High- versus low-dose ketamine for analgesia in older adults in the emergency department.

BACKGROUND AND OBJECTIVES: Ketamine is increasingly being utilized in the management of acute pain in the emergency department (ED), including for older adults, a population at increased risk of adverse effects from medications. We aimed to compare the safety and analgesic effects of high-dose (≥0.3mg/kg) to low-dose (<0.3mg/kg) intravenous (IV) ketamine among older ED patients. METHODS: Multi-center, retrospective cohort study of adults ≥60years who received IV ketamine for pain between 2018 and 2021. The primary outcome was pain improvement as measured by the Numerical Rating Scale (NRS) pain score within 60min after administration. Secondary outcomes included adverse effects (early discontinuation, nausea, rescue benzodiazepines and intubation) and the need for rescue analgesia. Linear regression was used to assess the association between the change in NRS pain scores and dose after adjusting for baseline pain, requiring an additional dose of ketamine, and receiving an opioid. RESULTS: A total of 130 older adults received ketamine as an analgesic (37 high-dose, 93 low-dose). Median age was 69.2years, 52 % were women, 40 % had a history of substance use disorder. Prior to ketamine, 76 % received alternate analgesics and 23 % antiemetics. Baseline mean pain score was lower in the high-dose group (6.7 vs. 8.3, difference -1.7 [95 % CI -2.6 to -0.7], p = 0.013). Change in NRS pain scores were similar between the high-dose and low-dose groups (-2.4 [95 % CI -3.6 to -1.3] vs -1.6 [95 % CI -2.2 to -0.9], p = 0.27). After adjustment for baseline pain score, the high-dose group had a larger reduction in pain scores (-1.3 [95 % CI -2.6 to -0.1], p = 0.042) and percent change of pain (-23.8 % [95 % CI -42.1 % to -5.4 %], p = 0.012). There was no significant difference in rates of rescue analgesia (35.1 % vs. 44.1 %, p = 0.35) or early discontinuation (29.7 % vs. 32.3 %, p = 0.78). Rates of adverse effects were similar. CONCLUSION: High-dose and low-dose ketamine reduced pain scores in older adults. High-dose ketamine led to a greater reduction in pain scores, and there was no observed difference in adverse effects or the need for rescue analgesia. One-third needed discontinuation of ketamine in both groups.

Impact of Family Structure on Adolescent Depression Outcomes in a Collaborative Care Program.

INTRODUCTION/OBJECTIVES: We aimed to investigate the effect of family structure on depression program outcomes for adolescents enrolled in a depression-focused, primary care-based collaborative care program. METHODS: This was a retrospective study of primary care patients ages 12 to 18 years seen at a Midwestern academic center with data obtained by medical record review. We used logistic regression models to assess the effect of family structure on program graduation and achievement of a single Patient Health Questionnaire 9-Modified for Adolescents (PHQ-9M) score <5 at any time while enrolled. RESULTS: Adolescents were divided into 2 groups, Both Parents in Household (n = 179) and Parents Not Together (n = 161). The Both Parents in Household group had higher rates of graduation (38.0% vs 23.6%, P = .005) and achieving single PHQ-9M scores <5 (64.1% vs 46.2%, P = .002) than the Parents Not Together group. DISCUSSION: Youth residing with both parents had higher rates of successful outcomes in a depression-focused collaborative care program.

Comparable outcomes of outpatient remdesivir and sotrovimab among high-risk patients with mild to moderate COVID-19 during the omicron BA.1 surge.

Studies conducted prior to SARS-CoV-2 Omicron demonstrated that sotrovimab and remdesivir reduced hospitalization among high-risk outpatients with mild to moderate COVID-19. However, their effectiveness has not been directly compared. This study examined all high-risk outpatients with mild to moderate COVID-19 who received either remdesivir or sotrovimab at Mayo Clinic during the Omicron BA.1 surge from January to March 2022. COVID-19-related hospitalization or death within 28 days were compared between the two treatment groups. Among 3257 patients, 2158 received sotrovimab and 1099 received remdesivir. Patients treated with sotrovimab were younger and had lower comorbidity but were more likely to be immunocompromised than remdesivir-treated patients. The majority (89%) had received at least one dose of COVID-19 vaccine. COVID-19-related hospitalization (1.5% and 1.0% in remdesivir and sotrovimab, respectively, p = .15) and mortality within 28 days (0.4% in both groups, p = .82) were similarly low. A propensity score weighted analysis demonstrated no significant difference in the outcomes between the two groups. We demonstrated favorable outcomes that were not significantly different between patients treated with remdesivir or sotrovimab.

Characterizing Proton-Induced Biological Effects in a Mouse Spinal Cord Model: A Comparison of Bragg Peak and Entrance Beam Response in Single and Fractionated Exposures.

PURPOSE: Proton relative biological effectiveness (RBE) is a dynamic variable influenced by factors like linear energy transfer (LET), dose, tissue type, and biological endpoint. The standard fixed proton RBE of 1.1, currently used in clinical planning, may not accurately represent the true biological effects of proton therapy (PT) in all cases. This uncertainty can contribute to radiation-induced normal tissue toxicity in patients. In late-responding tissues such as the spinal cord, toxicity can cause devastating complications. This study investigated spinal cord tolerance in mice subjected to proton irradiation and characterized the influence of fractionation on proton- induced myelopathy at entrance (ENT) and Bragg peak (BP) positions. METHODS AND MATERIALS: Cervical spinal cords of 8-week-old C57BL/6J female mice were irradiated with single- or multi-fractions (18x) using lateral opposed radiation fields at 1 of 2 positions along the Bragg curve: ENT (dose-mean LET = 1.2 keV/µm) and BP (LET = 6.9 keV/µm). Mice were monitored over 1 year for changes in weight, mobility, and general health, with radiation-induced myelopathy as the primary biological endpoint. Calculations of the RBE of the ENT and BP curve (RBEENT/BP) were performed. RESULTS: Single-fraction RBEENT/BP for 50% effect probability (tolerance dose (TD50), grade II paresis, determined using log-logistic model fitting) was 1.10 ± 0.06 (95% CI) and for multifraction treatments it was 1.19 ± 0.05 (95% CI). Higher incidence and faster onset of paralysis were seen in mice treated at the BP compared with ENT. CONCLUSIONS: The findings challenge the universally fixed RBE value in PT, indicating up to a 25% mouse spinal cord RBEENT/BP variation for multifraction treatments. These results highlight the importance of considering fractionation in determining RBE for PT. Robust characterization of proton-induced toxicity, aided by in vivo models, is paramount for refining clinical decision-making and mitigating potential patient side effects.

Impact of hypoalbuminemia on clinical outcomes among patients with obesity treated with ceftriaxone.

The use of ceftriaxone, a highly protein-bound drug, in the setting of hypoalbuminemia may result in suboptimal drug exposure. Patients with obesity also exhibit higher absolute drug clearance. We aimed to evaluate the impact of hypoalbuminemia on clinical success among hospitalized adults with obesity who were treated with ceftriaxone. This retrospective review included adult inpatients with weight >100 kg or body mass index >40 kg/m2 who received ceftriaxone 2 g intravenously every 12 hours for at least 72 hours. The primary outcome was clinical success, a composite of clinical cure and microbiologic cure. Secondary outcomes included clinical cure, microbiologic cure, length of stay, ICU length of stay, mortality, 30-day readmission, and adverse events. In all, 137 patients were included, 34 of whom had a serum albumin of ≤2.5 g/dL. In a propensity-score-weighted analysis, clinical success was significantly more common among those without hypoalbuminemia (91.2%) as compared to those with hypoalbuminemia (77.8%) (P = 0.038). Death within 30 days (13.7% vs 0%, P < 0.001) and 30-day readmission (31.6% vs 12.0%, P = 0.008) were more common in the hypoalbuminemia group. In a univariate analysis, serum albumin and indication for ceftriaxone use were found to be predictors of clinical success. Hypoalbuminemia was associated with a lower rate of clinical success among patients with obesity who were treated with ceftriaxone 2 g every 12 hours.

Impact of sex on antidepressant discontinuation in groups of similar cytochrome P450 phenotypes.

Introduction: Although there are studies assessing reasons for antidepressant discontinuation, little is known about the impact of sex differences or cytochrome P450 phenotypes. Our objective is to assess discontinuation rates between males and females and whether CYP450 phenotype influences discontinuation. Methods: This is a retrospective review of patients previously enrolled in the Right Drug, Right Dose, Right Time: Using Genomic Data to Individualize Treatment database with major depressive disorder. Patients were evaluated for antidepressants trialed between January 1, 2009, and September 30, 2019. Survival analyses with competing risks were used to analyze discontinuation reasons. A Kaplan-Meier estimation method was used to assess the time to discontinuation and discontinuation rates. Analyses were also completed to assess discontinuation between men and women by phenotypic groups. All tests were two-sided, and p-values ≤ .05 were considered statistically significant. Results: There were 620 antidepressant discontinuation events discovered from 1015 antidepressant trials included. Overall, the median time to discontinuation for males was 2.6 years and 1.9 years for females (hazard ratio [HR] 0.97 [95% confidence interval (CI): 0.80, 1.19], p = .77). The risk of discontinuation was not different between males and females in any of the phenotype groups, which was consistent in the multivariable analyses. Concomitant use of medications that inhibited or induced antidepressant metabolism increased the overall risk of discontinuation (HR 1.45, 95% CI [1.06, 1.99], p = .020) in a time-dependent analysis. Discussion: We did not detect a significant difference in risk of antidepressant discontinuation rates between males and females even when accounting for cytochrome P450 phenotype. Future studies should account for whether medications that inhibit or induce antidepressant metabolism may be a crucial factor in antidepressant discontinuation.

Posthospital Multidisciplinary Care for AKI Survivors: A Feasibility Pilot.

Rationale & Objective: Innovative models are needed to address significant gaps in kidney care follow-up for acute kidney injury (AKI) survivors. Study Design: This quasi-experimental pilot study reports the feasibility of the AKI in Care Transitions (ACT) program, a multidisciplinary approach to AKI survivor care based in the primary care setting. Setting & Participants: The study included consenting adults with stage 3 AKI discharged home without dialysis. Interventions: The ACT intervention included predischarge education from nurses and coordinated postdischarge follow-up with a primary care provider and pharmacist within 14 days. ACT was implemented in phases (Usual Care, Education, ACT). Outcomes: The primary outcome was feasibility. Secondary outcomes included process and clinical outcomes. Results: In total, 46 of 110 eligible adults were enrolled. Education occurred in 18/18 and 14/15 participants in the Education and ACT groups, respectively. 30-day urine protein evaluation occurred in 15%, 28%, and 87% of the Usual Care, Education, and ACT groups, respectively (P < 0.001). Cumulative incidence of provider (primary care or nephrologist) and laboratory follow-up at 14 and 30 days was different across groups (14 days: Usual care 0%, Education 11%, ACT 73% [P < 0.01]; 30 days: 0%, 22%, and 73% [P < 0.01]). 30-day readmission rates were 23%, 44%, and 13% in the Usual Care, Education, and ACT groups, respectively (P = 0.13). Limitations: Patients were not randomly assigned to treatment groups. The sample size limited the ability to detect some differences or perform multivariable analysis. Conclusions: This study demonstrated the feasibility of multidisciplinary AKI survivor follow-up beginning in primary care. We observed a higher cumulative incidence of laboratory and provider follow-up in ACT participants. Trial Registration: ClinicalTrials.gov (NCT04505891). Plain-Language Summary: Abrupt loss of kidney function in hospitalized patients, acute kidney injury (AKI), increases the chances of long-term kidney disease and a worse health care experience for patients. One out of 3 people who experience AKI do not get the follow-up kidney care they need. We performed a pilot study to test whether a program that facilitates structured AKI follow-up in primary care called the AKI in Care Transitions (ACT) program was possible. ACT brings together the unique expertise of nurses, doctors, and pharmacists to look at the patient's kidney health plan from all angles. The study found that the ACT program was possible and led to more complete kidney care follow-up after discharge than the normal approach to care.

Preventing substance use among Black and Hispanic adolescent girls: results from a computer-delivered, mother-daughter intervention approach.

This 2008 study involved 546 Black and Hispanic American adolescent girls and their mothers from New York, New Jersey, and Connecticut. Participants provided self-report data. Analysis of covariance indicated that the experimental intervention reduced risk factors, improved protective factors, and lowered girls' alcohol use and their future intentions to use substances. The study supports the value of computer-based and gender-specific interventions that involve girls and their mothers. Future work needs to replicate and strengthen study results.

Preventing substance use among early Asian-American adolescent girls: initial evaluation of a web-based, mother-daughter program.

PURPOSE: This study examined the efficacy and generalizability of a family-oriented, web-based substance use prevention program to young Asian-American adolescent girls. METHODS: Between September and December 2007, a total of 108 Asian-American girls aged 10-14 years and their mothers were recruited through online advertisements and from community service agencies. Mother-daughter dyads were randomly assigned to an intervention arm or to a test-only control arm. After pretest measurement, intervention-arm dyads completed a 9-session web-based substance use prevention program. Guided by family interaction theory, the program aimed to improve girls' psychological states, strengthen substance use prevention skills, increase mother-daughter interactions, enhance maternal monitoring, and prevent girls' substance use. Study outcomes were assessed using generalized estimating equations. RESULTS: At posttest, relative to control-arm girls, intervention-arm girls showed less depressed mood; reported improved self-efficacy and refusal skills; had higher levels of mother-daughter closeness, mother-daughter communication, and maternal monitoring; and reported more family rules against substance use. Intervention-arm girls also reported fewer instances of alcohol, marijuana, and illicit prescription drug use, and expressed lower intentions to use substances in the future. CONCLUSIONS: A family-oriented, web-based substance use prevention program was efficacious in preventing substance use behavior among early Asian-American adolescent girls.

Underage drinking among young adolescent girls: the role of family processes.

Guided by family interaction theory, this study examined the influences of psychological, peer, and familial processes on alcohol use among young adolescent girls and assessed the contributions of familial factors. An ethnically diverse sample of 1,187 pairs of girls (M age = 12.83 years), and their mothers completed surveys online. Questionnaires assessed girls' lifetime and recent alcohol use, as well as girls' demographic, psychological, peer, and family characteristics. Hierarchical logistic regression models showed that although girls' drinking was associated with a number of psychological and peer factors, the contributions of family domain variables to girls' drinking were above and beyond that of psychological and peer factors. The interaction analyses further highlighted that having family rules, high family involvement, and greater family communication may offset risks in psychological and peer domains. Study findings underscore the multifaceted etiology of drinking among young adolescent girls and assert the crucial roles of familial processes. Prevention programs should be integrative, target processes at multiple domains, and include work with parents.

Computer-delivered, parent-involvement intervention to prevent substance use among adolescent girls.

OBJECTIVE: To test a computer-delivered program for preventing substance use among adolescent girls. METHODS: Randomly, 916 girls aged 12.76+/-1.0 years and their mothers were assigned to an intervention arm or to a test-only control arm. Intervention-arm dyads engaged in exercises to improve the mother-daughter relationship, build girls' substance use prevention skills, and reduce associated risk factors. Study outcomes were girls' and mothers' substance use and mediator variables related to girls' substance use risk and protective factors. The study was conducted between September 2006 and February 2009 with participants from greater New York City, including southern Connecticut and eastern New Jersey. RESULTS: At 2-year follow-up and relative to control-arm girls, intervention-arm girls reported lower relevant risk factors and higher protective factors as well as less past 30-day use of alcohol (p<0.006), marijuana (p<0.016), illicit prescription drugs (p<0.03), and inhalants (p<0.024). Intervention-arm mothers showed more positive 2-year outcomes than control-arm mothers on variables linked with reduced risks of substance use among their daughters, and mothers reported lower rates of weekly alcohol consumption (p<0.0001). CONCLUSIONS: A computer-delivered prevention program for adolescent girls and their mothers was effective in changing girls' risk and protective factors and girls' and mothers' substance use behavior.

Preventing substance use among adolescent girls: 1-year outcomes of a computerized, mother-daughter program.

This study tested a computerized gender-specific, parent-involvement intervention program grounded in family interaction theory and aimed at preventing substance use among adolescent girls. Following program delivery and 1 year later, girls randomly assigned to the intervention arm improved more than girls in a control arm on variables associated with reduced risks for substance use, including communication with their mothers, knowledge of family rules about substance use, awareness of parental monitoring of their discretionary time, non-acceptance of peer substance use, problem-solving skills, and ability to refuse peer pressure to use substances. Relative to control-arm girls, those in the intervention arm also reported less 30-day use of alcohol and marijuana and lower intentions to smoke, drink, and take illicit drugs in the future. Girls' mothers in the intervention arm reported greater improvements after the program and relative to control-arm mothers in their communication with their daughters, establishment of family rules about substance use, and monitoring of their daughters' discretionary time. Study findings lend support to the potential of gender-specific, parent-involvement, and computerized approaches to preventing substance use among adolescent girls.

Gender-specific intervention to reduce underage drinking among early adolescent girls: a test of a computer-mediated, mother-daughter program.

OBJECTIVE: This study evaluated a gender-specific, computer-mediated intervention program to prevent underage drinking among early adolescent girls. METHOD: Study participants were adolescent girls and their mothers from New York, New Jersey, and Connecticut. Participants completed pretests online and were randomly divided between intervention and control arms. Intervention-arm girls and their mothers interacted with a computer program aimed to enhance mother-daughter relationships and to teach girls skills for managing conflict, resisting media influences, refusing alcohol and drugs, and correcting peer norms about underage drinking, smoking, and drug use. After intervention, all participants (control and intervention) completed posttest and follow-up measurements. RESULTS: Two months following program delivery and relative to control-arm participants, intervention-arm girls and mothers had improved their mother-daughter communication skills and their perceptions and applications of parental monitoring and rule-setting relative to girls' alcohol use. Also at follow-up, intervention-arm girls had improved their conflict management and alcohol use-refusal skills; reported healthier normative beliefs about underage drinking; demonstrated greater self-efficacy about their ability to avoid underage drinking; reported less alcohol consumption in the past 7 days, 30 days, and year; and expressed lower intentions to drink as adults. CONCLUSIONS: Study findings modestly support the viability of a mother-daughter, computer-mediated program to prevent underage drinking among adolescent girls. The data have implications for the further development of gender-specific approaches to combat increases in alcohol and other substance use among American girls.

Substance use among early adolescent girls: risk and protective factors.

Disquieting rates of alcohol and drug use among adolescent girls call for original research on gender-specific risk and protective factors for substance use. Particularly salient are data on theory-driven factors that can inform prevention programming. Surveying 781 adolescent girls and their mothers, we found relationships between girls' use of alcohol, prescription drugs, and inhalants and girls' after-school destinations, body images, depression, best friend's substance use, maternal drinking behavior, mother-daughter interactions, and family norms surrounding substance use. Study findings have implications for the design of responsive gender-specific prevention programs.

Reducing the risks of alcohol use among urban youth: three-year effects of a computer-based intervention with and without parent involvement.

OBJECTIVE: This study tested a CD-ROM intervention with and without a parent involvement component to reduce risk of alcohol use among an urban sample of early adolescents. METHOD: Youths (N = 514, mean age 11.5 years at recruitment) were assigned randomly by community site to receive the CD-ROM intervention, the CD-ROM plus parent intervention, or no intervention. All youths completed pretest, posttest and three annual follow-up measurements. After pretesting, youths and parents received their respective interventions. RESULTS: Main effects of the intervention and for measurement occasion as well as interaction effects of the intervention by measurement occasion were seen for substance use and related outcomes. Over time, youths in all 3 groups reported increased use of alcohol, tobacco and marijuana; youths who received the interventions reported smaller increases than control youths. At 3-year follow-up, alcohol use was lower for CD-ROM plus parent intervention youths than for CD-ROM only youths, who, in turn, reported less use than controls. Cigarette use was lower for youths in either intervention group than in the control group at posttest and at 1-, 2- and 3-year follow-ups. Marijuana use was lower for youths in either intervention than for controls at 1-, 2- and 3-year follow-ups. Youths in both intervention groups outperformed control youths at posttest and at 1- and 3-year follow-ups on levels of negative and peer influence toward substance use. Finally, at the 3-year follow-up, youths in the CD-ROM plus parent intervention group reported more family involvement in their alcohol use prevention efforts than did youths in the CD-ROM group, who, in turn, reported more positive levels of family involvement than youths in the control group. CONCLUSIONS: Study findings modestly support the CD-ROM intervention with and without the parent intervention to reduce alcohol use risks among urban early adolescents.