Effects of Socioeconomic Burden on Opioid Use Following Total Shoulder Arthroplasty.

BACKGROUND: Preoperative opioid users (POU) experience worse outcomes and higher complication rates compared to opioid naïve patients (ONP) following shoulder arthroplasty. This study evaluates the effects of socioeconomic status (SES), as measured by the distressed communities index (DCI), on pre- and postoperative opioid use and its influence on clinical outcomes such as readmission and revision surgery. METHODS: A retrospective review of patients who underwent primary shoulder arthroplasty (CPT code 23472) from 2014-2022 at a single academic institution was performed. Exclusion criteria included arthroplasty for fracture, active malignancy, and revision arthroplasty. Demographics, Charlson Comorbidity Index (CCI), DCI, and clinical outcomes including 90-day readmission and revision surgery were collected. Patients were classified according to the DCI score of their zip code. Using the Prescription Drug Monitoring Program database, patient pre- and postoperative opioid use in morphine milligram equivalents (MME) was gathered. RESULTS: Individuals from distressed communities utilized more opioids within 90 days preoperatively compared to patients from prosperous, comfortable, mid-tier, and at-risk populations respectively. Patients from distressed communities also used significantly more opioids within 90 days postoperatively compared to prosperous, comfortable, and mid-tier respectively. Of patients from distressed communities, 35.1% developed prolonged opioid use (filling prescriptions >30 days after surgery), significantly more than all other cohorts. Among all patients, 3.5% were readmitted within 90 days and were more likely to be prolonged opioid users (38.9 vs 21.3%, p<0.001). Similarly, 1.5% of patients underwent revision surgery. Those who underwent revision were significantly more likely to be prolonged opioid users (38.2 vs 21.7%, p=0.002). CONCLUSIONS: Shoulder arthroplasty patients from distressed communities use more opioids within 90 days before and after their surgery and are more likely to become prolonged opioid users placing them at risk for readmission and revision surgery. Identifying patients at an increased risk for excess opioid use is essential to employ appropriate strategies that minimize the detrimental effects of prolonged use following surgery.

CRISPR Advancements for Human Health.

CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) has emerged as a powerful gene editing technology that is revolutionizing biomedical research and clinical medicine. The CRISPR system allows scientists to rewrite the genetic code in virtually any organism. This review provides a comprehensive overview of CRISPR and its clinical applications. We first introduce the CRISPR system and explain how it works as a gene editing tool. We then highlight current and potential clinical uses of CRISPR in areas such as genetic disorders, infectious diseases, cancer, and regenerative medicine. Challenges that need to be addressed for the successful translation of CRISPR to the clinic are also discussed. Overall, CRISPR holds great promise to advance precision medicine, but ongoing research is still required to optimize delivery, efficacy, and safety.

Surgeon Factors and Trends Associated With the Use of Subacromial Decompression at the Time of Rotator Cuff Repair.

PURPOSE: Subacromial decompression (SAD) has historically been described as an essential part of the surgical treatment of rotator cuff disorders. However, investigations throughout the 21st century have increasingly questioned the need for routine SAD during rotator cuff repair (RCR). Our purpose was to assess for changes in the incidence of SAD performed during RCR over a 12-year period. In addition, we aimed to characterize surgeon and practice factors associated with SAD use. METHODS: Records from two large tertiary referral systems in the United States from 2010 to 2021 were reviewed. All cases of RCR with and without SAD were identified. The outcome of interest was the proportion of SAD performed during RCR across years and by surgeon. Surgeon-specific characteristics included institution, fellowship training, surgical volume, academic practice, and years in practice. Yearly trends were assessed using binomial logistic regression modeling, with a random effect accounting for surgeon-specific variability. RESULTS: During the study period, 37,165 RCR surgeries were performed by 104 surgeons. Of these cases, 71% underwent SAD during RCR. SAD use decreased by 11%. The multivariable model found that surgeons in academic practice, those with lower surgical volume, and those with increasing years in practice were significantly associated with increased odds of performing SAD. Surgeons with fellowship training were significantly more likely to use SAD over time, with the greatest odds of SAD noted for sports medicine surgeons (odds ratio = 3.04). CONCLUSIONS: Although SAD use during RCR appears to be decreasing, multiple surgeon and practice factors (years in practice, fellowship training, volume, and academic practice) are associated with a change in SAD use. CLINICAL RELEVANCE: These data suggest that early-career surgeons entering practice are likely driving the trend of declining SAD. Despite evidence suggesting limited clinical benefits, SAD remains commonly performed; future studies should endeavor to determine factors associated with practice changes among surgeons.

CRISPR-Cas9 Genome Editing of Rat Embryos using Adeno-Associated Virus (AAV) and 2-Cell Embryo Electroporation.

Genome editing technology is widely used to produce genetically modified animals, including rats. Cytoplasmic or pronuclear injection of DNA repair templates and CRISPR-Cas reagents is the most common delivery method into embryos. However, this type of micromanipulation necessitates access to specialized equipment, is laborious, and requires a certain level of technical skill. Moreover, microinjection techniques often result in lower embryo survival due to the mechanical stress on the embryo. In this protocol, we developed an optimized method to deliver large DNA repair templates to work in conjunction with CRISPR-Cas9 genome editing without the need for microinjection. This protocol combines AAV-mediated DNA delivery of single-stranded DNA donor templates along with the delivery of CRISPR-Cas9 ribonucleoprotein (RNP) by electroporation to modify 2-cell embryos. Using this novel strategy, we have successfully produced targeted knock-in rat models carrying insertion of DNA sequences from 1.2 to 3.0 kb in size with efficiencies between 42% and 90%.

The impact of preoperative benzodiazepine use on postoperative opioid use in total shoulder arthroplasty.

BACKGROUND: As the rate of total shoulder arthroplasty (TSA) and preoperative benzodiazepine use rise, there is an increased need to understand the impact of preoperative benzodiazepine use on postoperative opioid consumption following TSA, especially amid the current opioid epidemic. The relationship between preoperative benzodiazepine use and chronic opioid use postoperatively has been well described following other orthopedic procedures; however, the impact on patients undergoing TSA remains unclear. This study aims to identify the impact of preoperative benzodiazepine use on opioid use following TSA. METHODS: A retrospective chart review of 4488 patients undergoing primary TSA (Current Procedural Terminology code 23472) at a single institution from 2014 to 2022 was performed. Patient demographics, surgical variables, comorbidities, Distressed Communities Index (DCI), and clinical outcomes, including readmission and revision, were collected. The Charlson Comorbidity Index (CCI) was used to assess preoperative health status. Opioid use in morphine milligram equivalents (MMEs) and benzodiazepine use were also recorded using the Prescription Drug Monitoring Program Database. Opioid use was collected at 30-, 60-, and 90-day intervals both before and after each patient's date of surgery. Statistical analysis included stepwise logistic regression to identify variables independently affecting benzodiazepine use pre- and postoperatively. RESULTS: Overall, 16% of patients used benzodiazepines within 90 days before their date of surgery. Of those patients, 46.4% were also using preoperative opioids, compared with just 30.0% of patients who were benzodiazepine-naïve (P < .001). Preoperative benzodiazepine use was also associated with increased pre- and postoperative total opioid use in MMEs and the number of opioid prescriptions across all time points when compared to benzodiazepine-naïve patients (P < .001). Furthermore, 37.4% of preoperative benzodiazepine users went on to prolonged opioid use (filled prescriptions >30 days after surgery) compared to 19.0% of those who were benzodiazepine-naïve (P < .001). CONCLUSION: This study demonstrates a significant association between preoperative benzodiazepine use and increased and prolonged opioid use following TSA. Further exploration of risk factors contributing to preoperative benzodiazepine use may help to reduce overall opioid use in patients undergoing TSA.

Fatty acid oxidation fuels natural killer cell responses against infection and cancer.

Natural killer (NK) cells are a vital part of the innate immune system capable of rapidly clearing mutated or infected cells from the body and promoting an immune response. Here, we find that NK cells activated by viral infection or tumor challenge increase uptake of fatty acids and their expression of carnitine palmitoyltransferase I (CPT1A), a critical enzyme for long-chain fatty acid oxidation. Using a mouse model with an NK cell-specific deletion of CPT1A, combined with stable 13C isotope tracing, we observe reduced mitochondrial function and fatty acid-derived aspartate production in CPT1A-deficient NK cells. Furthermore, CPT1A-deficient NK cells show reduced proliferation after viral infection and diminished protection against cancer due to impaired actin cytoskeleton rearrangement. Together, our findings highlight that fatty acid oxidation promotes NK cell metabolic resilience, processes that can be optimized in NK cell-based immunotherapies.

Augmented Fixation in Transverse Midshaft Humerus Fractures Using a Nitinol Staple: Surgical Technique and Case Series.

Maintaining the reduction of a transverse humeral shaft fracture can be particularly challenging while applying a compression plate for definitive fixation. Nitinol compression staples are being increasingly utilized in orthopedic surgery due to their unique ability to apply continuous compression between staple legs at body temperature. We have found them to be particularly useful in the maintenance of the reduction of transverse humeral shaft fractures before compression plate application. This simple technique allows for the removal of reduction clamps and precise plate placement. We describe our technique for using nitinol compression staples to augment fracture fixation in transverse humeral shaft fractures as well as our experience using this technique in a case series of 4 patients.

Delirium detection tools show varying completion rates and positive score rates when used at scale in routine practice in general hospital settings: A systematic review.

BACKGROUND: Multiple short delirium detection tools have been validated in research studies and implemented in routine care, but there has been little study of these tools in real-world conditions. This systematic review synthesized literature reporting completion rates and/or delirium positive score rates of detection tools in large clinical populations in general hospital settings. METHODS: PROSPERO (CRD42022385166). Medline, Embase, PsycINFO, CINAHL, and gray literature were searched from 1980 to December 31, 2022. Included studies or audit reports used a validated delirium detection tool performed directly with the patient as part of routine care in large clinical populations (n ≥ 1000) within a general acute hospital setting. Narrative synthesis was performed. RESULTS: Twenty-two research studies and four audit reports were included. Tools used alone or in combination were the Confusion Assessment Method (CAM), 4 'A's Test (4AT), Delirium Observation Screening Scale (DOSS), Brief CAM (bCAM), Nursing Delirium Screening Scale (NuDESC), and Intensive Care Delirium Screening Checklist (ICDSC). Populations and settings varied and tools were used at different stages and frequencies in the patient journey, including on admission only; inpatient, daily or more frequently; on admission and as inpatient; inpatient post-operatively. Tool completion rates ranged from 19% to 100%. Admission positive score rates ranged from: CAM 8%-51%; 4AT 13%-20%. Inpatient positive score rates ranged from: CAM 2%-20%, DOSS 6%-42%, and NuDESC 5-13%. Postoperative positive score rates were 21% and 28% (4AT). All but two studies had moderate-high risk of bias. CONCLUSIONS: This systematic review of delirium detection tool implementation in large acute patient populations found clinically important variability in tool completion rates, and in delirium positive score rates relative to expected delirium prevalence. This study highlights a need for greater reporting and analysis of relevant healthcare systems data. This is vital to advance understanding of effective delirium detection in routine care.

Prostaglandin E2 impacts multiple stages of the natural killer cell antitumor immune response.

Tumor immune escape is a major factor contributing to cancer progression and unresponsiveness to cancer therapies. Tumors can produce prostaglandin E2 (PGE2 ), an inflammatory mediator that directly acts on Natural killer (NK) cells to inhibit antitumor immunity. However, precisely how PGE2 influences NK cell tumor-restraining functions remains unclear. Here, we report that following PGE2 treatment, human NK cells exhibited altered expression of specific activating receptors and a reduced ability to degranulate and kill cancer targets. Transcriptional analysis uncovered that PGE2 also differentially modulated the expression of chemokine receptors by NK cells, inhibiting CXCR3 but increasing CXCR4. Consistent with this, PGE2-treated NK cells exhibited decreased migration to CXCL10 but increased ability to migrate toward CXCL12. Using live cell imaging, we showed that in the presence of PGE2 , NK cells were slower and less likely to kill cancer target cells following conjugation. Imaging the sequential stages of NK cell killing revealed that PGE2 impaired NK cell polarization, but not the re-organization of synaptic actin or the release of perforin itself. Together, these findings demonstrate that PGE2 affects multiple but select NK cell functions. Understanding how cancer cells subvert NK cells is necessary to more effectively harness the cancer-inhibitory function of NK cells in treatments.

Drug-induced orthostatic hypotension: Cluster analysis of co-prescription patterns in older people in UK primary care.

PURPOSE: Over 250 medications are reported to cause orthostatic hypotension, associated with serious adverse outcomes in older adults. Studies suggest a harmful cumulative risk of orthostatic hypotension with multiple medication use. However, there is limited evidence on the potential for harm in practice, particularly which drugs is co-prescribed and may increase risk of orthostatic hypotension. METHODS: Retrospective cohort study and cluster analysis using general practice data from IQVIA Medical Research Data (IMRD) in patients aged ≥50 contributing data between 1 January 2018 and 31 December 2018. Thirteen drug groups known to be associated with orthostatic hypotension by mechanism, were analyzed and clusters generated by sex and age-band. RESULTS: A total of 602 713 individuals aged ≥50 with 283 912 (47%) men and 318 801 (53%) women were included. The most prevalent prescriptions that might contribute to orthostatic hypotension were ACE inhibitors, calcium-channel blockers, beta-blockers, selective serotonin reuptake inhibitors and uroselective alpha-blockers. We identified distinct clusters of cardiovascular system (cardiovascular system) drugs in men and women at all ages. cardiovascular system plus psychoactive drug clusters were common in women at all ages, and in men aged ≤70. cardiovascular system plus uroselective alpha-blockers were identified in men aged ≥70. CONCLUSIONS: Distinct clusters of drugs associated with orthostatic hypotension exist in practice, which change over the life course. Our findings highlight potentially harmful drug combinations that may cause cumulative risk of orthostatic hypotension in older people. This may guide clinicians about the potential of synergistic harm and to monitor for orthostatic hypotension if using combinations of cardiovascular system drugs, cardiovascular system plus psychoactive drugs and/or alpha-blockers-particularly in patients aged ≥70 or at high-risk due to comorbidity. Future research should consider quantifying the risk of drug-induced orthostatic hypotension with such drug combinations.

Outcomes after salvage reverse shoulder arthroplasty for failed primary fixation or hemiarthroplasty for proximal humerus fractures: A systematic review.

Background: Salvage reverse shoulder arthroplasty (RSA) for failed proximal humerus fractures (PHFs) fixation and hemiarthroplasty (HA) may maximize outcomes in the absence of tuberosity healing or a chronically torn rotator cuff. The purpose of this systematic review was to examine the improvement in clinical outcomes for patients after revision RSA was performed for failed PHFs fixation or HA. Methods: An electronic database search of SCOPUS, PubMed, Embase, MEDLINE, SPORTDiscus, CINAHL, and ClinicalTrials.gov was performed. A meta-analysis was carried out to determine weighted mean outcome differences between two primary intervention cohorts (failed fixation: open reduction and internal fixation, intramedullary nail, or K-wire vs. failed HA). Results: Fifteen studies were included (primary fixation: 208 patients; HA: 162 patients). Patients improved meaningfully in all clinical outcomes after revision surgery (constant: 18.5-48.3; abduction: 44-95; forward flexion: 47-107; external rotation: 5-10), with a 16.2% complication and 9.4% revision rate. The failed fixation group performed significantly better than the failed HA group in postoperative constant (fixation: 53.3 vs. HA: 45.1, p = 0.016) and shoulder abduction (fixation: 102 vs. HA: 87, p = 0.026). Conclusions: RSA is a successful revision intervention for primary PHF operative failures with the greatest benefit for failures of primary fixation versus HA.

Physiotherapist-led exercise versus usual care (waiting-list) control for patients awaiting rotator cuff repair surgery: A pilot randomised controlled trial (POWER).

BACKGROUND: Once a decision to undergo rotator cuff repair surgery is made, patients are placed on the waiting list. It can take weeks or months to receive surgery. There has been a call to move from waiting lists to 'preparation' lists to better prepare patients for surgery and to ensure it remains an appropriate treatment option for them. OBJECTIVE: To evaluate the feasibility, as measured by recruitment rates, treatment fidelity and follow-up rates, of a future multi-centre randomised controlled trial to compare the clinical and cost-effectiveness of undertaking a physiotherapist-led exercise programme while waiting for surgery versus usual care (waiting-list control). DESIGN: Two-arm, multi-centre pilot randomised controlled trial with feasibility objectives in six NHS hospitals in England. METHOD: Adults (n = 76) awaiting rotator cuff repair surgery were recruited and randomly allocated to a programme of physiotherapist-led exercise (n = 38) or usual care control (n = 38). RESULTS: Of 302 eligible patients, 76 (25%) were randomised. Of 38 participants randomised to physiotherapist-led exercise, 28 (74%) received the exercise programme as intended. 51/76 (67%) Shoulder Pain and Disability Index questionnaires were returned at 6-months. Of 76 participants, 32 had not received surgery after 6-months (42%). Of those 32, 20 were allocated to physiotherapist-led exercise; 12 to usual care control. CONCLUSIONS: A future multi-centre randomised controlled trial is feasible but would require planning for variable recruitment rates between sites, measures to improve treatment fidelity and opportunity for surgical exit, and optimisation of follow-up. A fully powered, randomised controlled trial is now needed to robustly inform clinical decision-making.

The use of a total bowel length measurement protocol may reduce reoperations and complications after single-anastomosis duodenal switch.

INTRODUCTION: Most surgeons who perform single-anastomosis duodeno-ileal switches (SADI-S) use a pre-determined common channel length without measuring total bowel length (TBL). However, TBL varies between patients, and a standardized common channel length could contribute to malabsorptive complications and reoperations following SADI-S. The purpose of this study was to determine whether using a TBL measurement protocol to individualize common channel length would be associated with reduced reoperations and complications. METHODS: A prospectively maintained data registry was retrospectively reviewed to identify all patients who underwent SADI-S between September 2017 and February 2022. In April 2021, we began using TBL measurements during SADI-S with 40% of the TBL used as the length for the common channel. Outcomes pre-TBL and post-TBL measurement protocol were compared. RESULTS: A total of 119 SADI-S recipients (59 pre-TBL; 60 post-TBL) were included. The pre-TBL group had a higher frequency of reoperations (23.7% vs 1.7%, p < 0.001) and late complications (29.3% vs 3.3%, p < 0.001). The mean time to reoperation was 13.7 months in the pre-TBL group and 6.7 months in the post-TBL group (p = 0.347). Patients in the post-TBL group had significantly higher serum albumin levels at 3 months (4.2 g/dL vs 3.5 g/dL, p < 0.001), 6 months (4.1 g/dL vs 3.6 g/dL, p < 0.001), and 12 months (4.2 g/dL vs 3.8 g/dL, p = 0.023) postoperatively when compared to the pre-TBL group. CONCLUSION: Using TBL measurements to individualize common channel length was associated with a significant reduction in reoperations and late complications following SADI-S.

Efficient DNA knock-in using AAV-mediated delivery with 2-cell embryo CRISPR-Cas9 electroporation.

Recent advances in CRISPR-Cas genome editing technology have been instrumental in improving the efficiency to produce genetically modified animal models. In this study we have combined four very promising approaches to come up with a highly effective pipeline to produce knock-in mouse and rat models. The four combined methods include: AAV-mediated DNA delivery, single-stranded DNA donor templates, 2-cell embryo modification, and CRISPR-Cas ribonucleoprotein (RNP) electroporation. Using this new combined approach, we were able to produce successfully targeted knock-in rat models containing either Cre or Flp recombinase sequences with knock-in efficiencies over 90%. Furthermore, we were able to produce a knock-in mouse model containing a Cre recombinase targeted insertion with over 50% knock-in efficiency directly comparing efficiencies to other commonly used approaches. Our modified AAV-mediated DNA delivery with 2-cell embryo CRISPR-Cas9 RNP electroporation technique has proven to be highly effective for generating both knock-in mouse and knock-in rat models.

Expert consensus on difficult airway assessment.

Background: Identifying a potentially difficult airway is crucial both in anaesthesia in the operating room (OR) and non-operation room sites. There are no guidelines or expert consensus focused on the assessment of the difficult airway before, so this expert consensus is developed to provide guidance for airway assessment, making this process more standardized and accurate to reduce airway-related complications and improve safety. Methods: Seven members from the Airway Management Group of the Chinese Society of Anaesthesiology (CSA) met to discuss the first draft and then this was sent to 15 international experts for review, comment, and approval. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) is used to determine the level of evidence and grade the strength of recommendations. The recommendations were revised through a three-round Delphi survey from experts. Results: This expert consensus provides a comprehensive approach to airway assessment based on the medical history, physical examination, comprehensive scores, imaging, and new developments including transnasal endoscopy, virtual laryngoscopy, and 3D printing. In addition, this consensus also reviews some new technologies currently under development such as prediction from facial images and voice information with the aim of proposing new research directions for the assessment of difficult airway. Conclusions: This consensus applies to anesthesiologists, critical care, and emergency physicians refining the preoperative airway assessment and preparing an appropriate intubation strategy for patients with a potentially difficult airway.

TIGIT can inhibit T cell activation via ligation-induced nanoclusters, independent of CD226 co-stimulation.

TIGIT is an inhibitory receptor expressed on lymphocytes and can inhibit T cells by preventing CD226 co-stimulation through interactions in cis or through competition of shared ligands. Whether TIGIT directly delivers cell-intrinsic inhibitory signals in T cells remains unclear. Here we show, by analysing lymphocytes from matched human tumour and peripheral blood samples, that TIGIT and CD226 co-expression is rare on tumour-infiltrating lymphocytes. Using super-resolution microscopy and other techniques, we demonstrate that ligation with CD155 causes TIGIT to reorganise into dense nanoclusters, which coalesce with T cell receptor (TCR)-rich clusters at immune synapses. Functionally, this reduces cytokine secretion in a manner dependent on TIGIT's intracellular ITT-like signalling motif. Thus, we provide evidence that TIGIT directly inhibits lymphocyte activation, acting independently of CD226, requiring intracellular signalling that is proximal to the TCR. Within the subset of tumours where TIGIT-expressing cells do not commonly co-express CD226, this will likely be the dominant mechanism of action.

Intraparenchymal convection enhanced delivery of AAV in sheep to treat Mucopolysaccharidosis IIIC.

BACKGROUND: Mucopolysaccharidosis IIIC (MPSIIIC) is one of four Sanfilippo diseases sharing clinical symptoms of severe cognitive decline and shortened lifespan. The missing enzyme, heparan sulfate acetyl-CoA: α-glucosaminide-N-acetyltransferase (HGSNAT), is bound to the lysosomal membrane, therefore cannot cross the blood-brain barrier or diffuse between cells. We previously demonstrated disease correction in MPSIIIC mice using an Adeno-Associated Vector (AAV) delivering HGSNAT via intraparenchymal brain injections using an AAV2 derived AAV-truetype (AAV-TT) serotype with improved distribution over AAV9. METHODS: Here, intraparenchymal AAV was delivered in sheep using catheters or Hamilton syringes, placed using Brainlab cranial navigation for convection enhanced delivery, to reduce proximal vector expression and improve spread. RESULTS: Hamilton syringes gave improved AAV-GFP distribution, despite lower vector doses and titres. AAV-TT-GFP displayed moderately better transduction compared to AAV9-GFP but both serotypes almost exclusively transduced neurons. Functional HGSNAT enzyme was detected in 24-37% of a 140g gyrencephalic sheep brain using AAV9-HGSNAT with three injections in one hemisphere. CONCLUSIONS: Despite variabilities in volume and titre, catheter design may be critical for efficient brain delivery. These data help inform a clinical trial for MPSIIIC.

Can the Oral Bioavailability of the Discontinued Prostate Cancer Drug Galeterone Be Improved by Processing Method? KinetiSol® Outperforms Spray Drying in a Head-to-head Comparison.

Galeterone, a novel prostate cancer candidate treatment, was discontinued after a Phase III clinical trial due to lack of efficacy. Galeterone is weakly basic and exhibits low solubility in biorelevant media (i.e., ~ 2 µg/mL in fasted simulated intestinal fluid). It was formulated as a 50-50 (w/w) galeterone-hypromellose acetate succinate spray-dried dispersion to increase its bioavailability. Despite this increase, the bioavailability of this formulation may have been insufficient and contributed to its clinical failure. We hypothesized that reformulating galeterone as an amorphous solid dispersion by KinetiSol® compounding could increase its bioavailability. In this study, we examined the effects of composition and manufacturing technology (Kinetisol and spray drying) on the performance of galeterone amorphous solid dispersions. KinetiSol compounding was utilized to create galeterone amorphous solid dispersions containing the complexing agent hydroxypropyl-ß-cyclodextrin or hypromellose acetate succinate with lower drug loads that both achieved a ~ 6 × increase in dissolution performance versus the 50-50 spray-dried dispersion. When compared to a spray-dried dispersion with an equivalent drug load, the KinetiSol amorphous solid dispersions formulations exhibited ~ 2 × exposure in an in vivo rat study. Acid-base surface energy analysis showed that the equivalent composition of the KinetiSol amorphous solid dispersion formulation better protected the weakly basic galeterone from premature dissolution in acidic media and thereby reduced precipitation, inhibited recrystallization, and extended the extent of supersaturation during transit into neutral intestinal media.

Distressed communities demonstrate increased readmission and health care utilization following shoulder arthroplasty.

BACKGROUND: Socioeconomic status (SES) has been shown to affect outcomes following total shoulder arthroplasty (TSA), but little is known regarding how SES and the communities in which patients reside can affect postoperative health care utilization. With the growing use of bundled payment models, understanding what factors put patients at risk for readmission and the ways in which patients utilize the health care system postoperatively is crucial for preventing excess costs for providers. This study helps surgeons predict which patients are high-risk and may require additional surveillance following shoulder arthroplasty. METHODS: A retrospective review of 6170 patients undergoing primary shoulder arthroplasty (anatomic and reverse; Current Procedural Terminology code 23472) from 2014-2020 at a single academic institution was performed. Exclusion criteria included arthroplasty for fracture, active malignancy, and revision arthroplasty. Demographics, patient zip code, and Charlson Comorbidity Index were attained. Patients were classified according to the Distressed Communities Index (DCI) score of their zip code. The DCI combines several metrics of socioeconomic well-being to generate a single score. Zip codes are then classified by scores into 5 categories based on national quintiles. The primary outcome of interest was 90-day readmissions. Secondary outcomes included number of postoperative medication prescriptions, patient telephone calls to the office, and follow-up office visits. RESULTS: Among all patients undergoing total shoulder arthroplasty, individuals from distressed communities were more likely than their prosperous counterparts to experience an unplanned readmission (odds ratio = 1.77, P = .045). Patients from comfortable (relative risk [RR] = 1.12, P < .001), midtier (RR = 1.13, P < .001), at-risk (RR = 1.20, P < .001), and distressed (RR = 1.17, P < .001) communities were all more likely to use more medications compared to those from prosperous communities. Likewise, those from comfortable (RR = 0.92, P < .001), midtier (RR = 0.88, P < .001), at-risk (RR = 0.93, P = .008), and distressed (RR = 0.93, P = .033) communities, respectively, were at a lower risk of making calls compared to prosperous communities. CONCLUSIONS: Following primary total shoulder arthroplasty, patients who reside in distressed communities are at significantly increased risk of experiencing an unplanned readmission and increased health care utilization postoperatively. This study revealed that patient socioeconomic distress is more associated with readmission than race following TSA. Increased awareness and employing strategies to maintain and ultimately improve communication with patients offers a potential solution to reduce excessive health care utilization, benefiting both patients and providers alike.

The effects of computerised cognitive training on post-CABG delirium and cognitive change: A prospective randomised controlled trial.

Background: Cognitive impairments, including delirium, are common after coronary artery bypass grafting (CABG). Improving cognition pre- and post-operatively using computerised cognitive training (CCT) may be an effective approach to improve cognitive outcomes in CABG patients. Objectives: Investigate the effect of remotely supervised CCT on cognitive outcomes, including delirium, in older adults undergoing CABG surgery. Methods: Thirty-six participants, were analysed in a single-blinded randomised controlled trial (CCT Intervention: n = 18, Control: n = 18). CCT was completed by the intervention group pre-operatively (every other day, 45-60-minute sessions until surgery) and post-operatively, beginning 1-month post-CABG (3 x 45-60-minute sessions/week for 12-weeks), while the control group maintained usual care plus weekly phone calls. Cognitive assessments were conducted pre- and post-operatively at multiple follow-ups (discharge, 4-months and 6-months). Post-operative delirium incidence was assessed daily until discharge. Cognitive change data were calculated at each follow-up for each cognitive test (Addenbrooke's Cognitive Examination III and CANTAB; z-scored). Results: Adherence to the CCT intervention (completion of three pre-operative or 66% of post-operative sessions) was achieved in 68% of pre-CABG and 59% of post-CABG participants. There were no statistically significant effects of CCT on any cognitive outcome, including delirium incidence. Conclusion: Adherence to the CCT program was comparatively higher than previous feasibility studies, possibly due to the level of supervision and support provided (blend of face-to-face and home-based training, with support phone calls). Implementing CCT interventions both pre- and post-operatively is feasible in those undergoing CABG. No statistically significant benefits from the CCT interventions were identified for delirium or cognitive function post-CABG, likely due to the sample size available (study recruitment greatly impacted by COVID-19). It also may be the case that multimodal intervention would be more effective.