Meta-analysis: hoarding symptoms associated with poor treatment outcome in obsessive-compulsive disorder.

DSM-5 recognizes hoarding disorder as distinct from obsessive-compulsive disorder (OCD), codifying a new consensus. Hoarding disorder was previously classified as a symptom of OCD and patients received treatments designed for OCD. We conducted a meta-analysis to determine whether OCD patients with hoarding symptoms responded differently to traditional OCD treatments compared with OCD patients without hoarding symptoms. An electronic search was conducted for eligible studies in PubMed. A trial was eligible for inclusion if it (1) was a randomized controlled trial, cohort or case-control study; (2) compared treatment response between OCD patients with and those without hoarding symptoms, or examined response to treatment between OCD symptom dimensions (which typically include hoarding) and (3) examined treatment response to pharmacotherapy, behavioral therapy or their combination. Our primary outcome was differential treatment response between OCD patients with and those without hoarding symptoms, expressed as an odds ratio (OR). Twenty-one studies involving 3039 total participants including 304 with hoarding symptoms were included. Patients with OCD and hoarding symptoms were significantly less likely to respond to traditional OCD treatments than OCD patients without hoarding symptoms (OR=0.50 (95% confidence interval 0.42-0.60), z=-7.5, P<0.0001). This finding was consistent across treatment modalities. OCD patients with hoarding symptoms represent a population in need of further treatment research. OCD patients with hoarding symptoms may benefit more from interventions specifically targeting their hoarding symptoms.

Meta-analysis of the dose-response relationship of SSRI in obsessive-compulsive disorder.

We sought to determine differences in efficacy and tolerability between different doses of selective serotonin reuptake inhibitors in the treatment of obsessive-compulsive disorder (OCD) using meta-analysis. We identified 9 studies involving 2268 subjects that were randomized, double-blind placebo-controlled clinical trials that compared multiple, fixed-doses of selective serotonin reuptake inhibitors (SSRIs) to each other and to placebo in the treatment of adults with OCD. Change in Y-BOCS score, proportion of treatment responders, and dropouts (all-cause and due to side-effects) were determined for each included study. Weighted mean difference was used to examine mean change in Y-BOCS score. Pooled absolute risk difference was used to examine dichotomous outcomes. Meta-analysis was performed using a fixed effects model in RevMan 4.2.8. We found that compared with either low or medium doses, higher doses of SSRIs were associated with improved treatment efficacy, using either Y-BOCS score or proportion of treatment responders as an outcome. Dose of SSRIs was not associated with the number of all-cause dropouts. Higher doses of SSRIs were associated with significantly higher proportion of dropouts due to side-effects. These results suggests that higher doses of SSRIs are associated with greater efficacy in the treatment of OCD. This SSRI efficacy pattern stands in contrast to other psychiatric disorders like Major Depressive Disorder. This greater treatment efficacy is somewhat counterbalanced by the greater side-effect burden with higher doses of SSRIs. At present, there are insufficient data to generalize these findings to children or adolescents with OCD.

A systematic review: antipsychotic augmentation with treatment refractory obsessive-compulsive disorder.

As many as half of obsessive-compulsive disorder (OCD) patients treated with an adequate trial of serotonin reuptake inhibitors (SRIs) fail to fully respond to treatment and continue to exhibit significant symptoms. Many studies have assessed the effectiveness of antipsychotic augmentation in SRI-refractory OCD. In this systematic review, we evaluate the efficacy of antipsychotic augmentation in treatment-refractory OCD. The electronic databases of PubMed, PsychINFO (1967-2005), Embase (1974-2000) and the Cochrane Central Register of Controlled Trials (CENTRAL, as of 2005, Issue 3) were searched for relevant double-blind trials using keywords 'antipsychotic agents' or 'neuroleptics' and 'obsessive-compulsive disorder'. Search results and analysis were limited to double-blind, randomized control trials involving the adult population. The proportion of subjects designated as treatment responders was defined by a greater than 35% reduction in Yale Brown Obsessive-Compulsive Scale (Y-BOCS) rating during the course of augmentation therapy. Nine studies involving 278 participants were included in the analysis. The meta-analysis of these studies demonstrated a significant absolute risk difference (ARD) in favor of antipsychotic augmentation of 0.22 (95% confidence interval (CI): 0.13, 0.31). The subgroup of OCD patients with comorbid tics have a particularly beneficial response to this intervention, ARD=0.43 (95% CI: 0.19, 0.68). There was also evidence suggesting OCD patients should be treated with at least 3 months of maximal-tolerated therapy of an SRI before initiating antipsychotic augmentation owing to the high rate of treatment response to continued SRI monotherapy (25.6%). Antipsychotic augmentation in SRI-refractory OCD is indicated in patients who have been treated for at least 3 months of maximal-tolerated therapy of an SRI. Unfortunately, only one-third of treatment-refractory OCD patients show a meaningful treatment response to antipsychotic augmentation. There is sufficient evidence in the published literature, demonstrating the efficacy of haloperidol and risperidone, and evidence regarding the efficacy of quetiapine and olanzapine is inconclusive. Patients with comorbid tics are likely to have a differential benefit to antipsychotic augmentation.

Positron emission mammography-guided breast biopsy.

UNLABELLED: Positron emission mammography (PEM) is a technique to obtain planar images of the breast for detection of potentially cancerous, radiotracer-avid tumors. To increase the diagnostic accuracy of this method, use of minimally invasive methods (e.g., core biopsy) may be desirable for obtaining tissue samples from lesions detected with PEM. The purpose of this study was to test the capabilities of a novel method for performing PEM-guided stereotactic breast biopsies. METHODS: The PEM system consisted of 2 square (10 x 10 cm) arrays of discrete scintillator crystals. The detectors were mounted on a stereotactic biopsy table. The stereotactic technique used 2 PEM images acquired at +/-15 degrees and a new trigonometric algorithm. The accuracy and precision of the guidance method was tested by placement of small point sources of (18)F at known locations within the field of view of the imager. The calculated positions of the sources were compared with the known locations. In addition, simulated stereotactic biopsies of a breast phantom consisting of a 10-mm-diameter gelatin sphere containing a concentration of (18)F-FDG consistent with that reported for breast cancer were performed. The simulated lesion was embedded in a 4-cm-thick slab of gelatin containing a commonly reported concentration of FDG, simulating a compressed breast (target-to-background ratio, approximately 8.5:1). An anthropomorphic torso phantom was used to simulate tracer uptake in the organs of a patient 1 h after a 370-MBq injection of FDG. Five trials of the biopsy procedure were performed to assess repeatability. Finally, a method for verifying needle positioning was tested. RESULTS: The positions of the point sources were successfully calculated to within 0.6 mm of their true positions with a mean error of +/-0.4 mm. The biopsy procedures, including the method for verification of needle position, were successful in all 5 trials in acquiring samples from the simulated lesions. CONCLUSION: The success of this new technique shows its potential for guiding the biopsy of breast lesions optimally detected with PEM.

The potential role of positron emission mammography for detection of breast cancer. A phantom study.

Positron emission mammography (PEM) is a new, specialized imaging modality utilizing PET radiopharmaceuticals to detect breast cancer. The capabilities and limitations of PEM in detecting breast tumors were investigated with a series of phantom experiments. The PEM imager was mounted on a standard Lorad biopsy table (separated by 18 cm). In the initial phase of the investigation, basic scanner parameters (resolution, sensitivity, and scatter fraction) were measured. The effects of a number of breast imaging parameters (length of acquisition, breast thickness, and breast density) on detection of breast lesions were then explored utilizing special phantoms. Moderately compressed breasts were simulated with a block of gelatin containing amounts of FDG consistent with 370 MBq injections. Lesions were simulated with four hollow spheres (inner diameters=5 mm, 8 mm, 12 mm, and 15 mm) filled with amounts of FDG representative of uptake in malignant breast tumors (target-to-background concentration ratio=8.5:1). Resolution at the center of the imager was 3.9 mm, sensitivity was 0.059 kcps/kBq/ml and the Compton scatter fraction was approximately 12%. Objects as small as 8 mm in diameter could be detected after 30 s of data acquisition; 5 mm spheres were detectable after 300 s. Object detection capabilities were reduced with increasing breast thickness. In thin compressed breasts (2 cm) even the smallest sphere (5 mm in diameter) could be detected; increasing breast thickness increased the minimum detectable sphere diameter to 8 mm. Increased background activity caused by FDG uptake in metabolically active normal tissue more prevalent in radiodense breasts compared to "fatty" breasts was simulated and shown to reduce the minimum detectable lesion size to 12 mm for the densest breasts. These results demonstrate the potential of PEM for the detection of breast lesions. The addition of the system to a standard biopsy apparatus indicates its potential for use to guide some core biopsies of breast cancers.

Performance of a PSPMT based detector for scintimammography.

In breast scintigraphy, compact detectors with high intrinsic spatial resolution and small inactive peripheries can provide improvements in extrinsic spatial resolution, efficiency and contrast for small lesions relative to larger conventional cameras. We are developing a pixelated small field-of-view gamma camera for scintimammography. Extensive measurements of the imaging properties of a prototype system have been made, including spatial resolution, sensitivity, uniformity of response, geometric linearity and energy resolution. An anthropomorphic torso phantom providing a realistic breast exit gamma spectrum has been used in a qualitative study of lesion detectability. A new type of breast imaging system that combines scintimammography and digital mammography in a single upright unit has also been developed. The system provides automatic co-registration between the scintigram and the digital mammogram, obtained with the breast in a single configuration. Intrinsic spatial resolution was evaluated via calculation of the phase-dependent modulation transfer function (MTF). Measurements of extrinsic spatial resolution, sensitivity and uniformity of response were made for two types of parallel hole collimator using NEMA (National Electrical Manufacturers Association) protocols. Geometric linearity was quantified using a line input and least squares analysis of the measured line shape. Energy resolution was measured for seven different crystal types, and the effectiveness of optical grease coupling was assessed. Exit gamma spectra were obtained using a cadmium zinc telluride based spectrometer. These were used to identify appropriate radioisotope concentrations for the various regions of an anthropomorphic torso phantom, such that realistic scatter conditions could be obtained during phantom measurements. For prone scintimammography, a special imaging table was constructed that permits simultaneous imaging of both breasts, as well as craniocaudal views. A dedicated breast imaging system was also developed that permits simultaneous acquisition and superposition of planar gamma images and digital x-ray images. The intrinsic MTF is nonstationary, and is dependent on the phase relationship between the signal and the crystal array matrix. Averaged over all phases, the MTF is approximately 0.75, 0.57 and 0.40 at spatial frequencies of 1.0, 1.5 and 2.0 cycles per cm, respectively. The phase averaged line spread function (LSF) has a FWHM value of 2.6 mm. Following uniformity corrections, the RMS deviations in flood images are only slightly greater than is predicted from counting statistics. Across an 80 mm section of the active area, the differential linearity is 0.83 mm and the absolute linearity 2.0 mm. Using an anthropomorphic torso phantom with detachable breasts, scatter radiation similar to that observed exiting the breast of scintimammography patients was observed. It was observed that scattered gamma rays can constitute the majority of the radiation incident on the detector, but that the scatter-to-primary ratio varies significantly across the field of view, being greatest in the caudal portion of the breast, where scatter from the liver is high. Using a lesion-to-breast concentration ratio of 6:1, a 1.0 cm3 simulated breast lesion was detectable in lateral images obtained with both the developmental camera and with a clinical camera, while a 0.35 cm3 lesion was detectable in neither. Utilization of the dual x-ray transmission, gamma emission breast imaging system greatly increases the conspicuity of scintimammographic lesions relative to prone imaging, as well as greatly facilitating the localization and identification of structures in the gamma image. The prototype imaging gamma detector exhibits spatial resolution superior to that of conventional cameras, and comparable uniformity of response and geometric linearity. Because of light losses in the crystals, the energy resolution is inferior to that of single crystal NaI(Tl) came

Preliminary results for positron emission mammography: real-time functional breast imaging in a conventional mammography gantry.

In order to optimally integrate radiotracer breast imaging within the breast clinic, anatomy and pathology should be easily correlated with functional nuclear medicine breast images. As a first step in the development of a hybrid functional/anatomic breast imaging platform with biopsy capability, a conventional X-ray mammography gantry was modified to image the compressed breast with positron emitters. Phantom studies with the positron emission mammography (PEM) device showed that a 1-cc hot spot could be detected within 5 min. A preliminary clinical trial demonstrated in vivo visualization of primary breast cancer within 4 min. For sites where positron-emitting radionuclides are available, PEM promises to achieve low-cost directed functional examination of breast abnormalities, with the potential for achieving X-ray correlation and image-guided biopsy.

Gamma-ray measurements from the space shuttle during a solar flare.

An X2/2B level solar flare occurred on 12 August, 1989, during the last day of the flight of the Space Shuttle Columbia (STS-28). Detectors on the GOES 7 satellite observed increased X-ray fluxes at approximately 1400 GMT and a solar particle event (SPE) at approximately 1600 GMT. Measurements with the bismuth germanate (BGO) detector of the Shuttle Activation Monitor (SAM) experiment on STS-28 showed factors of two to three increases in count rates at high latitudes comparable to those seen during South Atlantic Anomaly (SAA) passages beginning at about 1100 GMT. That increased activity was observed at both north and south high latitudes in the 57 degrees, 300 kilometer orbit and continued until the detector was turned off at 1800 GMT. Measurements made earlier in the flight over the same geographic coordinates did not produce the same levels of activity. This increase in activity may not be entirely accounted for by observed geomagnetic phenomena which were not related to the solar flare.

Effects of increased shielding on gamma-radiation levels within spacecraft.

The Shuttle Activation Monitor (SAM) experiment was flown on the Space Shuttle Columbia (STS-28) from 8-13 August, 1989 in a 57 degrees, 300 km orbit. One objective of the SAM experiment was to determine the relative effect of different amounts of shielding on the gamma-ray backgrounds measured with similarly configured sodium iodide (NaI) and bismuth germante (BGO) detectors. To achieve this objective twenty-four hours of data were taken with each detector in the middeck of the Shuttle on the ceiling of the airlock (a high-shielding location) as well as on the sleep station wall (a low-shielding location). For the cosmic-ray induced background the results indicate an increased overall count rate in the 0.2 to 10 MeV energy range at the more highly shielded location, while in regions of trapped radiation the low shielding configuration gives higher rates at the low energy end of the spectrum.

Photomultiplier for optically probing Comet Halley.

A low mass eight-color channel photopolarimeter was developed for the Giotto spacecraft. Utilizing the spin of the spacecraft, a multichannel plate photomultiplier, and a unique optical design, the instrument required no moving parts to measure color and linear polarization. The photopolarimeter collected data as the spacecraft passed through the coma of Comet Halley on 13 and 14 Mar. 1986. This instrument's design, calibration, and reduction are discussed and some final results are presented.