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Antidepressant plus benzodiazepine for major depression.

BACKGROUND: Anxiety frequently coexists with depression. There is no systematic review to show if adding benzodiazepines to antidepressants can bring about any advantage over antidepressants alone in the treatment of depression, although such a combination prescription appears to be widely practiced worldwide OBJECTIVES: To determine whether, among adult patients with major depression, adding benzodiazepines to antidepressants brings about any benefit in terms of symptomatic recovery or side-effects in the short term (less than 8 weeks) and long term (more than 2 months), in comparison with treatment by antidepressants alone. SEARCH STRATEGY: Electronic searches of MEDLINE, EMBASE, International Pharmaceutical Abstracts, Biological Abstracts, LILACS, PsycLit, the Cochrane Library and the trial register of the Cochrane Depression, Anxiety and Neurosis Group (January 1972 to December 1998), combined with hand searching, reference searching, SciSearch and personal contacts. SELECTION CRITERIA: All randomized controlled trials that compared combined antidepressant-benzodiazepine treatment with antidepressant alone for adult patients with major depression (Feighner criteria, RDC, DSM-III, DSM-III-R, DSM-IV or ICD-10). Exclusion criteria are: antidepressant dosage lower than 100 mg of imipramine or its equivalent daily and duration of trial shorter than 4 weeks. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed the eligibility and quality of the studies. Two reviewers independently extracted the data. Standardized weighted mean differences and relative risks were estimated with random effects model. The dropouts were assigned the least favorable outcome. Two sensitivity analyses examined the effect of this assumption as well as the effect of including medium quality studies. Three a priori subgroup analyses were performed with regard to the patients with or without comorbid anxiety and with regard to the types of benzodiazepines tested. MAIN RESULTS: Aggregating nine studies with a total of 679 patients, the combination therapy group was 37% (95%CI: 19 to 51%) less likely to drop out than the antidepressant alone group. The intention-to-treat analysis showed that the former were 63% (18 to 127%) to 38% (15 to 66%) more likely to show response (defined as 50% or greater reduction in the depression scale from baseline) up to 4 weeks. REVIEWER'S CONCLUSIONS: The potential benefits of adding a benzodiazepine to an antidepressant must be balanced judiciously against possible harms including development of dependence and accident proneness, on the one hand, and against continued suffering following no response and drop-out, on the other.

Adult↗

Liver transplantation for hepatocellular carcinoma: the MELD impact.

The new allocation policy of the United Network of Organ Sharing (UNOS) based on the model for end-stage liver disease (MELD) gives candidates with stage T1 or stage T2 hepatocellular carcinoma (HCC) a priority MELD score beyond their degree of hepatic decompensation. The aim of this study was to determine the impact of the new allocation policy on HCC candidates before and after the institution of MELD. The UNOS database was reviewed for all HCC candidates listed between July 1999 and July 2002. The candidates were grouped by two time periods, based on the date of implementation of new allocation policy of February 27, 2002. Pre-MELD candidates were listed for deceased donor liver transplantation (DDLT) before February 27,2002, and post-MELD candidates were listed after February 27, 2002. Candidates were compared by incidence of DDLT, time to DDLT, and dropout rate from the waiting list because of clinical deterioration or death, and survival while waiting and after DDLT. Incidence rates calculated for pre-MELD and post-MELD periods were expressed in person years. During the study, 2,074 HCC candidates were listed for DDLT in the UNOS database. The DDLT incidence rate was 0.439 transplant/person years pre-MELD and 1.454 transplant/person years post-MELD (P < 0.001). The time to DDLT was 2.28 years pre-MELD and 0.69 years post-MELD (P < 0.001). The 5-month dropout rate was 16.5% pre-MELD and 8.5% post-MELD (P < 0.001). The 5-month waiting-list survival was 90.3% pre-MELD and 95.7% post-MELD (P < 0.001). The 5-month survival after DDLT was similar for both time periods. The new allocation policy has led to an increased incidence rate of DDLT in HCC candidates. Furthermore, the 5-month dropout rate has decreased significantly. In addition, 5-month survival while waiting has increased in the post-MELD period. Thus, the new MELD-based allocation policy has benefited HCC candidates.

Carcinoma, Hepatocellular↗

Liver transplantation for hepatocellular carcinoma: lessons from the first year under the Model of End-Stage Liver Disease (MELD) organ allocation policy.

We examined the impact of the Model for End-Stage Liver Disease (MELD) organ allocation scheme on 44 patients with hepatocellular carcinoma (HCC) awaiting orthotopic liver transplantation (OLT) between February 2002 and January 2003, and compared the outcome with 58 patients listed in the 4 years before MELD implementation. Patients undergoing living-donor liver transplantation were excluded. The Kaplan-Meier probabilities for OLT at 3, 6, and up to 8.5 months were 22.5%, 64.0%, and 88.0%, respectively, under MELD versus 17.2%, 24.7%, and 35.8% at 3, 6 and 9 months, respectively, in the pre-MELD group (P =.0006). In Cox regression analysis, non-O blood group (hazard ratio 2.5; P =.047 versus blood group O) and 3 tumor nodules (hazard ratio 5.5; P =.005) were associated with a significantly higher probability for OLT under MELD. The probabilities of dropout were 5.6% at 6 and 8.5 months under MELD versus 7.2% and 37.8% at 6 and 12 months, respectively, in the pre-MELD group (P =.74). The lack of a significant difference in dropout may be due to low dropout rates in the first 6 months in either group. No HCC was found in the explant in 1 patient from each group. In conclusion, the HCC-adjusted MELD system significantly improved the probability of timely OLT, albeit a significant disadvantage for blood group O was evident. Compared with preliminary UNOS data, in which 90% of patients with HCC have received OLT within 3 months, our results reflect the wide regional variation in the impact of MELD.

ABO Blood-Group System↗

Dual-echo spiral in/in acquisition method for reducing magnetic susceptibility artifacts in blood-oxygen-level-dependent functional magnetic resonance imaging.

MRI signal dropout in gradient recalled echo acquisitions limits the capability of blood-oxygen-level-dependent functional magnetic resonance imaging (fMRI) to study activation tasks that involve the orbitofrontal, temporal, and basal areas of the brain where significant macroscopic magnetic susceptibility differences exist. Among the various approaches aimed to address this issue, the acquisition method based on spiral in/out trajectories is one of the most time-efficient and effective techniques. In this study, we extended further the spiral in/out approach into 3D acquisition and compared the effectiveness of the different spiral in/out trajectory combinations in reducing signal dropout. The activation results from whole brain fMRI studies using complex finger tapping and breath-holding tasks demonstrate that the acquisition method based on dual-echo spiral in/in (DSPIN) trajectories is the most favorable. The DSPIN acquisition method has the following advantages: (1) It reduces most effectively signal dropout in the brain where magnetic susceptibility inhomogeneity is problematic and significantly improves the sensitivity to detect functional activations in those regions. (2) It significantly improves SNR in the whole brain by dual echo averaging without compromising functional contrast. (3) There is no reduction in time-efficiency and spatial resolution.

Adult↗

Shared parameter models for the joint analysis of longitudinal data and event times.

Longitudinal studies often gather joint information on time to some event (survival analysis, time to dropout) and serial outcome measures (repeated measures, growth curves). Depending on the purpose of the study, one may wish to estimate and compare serial trends over time while accounting for possibly non-ignorable dropout or one may wish to investigate any associations that may exist between the event time of interest and various longitudinal trends. In this paper, we consider a class of random-effects models known as shared parameter models that are particularly useful for jointly analysing such data; namely repeated measurements and event time data. Specific attention will be given to the longitudinal setting where the primary goal is to estimate and compare serial trends over time while adjusting for possible informative censoring due to patient dropout. Parametric and semi-parametric survival models for event times together with generalized linear or non-linear mixed-effects models for repeated measurements are proposed for jointly modelling serial outcome measures and event times. Methods of estimation are based on a generalized non-linear mixed-effects model that may be easily implemented using existing software. This approach allows for flexible modelling of both the distribution of event times and of the relationship of the longitudinal response variable to the event time of interest. The model and methods are illustrated using data from a multi-centre study of the effects of diet and blood pressure control on progression of renal disease, the modification of diet in renal disease study.

Blood Pressure↗

A note on the analysis of titration studies.

We propose a method to incorporate all types of dropouts in the evaluation of an intervention based on binary data from a titration study. The proposed procedure does not require that the dropouts occur randomly, but instead examines each outcome individually. Our procedure has a built-in penalty factor in the estimation process that determines the amount of penalty on efficacy parameters due to efficacy-related dropouts. We also propose a method to estimate the variances associated with the estimates. The results have use in exploration of a potential dose-response relationship or to answer questions pertinent for phase III studies. We use data from a phase III antihypertension study to illustrate the procedure.

Algorithms↗

Attrition in prevention research.

Selective attrition can detract from the internal and external validity of longitudinal research. Four tests of selective attrition applicable to longitudinal prevention research were conducted on data bases from two recent studies. These tests assessed (1) differences between dropouts and stayers in terms of pretest indices of primary outcome variables (substance use), (2) differences in change scores for dropouts and stayers, (3) differences in rates of attrition among experimental conditions, and (4) differences in pretest indices for dropouts among conditions. Results of these analyses indicate that cigarette smokers, alcohol drinkers, and marijuana users are more likely to drop out than nonusers, limiting the external validity of both studies. For one project, differential rates of attrition among conditions suggested a possible attrition artifact which will interfere with interpretation of outcome results, possibly masking true program effectiveness. Recommendations for standardizing reports of attrition and for avoiding attrition through second efforts are made.

Adolescent↗

[Evaluation of risk assessment instruments for sex offenders].

In order to evaluate risk assessment instruments for sex offenders in Germany, we compared the predictive validity of the Static-99, HCR-20, SVR-20, and PCL-R scales for 134 sex offenders. The mean follow-up time was 9 years (range 1-340 months), using the first entry into the National Register of Criminal Convictions as endpoint variable. For the estimate of predictive power, the area under the curve (AUC) of receiver operating characteristic (ROC) analysis was calculated. The AUC plots accurately identified violent or sexual recidivists and "false positives" at all scale levels. Comparing the predictive validity of these four instruments, the results favored Static-99. As for the limited sample size, differences between the assessment instruments were, however, not statistically significant. The ROC analysis for Static-99 showed that including treatment dropouts does not improve predictive accuracy (including dropouts: AUC 0.710; excluding dropouts: AUC 0.721). Kaplan-Meier survival analyses yielded highly a significant correlation to recidivism time point for two Static-99 and SVR-20 risk categories. Higher-risk categories were related to earlier recidivism. However, relying on the Static-99 and SVR-20 alone showed false positive results: for up to two out of three sex offenders, they predicted recidivism which did not occur.

Forensic Psychiatry↗

Ocular discomfort at the initial wearing of rigid gas permeable contact lenses.

PURPOSE: To evaluate the relationship between ocular discomfort in the initial wearing of rigid gas permeable contact lenses (RGPCL) and the time required to adapt to RGPCL as measured by using the visual analogue scale (VAS). METHODS: RGPCL were prescribed for 89 patients (178 eyes) with myopia or myopic astigmatism and no history of wearing contact lenses. The patients who stopped wearing RGPCL after 1 week because of ocular discomfort were defined as dropouts, and those who adapted to regular full-time RGPCL wear were defined as successful wearers. VAS scores were measured at several intervals for 1 month after the initial wearing of the lenses. The number of days required to adapt to wearing RGPCL was defined as the adaptation time. RESULTS: Four patients were dropouts due to ocular discomfort (eight eyes; 4.5%). VAS scores were significantly lower in successful wearers than in dropouts at 1 week, although their VAS scores were not different at 1 day. VAS scores of the successful wearers at 1 week were significantly lower than those at 1 day. The average time required to adapt to RGPCL was 23.0 +/- 22.1 days for the 85 successful wearers. Lower VAS scores at 1 day or 1 week were significantly correlated with a shorter adaptation time in the successful RGPCL wearers. CONCLUSIONS: Our results indicate that the VAS score might be useful for predicting successful RGPCL use and the adaptation time required by successful wearers.

Adaptation, Ocular↗

Inpatient treatment for substance abuse patients with psychiatric disorders: a national study of determinants of readmission.

This study examined the patient case mix and program determinants of 6-month readmission rates and early treatment dropout for 7,711 VA inpatients with both substance abuse and major psychiatric disorders treated in one of 104 substance abuse programs. Patients were treated in one of three types of inpatient programs: explicitly designed dual diagnosis specialty programs, substance abuse programs with a dual diagnosis psychotherapy group or standard substance abuse programs. Dual diagnosis specialty programs differed from regular substance abuse programs in that they had a more severe case mix, a higher 180-day readmission rate, greater dual diagnosis treatment orientation, used more psychotropic medication, had longer lengths of stay, had greater tolerance of relapse and medication noncompliance, and a higher rate of psychiatric aftercare in the 30 days after discharged. Programs with less severe case mix, longer intended and actual length of stay, lower 7-day dropout rates, greater tolerance of problem behavior, 12-step groups, and higher immediate postdischarge utilization of outpatient mental health treatment lower 180-day readmission rates. Programs with less severe patient case mix, more use of psychotropic medications but less of methadone and antabuse, less varied and diverse treatment activities, and low use of patient-led groups had lower dropout rates.

Adolescent↗

A poor response in the first in vitro fertilization cycle is not necessarily related to a poor prognosis in subsequent cycles.

OBJECTIVE: To calculate the cumulative ongoing pregnancy rate in patients with a poor response in their first IVF cycle. DESIGN: Retrospective cohort study. SETTING: In vitro fertilization unit of a university hospital. PATIENT(S): Two hundred twenty-five women who experienced a poor response in their first IVF or intracytoplasmic sperm injection cycle. These patients were divided into 64 expected (aged > or =41 years and/or elevated FSH level) and 161 unexpected poor responders (aged <41 years and FSH level not elevated). INTERVENTION(S): In vitro fertilization treatment with a long-suppression protocol with FSH-urofollitropin or recombinant FSH. MAIN OUTCOME MEASURE(S): Cumulative ongoing pregnancy rate. This rate was calculated in two ways to correct for dropouts: pessimistic (zero chance of pregnancy for the dropouts) and optimistic (the same chance for the dropouts as for patients who continued). RESULT(S): The cumulative ongoing pregnancy rate of women with an unexpected poor response in the first cycle was 37% (pessimistic) to 47% (optimistic) after three cycles. Women with an expected poor response had a cumulative ongoing pregnancy rate of 16% (pessimistic) to 19% (optimistic) after 3 cycles. Sixty-four percent of the unexpected poor responders and 31% of the expected poor responders had a normal response in the second cycle, most of them after receiving a higher dose of gonadotropins. CONCLUSION(S): Most patients with an unexpected poor response in the first cycle had a normal response in the second cycle, leading to an acceptable cumulative ongoing pregnancy rate after three cycles. Patients with an expected poor response in the first cycle should be advised to withdraw from treatment after the first cycle because of a poor prognosis.

Adult↗

Is alcoholism typology a predictor of both Alcoholics Anonymous affiliation and disaffiliation after treatment?

Twelve Steps (TS) has demonstrated effectiveness; induction into Alcoholics Anonymous (AA) is a primary objective of TS and is a pivotal mechanism explaining its effectiveness. However, evidence suggests that, after treatment, dropout from AA is high. This study investigated whether alcohol problem severity predicted both AA affiliation and disaffiliation among clients receiving TS. This study of a Project MATCH sample included 453 alcohol-dependent clients randomly assigned to TS who reported AA attendance during treatment. Greater alcohol problem severity predicted AA attendance; opposite to prediction, less alcohol-impaired clients were more than twice as likely to discontinue AA attendance after treatment. When sustained AA attendance is desired, the evaluation of client pretreatment alcohol involvement may be useful for identifying potential AA dropout after TS treatment. Findings also indicate that, among treatment-seeking problem drinkers, AA dropout and disaffiliation are distinct, albeit correlated, constructs that require future investigation.

Adaptation, Psychological↗

Comparison of spiral-in/out and spiral-out BOLD fMRI at 1.5 and 3 T.

Spiral-in/out functional magnetic resonance imaging (fMRI) methods acquire one image before the echo time (TE) and a second image after TE during each scan. Weighted combination of the two images provides a time series with reduced susceptibility dropout in frontal and medial temporal regions as well as increased signal-to-noise ratio (SNR) in regions of uniform cortex. In this study, task activation with the spiral-in/out method was compared to that with conventional spiral-out acquisitions at two field strengths (1.5 and 3.0 T) using episodic memory encoding, verbal working memory, and affective processing tasks in eight human volunteers. With the conventional spiral-out sequence, greater signal dropout is observed in lateral and medial prefrontal, amygdalar, and medial temporal regions at 3 T relative to 1.5 T, whereas such dropout at 3 T is reduced or mitigated with the spiral-in/out method. Similarly, activation volumes for frontal, amygdalar, and medial temporal regions are reduced for spiral-out acquisitions relative to spiral-in/out, and this difference is more apparent at 3 T than at 1.5 T. In addition, significant regionally specific increases in Z scores are obtained with the spiral-in/out sequence relative to spiral-out acquisitions at both field strengths. It is concluded the spiral-in/out sequence may provide significant advantages over conventional spiral methods, especially at 3 T.

Adult↗

Improved BOLD detection in the medial temporal region using parallel imaging and voxel volume reduction.

Using gradient-echo EPI, signal dropout due to macroscopic off resonance effects can prevent blood-oxygenation-level-dependent (BOLD) signal change detection. The anterior medial temporal lobe (MTL) is located near these susceptibility gradients and therefore shows considerable signal dropout with GE-EPI. Reducing the volume of the image voxel reduces susceptibility-related signal dropout. However, this is accompanied by a prohibitive reduction in signal-to-noise ratio (SNR). To compensate for SNR loss with smaller voxels, we used a multi-channel MRI receiver with an array of receive-only 16-element surface coils at 3 T. We demonstrate that the reduction of susceptibility artifacts, through use of high resolution images, coupled with the gains in image SNR from the array coil improves the temporal signal-to-noise ratio (TSNR) and enhances the contrast-to-noise ratio (CNR). Furthermore, a comparison of 2 mm with 4-mm-thick axial images both with the same in-plane resolution showed that thinner slices enhanced TSNR and CNR throughout the ventral-medial regions of the temporal lobes, with the greatest improvement in the most anterior regions of the MTL. Further improvements were seen when adjacent 2 mm slices were combined to match overall voxel volume. These results demonstrate that BOLD investigation of anterior MTL function can be enhanced by decreasing voxel size but only in combination with the SNR gained by using the 16-channel head coil system.

Adult↗

Meibomian gland function and giant papillary conjunctivitis.

We examined 42 contact lens-wearing patients for clinical evidence of giant papillary conjunctivitis and for meibomian gland dysfunction with gland dropout. Fifteen patients were free of clinical signs and symptoms of giant papillary conjunctivitis, whereas 27 had clinical symptoms and evidence of giant papillary conjunctivitis. Patients with giant papillary conjunctivitis had significantly more gland dropout with an average of 0.6 +/- 1.2 gland absent in both lower eyelids compared with 0.2 +/- 0.4 gland absent in patients without giant papillary conjunctivitis. Additionally, the viscosity of meibomian gland excreta was greater in the giant papillary conjunctivitis group. There was no difference in tear osmolarity or in the Schirmer test results between the two groups. These results indicated patients with giant papillary conjunctivitis were more likely to have meibomian gland dysfunction with gland dropout than patients without giant papillary conjunctivitis.

Adult↗

A systematic review of the treatment of depression with antidepressant drugs in patients who also have a physical illness.

To determine whether antidepressants are clinically effective and acceptable for the treatment of depression in people who also have a physical illness. The method used was a systematic review of all randomised controlled trials (found by computer and hand searches) comparing any antidepressant drug with placebo or no treatment, in depressed adults with a specified physical disorder. The main outcome measures are numbers of individuals who recover/improve at the end of the trial and, as a proxy for treatment acceptability, numbers who complete treatment. 18 studies were included, covering 838 patients with a range of physical diseases. 6 studies used SSRIs, 3 atypical antidepressants, and the remainder tricyclics. Patients treated with antidepressants were significantly more likely to improve than those given placebo: about 4 patients would need to be treated with antidepressants to produce one recovery from depression which would not have occurred had they been given placebo (NNT 4.2, 95% CI 3.2-6.4). Most antidepressants (tricyclics and SSRIs together, 15 trials) produced a small but significant increase in dropout (OR 1.66, 95% CI 1.14-2.40. NNH 9.8, 95% CI 5.4-42.9). The "atypical" antidepressant mianserin produced significantly less dropout than placebo. Trends towards tricyclics being more effective than SSRIs, but also more likely to produce dropout were noted. The review provides evidence that antidepressants, significantly more frequently than either placebo or no treatment, cause improvement in depression in patients with a wide range of physical diseases.

Adult↗

Effect of probe design on accuracy and reliability of pulse oximetry in pediatric patients.

STUDY OBJECTIVE: To determine if the traditional band-wrap disposable pulse oximeter probe is more accurate or reliable for oxygen monitoring in children than the reusable clip-type probe. DESIGN: Prospective, observational clinical study. SETTING: Operating room of a large university hospital. PATIENTS: 18 children 11 years of age or younger, who were scheduled for general anesthesia with placement of an intraarterial catheter. INTERVENTIONS: Pulse oximetry values were obtained using both band and clip probes of three pulse oximeters (Nellcor, Hayward CA; Novametrix, Wallingford, CT; Ohmeda, Boulder, CO) and compared with simultaneous hemoximetry values. Dropout rate (percent of down time) also was recorded for each probe-machine combination. MEASUREMENTS AND MAIN RESULTS: Data were analyzed using bias and precision and t-test. p < 0.05 is considered significant. Bias (mean SpO2-SaO2) is less than 2% for all probe-machine combinations. The range of error observed between SpO2 and SaO2 for all data points was greatest using the Nellcor band (27.8%) and least using the Ohmeda band (11.4%). In cyanotic children, the greatest bias and precision were observed with Nellcor band (N = 11, -5.12 +/- 9.74) and the best agreement with Novametrix band (N = 17, 0.08 +/- 4.21). The difference in bias for any test units above or below the median weight of 13.75 kg did not vary by more than 1%. Dropout rate was minimal for all units in nonbypass situations. After cardiopulmonary bypass, no data dropout was observed with Ohmeda band; observed down time with the other units varied between 34% and 55%. CONCLUSIONS: The type of probe selected has little effect on accuracy of pulse oximetry in children. After cardiopulmonary bypass, using the Ohmeda band combination may improve the likelihood of obtaining consistent readings and decreasing down time.

Anesthesia, General↗

Comparison of fMRI activation at 3 and 1.5 T during perceptual, cognitive, and affective processing.

Previous studies comparing fMRI data acquired at 1.5 T and higher field strengths have focused on examining signal increases in the visual and motor cortices. No information is, however, available on the relative gain, or the comparability of data, obtained at higher field strengths for other brain regions such as the prefrontal and other association cortices. In the present study, we investigated fMRI activation at 1.5 and 3 T during visual perception, visuospatial working memory, and affect-processing tasks. A 23% increase in striate and extrastriate activation volume was observed at 3 T compared with that for 1.5 T during the visual perception task. During the working memory task significant increases in activation volume were observed in frontal and parietal association cortices as well as subcortical structures, including the caudate, globus pallidus, putamen, and thalamus. Increases in working memory-related activation volume of 82, 73, 83, and 36% were observed in the left frontal, right frontal, left parietal, and right parietal lobes, respectively, for 3 T compared with 1.5 T. These increases were characterized by increased activation at 3 T in several prefrontal and parietal cortex regions that showed activation at 1.5 T. More importantly, at 3 T, activation was detected in several regions, such as the ventral aspects of the inferior frontal gyrus, orbitofrontal gyrus, and lingual gyrus, which did not show significant activation at 1.5 T. No difference in height or extent of activation was detected between the two scanners in the amygdala during affect processing. Signal dropout in the amygdala from susceptibility artifact was greater at 3 T, with a 12% dropout at 3 T compared with a 9% dropout at 1.5 T. The spatial smoothness of T2* images was greater at 3 T by less than 1 mm, suggesting that the greater extent of activation at 3 T beyond these spatial scales was not due primarily to increased intrinsic spatial correlations at 3 T. Rather, the increase in percentage of voxels activated reflects increased sensitivity for detection of brain activation at higher field strength. In summary, our findings suggest that functional imaging of prefrontal and other association cortices can benefit significantly from higher magnetic field strength.

Adolescent↗