Treatment Initiation (treatment + initiation)

Distribution by Scientific Domains
Distribution within Medical Sciences

Selected Abstracts

Quality of life in 1000 patients with early relapsing,remitting multiple sclerosis

N. Putzki
Background and purpose:, To examine the quality of life (QoL) in a large cohort of untreated patients with relapsing,remitting multiple sclerosis (RRMS) and to investigate the impact of intramuscular (IM) interferon beta-1a (IFNß-1a) treatment. Methods:, Prospective, observational, open-label, multicentre study conducted in Germany. Untreated patients with RRMS who initiated treatment with IM IFNß-1a were included and followed for 12 months. QoL was measured using the EQ-5D questionnaire. Clinical response was assessed by relapse rate and disability (Expanded Disability Status Scale; EDSS). Results:, A total of 1157 patients were included [mean age 37.6 years, median disease duration 13 months, mean relapse rate 1.7 (95%CI: 1.58,1.73), median EDSS score 2.0]. Relapse rate was reduced to 0.6 at 12 months (95%CI: 0.51,0.69, P < 0.0001). EDSS did not change significantly. At baseline, QoL was considerably lower in MS patients compared with the general German population, but was improved after treatment initiation [utilities of EQ-5D: 0.77 (95%CI: 0.75,0.78) vs. 0.75 (95%CI: 0.74,0.76) at baseline, 95%CI for difference: 0.01,0.03, P = 0.0046]. Higher disease activity and inability to work were negative predictors of QoL. 14.7% of patients were incapable of working for MS-related reasons. Conclusions:, Quality of life is considerably impaired in early stages of MS. Treatment initiation with IM IFNß attenuates MS disease activity and improves QoL. Inability to work early during the disease is a major challenge for the social security systems. [source]

Volume Overload and Cardiorenal Syndromes

Claudio Ronco MD
To include the vast array of interrelated derangements and to stress the bidirectional nature of the heart-kidney interactions, the classification of the cardiorenal syndrome today includes 5 subtypes whose terminology reflects their primary and secondary pathology, time frame, and the presence of concomitant cardiac and renal dysfunction. Cardiorenal syndromes (CRSs) are pathophysiologic disorders of the heart and kidneys whereby acute or chronic dysfunction of one organ may induce acute or chronic dysfunction of the other. Type 1 CRS reflects an abrupt worsening of cardiac function leading to acute kidney injury. Type 2 CRS describes chronic abnormalities in cardiac function causing progressive chronic kidney disease. Type 3 CRS consists in an abrupt worsening of renal function causing acute cardiac disorder. Type 4 CRS describes a state of chronic kidney disease contributing to decreased cardiac function, cardiac hypertrophy, and/or increased risk of adverse cardiovascular events. Type 5 CRS reflects a systemic condition (eg, sepsis) simultaneously causing both cardiac and renal dysfunction. Biomarkers can help characterize the subtypes of CRS as well as suggest the timing of treatment initiation and its likely effectiveness. The identification of patients and the pathophysiologic mechanisms underlying each syndrome subtype, including fluid overload or, in general, altered conditions of fluid status, can help physicians understand clinical derangements, provide the rationale for management strategies, and allow the design of future clinical trials with more accurate selection and stratification of the population under investigation. Congest Heart Fail. 2010;16(4)(suppl 1):Si,Siv. ©2010 Wiley Periodicals, Inc. [source]

Stigma and treatment delay in first-episode psychosis: a grounded theory study

Lauren Franz
Abstract Aim: A longer duration of untreated psychosis (DUP) is associated with greater morbidity in the early course of schizophrenia. This formative, hypothesis-generating study explored the effects of stigma, as perceived by family members, on DUP. Methods: Qualitative interviews were conducted with 12 African American family members directly involved in treatment initiation for a relative with first-episode psychosis. Data analysis relied on a grounded theory approach. A testable model informed by constructs of Link's modified labelling theory was developed. Results: Four main themes were identified, including: (i) society's beliefs about mental illnesses; (ii) families' beliefs about mental illnesses; (iii) fear of the label of a mental illness; and (iv) a raised threshold for the initiation of treatment. A grounded theory model was developed as a schematic representation of the themes and subthemes uncovered in the family members' narratives. Conclusions: The findings suggest that due to fear of the official label of a mental illness, certain coping mechanisms may be adopted by families, which may result in a raised threshold for treatment initiation, and ultimately treatment delay. If the relationships within the grounded theory model are confirmed by further qualitative and quantitative research, public educational programs could be developed with the aim of reducing this threshold, ultimately decreasing DUP. [source]

The rationale for early intervention in schizophrenia and related disorders

Merete Nordentoft
Abstract Aim: To examine the rationale and evidence supporting an early intervention approach in schizophrenia. Methods: A selective literature review was conducted. Results: During the onset of schizophrenia, there is often a significant delay between the emergence of psychotic symptoms and the initiation of treatment. The average duration of untreated psychosis is around 1,2 years. During this period, brain function may continue to deteriorate and social networks can be irreversibly damaged. Studies have consistently linked longer duration of untreated psychosis with poorer outcomes and this relationship holds even after controlling for the potential confounding variable of premorbid functioning. In Norway, the early Treatment and Intervention in PSychosis study demonstrated that duration of untreated psychosis is amenable to intervention with the combination of educational campaigns and specialized early detection units substantially decreasing the period from onset of symptoms to treatment initiation. Furthermore, recent evidence from the randomized controlled OPUS and the Lambeth Early Onset trial studies have linked phase-specific early interventions to improved outcomes spanning symptoms, adherence to treatment, comorbid drug abuse, relapse and readmission. Some benefits persist after cessation of the intervention. Conclusions: Early intervention in schizophrenia is justified to reduce the negative personal and social impact of prolonged periods of untreated symptoms. Furthermore, phase-specific interventions are associated with improved outcomes, at least in the short term. Further research is needed to establish the optimum duration of such programmes. [source]

Comparison of costs and utilization among buprenorphine and methadone patients

ADDICTION, Issue 6 2009
Paul G. Barnett
ABSTRACT Aims Buprenorphine is an effective alternative to methadone for treatment of opioid dependence, but economic concerns represent a barrier to implementation. The economic impacts of buprenorphine adoption by the US Veterans Health Administration (VHA) were examined. Design Prescriptions of buprenorphine, methadone treatment visits, health-care utilization and cost, and diagnostic data were obtained for 2005. Findings VHA dispensed buprenorphine to 606 patients and methadone to 8191 other patients during the study year. An analysis that controlled for age and diagnosis found that the mean cost of care for the 6 months after treatment initiation was $11 597 for buprenorphine and $14 921 for methadone (P < 0.001). Cost was not significantly different in subsequent months. The first 6 months of buprenorphine treatment included an average of 66 ambulatory care visits, significantly fewer than the 137 visits in methadone treatment (P < 0.001). In subsequent months, buprenorphine patients had 8.4 visits, significantly fewer than the 21.0 visits of methadone patients (P < 0.001). Compared to new methadone episodes, new buprenorphine episodes had 0.634 times the risk of ending [95% confidence interval 0.547,0.736]. Implementation of buprenorphine treatment was not associated with an influx of new opioid-dependent patients. Conclusion Despite the higher cost of medication, buprenorphine treatment was no more expensive than methadone treatment. VHA methadone treatment costs were higher than reported by other providers. Although new buprenorphine treatment episodes lasted longer than new methadone episodes, buprenorphine is recommended for more adherent patients. [source]

Rate of detoxification service use and its impact among a cohort of supervised injecting facility users

ADDICTION, Issue 6 2007
Evan Wood
ABSTRACT Background Vancouver, Canada recently opened a medically supervised injecting facility (SIF) where injection drug users (IDU) can inject pre-obtained illicit drugs. Critics suggest that the facility does not help IDU to reduce their drug use. Methods We conducted retrospective and prospective database linkages with residential detoxification facilities and used generalized estimating equation (GEE) methods to examine the rate of detoxification service use among SIF participants in the year before versus the year after the SIF opened. In secondary analyses, we used Cox regression to examine if having been enrolled in detoxification was associated with enrolling in methadone or other forms of addiction treatment. We also evaluated the impact of detoxification use on the frequency of SIF use. Results Among 1031 IDU, there was a statistically significant increase in the uptake of detoxification services the year after the SIF opened. [odds ratio: 1.32 (95% CI, 1.11,1.58); P = 0.002]. In turn, detoxification was associated independently with elevated rates of methadone initiation [relative hazard = 1.56 (95% CI, 1.04,2.34); P = 0.031] and elevated initiation of other addiction treatment [relative hazard = 3.73 (95% CI, 2.57,5.39); P < 0.001]. Use of the SIF declined when the rate of SIF use in the month before enrolment into detoxification was compared to the rate of SIF use in the month after discharge (24 visits versus 19 visits; P = 0.002). Conclusions The SIF's opening was associated independently with a 30% increase in detoxification service use, and this behaviour was associated with increased rates of long-term addiction treatment initiation and reduced injecting at the SIF. [source]

Quality of life in 1000 patients with early relapsing,remitting multiple sclerosis

N. Putzki
Background and purpose:, To examine the quality of life (QoL) in a large cohort of untreated patients with relapsing,remitting multiple sclerosis (RRMS) and to investigate the impact of intramuscular (IM) interferon beta-1a (IFNß-1a) treatment. Methods:, Prospective, observational, open-label, multicentre study conducted in Germany. Untreated patients with RRMS who initiated treatment with IM IFNß-1a were included and followed for 12 months. QoL was measured using the EQ-5D questionnaire. Clinical response was assessed by relapse rate and disability (Expanded Disability Status Scale; EDSS). Results:, A total of 1157 patients were included [mean age 37.6 years, median disease duration 13 months, mean relapse rate 1.7 (95%CI: 1.58,1.73), median EDSS score 2.0]. Relapse rate was reduced to 0.6 at 12 months (95%CI: 0.51,0.69, P < 0.0001). EDSS did not change significantly. At baseline, QoL was considerably lower in MS patients compared with the general German population, but was improved after treatment initiation [utilities of EQ-5D: 0.77 (95%CI: 0.75,0.78) vs. 0.75 (95%CI: 0.74,0.76) at baseline, 95%CI for difference: 0.01,0.03, P = 0.0046]. Higher disease activity and inability to work were negative predictors of QoL. 14.7% of patients were incapable of working for MS-related reasons. Conclusions:, Quality of life is considerably impaired in early stages of MS. Treatment initiation with IM IFNß attenuates MS disease activity and improves QoL. Inability to work early during the disease is a major challenge for the social security systems. [source]

A longitudinal observational study of a cohort of patients with relapsing,remitting multiple sclerosis treated with glatiramer acetate

M. Debouverie
Immunomodulatory treatments for relapsing,remitting multiple sclerosis (RRMS) are not efficacious or tolerated in all patients. It is important to evaluate alternative classes of treatment in patients failing first-line therapy. The objective of this prospective observational study was to evaluate the efficacy and safety of glatiramer acetate in patients, to whom , -interferons could not be administered. The study included patients with RRMS who were intolerant to or had contraindications to , -interferon. After initiation of glatiramer acetate treatment, follow-up visits were made every 3 months, when data on neurologist-ascertained relapses and disability [Expanded Disability Status Scale (EDSS) score] were collected. Tolerability was evaluated by spontaneous adverse event reporting. Overall, 205 patients were studied and 113 (55.1%) treated for at least 4 years. The proportion of patients presenting over three relapses per year decreased from 51.2% to 8.4% in the 2 years following treatment initiation. Over 5 years of treatment, mean annualized relapse rates and mean EDSS scores remained stable (0.4,0.6 relapses/year and 3.6 ± 1.8,3.3 ± 2.1 respectively). Adverse events were reported by 179 patients, leading to discontinuation of treatment in 10 patients. Patients with RRMS to whom , -interferons cannot be prescribed can benefit from treatment with glatiramer acetate. [source]

The value of early treatment in patients with haemophilia and inhibitors

HAEMOPHILIA, Issue 3 2010
Summary., Development of inhibitors to infused factor concentrates represents a major clinical and economic challenge in the treatment of haemophilic patients. It has been shown that a delay in initiation of treatment leads to requirement of a larger number of injections to stop the bleeding but this has never been formally linked to costs associated with the bleeding. The objectives of this study were to assess the relationship between time to initiation of NovoSeven® and total costs, number of doses administered and time to bleeding resolution in mild to moderate bleeding episodes. Data on time to treatment initiation, time to bleeding resolution and on all resource use related to the bleeding were extracted from medical records in Turkey for 129 bleeding episodes. Regression analysis was used to assess the impact of time to treatment on outcomes. Longer time to treatment initiation increased both total costs associated with the bleeding, the number of doses needed and the time to bleeding resolution. Treatment in hospital was associated with significantly longer time to treatment, higher costs and longer time to bleeding resolution as compared with home treatment or outpatient treatment. When controlling for other bleeding characteristics, the cost of bleedings treated in hospital was more than 150% higher. This study shows that treatment with NovoSeven® should be initiated as soon as possible after the onset of bleeding in order to minimize costs and optimize outcomes. Home treatment reduces time to treatment initiation and also reduces costs related to the bleeding. [source]

An Incenter Nocturnal Hemodialysis Program,Three Years Experience

M. Gene Radford
We report our experience with a program of long, slow, overnight hemodialysis (HD) performed 3 times a week in an existing dialysis facility. Beginning in April 1999, 14 chairs in one bay of our facility were replaced with beds, subdued lighting was installed, and machine alarms were decreased to minimum volume. Fresenius F60 dialyzers were selected with a QB of 220,300 ml/min and a QD of 400,500 ml/min. Patients dialyze for 7,8 hrs overnight. Staffing is with 1 nurse and 1 PCT for 10 patients. Standard dialysate is used, and heparin is dosed 100 U/kg at treatment initiation and again at mid-treatment. All access types are utilized. The program is open to all patients in our area. A total of 65 patients have participated, with a current census of 20 patients. Participants have tried nocturnal dialysis for a variety of reasons including work/school schedules, excessive interdialytic weight gains, inadequate dialysis (due to poor access function or large body mass), and hemodynamic instability with standard daytime HD. Blood pressure control has improved among the participants in the program, perhaps due to more gentle ultrafiltration and improvement in maintenance of dry weight. Among 31 patients who remained on nocturnal dialysis for over 6 months, 21 started the program on an average of 2.5 antihypertensive agents (AHA). After 6 months, 9 patients no longer needed AHA while 12 patients remain on an average of 1.3 AHA. URR also improved by an average of 4.35 among 13 patients who transferred from standard incenter HD to the nocturnal program. In all, 45 patients have left the program, for reasons which include insomnia/social (15), death (9), transfer to home HD (8), renal transplantation (6), noncompliance (3), moved away (2), and other (2). In conclusion, long overnight HD can be performed in an existing dialysis facility, providing patients with another HD option. Patients who may benefit from this modality include those with daytime jobs, patients with inadequate clearance on standard HD, patients with excessive interdialytic weight gains, and those who poorly tolerate standard HD. [source]

Potential role for Interleukin-28B genotype in treatment decision-making in recent hepatitis C virus infection,

HEPATOLOGY, Issue 4 2010
Jason Grebely
Polymorphisms in the IL28B (interleukin-28B) gene region are important in predicting outcome following therapy for chronic hepatitis C virus (HCV) infection. We evaluated the role of IL28B in spontaneous and treatment-induced clearance following recent HCV infection. The Australian Trial in Acute Hepatitis C (ATAHC) was a study of the natural history and treatment of recent HCV, as defined by positive anti-HCV antibody, preceded by either acute clinical HCV infection within the prior 12 months or seroconversion within the prior 24 months. Factors associated with spontaneous and treatment-induced HCV clearance, including variations in IL28B, were assessed. Among 163 participants, 132 were untreated (n = 52) or had persistent infection (infection duration ,26 weeks) at treatment initiation (n = 80). Spontaneous clearance was observed in 23% (30 of 132 participants). In Cox proportional hazards analysis (without IL28B), HCV seroconversion illness with jaundice was the only factor predicting spontaneous clearance (adjusted hazards ratio = 2.86; 95% confidence interval = 1.24, 6.59; P = 0.014). Among participants with IL28B genotyping (n = 102 of 163 overall and 79 of 132 for the spontaneous clearance population), rs8099917 TT homozygosity (versus GT/GG) was the only factor independently predicting time to spontaneous clearance (adjusted hazard ratio = 3.78; 95% confidence interval = 1.04, 13.76; P = 0.044). Participants with seroconversion illness with jaundice were more frequently rs8099917 TT homozygotes than other (GG/GT) genotypes (32% versus 5%, P = 0.047). Among participants adherent to treatment and who had IL28B genotyping (n = 54), sustained virologic response was similar among TT homozygotes (18 of 29 participants, 62%) and those with GG/GT genotype (16 of 25, 64%, P = 0.884). Conclusion: During recent HCV infection, genetic variations in IL28B region were associated with spontaneous but not treatment-induced clearance. Early therapeutic intervention could be recommended for individuals with unfavorable IL28B genotypes. (HEPATOLOGY 2010;) [source]

Head-to-head comparison of risedronate vs. teriparatide on bone turnover markers in women with postmenopausal osteoporosis: a randomised trial

A. D. Anastasilakis
Summary Aims:, We aimed to compare the effect of risedronate (RIS) and teriparatide (TPTD) (recombinant human parathyroid hormone 1,34) on bone turnover markers in women with postmenopausal osteoporosis. Methods:, Forty-four Caucasian women (age 65.1 ± 1.6 years) with postmenopausal osteoporosis were randomly assigned to receive either RIS 35 mg once weekly (n = 22) or TPTD 20 ,g once daily (n = 22) for 12 months. Serum N-terminal propeptide of type 1 collagen (P1NP), C-terminal telopeptide of type 1 collagen (CTx), total alkaline phosphatase (ALP) and intact parathyroid hormone (iPTH) were obtained from all women before, 3 and 6 months after treatment initiation. Lumbar spine bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry before and 12 months after treatment initiation. Results:, P1NP, CTx and total ALP levels decreased in RIS group (p < 0.001) and increased in TPTD group (p < 0.001) throughout the treatment. iPTH increased significantly in RIS group (p < 0.05) and decreased in TPTD group (p < 0.001). Finally, lumbar spine BMD increased significantly in both RIS (p = 0.003) and TPTD groups (p < 0.001) without significant differences between them. Conclusions:, Our data suggest that both serum P1NP and CTx are reliable markers of RIS and TPTD action in women with postmenopausal osteoporosis. In a similar way, serum total ALP can be used as an alternative marker for monitoring both RIS and TPTD action, while iPTH can be used only for TPTD-treated women. The increase in P1NP and CTx after 3 months of treatment with RIS or TPTD can predict the increase in BMD after 12 months of treatment. [source]

A double blind, randomized clinical trial assessing the efficacy and safety of augmenting standard antidepressant therapy with nimodipine in the treatment of ,vascular depression'

Fernando E. Taragano
Abstract Background ,Vascular depression' may be caused by cerebrovascular disease. Calcium channel blockers, which are putative treatments for cerebrovascular disease, might be expected to improve depression reduction and to prevent recurrence of depression in this patient population. This clinical trial was designed to test these hypotheses. Design This was a controlled, double blind, randomized clinical trial in which 84 patients with vascular depression (Alexopoulos criteria) were treated with antidepressants at standard doses. Patients were also randomized to nimodipine (n,=,40) or an inactive comparator, vitamin C (n,=,44). Treatment outcomes were assessed using the Hamilton depression rating scale (HDRS) regularly up to 300 days after treatment initiation. Results As expected, depression reduction was successful in most patients. In addition, those treated with nimodipine plus an antidepressant had greater improvements in depression overall in repeated measures ANCOVA (F(1,81),=,8.64, p,=,0.004). As well a greater proportion of nimodipine-treated participants (45 versus 25%) exhibited a full remission (HDRS,,10) (,2(df, 1),=,3.71, p,=,0.054). Among those experiencing a substantial response in the first 60 days (50% reduction in HDRS), fewer patients on nimodipine (7.4%) had a recurrence of major depression when compared to those on antidepressant alone (32%) (,2(df, 1),=,3.59, p,=,0.058). Conclusions In treating vascular depression, augmentation of antidepressant therapy with a calcium-channel blocker leads to greater depression reduction and lower rates of recurrence. These findings support the argument that cerebrovascular disease is involved in the pathogenesis and recurrence of depression in these patients. Copyright © 2001 John Wiley & Sons, Ltd. [source]

Intravenous dexamethasone-cyclophosphamide pulse therapy in comparison with oral methylprednisolone-azathioprine therapy in patients with pemphigus: Results of a multicenter prospectively randomized study

Intravenöse Dexamethason-Cyclophosphamid-Pulstherapie im Vergleich zu einer oralen Methylprednisolon-Azathioprin-Therapie bei Patienten mit Pemphigus-Erkrankungen: Ergebnisse einer multizentrischen, prospektiven, randomisierten Studie
Azathioprin; Cyclophosphamid; Pemphigus; Pulstherapie Summary Background: Pemphigus is a potentially life-threatening autoimmune blistering skin disease usually treated with high-dose corticosteroids in combination with immunosuppressive drugs. In a multicenter, prospectively randomized study we compared efficacy and side effects of a dexamethasone-cyclophosphamide (D/C) pulse therapy with a methylprednisolone-azathioprine (M/A) therapy in 22,patients with newly diagnosed pemphigus vulgaris and pemphigus foliaceus. Patients and methods: The 11,patients of the M/A group were treated with daily doses of methylprednisolone (initially 2,mg/kg body weight) and azathioprine (2,,,2,5,mg/kg body weight) which were subsequently tapered. D/C pulse therapy in 11,patients consisted of intravenous administration of 100,mg dexamethasone/d on 3 consecutive days along with cyclophosphamide (500,mg) on day one. Pulses were initially repeated every 2,,,4 weeks and then at increasing intervals. In between the pulses, oral cyclophosphamide (50,mg) was given daily for 6,months. Results: Within 24,months after treatment initiation, 5/11,patients of the D/C group had a remission (complete remissions after discontinuation of therapy in 3,patients) and 6/11,patients had a progression. In the M/A group, there were remissions in 9/11,patients (complete remissions after discontinuation of therapy in 3,patients) and progression in 1/11,patients. There were more relapses in M/A therapy after remission than in D/C therapy. Side effects were more common in the M/A group. These differences were not significant (p > 0,05). Conclusion: Because of the high number of progressions in patients treated with D/C therapy, we can not confirm the encouraging results of earlier reports about pulse D/C therapy. Nevertheless D/C therapy seemed to be better tolerated and, in case of primary efficacy, was associated with fewer recurrences than M/A therapy. Zusammenfassung Hintergrund: Pemphiguserkrankungen sind potentiell lebensbedrohliche blasenbildende Autoimmunerkrankungen, die üblicherweise mit hochdosierten Kortikosteroiden in Kombination mit Immunsuppressiva behandelt werden. In einer multizentrischen, prospektiven, randomisierten Studie verglichen wir die Wirksamkeit und Nebenwirkungen einer Dexamethason-Cyclophosphamid (D/C)-Pulstherapie mit einer Methylprednisolon-Azathioprin (M/A)-Therapie bei 22,Patienten mit neu diagnostiziertem Pemphigus vulgaris und Pemphigus foliaceus. Patienten und Methoden: 11,Patienten der M/A-Gruppe wurden kontinuierlich oral mit Methylprednisolon (initial 2,mg/kg Körpergewicht/Tag) und Azathioprin (2,,,2,5,mg/kg Körpergewicht/Tag) behandelt; die Dosen wurden schrittweise reduziert. Die Therapie bei den 11,Patienten der D/C-Gruppe erfolgte durch intravenöse Gabe von 100,mg Dexamethason/Tag an 3 aufeinander folgenden Tagen und 500,mg Cyclophosphamid am ersten Tag. Die Pulstherapie wurde zunächst alle 2,,,4 Wochen, dann in längeren Abständen wiederholt. Im Intervall wurden 50,mg Cyclophosphamid/Tag oral für 6,Monate verabreicht. Ergebnisse: Innerhalb von 24,Monaten nach Therapiebeginn kam es bei 5 von 11,Patienten der D/C-Gruppe zu einer Remission (komplette Remission nach Absetzen der Therapie bei 3,Patienten); bei 6 der 11,Patienten verlief die Erkrankung progredient. In der M/A-Gruppe kam es bei 9 von 11,Patienten zu einer Remission (komplette Remission nach Absetzen der Therapie bei 3,Patienten) und bei einem Patienten zu einer Progression. In der M/A-Gruppe traten häufiger Rezidive nach Remission auf als in der D/C-Gruppe. Therapienebenwirkungen kamen in der M/A-Gruppe häufiger vor. Diese Unterschiede waren nicht signifikant (p > 0,05). Schlußfolgerungen: Aufgrund der hohen Anzahl von Progressionen bei Patienten der D/C-Gruppe können wir die positiven Ergebnisse früherer Berichte über die D/C-Pulstherapie nicht bestätigen. Dennoch scheint die D/C-Therapie, beim einzelnen Patienten einmal erfolgreich, seltener zu Rezidiven zu führen und möglicherweise auch besser verträglich zu sein als die M/A-Therapie. [source]

Periodontal therapy alters gene expression of peripheral blood monocytes

Panos N. Papapanou
Abstract Aims: We investigated the effects of periodontal therapy on gene expression of peripheral blood monocytes. Methods: Fifteen patients with periodontitis gave blood samples at four time points: 1 week before periodontal treatment (#1), at treatment initiation (baseline, #2), 6-week (#3) and 10-week post-baseline (#4). At baseline and 10 weeks, periodontal status was recorded and subgingival plaque samples were obtained. Periodontal therapy (periodontal surgery and extractions without adjunctive antibiotics) was completed within 6 weeks. At each time point, serum concentrations of 19 biomarkers were determined. Peripheral blood monocytes were purified, RNA was extracted, reverse-transcribed, labelled and hybridized with AffymetrixU133Plus2.0 chips. Expression profiles were analysed using linear random-effects models. Further analysis of gene ontology terms summarized the expression patterns into biologically relevant categories. Differential expression of selected genes was confirmed by real-time reverse transcriptase-polymerase chain reaction in a subset of patients. Results: Treatment resulted in a substantial improvement in clinical periodontal status and reduction in the levels of several periodontal pathogens. Expression profiling over time revealed more than 11,000 probe sets differentially expressed at a false discovery rate of <0.05. Approximately 1/3 of the patients showed substantial changes in expression in genes relevant to innate immunity, apoptosis and cell signalling. Conclusions: The data suggest that periodontal therapy may alter monocytic gene expression in a manner consistent with a systemic anti-inflammatory effect. [source]

Serum concentrations of ribavirin and pegylated interferon and viral responses in patients infected with HIV and HCV

Florence Nicot
Abstract The hepatitis C virus (HCV) infects a substantial proportion of patients infected with human immunodeficiency virus (HIV). Patients infected with both HCV and HIV respond poorly to anti-HCV treatment with pegylated interferon alpha and ribavirin. But few data are available on the influence of ribavirin and interferon concentrations on treatment outcome for these patients. This study investigated the relationship between the serum pegylated interferon and ribavirin concentrations 3 and 6 months after treatment initiation, and treatment outcome in 35 HCV-HIV coinfected patients. The pegylated interferon and ribavirin concentrations at months 3 and 6 were similar. The pegylated interferon concentrations at 3 months in responders and nonresponders were similar. However, responders tended to have higher ribavirin concentrations (2,322 ng/ml) than nonresponders (1,833 ng/ml; P,=,0.08). Responders infected with HCV genotype 1 or 4 had higher ribavirin concentrations (2,672 ng/ml) than did similarly infected nonresponders (1,758 ng/ml; P,=,0.04). ROC curve analysis showed that a ribavirin concentration of 2,300 ng/ml was the best threshold for predicting a nonresponse (ROC area,=,0.80,±,0.12). Thus ribavirin concentrations influence treatment outcome in HIV patients infected with HCV genotype 1 or 4. Monitoring ribavirin concentrations could help adapt ribavirin concentrations and improve the sustained virological response. J. Med. Virol. 80:1523,1529, 2008. © 2008 Wiley-Liss, Inc. [source]

Excess nickel,induced changes in antioxidative processes in maize leaves

Praveen Kumar
Abstract Maize (Zea mays L. cv. 777) plants grown in hydroponic culture were treated with 100 µM NiSO4 (moderate nickel (Ni) excess). In addition to growth parameters, metabolic parameters representative of antioxidant responses in leaves were assessed 24 h and 3, 7, and 14 d after initiating the Ni treatment. Extent of oxidative damage was measured as accumulation of malondialdehyde and hydrogen peroxide in leaves 7 and 14 d after treatment initiation. Apart from increasing membrane-lipid peroxidation and H2O2 accumulation, excess supply of Ni suppressed plant growth and dry mass of shoots but increased dry mass of roots and decreased the concentrations of chloroplastic pigments. Excess supply of Ni, though inhibited the catalase (EC activity, increased peroxidase (EC, ascorbate peroxidase (EC, and superoxide dismutase (EC activities. Localization of isoforms of these enzymes (peroxidase, ascorbate peroxidase, and superoxide dismutase) on native gels also revealed increases in the intensities of pre-existing bands. Enhanced activities of peroxidase, ascorbate peroxidase, and superoxide dismutase, however, did not appear to be sufficient to ameliorate the effects of excessively generated reactive oxygen species due to excess supply of Ni. [source]

Long-Term Posttreatment Functioning Among Those Treated for Alcohol Use Disorders

ALCOHOLISM, Issue 2 2006
Patrick R. Clifford
This article summarizes the proceedings of a symposium that was organized and chaired by Patrick R. Clifford and presented at the 2005 Research Society on Alcoholism meeting in Santa Barbara, California. The aims of the presentation were to focus on the prediction and explanation of longer-term functioning following alcohol use disorders (AUD) treatment. Along these lines, Stephen A. Maisto, PhD, presented data (i.e., Project MATCH outpatient sample) on the relationship between drinking behavior in the first year following AUD outpatient treatment initiation and functioning at 3-year follow-up. Robert L. Stout, PhD, using data from the Extended Case Monitoring Study, analyzed long-term drinking patterns using shorter-term information. James R. McKay, PhD, examined the relationship between treatment services received and problem severities across a 2-year follow-up period. J. Scott Tonigan, PhD, served as the panel discussant. [source]

Occult hepatitis B virus infection in patients with autoimmune liver diseases

Sarah P. Georgiadou
Abstract Background: Occult hepatitis B virus (HBV) infection is characterized by undetectable serum HBV surface antigen (HBsAg) but detectable HBV-DNA in serum or liver. Aims: To determine the prevalence and clinical impact of occult HBV in autoimmune liver diseases as similar data are missing. Methods: One hundred and ninety-six sera samples from HBsAg-negative patients, including 66 autoimmune hepatitis (AIH), 93 primary biliary cirrhosis (PBC) and 37 primary sclerosing cholangitis (PSC), were investigated for HBV-DNA using the polymerase chain reaction (PCR) before treatment initiation. One hundred and three serial samples from 38 AIH patients under immunosuppression and 282 selected blood donors (HBsAg negative; antibodies to HBV-core antigen positive) were also investigated. Fourteen available paraffin-embedded AIH liver samples were also investigated for HBV-DNA by nested-PCR. Results: Hepatitis B virus DNA was detected in the serum of 24/196 patients (12.2%) and 0/282 donors (P=0.0000). Nine patients had AIH (13.6%), eight had PBC (8.6%) and seven had PSC (18.9%) (P=0.0000 vs healthy). HBV-DNA detection in AIH livers was higher than in serum. HBV-DNA was associated neither with HBV markers nor with epidemiological, laboratory and clinical data. Serial testing of AIH patients revealed two HBV-DNA-negative patients before treatment becoming positive during treatment, while all HBV-DNA-positive patients before immunosuppression became negative. Conclusion: Based mainly on serum HBV-DNA, we found a significant proportion of autoimmune liver disease patients with occult HBV compared with donors. However, taking into account our results in a small number of liver tissues, it should be emphasized that occult HBV could be even higher when both serum and liver specimens are investigated. Occult HBV does not seem to affect the clinical and laboratory features of the diseases, while AIH patients with occult HBV under immunosuppression do not deteriorate during follow-up. [source]

Treatment of dermatophyte onychomycosis with three pulses of terbinafine (500 mg day,1 for a week)

MYCOSES, Issue 1 2009
Y. Takahata
Summary We assessed the safety and efficacy of pulse therapy with terbinafine tablets in 55 patients with dermatophytic onychomycosis. One pulse consisted of oral terbinafine tablets (500 mg day,1) given for 1 week usually followed by a 3-week interval. This regimen was repeated twice. Topical 1% terbinafine cream was applied daily. Efficacy was assessed based on both clinical and mycological examinations 1 year after treatment initiation. We observed a complete cure in 41 patients (74.5%), marked improved in three patients (5.6%), slight improvement in three patients (5.6%) and drop out in six patients (10.7%). Two patients (3.6%) discontinued terbinafine because of gastrointestinal disturbance (one patient) and drug-induced eruption (one patient). No patient had abnormal laboratory findings, including liver function tests. In summary, a regimen of three pulses of terbinafine therapy given daily for 1 week in combination with topical application of terbinafine cream appears to be safe and effective in treating dermatophytic onychomycosis and offers advantages in convenience and cost-effectiveness compared with continuous dosing. [source]

Defining Patient-Centered, Multidimensional Success Criteria for Treatment of Chronic Spine Pain

PAIN MEDICINE, Issue 7 2008
Jennifer L. Brown PhD
ABSTRACT Objective., This study aimed to define patient-determined success criteria for treatment of chronic spine pain across four domains: pain, fatigue, emotional distress, and interference with daily activities. Patients., Seventy chronic spine pain patients were recruited from university-affiliated pain clinics. Design., The study design was longitudinal, with pretreatment and post-treatment assessments. Post-treatment assessment occurred approximately 2 months after treatment initiation. Outcome Measures., Participants completed the Patient-Centered Outcomes Questionnaire and Follow-Up Patient-Centered Outcomes Questionnaire. Results., At pretreatment, patient requirements for success were a 58% reduction in pain, 61% reduction in fatigue, 64% reduction in distress, and 66% reduction in interference. These criteria, derived using a direct-scaling approach, are more stringent than criteria developed using other methods. However, patients adjusted their success criteria over time by becoming less stringent, and they used these less stringent criteria to make global judgments of treatment success. Using a scale comparison approach, success criteria for pain were a raw change of 17.5 points (0,100 numerical rating scale) and percent change of 25%. Other criteria were 7.5 (11%) for fatigue, 5.0 (13%) for distress, and 9.5 (12%) for interference. Conclusions., Future research should validate these success criteria, particularly for the less studied domains of fatigue, distress, and interference, and investigate how these criteria evolve over the course of different treatments. [source]

A Novel Gel Formulation of 0.25% Tretinoin and 1.2% Clindamycin Phosphate: Efficacy in Acne Vulgaris Patients Aged 12 to 18 Years

Lawrence F. Eichenfield M.D.
Recently, the US FDA approved the combination of 1.2% clindamycin (CLIN) and 0.025% tretinoin (RA) in a novel gel formulation for the treatment of mild to moderate acne, based on results from two 12-week, multicenter, double-blind Phase 3 trials in which patients were randomized to four treatment arms: CLIN/RA, CLIN, RA, and vehicle. The trials studied more than 4500 patients 12 years of age or older. In both trials, CLIN/RA gel produced significantly greater clinical improvements than vehicle or either monotherapy. CLIN/RA was safe and well tolerated in both trials and in a 52-week safety follow-up evaluation. The current study is a subgroup analysis that evaluates CLIN/RA's effects on acne lesion prevalence in 12- to 18-year-old patients with mild to severe baseline acne severity. CLIN/RA significantly reduced the number of inflammatory, noninflammatory, and total acne lesions after 12 weeks of treatment (p , 0.004) in 1,710 patients aged 12 to 18 years. Relatively greater improvements were seen following CLIN/RA treatment compared to CLIN or RA monotherapy, or the vehicle gel beginning as early as 2 weeks following treatment initiation. This novel CLIN/RA gel for treating acne is tolerable and safe and offers clinicians and teen aged patients a new and efficacious intervention for acne vulgaris. [Abstract amended after online publication date June 8, 2009] [source]

Determinants of prognosis of acute transverse myelitis in children

Reiko Miyazawa
Abstract Background: Acute transverse myelitis (ATM) is a severe disorder; recovery requires several months and often leaves neurologic residua. To determine what features of patients with acute transverse myelitis significantly influence prognosis, the authors reviewed reports of ATM in Japanese children published in the last 15 years (from 1987 to 2001). Methods: The authors studied reports of 50 Japanese patients (17 boys, 26 girls, 7 children of unspecified sex; mean age ± SD, 8.0 ± 3.8 years). Acute-phase and demographic features including age, increased deep tendon reflexes, Babinski reflex, sex, preceding infection, decreased deep tendon reflexes, time course of peak neurologic impairment, treatment with prednisolone and/or high-dose methylprednisolone, and the day of illness when treatment was started were used as independent variables in a regression analysis. The dependent variable was long-term persistence of neurologic deficits. Results: Younger patients and those without increased deep tendon reflexes or a Babinski reflex were more likely to have residual neurologic deficits such as paraplegia or tetraplegia, sensory loss and sphincter disturbance. No relationship was seen between prognosis and sex, preceding infections, decreased deep tendon reflexes, time course of peak neurologic impairment, treatment with prednisolone or high-dose methylprednisolone, or timing of treatment initiation. Conclusions: Age at onset and neurologic features were important for outcome prediction in ATM. Steroid therapy did not associate with better outcome. [source]

Antiepileptic drugs and risk of suicide: a nationwide study

Jonas Bjerring Olesen MB
Abstract Purpose Patients with epilepsy or psychiatric diseases have increased risk of suicide, but whether the risk is influenced by antiepileptic drug (AED) treatment is unclear. Studies have suggested that AEDs in general increase the risk of suicidal behaviour shortly after initiation. This study investigated possible differences in suicide risk associated with different AEDs. Methods The use of AEDs in the Danish population from 1997 to 2006 was determined by prescription claims. The risk of suicide associated with use of AEDs was estimated by case-crossover analyses, where each case serves at its own control during different periods. For sensitivity, the risk of suicide was estimated by a time-dependent Cox proportional-hazard analysis in AED treatment-naïve patients. Results There were 6780 cases committing suicide in the 10-year study period, of which 422 received AED treatment at the time of suicide. The case-crossover analysis estimated AED treatment initiation to increase the risk of suicide (odds ratio (OR): 1.84, 95% confidence interval (CI): 1.36,2.49). Clonazepam (OR: 2.01, CI: 1.25,3.25), valproate (OR: 2.08, CI: 1.04,4.16), lamotrigine (OR: 3.15, CI: 1.35,7.34) and phenobarbital (OR: 1.96, CI: 1.02,3.75) were associated with a significant increased risk, while the remaining examined AEDs did not significantly influence the risk. In the cohort comprising of 169,725 AED treatment-naïve patients, the Cox proportional-hazard analysis yielded similar results. Conclusions This study suggests that clonazepam, valproate, lamotrigine and phenobarbital relatively shortly after treatment initiation may increase the risk of suicide. The increased risk of suicide associated with these AEDs appears to be a consistent finding. Copyright © 2010 John Wiley & Sons, Ltd. [source]

Atypical antipsychotics in the treatment of delirium

Vaios Peritogiannis md
Delirium is common in all medical settings. Atypical antipsychotics are increasingly used for the management of delirium symptomatology but their effectiveness has not been systematically studied. The aim of the present study was therefore to provide an up-to-date review on the use of atypical antipsychotics in the treatment of delirium. A search was conducted of the databases of MEDLINE, PsycINFO and EMBASE from 1997 to 2008 for English-language articles using the key words ,delirium' and the names of all the atypical antipsychotics. A total of 23 studies were used for this review. Fifteen of the studies were single-agent trials. Four studies were comparison trials, including one double-blind trial, and four studies were retrospective, including three comparison studies. All studies reported improvement of delirium symptomatology after the administration of atypical antipsychotics. No study included a placebo group. Other limitations included sample heterogeneity, small sample size, different rating scales for delirium, and lack of adequate controls. The improvement in delirium was observed within a few days after treatment initiation and the doses given were relatively low. Atypical antipsychotics were well tolerated, but safety was not evaluated systematically. Atypical antipsychotics appear to be effective and safe in symptomatic treatment of delirium but the evidence is limited and inconclusive. There are no double-blind, placebo-controlled studies assessing the efficacy and safety of these agents in delirium. Further research is needed with well-designed studies. [source]

A phase I clinical trial of interferon-beta gene therapy for high-grade glioma: novel findings from gene expression profiling and autopsy

Toshihiko Wakabayashi
Background High-grade gliomas are highly lethal neoplasms representing approximately 20% of all intracranial tumors. Cationic liposome-mediated interferon-beta (IFN- ,) gene transfer has been found to induce regression of experimental glioma. We have previously performed a pilot clinical trial to evaluate the safety and effectiveness of this IFN- , gene therapy in five patients with high-grade glioma. Two patients showed more than 50% reduction while others had stable disease 10 weeks after treatment initiation. Methods To identify alterations in gene expression in brain tumors 2 weeks after the gene therapy trial, we used a microarray technology and Gene Ontology analysis. The results were validated by patients' clinical course and findings of histology and autopsy. Results and conclusions Using hierarchical clustering and principal component analysis, five series of gene therapy trials were classified according to the response to IFN- , gene therapy. Significant changes in gene expression related to immunoresponse and apoptosis were observed. Moreover, novel patterns of altered gene expression, such as inhibition of neovascularization, were identified, suggesting the involvement of pathways reported previously as not involved. Autopsy and histological examinations revealed dramatic changes in the tumor tissues after therapy in all patients. Many tumor cells showed necrotic changes, and immunohistochemistry identified numerous CD8-positive lymphocytes and macrophages infiltrating the tumor and surrounding tissues; these were probably the effects of therapy. Simultaneously, CD34-immunoreactive vessels were notably decreased in the vector-injected brain. This study facilitates the understanding of the antitumor mechanism and helps identify candidate target molecules for new approaches. However, additional clinical trials are warranted. Copyright © 2008 John Wiley & Sons, Ltd. [source]

Clomiphene Citrate and Testosterone Gel Replacement Therapy for Male Hypogonadism: Efficacy and Treatment Cost

Frederick Taylor MD
ABSTRACT Introduction., The efficacy of oral clomiphene citrate (CC) in the treatment of male hypogonadism and male infertility (MI) with low serum testosterone and normal gonadotropin levels has been reported. Aim., The aim of this article is to evaluate CC and testosterone gel replacement therapy (TGRT) with regard to biochemical and clinical efficacy and cost. Main Outcome Measures., The main outcome measures were change in serum testosterone with CC and TGRT therapy, and change in the androgen deficiency in aging male (ADAM) questionnaire scores with CC therapy. Methods., Men receiving CC or TGRT with either Androgel® 1% or Testim® 1% for hypogonadism (defined as testosterone < 300 ng/mL) or MI were included. Serum values were collected 1,2 months after treatment initiation and semi-annually thereafter. Retrospective data collection was performed via chart review. Subjective follow up of patients receiving CC was performed via telephone interview using the ADAM questionnaire. Results., A hundred and four men (65 CC and 39 TGRT) were identified who began CC (50 mg every other day) or TGRT (5 g). Average age (years) was 42(CC) vs. 57 (TGRT). Average follow up was 23 months (CC, range 8,40 months) vs. 46 months (TGRT, range 6,149 months). Average posttreatment testosterone was 573 ng/dL in the CC group and 553 ng/dL in the TGRT group (P value < 0.001). The monthly cost of Testim® 1% (5 gm daily) is $270, Androgel® 1% (5 gm daily) is $265, and CC (50 mg every other day) is $83. Among CC patients, the average pretreatment ADAM score was 4.9 vs. 2.1 at follow up (P < 0.05). Average pretreatment ADAM sexual function domain score was 0.76 vs. 0.23 at follow up (P < 0.05). There were no adverse events reported. Conclusion., CC represents a treatment option for men with hypogonadism, demonstrating biochemical and clinical efficacy with few side effects and lower cost as compared with TGRT. Taylor F, and Levine L. Clomiphene citrate and testosterone gel replacement therapy for male hypogonadism: Efficacy and treatment cost. J Sex Med 2010;7:269,276. [source]

Real-life impact of early interferon, therapy in relapsing multiple sclerosis,

M. Trojano MD
Objective Recent findings support greater efficacy of early vs. delayed interferon beta (IFN,) treatment in patients with a first clinical event suggestive of multiple sclerosis (MS). We aimed to evaluate the effectiveness of early IFN, treatment in definite relapsing-remitting MS (RRMS) and to assess the optimal time to initiate IFN, treatment with regard to the greatest benefits on disability progression. Methods A cohort of 2,570 IFN,-treated RRMS patients was prospectively followed for up to 7 years in 15 Italian MS Centers. A Cox proportional hazards regression model adjusted for propensity score (PS) quintiles was used to assess differences between groups of patients with early vs. delayed IFN, treatment on risk of reaching a 1-point progression in the Expanded Disability Status Scale (EDSS) score, and the EDSS 4.0 and 6.0 milestones. A set of PS-adjusted Cox hazards regression models were calculated according to different times of treatment initiation (within 1 year up to within 5 years from disease onset). A sensitivity analysis was performed to assess the robustness of findings. Results The lowest hazard ratios (HRs) for the three PS quintiles,adjusted models were obtained by a cutoff of treatment initiation within 1 year from disease onset. Early treatment significantly reduced the risk of reaching a 1-point progression in EDSS score (HR = 0.63; 95% CI = 0.48,0.85; p < 0.002), and the EDSS 4.0 milestone (HR = 0.56; 95% CI = 0.36,0.90; p = 0.015). Sensitivity analysis showed the bound of significance for unmeasured confounders. Interpretation Greater benefits on disability progression may be obtained by an early IFN, treatment in RRMS. Ann Neurol 2009;66:513,520 [source]

Sustained improvement of spinal muscular atrophy mice treated with trichostatin a plus nutrition

Heather L. Narver VMD
Early treatment with the histone deacetylase inhibitor, trichostatin A, plus nutritional support extended median survival of spinal muscular atrophy mice by 170%. Treated mice continued to gain weight, maintained stable motor function, and retained intact neuromuscular junctions long after trichostatin A was discontinued. In many cases, ultimate decline of mice appeared to result from vascular necrosis, raising the possibility that vascular dysfunction is part of the clinical spectrum of severe spinal muscular atrophy. Early spinal muscular atrophy disease detection and treatment initiation combined with aggressive ancillary care may be integral to the optimization of histone deacetylase inhibitor treatment in human patients. Ann Neurol 2008; 64:465,470 [source]

Long-term efficacy of the interleukin-1 receptor antagonist anakinra in ten patients with neonatal-onset multisystem inflammatory disease/chronic infantile neurologic, cutaneous, articular syndrome

Bénédicte Neven
Objective Cryopyrin-associated periodic syndromes (CAPS) are a group of rare autoinflammatory diseases. Neonatal-onset multisystem inflammatory disease (NOMID)/chronic infantile neurologic, cutaneous, articular syndrome (CINCA syndrome) is the most severe phenotype, with fever, rash, articular manifestations, and neurologic and neurosensory involvement. CAPS are caused by mutations in CIAS1, the gene encoding NLRP3, which plays a critical role in interleukin-1 (IL-1) processing. Anakinra, an IL-1 receptor antagonist, has been shown to be an effective treatment; however, data on long-term efficacy and safety have been sparse. This study was undertaken to assess the long-term efficacy and safety of anakinra treatment in patients with NOMID/CINCA syndrome. Methods We retrospectively analyzed the medical records of NOMID/CINCA syndrome patients referred to 2 centers, who had started anakinra treatment before June 2007. Results There were 10 patients with NOMID/CINCA syndrome who had been treated with anakinra. The patients' ages at the time anakinra treatment was initiated ranged from 3 months to 20 years. They had been followed up for 26,42 months. Sustained efficacy in the treatment of systemic inflammation and, in some cases, neurologic involvement and growth parameters, was achieved. The dosage of anakinra required for efficacy ranged from 1 to 3 mg/kg/day in the 8 oldest patients and from 6 to 10 mg/kg/day in the 2 youngest. Residual central nervous system inflammation and deafness persisted in some patients, especially if there had been a delay in diagnosis and treatment. Secondary amyloidosis persisted in cases in which it was present at treatment initiation, but no new lesions developed. No effect on overgrowth arthropathy was observed. Adverse events consisted of mild injection-site reactions. Conclusion The present results indicate that anakinra treatment is effective over the long term in NOMID/CINCA syndrome. However, treatment has to be initiated before irreversible lesions develop, and, particularly in very young patients, dosage adjustment is required. [source]