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Introduction: Concurrent prescribing of opioids and benzodiazepines is associated with increased risk of emergency department visits and overdose. Postpartum women commonly receive opioids for pain after delivery and are at risk for postpartum depression/anxiety. Although prior research finds increases in opioid prescribing and symptoms of depression/anxiety during COVID-19, concurrent prescribing among postpartum women has not been examined in the context of COVID-19. Methods: Using data from a large sample of privately insured postpartum women (N=514,120), the authors compared concurrent prescription fills of opioids and benzodiazepines before March 1, 2020, and after March 1, 2020. Primary outcome variables measured whether a patient ever filled concurrent opioid and benzodiazepine prescriptions and the number of concurrent prescription fills per patient in the 6 months after delivery. Results: Roughly 46.4% of postpartum women filled an opioid prescription, 2.4% filled a benzodiazepine prescription, and 1.2% of women filled a concurrent prescription. Among postpartum women filling a benzodiazepine prescription, 50.7% filled a concurrent opioid prescription. The number of concurrent fills among postpartum women significantly increased during the early period of COVID-19. On average, postpartum women filled 0.009 more concurrent prescriptions than expected on the basis of the preexisting trend, representing a 22.0% increase in the number of concurrent prescriptions relative to the sample mean. Conclusions: Concurrent prescribing of opioids and benzodiazepines places postpartum women at higher risk of emergency department visits and overdose. To reduce the harms associated with concurrent prescribing, clinicians should carefully consider whether opioids and/or benzodiazepines are clinically necessary for treatment and consult their state prescription drug monitoring program prior to prescribing these medications.

In many commercial steel processing routes, steel microstructures are reverted to an austenitic condition prior to the final processing steps. Understanding the microstructure development during austenitization is crucial for improving the performance and reliability of the microstructure that forms from austenite. In this work, austenite formation in a high-C steel (0.85 wt%) from a microstructure containing martensite/austenite and bainite bands is investigated. It is shown that austenite formation from bainite results in a refined austenite grain structure, and the martensite matrix thus obtained on quenching has a homogeneous distribution of carbides with a relatively low fraction of retained austenite (24%). On the other hand, a coarser austenite microstructure is obtained when austenite forms from a mixture of martensite and retained austenite. The reason for the coarse austenite grains is argued to be a memory effect, which is substantiated by in situ X-ray diffraction analysis. After quenching, an inhomogeneous carbide distribution and a higher retained austenite fraction (30%) are observed in the regions that were initially martensite/austenite. The global microstructure, hence, has a bimodal size distribution of prior austenite grains and carbide-dense bands. The causes for these heterogeneities are discussed with the help of interrupted quench experiments, equilibrium phase calculations, and DICTRA simulations.

Background: Fully porous acetabular shells are an appealing choice for patients with extensive acetabular defects undergoing revision total hip arthroplasty (rTHA). This study reports on the early outcomes of a novel 3-D printed fully porous titanium acetabular shell in revision acetabular reconstruction. Methods: A multicenter retrospective study of patients who received a fully porous titanium acetabular shell for rTHA with a minimum of 2 years of follow-up was conducted. The primary outcome was rate of acetabular revision. Results: The final study cohort comprised 68 patients with a mean age of 67.6 years (standard deviation 10.4) and body mass index of 29.5 kg/m2 (standard deviation 5.9). Ninety-four percent had a preoperative Paprosky defect grade of 2A or higher. The average follow-up duration was 3.0 years (range 2.0-5.1). Revision-free survivorship at 2 years was 81% for all causes, 88% for acetabular revisions, and 90% for acetabular revision for aseptic acetabular shell failure. Eight shells were explanted within 2 years (12%): 3 for failure of osseointegration/aseptic loosening (4%) after 15, 17, and 20 months; 3 for infection (4%) after 1, 3, and 6 months; and 2 for instability (3%). At the latest postoperative follow-up, all unrevised shells showed radiographic signs of osseointegration, and none had migrated. Conclusions: This novel 3-D printed fully porous titanium shell in rTHA demonstrated good survivorship and osseointegration when used in complex acetabular reconstruction at a minimum of 2 years. Level of evidence: IV, case series.

Summary: Genes that are key to cell identity are generally regulated by cell-type-specific enhancer elements bound by transcription factors, some of which facilitate looping to distant gene promoters. In contrast, genes that encode housekeeping functions, whose regulation is essential for normal cell metabolism and growth, generally lack interactions with distal enhancers. We find that Ronin (Thap11) assembles multiple promoters of housekeeping and metabolic genes to regulate gene expression. This behavior is analogous to how enhancers are brought together with promoters to regulate cell identity genes. Thus, Ronin-dependent promoter assemblies provide a mechanism to explain why housekeeping genes can forgo distal enhancer elements and why Ronin is important for cellular metabolism and growth control. We propose that clustering of regulatory elements is a mechanism common to cell identity and housekeeping genes but is accomplished by different factors binding distinct control elements to establish enhancer-promoter or promoter-promoter interactions, respectively.

Objectives: For patients with geriatric frailty, reducing inappropriate medication is an important goal to improve patient safety in primary care. GP-side barriers include knowledge gaps, legal concerns, and lack of communication between the actors involved. The aim was to develop a multi-faceted intervention to facilitate deprescribing and shared prioritisation among frail elderlies with polypharmacy living at home. Methods: Mixed methods study including: 1) scoping review on family conferences, expert panels; 2) group discussions with GPs, mapping of needs and challenges in Primary Care; 3) workshops and expert interviews with GPs, patient advocates, researchers as a basis for a theoretical intervention model; 4) piloting. Results: A major challenge for GPs is to conduct a productive discussion with patients and family cares on deprescribing and drug safety. A guideline for a structured family conference with a medication check and geriatric assessment was developed and proved to be feasible in the pilot study. Conclusion: The intervention developed to facilitate deprescribing and shared prioritisation of drug therapy based on family conferences seems suitable to be tested in a subsequent cRCT. Innovation: Adapting family conferences to primary care for frail patients with polypharmacy.

Summary: Modulating R-loop triplex nucleic acid structures reveals their roles across the genome. However, common approaches cannot ascribe functions to R-loops in a locus-associated manner. This protocol presents the use of a locus-associated R-loop-modulating system (dubbed LasR), which employs an inducible RNaseH1-EGFP-dCas9 chimaera. We detail the in silico design of sgRNAs and their transfection with the chimaera, and outline steps confirming RNaseH1-EGFP-dCas9 expression, localization, locus-targeted association, and R-loop modulation in cis or trans using immunoblotting, microscopy, and chromatin and DNA-RNA immunoprecipitation.For complete details on the use and execution of this protocol, please refer to Abraham et al. (2020). : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Bainite to austenite reversal is one of the grain refinement techniques employed in carburized steels. However, chemical segregation influences the homogeneity of the bainitic structure, which is seminal to exploit the advantages associated with austenite reversal. It is therefore important to understand the influence of chemical segregation on bainite formation, which is investigated in this work. Characterizations were performed on the microstructures obtained from the case and core regions of a carburized steel after 30 h of bainite treatment at 320 °C for two carbon compositions: 0.85 wt% C (zcase) and 0.16 wt% C (zcore). The microstructure of zcase is shown to contain bands with bainite in alloy-lean regions and martensite/austenite in alloy-rich regions. For zcore, although the chemical bands are not composed of different phases, the alloy-rich regions have a fraction of martensite-austenite (MA) islands that is twice the fraction in alloy-lean regions. Despite this difference, the austenite phase fractions in the chemical bands of zcore are low and almost similar, indicating that the MA islands are mostly martensite. From experimental results and thermodynamic and kinetic simulations, it is elucidated that a different rate of phase transformation in the chemical bands is the cause for the observed microstructural inhomogeneities.

Giardia duodenalis is an ubiquitous parasitic pathogen that causes significant morbidity and mortality worldwide. Failures in drug therapy are commonly due to poor patient compliance as a result of the need for repeated administration, off target drug effects and increasing parasite drug resistance. In this study the in vitro efficacy and selectivity of the aminoguanidine compound robenidine and 2 structural analogues against Giardia were determined. After 5 h exposure to each compound the IC50 was as low as 0.2 μM with corresponding MLCs as low as 2.8 μM. This is in contrast to metronidazole which required 24 h to exhibit inhibitory activity. A modified adherence assay, developed for this study, demonstrated that three of the compounds inhibited in vitro adherence of the parasite. The lead compound exhibited rapid giardicidal activity (

Mango consumption has shown bioactive properties against several diseases like diabetes, therefore, we evaluated how a mango-supplemented diet affects metabolic pathways in diabetic rats. Serum and liver samples were collected from 26 rats divided into 3 groups (healthy, untreated diabetic and mango-treated diabetic) after dietary intervention and analysed using an LC-MS untargeted metabolomic strategy. Twenty-six and 29 metabolites in serum and liver were potentially annotated, showing significant differences among groups. Several affected pathways were due to the disease state [fatty acids (i.e. palmitoleic, linolenic, stearidonic, eicosapentaenoic, docosahexaenoic acids and others), bile acids (i.e. glycocholic acid) and amino acids (i.e. leucine, isoleucine and valine)], and others due to mango supplementation (increased hepatic bioaccumulation of euxanthone, a mangiferin metabolite, and increased glutathione concentration). These results suggest that a mango-supplemented diet exerted a significant antioxidant effect in the liver of diabetic rats, likely due to its phenolic compounds, like mangiferin and its metabolites.

Summary: Cdk7, the CDK-activating kinase and transcription factor IIH component, is a target of inhibitors that kill cancer cells by exploiting tumor-specific transcriptional dependencies. However, whereas selective inhibition of analog-sensitive (AS) Cdk7 in colon cancer-derived cells arrests division and disrupts transcription, it does not by itself trigger apoptosis efficiently. Here, we show that p53 activation by 5-fluorouracil or nutlin-3 synergizes with a reversible Cdk7as inhibitor to induce cell death. Synthetic lethality was recapitulated with covalent inhibitors of wild-type Cdk7, THZ1, or the more selective YKL-1-116. The effects were allele specific; a CDK7as mutation conferred both sensitivity to bulky adenine analogs and resistance to covalent inhibitors. Non-transformed colon epithelial cells were resistant to these combinations, as were cancer-derived cells with p53-inactivating mutations. Apoptosis was dependent on death receptor DR5, a p53 transcriptional target whose expression was refractory to Cdk7 inhibition. Therefore, p53 activation induces transcriptional dependency to sensitize cancer cells to Cdk7 inhibition. : Kalan et al. find that activation of the p53 tumor suppressor protein in human colon cancer-derived cells can induce transcriptional dependency on Cdk7, analogous to constitutive dependencies described in other tumors driven by oncogenic transcription factors. This work provides a proof of concept for combining p53-activating agents with Cdk7 inhibitors to elicit synthetic lethality. Keywords: Cdk7, p53, colon cancer, synthetic lethality, transcription, 5-fluorouracil, nutlin-3, apoptosis, chemical genetics, CDK inhibitor

Background: Anaesthesiologists might be able to mitigate risk if they know which patients are at greatest risk for postoperative complications. This trial examined the impact of machine learning models on clinician risk assessment., Methods: This single-centre, prospective, randomised clinical trial enrolled surgical patients aged ≥18 yr. Anaesthesiologists and nurse anaesthetists providing remote telemedicine support reviewed electronic health records with (assisted group) or without (unassisted group) reviewing machine learning predictions. Clinicians predicted the likelihood of postoperative 30-day all-cause mortality and postoperative acute kidney injury (AKI) within 7 days. The primary outcome was area under the receiver operating characteristic curve (AUROC) for clinician predictions of mortality and AKI, comparing AUROCs between assisted and unassisted assessments., Results: We analysed 5071 patients (mean [range] age: 58 [18-100] yr; 52% female) assessed by 89 clinicians. Of these, 98 (2.2%) patients died within 30 days of surgery and 450 (11.1%) patients sustained AKI. Clinician predictions agreed with the models more strongly in the assisted vs unassisted group (weighted kappa 0.75 vs 0.62 for death, mean difference: 0.13 [95% CI 0.10-0.17]; and 0.79 vs 0.54 for AKI, mean difference: 0.25 [95% CI 0.21-0.29]). Clinical prediction of death was similar between the assisted (AUROC 0.793) and unassisted (AUROC 0.780) groups (mean difference: 0.013 [95% CI -0.070 to 0.097]; P=0.76). Prediction of AKI had an AUROC of 0.734 in the assisted group vs 0.688 in the unassisted group (difference 0.046 [95% CI -0.003 to 0.091]; P=0.06)., Conclusions: Clinician performance was not improved by machine learning assistance. Further work is needed to clarify the role of machine learning in real-time perioperative risk stratification., Clinical Trial Registration: NCT05042804., (Copyright © 2024 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Objectives: Perioperative mental health of older Black surgical patients is associated with poor surgical outcomes; however, evidence-based perioperative interventions are lacking. Our two study objectives included: first, examine factors affecting perioperative care experiences of older Black surgical patients with mental health problems, and second, ascertain design and implementation requirements for a culturally-adapted perioperative mental health intervention., Design Setting and Participants: We conducted six focus groups with older Black patients (n = 15; ≥50 years; surgery within the past 5 years and/or interest in mental health research; history of distress, anxiety, or depression coping with surgery/hospitalization/) from a large academic medical center. We engaged study partners, including interventionists and community members, to gather insights on intervention and implementation needs. We followed a hybrid inductive-deductive thematic approach using open coding and the National Institute on Minority Health and Health Disparities Research Framework., Results: Patients reported that their psychological well-being and long-term mental health outcomes were not appropriately considered during perioperative care. Perceived stressors included interpersonal and structural barriers to using mental healthcare services, clinician treatment biases and ageism in care, and lack of healthcare professional connections/resources. Patients utilized various coping strategies, including talk therapy, faith/spirituality, and family and friends., Conclusion: This study offers valuable insights into the experiences of older Black surgical patients and the critical elements for developing a personalized perioperative mental health intervention to support their well-being before, during, and after surgery. Our findings demonstrated a need for a patient-centered and culturally adapted intervention targeting the individual/behavioral and interpersonal levels. Informed by the cultural adaptation framework, we propose a multi-component intervention that integrates psychological and pharmacological components., Competing Interests: DISCLOSURES The authors declare none. The data has not been previously presented orally or by poster at scientific meetings., (Copyright © 2024 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: We lack evidence on the cumulative effectiveness of machine learning (ML)-driven interventions in perioperative settings. Therefore, we conducted a systematic review to appraise the evidence on the impact of ML-driven interventions on perioperative outcomes., Methods: Ovid MEDLINE, CINAHL, Embase, Scopus, PubMed, and ClinicalTrials.gov were searched to identify randomised controlled trials (RCTs) evaluating the effectiveness of ML-driven interventions in surgical inpatient populations. The review was registered with PROSPERO (CRD42023433163) and conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Meta-analysis was conducted for outcomes with two or more studies using a random-effects model, and vote counting was conducted for other outcomes., Results: Among 13 included RCTs, three types of ML-driven interventions were evaluated: Hypotension Prediction Index (HPI) (n=5), Nociception Level Index (NoL) (n=7), and a scheduling system (n=1). Compared with the standard care, HPI led to a significant decrease in absolute hypotension (n=421, P=0.003, I 2 =75%) and relative hypotension (n=208, P<0.0001, I 2 =0%); NoL led to significantly lower mean pain scores in the post-anaesthesia care unit (PACU) (n=191, P=0.004, I 2 =19%). NoL showed no significant impact on intraoperative opioid consumption (n=339, P=0.31, I 2 =92%) or PACU opioid consumption (n=339, P=0.11, I 2 =0%). No significant difference in hospital length of stay (n=361, P=0.81, I 2 =0%) and PACU stay (n=267, P=0.44, I 2 =0) was found between HPI and NoL., Conclusions: HPI decreased the duration of intraoperative hypotension, and NoL decreased postoperative pain scores, but no significant impact on other clinical outcomes was found. We highlight the need to address both methodological and clinical practice gaps to ensure the successful future implementation of ML-driven interventions., Systematic Review Protocol: CRD42023433163 (PROSPERO)., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: A subpopulation of women with ductal carcinoma in situ (DCIS) remains at risk for in-breast recurrence (IBR) following breast-conserving surgery (BCS) and radiation therapy (RT). The NSABP B-43 trial evaluated the role of concurrent RT and trastuzumab in patients with HER2-positive DCIS but did not reach the prespecified endpoint. We hypothesized that a 7-gene biosignature (DCISionRT) with its Residual Risk subtype (RRt) could identify 2 groups of HER2(3+) patients with significantly different IBR risks after BCS plus RT., Patients and Methods: All patients with HER2(3+) DCIS (n = 178) treated with BCS plus RT were selected from a combined multinational patient cohort. Treatment decisions were neither randomized nor strictly rules-based. Biosignature testing was performed on all patients and stratified with previously defined groups: (1) Combined Low Risk group (DS ≤ 2.8) and Elevated Risk group (DS > 2.8) without RRt or (2) Residual Risk subtype. Kaplan-Meier analysis was used to compute IBR curves., Results: Sixty-three percent of HER2(3+) patients (113/178) were classified into the Residual Risk subtype. These patients had significantly higher 10-year rates of IBR compared to the nonresidual risk group (16.2% vs. 1.6%, P = .01). The Residual Risk subtype had more nuclear grade 3 disease (87% vs. 63%, P < .001), but age, size, and grade were not associated with IBR rate (P = NS) on univariate and multivariable analysis. Only the Residual Risk group was associated with IBR (P = .05) in multivariate analysis., Conclusion: The 7-gene biosignature with RRt identified a subset of HER2(3+) patients with greater IBR rates following BCS and RT beyond traditional clinical and pathologic features. Consideration of therapies to reduce these elevated IBR rates should be evaluated, including the incorporation of HER2-targeted therapy., Competing Interests: Disclosure FV is a research advisor for PreludeDx and PreludeDx supported his institution for the conduct and management of a separate clinical trial. FV is also a consultant for ImpediMed, unrelated to this research. CS is a consultant for and has received research funding from PreludeDx for separate research projects. CS is also a consultant for ImpediMed, Videra Surgical and Evicore and has received grant funding from Varian Medical Systems, and VisionRT unrelated to this research. KM and SS are employees of PreludeDx and have stock options for PreludeDx. SW and ML have received grant support from PreludeDx for a previously published validation study. RR has received research funding from PreludeDx for a separate clinical study. Unrelated to this study, RR has stock and other ownership interests in Abbott Laboratories, Bristol-Myers Squibb, Intuitive Surgical, IDEXX Laboratories. FW is a consultant for PreludeDx and was supported by PreludeDx for the conduct and management of previous studies. PW is on an advisory board and has received research funding from PreludeDx. Unrelated to this study, PW has stock and other ownership interests in Reverse Medical, Rebound Medical, Lazarus, Cerebrotech, Targeted Medical Education and Medtronic, is on advisory boards for Medtronic, Lumicell, ImpediMed, and Cianna Medical, and has received research funding from Invitae, Intact Medical, Agendia and ImpediMed. BC has intellectual property rights for ImmunoRestoration and receives consulting fees from Merit Medical unrelated to this research. TB is an employee of PreludeDx, holds intellectual property rights for the DCISionRT test, and has an ownership interest in PreludeDx. JA and MK have no competing interests (Figure 1, Supplemental Figures 1 and 2, Table 1, Table 2, Table 3, Table 4)., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The Impella 5.0 and 5.5 pumps (Abiomed, Danvers, MA) are large-bore transvalvular micro-axial assist devices used in cardiogenic shock (CS) for patients requiring high-capacity flow. Despite their increasing use, real-world data regarding indications, rates of utilization and clinical outcomes with this therapy are limited. The objective of our study was to examine clinical profiles and outcomes of patients in a contemporary, real-world CS registry of patients who received an Impella 5.0/5.5 alone or in combination with other temporary mechanical circulatory support (tMCS) devices., Methods: The CS Working Group (CSWG) Registry includes patients from 34 US hospitals. For this analysis, data from patients who received an Impella 5.0/5.5 between 2020-2023 were analyzed. Use of Impella 5.0/5.5 with or without additional tMCS therapies, duration of support, adverse events and outcomes at hospital discharge were studied. Adverse events including stroke, limb ischemia, bleeding and hemolysis were not standardized by the registry but reported per individual CSWG Primary Investigator discretion. For those who survived, rates of native heart recovery (NHR) or heart replacement therapy (HRT) including heart transplant (HT), or durable ventricular assist device (VAD) were recorded. We also assessed outcomes based on shock etiology (acute myocardial infarction or MI-CS vs. heart failure-related CS or HF-CS)., Results: Among 6,205 patients, 754 received an Impella 5.0/5.5 (12.1%), including 210 MI-CS (27.8%) and 484 HF-CS (64.1%) patients. Impella 5.0/5.5 was used as the sole tMCS device in 32% of patients, while 68% of patients received a combination of tMCS devices. Impella cannulation sites were available for 524/754 (69.4%) of patients, with 93.5% axillary configuration. Survival to hospital discharge for those supported with an Impella 5.0/5.5 was 67%, with 20.4% NHR and 45.5% HRT. Compared to HF-CS, patients with MI-CS supported on Impella 5.0/5.5 had higher in-hospital mortality (45.2% vs 26.2%, p < 0.001) and were less likely to receive HRT (22.4% vs 56.6%, p < 0.001. For patients receiving a combination of tMCS during hospitalization, this was associated with higher rates of limb ischemia (9% vs. 3%, p < 0.01), bleeding (52% vs 33%, p < 0.01), and mortality (38% vs 25%; p < 0.001) compared to Impella 5.0/5.5 alone. Among Impella 5.0/5.5 recipients, the median duration of pump support was 12.9 days (IQR: 6.8-22.9) and longer in patients bridged to HRT (14 days; IQR: 7.7-28.4)., Conclusions: In this multi-center cohort of patients with CS, use of Impella 5.0/5.5 was associated with an overall survival of 67.1% and high rates of HRT. Lower adverse event rates were observed when Impella 5.0/5.5 was the sole support device used. Further study is required to determine whether a strategy of early Impella 5.0/5.5 use for CS improves survival., Condensed Abstract: High capacity Impella heart pumps are capable of provide up to 5.5 liter/min of flow while upper body surgical placement allows for ambulation. Patients with advanced cardiogenic shock from acute myocardial infarction or heart failure requiring temporary mechanical circulatory support may benefit from upfront use of Impella 5.5 to improve overall survival, including native heart recovery or successful bridge to durable left ventricular assist device surgery or heart transplantation., (Copyright © 2024. Published by Elsevier Inc.)

Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: A. S. has received research funding from Abbott, Edwards Lifesciences, Vifor, Pfizer, Bayer, General Prognostics, Story Health, Acorai, Boston Scientific, and Impulse Dynamics; is on the steering committees of Abbott, Boston Scientific, Biotronik, Story Health, RIVUS, Bayer, and General Prognostics; and is a consultant for Abbott, Boston Scientific, Edwards Lifesciences, Impulse Dynamics, Acorai, Story Health, General Prognostics, and Bayer. None declared (M. G., K. M., H. S., E. V., M. B., T. A. B., K. B., A. B., A. G., T. F., M. F., J. T. H., E. M., O. J., L. K., P. M., M. R.).

Topic Importance: With telemedicine's expansion during the COVID-19 pandemic, it has become critical to evaluate whether patients have equitable access and capabilities to use televisits optimally for improved COPD outcomes such as reduced hospitalizations. This scoping review evaluated whether televisit-based interventions are evaluated and equitably effective in improving health care use outcomes among diverse patient populations with COPD., Review Findings: Using a systematic search for televisit-based COPD self-management interventions, we found 20 studies for inclusion, all but one of which were published before the COVID-19 pandemic. Most (11/20) were considered good-quality studies. Most studies (19/20) reported age and sex; few provided race (3/20) or income (1/20) data. The most frequently used televisit-based methods were in person plus phone (6/20), video only (6/20), and phone only (4/20). Most studies (12/20) showed a significant reduction in at least one health care use metric; nine studies found hospitalization-related reductions. Effective interventions typically used two methods (eg, in person plus televisits), a video methods, or both., Summary: Most studies failed to report on participants' race or income, leading to a lack of data on the equity of interventions' effectiveness across diverse patient populations. Multimethod televisit-based interventions, particularly with an in-person component, most commonly were effective; no associations were seen with study quality or size. With the increasing reliance on telemedicine to provide chronic disease care, the lack of data among diverse populations since the COVID-19 pandemic began limits generalizability of these findings for real-world clinical settings. More comprehensive evaluations of televisit-based interventions are needed in the era after the pandemic within and across diverse patient populations., Competing Interests: Financial/Nonfinancial Disclosures None declared., (Copyright © 2024 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: There are limited data depicting the prevalence and ramifications of acute limb ischemia (ALI) among cardiogenic shock (CS) patients., Methods: We employed data from the Cardiogenic Shock Working Group (CSWG), a consortium including 33 sites. We constructed a multi-variable logistic regression to examine the association between clinical factors and ALI, we generated another logistic regression model to ascertain the association of ALI with mortality., Results: There were 7,070 patients with CS and 399 (5.6%) developed ALI. Patients with ALI were more likely to be female (40.4% versus 29.4%) and have peripheral arterial disease (13.8% versus 8.3%). Stratified by maximum SCAI shock stage, the rates of ALI were stage B 0.0%, stage C 1.8%, stage D 4.1%, and stage E 10.3%. Factors associated with higher risk for ALI included: peripheral vascular disease OR 2.24 (95% CI: 1.53 - 3.23; p < 0.01) and ≥ 2 mechanical circulatory support (MCS) devices OR 1.66 (95% CI: 1.24 - 2.21, p < 0.01). ALI was highest for VA-ECMO patients (11.6%) or VA-ECMO + IABP/Impella CP (16.6%) yet use of distal perfusion catheters was less than 50%. Mortality was 38.0% for CS patients without ALI but 57.4% for CS patients with ALI. ALI was significantly associated with mortality, adjusted OR 1.40 (95% CI 1.01 - 1.95, p < 0.01)., Conclusions: The rate of ALI was 6% among CS patients. Factors most associated with ALI include peripheral vascular disease and multiple MCS devices. The downstream ramifications of ALI were dire with a considerably higher risk of mortality., (Copyright © 2024. Published by Elsevier Inc.)

Objectives: The perioperative period is challenging and stressful for older adults. Those with depression and/or anxiety have an increased risk of adverse surgical outcomes. We assessed the feasibility of a perioperative mental health intervention composed of medication optimization and a wellness program following principles of behavioral activation and care coordination for older surgical patients., Methods: We included orthopedic, oncologic, and cardiac surgical patients aged 60 and older. Feasibility outcomes included study reach, the number of patients who agreed to participate out of the total eligible; and intervention reach, the number of patients who completed the intervention out of patients who agreed to participate. Intervention efficacy was assessed using the Patient Health Questionnaire for Anxiety and Depression (PHQ-ADS). Implementation potential and experiences were collected using patient surveys and qualitative interviews. Complementary caregiver feedback was also collected., Results: Twenty-three out of 28 eligible older adults participated in this study (mean age 68.0 years, 65% women), achieving study reach of 82% and intervention reach of 83%. In qualitative interviews, patients (n = 15) and caregivers (complementary data, n = 5) described overwhelmingly positive experiences with both the intervention components and the interventionist, and reported improvement in managing depression and/or anxiety. Preliminary efficacy analysis indicated improvement in PHQ-ADS scores (F = 12.13, p <0.001)., Conclusions: The study procedures were reported by participants as feasible and the perioperative mental health intervention to reduce anxiety and depression in older surgical patients showed strong implementation potential. Preliminary data suggest its efficacy for improving depression and/or anxiety symptoms. A randomized controlled trial assessing the intervention and implementation effectiveness is currently ongoing., (Copyright © 2023 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Studies reporting cardiogenic shock (CS) outcomes in women are scarce., Objectives: The authors compared survival at discharge among women vs men with CS complicating acute myocardial infarction (AMI-CS) and heart failure (HF-CS)., Methods: The authors analyzed 5,083 CS patients in the Cardiogenic Shock Working Group. Propensity score matching (PSM) was performed with the use of baseline characteristics. Logistic regression was performed for log odds of survival., Results: Among 5,083 patients, 1,522 were women (30%), whose mean age was 61.8 ± 15.8 years. There were 30% women and 29.1% men with AMI-CS (P = 0.03). More women presented with de novo HF-CS compared with men (26.2% vs 19.3%; P < 0.001). Before PSM, differences in baseline characteristics and sex-specific outcomes were seen in the HF-CS cohort, with worse survival at discharge (69.9% vs 74.4%; P = 0.009) and a higher rate of maximum Society for Cardiac Angiography and Interventions stage E (26% vs 21%; P = 0.04) in women than in men. Women were less likely to receive pulmonary artery catheterization (52.9% vs 54.6%; P < 0.001), heart transplantation (6.5% vs 10.3%; P < 0.001), or left ventricular assist device implantation (7.8% vs 10%; P = 0.01). Regardless of CS etiology, women had more vascular complications (8.8% vs 5.7%; P < 0.001), bleeding (7.1% vs 5.2%; P = 0.01), and limb ischemia (6.8% vs 4.5%; P = 0.001). More vascular complications persisted in women after PSM (10.4% women vs 7.4% men; P = 0.06)., Conclusions: Women with HF-CS had worse outcomes and more vascular complications than men with HF-CS. More studies are needed to identify barriers to advanced therapies, decrease complications, and improve outcomes of women with CS., Competing Interests: Funding Support and Author Disclosures This work was supported by institutional grants from Abiomed, Boston Scientific, Abbott Laboratories, Getinge, and LivaNova to Tufts Medical Center. The sponsors had no input on collection, analysis, and interpretation of the data, nor in the preparation, review, or approval of the manuscript. Dr Kanwar has served on the advisory board for Abiomed, Abbott Laboratories, and CorWave. Dr Sinha has served as a consultant for Abiomed. Dr Hall has served as a consultant to Abiomed, Abbott, and Medtronic. Dr Hernandez-Montfort has served as a consultant for Abiomed. Dr Garan has served as a consultant for NuPulseCV, has been on the scientific advisory board for Abiomed; and has received research support from Verantos and Abbott. Dr Nathan has received consulting honoraria from Abiomed, Getinge, and CSI. Dr Abraham has served as a consultant for Abbott Laboratories and Abiomed. Dr Mahr has served as a consultant to Abbott, Abiomed, and Syncaria. Dr Burkhoff has received an unrestricted educational grant from Abiomed. Dr Kapur has received consulting honoraria and institutional grant support from Abbott Laboratories, Abiomed, Boston Scientific, Medtronic, LivaNova, Getinge, and Zoll. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023. Published by Elsevier Inc.)

Background: The aim for 95% maternal health care coverage and zero-unmet need for family planning in Pacific Island countries by 2030 could be achieved by strengthening the midwifery workforce. To enable health services to provide accessible, locally acceptable, and high-quality care, the midwifery workforce must be regulated and educated to global standards and supported to practice in enabling environments. In 2019, around 64,000 live births occurred in Pacific Island countries, yet information regarding the state the midwifery workforce and midwifery education is limited., Aim: Using data from recent reports and country case studies, this paper provides an overview of the current midwifery education situation in Pacific Island countries and discusses strategic directions for strengthening quality midwifery education and therefore quality midwifery care provision in Pacific Island countries., Discussion: Six Pacific Island countries have midwifery curricula, all post-nursing programs, although few offer midwifery education programs on a regular annual basis. Current programs do not meet ICM Global Standards for Midwifery Education. Critical areas for strengthening include making underpinning philosophical frameworks, the vision for midwifery education, and program intended learning outcomes explicit in curricula documents and ensuring integration of these in program implementation. Fortunately, five of six midwifery education programs are under processes of renewal and strengthening against global, regional, and national standards., Conclusion: Strengthening the midwifery workforce in the Pacific to meet maternal and newborn health targets can be achieved through supporting the existing midwifery education programs to meet global standards. Strengthened midwifery education programs in Pacific Island countries offer an opportunity to meet each country's maternal and newborn health targets., Competing Interests: Declaration of Competing Interest None declared. All authors declare no conflict of interest associated with this publication and there has been no financial support for this work., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The intervals before and after major surgery is a high-risk period for older adults; in this setting, anxiety and depression are common and serious problems. We comprehensively reviewed current evidence on perioperative anxiety and depression in older adults, focusing on epidemiology, impact, correlates, medication risks, and treatment. Principles of perioperative mental healthcare are proposed based on the findings. Prevalence estimates of clinically significant anxiety and depression range from 5% to 45% for anxiety and 6% to 52% for depression, depending on surgical populations and measurement tools. Anxiety and depression may increase risk for surgical complications and reduce patient participation during rehabilitation. Medical comorbidities, pain, insomnia, cognitive impairment, and delirium are common co-occurring problems. Concomitant uses of central nervous system acting medications (benzodiazepines, anticholinergics, and opioids) amplify the risks of delirium and falls. Based on these findings, we propose that anxiety and depression care should be part of perioperative management in older adults; components include education, psychological support, opioid-sparing pain management, sleep management, deprescribing central nervous system active medications, and continuation and optimization of existing antidepressants. More research is needed to test and improve these care strategies., (Copyright © 2023 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Cardiogenic shock (CS) patients remain at 30% to 60% in-hospital mortality despite therapeutic innovations. Heterogeneity of CS has complicated clinical trial design. Recently, 3 distinct CS phenotypes were identified in the CSWG (Cardiogenic Shock Working Group) registry version 1 (V1) and external cohorts: I, "noncongested;" II, "cardiorenal;" and III, "cardiometabolic" shock., Objectives: The aim was to confirm the external reproducibility of machine learning-based CS phenotypes and to define their clinical course., Methods: The authors included 1,890 all-cause CS patients from the CSWG registry version 2. CS phenotypes were identified using the nearest centroids of the initially reported clusters., Results: Phenotypes were retrospectively identified in 796 patients in version 2. In-hospital mortality rates in phenotypes I, II, III were 23%, 41%, 52%, respectively, comparable to the initially reported 21%, 45%, and 55% in V1. Phenotype-related demographic, hemodynamic, and metabolic features resembled those in V1. In addition, 58.8%, 45.7%, and 51.9% of patients in phenotypes I, II, and III received mechanical circulatory support, respectively (P = 0.013). Receiving mechanical circulatory support was associated with increased mortality in cardiorenal (OR: 1.82 [95% CI: 1.16-2.84]; P = 0.008) but not in noncongested or cardiometabolic CS (OR: 1.26 [95% CI: 0.64-2.47]; P = 0.51 and OR: 1.39 [95% CI: 0.86-2.25]; P = 0.18, respectively). Admission phenotypes II and III and admission Society for Cardiovascular Angiography and Interventions stage E were independently associated with increased mortality in multivariable logistic regression compared to noncongested "stage C" CS (P < 0.001)., Conclusions: The findings support the universal applicability of these phenotypes using supervised machine learning. CS phenotypes may inform the design of future clinical trials and enable management algorithms tailored to a specific CS phenotype., Competing Interests: Funding Support and Author Disclosures This work was supported by National Institutes of Health R01 grants (to Dr Kapur) (R01HL139785-01; R01HL159089-01) and institutional grants from Abiomed Inc, Boston Scientific Inc, Abbott Laboratories, Getinge Inc, and LivaNova Inc to Tufts Medical Center. The sponsors had no input on collection, analysis, and interpretation of the data, nor in the preparation, review, or approval of the manuscript. Dr Kapur has received consulting honoraria and institutional grant support from Abbott Laboratories, Abiomed Inc, Boston Scientific, Medtronic, LivaNova, Getinge, and Zoll. Dr Kanwar has served on the Advisory Board for Abiomed Inc. Dr Sinha has served as a consultant for Abiomed Inc. Dr Garan has served as a consultant for NuPulseCV, has served on the Scientific Advisory Board for Abiomed, and is a recipient of research support from Verantos and Abbott. Dr Hernandez-Montfort has served as a consultant for Abiomed Inc. Dr Abraham has served as a consultant for Abbott Laboratories and Abiomed Inc. Dr Nathan has received consulting honoraria from Abiomed, Getinge, and CSI. Dr Hall has served as a consultant to Abiomed, Abbott, and Medtronic. Dr Mahr has served as a consultant to Abbott, Abiomed, and Syncaria. Dr Westenfeld has received research support from Abiomed Inc and accepted a position at Abiomed Inc after submission of this manuscript. Dr Burkhoff has received an unrestricted educational grant from Abiomed Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)