Systematic review and meta-analysis of neurofeedback and its effect on posttraumatic stress disorder.

Background: To date, only one systematic review and meta-analysis of randomized controlled trials (RCTs) has evaluated the effect of neurofeedback in PTSD, which included only four studies and found an uncertainty of the effect of EEG-NF on PTSD symptoms. This meta-analysis is an update considering that numerous studies have since been published. Additionally, more recent studies have included fMRI-NF as well as fMRI-guided or -inspired EEG NF. Methods: Systematic literature searches for RCTs were conducted in three online databases. Additional hand searches of each study identified and of systematic reviews and meta-analyses published were also undertaken. Outcomes evaluated the effect of neurofeedback vs. a control (active, sham, and waiting list) on their effects in reducing PTSD symptoms using various health instruments. Meta-analytical methods used were inverse variance random-effects models measuring both mean and standardized mean differences. Quality and certainty of the evidence were assessed using GRADE. Adverse events were also evaluated. Results: A total of 17 studies were identified evaluating a total of 628 patients. There were 10 studies used in the meta-analysis. Results from all studies identified favored neurofeedback's effect on reducing PTSD symptoms including BDI pretest-posttest [mean difference (MD): 8.30 (95% CI: 3.09 to 13.52; P = 0.002; I 2 = 0%)]; BDI pretest-follow-up (MD: 8.75 (95% CI: 3.53 to 13.97; P < 0.00001; I 2 = 0%); CAPS-5 pretest-posttest [MD: 7.01 (95% CI: 1.36 to 12.66; P = 0.02; I 2 = 86%)]; CAPS-5 pretest-follow-up (MD: 10 (95% CI: 1.29 to 21.29; P = 0.006; I 2 = 77%); PCL-5 pretest-posttest (MD: 7.14 (95% CI: 3.08 to 11.2; P = 0.0006; I 2 = 0%); PCL-5 pretest-follow-up (MD: 14.95 (95% CI: 7.95 to 21.96; P < 0.0001; I 2 = 0%). Other studies reported improvements using various other instruments. GRADE assessments of CAPS, PCL, and BDI demonstrated a moderate/high level in the quality of the evidence that NF has a positive clinical effect. Conclusion: Based on newer published studies and the outcomes measured, NF has demonstrated a clinically meaningful effect size, with an increased effect size at follow-up. This clinically meaningful effect appears to be driven by newer fMRI-guided NF and deeper brain derivates of it.

Lifetime cost-effectiveness analysis osseointegrated transfemoral versus socket prosthesis using Markov modelling.

Aims: Prior cost-effectiveness analyses on osseointegrated prosthesis for transfemoral unilateral amputees have analyzed outcomes in non-USA countries using generic quality of life instruments, which may not be appropriate when evaluating disease-specific quality of life. These prior analyses have also focused only on patients who had failed a socket-based prosthesis. The aim of the current study is to use a disease-specific quality of life instrument, which can more accurately reflect a patient's quality of life with this condition in order to evaluate cost-effectiveness, examining both treatment-naïve and socket refractory patients. Methods: Lifetime Markov models were developed evaluating active healthy middle-aged male amputees. Costs of the prostheses, associated complications, use/non-use, and annual costs of arthroplasty parts and service for both a socket and osseointegrated (OPRA) prosthesis were included. Effectiveness was evaluated using the questionnaire for persons with a transfemoral amputation (Q-TFA) until death. All costs and Q-TFA were discounted at 3% annually. Sensitivity analyses on those cost variables which affected a change in treatment (OPRA to socket, or socket to OPRA) were evaluated to determine threshold values. Incremental cost-effectiveness ratios (ICERs) were calculated. Results: For treatment-naïve patients, the lifetime ICER for OPRA was $279/quality-adjusted life-year (QALY). For treatment-refractory patients the ICER was $273/QALY. In sensitivity analysis, the variable thresholds that would affect a change in the course of treatment based on cost (from socket to OPRA), included the following for the treatment-naïve group: yearly replacement components for socket > $8,511; cost yearly replacement parts OPRA < $1,758; and for treatment-refractory group: yearly replacement component for socket of > $12,467. Conclusion: The use of the OPRA prosthesis in physically active transfemoral amputees should be considered as a cost-effective alternative in both treatment-naïve and treatment-refractory socket prosthesis patients. Disease-specific quality of life assessments such as Q-TFA are more sensitive when evaluating cost-effectiveness.

Amygdala-derived-EEG-fMRI-pattern neurofeedback for the treatment of chronic post-traumatic stress disorder. A prospective, multicenter, multinational study evaluating clinical efficacy.

We conducted a prospective, single arm, multisite, multinational, open label trial assessing the safety and efficacy of a novel amygdala derived neurofeedback treatment, designated Amygdala-Derived-EFP, for chronic PTSD. Participants, including veterans and civilians, underwent screening, training, 15 neurofeedback sessions over 8 weeks and; baseline, termination (8 weeks) and 3 month post treatment assessments with validated measures. The primary endpoint was more than 50 % of the participants demonstrating a Minimally Clinically Important Difference (MCID) defined as a 6-point reduction, on the Clinician Administered PTSD Scale (CAPS-5) total score at 3 months. Secondary measures included the PCL-5, ERQ, PHQ-9, and CGI. Statistical analyses were performed using SAS®V9.4. The primary endpoint was met, with a CAPS-5 MCID response rate of 66.7 %. The average reduction in CAPS-5 total scores at 3 month follow up was 13.5 points, more than twice the MCID. Changes from baseline in CAPS-5, PCL-5, PHQ-9 scores at 8 weeks and the 3 month follow-up demonstrated statistically significant improvements in response and; demonstrated effect sizes ranging from 0.46 to 1.07. Adverse events were mild and resolved after treatment. This study builds on prior research demonstrating similar outcomes using amygdala-derived neurofeedback. Positive attributes of this therapy include monitoring by non-physician personnel, affordability, accessibility, and tolerability.

Multicenter Registry Using Propensity Score Analysis to Compare a Novel Transport/Preservation System to Traditional Means on Postoperative Hospital Outcomes and Costs for Heart Transplant Patients.

The standard method for cardiac allograft preservation for the past 50 years has been static storage using crushed ice. A heart transplant transportation system designed to improve preservation quality with temperature monitoring, the Paragonix SherpaPak Cardiac Transport System (SCTS), was evaluated for its impact on postoperative costs relative to conventional ice storage. Observational US multicenter registry data collected during the August 2015 to November 2021 timeframe from 12 transplant hospitals were analyzed using logistic regression analysis and propensity matching to balance measured baseline covariates and to reduce selection bias. Hospital cost and outcome data post-transplant were then evaluated using various statistical methods. One hundred seventy-four (174) patients were identified resulting in 87 matches. Baseline characteristics were similar between groups. The SCTS group had a significantly lower proportion of ICU days on post-transplant mechanical circulatory support ( p < 0.0001); significantly fewer patients on extracorporeal membrane oxygenation ( p = 0.017); and significantly fewer patients experiencing severe primary graft dysfunction (PGD) ( p = 0.03). Overall hospital plus mechanical circulatory support post-transplant costs were significantly lower by $26.7K in the CTS cohort ( p = 0.03). Use of the SCTS is associated with improved clinical outcomes resulting in significantly lower overall hospital care costs.

Examining spoken words and acoustic features of therapy sessions to understand family caregivers' anxiety and quality of life.

BACKGROUND: Speech and language cues are considered significant data sources that can reveal insights into one's behavior and well-being. The goal of this study is to evaluate how different machine learning (ML) classifiers trained both on the spoken word and acoustic features during live conversations between family caregivers and a therapist, correlate to anxiety and quality of life (QoL) as assessed by validated instruments. METHODS: The dataset comprised of 124 audio-recorded and professionally transcribed discussions between family caregivers of hospice patients and a therapist, of challenges they faced in their caregiving role, and standardized assessments of self-reported QoL and anxiety. We custom-built and trained an Automated Speech Recognition (ASR) system on older adult voices and created a logistic regression-based classifier that incorporated audio-based features. The classification process automated the QoL scoring and display of the score in real time, replacing hand-coding for self-reported assessments with a machine learning identified classifier. FINDINGS: Of the 124 audio files and their transcripts, 87 of these transcripts (70%) were selected to serve as the training set, holding the remaining 30% of the data for evaluation. For anxiety, the results of adding the dimension of sound and an automated speech-to-text transcription outperformed the prior classifier trained only on human-rendered transcriptions. Specifically, precision improved from 86% to 92%, accuracy from 81% to 89%, and recall from 78% to 88%. INTERPRETATION: Classifiers can be developed through ML techniques which can indicate improvements in QoL measures with a reasonable degree of accuracy. Examining the content, sound of the voice and context of the conversation provides insights into additional factors affecting anxiety and QoL that could be addressed in tailored therapy and the design of conversational agents serving as therapy chatbots.

Theta burst stimulation for the acute treatment of major depressive disorder: A systematic review and meta-analysis.

Patients with major depressive disorder (MDD) may be refractory to or have contraindications that preclude treatment with antidepressant pharmacotherapies. Alternative therapies such as repetitive transcranial magnetic stimulation (rTMS) continue to evolve, and include theta burst stimulation (TBS), which has advantages over conventional rTMS. The aim of this study was to identify and meta-analyze efficacy data from all randomized controlled trials (RCTs) investigating TBS as a treatment for MDD. Published reports of RCTs (January 1, 2010 to October 23, 2020) were identified via systematic searches in computerized databases, followed by review of individual reports for inclusion. Inclusion criteria included primary diagnosis of MDD ≥ 1 week duration of therapy with ≥10 sessions, and treatment with any form of TBS. The Cochrane GRADE methodology and PRISMA criteria were used for evaluation of individual trials. Data from ten RCTs were included, representing 667 patients. Of these, 8 RCTs compared TBS to sham treatment and one compared TBS to standard rTMS (i.e., high frequency stimulation over left dorsolateral prefrontal cortex [HFL]). Quality of evidence assessment yielded high confidence in the finding of TBS being superior to sham on response measured by the Hamilton Depression Rating Scale (HRSD) (RR = 2.4; 95% CI: 1.27 to 4.55; P = 0.007; I2 = 40%). Comparison of HRSD response rates for TBS versus rTMS produced no statistically significant difference (RR = 1.02; 95% CI: 0.85 to 1.23; P = 0.80; I2 = 0%). The incidence of adverse events between TBS and rTMS was not statistically different. The findings of a positive effect of TBS vs. sham, and noninferiority of TBS vs. standard HFL rTMS support the continued development of TBS to treat depression.

Spoken words as biomarkers: using machine learning to gain insight into communication as a predictor of anxiety.

OBJECTIVE: The goal of this study was to explore whether features of recorded and transcribed audio communication data extracted by machine learning algorithms can be used to train a classifier for anxiety. MATERIALS AND METHODS: We used a secondary data set generated by a clinical trial examining problem-solving therapy for hospice caregivers consisting of 140 transcripts of multiple, sequential conversations between an interviewer and a family caregiver along with standardized assessments of anxiety prior to each session; 98 of these transcripts (70%) served as the training set, holding the remaining 30% of the data for evaluation. RESULTS: A classifier for anxiety was developed relying on language-based features. An 86% precision, 78% recall, 81% accuracy, and 84% specificity were achieved with the use of the trained classifiers. High anxiety inflections were found among recently bereaved caregivers and were usually connected to issues related to transitioning out of the caregiving role. This analysis highlighted the impact of lowering anxiety by increasing reciprocity between interviewers and caregivers. CONCLUSION: Verbal communication can provide a platform for machine learning tools to highlight and predict behavioral health indicators and trends.

Use of the 4Kscore test to predict the risk of aggressive prostate cancer prior to prostate biopsy: Overall cost savings and improved quality of care to the us healthcare system.

The 4Kscore® Test (BioReference Laboratories, Elmwood Park, NJ) is a blood test that accurately determines the risk of aggressive prostate cancer and significantly reduces prostate biopsies and associated overdiagnosis and overtreatment of indolent cancer. A budget impact model was developed to test the hypothesis that the 4Kscore Test can improve quality of care and deliver cost savings for patients who are suspected of having prostate cancer and would otherwise undergo prostate biopsy under the current standard of care (SOC) in the United States. The direct costs (diagnosis plus treatment) utilized in the model are based on Medicare payment data and were calculated over a 1-year time horizon. The model compares SOC, in which all patients have prostate biopsy, to a "4Kscore strategy," in which the 4Kscore Test is used to guide the decision to biopsy the prostate. A set of one-way sensitivity analyses was conducted to examine the robustness of the findings. Savings of more than $169 million (15.6% of total SOC costs) were realized in the 4Kscore strategy versus SOC ($917 M versus $1,086 M, respectively) in a cohort of 100,000 patients. Sensitivity analyses demonstrated that the findings are robust. Most cost savings for the 4Kscore strategy were realized in patients who, when managed by SOC, are found to have no prostate cancer or Gleason score 6 pathology. The patients with Gleason score 6 exhibited the greatest benefits from the 4Kscore strategy, avoiding both an unnecessary prostate biopsy and subsequent overtreatment. The 4Kscore Test was shown to significantly reduce costs to the healthcare system while improving patients' quality of care. Providers and their patients suspected of having prostate cancer should consider using the 4Kscore Test prior to proceeding with prostate biopsy.

A Systematic Review and Meta-Analysis of Studies Examining the Use of Brain Laser Interstitial Thermal Therapy versus Craniotomy for the Treatment of High-Grade Tumors in or near Areas of Eloquence: An Examination of the Extent of Resection and Major Complication Rates Associated with Each Type of Surgery.

BACKGROUND: The extent of resection (EOR) of high-grade gliomas (WHO grade III or IV) in or near areas of eloquence is associated with overall patient survival, but with higher major neurocognitive complications. METHODS: A systematic review and meta-analysis was undertaken of the peer-reviewed literature in order to identify studies which examined EOR or extent of ablation (EOA) and major complications (defined as neurocognitive or functional complications which last >3 months duration after surgery) associated with either brain laser interstitial thermal therapy (LITT) or open craniotomy in high-grade tumors in or near areas of eloquence. RESULTS: Eight studies on brain LITT (n = 79 patients) and 12 craniotomy studies (n = 1,036 patients) were identified which examined either/both EOR/EOA and complications. Meta-analysis demonstrated an EOA/EOR of 85.4 ± 10.6% with brain LITT versus 77.0 ± 40% with craniotomy (mean difference: 8%; 95% CI: 2-15; p = 0.01; inverse variance, random effects model). Meta-analysis of proportions of major complications for each individual therapy demonstrated major complications of 5.7% (95% CI: 1.8-11.6) and 13.8% (95% CI: 10.3-17.9) for LITT and craniotomy, respectively. CONCLUSION: In patients presenting with high-grade gliomas in or near areas of eloquence, early results demonstrate that brain LITT may be a viable surgical alternative.

The value of using a brain laser interstitial thermal therapy (LITT) system in patients presenting with high grade gliomas where maximal safe resection may not be feasible.

BACKGROUND: The objective of this analysis was to determine the value (incremental cost/increment benefit) of a brain LITT system versus employing current surgical options recommended by NCCN guidelines, specifically open resection (i.e. craniotomy) methods or biopsy (collectively termed CURRENT TREATMENTS) in patients where maximal safe resection may not be feasible. As has been demonstrated in the literature, extent of resection/ablation with minimal complications are independently related to overall survival. METHODS: A cost effectiveness analysis from a societal perspective was employed using TreeAge Pro 2014 software. Direct costs (using national average Medicare reimbursement amounts), outcomes (overall survival), and value [defined as increment cost/incremental survival-evaluated as cost/life year gained (LYG)] were evaluated. Sensitivity analysis was also performed to determine which variables had the largest effect on incremental costs and outcomes. RESULTS: In the base case, the overall survival was improved with brain LITT versus CURRENT TREATMENTS by 3.07 months at an additional cost of $7508 (or $29,340/LYG). This amount was significantly less than the current international threshold value for $32,575/LYG and considerably less than the US threshold value of $50,000/LYG. This incremental cost may also qualify under NICE criteria for end of life therapies. In sensitivity analysis: As percent local recurrence GBM increased; cost of DRG25/26 increased; percent GTR increased; and gliadel use increased-the value of brain LITT improved. Additionally, in those patients where a biopsy is the only option, brain LITT extended life by 7 months. CONCLUSIONS: Brain LITT should be considered a viable option for treatment of high grade gliomas as it improves survival at a cost which appears to be of good value to society. This incremental cost is less than the international and US thresholds for good value.

Diagnostic needle arthroscopy and the economics of improved diagnostic accuracy: a cost analysis.

BACKGROUND: Hundreds of thousands of surgical arthroscopy procedures are performed annually in the United States (US) based on MRI findings. There are situations where these MRI findings are equivocal or indeterminate and because of this clinicians commonly perform the arthroscopy in order not to miss pathology. Recently, a less invasive needle arthroscopy system has been introduced that is commonly performed in the physician office setting and that may help improve the accuracy of diagnostic findings. This in turn may prevent unnecessary follow-on arthroscopy procedures from being performed. OBJECTIVE: The purpose of this analysis is to determine whether the in-office diagnostic needle arthroscopy system can provide cost savings by reducing unnecessary follow on arthroscopy procedures. METHODS: Data obtained from a recent trial and from a systematic review were used in comparing the accuracy of MRI and VisionScope needle arthroscopy (VSI) with standard arthroscopy (gold standard). The resultant false positive and false negative findings were then used to evaluate the costs of follow-on procedures. These differences were then modeled for the US patient population diagnosed and treated for meniscal knee pathology (most common disorder) to determine if a technology such as VSI could save the US healthcare system money. Data on surgical arthroscopy procedures in the US for meniscal knee pathology were used (calendar year [CY] 2010). The costs of performing diagnostic and surgical arthroscopy procedures (using CY 2013 Medicare reimbursement amounts), costs associated with false negative findings, and the costs for treating associated complications arising from diagnostic and therapeutic arthroscopy procedures were assessed. RESULTS: In patients presenting with medial meniscal pathology (International Classification of Diseases, 9th edition, Clinical Modification [ICD9CM] diagnosis 836.0), VSI in place of MRI (standard of care) resulted in a net cost savings to the US system of US$115-US$177 million (CY 2013) (use of systematic review and study data, respectively). In patients presenting with lateral meniscus pathology (ICD9CM 836.1), VSI in place of MRI cost the healthcare system an additional US$14-US$97 million (CY 2013). Overall aggregate savings for meniscal (lateral plus medial) pathology were identified in representative care models along with more appropriate care as fewer patients were exposed to higher risk surgical procedures. CONCLUSIONS: Since in-office arthroscopy is significantly more accurate, patients can be treated more appropriately and the US healthcare system can save money, most especially in medial meniscal pathology.

In-office diagnostic arthroscopy for knee and shoulder intra-articular injuries its potential impact on cost savings in the United States.

BACKGROUND: The purpose of this analysis was to determine whether in office diagnostic needle arthroscopy (Visionscope Imaging System [VSI]) can provide for improved diagnostic assessment and; more cost effective care. METHODS: Data on arthroscopy procedures in the US for deep seated pathology in the knee and shoulder were used (Calendar Year 2012). These procedures represent approximately 25-30% of all arthroscopic procedures performed annually. Sensitivities, specificities, positive predictive, and negative predictive values for MRI analysis of this deep seated pathology from systematic reviews and meta-analyses were used in assessing for false positive and false negative MRI findings. The costs of performing diagnostic and surgical arthroscopy procedures (using 2013 Medicare reimbursement amounts); costs associated with false negative findings; and the costs for treating associated complications arising from diagnostic and therapeutic arthroscopy procedures were then assessed. RESULTS: In patients presenting with medial meniscal pathology (ICD9CM diagnosis 836.0 over 540,000 procedures in CY 2012); use of the VSI system in place of MRI assessment (standard of care) resulted in a net cost savings to the system of $151 million. In patients presenting with rotator cuff pathology (ICD9CM 840.4 over 165,000 procedures in CY2012); use of VSI in place of MRI similarly saved $59 million. These savings were realized along with more appropriate care as; fewer patients were exposed to higher risk surgical arthroscopic procedures. CONCLUSIONS: The use of an in-office arthroscopy system can: possibly save the US healthcare system money; shorten the diagnostic odyssey for patients; potentially better prepare clinicians for arthroscopic surgery (when needed) and; eliminate unnecessary outpatient arthroscopy procedures, which commonly result in surgical intervention.

The Kallikrein Panel for prostate cancer screening: its economic impact.

BACKGROUND: Current diagnostic testing for prostate cancer results in numerous unnecessary biopsy procedures and creates a substantial financial burden. A statistical prediction model for prostate cancer has been developed, based on four Kallikrein markers in blood. This systematic review and meta-analysis examines the aggregated results from published studies of the Kallikrein Panel. METHODS: Literature searches to identify relevant studies were conducted. A meta-analysis of the results was performed using inverse variance, mean difference with corresponding 95% confidence intervals (CI). The results of the meta-analysis were used to assess the Kallikrein Panel's effect on healthcare costs. RESULTS: The Kallikrein Panel has been evaluated in more than 8,500 patients (2,780 with prostate cancer and 598 with high grade prostate cancer). Meta-analysis demonstrates a statistically significant improvement of 8-10% in predictive accuracy. In addition, 48% to 56% of current prostate biopsies could be avoided. Use of the Kallikrein Panel could result in annual US savings approaching $1 billion. CONCLUSIONS: The Kallikrein Panel has the potential to improve patient outcomes and reduce costs. The panel provides significantly improved specificity. Because the Kallikrein Panel has been studied in a range of clinical settings, it is a test that could be readily and widely used in practice.

Cemented all-polyethylene acetabular implants vs other forms of acetabular fixation: a systematic review and meta-analysis of randomized controlled trials.

The cost of primary total hip replacement products approaches 65% of the total reimbursement. Durability of total hip replacement resides with the acetabular component. This systematic review and meta-analysis determined if the outcomes of durability, function, and adverse events associated with cemented all-polyethylene acetabular components was similar to other acetabular designs, holding other variables constant. Randomized controlled trials only were evaluated. Two independent reviewers collected the data from 6 randomized controlled trials. Appropriate statistical analysis was performed. There was no statistical difference in regard to the outcomes at various time points (≤3, 4-8, and ≥10 years) in the 907 implants evaluated. There does, however, appear to be a trend toward abject failure with cemented all-polyethylene acetabular component implants consistent with findings of increased radiolucencies more than 10 years out. The issue of increased radiolucencies over time and failure with these types of implants bears closer scrutiny.

Hydroxyapatite (HA) coating appears to be of benefit for implant durability of tibial components in primary total knee arthroplasty.

BACKGROUND: It is unclear whether there is a clinical benefit to adding hydroxyapatite (HA) coatings to total knee implants, especially with the tibial component, where failure of the implant more often occurs. A systematic review of the literature was undertaken to identify all prospective randomized trials for determining whether the overall clinical results (as a function of durability, function, and adverse events) favored HA-coated tibial components. METHODS: A comprehensive literature search was performed for the years 1990 to September 16, 2010. We restricted our search to randomized controlled trials involving participants receiving either an HA-coated tibia or other forms of tibial fixation. The primary outcome measures evaluated were durability, function, and acute adverse events. RESULTS: Data from 926 evaluable primary total knee implants in 14 studies were analyzed. Using an RSA definition for durability, HA-coated tibial components (porous or press-fit) without screw fixation were less likely to be unstable at 2 years than porous and cemented metal-backed tibial components (RR = 0.58, 95% CI: 0.34-0.98; p = 0.04, I(2) = 39%, M-H random effects model). There was no significant difference in durability, as measured from revision and evaluated at 2 and 8-10 years, between groups. Also, functional status using different validated measures showed no significant difference at 2 and 5 years, no matter what measure was used. Lastly, there was no significant difference in adverse events. Limitations included small numbers of evaluable patients (≤ 50) in 7 of the 14 trials identified, and a lack of "hard" evidence of durability with need for replacement (i.e. frank failure, pain, or loss of functionality). INTERPRETATION: In patients > 65 years of age, an HA-coated tibial implant may provide better durability than other forms of tibial fixation. Larger trials should be undertaken comparing the long-term durability, function, and adverse events of HA-coated implants with those of other porous-coated tibial implants in younger, more active OA patients.