A systematic review of patient outcomes for primary pediatric flexor tendon repairs.

Background: Literature on pediatric flexor tendon repairs remains sparse. Given the various repair techniques and rehabilitation protocols available, the aim of this systematic review is to investigate outcomes of primary pediatric flexor tendon repairs. Methods: MEDLINE, Embase, PubMed, and Cochrane Central Register of Controlled Trials databases were searched from inception to June 2022 in concordance with PRISMA guidelines. Studies were included if patients were under the age of 18, sustained a flexor tendon injury repaired primarily, and had documented functional outcomes. Quality assessment was completed using the Newcastle-Ottawa Scale. The study was registered with PROSPERO (CRD42018089089). Results: This study includes 20 articles representing 577 patients with 748 injured digits, most frequently injured by a laceration from glass. The number of tendon injuries in zones I, II, III, IV, and V were 78, 431, 62, 2, and 19, respectively. In total, 594 FDP, 374 FDS, and 77 FPL tendons were lacerated. Concurrent digital nerve injuries occurred in 251 digits. Time of repair was 15 â€‹h-187 days post-injury, most commonly via the modified Kessler (n â€‹= â€‹266 digits) and Kessler (n â€‹= â€‹162 digits). Post-operatively, 170 patients were immobilized and 261 patients underwent early active (n â€‹= â€‹96) or passive (n â€‹= â€‹165) protocols. Functional outcomes were reported in 466 digits (excellent â€‹= â€‹306, good â€‹= â€‹132, fair â€‹= â€‹19, and poor â€‹= â€‹9, per the respective assessment tool used). There were 15 tendon ruptures. Conclusions: Despite heterogeneity in both operative and post-operative protocols, there is low level evidence that low complication rates and good outcomes are expected following primary repair of pediatric flexor tendons.

Rapid metastatic recurrence after pancreatic cancer resection: a multi-center, regional analysis of trends in surgical failure over two decades.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAc) is a lethal malignancy, attributed in part to high rates of rapid recurrence (rrPDAc) following resection. We sought to characterize recurrence rates over time and investigate factors predictive of rrPDAc. METHODS: A regional multi-institutional cancer registry, augmented with data from the National Surgical Quality Improvement Program database, was queried for patients with PDAc from 1996 to 2020. rrPDAc was defined as recurrence within 6 months following curative-intent resection. RESULTS: We identified 924 patients who underwent resection for PDAc; rrPDAc occurred in 236 (26%) patients. Median incidence of rrPDAc was 25.3% (IQR 22-30.2%) per year. Median survival in rrPDAc, non-rapid recurrence, and no recurrence was 10.3, 25.2, and 56.1 months respectively (p < 0.001). Variables independently associated with greater odds of rrPDAc included surgical site infection (SSI) (OR 2.06) and nodal positivity (OR 2.05); adjuvant therapy was associated with lower odds (OR 0.38). Neoadjuvant chemotherapy did not alter risk of rrPDAc. Three-year post-recurrence survival was no different in rrPDAc versus those without. CONCLUSION: Despite therapeutic advances, incidence of rrPDAc remains unchanged. SSIs and nodal positivity are independently associated with increased risk of rrPDAc, while adjuvant chemotherapy is associated with lower risk. Strategies focused on preventing rapid recurrence may improve survival.

Supporting General Practitioners and people with hypertension to maximise medication use to control blood pressure: the contribution of Collective Intelligence to the development of the 'Maximising Adherence, Minimising Inertia' (MIAMI) intervention.

Background: Hypertension remains one of the most important modifiable risk factors for stroke and heart disease. Anti-hypertensive medications are effective, but are often not used to maximum benefit. Sub-optimal dosing by prescribers and challenges with medication-taking for patients remain barriers to effective blood pressure control. Objectives: We aimed to systematically develop a theory-based complex intervention to support General Practitioners (GPs) and people with hypertension to maximise medication use to control blood pressure. Methods: We used the three-phase Behaviour Change Wheel (BCW) as the overarching intervention development framework. Collective Intelligence methodology was used to operationalise the stakeholder input to Phases 2 and 3 of the BCW. This took the form of a Collective Intelligence workshop with 19 stakeholders from diverse backgrounds including lived experience, general practice, nursing, pharmacy and health psychology. Techniques such as barrier identification, idea-writing and scenario-based design were used to generate possible intervention options. Intervention options were then selected and refined using the Acceptability, Practicability, Effectiveness, Affordability, Side-effects and Equity (APEASE) criteria and guidance from the MIAMI Public and Patient Involvement Panel. Results: The finalised MIAMI intervention consists of both GP and patient supports. GP supports include a 30-minute online training, information booklet and consultation guide (drop-down menu) embedded within the patient electronic health system. Patient supports include a pre-consultation plan, website, and a structured GP consultation with results from an Ambulatory Blood Pressure Monitor and urine chemical adherence test. The intervention components have been mapped to the intervention functions of the BCW and Behaviour Change Technique Ontology. Conclusion: Collective Intelligence offered a novel method to operationalise stakeholder input to Phases 2 and 3 of the BCW. The MIAMI intervention is now at pilot evaluation stage.

Naturalistic use of a digital mental health intervention for depression and anxiety: A randomized clinical trial.

BACKGROUND: Digital mental health interventions (DMHI) may offer scalable treatment for common mental health conditions. However, many commercially available apps have not been subjected to rigorous evaluation of effectiveness, particularly among users experiencing clinically significant symptomatology. We examined depression and anxiety symptom outcomes associated with a top-rated, commercially available self-guided DMHI based on cognitive behavioral therapy ("Sanvello") relative to waitlist control. METHODS: This preregistered web-based, 2-arm, parallel-group randomized trial enrolled U.S. adults with self-reported elevated symptoms of depression and/or anxiety. Those assigned to the treatment condition were provided 8 weeks of access to Sanvello. Co-primary outcomes of depression (Patient Health Questionnaire [PHQ-9]) and anxiety (Generalized Anxiety Disorder 7-item scale [GAD-7]) severity were assessed at baseline and 2, 4, 6, and 8 weeks. RESULTS: Intention-to-treat analyses included 280 participants (mean age 32.47 ± 9.32 years; 86.1 % women). Generalized linear mixed models showed a significant improvement in depression (F(4,779) = 6.51, p < .001) and anxiety (F(4,907) = 3.28, p = .01) associated with the DMHI over time. The intervention was also associated with a greater proportion of participants exhibiting depression response (25 [45.5 %] vs 26 [16.9 %]) and remission (10 [18.2 %] vs 7 [4.5 %]) on the PHQ-9, and anxiety response (31 [44.9 %] vs 39 [22.8 %]) and remission (20 [29.0 %] vs 27 [15.8 %]) on the GAD-7, relative to waitlist. LIMITATIONS: Findings may not represent people with serious mental illness, suicidality, or the broader population of DMHI users. CONCLUSIONS: A commercially available, self-guided DMHI was effective at improving symptoms in individuals experiencing depression or anxiety. TRIAL REGISTRATION: ClinicalTrials.gov [NCT05373329].

Synergistic Toxicity of Pollutant and Ultraviolet Exposure from a Mitochondrial Perspective.

Ultraviolet (UV) exposure and atmospheric pollution are both independently implicated in skin diseases such as cancer and premature aging. UVA wavelengths, which penetrate in the deep layers of the skin dermis, exert their toxicity mainly through chromophore photosensitization reactions. Benzo[a]pyrene (BaP), the most abundant polycyclic aromatic hydrocarbon originating from the incomplete combustion of organic matter, could act as a chromophore and absorb UVA. We and other groups have previously shown that BaP and UVA synergize their toxicity in skin cells, which leads to important oxidation. Even if mitochondria alterations have been related to premature skin aging and other skin disorders, no studies have focused on the synergy between UV exposure and pollution on mitochondria. Our study aims to investigate the combined effect of UVA and BaP specifically on mitochondria in order to assess the effect on mitochondrial membranes and the consequences on mitochondrial activity. We show that BaP has a strong affinity for mitochondria and that this affinity leads to an important induction of lipid peroxidation and membrane disruption when exposed to UVA. Co-exposure to UVA and BaP synergizes their toxicity to negatively impact mitochondrial membrane potential, mitochondrial metabolism and the mitochondrial network. Altogether, our results highlight the implication of mitochondria in the synergistic toxicity of pollution and UV exposure and the potential of this toxicity on skin integrity.

Evaluation of the bioavailability of a Tamiflu taste-masking pediatric formulation using a juvenile pig model and LC-MS/MS.

Aim: To improve the palatability and increase compliance in pediatric patients, different taste-masking technologies have been evaluated to support the NIH Pediatric Formulation Initiative.Methods: This bioavailability approach combined a juvenile porcine model which represented the pediatric population, and an advanced UHPLCMS/MS method. Juvenile pigs were administered with either commercial Tamiflu or its taste-masking formulation and plasma samples were obtained from 0 to 48 h. The mass spectrometer was operated in positive mode with electrospray ionization.Results: The bioavailability profiles were not significantly different between the two formulations which demonstrated that taste-masking by forming an ionic complex was a promising approach for formulation modification.Conclusion: The pre-clinical study revealed a promising model platform for developing and screening taste-masking formulations.

[Box: see text].

Subject-level spinal osteoporotic fracture prediction combining deep learning vertebral outputs and limited demographic data.

Automated screening for vertebral fractures could improve outcomes. We achieved an AUC-ROC = 0.968 for the prediction of moderate to severe fracture using a GAM with age and three maximal vertebral body scores of fracture from a convolutional neural network. Maximal fracture scores resulted in a performant model for subject-level fracture prediction. Combining individual deep learning vertebral body fracture scores and demographic covariates for subject-level classification of osteoporotic fracture achieved excellent performance (AUC-ROC of 0.968) on a large dataset of radiographs with basic demographic data. PURPOSE: Osteoporotic vertebral fractures are common and morbid. Automated opportunistic screening for incidental vertebral fractures from radiographs, the highest volume imaging modality, could improve osteoporosis detection and management. We consider how to form patient-level fracture predictions and summarization to guide management, using our previously developed vertebral fracture classifier on segmented radiographs from a prospective cohort study of US men (MrOS). We compare the performance of logistic regression (LR) and generalized additive models (GAM) with combinations of individual vertebral scores and basic demographic covariates. METHODS: Subject-level LR and GAM models were created retrospectively using all fracture predictions or summary variables such as order statistics, adjacent vertebral interactions, and demographic covariates (age, race/ethnicity). The classifier outputs for 8663 vertebrae from 1176 thoracic and lumbar radiographs in 669 subjects were divided by subject to perform stratified fivefold cross-validation. Models were assessed using multiple metrics, including receiver operating characteristic (ROC) and precision-recall (PR) curves. RESULTS: The best model (AUC-ROC = 0.968) was a GAM using the top three maximum vertebral fracture scores and age. Using top-ranked scores only, rather than all vertebral scores, improved performance for both model classes. Adding age, but not ethnicity, to the GAMs improved performance slightly. CONCLUSION: Maximal vertebral fracture scores resulted in the highest-performing models. While combining multiple vertebral body predictions risks decreasing specificity, our results demonstrate that subject-level models maintain good predictive performance. Thresholding strategies can be used to control sensitivity and specificity as clinically appropriate.

EEG measures of brain arousal in relation to symptom improvement in patients with major depressive disorder: Results from a randomized placebo-controlled clinical trial.

Hyperstable arousal regulation during a 15-min resting electroencephalogram (EEG) has been linked to a favorable response to antidepressants. The EMBARC study, a multicenter randomized placebo-controlled clinical trial, provides an opportunity to examine arousal stability as putative antidepressant response predictor in short EEG recordings. We tested the hypothesis that high arousal stability during a 2-min resting EEG at baseline is related to better outcome in the sertraline arm and explored the specificity of this effect. Outpatients with chronic/recurrent MDD were recruited from four university hospitals and randomized to treatment with sertraline (n = 100) or placebo (n = 104). The change in the Hamilton Rating Scale for Depression (HRSD-17) was the main outcome. Patients were stratified into high and low arousal stability groups. In mixed-model repeated measures (MMRM) analysis HRSD-17 change differed significantly between arousal groups, with high arousal stability being associated with a better outcome in the sertraline arm, and worse outcome in the placebo arm at week 4, with moderate effect sizes. When considering both treatment arms, a significant arousal group x time x treatment interaction emerged, highlighting specificity to the sertraline arm. Although findings indicate that arousal stability is likely to be a treatment-specific marker of response, further out-of-sample validation is warranted.

COPD treatment ratio: a measure for improving COPD population health.

OBJECTIVES: Despite chronic obstructive pulmonary disease (COPD) being a leading cause of death in the US, there are few COPD measures in current quality programs. The objective of this study was to assess the validity and applicability of the COPD treatment ratio (CTR) as a surrogate marker of COPD exacerbation risk for use in quality measurement. CTR is defined as the ratio of COPD maintenance medications to all COPD medications (maintenance and rescue). STUDY DESIGN: This retrospective cohort study used 2016-2019 administrative claims from Optum Clinformatics Data Mart to evaluate CTR values over a 12-month baseline period, with exacerbations measured the following year. Patients 40 years or older with Medicare Advantage or commercial insurance and with a COPD diagnosis were included. METHODS: Logistic regression models were used to examine relationships between CTR values and COPD exacerbations. Prediction model performance was evaluated using C statistics, and receiver operating characteristics were used to determine the optimal cut point for CTR. RESULTS: Of 132,960 patients included in the analysis, 79.5% were Medicare Advantage beneficiaries, and the mean age was 69.6 years. Higher CTR values were significantly associated with reduced risk of any, moderate, and severe exacerbations in the total population and when stratified by insurance type. CTR performed fairly to moderately well in predicting COPD exacerbations. The optimal cut point for COPD exacerbation prediction was 0.7. CONCLUSIONS: Study results substantiated CTR as a valid measure of COPD exacerbation risk and support the use of CTR in quality improvement to drive evidence-based care for individuals with COPD.

A neural basis of choking under pressure.

Incentives tend to drive improvements in performance. But when incentives get too high, we can "choke under pressure" and underperform right when it matters most. What neural processes might lead to choking under pressure? We studied rhesus monkeys performing a challenging reaching task in which they underperformed when an unusually large "jackpot" reward was at stake, and we sought a neural mechanism that might result in that underperformance. We found that increases in reward drive neural activity during movement preparation into, and then past, a zone of optimal performance. We conclude that neural signals of reward and motor preparation interact in the motor cortex (MC) in a manner that can explain why we choke under pressure.

Vertebral Body Erosions After Glue Embolization of an Aortic Endograft Type II Endoleak: A Case Report.

CASE: We present a case of a 66-year-old man with lumbar vertebral body erosions after glue embolization of a Type II endoleak secondary to endovascular repair of an infrarenal aortic aneurysm. Multiple biopsies of the affected vertebrae were culture-negative confirming no evidence of infection. He underwent posterior spinal fusion from L2 to L5 with complete resolution of mechanical low back pain and improved functional outcomes. CONCLUSION: Vertebral body osseous erosion is a rare complication of aortic endoleak intervention that can be successfully treated with spinal fusion.

Enumerative Discovery of Noncanonical Polypeptide Secondary Structures.

Energetically favorable local interactions can overcome the entropic cost of chain ordering and cause otherwise flexible polymers to adopt regularly repeating backbone conformations. A prominent example is the α helix present in many protein structures, which is stabilized by i, i + 4 hydrogen bonds between backbone peptide units. With the increased chemical diversity offered by unnatural amino acids and backbones, it has been possible to identify regularly repeating structures not present in proteins, but to date, there has been no systematic approach for identifying new polymers likely to have such structures despite their considerable potential for molecular engineering. Here we describe a systematic approach to search through dipeptide combinations of 130 chemically diverse amino acids to identify those predicted to populate unique low-energy states. We characterize ten newly identified dipeptide repeating structures using circular dichroism spectroscopy and comparison with calculated spectra. NMR and X-ray crystallographic structures of two of these dipeptide-repeat polymers are similar to the computational models. Our approach is readily generalizable to identify low-energy repeating structures for a wide variety of polymers, and our ordered dipeptide repeats provide new building blocks for molecular engineering.

Axon-like active signal transmission.

Any electrical signal propagating in a metallic conductor loses amplitude due to the natural resistance of the metal. Compensating for such losses presently requires repeatedly breaking the conductor and interposing amplifiers that consume and regenerate the signal. This century-old primitive severely constrains the design and performance of modern interconnect-dense chips1. Here we present a fundamentally different primitive based on semi-stable edge of chaos (EOC)2,3, a long-theorized but experimentally elusive regime that underlies active (self-amplifying) transmission in biological axons4,5. By electrically accessing the spin crossover in LaCoO3, we isolate semi-stable EOC, characterized by small-signal negative resistance and amplification of perturbations6,7. In a metallic line atop a medium biased at EOC, a signal input at one end exits the other end amplified, without passing through a separate amplifying component. While superficially resembling superconductivity, active transmission offers controllably amplified time-varying small-signal propagation at normal temperature and pressure, but requires an electrically energized EOC medium. Operando thermal mapping reveals the mechanism of amplification-bias energy of the EOC medium, instead of fully dissipating as heat, is partly used to amplify signals in the metallic line, thereby enabling spatially continuous active transmission, which could transform the design and performance of complex electronic chips.

Rib-on-pelvis deformity: a modifiable driver of pain and poor health-related quality of life in cerebral palsy.

PURPOSE: Cerebral Palsy (CP) often presents with a sweeping thoracolumbar scoliosis and pelvic obliquity. With severe pelvic obliquity, the ribs come into contact with the high side of the oblique pelvis, termed rib-on-pelvis deformity (ROP). ROP can result in costo-iliac impingement, or pain associated with ROP, and can also adversely affect breathing and sitting balance. The goal of this study was to evaluate whether CP patients with ROP have worse health-related quality of life (HRQOL) before surgery and a greater improvement in HRQOL after surgery. METHODS: A retrospective analysis of a prospectively collected, multicenter, international registry was performed for all nonambulatory patients with CP treated with spinal fusion with at least two-year follow-up. HRQOL was measured via the Caregiver Priorities & Child Health Index of Life with Disabilities (CPCHILD) questionnaire domains (0 = most disability, 100 = least disability). ROP was defined as having a rib distal to the superior portion of the iliac crest on preop upright radiographs. The ROP group and control group without ROP were compared regarding six domain scores and total score of CPCHILD. Multiple linear regression was used to control for curve apex location, major coronal Cobb angle, type of tone, and pelvic obliquity. RESULTS: 340 patients met inclusion criteria (52% female, mean age 14.0 years). The mean major coronal Cobb angle was 81 degrees and mean pelvic obliquity was 22 degrees. 176 patients (51.8%) had ROP while 164 patients (48.2%) did not. ROP was independently associated with worse preoperative Positioning/Transfers/Mobility (PTM), Comfort & Emotions (C&E), and total CPCHILD score via the CPCHILD questionnaire (p < 0.05). Patients with preoperative ROP experienced a greater improvement in the C&E and PTM domains as well as total CPCHILD score than patients without ROP (p < 0.05). CONCLUSION: CP patients with rib-on-pelvis deformity experience more pain and worse HRQOL than patients without this deformity. These patients experienced a greater improvement in HRQOL after spinal fusion measured via the CPCHILD questionnaire.

Knee Pain, Joint Loading, and Structural Abnormalities on MRI in 13-Year-Old Children in a Population-Based Birth Cohort.

BACKGROUND: Knee pain is a common problem in children and adolescents, and it often has a chronic character. PURPOSE: To examine the prevalence of knee pain in 13-year-old children and assess associations of knee pain with physical factors and the presence of structural abnormalities on magnetic resonance imaging (MRI). STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: Data from the Generation R Study, a population-based birth cohort, were used. Prevalence and characteristics of knee pain were assessed, using a pain mannequin, in children 13 years of age (N = 1849). Patient characteristics and data on physical activity were extracted from questionnaires. The body mass index standard deviation score and waist-hip ratio were calculated from objectively measured weight and height. Structural abnormalities were assessed by MRI. The differences between children with and without knee pain were also analyzed. RESULTS: A prevalence of 8.0% was found for knee pain in children, of which 92.3% persisted for >3 months (ie, chronic); 37.5% of the children experienced pain daily, and the pain was almost always located on the anterior side of the knee (98.6%). Higher body mass index standard deviation scores were seen in children with knee pain than in the children without knee pain. No differences in physical activity were seen between children with and without knee pain. Moreover, in children with knee pain compared with children without knee pain, characteristics of Osgood-Schlatter disease (6.8% vs 1.9%) and bipartite patella type 3 (4.7% vs 0.3%) were more often seen on MRI. CONCLUSION: This study shows that knee pain is a relatively frequent problem in children. It is almost always located on the anterior aspect, has a chronic character, and is often experienced daily. However, the possible implication of structural abnormalities on MRI in children with knee pain and the possible relationship with the development of future knee complaints are still unclear.

A Cross-Sectional Study Examining Andrews' Analysis in Caucasian and African.

BACKGROUND: Andrews' analysis is a commonly utilized instrument to aid in esthetic positioning of the anteroposterior position of the maxillomandibular complex; however, there is limited data regarding use in non-Caucasian subjects. PURPOSE: The purpose of this study was to document laypersons preferences of anteroposterior position of the maxillomandibular complex in relation to Andrews' lateral profile analysis in African American (AA) and Caucasian subjects. STUDY DESIGN, SETTING, SAMPLE: A cross-sectional study was implemented to evaluate the esthetics of AA and Caucasian subjects. Photographs were taken and simulated with anteroposterior maxillomandibular complex positioning in varying relationships to Andrews' goal anterior line limit. A survey was then designed to select the preferred simulation of the facial profile of each subject. INDEPENDENT VARIABLE: The independent variable was the race of the study subjects. MAIN OUTCOME VARIABLE: The main outcome was the layperson's preferred lateral facial profile for each subject. COVARIATES: The covariates included age, race, sex, education level, income, of the laypersons. ANALYSES: A proportion test was used to decide which profile was preferred. Logistic regression analyses were conducted to assess the association between the preference and respondent demographics. P < .05 was considered significant. RESULTS: A total of 264 surveys were distributed, and 250 complete surveys were utilized (response rate = 95%). Respondents were majority male (51.2%), aged 35-44 (37.2%), college-educated (57.2%), earning between $20,000 and $50,000 annually (44%), and identified as Caucasian (77.2%). For the female subjects, the respondents preferred +4 and + 6 mm anterior to goal anterior line limit with 54.2% for the Caucasian and 65.9% for the AA subjects (difference = 11.7%; 95% CI:2.7 to 20.7%; P = .008). For the males, 47.4% of the respondents chose 0 mm and +2 mm for the AA subject, while only 24.9% preferred +2 mm for the Caucasian male (difference = 22.5%; 95% CI: 13.8 to 31.1%; P < .0001). Respondent demographics were not found to influence selection. CONCLUSION AND RELEVANCE: The preferred facial profile as judged by laypersons differs between Caucasian and AA subjects when defined through Andrews' analysis.

The Reverse Fragility Index: Interpreting the Evidence for Arthroscopic Rotator Cuff Repair Healing Associated With Early Versus Delayed Mobilization.

Background: The American Academy of Orthopaedic Surgeons (AAOS) clinical practice guidelines (CPGs) note "strong" evidence that early and delayed mobilization protocols after small to medium arthroscopic rotator cuff repairs achieve similar rotator cuff healing rates. Purpose: We utilized the reverse fragility index (RFI) to assess the fragility of randomized controlled trials (RCTs) reporting no statistically significant difference in tendon re-tear rates after rotator cuff repair in those undergoing early versus delayed rehabilitation. Methods: Randomized controlled trials used in the most recent AAOS CPGs on the timing of postoperative mobilization after arthroscopic rotator cuff repairs were analyzed. Only RCTs with a reported P value ≥ .05 were included. The RFI at a threshold of P < .05 was calculated for each study. The reverse fragility quotient (RFQ) was calculated by dividing the RFI by the study sample size. Results: In 6 clinical trials with a total of 542 patients, the number of tendon re-tear events was 48. The median RFI at the P < .05 threshold was 4 (range: 3.25-4.75), and the median RFQ was .05 (range: 0.03-0.08). The median loss to follow-up was 6 patients. Of the 6 studies investigated, 3 reported a loss to follow-up greater than their respective RFI. Conclusion: The equivalence in rotator cuff repair healing rates associated with early and delayed mobilization protocols rests on fragile studies, as their statistical non-significance can be reversed by changing the outcome status of only a handful of patients. Consideration should be given to the routine reporting of RFI in clinical practice guidelines including RCTs with statistically non-significant results.

INTRAVITREAL METHOTREXATE INJECTION FOR THE TREATMENT AND PREVENTION OF PROLIFERATIVE VITREORETINOPATHY.

PURPOSE: To report on our experience using intravitreal methotrexate (MTX) in patients with retinal detachment associated with proliferative vitreoretinopathy and/or open globe injury. METHODS: This study performed a retrospective chart review of a consecutive series of 21 eyes of 21 patients who underwent serial intravitreal MTX injection for treatment and/or prevention of proliferative vitreoretinopathy from December 2021 to January 2024. RESULTS: Twenty-one patients underwent pars plana vitrectomy, membrane peeling, laser photocoagulation, silicone oil infusion, and intravitreal MTX injection. Postoperatively, all eyes received a series of intravitreal MTX (400 µg/0.1 mL) injections. Optimally, injections were administered weekly for 8 weeks and every 2 weeks for four weeks for a total of 13 injections, beginning intraoperatively at the conclusion of retinal reattachment surgery. Mean baseline preoperative and postoperative visual acuity was logarithm of the minimum angle of resolution 3.2 (approximately hand motions vision) and 2.5 (between CF and hand motions vision), respectively, yielding an average improvement in visual acuity of 0.7 logarithm of the minimum angle of resolution units (0 ETDRS lines/letters). These 21 patients received an average of 10.5 injections. With a single operation, detachments in 19 (90%) of 21 eyes were successfully reattached. Corneal epithelial defects were noted in 7 (33%) of 21 patients. CONCLUSION: Serial intravitreal MTX injection was associated with 90% single operation retinal reattachment rate in the setting of retinal detachment with proliferative vitreoretinopathy or retinal detachment at high risk of proliferative vitreoretinopathy.

Collaborating to heal addiction and mental health in primary care (CHAMP): A protocol for a hybrid type 2a trial.

BACKGROUND: The gold-standard treatment for opioid use disorder (OUD) is medication for OUD (MOUD). However, less than a quarter of people with OUD initiate MOUD. Expanding the Collaborative Care Model (CoCM) to include primary care patients with OUD could improve access to and initiation of MOUD. This paper presents the methods and baseline sample characteristics of a Hybrid Type 2a trial comparing the effectiveness of CoCM for OUD and co-occurring mental health symptoms (MHS) to CoCM for MHS only. METHOD: 42 primary care clinics were cluster randomized and 254 primary care patients with OUD and elevated MHS were enrolled. Recruitment was terminated early by the Data and Safety Monitoring Board for futility. Participants completed research assessments at baseline, 3 months, and 6 months. The multiple primary outcomes were past-month number of days of nonmedical opioid use and SF12 Mental Health Component Summary (MCS) scores. RESULTS: MCS scores were over a standard deviation below the national mean (M = 34.5). Nearly half (47.6 %) of participants had previously overdosed in their lifetimes. Three quarters (76.0 %) were already being prescribed MOUD at baseline, only 30.4 % reported non-medical use of opioids, and only 33.9 % reported being bothered by opioid cravings. CONCLUSION: The unexpectedly high proportion of enrollees already prescribed MOUD at baseline indicates that most patients were in the maintenance rather than acute phase of treatment. Challenges identifying and enrolling patients in the acute phase of OUD treatment implies that intervention effectiveness will depend on its success preventing the discontinuation of MOUD rather than initiating MOUD.

Radical Reactions with Chiral Acylammonium Salts: Synthesis of Functionalized δ-Lactams through Giese-Initiated Organocascades.

Enantioselective Giese reactions employing chiral α,ß-unsaturated acylammonium salts and subsequent diastereoselective trapping followed by lactamization deliver optically active δ-lactams. Alkyl iodides bearing tosylamides undergo radical initiation using triethylborane at low temperatures to provide carbon-centered radicals to initiate the described organocascade. Subsequent diastereoselective inter- or intramolecular trapping of the incipient α-radical leads to highly functionalized, enantioenriched mono- and bicyclic δ-lactams (up to 99:1 er, > 19:1 dr) bearing up to three stereogenic centers. Interestingly, benzotetramisole imparts diastereoselectivity that contradicts steric considerations alone. Results from DFT calculations rationalized the observed enantio- and diastereoselectivities, revealed an electrostatic interaction between the sulfone oxygens and the ammonium cation in the initial α-radical intermediate, and aided in application of this methodology to bicyclic δ-lactams through intramolecular trapping of the α-radical intermediate.