Placebo effects in randomized trials of pharmacological and neurostimulation interventions for mental disorders: An umbrella review.

There is a growing literature exploring the placebo response within specific mental disorders, but no overarching quantitative synthesis of this research has analyzed evidence across mental disorders. We carried out an umbrella review of meta-analyses of randomized controlled trials (RCTs) of biological treatments (pharmacotherapy or neurostimulation) for mental disorders. We explored whether placebo effect size differs across distinct disorders, and the correlates of increased placebo effects. Based on a pre-registered protocol, we searched Medline, PsycInfo, EMBASE, and Web of Knowledge up to 23.10.2022 for systematic reviews and/or meta-analyses reporting placebo effect sizes in psychopharmacological or neurostimulation RCTs. Twenty meta-analyses, summarising 1,691 RCTs involving 261,730 patients, were included. Placebo effect size varied, and was large in alcohol use disorder (g = 0.90, 95% CI [0.70, 1.09]), depression (g = 1.10, 95% CI [1.06, 1.15]), restless legs syndrome (g = 1.41, 95% CI [1.25, 1.56]), and generalized anxiety disorder (d = 1.85, 95% CI [1.61, 2.09]). Placebo effect size was small-to-medium in obsessive-compulsive disorder (d = 0.32, 95% CI [0.22, 0.41]), primary insomnia (g = 0.35, 95% CI [0.28, 0.42]), and schizophrenia spectrum disorders (standardized mean change = 0.33, 95% CI [0.22, 0.44]). Correlates of larger placebo response in multiple mental disorders included later publication year (opposite finding for ADHD), younger age, more trial sites, larger sample size, increased baseline severity, and larger active treatment effect size. Most (18 of 20) meta-analyses were judged 'low' quality as per AMSTAR-2. Placebo effect sizes varied substantially across mental disorders. Future research should explore the sources of this variation. We identified important gaps in the literature, with no eligible systematic reviews/meta-analyses of placebo response in stress-related disorders, eating disorders, behavioural addictions, or bipolar mania.

Transcranial Magnetic Stimulation and Transcranial Direct Current Stimulation Across Mental Disorders: A Systematic Review and Dose-Response Meta-Analysis.

Importance: Noninvasive brain stimulation (NIBS) interventions have been shown to be efficacious in several mental disorders, but the optimal dose stimulation parameters for each disorder are unknown. Objective: To define NIBS dose stimulation parameters associated with the greatest efficacy in symptom improvement across mental disorders. Data Sources: Studies were drawn from an updated (to April 30, 2023) previous systematic review based on a search of PubMed, OVID, and Web of Knowledge. Study Selection: Randomized clinical trials were selected that tested transcranial magnetic stimulation (TMS) or transcranial direct current stimulation (tDCS) for any mental disorder in adults aged 18 years or older. Data Extraction and Synthesis: Two authors independently extracted the data. A 1-stage dose-response meta-analysis using a random-effects model was performed. Sensitivity analyses were conducted to test robustness of the findings. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Main Outcomes and Measures: The main outcome was the near-maximal effective doses of total pulses received for TMS and total current dose in coulombs for tDCS. Results: A total of 110 studies with 4820 participants (2659 men [61.4%]; mean [SD] age, 42.3 [8.8] years) were included. The following significant dose-response associations emerged with bell-shaped curves: (1) in schizophrenia, high-frequency (HF) TMS on the left dorsolateral prefrontal cortex (LDLPFC) for negative symptoms (χ2 = 9.35; df = 2; P = .009) and TMS on the left temporoparietal junction for resistant hallucinations (χ2 = 36.52; df = 2; P < .001); (2) in depression, HF-DLPFC TMS (χ2 = 14.49; df = 2; P < .001); (3) in treatment-resistant depression, LDLPFC tDCS (χ2 = 14.56; df = 2; P < .001); and (4) in substance use disorder, LDLPFC tDCS (χ2 = 33.63; df = 2; P < .001). The following significant dose-response associations emerged with plateaued or ascending curves: (1) in depression, low-frequency (LF) TMS on the right DLPFC (RDLPFC) with ascending curve (χ2 = 25.67; df = 2; P = .001); (2) for treatment-resistant depression, LF TMS on the bilateral DLPFC with ascending curve (χ2 = 5.86; df = 2; P = .004); (3) in obsessive-compulsive disorder, LF-RDLPFC TMS with ascending curve (χ2 = 20.65; df = 2; P < .001) and LF TMS on the orbitofrontal cortex with a plateaued curve (χ2 = 15.19; df = 2; P < .001); and (4) in posttraumatic stress disorder, LF-RDLPFC TMS with ascending curve (χ2 = 54.15; df = 2; P < .001). Sensitivity analyses confirmed the main findings. Conclusions and Relevance: The study findings suggest that NIBS yields specific outcomes based on dose parameters across various mental disorders and brain regions. Clinicians should consider these dose parameters when prescribing NIBS. Additional research is needed to prospectively validate the findings in randomized, sham-controlled trials and explore how other parameters contribute to the observed dose-response association.

Transverse patella fracture fixation: A cadaveric biomechanical comparison of cannulated screws and anterior tension band versus low-profile, multiplanar mesh plating.

INTRODUCTION: Multiplanar mesh plating of patella fractures has become more popular in recent years. It was the goal of this study to compare the biomechanical stability of cannulated screw with anterior tension band to multiplanar mesh plating for fixation of transverse patella fractures in cadaver specimens. MATERIALS AND METHODS: Eight matched pairs of fresh frozen cadaveric knees were obtained and soft tissues dissected leaving the extensor mechanism, joint capsule, and retinaculum intact. Transverse fractures were created at the mid-portion of the patella. For each pair, one specimen was repaired using cannulated screws with anterior tension band, and the second was repaired using multiplanar mesh plating. Each specimen underwent cyclic extension loading with loads increasing by 1.1 kg after every 50 cycles. Interfragmentary displacement was measured at the end of each interval at both 5° and 45° of knee flexion angle, with fixation failure defined by >2 mm displacement. RESULTS: The specimens fixed with multiplanar mesh plating survived more cycles and higher loads than the specimens fixed with cannulated screws with anterior tension band (p = 0.011 comparing survival plots). After 150 cycles of extension loading, 3 of 8 of the specimens fixed with screws/tension band had failed, whereas none of the mesh plated specimens had failed. After 400 cycles, 7 of 8 of the screws/tension band had failed, whereas half of the mesh plated specimens had failed. CONCLUSIONS: While a more technically challenging and expensive technique, mesh plating for patella fractures appears to offer greater durability than traditional cannulated screw with tension banding.

Placebo Effects Are Small on Average in the 7.5% CO2 Inhalational Model of Generalized Anxiety.

BACKGROUND: Anxiety disorders are highly prevalent and socio-economically costly. Novel pharmacological treatments for these disorders are needed because many patients do not respond to current agents or experience unwanted side effects. However, a barrier to treatment development is the variable and large placebo response rate seen in trials of novel anxiolytics. Despite this, the mechanisms that drive placebo responses in anxiety disorders have been little investigated, possibly due to low availability of convenient experimental paradigms. We aimed to develop and test a novel protocol for inducing placebo anxiolysis in the 7.5% CO2 inhalational model of generalized anxiety in healthy volunteers. METHODS: Following a baseline 20-minute CO2 challenge, 32 healthy volunteers were administered a placebo intranasal spray labelled as either the anxiolytic "lorazepam" or "saline." Following this, participants surreptitiously underwent a 20-minute inhalation of normal air. Post-conditioning, a second dose of the placebo was administered, after which participants completed another CO2 challenge. RESULTS: Participants administered sham "lorazepam" reported significant positive expectations of reduced anxiety (P = .001), but there was no group-level placebo effect on anxiety following CO2 challenge post-conditioning (Ps > .350). Surprisingly, we found many participants exhibited unexpected worsening of anxiety, despite positive expectations. CONCLUSIONS: Contrary to our hypothesis, our novel paradigm did not induce a placebo response, on average. It is possible that effects of 7.5% CO2 inhalation on prefrontal cortex function or behavior in line with a Bayesian predictive coding framework attenuated the effect of expectations on subsequent placebo response. Future studies are needed to explore these possibilities.

The Kidney Not Taken: Single-Kidney Use in Deceased Donors.

BACKGROUND: The nonuse rate for kidneys recovered from deceased donors is increasing, rising to 27% in 2023. In 10% of these cases, 1 kidney is transplanted but the mate kidney is not. STUDY DESIGN: We conducted a retrospective, single-center cohort study from December 2001 to May 2023 comparing single kidneys transplanted at our center (where the contralateral kidney was not used) to kidneys where both were transplanted separately, at least 1 of which was at our center. RESULTS: We performed 395 single deceased-donor kidney transplants in which the mate kidney was not transplanted. Primary reasons for mate kidney nonuse were as follows: no recipient located or list exhausted (33.4%), kidney trauma or injury or anatomic abnormalities (18.7%), biopsy findings (16.7%), and poor renal function (13.7%). Mean donor and recipient ages were 51.5 ± 14.2 and 60 ± 12.6 years, respectively. Mean kidney donor profile index was 73% ± 22%, and 104 donors (26.3%) had kidney donor profile index >85%. Mean cold ischemia was 25.6 ± 7.4 hours, and 280 kidneys (70.7%) were imported. Compared with 2,303 concurrent control transplants performed at our center, primary nonfunction or thrombosis (5.1% single vs 2.8% control) and delayed graft function (35.4% single vs 30.1% control) were greater with single-kidney use (both p < 0.05). Median patient and death-censored graft survival were shorter in the single group (11.6 vs 13.5 years, p = 0.03 and 11.6 vs 19 years, p = 0.003), although the former was at least double median survival on the waiting list. In patients with functioning grafts in the single-kidney group, 1-year mean serum creatinine was 1.77 ± 0.8 mg/dL and estimated glomerular filtration rate was 44.8 ± 20 mL/min/1.73 m 2 . CONCLUSIONS: These findings suggest that many mate kidneys are being inappropriately rejected, given the acceptable outcomes that can be achieved by transplanting the single kidney in appropriately selected recipients.

Placebo effects in mental health disorders: protocol for an umbrella review.

INTRODUCTION: Given the high prevalence of mental health disorders and their significant socioeconomic burden, there is a need to develop improved treatments, and to evaluate them through placebo-controlled trials. However, the magnitude of the placebo response in randomised controlled trials to test medications may be substantial, affecting their interpretation. Therefore, improved understanding of the patient, trial and mental disorder factors that influence placebo responses would inform clinical trial design to better detect active treatment effects. There is a growing literature exploring the placebo response within specific mental health disorders, but no overarching synthesis of this research has been produced to date. We present a protocol for an umbrella review of systematic reviews and/or meta-analyses in which we aim to understand the effect size and potential predictors of placebo response within, and across, mental health disorders. METHODS AND ANALYSIS: We will systematically search databases (Medline, PsycINFO, EMBASE+EMBASE Classic, Web of Knowledge) for systematic reviews and/or meta-analyses that report placebo effect size in clinical trials in patients with mental health disorders (initial search date 23 October 2022). Screening of abstracts and full texts will be done in pairs. We will extract data to qualitatively examine how placebo effect size varies across mental health disorders. We also plan to qualitatively summarise predictors of increased placebo response identified either quantitatively (eg, through meta-regression) or qualitatively. Risk of bias will be assessed using the AMSTAR-2 tool. We aim to not only summarise the current literature but also to identify gaps in knowledge and generate further hypotheses. ETHICS AND DISSEMINATION: We do not believe there are any specific ethical considerations relevant to this study. We will publish the results in a peer-reviewed journal.

Single center experience and literature review of kidney transplantation from non-ideal donors with acute kidney injury: Risk and reward.

INTRODUCTION: There is limited experience transplanting kidneys from either expanded criteria donors (ECD) or donation after circulatory death (DCD) deceased donors with terminal acute kidney injury (AKI). METHODS: AKI kidneys were defined by a donor terminal serum creatinine level >2.0 mg/dL whereas non-ideal deceased donor (NIDD) kidneys were defined as AKI/DCD or AKI/ECDs. RESULTS: From February 2007 to March 2023, we transplanted 266 single AKI donor kidneys including 29 from ECDs, 29 from DCDs (n = 58 NIDDs), and 208 from brain-dead standard criteria donors (SCDs). Mean donor age (43.7 NIDD vs. 33.5 years SCD), KDPI (66% NIDD vs. 45% SCD), and recipient age (57 NIDD vs. 51 years SCD) were higher in the NIDD group (all p < .01). Mean waiting times (17.8 NIDD vs. 24.2 months SCD) and dialysis duration (34 NIDD vs. 47 months SCD) were shorter in the NIDD group (p < .05). Delayed graft function (DGF, 48%) and 1-year graft survival (92.7% NIDD vs. 95.9% SCD) was similar in both groups. Five-year patient and kidney graft survival rates were 82.1% versus 89.9% and 82.1% versus 75.2% (both p = NS) in the NIDD versus SCD groups, respectively. CONCLUSIONS: The use of kidneys from AKI donors can be safely liberalized to include selected ECD and DCD donors.

The role of computed tomography in the detection of traumatic arthrotomies of the elbow: a cadaveric study.

Purpose: To evaluate the use of computed tomography (CT) imaging as a diagnostic tool for elbow arthrotomies using a standardized cadaveric arthrotomy model. Method: Nineteen intact fresh frozen cadaver elbows were CT scanned using 2 mm cuts with sagittal and coronal reformats in the plane of the joint and used as controls. An elbow arthrotomy at the posterocentral arthroscopic portal site was performed in all specimens using a 4.5 millimeter trocar. After arthrotomy, all elbows underwent a second CT scan followed by a standard saline load test (SLT). Images were randomized and reviewed by 2 blinded, independent reviewers. Bimodal scoring was performed for each specimen with regard to the presence of an arthrotomy indicated by presence of air in the joint. Regarding the SLT, saline exiting the arthrotomy wound was considered a positive test. Results: CT scans were found to have 100% sensitivity and 86% specificity for diagnosing elbow arthrotomies. Interrater reliability calculated with Cohen kappa statistic was near perfect at r = 0.89. The SLT had a sensitivity of 79% when 20 mL was injected. A total of 25 mL of saline was required to be injected for a sensitivity greater than 95%. Conclusion: This study demonstrates that CT scan is a reliable and less technically demanding method of diagnosis arthrotomies with high interrater reliability and high sensitivity and with results comparable with SLT. This technique may be useful in centers where trained providers are not readily available to perform SLT. Clinical study is required to validate our results. Level of Evidence: Level II.

Does dialysis modality or duration influence outcomes in simultaneous pancreas-kidney transplant recipients? Single center experience and review of the literature.

AIM: The influence of dialysis modality and duration on outcomes following simultaneous pancreas-kidney transplantation (SPKT) remains uncertain. METHODS: We performed a single-center retrospective review in 255 SPKT recipients according to dialysis modality (55 preemptive/no dialysis-ND, 70 peritoneal dialysis-PD, 130 hemodialysis-HD) and duration (55 none, 137 < 2 years, 41 2-4 years, 22 > 4 years). RESULTS: Mean follow-up was 9.4 years (median 9.2 years). Early (3-month) relaparotomy rate (20% ND vs. 36% PD/HD, p = .03) was lower in ND patients. There were no differences in early graft loss, patient survival, overall or death-censored kidney or pancreas graft survival rates (GSR) at 1 or 10 years follow-up. When analyzing dialysis duration, there were no differences in rates of pancreas thrombosis or early pancreas graft loss. Kidney delayed graft function (DGF) was lower in the ND/short dialysis groups combined (1.0%), compared to the intermediate/long dialysis groups combined (9.5%, p = .003). Early relaparotomy rates were higher with longer duration of dialysis (p = .045 between ND and >4 years of dialysis). Patient survival in the long dialysis group was 50% compared to 69.5% in the other three groups combined (p = .09). However, both overall and death-censored kidney and pancreas GSR were comparable. CONCLUSIONS: Preemptively transplanted patients had a lower incidence of kidney DGF and relaparotomy whereas patient survival was slightly lower with longer dialysis vintage prior to SPKT. Dialysis modality and duration did not influence either overall or death-censored pancreas or kidney GSR in patients with short waiting times, low KDPI donor organs, and dialysis duration up to 4 years.

Knowing When to Ignore the Numbers: Single-Center Experience Transplanting Deceased Donor Kidneys with Poor Perfusion Parameters.

BACKGROUND: Hypothermic machine perfusion is frequently used in evaluating marginal kidneys with poor perfusion parameters (PPP) contributing to delays in kidney placement or discard. We examined outcomes in deceased donor kidney transplants with PPP compared with those with optimal perfusion parameters (OPP). STUDY DESIGN: We conducted a retrospective single-center cohort study from 2001 to 2021 comparing PPP (n = 91) with OPP (n = 598) deceased donor kidney transplants. PPP was defined as terminal flow ≤80 mL/min and terminal resistance ≥0.40 mmHg/mL/min. OPP was defined as terminal flow ≥120 mL/min and terminal resistance ≤0.20 mmHg/mL/min. RESULTS: Mean terminal flow was PPP 66 ± 16 vs OPP 149 ± 21 mL/min and resistance was PPP 0.47 ± 0.10 vs OPP 0.15 ± 0.04 mmHg/mL/min (both p < 0.001). Donor age, donation after cardiac death, and terminal serum creatinine levels were similar between groups. Mean Kidney Donor Profile Index was higher among PPP donors (PPP 65 ± 23% vs OPP 52 ± 27%, p < 0.001). The PPP transplant group had more females and lower weight and BMI. Delayed graft function was comparable (PPP 32% vs OPP 27%, p = 0.33) even though cold ischemia times trended toward longer in PPP kidneys (PPP 28 ± 10 vs OPP 26 ± 9 hours, p = 0.09). One-year patient survival (PPP 98% vs OPP 97%, p = 0.84) and graft survival (PPP 91% vs OPP 92%, p = 0.23) were equivalent. PPP did predict inferior overall and death-censored graft survival long-term (overall hazard ratio 1.63, 95% CI 1.19 to 2.23 and death-censored hazard ratio 1.77, 95% CI 1.15 to 2.74). At 1 year, the estimated glomerular filtration rate was higher with OPP kidneys (PPP 40 ± 17 vs OPP 52 ± 19 mL/min/1.73 m 2 , p < 0.001). CONCLUSIONS: Short-term outcomes in PPP kidneys were comparable to OPP kidneys despite higher Kidney Donor Profile Index and longer cold ischemia times, suggesting a role for increased utilization of these organs with careful recipient selection.

Feasibility, acceptability and practicality of transcranial stimulation in obsessive compulsive symptoms (FEATSOCS): A randomised controlled crossover trial.

BACKGROUND: Transcranial direct current stimulation (tDCS) is a non-invasive form of neurostimulation with potential for development as a self-administered intervention. It has shown promise as a safe and effective treatment for obsessive compulsive disorder (OCD) in a small number of studies. The two most favourable stimulation targets appear to be the left orbitofrontal cortex (L-OFC) and the supplementary motor area (SMA). We report the first study to test these targets head-to-head within a randomised sham-controlled trial. Our aim was to inform the design of future clinical research studies, by focussing on the acceptability and safety of the intervention, feasibility of recruitment, adherence to and tolerability of tDCS, and the size of any treatment-effect. METHODS: FEATSOCS was a randomised, double-blind, sham-controlled, cross-over, multicentre study. Twenty adults with DSM-5-defined OCD were randomised to treatment, comprising three courses of clinic-based tDCS (SMA, L-OFC, Sham), randomly allocated and delivered in counterbalanced order. Each course comprised four 20-min 2 mA stimulations, delivered over two consecutive days, separated by a 'washout' period of at least four weeks. Assessments were carried out by raters who were blind to stimulation-type. Clinical outcomes were assessed before, during, and up to four weeks after stimulation. Patient representatives with lived experience of OCD were actively involved at all stages. RESULTS: Clinicians showed willingness to recruit participants and recruitment to target was achieved. Adherence to treatment and study interventions was generally good, with only two dropouts. There were no serious adverse events, and adverse effects which did occur were transient and mostly mild in intensity. Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores were numerically improved from baseline to 24 h after the final stimulation across all intervention groups but tended to worsen thereafter. The greatest effect size was seen in the L-OFC arm, (Cohen's d = -0.5 [95% CI -1.2 to 0.2] versus Sham), suggesting this stimulation site should be pursued in further studies. Additional significant sham referenced improvements in secondary outcomes occurred in the L-OFC arm, and to a lesser extent with SMA stimulation. CONCLUSIONS: tDCS was acceptable, practicable to apply, well-tolerated and appears a promising potential treatment for OCD. The L-OFC represents the most promising target based on clinical changes, though the effects on OCD symptoms were not statistically significant compared to sham. SMA stimulation showed lesser signs of promise. Further investigation of tDCS in OCD is warranted, to determine the optimal stimulation protocol (current, frequency, duration), longer-term effectiveness and brain-based mechanisms of effect. If efficacy is substantiated, consideration of home-based approaches represents a rational next step. TRIAL REGISTRATION: ISRCTN17937049. https://doi.org/10.1186/ISRCTN17937049.

Risk Factors For Prolonged Opioid Use After Spine Surgery.

STUDY DESIGN: Retrospective review. OBJECTIVE: Our purpose was to evaluate factors associated with increased risk of prolonged post-operative opioid pain medication usage following spine surgery, as well as identify the risk of various post-operative complications that may be associated with pre-operative opioid usage. METHODS: The MarketScan commercial claims and encounters database includes approximately 39 million patients per year. Patients undergoing cervical and lumbar spine surgery between the years 2005-2014 were identified using CPT codes. Pre-operative comorbidities including DSM-V mental health disorders, chronic pain, chronic regional pain syndrome (CRPS), obesity, tobacco use, medications, and diabetes were queried and documented. Patients who utilized opioids from 1-3 months prior to surgery were identified. This timeframe was chosen to exclude patients who had been prescribed pre- and post-operative narcotic medications up to 1 month prior to surgery. We utilized odds ratios (OR), 95% Confidence Intervals (CI), and regression analysis to determine factors that are associated with prolonged post-operative opioid use at 3 time intervals. RESULTS: 553,509 patients who underwent spine surgery during the 10-year period were identified. 34.9% of patients utilized opioids 1-3 months pre-operatively. 25% patients were still utilizing opioids at 6 weeks, 17.3% at 3 months, 12.7% at 6 months, and 9.0% at 1 year after surgery. Pre-operative opioid exposure was associated with increased likelihood of post-operative use at 6-12 weeks (OR 5.45, 95% CI 5.37-5.53), 3-6 months (OR 6.48, 95% CI 6.37-6.59), 6-12 months (OR 6.97, 95% CI 6.84-7.11), and >12 months (OR 7.12, 95% CI 6.96-7.29). Mental health diagnosis, tobacco usage, diagnosis of chronic pain or CRPS, and non-narcotic neuromodulatory medications yielded increased likelihood of prolonged post-op opioid usage. CONCLUSIONS: Pre-operative narcotic use and several patient comorbidities diagnoses are associated with prolonged post-operative opioid usage following spine surgery. Chronic opioid use, diagnosis of chronic pain, or use of non-narcotic neuromodulatory medications have the highest risk of prolonged post-operative opioid consumption. Patients using opiates pre-operatively did have an increased 30 and 90-day readmission risk, in addition to a number of serious post-operative complications. This data provides spine surgeons a number of variables to consider when determining post-operative analgesia strategies, and provides health systems, providers, and payers with information on complications associated with pre-operative opioid utilization.

Long-term outcomes of kidney transplantation from deceased donors with terminal acute kidney injury: Single center experience and literature review.

INTRODUCTION: Long-term outcomes of kidney transplantation from deceased donors (DDKTs) with terminal acute kidney injury (AKI) are not well defined. METHODS: Single center retrospective review of DDKTs from 1/31/07-12/31/19. AKI kidneys were defined by a doubling of the donor's admission serum creatinine (SCr) level AND a terminal SCr ≥2.0 mg/dl. RESULTS: A total of 188 AKI DDKTs were performed, including 154 from brain-dead standard criteria donors (SCD). Mean donor age was 36 years and mean Kidney Donor Profile Index was 50%; mean admission and terminal SCr levels were 1.3 and 3.1 mg/dl, respectively. With a mean follow-up of 94 months (median 89 months), overall patient (both 71.3%) and graft survival (54% AKI vs. 57% non-AKI) rates were comparable to concurrent DDKTs from brain-dead non-AKI SCDs (n = 769). Delayed graft function (DGF) was higher in AKI kidney recipients (47% vs. 20% non-AKI DDKTs, p < .0001). DGF was associated with lower graft survival in recipients of both AKI and non-AKI SCD kidneys but the impact was earlier and more pronounced in non-AKI recipients. CONCLUSIONS: Despite having more than twice the incidence of DGF, kidneys from deceased donors with terminal AKI have long-term outcomes comparable to non-AKI SCD kidneys and represent a safe and effective method to expand the donor pool.

Influence of donor and recipient sex on outcomes following simultaneous pancreas-kidney transplantation in the new millennium: Single-center experience and review of the literature.

INTRODUCTION: The influence of sex on outcomes following simultaneous pancreas-kidney transplantation (SPKT) in the modern era is uncertain. METHODS: We retrospectively studied 255 patients undergoing SPKT from 11/2001 to 8/2020. Cases were stratified according to donor (D) sex, recipient (R) sex, 4 D/R sex categories, and D/R sex-matched versus mismatched. RESULTS: D-male was associated with slightly higher patient (p = .08) and kidney (p = .002) but not pancreas (p = .23) graft survival rates (GSR) compared to D-female. There were no differences in recipient outcomes other than slightly higher pancreas thrombosis (8% R-female vs. 4.2% R-male, p = .28) and early relaparotomy rates in female recipients (38% R-female vs. 29% R-male, p = .14). When analyzing the 4 D/R sex categories, the two D-male groups had higher kidney GSRs compared to the two D-female groups (p = .01) whereas early relaparotomy and pancreas thrombosis rates were numerically higher in the D-female/R-female group compared to the other three groups. Finally, there were no significant differences in outcomes between sex-matched and sex-mismatched groups although overall survival outcomes were lower with female donors irrespective of recipient sex. CONCLUSIONS: The influence of D/R sex following SPKT is subject to multiple confounding issues but survival rates appear to be higher in D-male/R-male and lower in D-female/R-male categories.

Improved surgical outcomes following simultaneous pancreas-kidney transplantation in the contemporary era.

BACKGROUND: Complications leading to early technical failure have been the Achilles' heel of simultaneous pancreas-kidney transplantation (SPKT). The study purpose was to analyze longitudinally our experience with early surgical complications following SPKT with an emphasis on changes in practice that improved outcomes in the most recent era. STUDY DESIGN: Single center retrospective review of all SPKTs from 11/1/01 to 8/12/20 with enteric drainage. Early relaparotomy was defined as occurring within 3 months of SPKT. Patients were stratified into two sequential eras: Era 1 (E1): 11/1/01-5/30/13; Era 2 (E2) 6/1/13-8/12/20 based on changes in practice that occurred pursuant to donor age and pancreas cold ischemia time (CIT). RESULTS: 255 consecutive SPKTs were analyzed (E1, n = 165; E2, n = 90). E1 patients received organs from older donors (mean E1 27.3 vs. E2 23.1 years) with longer pancreas cold CITs) (mean E1 16.1 vs. E2 13.3 h, both p < .05). E1 patients had a higher early relaparotomy rate (E1 43.0% vs. E2 14.4%) and were more likely to require allograft pancreatectomy (E1 9.1% vs. E2 2.2%, both p < .05). E2 patients underwent systemic venous drainage more frequently (E1 8% vs. E2 29%) but pancreas venous drainage did not influence either relaparotomy or allograft pancreatectomy rates. The most common indications for early relaparotomy in E1 were allograft thrombosis (11.5%) and peri-pancreatic phlegmon/abscess (8.5%) whereas in E2 were thrombosis, pancreatitis/infection, and bowel obstruction (each 3%). CONCLUSION: Maximizing donor quality (younger donors) and minimizing pancreas CIT are paramount for reducing early surgical complications following SPKT.

The effect of cigarette smoke versus vaporized nicotine on healing of a rat femur.

INTRODUCTION: Little data exists regarding the effects of vaporized nicotine on healing. Our goal was to compare vaporized nicotine, combusted nicotine and control with respect to bone healing in a rat femur fracture model. MATERIALS AND METHODS: Forty-five male Sprague Dawley rats were divided into three equal cohorts. Rats were exposed to two cigarettes daily, an equivalent dose of vaporized nicotine, or control, six days a week. Exposures occurred for 4 weeks prior to iatrogenic femur fracture and intramedullary repair. Four additional weeks of exposure occurred prior to sacrifice. Radiographic, biomechanical and histologic analysis was conducted. RESULTS: No significant difference between the three groups was identified for total mineralized bone volume (p = 0.14), total volume of mature bone (p = 0.12) or immature bone (p = 0.15). Importantly, less total mineralized bone volume and immature bone volume was seen in the vaporized nicotine group compared to combusted tobacco, but results were not significant. Biomechanical testing revealed no significant difference in group torsional stiffness (p = 0.92) or maximum torque (p = 0.31) between the three groups. On histologic analysis, chi-square testing showed no significant difference in any category. CONCLUSIONS: This exploratory study compared combusted nicotine, vaporized nicotine and a control on rat femur fractures. While no statistically significant differences were identified, there were trends showing less total mineralized bone volume and immature bone volume in the vaporized nicotine group compared to the other groups. Additional study is warranted based on our findings.

A novel procedure to investigate social anxiety using videoconferencing software: A proof-of-concept study.

Social anxiety disorder (SAD) is very common and can be significantly disabling. New treatments are needed as the remission rate for SAD is the lowest of all the anxiety disorders. Experimental medicine models, in which features resembling a clinical disorder are experimentally induced, are a cost-effective and timely approach to explore potential novel treatments for psychiatric disorders. Following the emergence of SARS-CoV-2, there is a need to develop experimental medicine models that can be carried out remotely. We developed a novel procedure to investigate SAD (the InterneT-based Stress test for Social Anxiety Disorder; ITSSAD) that can be carried out entirely online by a single investigator, potentially reducing costs and maximising internal reliability. The procedure involves an anticipatory period followed by a naturalistic social interaction task. In a sample of 20 non-treatment-seeking volunteers with symptoms of SAD, the ITSSAD induced significant subjective anxiety and reduced positive affect. Further, increased social anxiety symptoms at baseline predicted increased anxiety during the social interaction task. This protocol needs further validation with physiological measures. The ITSSAD is a new tool for researchers to investigate mechanisms underlying social anxiety disorder.

Efficacy of neurostimulation across mental disorders: systematic review and meta-analysis of 208 randomized controlled trials.

Non-invasive brain stimulation (NIBS), including transcranial magnetic stimulation (TMS), and transcranial direct current stimulation (tDCS), is a potentially effective treatment strategy for a number of mental conditions. However, no quantitative evidence synthesis of randomized controlled trials (RCTs) of TMS or tDCS using the same criteria including several mental conditions is available. Based on 208 RCTs identified in a systematic review, we conducted a series of random effects meta-analyses to assess the efficacy of NIBS, compared to sham, for core symptoms and cognitive functioning within a broad range of mental conditions. Outcomes included changes in core symptom severity and cognitive functioning from pre- to post-treatment. We found significant positive effects for several outcomes without significant heterogeneity including TMS for symptoms of generalized anxiety disorder (SMD = -1.8 (95% CI: -2.6 to -1), and tDCS for symptoms of substance use disorder (-0.73, -1.00 to -0.46). There was also significant effects for TMS in obsessive-compulsive disorder (-0.66, -0.91 to -0.41) and unipolar depression symptoms (-0.60, -0.78 to -0.42) but with significant heterogeneity. However, subgroup analyses based on stimulation site and number of treatment sessions revealed evidence of positive effects, without significant heterogeneity, for specific TMS stimulation protocols. For neurocognitive outcomes, there was only significant evidence, without significant heterogeneity, for tDCS for improving attention (-0.3, -0.55 to -0.05) and working memory (-0.38, -0.74 to -0.03) in individuals with schizophrenia. We concluded that TMS and tDCS can benefit individuals with a variety of mental conditions, significantly improving clinical dimensions, including cognitive deficits in schizophrenia which are poorly responsive to pharmacotherapy.

Functional Neuroimaging Correlates of Placebo Response in Patients With Depressive or Anxiety Disorders: A Systematic Review.

BACKGROUND: The mechanisms underlying placebo effects of psychotropic drugs remain poorly understood. We carried out the first, to our knowledge, systematic review of functional neuroimaging correlates of placebo response in adults with anxiety/depressive disorders. METHODS: We systematically searched a large set of databases up to February 2021 based on a pre-registered protocol (PROSPERO CRD42019156911). We extracted neuroimaging data related to clinical improvement following placebo or related to placebo mechanisms. We did not perform a meta-analysis due to the small number of included studies and significant heterogeneity in study design and outcome measures. RESULTS: We found 12 relevant studies for depressive disorders and 4 for anxiety disorders. Activity in the ventral striatum, rostral anterior cingulate cortex and other default mode network regions, orbitofrontal cortex, and dorsolateral prefrontal cortex correlated with placebo antidepressant responses. Activity in regions of the default mode network, including posterior cingulate cortex, was associated with placebo anxiolysis. There was also evidence for possible involvement of the endogenous opioid, dopamine, and serotonin systems in placebo antidepressant and anxiolytic effects. CONCLUSIONS: Several brain regions and molecular systems may be involved in these placebo effects. Further adequately powered studies exploring causality and controlling for confounders are required.

Opioid Use, Perioperative Risks, and Associated Postoperative Complications in Foot and Ankle Surgery.

INTRODUCTION: Opioid abuse has become a national crisis. Published data demonstrate that patients undergoing foot and ankle surgery are left with excess narcotic medications postoperatively. The purpose of our study was to evaluate factors associated with prolonged postoperative opioid use following foot and ankle surgery and identify associations between preoperative opioid use and postoperative complications. METHODS: MarketScan commercial claims and encounters database was searched to identify foot and ankle patients. Preoperative comorbidities were queried and documented. Patients utilizing opioids 1 to 3 months prior to surgery were identified. Adjusted odds ratios and 95% CIs were calculated using multivariable logistic regression to determine associations between opioid use (preoperatively and postoperatively), readmission, and complications. RESULTS: A total of 112 893 patients were included in the study. Preoperative use had a statistically significant association with postoperative use out to 1 year. Tobacco use, chronic pain, mental health diagnosis, and nonopioid medications had a statistically significant association with postoperative use. Preoperative opioid use had a statistically significant association with readmission and postoperative complications. CONCLUSION: Our study found a number of factors associated with prolonged postoperative opioid use (preoperative use, tobacco use, chronic pain, mental health disorders, and certain nonopioid medications). We identified an association between preoperative opioid use and postoperative complications and readmission. LEVELS OF EVIDENCE: Prognostic Level IV Evidence.