Early Course Of Treatment Research Articles

Treatment decision making based on the published natural history and growth rate of small meningiomas

Definitive data allowing clinicians to predict which meningioma patients will fail to respond to conservative management are lacking. To address this need, the authors systematically reviewed the published literature regarding the natural history of small, untreated meningiomas. The authors performed a systematic review of the existing literature on untreated meningiomas that were followed with serial MR imaging. They summarize the published linear rates of tumor growth, and the risk factors for development of new or worsened symptoms during follow-up by using a stratified chi-square test. The search methods identified 22 published studies reporting on 675 patients with untreated meningiomas followed by serial MR imaging. Linear growth rates varied significantly: no growth was the most common rate, although reports of more aggressive tumors noted growth rates of up to a 93% linear increase in size per year. The authors found that few patients with initial tumor diameters < 2 cm went on to develop new or worsened symptoms over a median follow-up period of 4.6 years. Patients with initial tumor diameters of 2-2.5 cm demonstrated a marked difference in the rate of symptom progression if their tumors grew > 10% per year, compared with those tumors growing ≤ 10% per year (42% vs 0%; p < 0.001, chi-square test). Patients with tumors between > 2.5 and 3 cm in initial size went on to develop new or worsened symptoms 17% of the time. This systematic review of the literature regarding the clinical behavior of untreated meningiomas suggests that most meningiomas ≤ 2.5 cm in diameter do not proceed to cause symptoms in the approximately 5-year period following their discovery. Those that do cause symptoms can usually be predicted with close radiographic follow-up. Based on these findings, the authors suggest the importance of observation in the early course of treatment for small asymptomatic meningiomas, especially those with an initial diameter < 2 cm.

Bifrontal, bitemporal and right unilateral electrode placement in ECT: randomised trial.

Electroconvulsive therapy (ECT) is an effective treatment for major depression. Optimising efficacy and minimising cognitive impairment are goals of ongoing technical refinements. To compare the efficacy and cognitive effects of a novel electrode placement, bifrontal, with two standard electrode placements, bitemporal and right unilateral in ECT. This multicentre randomised, double-blind, controlled trial (NCT00069407) was carried out from 2001 to 2006. A total of 230 individuals with major depression, bipolar and unipolar, were randomly assigned to one of three electrode placements during a course of ECT: bifrontal at one and a half times seizure threshold, bitemporal at one and a half times seizure threshold and right unilateral at six times seizure threshold. All three electrode placements resulted in both clinically and statistically significant antidepressant outcomes. Remission rates were 55% (95% CI 43-66%) with right unilateral, 61% with bifrontal (95% CI 50-71%) and 64% (95% CI 53-75%) with bitemporal. Bitemporal resulted in a more rapid decline in symptom ratings over the early course of treatment. Cognitive data revealed few differences between the electrode placements on a variety of neuropsychological instruments. Each electrode placement is a very effective antidepressant treatment when given with appropriate electrical dosing. Bitemporal leads to more rapid symptom reduction and should be considered the preferred placement for urgent clinical situations. The cognitive profile of bifrontal is not substantially different from that of bitemporal.

P01-92 - Early changes are associated with late changes of BDNF serum levels in inpatients with major depression during short-term antidepressant treatment

ObjectivesMean BDNF serum concentration is lower in patients with major depression (MD) as compared to healthy controls. BDNF increases during the course of antidepressant treatment. This increase has been associated with symptom amelioration. The aim of this study was to analyse the relation between early and late BDNF changes during antidepressant treatment.MethodsForty-six patients with MD according to DSM-IV were included for this study. Patients were treated as clinically indicated. Depression severity was assessed by HAMD-17 by trained raters from baseline to week 6 in weekly intervals. Serum at each visit (baseline, V1-V6) was obtained from whole blood after centrifugation with 1.000 × g for 15 minutes. Aliquots were frozen at −80°C until analysis. BDNF serum concentration was determined with ELISA (R&amp;D Systems). We analysed correlations between early changes of BDNF level (baseline to weeks 1 and 2) with BDNF changes in the later course of treatment (change from baseline to weeks 4, 5 and 6). Further, the association between early and late BDNF changes was calculated by means of linear regression analysis.ResultsThere was a high correlation between BDNF changes in the early course of treatment and final BDNF changes (p&lt; 0.05 for each analysis). Early BDNF changes accounted for a high percentage of the variance of late BDNF changes (p&lt; 0.05 for each analysis).ConclusionsThese results suggest that an early change of BDNF serum level is predictive for BDNF change in the later course of antidepressant treatment in patients with Major Depression.

Early response as predictor of final remission in elderly depressed patients

Several studies have attempted to predict the final response or remission based on improvement during the early course of treatment of major depression. There is however a great variation in cut offs used to define early response and in the optimal week to predict final results. To compare different cut offs at different time points early in the treatment of elderly depressed patients. A 12 week randomised, controlled trial in 81 elderly inpatients with DSM-IV major depression comparing venlafaxine with nortriptyline. At least 20, 25, 30 or 50% improvement was analysed after 1, 3 and 5 weeks using the Hamilton Depression Rating Scale and the Montgomery Asberg Depression Rating Scale. We plotted sensitivity against 1-specificity and calculated areas under the curve (AUCs). The highest percentage of correctly classified patients is found using at least 50% decrease as cut off in week 5, with acceptable sensitivity (81.8%) and specificity (87.4%). In week 5, the AUCs were 0.891 (95% CI 0.798-0.984) and 0.866 (95% CI 0.789-0.983) for the HAM-D and MADRS, respectively. Combining the results from our study and the other studies addressing this issue, we suggest that the treatment should be changed in the elderly if after 3-4 weeks less than 30% improvement in depression score has been achieved.

Early improvement is a predictor of treatment outcome in patients with mild major, minor or subsyndromal depression

Background There is substantial evidence that early improvement (EI) under antidepressant treatment is a clinically useful predictor of later treatment outcome in patients with major depressive disorders. The aim of this study was to test whether EI can also be used as a predictor for treatment outcome in patients with mild major, minor or subsyndromal depression, i.e. patients, who are typically treated by general practitioners. Methods Analyses were carried out using data from 223 patients of a 10-weeks randomized, placebo-controlled trial comparing the effectiveness of sertraline and cognitive-behavioural therapy (CBT) in patients with mild major, minor or subsyndromal depression. EI was defined as a reduction of ≥ 20% on the 17-item Hamilton Rating Scale for Depression (HAMD-17) compared with baseline within the first 2 weeks of treatment. The predictive value of EI for stable response at week 8 and 10 (≥ 50% HAMD-17 sum score reduction at weeks 8 and 10) and stable remission (HAMD-17 sum score ≤ 7 at weeks 8 and 10) was evaluated. Results In both the sertraline- and CBT-treatment group, EI was a highly sensitive predictor for later stable response (76% and 82%, respectively) and stable remission (70% and 75%, respectively). In patients without EI, only a small proportion of sertraline or CBT-treated patients achieved stable response (20.9% and 5.9%, respectively) or stable remission (18.6% and 8.8%, respectively). Patients with EI were by far more likely to achieve stable response or stable remission than patients without as indicated by high odds ratios (95% confidence interval) of 8.1 (3.0–21.8) and 3.8 (1.4–10.1) for sertraline, and 11.1 (2.1–58.4) and 7.2 (1.7–30.8) for CBT-treated patients, respectively. Limitations Sample sizes were relatively low in different treatment groups. Conclusion The identification of early improvement might be useful in clinical decision making in the early course of treatment of patients with mild major, minor and subthreshold depression.

Sorafenib投与後早期に代謝性脳症を併発し死亡した進行肝細胞癌の1例

Sorafenib投与後早期に代謝性脳症を併発し死亡した進行肝細胞癌の1例

Orthodontic treatment for prominent upper front teeth in children

Background: Prominent upper front teeth are an important and potentially harmful type of orthodontic problem. This condition develops when the childs permanent teeth erupt and children are often referred to an orthodontist for treatment with dental braces to reduce the prominence of the teeth. If a child is referred at a young age, the orthodontist is faced with the dilemma of whether to treat the patient early or to wait until the child is older and provide treatment in early adolescence. When treatment is provided during adolescence the orthodontist may provide treatment with various orthodontic braces, but there is currently little evidence of the relative effectiveness of the different braces that can be used. Objectives: To assess the effectiveness of orthodontic treatment for prominent upper front teeth, when this treatment is provided when the child is 7 to 9 years old or when they are in early adolescence or with different dental braces or both. Search strategy: The Cochrane Oral Health Groups Trials Register, CENTRAL, MEDLINE and EMBASE were searched. The handsearching of the key international orthodontic journals was updated to December 2006. There were no restrictions in respect to language or status of publication. Date of most recent searches: February 2007. * design - randomized and controlled clinical trials; * participants - children or adolescents (age < 16 years) or both receiving orthodontic treatment to correct prominent upper front teeth; * interventions - active: any orthodontic brace or head-brace, control: no or delayed treatment or another active intervention; * primary outcomes - prominence of the upper front teeth, relationship between upper and lower jaws; * secondary outcomes: self esteem, any injury to the upper front teeth, jaw joint problems, patient satisfaction, number of attendances required to complete treatment. Data collection and analysis: Information regarding methods, participants, interventions, outcome measures and results were extracted independently and in duplicate by two review authors. The Cochrane Oral Health Groups statistical guidelines were followed and mean differences were calculated using random-effects models. Potential sources of heterogeneity were examined. Main results: The search strategy identified 185 titles and abstracts. From this we obtained 105 full reports for the review. Eight trials, based on data from 592 patients who presented with Class II Division 1 malocclusion, were included in the review. Early treatment comparisons: Three trials, involving 432 participants, compared early treatment with a functional appliance with no treatment. There was a significant difference in final overjet of the treatment group compared with the control group of ?4.04 mm (95% CI ?7.47 to ?0.6, chi squared 117.02, 2 df, P < 0.00001, I2 = 98.3%). There was a significant difference in ANB (?1.35 mm; 95% CI ?2.57 to ?0.14, chi squared 9.17, 2 df, P = 0.01, I2 = 78.2%) and change in ANB (?0.55; 95% CI ?0.92 to ?0.18, chi squared 5.71, 1 df, P = 0.06, I2 = 65.0%) between the treatment and control groups. The comparison of the effect of treatment with headgear versus untreated control revealed that there was a small but significant effect of headgear treatment on overjet of ?1.07 (95% CI ?1.63 to ?0.51, chi squared 0.05, 1 df, P = 0.82, I2 = 0%). Similarly, headgear resulted in a significant reduction in final ANB of ?0.72 (95% CI ?1.18 to ?0.27, chi squared 0.34, 1 df, P = 0.56, I2 = 0%). No significant differences, with respect to final overjet, ANB, or ANB change, were found between the effects of early treatment with headgear and the functional appliances. Adolescent treatment (Phase II): At the end of all treatment we found that there were no significant differences in overjet, final ANB or PAR score between the children who had a course of early treatment, with headgear or a functional appliance, and those who had not received early treatment. Similarly, there were no significant differences in overjet, final ANB or PAR score between children who had received a course of early treatment with headgear or a functional appliance. One trial found a significant reduction in overjet (?5.22 mm; 95% CI ?6.51 to ?3.93) and ANB (?2.27 degrees; 95% CI ?3.22 to ?1.31, chi squared 1.9, 1 df, P = 0.17, I2 = 47.3%) for adolescents receiving one-phase treatment with a functional appliance versus an untreated control. A statistically significant reduction of ANB (?0.68 degrees; 95% CI ?1.32 to ?0.04, chi squared 0.56, 1 df, P = 0.46, I2 = 0%) with the Twin Block appliance when compared to other functional appliances. However, there was no significant effect of the type of appliance on the final overjet. Authors conclusions: The evidence suggests that providing early orthodontic treatment for children with prominent upper front teeth is no more effective than providing one course of orthodontic treatment when the child is in early adolescence.

Clinical significance of early treatment of overjet is questionable

Literature searches were made within the Cochrane Oral Health Group's Trials Register, Cochrane Central Register of Controlled Trials, Medline and Embase, and articles were also identified as part of the Cochrane Oral Health Group's handsearching programme from the following sources: American Journal of Orthodontics and Dentofacial Orthopedics, The Angle Orthodontist, European Journal of Orthodontics and Journal of Orthodontics. In addition, the journals Seminars in Orthodontics, Clinical Orthodontics and Research and Australian Journal of Orthodontics were searched by hand. Bibliographies of identified trials were checked and first-named authors of all trial reports were contacted in an attempt to identify unpublished studies and to obtain any further information about the trials. There were no language restrictions. Randomised and controlled clinical trials were chosen if participants were children and/or adolescents (age <16 years) who were receiving orthodontic treatment to correct prominent upper front teeth using any orthodontic brace or head-brace, and where the control was no or delayed treatment or another active intervention. Primary outcomes considered were prominence of the upper front teeth, relationship between upper and lower jaws. Secondary outcomes were self esteem, any injury to the upper front teeth, jaw joint problems, patient satisfaction, and the number of attendances required to complete treatment. Information regarding methods, participants, interventions, outcome measures and results were extracted independently and in duplicate by two review authors. The Cochrane Oral Health Group's statistical guidelines were followed and mean differences were calculated using random-effects models. Potential sources of heterogeneity were examined. Eight trials, based on data from 592 patients who presented with Class II Division 1 malocclusion, were included in the review. Within these, three trials (432 participants) considered early treatment, comparing a functional appliance with no treatment. There was a significant difference in final overjet in the treatment group versus control group of −4.04 mm [95% confidence interval (CI), −7.47–−0.60; X2 117.02; 2 degrees freedom (df); P<0.00001, I2 98.3%)]. There was a significant difference in ANB (−1.35 mm; 95% CI, 2.57–−0.14; X2 9.17; 2 df; P 0.01; I2 78.2%) and change in ANB (−0.55; 95% CI, −0.92–−0.18; X2 5.71; 1 df; P 0.06; I2 65.0%) between treatment and control groups. The comparison of the effect of treatment with headgear versus an untreated control revealed that there was a small but significant effect of headgear treatment on overjet of −1.07 (95% CI, −1.63–−0.51; X2 0.05; 1 df; P 0.82; I2 0%). Similarly, headgear resulted in a significant reduction in final ANB of −0.72 (95% CI, −1.18–−0.27; X2 0.34; 1 df; P 0.56; I2 0%). No significant differences, with respect to final overjet, ANB or ANB change, were found between early treatment with headgear and the functional appliances. For trials considering adolescent treatment (phase II), at the end of all treatment there was found to be no significant difference between overjet, final ANB or PAR score in participants who had a course of early treatment with headgear or a functional appliance and in those who had not received early treatment. Similarly, there were no significant differences in overjet, final ANB or PAR score between children who had received a course of early treatment with headgear or a functional appliance. One trial found a significant reduction in overjet (−5.22 mm; 95% CI, −6.51–−3.93) and ANB (−2.27 degrees; 95% CI, −3.22–−1.31; X2 1.9; 1 df; P 0.17; I2 47.3%) for adolescents receiving one-phase treatment with a functional appliance versus an untreated control. There was a statistically significant reduction of ANB (−0.68 degrees; 95% CI, −1.32–−0.04; X2 0.56; 1 df; P 0.46; I2 0%) with the twinblock appliance compared with other functional appliances, but there was no significant effect of the type of appliance on the final overjet. The evidence suggests that providing early orthodontic treatment for children with prominent upper front teeth is no more effective than providing one course of orthodontic treatment when the child is in early adolescence.

Antiviral efficacy of adefovir dipivoxil versus lamivudine in patients with chronic hepatitis B sequentially treated with lamivudine and adefovir due to lamivudine resistance

To compare the antiviral efficacy of adefovir (ADV) in lamivudine (LMV)-resistant patients with LMV treatment in nucleoside-naive patients, using serum samples collected sequentially during the course of treatment progressing from LMV to ADV. Forty-four patients with chronic hepatitis B (CHB) were included. The patients were initially treated with LMV and then switched to ADV when LMV resistance developed. Antiviral efficacy was assessed by measuring the following: reduction in serum HBV DNA from baseline, HBV DNA negative conversion (defined as HBV DNA being undectable by the hybridization assay), and HBV DNA response (either HBV DNA level <or= 10(5) copies/mL or a >or= 2 log10 reduction from baseline HBV DNA level). After two and six months of treatment, HBV DNA reduction was greater with LMV compared to ADV treatment (P = 0.021). HBV DNA negative conversion rates were 64% and 27% after one month of LMV and ADV treatment respectively (P = 0.001). Similarly, HBV DNA response rates were 74% and 51% after two months of LMV and ADV treatment respectively (P = 0.026). The time taken to HBV DNA negative conversion and to HBV DNA response were both delayed in ADV treatment compared with LMV. The antiviral efficacy of ADV in LMV-resistant patients is slower and less potent than that with LMV in nucleoside-naive patients during the early course of treatment.

Induction Therapy of Interferon alfa-2b in Combination with Ribavirin as Initial Treatment for Chronic Hepatitis C Genotype 1

Purpose: To evaluate the efficacy and effect of a daily dose induction therapy of interferon alfa-2b and ribavirin for previously untreated patients with chronic hepatitis C genotype 1. Methods: Fifty-five treatment naive patients (age 18 and older) diagnosed with chronic hepatitis C (CHC) genotype 1 were given an induction therapy with a daily dose of interferon alfa-2b (IFN) at 3 MU for 16 weeks followed by 3MU three times a week for 32 weeks in combination with ribavirin (800–1000 mg, weight adjusted). All patients who remained in therapy continued the standard treatment from week 17 to 48. Efficacy of treatment was evaluated by determining sustained virological responses (SVR) and normalization of ALT. A comparison of selected parameters were made between patients who were responding to treatment vs. those not responding to treatment. Results: Out of 55 CHC genotype 1 patients, 51 finished the study up to follow-up and 37 completed the treatment regimen. The SVR was 42% for all patients in the study with 95% confidence interval (CI) of 28.7%–55.9%. The SVR was 45% (95% CI 31.1–59.7) for all patients who finished the study, and 62% (95% CI 44.8–77.5) for all patients who completed the treatment regimen (23 cured vs. 14 not cured). Principal component analysis was used to select parameters to better understand the mechanism of the combination therapy. Poor prognosis or treatment success statistically correlated with the following parameters: low WBC in early course of treatment, high WBC in late course of treatment, elevated basophils, low rbc, low eosinophils during week 1, high eosinophils in weeks 2–8, high CO2 level, hypercalcemia, elevated direct bilirubin, and elevated TSH. Conclusions: Our study suggests that an induction therapy composed of a daily dose IFN for 16 weeks given in combination with ribavirin for patients with CHC genotype 1 increased the rate of SVR to 42%, a significant improvement on FDA approved regimen for the drug, and compared favorably to the newer regimen. Further research is needed to investigate the newly identified prognostic parameters so as to improve outcome.

Clinical investigation survival prediction in high-grade gliomas by MRI perfusion before and during early stage of RT

To determine whether cerebral blood volume (CBV) and cerebral blood flow can predict the response of high-grade gliomas to radiotherapy (RT) by taking into account spatial heterogeneity and temporal changes in perfusion.Twenty-three patients with high-grade gliomas underwent conformal RT, with magnetic resonance imaging perfusion before and at Weeks 1-2 and 3-4 during RT. Tumor perfusion was classified as high, medium, or low. The prognostic values of pre-RT perfusion and the changes during RT for early prediction of tumor response to RT were evaluated.The fractional high-CBV tumor volume before RT and the fluid-attenuated inversion recovery imaging tumor volume were identified as predictors for survival (p = 0.01). Changes in tumor CBV during the early treatment course also predicted for survival. Better survival was predicted by a decrease in the fractional low-CBV tumor volume at Week 1 of RT vs. before RT, a decrease in the fractional high-CBV tumor volume at Week 3 vs. Week 1 of RT, and a smaller pre-RT fluid-attenuated inversion recovery imaging tumor volume (p = 0.01).Early temporal changes during RT in heterogeneous regions of high and low perfusion in gliomas might predict for different physiologic responses to RT. This might also open the opportunity to identify tumor subvolumes that are radioresistant and might benefit from intensified RT.

Thiopurine Methyltransferase (&lt;EMPH TYPE="ITAL"&gt;TPMT&lt;/EMPH&gt;) Genotype and Early Treatment Response to Mercaptopurine in Childhood Acute Lymphoblastic Leukemia

Early response to multiagent chemotherapy, including mercaptopurine, as measured by minimal residual disease is an important prognostic factor for children with acute lymphoblastic leukemia (ALL). Thiopurine methyltransferase (TPMT) is involved in the metabolism of mercaptopurine and subject to genetic polymorphism, with heterozygous individuals having intermediate and homozygous mutant individuals having very low TPMT activity. To assess the association of TPMT genotype with minimal residual disease load before and after treatment with mercaptopurine in the early treatment course of childhood ALL. TPMT genotyping of childhood ALL patients (n = 814) in Germany consecutively enrolled in the ALL-BFM (Berlin-Frankfurt-Münster) 2000 study from October 1999 to September 2002. Minimal residual disease was analyzed on treatment days 33 and 78 for risk-adapted treatment stratification. A 4-week cycle of mercaptopurine was administered between these 2 minimal residual disease measurements. Patients (n = 4) homozygous for a mutant TPMT allele, and consequently deficient in TPMT activity, were treated with reduced doses of mercaptopurine and, therefore, not included in the analyses. Minimal residual disease load before (day 33) and after (day 78) mercaptopurine treatment. Loads smaller than 10(-4) were defined as negative. Patients (n = 55) heterozygous for allelic variants of TPMT conferring lower enzyme activity had a significantly lower rate of minimal residual disease positivity (9.1%) compared with patients (n = 755) with homozygous wild-type alleles (22.8%) on day 78 (P = .02). This translated into a 2.9-fold reduction in risk for patients with wild-type heterozygous alleles (relative risk, 0.34; 95% confidence interval, 0.13-0.86). TPMT genotype has a substantial impact on minimal residual disease after administration of mercaptopurine in the early course of childhood ALL, most likely through modulation of mercaptopurine dose intensity. Our findings support a role for minimal residual disease analyses in the assessment of genotype-phenotype associations in multiagent chemotherapeutic trials.

Evaluating the Phase Model of Change During Short-Term Psychodynamic Psychotherapy

This study examined the phase model of psychotherapy change (Howard, Lueger, Maling, & Martinovich, 1993; Howard, Moras, Brill, Martinovich, & Lutz, 1996) and assessed the domains of subjective well-being, symptomatic distress, and social/interpersonal functioning during short-term psychodynamic psychotherapy. Specifically, we assessed evaluation/third-session to ninth-session changes in a group of 20 treated patients. These three domains were examined for both statistical and clinically significant change (Jacobson & Truax, 1991). Treatment fidelity and credibility were also evaluated. Statistical and clinically significant improvement in the domains of subjective well-being and symptom distress were evident by the ninth session of short-term dynamic psychotherapy. Statistical and reliable improvement were observed in relational functioning during the same time period. In addition, changes in both subjective well-being and symptomatic distress contributed unique and separate variance to predicting changes in social/interpersonal functioning. The results with respect to the differential effects predicted by the phase model of change during the early course of treatment are discussed.

Effect of initial treatment with antidepressants as a predictor of outcome after 8 weeks

Most findings of antidepressant treatment prediction have not been replicated, and this applies to biological predictors as well as sociodemographic and early course predictors. One exception might be early psychopathological improvement. To reevaluate this question, we examined the results of two large-scale controlled clinical trials comparing the selective and reversible inhibitor of monoamine oxidase type A (MAO-A) brofaromine with the standard tricyclic compound imipramine. One trial was carried out in a normal-aged patient group; the other, in elderly patients. Above all, we were interested in determining whether early treatment course would prove predictive of later outcome. The main finding was that the initial antidepressant effect (measured after 1 and 2 weeks) predicted longer term outcome. Although this association was not as strong in the elderly patient group, its predictive value did possess a certain clinical relevance.