A Qualitative Study of the Work Systems and Culture Around End-of-Day Intraoperative Anesthesia Handoffs in a Tertiary Care Center.

BACKGROUND: Intraoperative handoffs have been implicated as a contributing factor in many perioperative adverse events. Despite conflicting data around their impact on perioperative outcomes, they remain a vulnerable point in the perioperative system with significant attention focused on improving them. This study aimed to understand the processes in place surrounding the point of information transfer in intraoperative handoffs. METHODS: We used semistructured interviews with anesthesia clinicians to understand the processes and systems surrounding intraoperative handoffs. Interview data were coded deductively using the Systems Engineering Initiative for Patient Safety model as a framework, with subthemes developed inductively. RESULTS: Clinicians do a significant amount of work before and after the point of information transfer to ensure a smooth handoff and safe patient care. Despite not having standardization of handoffs, most clinicians have a typical handoff organization and largely agree on content that should be included. However, there is variability based on clinician and patient characteristics, including clinician discipline and patient acuity. These handoffs are additionally impacted by the overall culture in the operating room, including the teamwork and hierarchies present among the surgical and anesthesia teams. Finally, the broader operating room logistics, including scheduling practices for surgical cases and anesthesia teams, impact the quality of intraoperative handoffs and the ability of clinicians to prepare for these handoffs. CONCLUSIONS: Handoffs involve processes beyond the point of information transfer and are embedded in the systems and culture of the operating rooms. These considerations are important when seeking to improve the quality of intraoperative handoffs.

Mortality after emergency unit fluid bolus in febrile Ugandan children.

OBJECTIVES: Pediatric fluid resuscitation in sub-Saharan Africa has traditionally occurred in inpatients. The landmark Fluid Expansion as Supportive Therapy (FEAST) trial showed fluid boluses for febrile children in this inpatient setting increased mortality. As emergency care expands in sub-Saharan Africa, fluid resuscitation increasingly occurs in the emergency unit. The objective of this study was to determine the mortality impact of emergency unit fluid resuscitation on febrile pediatric patients in Uganda. METHODS: This retrospective cohort study used data from 2012-2019 from a single emergency unit in rural Western Uganda to compare three-day mortality for febrile patients that did and did not receive fluids in the emergency unit. Propensity score matching was used to create matched cohorts. Crude and multivariable logistic regression analysis (using both complete case analysis and multiple imputation) were performed on matched and unmatched cohorts. Sensitivity analysis was done separately for patients meeting FEAST inclusion and exclusion criteria. RESULTS: The analysis included 3087 febrile patients aged 2 months to 12 years with 1,526 patients receiving fluids and 1,561 not receiving fluids. The matched cohorts each had 1,180 patients. Overall mortality was 4.0%. No significant mortality benefit or harm was shown in the crude unmatched (Odds Ratio [95% Confidence Interval] = 0.88 [0.61-1.26] or crude matched (1.00 [0.66-1.50]) cohorts. Adjusted cohort analysis (including both complete case analysis and multiple imputation) and sensitivity analysis of patients meeting FEAST inclusion and exclusion criteria all also failed to show benefit or harm. Post-hoc power calculations showed the study was powered to detect the absolute harm seen in FEAST but not the relative risk increase. CONCLUSIONS: This study's primary finding is that fluid resuscitation in the emergency unit did not significantly increase or decrease three-day mortality for febrile children in Uganda. Universally aggressive or fluid-sparing emergency unit protocols are unlikely to be best practices, and choices about fluid resuscitation should be individualized.

Quality Assurance: Compounding Record Audits for Error Prevention.

This article looks at taking a proactive approach in discovering inconsistencies in pharmaceutical compounding at a facility level. Details on the requirements for master formulation and compounding records in nonsterile and sterile compounding as laid out in the 2022 publications of United States Pharmacopeia Chapter <795> Pharmaceutical Compounding- Nonsterile Preparations and United States Pharmacopeia Chapter <797> Pharmaceutical Compounding-Sterile Preparations are reviewed. Following this summary, information is then presented on how to utilize the record-keeping requirements to a facility's advantage through regular auditing and reporting and how to incorporate these audits or reports into a facility's quality-assurance program to fulfill error detection and prevention requirements.

Aboriginal people's perceptions of patient-reported outcome measures in the assessment of diabetes health-related quality of life.

BACKGROUND: Patient-reported outcome measures (PROMs) provide clinicians and consumers a platform to inform and improve healthcare planning and management. Aboriginal people experience disproportionately high rates of chronic diseases, including type 2 diabetes. Treatment and management require holistic approaches that draw on culturally relevant resources and assessment tools. This study explored perceptions of Aboriginal people about two diabetes management-related PROMs (PROMIS-29, PAID Scale). METHODS: Twenty-nine Aboriginal people living with diabetes in the Shoalhaven discussed two PROMs in one of four focus groups or at an individual interview. Preliminary data coding was conducted by clinician researchers, with thematic analysis overseen by Aboriginal co-researchers. Subsequent individual interviews with participants were undertaken to seek further feedback and articulate what is needed to improve methods of evaluating Aboriginal people's self-reported quality of life and diabetes management. RESULTS: The PROMs did not capture information or knowledge that Aboriginal people considered relevant to their diabetes-related health care. Participants' recommendations included adapting survey materials to be more culturally sensitive; for example, by improving the alignment of measures with common day-to-day activities. This study also describes a genuine collaborative, Aboriginal community-guided approach to evaluate 'fit-for-purpose' diabetes management tools. CONCLUSIONS: Appropriate evaluation methods are paramount to address the disproportionate burden of diabetes experienced by Aboriginal peoples and overcome inverse diabetes care. Our learnings will contribute to development of tools, resources or methods that capture culturally tailored outcome measures. Study findings are relevant to clinicians and researchers using and/or developing Patient Reported Measures, particularly in relation to the practicality of tools for First Nations peoples.

Bridging the know-do gap in low-income surgical environments: Creating contextually appropriate training videos to promote safer surgery in Ethiopia.

Although international guidelines exist for the prevention of surgical site infections, their implementation in diverse clinical contexts, especially in low and middle-income countries, is challenging due to the lack of available resources and organizational structure of facilities. The goal of this project was to develop a series of video training aids to highlight best practices in surgical infection prevention in hospitals with limited resources and to provide practical solutions to common challenges faced in these settings. Using the validated Clean Cut education framework for infection prevention developed by Lifebox, a charity devoted to improving surgical and anesthetic safety, we partnered with clinicians in one Ethiopian hospital to create six educational videos giving practical guidelines for infection prevention under resource variable conditions. These include: 1) proper use of the WHO Surgical Safety Checklist, 2) hand and skin antisepsis, 3) confirming instrument sterility, 4) maintaining the sterile field, 5) antibiotic prophylaxis, and 6) gauze counting. Gaps in available online educational materials were identified in each of the six areas. Videos were created providing setting-specific education and addressing gaps in existing materials for each of the infection prevention topics. These videos are now integrated into infection prevention curricula through Lifebox in Ethiopia and ongoing data collection to evaluate acceptability and efficacy is ongoing. Surgical education videos on infection prevention topics addressing location-specific resources and workarounds can be useful to hospitals operating in resource-limited settings for training staff and supporting quality and safety efforts in surgery.

Medical students' experiences of compulsory rural service in Guatemala: a qualitative study.

INTRODUCTION: Compulsory rural service is one method of addressing limitations in health care access in marginalized areas of low- and middle-income countries, including Guatemala. This study aimed to explore Guatemalan medical students' experiences of compulsory rural service and the impact of rural service on their professional development. METHODS: Qualitative semi-structured interviews were conducted with 40 medical school graduates who completed compulsory rural service between 2012 and 2017. Interview transcripts were coded for dominant themes using an inductive approach. RESULTS: The majority of interviewees felt that rural service contributed to their professional development by increasing their clinical autonomy, awareness of social determinants of health, and humanistic practice. Interviewees identified limited supervision as a key challenge during the rotation. The majority found rural service rewarding. CONCLUSION: Guatemalan medical students felt that rural service contributed to their professional and personal development. Rural rotations build primary care skills and may increase awareness of health inequity among clinical trainees. Given ongoing healthcare worker shortages in Guatemala, innovative approaches to improving professional supervision and rural health mentoring are needed.

Assessing cultural appropriateness of patient-reported outcome measures for Aboriginal people with diabetes: study protocol.

BACKGROUND: Patient-reported outcome measures (PROMs) provide patients with a platform to report on healthcare services and interventions, including the management of diabetes and other chronic diseases. Given the major disparity in incidence and prevalence of diabetes between Aboriginal and non-Aboriginal people, it is crucial that PROMs meet the cultural, spiritual and medical needs of this high-risk population. Anecdotal evidence indicates that PROMs do not capture accurate information about the healthcare of Aboriginal people with Type 2 diabetes. Therefore, the aim of this study is to explore the perceptions of Aboriginal people in regional New South Wales (NSW), Australia, about the cultural appropriateness of a set of PROMs relating to diabetes management. METHODS/DESIGN: Up to 50 Aboriginal people aged 18 years or older with type 1 or type 2 diabetes living in the Shoalhaven region in NSW, will be recruited. Eligible, consenting participants will attend a focus group or individual interview where they will review the PROM tools (PROMIS 29 and PAID scale) currently used for diabetes management. Semi-structured questions will be used to gather information about PROMs and discussions will be recorded for analysis. Research team members will yarn about the data with Aboriginal co-researchers and community stakeholders to apply an Indigenous lens to coding and thematic analysis. CONCLUSION: This study will explore the cultural appropriateness of government-initiated evaluation of health outcomes, and make recommendations about how these evaluations can be better suited to Aboriginal people. The lessons from this study will be of interest to those conducting research or quality assessment activities related to PROMs, and those involved with Aboriginal-focused research and project implementation.

Stanford Neuromodulation Therapy (SNT): A Double-Blind Randomized Controlled Trial.

OBJECTIVE: Depression is the leading cause of disability worldwide, and half of patients with depression have treatment-resistant depression. Intermittent theta-burst stimulation (iTBS) is approved by the U.S. Food and Drug Administration for the treatment of treatment-resistant depression but is limited by suboptimal efficacy and a 6-week duration. The authors addressed these limitations by developing a neuroscience-informed accelerated iTBS protocol, Stanford neuromodulation therapy (SNT; previously referred to as Stanford accelerated intelligent neuromodulation therapy, or SAINT). This protocol was associated with a remission rate of ∼90% after 5 days of open-label treatment. Here, the authors report the results of a sham-controlled double-blind trial of SNT for treatment-resistant depression. METHODS: Participants with treatment-resistant depression currently experiencing moderate to severe depressive episodes were randomly assigned to receive active or sham SNT. Resting-state functional MRI was used to individually target the region of the left dorsolateral prefrontal cortex most functionally anticorrelated with the subgenual anterior cingulate cortex. The primary outcome was score on the Montgomery-Åsberg Depression Rating Scale (MADRS) 4 weeks after treatment. RESULTS: At the planned interim analysis, 32 participants with treatment-resistant depression had been enrolled, and 29 participants who continued to meet inclusion criteria received either active (N=14) or sham (N=15) SNT. The mean percent reduction from baseline in MADRS score 4 weeks after treatment was 52.5% in the active treatment group and 11.1% in the sham treatment group. CONCLUSIONS: SNT, a high-dose iTBS protocol with functional-connectivity-guided targeting, was more effective than sham stimulation for treatment-resistant depression. Further trials are needed to determine SNT's durability and to compare it with other treatments.

Adhesive Taping Shows Better Cosmetic Outcomes Than Tissue Adhesives for Sutured Upper Extremity Incisions: A Single-Blind Prospective Randomized Controlled Trial.

Adhesive taping is commonly used to reinforce wound closure and approximate minor lacerations. Recently, tissue adhesives such as 2-octylcyanoacrylate have gained popularity because of their high tensile strength, bacteriostatic properties, and spontaneous peeling. We sought to evaluate the cosmetic result of upper extremity incisions closed primarily by subcuticular suture, randomizing the application of tissue adhesive vs adhesive taping to different halves of the same surgical incision. Subjects were recruited from patients undergoing common procedures at the senior surgeon's hand surgery clinic. After primary closure, we applied either quarter-inch adhesive tape or tissue adhesive to the proximal and distal aspects of the wounds, based on a preoperative randomization protocol. We assessed the scars at approximately 3 months (range, 2-5 months). Subjects completed a validated scar assessment questionnaire, and a blinded photograph was obtained to allow 2 independent surgeons to assess the scar. Mean age was 63 years (SD, 11.8 years; range, 21-88 years); 56% of patients were women, and 44% were men. Most of the incisions were open carpal tunnel release and thumb carpometacarpal arthroplasty (14 each). Adhesive taping showed a better overall mean score based on evaluation by the hand surgeons, a finding that was statistically significant. The greatest differences were observed between color and size, but no subcategories were significantly different. Patients reported nonstatistical, but slightly better overall cosmetic outcomes with adhesive taping rather than tissue adhesive. Adhesive strips provide a modest but significant improvement in cosmetic outcomes vs more expensive tissue adhesive. Future evaluation of closure methods that evaluate cost, speed of application, suture technique, and dressing will optimize scar appearance. [Orthopedics. 2022;45(1):e42-e46.].

A systematic review of patient-reported outcome measures to assess postpartum pain using Consensus Based Standards for the Selection of Health Measurement Instruments (COSMIN) guidelines.

BACKGROUND: We performed a systematic review using Consensus Based Standards for the Selection of Health Measurement Instruments (COSMIN) guidelines to identify the best available patient-reported outcome measure (PROM) of postpartum pain. METHODS: This review follows COSMIN guidelines. We searched four databases with no date limiters, for previously identified validated PROMs used to assess postpartum pain. PROMs evaluating more than one author-defined domain of postpartum pain were assessed. We sought studies evaluating psychometric properties. An overall rating was then assigned based upon COSMIN analysis, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to assess the level of evidence for psychometric properties of included PROMs. These assessments were used to make recommendations and identify the best PROM to assess postpartum pain. RESULTS: We identified 19 studies using seven PROMs (involving 3511 women), which evaluated postpartum pain. All included studies evaluated ≥1 psychometric property of the included PROMs. An adequate number of pain domains was assessed by the Brief Pain Inventory (BPI), Short Form-BPI (SF-BPI), and McGill Pain Questionnaire (MPQ). The SF-BPI was the only PROM to demonstrate adequate content validity and at least a low-level of evidence for sufficient internal consistency, resulting in a Class A recommendation (the best performing instrument, recommended for use). CONCLUSION: SF-BPI is the best currently available PROM to assess postpartum pain. However, it fails to assess several important domains and only just met the criteria for a Class A recommendation. Future studies are warranted to develop, evaluate, and implement a new PROM designed to specifically assess postpartum pain.

Sugar sweetened beverage consumption is positively associated with Klotho levels at two years of age in LatinX youth.

BACKGROUND: Klotho is an anti-aging protein mainly expressed in the kidneys with a smaller amount expressed in adipose tissue. Klotho effects include roles in reducing oxidative stress, insulin signaling, adipogenesis and glucose metabolism. Few studies have investigated the role of dietary factors such as sugar sweetened beverages (SSBs) on serum α-klotho levels in young children. METHODS: Data was collected from 60 low-income Latina pregnant women and their infants in San Francisco from birth until 2 years of life and examined for associations between dietary factors and child secreted α-klotho protein levels at 2 years. RESULTS: Mean α-klotho levels were 1782.96 ± 874.56 pg/mL at 2 years of age. Any consumption of SSBs was independently associated with increased α-klotho levels (Beta = 682.79, 95%CI 67.50, 1298.09; p = 0.03). Household income ranging from $25,000 to $50,000 was also correlated to higher levels of α-klotho in children compared with lower income levels (<$25,000) (Beta = 1613.35, 95%CI 527.37, 2699.33; p = 0.005). CONCLUSIONS: The positive association between SSB intake and α-klotho levels at 2 years may reflect higher phosphate levels consistent with SSB intake. Higher socioeconomic status may be a proxy for reduced stress exposure in children, also associated with higher α-klotho levels. Future studies should evaluate the early impact of exposures to SSBs, stress and accelerated aging in children.

Obesity at Age 6 Months Is Associated with Shorter Preschool Leukocyte Telomere Length Independent of Parental Telomere Length.

OBJECTIVE: To assess whether early modifiable dietary factors and obesity measures are associated with leukocyte telomere length at 3-5 years of age after controlling for the heritability of leukocyte telomere length in a prospective cohort of low-income Latina mothers and their children in San Francisco. STUDY DESIGN: We analyzed data from the Latinx, Eating and Diabetes cohort, a prospective study of 97 woman-infant dyads. We used linear regression models to evaluate associations between early dietary factors and obesity measures and child leukocyte telomere length at 3-5 years of age. Multivariable models included child age at the time of telomere collection, breastfeeding at 6 months (yes/no), obesity at 6 months, maternal education, child sex, and maternal and paternal leukocyte telomere length. RESULTS: Data for 73 of the 97 children at 3-5 years of age were analyzed. Any breastfeeding at 6 months was positively associated (ß = 0.14; P = .02) and obesity at 6 months was negatively associated (ß = -0.21; P < .001) with leukocyte telomere length in bivariate analyses. In multivariable models including parental leukocyte telomere length, obesity at 6 months was associated with a shorter leukocyte telomere length at 3-5 years of age (ß = -0.15; P = .02). Analyses of dietary factors showed high flavored milk consumption at 3 years of age was associated with shorter leukocyte telomere length after adjustment for possible confounders. CONCLUSIONS: In a low-income Latinx population, obesity at 6 months of age is negatively associated with cellular health at 3-5 years of age after controlling for genetic factors (parental leukocyte telomere length) associated with leukocyte telomere length. Early life obesity may be more deleterious for cellular health than obesity later in childhood.

Developing Virtual Reality Trauma Training Experiences Using 360-Degree Video: Tutorial.

Historically, medical trainees were educated in the hospital on real patients. Over the last decade, there has been a shift to practicing skills through simulations with mannequins or patient actors. Virtual reality (VR), and in particular, the use of 360-degree video and audio (cineVR), is the next-generation advancement in medical simulation that has novel applications to augment clinical skill practice, empathy building, and team training. In this paper, we describe methods to design and develop a cineVR medical education curriculum for trauma care training using real patient care scenarios at an urban, safety-net hospital and Level 1 trauma center. The purpose of this publication is to detail the process of finding a cineVR production partner; choosing the camera perspectives; maintaining patient, provider, and staff privacy; ensuring data security; executing the cineVR production process; and building the curriculum.

A Trimeric Autotransporter Enhances Biofilm Cohesiveness in Yersinia pseudotuberculosis but Not in Yersinia pestis.

Cohesion of biofilms made by Yersinia pestis and Yersinia pseudotuberculosis has been attributed solely to an extracellular polysaccharide matrix encoded by the hms genes (Hms-dependent extracellular matrix [Hms-ECM]). However, mutations in the Y. pseudotuberculosis BarA/UvrY/CsrB regulatory cascade enhance biofilm stability without dramatically increasing Hms-ECM production. We found that treatment with proteinase K enzyme effectively destabilized Y. pseudotuberculosiscsrB mutant biofilms, suggesting that cell-cell interactions might be mediated by protein adhesins or extracellular matrix proteins. We identified an uncharacterized trimeric autotransporter lipoprotein (YPTB2394), repressed by csrB, which has been referred to as YadE. Biofilms made by a ΔyadE mutant strain were extremely sensitive to mechanical disruption. Overexpression of yadE in wild-type Y. pseudotuberculosis increased biofilm cohesion, similar to biofilms made by csrB or uvrY mutants. We found that the Rcs signaling cascade, which represses Hms-ECM production, activated expression of yadE The yadE gene appears to be functional in Y. pseudotuberculosis but is a pseudogene in modern Y. pestis strains. Expression of functional yadE in Y. pestis KIM6+ weakened biofilms made by these bacteria. This suggests that although the YadE autotransporter protein increases Y. pseudotuberculosis biofilm stability, it may be incompatible with the Hms-ECM production that is essential for Y. pestis biofilm production in fleas. Inactivation of yadE in Y. pestis may be another instance of selective gene loss in the evolution of flea-borne transmission by this species.IMPORTANCE The evolution of Yersinia pestis from its Y. pseudotuberculosis ancestor involved gene acquisition and gene losses, leading to differences in biofilm production. Characterizing the unique biofilm features of both species may provide better understanding of how each adapts to its specific niches. This study identifies a trimeric autotransporter, YadE, that promotes biofilm stability of Y. pseudotuberculosis but which has been inactivated in Y. pestis, perhaps because it is not compatible with the Hms polysaccharide that is crucial for biofilms inside fleas. We also reveal that the Rcs signaling cascade, which represses Hms expression, activates YadE in Y. pseudotuberculosis The ability of Y. pseudotuberculosis to use polysaccharide or YadE protein for cell-cell adhesion may help it produce biofilms in different environments.

A Randomized Controlled Trial of the Lowest Effective Dose of Acetazolamide for Acute Mountain Sickness Prevention.

BACKGROUND: Acetazolamide is the most common medication used for acute mountain sickness prevention, with speculation that a reduced dose may be as efficacious as standard dosing with fewer side effects. METHODS: This double-blind, randomized, controlled noninferiority trial compared acetazolamide 62.5 mg twice daily to the standard dose acetazolamide 125 mg twice daily starting the evening prior to ascent from 1240 m (4100 ft) to 3810 m (12,570 ft) over 4 hours. The primary outcome was acute mountain sickness incidence (ie, headache, Lake Louise Questionnaire ≥3, and another symptom). RESULTS: A total of 106 participants were analyzed, with 51 (48%) randomized to 125 mg and 55 (52%) to 62.5 mg, with a combined acute mountain sickness incidence of 53 (50%) and mean severity of 3 (± 2.1). The 62.5-mg group failed to fall within the prespecified 26% noninferiority margin for acute mountain sickness incidence (62.5 mg = 30 [55%] vs 125 mg = 23 [45%], 95% confidence interval [CI] -11% to 30%). Participants in the 62.5-mg group had a higher risk of acute mountain sickness (odds ratio = 1.5, 95% CI 0.7-3.2) and moderate acute mountain sickness (odds ratio = 1.8, 95% CI 0.6-5.9), with a number needed to harm (NNH) of 9, with a number needed to treat (NNT) in the 125-mg group of 4.8. Increased acute mountain sickness incidence and symptom severity corresponded to lower weight-based and body mass index dosing, with similar side effects between groups. CONCLUSION: Acetazolamide 62.5 mg twice daily failed to demonstrate equal effectiveness to 125 mg twice daily for prevention of acute mountain sickness. With increased risk and no demonstrable symptomatic or physiologic benefits, acetazolamide 62.5 mg twice daily should not be recommended for acute mountain sickness prevention.

Stanford Accelerated Intelligent Neuromodulation Therapy for Treatment-Resistant Depression.

OBJECTIVE: New antidepressant treatments are needed that are effective, rapid acting, safe, and tolerable. Intermittent theta-burst stimulation (iTBS) is a noninvasive brain stimulation treatment that has been approved by the U.S. Food and Drug Administration for treatment-resistant depression. Recent methodological advances suggest that the current iTBS protocol might be improved through 1) treating patients with multiple sessions per day at optimally spaced intervals, 2) applying a higher overall pulse dose of stimulation, and 3) precision targeting of the left dorsolateral prefrontal cortex (DLPFC) to subgenual anterior cingulate cortex (sgACC) circuit. The authors examined the feasibility, tolerability, and preliminary efficacy of Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT), an accelerated, high-dose resting-state functional connectivity MRI (fcMRI)-guided iTBS protocol for treatment-resistant depression. METHODS: Twenty-two participants with treatment-resistant depression received open-label SAINT. fcMRI was used to individually target the region of the left DLPFC most anticorrelated with sgACC in each participant. Fifty iTBS sessions (1,800 pulses per session, 50-minute intersession interval) were delivered as 10 daily sessions over 5 consecutive days at 90% resting motor threshold (adjusted for cortical depth). Neuropsychological testing was conducted before and after SAINT. RESULTS: One participant withdrew, leaving a sample size of 21. Nineteen of 21 participants (90.5%) met remission criteria (defined as a score <11 on the Montgomery-Åsberg Depression Rating Scale). In the intent-to-treat analysis, 19 of 22 participants (86.4%) met remission criteria. Neuropsychological testing demonstrated no negative cognitive side effects. CONCLUSIONS: SAINT, an accelerated, high-dose, iTBS protocol with fcMRI-guided targeting, was well tolerated and safe. Double-blinded sham-controlled trials are needed to confirm the remission rate observed in this initial study.

Attenuation of antidepressant and antisuicidal effects of ketamine by opioid receptor antagonism.

We recently reported that naltrexone blocks antidepressant effects of ketamine in humans, indicating that antidepressant effects of ketamine require opioid receptor activation. However, it is unknown if opioid receptors are also involved in ketamine's antisuicidality effects. Here, in a secondary analysis of our recent clinical trial, we test whether naltrexone attenuates antisuicidality effects of ketamine. Participants were pretreated with naltrexone or placebo prior to intravenous ketamine in a double-blinded crossover design. Suicidality was measured with the Hamilton Depression Rating Scale item 3, Montgomery-Åsberg Depression Rating Scale item 10, and Columbia Suicide Severity Rating Scale. In the 12 participants who completed naltrexone and placebo conditions, naltrexone attenuated the antisuicidality effects of ketamine on all three suicidality scales/subscales (linear mixed model, fixed pretreatment effect, p < 0.01). Results indicate that opioid receptor activation plays a significant role in the antisuicidality effects of ketamine.

Attenuation of Antidepressant Effects of Ketamine by Opioid Receptor Antagonism.

OBJECTIVE: In addition to N-methyl-d-aspartate receptor antagonism, ketamine produces opioid system activation. The objective of this study was to determine whether opioid receptor antagonism prior to administration of intravenous ketamine attenuates its acute antidepressant or dissociative effects. METHOD: In a proposed double-blind crossover study of 30 adults with treatment-resistant depression, the authors performed a planned interim analysis after studying 14 participants, 12 of whom completed both conditions in randomized order: placebo or 50 mg of naltrexone preceding intravenous infusion of 0.5 mg/kg of ketamine. Response was defined as a reduction ≥50% in score on the 17-item Hamilton Depression Rating Scale (HAM-D) score on postinfusion day 1. RESULTS: In the interim analysis, seven of 12 adults with treatment-resistant depression met the response criterion during the ketamine plus placebo condition. Reductions in 6-item and 17-item HAM-D scores among participants in the ketamine plus naltrexone condition were significantly lower than those of participants in the ketamine plus placebo condition on postinfusion days 1 and 3. Secondary analysis of all participants who completed the placebo and naltrexone conditions, regardless of the robustness of response to ketamine, showed similar results. There were no differences in ketamine-induced dissociation between conditions. Because naltrexone dramatically blocked the antidepressant but not the dissociative effects of ketamine, the trial was halted at the interim analysis. CONCLUSIONS: The findings suggest that ketamine's acute antidepressant effect requires opioid system activation. The dissociative effects of ketamine are not mediated by the opioid system, and they do not appear sufficient without the opioid effect to produce the acute antidepressant effects of ketamine in adults with treatment-resistant depression.

Screening for chronic kidney disease in a community-based diabetes cohort in rural Guatemala: a cross-sectional study.

OBJECTIVE: Screening is a key strategy to address the rising burden of chronic kidney disease (CKD) in low-income and middle-income countries. However, there are few reports regarding the implementation of screening programmes in resource-limited settings. The objectives of this study are to (1) to share programmatic experiences implementing CKD screening in a rural, resource-limited setting and (2) to assess the burden of renal disease in a community-based diabetes programme in rural Guatemala. DESIGN: Cross-sectional assessment of glomerular filtration rate (GFR) and urine albumin. SETTING: Central Highlands of Guatemala. PARTICIPANTS: We enrolled 144 adults with type 2 diabetes in a community-based CKD screening activity carried out by the sponsoring institution. OUTCOME MEASURES: Prevalence of renal disease and risk of CKD progression using Kidney Disease: Improving Global Outcomes definitions and classifications. RESULTS: We found that 57% of the sample met GFR and/or albuminuria criteria suggestive of CKD. Over half of the sample had moderate or greater increased risk for CKD progression, including nearly 20% who were classified as high or very high risk. Hypertension was common in the sample (42%), and glycaemic control was suboptimal (mean haemoglobin A1c 9.4%±2.5% at programme enrolment and 8.6%±2.3% at time of CKD screening). CONCLUSIONS: The high burden of renal disease in our patient sample suggests an imperative to better understand the burden and risk factors of CKD in Guatemala. The implementation details we share reveal the tension between evidence-based CKD screening versus screening that can feasibly be delivered in resource-limited global settings.