Brief Cognitive Behavioral Therapy for Suicidal Inpatients: A Randomized Clinical Trial.

Importance: Suicide risk is elevated after discharge from inpatient level of care. Empirically supported inpatient suicide prevention treatments are needed. Objective: To determine whether adding an inpatient version of brief cognitive behavioral therapy for suicide prevention to treatment as usual reduces postdischarge suicide attempts, suicidal ideation, and psychiatric readmissions and to determine whether substance use disorder moderates treatment effects. Design, Setting, and Participants: This randomized clinical trial compared treatment as usual (n = 106) to treatment as usual plus brief cognitive behavioral therapy for inpatients (n = 94) at a private psychiatric hospital in Connecticut. Follow-up assessments were completed monthly for 6 months postdischarge. Participants were enrolled from January 2020 through February 2023. Inpatients admitted following a suicidal crisis (past-week suicide attempt or ideation with plan on admission and attempt within previous 2 years) were included. Medical records of consecutive admissions (n = 4137) were screened, 213 were study eligible and randomized, and 200 were analyzed. A total of 114 participants (57.0%) completed 6-month follow-up assessments. Data from medical records were also obtained through 6-month follow-up. Intervention: Up to 4 individual sessions of brief cognitive behavioral therapy for suicide prevention designed for inpatients. Main Outcomes and Measures: Suicide attempts and readmissions were assessed via blind interviews and medical record review. Suicidal ideation was assessed via self-report. Results: The mean (SD) age among 200 analyzed participants was 32.8 (12.6) years; 117 participants were female and 83 were male. Brief cognitive behavioral therapy-inpatient reduced the occurrence of suicide attempt over 6 months postdischarge by 60% (odds ratio, 0.40; 95% CI, 0.20-0.80; number needed to treat, 7) in the entire patient group, and the rate of psychiatric readmissions by 71% (rate ratio, 0.29; 95% CI, 0.09-0.90) in those without a substance use disorder. The effect of treatment condition on suicidal ideation was less clear, although post hoc analyses indicated less severe suicidal ideation following brief cognitive behavioral therapy-inpatient vs treatment as usual at 1 and 2 months postdischarge. Conclusions and Relevance: Brief cognitive behavioral therapy-inpatient reduced 6-month postdischarge suicide reattempts and rate of readmissions when added to treatment as usual. Substance use disorder moderated the treatment's effect on readmission rates. Treatment effects on suicidal ideation were less clear. Implementation research is needed to facilitate dissemination. Additional research is also needed to optimize outcomes for individuals with substance use disorders. Trial Registration: ClinicalTrials.gov Identifier: NCT04168645.

Uncovering the role of substance use in suicide attempts using a mixed-methods approach.

INTRODUCTION: Substance use is an established risk factor for suicide attempt. Clarifying the role of substance use in suicide attempts may identify modifiable treatment targets. This study used mixed methods to associate substance use with suicide attempt history and identify pathways through which substance use contributes to attempts. METHODS: Study 1 included 213 adult inpatients (n = 127 with substance use disorder [SUD]), who completed assessments of suicide attempt history as well as demographic and clinical suicide risk factors. Study 2 was a narrative analysis of suicide attempt stories described by 20 inpatients diagnosed with SUD. RESULTS: In Study 1, patients with co-occurring alcohol and drug use disorders reported more actual lifetime suicide attempts than did those without SUD. In addition, alcohol and drug use disorders were independently associated with lifetime suicide attempts after controlling for demographic and clinical confounders. In Study 2, substance use played a role in all suicide attempts through at least one pathway before, during, or after a triggering stressor, or as suicide attempt method. CONCLUSIONS: Substances play a role in suicide attempt baseline risk, acute risk and as means. It is important to target chronic and acute substance use in suicide prevention treatment plans.

A Real-Time Blood Flow Measurement Device for Patients with Peripheral Artery Disease.

PURPOSE: To evaluate the feasibility of a new optical device that measures peripheral blood flow as a diagnostic and monitoring tool for patients with peripheral artery disease (PAD). MATERIALS AND METHODS: In this prospective study, 167 limbs of 90 patients (mean age, 76 y; 53% men) with suspected PAD were evaluated with the FlowMet device, which uses a new type of dynamic light-scattering technology to assess blood flow in real time. Measurements of magnitude and phasicity of blood flow were combined into a single-value flow-waveform score and compared vs ankle-brachial index (ABI), toe-brachial index (TBI), and clinical presentation of patients per Rutherford category (RC). Receiver operating characteristic curves were constructed to predict RC. Area under the curve (AUC), sensitivity, and specificity were compared among flow-waveform score, ABI, and TBI. RESULTS: Qualitatively, the FlowMet waveforms were analogous to Doppler velocity measurements, and degradation of waveform phasicity and amplitude were observed with increasing PAD severity. Quantitatively, the flow, waveform, and composite flow-waveform scores decreased significantly with decreasing TBI. In predicting RC ≥ 4, the flow-waveform score (AUC = 0.83) showed a linear decrease with worsening patient symptoms and power comparable to that of TBI (AUC = 0.82) and better than that of ABI (AUC = 0.71). Optimal sensitivity and specificity pairs were found to be 56%/83%, 72%/81%, and 89%/74% for ABI, TBI, and flow-waveform score, respectively. CONCLUSIONS: The technology tested in this pilot study showed a high predictive value for diagnosis of critical limb ischemia. The device showed promise as a diagnostic tool capable of providing clinical feedback in real time.

Effect of skin optical absorption on speckleplethysmographic (SPG) signals.

Recent advances in optical technology have emerged for measuring blood flow in the extremities using speckleplethysmography (SPG), which may address needs in vascular medicine and other fields. SPG has demonstrated a highly linear response with flow rate, but the susceptibility to differences in skin tone is unclear. Two validation studies using skin-simulating phantoms and a simple clinical protocol were conducted to determine the impact of absorbing skin layers on SPG measurements. Benchtop results demonstrated that the coefficient of determination between known flow rate and SPG was highly linear (R2 = 0.990) and was unaffected by the addition of skin-phantom layers with variable absorption (R2 = 0.996-0.999). Additionally, no significant trend was found between the fit residuals of SPG and flow rate with increasing skin-phantom absorption (R2=0.025, p = 0.29). In clinical testing, no significant difference was found using both a 4-way ANOVA between demographic classifications (F = 0.89, p = 0.45), and a 2-way ANOVA test between lower- and higher-melanin subclassifications (F = 0.4, p = 0.52).

Wearable speckle plethysmography (SPG) for characterizing microvascular flow and resistance.

In this work we introduce a modified form of laser speckle imaging (LSI) referred to as affixed transmission speckle analysis (ATSA) that uses a single coherent light source to probe two physiological signals: one related to pulsatile vascular expansion (classically known as the photoplethysmographic (PPG) waveform) and one related to pulsatile vascular blood flow (named here the speckle plethysmographic (SPG) waveform). The PPG signal is determined by recording intensity fluctuations, and the SPG signal is determined via the LSI dynamic light scattering technique. These two co-registered signals are obtained by transilluminating a single digit (e.g. finger) which produces quasi-periodic waveforms derived from the cardiac cycle. Because PPG and SPG waveforms probe vascular expansion and flow, respectively, in cm-thick tissue, these complementary phenomena are offset in time and have rich dynamic features. We characterize the timing offset and harmonic content of the waveforms in 16 human subjects and demonstrate physiologic relevance for assessing microvascular flow and resistance.

Multifrequency synthesis and extraction using square wave projection patterns for quantitative tissue imaging.

We present a method for spatial frequency domain data acquisition utilizing a multifrequency synthesis and extraction (MSE) method and binary square wave projection patterns. By illuminating a sample with square wave patterns, multiple spatial frequency components are simultaneously attenuated and can be extracted to determine optical property and depth information. Additionally, binary patterns are projected faster than sinusoids typically used in spatial frequency domain imaging (SFDI), allowing for short (millisecond or less) camera exposure times, and data acquisition speeds an order of magnitude or more greater than conventional SFDI. In cases where sensitivity to superficial layers or scattering is important, the fundamental component from higher frequency square wave patterns can be used. When probing deeper layers, the fundamental and harmonic components from lower frequency square wave patterns can be used. We compared optical property and depth penetration results extracted using square waves to those obtained using sinusoidal patterns on an in vivo human forearm and absorbing tube phantom, respectively. Absorption and reduced scattering coefficient values agree with conventional SFDI to within 1% using both high frequency (fundamental) and low frequency (fundamental and harmonic) spatial frequencies. Depth penetration reflectance values also agree to within 1% of conventional SFDI.

Visible spatial frequency domain imaging with a digital light microprojector.

There is a need for cost effective, quantitative tissue spectroscopy and imaging systems in clinical diagnostics and pre-clinical biomedical research. A platform that utilizes a commercially available light-emitting diode (LED) based projector, cameras, and scaled Monte Carlo model for calculating tissue optical properties is presented. These components are put together to perform spatial frequency domain imaging (SFDI), a model-based reflectance technique that measures and maps absorption coefficients (µa) and reduced scattering coefficients (µs') in thick tissue such as skin or brain. We validate the performance of the flexible LED and modulation element (FLaME) system at 460, 530, and 632 nm across a range of physiologically relevant µa values (0.07 to 1.5 mm-1) in tissue-simulating intralipid phantoms, showing an overall accuracy within 11% of spectrophotometer values for µa and 3% for µs'. Comparison of oxy- and total hemoglobin fits between the FLaME system and a spectrophotometer (450 to 1000 nm) is differed by 3%. Finally, we acquire optical property maps of a mouse brain in vivo with and without an overlying saline well. These results demonstrate the potential of FLaME to perform tissue optical property mapping in visible spectral regions and highlight how the optical clearing effect of saline is correlated to a decrease in µs' of the skull.

System analysis of spatial frequency domain imaging for quantitative mapping of surgically resected breast tissues.

The feasibility of spatial frequency domain imaging (SFDI) for breast surgical margin assessment was evaluated in tissue-simulating phantoms and in fully intact lumpectomy specimens at the time of surgery. Phantom data was evaluated according to contrast-detail resolution, quantitative accuracy and model-data goodness of fit, where optical parameters were estimated by minimizing the residual sum of squares between the measured modulation amplitude and its solutions, modeled according to diffusion and scaled-Monte Carlo simulations. In contrast-detail phantoms, a 1.25-mm-diameter surface inclusion was detectable for scattering contrast >28%; a fraction of this scattering contrast (7%) was detectable for a 10 mm surface inclusion and at least 33% scattering contrast was detected up to 1.5 mm below the phantom surface, a probing depth relevant to breast surgical margin assessment. Recovered hemoglobin concentrations were insensitive to changes in scattering, except for overestimation at visible wavelengths for total hemoglobin concentrations <15 µM. The scattering amplitude increased linearly with scattering concentration, but the scattering slope depended on both the particle size and number density. Goodness of fit was comparable for the diffusion and scaled-Monte Carlo models of transport in spatially modulated, near-infrared reflectance acquired from 47 lumpectomy tissues, but recovered absorption parameters varied more linearly with expected hemoglobin concentration in liquid phantoms for the scaled-Monte Carlo forward model. SFDI could potentially reduce the high secondary excision rate associated with breast conserving surgery; its clinical translation further requires reduced image reconstruction time and smart inking strategies.

Quantitative, depth-resolved determination of particle motion using multi-exposure, spatial frequency domain laser speckle imaging.

Laser Speckle Imaging (LSI) is a simple, noninvasive technique for rapid imaging of particle motion in scattering media such as biological tissue. LSI is generally used to derive a qualitative index of relative blood flow due to unknown impact from several variables that affect speckle contrast. These variables may include optical absorption and scattering coefficients, multi-layer dynamics including static, non-ergodic regions, and systematic effects such as laser coherence length. In order to account for these effects and move toward quantitative, depth-resolved LSI, we have developed a method that combines Monte Carlo modeling, multi-exposure speckle imaging (MESI), spatial frequency domain imaging (SFDI), and careful instrument calibration. Monte Carlo models were used to generate total and layer-specific fractional momentum transfer distributions. This information was used to predict speckle contrast as a function of exposure time, spatial frequency, layer thickness, and layer dynamics. To verify with experimental data, controlled phantom experiments with characteristic tissue optical properties were performed using a structured light speckle imaging system. Three main geometries were explored: 1) diffusive dynamic layer beneath a static layer, 2) static layer beneath a diffuse dynamic layer, and 3) directed flow (tube) submerged in a dynamic scattering layer. Data fits were performed using the Monte Carlo model, which accurately reconstructed the type of particle flow (diffusive or directed) in each layer, the layer thickness, and absolute flow speeds to within 15% or better.

Determination of the effect of source intensity profile on speckle contrast using coherent spatial frequency domain imaging.

Laser Speckle Imaging (LSI) is fast, noninvasive technique to image particle dynamics in scattering media such as biological tissue. While LSI measurements are independent of the overall intensity of the laser source, we find that spatial variations in the laser source profile can impact measured flow rates. This occurs due to differences in average photon path length across the profile, and is of significant concern because all lasers have some degree of natural Gaussian profile in addition to artifacts potentially caused by projecting optics. Two in vivo measurement are performed to show that flow rates differ based on location with respect to the beam profile. A quantitative analysis is then done through a speckle contrast forward model generated within a coherent Spatial Frequency Domain Imaging (cSFDI) formalism. The model predicts remitted speckle contrast as a function of spatial frequency, optical properties, and scattering dynamics. Comparison with experimental speckle contrast images were done using liquid phantoms with known optical properties for three common beam shapes. cSFDI is found to accurately predict speckle contrast for all beam shapes to within 5% root mean square error. Suggestions for improving beam homogeneity are given, including a widening of the natural beam Gaussian, proper diffusing glass spreading, and flat top shaping using microlens arrays.

Quantitative determination of dynamical properties using coherent spatial frequency domain imaging.

Laser speckle imaging (LSI) is a fast, noninvasive method to obtain relative particle dynamics in highly light scattering media, such as biological tissue. To make quantitative measurements, we combine LSI with spatial frequency domain imaging, a technique where samples are illuminated with sinusoidal intensity patterns of light that control the characteristic path lengths of photons in the sample. We use both diffusion and radiative transport to predict the speckle contrast of coherent light remitted from turbid media. We validate our technique by measuring known Brownian diffusion coefficients (D(b)) of scattering liquid phantoms. Monte Carlo (MC) simulations of radiative transport were found to provide the most accurate contrast predictions. For polystyrene microspheres of radius 800 nm in water, the expected and fit D(b) using radiative transport were 6.10E-07 and 7.10E-07 mm²/s, respectively. For polystyrene microspheres of radius 1026 nm in water, the expected and fit D(b) were 4.7E-07 and 5.35 mm²/s, respectively. For scattering particles in water-glycerin solutions, the fit fractional changes in D(b) with changes in viscosity were all found to be within 3% of the expected value.

Laser speckle imaging in the spatial frequency domain.

Laser Speckle Imaging (LSI) images interference patterns produced by coherent addition of scattered laser light to map subsurface tissue perfusion. However, the effect of longer path length photons is typically unknown and poses a limitation towards absolute quantification. In this work, LSI is integrated with spatial frequency domain imaging (SFDI) to suppress multiple scattering and absorption effects. First, depth sensitive speckle contrast is shown in phantoms by separating a deep source (4 mm) from a shallow source (2 mm) of speckle contrast by using a high spatial frequency of illumination (0.24 mm(-1)). We develop an SFD adapted correlation diffusion model and show that with high frequency (0.24 mm(-1)) illumination, doubling of absorption contrast results in only a 1% change in speckle contrast versus 25% change using a planar unmodulated (0 mm(-1)) illumination. Similar absorption change is mimicked in vivo imaging a finger occlusion and the relative speckle contrast change from baseline is 10% at 0.26 mm(-1) versus 60% at 0 mm(-1) during a finger occlusion. These results underscore the importance of path length and optical properties in determining speckle contrast. They provide an integrated approach for simultaneous mapping of blood flow (speckle contrast) and oxygenation (optical properties) which can be used to inform tissue metabolism.

Spatial frequency domain imaging of intrinsic optical property contrast in a mouse model of Alzheimer's disease.

Extensive changes in neural tissue structure and function accompanying Alzheimer's disease (AD) suggest that intrinsic signal optical imaging can provide new contrast mechanisms and insight for assessing AD appearance and progression. In this work, we report the development of a wide-field spatial frequency domain imaging (SFDI) method for non-contact, quantitative in vivo optical imaging of brain tissue composition and function in a triple transgenic mouse AD model (3xTg). SFDI was used to generate optical absorption and scattering maps at up to 17 wavelengths from 650 to 970 nm in 20-month-old 3xTg mice (n = 4) and age-matched controls (n = 6). Wavelength-dependent optical properties were used to form images of tissue hemoglobin (oxy-, deoxy-, and total), oxygen saturation, and water. Significant baseline contrast was observed with 13-26% higher average scattering values and elevated water content (52 ± 2% vs. 31 ± 1%); reduced total tissue hemoglobin content (127 ± 9 µM vs. 174 ± 6 µM); and lower tissue oxygen saturation (57 ± 2% vs. 69 ± 3%) in AD vs. control mice. Oxygen inhalation challenges (100% oxygen) resulted in increased levels of tissue oxy-hemoglobin (ctO(2)Hb) and commensurate reductions in deoxy-hemoglobin (ctHHb), with ~60-70% slower response times and ~7 µM vs. ~14 µM overall changes for 3xTg vs. controls, respectively. Our results show that SFDI is capable of revealing quantitative functional contrast in an AD model and may be a useful method for studying dynamic alterations in AD neural tissue composition and physiology.