hispanics, with comparable efficacy to previous controlled trials among non-Hispanic subjects. Double-blind studies are required to confirm this comparable efficacy. Mean endpoint doses and adverse effect rates similar to previous trials do not support the need for reduced doses of nefazodone among Hispanics. However, an elevated rate of treatment discontinuation threatens treatment efficacy among this population. Causes for this elevated rate require explanation, given the apparently unremarkable pattern of adverse effect reports. Depression and Anxiety 13:118,124, 2001. © 2001 Wiley-Liss, Inc. [source] Imiquimod Treatment of Superficial and Nodular Basal Cell Carcinoma: 12-Week Open-Label TrialDERMATOLOGIC SURGERY, Issue 3 2005Ketty Peris MD Background Imiquimod is an immune response modifier shown to be effective in basal cell carcinoma (BCC). Objective To evaluate the efficacy, tolerability, and response durability of imiquimod 5% cream in selected patients with superficial and/or nodular BCCs. Methods Seventy-five superficial and 19 nodular BCCs in 49 patients were treated with imiquimod once daily three times a week for up to 12 weeks. Results Of the 49 enrolled patients, 1 discontinued the study and 1 was lost to follow-up. After 12 weeks of treatment, a complete response occurred in 70 of 75 (93.3%) superficial BCCs and a partial response in 4 of 75 (5.3%) superficial BCCs. Ten of 19 (52.6%) nodular BCCs cleared after 12 weeks, whereas 7 (36.8%) showed partial remission. Adverse side effects were limited to local skin reactions. Recurrence was observed in 2 of 70 (2.9%) successfully treated superficial BCCs 6 and 8 months after treatment discontinuation. No recurrence was detected in 68 of 70 (97.1%) superficial BCCs and in 10 successfully treated nodular BCCs after 12 to 34 months of follow-up (mean 23 months). Conclusions In our patient population, treatment of superficial BCCs with topical imiquimod for 12 weeks produced an excellent clinical response overall, with complete remission maintained after a mean of 23 months. KETTY PERIS, MD, ELENA CAMPIONE, MD, TAMARA MICANTONIO, MD, GEORGIANA CLARE MARULLI, MD, MARIA CONCETTA FARGNOLI, MD, AND SERGIO CHIMENTI, MD, HAVE INDICATED NO SIGNIFICANT INTEREST WITH COMMERCIAL SUPPORTERS. [source] THERAPEUTIC HOTLINE: Alefacept in the treatment of hyperkeratotic palmoplantar psoriasisDERMATOLOGIC THERAPY, Issue 5 2010Sagi Lior ABSTRACT Plaque-type palmoplantar psoriasis (PPP) is associated with marked morbidity and frequently resistant to conventional therapies. Patients with long-standing plaque-type PPP failing previous treatments were included and treated with a 12-week intramuscular alefacept. The biweekly evaluation included hyperkeratosis, itching, and pain grading. In all of the seven treated patients significant to complete improvement in hyperkeratosis, pruritus and pain were observed, along with dose reduction or complete discontinuation of additional systemic treatments and without any recorded side effects. Alefacept should be considered as a therapeutic option for plaque-type PPP. [source] Outcomes for 236 patients from a 2-year early intervention in psychosis serviceACTA PSYCHIATRICA SCANDINAVICA, Issue 2 2009M. A. Turner Objective:, To examine: i) changes in key outcome measures over time in treatment in a representative first-episode psychosis treatment cohort and ii) baseline predictors of service disengagement. Method:, Baseline characteristics of 236 patients were examined for associations with outcomes over time using generalized estimating equation models. The data on disengagement were analysed using logistic regression. Results:, After controlling for admission scores, patients showed consistently improved outcomes while in treatment on functional recovery (unemployment, P < 0.01; HoNOS, P < 0.001; the Quality of Life Scale, P < 0.001; GAF, P < 0.05) but not symptomatology (as assessed by the PANSS and substance abuse). The 64 (33%) who disengaged were more likely to be unemployed (P < 0.01) and have higher HoNOS (P < 0.01) and GAF (P < 0.05) scores at baseline. Conclusion:, This evaluation has shown significant improvements in psychosocial functioning but not psychopathology during treatment at an Early Intervention for Psychosis Service. Despite attempts to retain patients, there is a high rate of treatment discontinuation. [source] | |||||||||||||||||||||||||||||||||||||||||||