Interventional approaches to treatment resistant depression (DTR) in children and adolescents: A systematic review and meta-analysis.

BACKGROUND: Major depressive disorder (MDD) is highly prevalent in youth. Conventional treatment paradigms primarily involve selective serotonin reuptake inhibitors (SSRIs) and psychotherapy, yet a significant proportion of this population exhibits treatment-resistant depression (TRD). In adults, interventional therapies like Electroconvulsive Therapy (ECT), repetitive Transcranial Magnetic Stimulation (rTMS), and ketamine have shown promise for TRD, but their comparative efficacy remains underexplored in Adolescent and pediatric population. This systematic review and meta-analysis aims to assess the relative effectiveness of ECT, rTMS, and ketamine in treating TRD among adolescents. METHODS: Following PRISMA guidelines, we systematically searched databases for studies of ECT, rTMS, or ketamine for treatment-resistant depression in youth ages 10-24. Three reviewers independently screened for inclusion based on predefined criteria. Included observational and randomized controlled trials reported depression symptoms with measures like HDRS and MADRS in youth treated with ECT, rTMS, or ketamine. Two reviewers extracted data on interventions, patients, and depression symptom outcomes. Chance-adjusted inter-reviewer agreement was calculated. For meta-analysis, we pooled standardized mean differences (SMDs) in depression scores using random effects models and assessed heterogeneity with I2 statistics. RESULTS: Meta-analysis of 10 observational studies examined SMD in depression scores for treatment resistant depression patients treated with ECT, ketamine, or rTMS. Patients treated with ECT had a significantly lower SMD of 1.99 (95 % CI 0.92-3.05, p < 0.001) compared to baseline. Patients treated with ketamine also had a significantly lower SMD of 1.58 (95 % CI 1.04-2.12, p < 0.001). Patients treated with rTMS had the lowest SMD of 2.79 (95 % CI 0.79-4.80, p = 0.006). There was no significant difference between the three groups overall (p > 0.05). Comparative analysis between ECT and ketamine found no significant difference in SMD (p = 0.387). Comparison of ECT versus rTMS found a significant difference in SMD favoring rTMS (p = 0.004). Comparison of ketamine versus rTMS suggested a potential difference in SMD favoring rTMS (p = 0.058). In summary, rTMS resulted in significantly larger reductions in depression scores than ECT, and potentially larger reductions than ketamine. CONCLUSIONS: This meta-analysis illustrates the ability of rTMS, ECT, and ketamine to improve depression in youth. rTMS resulted in the largest improvements, highlighting its potential as a first-line treatment for pediatric treatment-resistant depression given its favorable side effect profile compared to ECT. Further research directly comparing these modalities is needed.

African American Family Caregivers' Experiences and Mental Health: A Convergent Mixed-Methods Study.

BACKGROUND: Caregiving in the African American community is informed by strong cultural expectations but may be associated with negative experiences and poor mental health outcomes. OBJECTIVE: The purpose of this convergent mixed-methods study is to understand the relationship between caregiving experiences and mental health and explore stress management strategies in African American family caregivers of adults with chronic or disabling conditions. METHODS: African American family caregivers (N = 100) were recruited using community-engaged methods and completed a sociodemographic questionnaire, the Caregiver Reaction Assessment scale, and the Center for Epidemiologic Studies Depression (CES-D-10) Scale. A subsample (n = 24) participated in semi-structured interviews. Data were analyzed using linear regression and content analysis. A matrix was developed to integrate quantitative and qualitative results. RESULTS: Participants were on average 59 years old. Most were women and provided care to a parent. Lack of family support (B = 1.37, P = .03) and impact of caregiving on caregivers' finances (B = 1.74, P = .004), schedule (B = 2.92, P < .001), and health (B = 3.26, P < .001) were associated with depressive symptoms and were reported as stressful experiences. Negative interactions with the care recipient and caring for multiple people emerged as other sources of stress. Participants used independent and interpersonal coping strategies, as well as strategies to facilitate their caregiving role to reduce their stress. Values of reciprocity, limited use of community-based resources, and mental health stigma emerged as important cultural considerations. CONCLUSIONS: Our findings suggest the need for culturally-sensitive interventions to improve communication and care coordination within African American family caregiving networks and educational programs about mental health and caregiving resources endorsed by trusted community sources.

Symptom Burden and Its Impact on Quality of Life in Patients With Moderate to Severe CKD: The International Chronic Kidney Disease Outcomes and Practice Patterns Study (CKDopps).

RATIONALE & OBJECTIVE: Recent evidence suggests substantial burden of symptoms experienced by people with non-dialysis chronic kidney disease (ND-CKD), but informative large-scale studies are scarce. We aimed to assess the prevalence of symptoms, and the association of overall symptom burden with quality of life in patients with moderate to severe CKD. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: 4430 patients with ND-CKD stages 3-5 enrolled into the CKDopps Study in Brazil, France, and the US between 2013 and 2021. EXPOSURES: 13 individual patient-reported symptoms from the KDQOL-SF questionnaire and an overall symptom burden score (low, intermediate, and high). OUTCOMES: Physical and mental component summary scores (PCS, MCS) of the KDQOL-SF. ANALYTICAL APPROACH: Adjusted prevalence ratios and generalized estimating equations. RESULTS: Patients (mean age: 68 years; 40% women; mean baseline eGFR: 30 mL/min/1.73m2) were very much to extremely bothered by numerous symptoms ["soreness in muscles" (23%), "washed out or drained" (21%), "cramps, shortness of breath, dry skin, diminished sex life, or numbness in hands or feet" (14-17%)]. The adjusted prevalences of "cramps", "washed out or drained", "lack of appetite", "nausea/upset stomach", and "sex life" were greater with more severe CKD, and, except for "sex life", in women. A high overall symptom burden was more common in women, in France, and in patients with severe albuminuria and various comorbidities, but not with lower eGFR. PCS and MCS scores were 13.4 and 7.7 points lower, respectively, for high vs. low overall symptom burden. LIMITATIONS: Generalizability limited to patients under nephrology care, residual confounding and inaccurate Brazilian translation of some symptoms. CONCLUSIONS: The high symptom burden observed in this large cohort of ND-CKD patients across three diverse countries and its strong association with poorer HRQOL should inform clinical management of and clinical research in CKD.

Muscle quality index comparisons between Hispanics and non-Hispanic Caucasians using dual energy X-ray absorptiometry and handgrip strength.

BACKGROUND & AIMS: Muscle quality index (MQI) can be computed in various ways. Also, many studies have evaluated MQI in older adults and non-Hispanic populations. The aim of this study was to compare various muscle quality indexes between Hispanics and non-Hispanic Caucasians when stratifying grip strength and appendicular lean mass measurements. METHODS: 235 participants (aged 25.5 ± 9.5 for males and 26.4 ± 9.9 for females) completed a dual energy X-ray absorptiometry (DXA) scan to assess appendicular lean mass (ALM). Handgrip strength (HGS) was assessed using a handheld dynamometer. MQI was computed using four different models: 1). MQIRA: ALM and HGS of right arm and hand, respectively; 2). MQILA: ALM and HGS of left arm and hand, respectively; 3). MQIARMS: ALM and HGS of both arms and hands, respectively; and 4). MQITOTAL: ALM of upper and lower-limbs and HGS of left and right hand. RESULTS: Hispanic males and females exhibited lower HGS compared to Caucasians with effect sizes ranging from trivial (d = 0.17) to moderate (d = 0.80). Females demonstrated higher MQI values compared to males for MQIARMS (d = 0.70), MQIRA (d = 0.75), and MQILA (d = 0.57). However, MQITOTAL yielded a small practical effect (d = 0.33) in favor of males (3.2 ± 0.5 kg/kg vs. 3.1 ± 0.5 kg/kg). After factoring by sex and ethnicity, Hispanic males and females, compared to non-Hispanic Caucasians males and females, showed trivial-to-small practical differences (d values ranging from 0.03 to 0.39). CONCLUSIONS: These results demonstrate MQI models vary across sex, particularly when utilizing models that account for upper extremity strength and ALM (i.e., MQIARMS, MQIRA, and MQILA). Lastly, to establish consistency in future research, the present study recommends using MQI models that account for ALM of upper- and lower-limbs (i.e., MQITOTAL). However, research measuring muscular strength via one upper-limb (e.g., left hand) might consider measuring ALM of the corresponding arm (e.g., left arm) when computing muscle quality (e.g., MQILA).

Psychometric Evaluation of the Decision Fatigue Scale among Korean Registered Nurses.

Nurses make decision for patients and the quality of nurses' decision making can affect patient outcomes. For some reason, nurses are experiencing impaired decision making and it can negatively impact patient care. A valid and reliable instrument to assess decision fatigue may let people know about the concept and guide the development of new policies or interventions for Korean nurses' decision fatigue. This study aimed to evaluate the psychometric properties of the Korean version of the decision fatigue scale. The design was a cross-sectional descriptive study and convenience sampling was used to recruit participants. A total of 247 nurses from across South Korea participated in an online survey. The survey consisted of demographic questionnaires, decision fatigue scale, nursing practice environment scale, and compassion fatigue scale. It was validated through confirmatory factor analysis that the Korean version of the decision fatigue scale was a single factor with the same structure as the original scale. The Korean version of the decision fatigue scale showed significant correlations with compassion fatigue, and the scale showed appropriate internal consistency. This study established well enough the psychometric characteristics of the Korean version of decision fatigue.

Explaining International Trends in Mortality on Hemodialysis Through Changes in Hemodialysis Practices in the Dialysis Outcomes and Practice Patterns Study (DOPPS).

RATIONALE & OBJECTIVE: Case-mix adjusted hemodialysis mortality has decreased since 1998. Many factors that influence mortality may have contributed to this trend and these associations may differ by continental region. We studied changes in hemodialysis facility practices over time and their potential role in mediating changes in patient survival. STUDY DESIGN: Observational prospective cohort study. SETTING & PARTICIPANTS: Adult hemodialysis patients treated in hemodialysis 500 facilities participating in the Dialysis Outcomes Practice Patterns Study (DOPPS) between 1999 and 2015 in the US, Japan, and 4 four European countries: Germany, Italy, Spain, and UK. PREDICTORS: Four practice measures at each facility: the percentages of patients with Kt/V>1.2, interdialytic weight gain [IDWG]<5.7%, phosphorus<6 mg/dL, and using AV fistulae. OUTCOMES: Patient survival. ANALYTICAL APPROACH: Mediation analyses, adjusted for case mix, were conducted using 3-year study phase as the exposure and facility practice measures as potential mediators. RESULTS: In Europe, we observed a 13% improvement in overall case-mix adjusted survival per decade. Trends in facility practice measures, especially Kt/V and phosphorus, explained 10% improvement in case-mix survival per decade, representing 77% (10% explained of 13% improvement) of the observed improvement. In Japan, 73% of the observed 12%/decade improvement in case-mix adjusted survival could be attributed to facility practices, especially Kt/V and IDWG. In the US, 56% of the observed 47%/decade improvement in case-mix adjusted survival could be attributed to facility practices, especially AV fistula use and phosphorus control. LIMITATIONS: Unmeasured changes in the characteristics of the patient population over this period may confound the observed associations. CONCLUSION: The improvements in adjusted hemodialysis patient survival in Europe, Japan, and the US from 1999 to 2015 can be largely explained by improvements in specific facility practices. Future changes in patient survival may be responsive to further evolution in the implementation of common clinical practices.

Sialylated keratan sulfates on MUC5B are Siglec-8 ligands in the human esophagus.

Human sialic acid-binding immunoglobulin-like lectins (Siglecs) are expressed on subsets of immune cells. Siglec-8 is an immune inhibitory Siglec on eosinophils and mast cells, which are effectors in allergic disorders including eosinophilic esophagitis. Inhibition occurs when Siglec-8 is crosslinked by multivalent Siglec ligands in target tissues. Previously we discovered a high-affinity Siglec-8 sialoglycan ligand on human airways composed of terminally sialylated keratan sulfate chains carried on a single protein, DMBT1. Here we extend that approach to another allergic inflammatory target tissue, human esophagus. Lectin overlay histochemistry revealed that Siglec-8 ligands are expressed predominantly by esophageal submucosal glands, and are densely packed in submucosal ducts leading to the lumen. Expression is tissue-specific; esophageal glands express Siglec-8 ligand whereas nearby gastric glands do not. Extraction and resolution by gel electrophoresis revealed a single predominant human esophageal Siglec-8 ligand migrating at >2 MDa. Purification by size exclusion and affinity chromatography, followed by proteomic mass spectrometry, revealed the protein carrier to be MUC5B. Whereas all human esophageal submucosal cells express MUC5B, only a portion convert it to Siglec-8 ligand by adding terminally sialylated keratan sulfate chains. We refer to this as MUC5B S8L. Material from the esophageal lumen of live subjects revealed MUC5B S8L species ranging from ~1-4 MDa. We conclude that MUC5B in the human esophagus is a protein canvas on which Siglec-8 binding sialylated keratan sulfate chains are post-translationally added. These data expand understanding of Siglec-8 ligands and may help us understand their roles in allergic immune regulation.

Effect of Obesity on the Use of Antiarrhythmics in Adults With Atrial Fibrillation: A Narrative Review.

BACKGROUND: Atrial fibrillation (AF) and obesity coexist in approximately 37.6 million and 650 million people globally, respectively. The anatomical and physiological changes in individuals with obesity may influence the pharmacokinetic properties of drugs. AIM: This review aimed to describe the evidence of the effect of obesity on the pharmacokinetics of antiarrhythmics in people with AF. METHODS: Three databases were searched from inception to June 2023. Original studies that addressed the use of antiarrhythmics in adults with AF and concomitant obesity were included. RESULTS: A total of 4549 de-duplicated articles were screened, and 114 articles underwent full-text review. Ten studies were included in this narrative synthesis: seven cohort studies, two pharmacokinetic studies, and a single case report. Samples ranged from 1 to 371 participants, predominately males (41%-85%), aged 59-75 years, with a body mass index (BMI) of 23-66 kg/m2. The two most frequently investigated antiarrhythmics were amiodarone and dofetilide. Other drugs investigated included diltiazem, flecainide, disopyramide, propafenone, dronedarone, sotalol, vernakalant, and ibutilide. Findings indicate that obesity may affect the pharmacokinetics of amiodarone and sodium channel blockers (e.g., flecainide, disopyramide, and propafenone). Factors such as drug lipophilicity may also influence the pharmacokinetics of the drug and the need for dose modification. DISCUSSION: Antiarrhythmics are not uniformly affected by obesity. This observation is based on heterogeneous studies of participants with an average BMI and poorly controlled confounding factors such as multimorbidity, concomitant medications, varying routes of administration, and assessment of obesity. Controlled trials with stratification at the time of recruitment for obesity are necessary to determine the significance of these findings.

An International, Expert-based, Delphi Consensus Document on Controversial Issues in the Management of Abdominal Aortic Aneurysms.

OBJECTIVE: As a result of conflicting, inadequate or controversial data in the literature, several issues concerning the management of patients with abdominal aortic aneurysms (AAAs) remain unanswered. The aim of this international, expert-based Delphi Consensus document was to provide some guidance for clinicians on these controversial topics. METHODS: A 3-Round Delphi Consensus document was produced with 44 experts on 6 pre-specified topics regarding the management of AAAs. All answers were provided anonymously. The response rate for each round was 100%. RESULTS: Most participants (42 of 44; 95.4%) agreed that a minimum case volume/year is essential (or probably essential) for a center to offer open/endovascular AAA repair (EVAR). Furthermore, 33 of 44 (75.0%) believed that AAA screening programs are (probably) still clinically effective and cost-effective. Additionally, most panelists (36 of 44; 81.9%) voted that surveillance after EVAR should be (or should probably be) lifelong. Finally, 35 of 44 (79.7%) participants thought that women smokers should (or should probably/possibly) be considered for screening at 65 years of age similar to men. No consensus was achieved regarding lowering the threshold for AAA repair and the need for deep venous thrombosis prophylaxis in patients undergoing EVAR. CONCLUSIONS: This expert-based Delphi Consensus document provides guidance for clinicians regarding specific unresolved issues. Consensus could not be achieved in some topics, highlighting the need for further research in those areas.

Associations of mitochondrial genomic variation with successful neurological aging.

Mitochondrial health is an integral factor in aging, with mitochondrial dysfunction known to increase with age and contribute to the development of age-related neurodegenerative disorders. Additionally, the mitochondrial genome (mtDNA) has been shown to acquire potentially damaging somatic variation as part of the aging process, while mtDNA single nucleotide polymorphism (SNPs) have been shown to be both protective and detrimental for various neurodegenerative diseases. Yet, little is known about the involvement of mtDNA variation in longevity and successful neurological aging. In this study, we examined the association of mtDNA SNPs, in the form of mitochondrial haplogroups, with successful neurological aging in 1,405 unrelated neurologically healthy subjects. Although not quite significant after correcting for multiple testing (P < 0.0017 considered as significant), we detected a nominally significant association between the I haplogroup (N = 45, 3.2 %) and a younger age (ß: -5.00, P = 0.006), indicating that this haplogroup is observed less frequently in older neurologically healthy individuals and may be associated with decreased survival. Replication of this finding in independent neurologically healthy cohorts will be imperative for shaping our understanding of the biological processes underlying healthy neurological aging.

A human monoclonal antibody based immunoenzymetric assay to measure Fel d 1 concentrations in cat hair and pelt allergenic extracts.

In the United States, 19 allergen extracts of different specificities are standardized, which means that their potencies are determined in comparison to a US reference standard. For cat allergen extracts, potency is determined by measuring Fel d 1 content expressed in in Fel d 1 units, and with a unitage that correlates with skin test reactions (bioequivalent allergy units or BAU). Currently, Fel d 1 content is measured with a radial immunodiffusion (RID) assay that uses polyclonal sheep antisera to detect the allergenic protein by producing a white precipitin line in agar gel. However, the RID is considered cumbersome, and the polyclonal sera may qualitatively vary among animals and may recognize epitopes irrelevant to human allergic disease. In this report, we describe a quantitative two-site immunoenzymetric assay (IEMA) for Fel d 1 that uses immobilized capture and soluble biotin-labeled detection Fel d 1-specific human IgE monoclonal antibodies (mAb) that have been class-switched to IgG4. Together, they sandwich Fel d 1 molecules from extracts. Using purified natural Fel d 1 as a calibrator, the historically reported ∼4 micrograms Fel d 1/Fel d 1 unit assignment was directly measured in this mAb-based IEMA at 3.12 ± 0.24 micrograms of Fel d 1 per Fel d 1 unit. This IEMA appears to be equivalent to RID in the measurement of biological potencies of commercial cat hair and cat pelt extracts marketed in the United States.

Association of personalized and tumor-informed ctDNA with patient survival outcomes in pancreatic adenocarcinoma.

INTRODUCTION: Personalized and tumor-informed circulating tumor DNA (ctDNA) testing is feasible and allows for molecular residual disease (MRD) identification in patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: In this retrospective analysis of commercial cases from multiple US institutions, personalized, tumor-informed, whole-exome sequenced, and germline-controlled ctDNA levels were quantified and analyzed in patients with PDAC. Plasma samples (n = 1329) from 299 clinically validated patients were collected at diagnosis, perioperatively (MRD-window; within 2-12 weeks after surgery, before therapy), and during surveillance (>12 weeks post-surgery if no ACT or starting 4 weeks post-ACT) from November 2019 to March 2023. RESULTS: Of the initially diagnosed patients with stages I-III PDAC who went for resection, the median follow-up time from surgery was 13 months (range 0.1-214). Positive ctDNA detection rates were 29% (29/100) and 29.6% (45/152) during the MRD and surveillance windows, respectively. Positive ctDNA detection was significantly associated with shorter DFS within the MRD window (median DFS of 6.37 months for ctDNA-positive vs 33.31 months for ctDNA-negative patients; HR: 5.45, P < .0001) as well as during the surveillance period (median DFS: 11.40 months for ctDNA-positive vs NR for ctDNA-negative; HR: 12.38, P < .0001). Additionally, DFS was significantly better with KRAS wildtype status followed by KRASG12R (HR: 0.99, P = .97), KRASG12D (HR: 1.42, P = .194), and worse with KRASG12V (HR: 2.19, P = .002) status. In multivariate analysis, ctDNA detection at surveillance was found to be the most significant prognostic factor for recurrence (HR: 24.28, P < .001). CONCLUSIONS: Perioperative tumor-informed ctDNA detection in PDAC is feasible across all stages and is associated with patient survival outcomes.

Weight of Evidence: Is an Animal Study Warranted? Assessments for Carcinogenicity, Drug Abuse Liability, and Pediatric Safety.

Nonclinical safety studies are typically conducted to establish a toxicity profile of a new pharmaceutical in clinical development. Such a profile may encompass multiple differing types of animal studies, or not! Some types of animal studies may not be warranted for a specific program or may only require a limited evaluation if scientifically justified. The goal of this course was to provide a practical perspective on regulatory writing of a dossier(s) using the weight of evidence (WOE) approach for carcinogenicity, drug abuse liability and pediatric safety assessments. These assessments are typically done after some clinical data are available and are highly bespoke to the pharmaceutical being developed. This manuscript will discuss key data elements to consider and strategy options with some case studies and examples. Additionally, US FDA experience with dossier(s) including WOE arguments is discussed.

Impact of Discontinuing Both Hypertonic Saline and Dornase Alfa After Elexacaftor/Tezacaftor/Ivacaftor in Cystic Fibrosis.

Rationale Evaluating approaches to reduce treatment burden is a research priority among people with CF (pwCF) on highly effective modulators including elexacaftor/tezacaftor/ivacaftor (ETI). Objective To evaluate the impact of discontinuing both hypertonic saline (HS) and dornase alfa (DA) versus continuing both therapies among a subgroup of participants in the SIMPLIFY study who sequentially participated in trials evaluating the independent clinical effects of discontinuing HS and DA. Methods SIMPLIFY participants ≥12 years old on ETI and comprising a subgroup using both HS and DA at study entry were randomized to the HS or DA trial, and then randomized 1:1 to continue or discontinue the applicable therapy for 6 weeks. After completion of the first trial, eligible participants could enroll in the second trial beginning with a 2-week run in. Study outcomes were compared across the duration of SIMPLIFY participation between a cohort remaining on both therapies during SIMPLIFY versus a cohort that sequentially discontinued both as a result of trial randomizations. Multivariable regression models were used to estimate treatment differences, adjusted for time between trials, trial order, baseline age, sex at birth and percent predicted forced expiratory volume in one second (ppFEV1) at study entry. Results There were 43 participants who discontinued both therapies by the end of SIMPLIFY and 63 who remained on both, with overall average ppFEV1 at study entry 96.7% and average duration of follow up from beginning of the first trial to completion of the second trial 3.9 months, including time between trials. No clinically meaningful difference in the change in ppFEV1 from baseline to completion of the second trial was observed between those who discontinued versus remained on both therapies (difference: 0.22% Off-On, 95% CI: -1.60,2.03). Changes in LCI2.5, patient reported, and safety outcomes were also comparable. Patient reported treatment burden, as measured by a CFQ-R subscale, significantly decreased in those discontinuing both therapies. Conclusions SIMPLIFY participants who sequentially discontinued both HS and DA experienced no meaningful changes in clinical outcomes and reported decreased treatment burden as compared to those who remained on both therapies. These data continue to inform a new era of post-modulator care of pwCF.

Cannabis use and acute postoperative pain outcomes in older adults: a propensity matched retrospective cohort study.

INTRODUCTION: Cannabis use is increasing among older adults, but its impact on postoperative pain outcomes remains unclear in this population. We examined the association between cannabis use and postoperative pain levels and opioid doses within 24 hours of surgery. METHODS: We conducted a propensity score-matched retrospective cohort study using electronic health records data of 22 476 older surgical patients with at least 24-hour hospital stays at University of Florida Health between 2018 and 2020. Of the original cohort, 2577 patients were eligible for propensity-score matching (1:3 cannabis user: non-user). Cannabis use status was determined via natural language processing of clinical notes within 60 days of surgery and structured data. The primary outcomes were average Defense and Veterans Pain Rating Scale (DVPRS) score and total oral morphine equivalents (OME) within 24 hours of surgery. RESULTS: 504 patients were included (126 cannabis users and 378 non-users). The median (IQR) age was 69 (65-72) years; 295 (58.53%) were male, and 442 (87.70%) were non-Hispanic white. Baseline characteristics were well balanced. Cannabis users had significantly higher average DVPRS scores (median (IQR): 4.68 (2.71-5.96) vs 3.88 (2.33, 5.17); difference=0.80; 95% confidence limit (CL), 0.19 to 1.36; p=0.01) and total OME (median (IQR): 42.50 (15.00-60.00) mg vs 30.00 (7.50-60.00) mg; difference=12.5 mg; 95% CL, 3.80 mg to 21.20 mg; p=0.02) than non-users within 24 hours of surgery. DISCUSSION: This study showed that cannabis use in older adults was associated with increased postoperative pain levels and opioid doses.

Cannabis Use and Inhalational Anesthesia Administration in Older Adults: A Propensity Matched Retrospective Cohort Study.

BACKGROUND: Cannabis use is associated with higher intravenous anesthetic administration. Similar data regarding inhalational anesthetics are limited. With rising cannabis use prevalence, understanding any potential relationship with inhalational anesthetic dosing is crucial. We compared average intraoperative isoflurane/sevoflurane minimum alveolar concentration equivalents between older adults with and without cannabis use. METHODS: The electronic health records of 22,476 surgical patients ≥65 years old at the University of Florida Health System between 2018-2020 were reviewed. The primary exposure was cannabis use within 60 days of surgery, determined via i) a previously published natural language processing algorithm applied to unstructured notes and ii) structured data, including International Classification of Disease codes for cannabis use disorders and poisoning by cannabis, laboratory cannabinoids screening results, and RxNorm codes. The primary outcome was the intraoperative time-weighted average of isoflurane/sevoflurane minimum alveolar concentration equivalents at one-minute resolution. No a priori minimally clinically important difference was established. Patients demonstrating cannabis use were matched 4:1 to non-cannabis use controls using a propensity score. RESULTS: Among 5,118 meeting inclusion criteria, 1,340 patients (268 cannabis users and 1,072 nonusers) remained after propensity score matching. The median and interquartile range (IQR) age was 69 (67, 73) years; 872 (65.0%) were male, and 1,143 (85.3%) were non-Hispanic White. The median (IQR) anesthesia duration was 175 (118, 268) minutes. After matching, all baseline characteristics were well-balanced by exposure. Cannabis users had statistically significantly higher average minimum alveolar concentrations than nonusers [mean±SD: 0.58±0.23 versus 0.54±0.22, respectively; mean difference=0.04; 95% confidence limits, 0.01 to 0.06; p=0.020]. CONCLUSION: Cannabis use was associated with administering statistically significantly higher inhalational anesthetic minimum alveolar concentration equivalents in older adults, but the clinical significance of this difference is unclear. These data do not support the hypothesis that cannabis users require clinically meaningfully higher inhalational anesthetics doses.

Risk factors of peritoneal dialysis-related peritonitis in the Japan Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS).

Background: Peritoneal dialysis (PD)-related peritonitis is a major complication of PD. Wide variations in peritonitis prevention, treatment strategies and consequences are seen between countries. These between-country differences may result from modifiable risk factors and clinical practices. Methods: A total of 1225 Japanese PD patients were included and prospectively followed in the Peritoneal Dialysis Outcomes and Practice Patterns Study phase 1 (2014-2018) and phase 2 (2018-2022). Associations between PD-related peritonitis and various risk factors were assessed by Cox proportional hazards survival models. Results: During follow-up (median 1.52 years), 539 peritonitis episodes were experienced by 364 patients. The country crude peritonitis rate was 0.27 episodes/patient-year. In the fully adjusted model, noticeable patient-level factors associated with experiencing any peritonitis included age {hazard ratio [HR] 1.07 per 5-year increase [95% confidence interval (CI) 1.01-1.14]}, serum albumin level [HR 0.63 per 1 g/dl higher (95% CI 0.48-0.82)] and continuous ambulatory peritoneal dialysis (PD) [HR 1.31 versus automated PD (95% CI 1.05-1.63)]. The adoption of antibiotic prophylaxis practice at the time of PD catheter insertion [HR 0.63 (95% CI 0.51-0.78)] or when having complicated dental procedures [HR 0.74 (95% CI 0.57-0.95)] or lower endoscopy [HR 0.69 (95% CI 0.54-0.89)] were associated with lower hazards of any peritonitis, while a routine facility practice of having more frequent regular medical visits was associated with a higher hazard. Conclusion: Identification of risk factors in Japan may be useful for developing future versions of guidelines and improving clinical practices in Japan. Investigation of country-level risk factors for PD-related peritonitis is useful for developing and implementing local peritonitis prevention and treatment strategies.