Enterococci enhance Clostridioides difficile pathogenesis.

Enteric pathogens are exposed to a dynamic polymicrobial environment in the gastrointestinal tract1. This microbial community has been shown to be important during infection, but there are few examples illustrating how microbial interactions can influence the virulence of invading pathogens2. Here we show that expansion of a group of antibiotic-resistant, opportunistic pathogens in the gut-the enterococci-enhances the fitness and pathogenesis of Clostridioides difficile. Through a parallel process of nutrient restriction and cross-feeding, enterococci shape the metabolic environment in the gut and reprogramme C. difficile metabolism. Enterococci provide fermentable amino acids, including leucine and ornithine, which increase C. difficile fitness in the antibiotic-perturbed gut. Parallel depletion of arginine by enterococci through arginine catabolism provides a metabolic cue for C. difficile that facilitates increased virulence. We find evidence of microbial interaction between these two pathogenic organisms in multiple mouse models of infection and patients infected with C. difficile. These findings provide mechanistic insights into the role of pathogenic microbiota in the susceptibility to and the severity of C. difficile infection.

Cerclage plus Adjuvant Vaginal Progesterone for Preterm Birth Prevention in Patients with a Short or Dilated Cervix without Prior Preterm Birth.

OBJECTIVE: The primary objective was to determine if vaginal progesterone following cerclage for cervical length <10 mm or cervical dilation in patients without a history of spontaneous preterm birth (sPTB) decreased the risk of preterm birth at <34 weeks' gestation compared with cerclage alone. Secondary objectives were to determine if vaginal progesterone following cerclage (1) decreased the risk of preterm birth at <24, <28, and <37 weeks' gestation and (2) increased the latency period from cerclage placement to delivery compared with treatment with cerclage alone. STUDY DESIGN: Multicenter retrospective cohort study from 2015 to 2020 of singleton pregnancies, without prior sPTB, who had cerclage placement <24 weeks' gestation for cervical length <10 mm or cervical dilation. Exposure defined as cerclage plus vaginal progesterone postoperatively (dual therapy) and unexposed as cerclage alone (monotherapy), based on surgeon preference. RESULTS: We included 122 patients, 78 (64%) treated with dual therapy and 44 (36%) treated with monotherapy. In the crude analysis, dual therapy was associated with a lower risk of delivery at <28 weeks' gestation (13%) compared with monotherapy (34%; crude risk ratio: 0.38 [95% confidence interval, CI: 0.19-0.75]). When adjusted for preoperative vaginal progesterone, results were attenuated (adjusted risk ratio: 0.45 [95% CI: 0.20-1.01]). In both the crude and adjusted analyses, the risk of sPTB was not statistically different at <24, <34 or <37 weeks' gestation. Dual therapy was associated with a greater pregnancy latency from cerclage to delivery (16.3 vs. 14.4 weeks; p = 0.04), and greater gestational age at delivery (37.3 vs. 35.8 weeks' gestation; p = 0.02) compared with monotherapy. CONCLUSION: While not statistically significant, the risk of sPTB was lower at all gestational ages studied in patients treated with dual therapy compared with monotherapy. Dual therapy was associated with longer pregnancy latency and greater gestational age at delivery compared with monotherapy. KEY POINTS: · Dual therapy did not decrease preterm birth risk compared with monotherapy.. · Dual therapy prolonged pregnancy compared with monotherapy.. · Dual therapy can be considered but further studies are needed..

Risk-Factor Based Lead Screening and Correlation with Blood Lead Levels in Pregnancy.

OBJECTIVES: Lead exposure has devastating neurologic consequences for children and may begin in utero. The American College of Obstetricians and Gynecologists recommends prenatal lead screening using a risk factor-based approach rather than universal blood testing. The clinical utility of this approach has not been studied. We evaluated a risk-factor based questionnaire to detect elevated blood lead levels in pregnancy. METHODS: We performed a secondary analysis of a cohort of parturients enrolled to evaluate the association of lead with hypertensive disorders of pregnancy. We included participants in this analysis if they had a singleton pregnancy ≥ 34 weeks' gestation with blood lead levels recorded. Participants completed a lead risk factor survey modified for pregnancy. We defined elevated blood lead as ≥ 2 µg/dL, as this was the clinically reportable level. RESULTS: Of 102 participants enrolled in the cohort, 92 had blood lead measured as part of the study. The vast majority (78%) had 1 or more risk factor for elevated lead using the questionnaire yet none had clinical blood lead testing during routine visits. Only two participants (2.2%) had elevated blood lead levels. The questionnaire had high sensitivity but poor specificity for predicting detectable lead levels (sensitivity 100%, specificity 22%). CONCLUSIONS FOR PRACTICE: Prenatal risk-factor based lead screening appears underutilized in practice and does not adequately discriminate between those with and without elevated blood levels. Given the complexity of the risk factor-based approach and underutilization, the benefit and cost-effectiveness of universal lead testing should be further explored.

Regional differences in utilization of 17α-hydroxyprogesterone caproate (17-OHP).

OBJECTIVES: To describe regional differences in utilization of 17α-hydroxyprogesterone caproate (17-OHP). METHODS: Retrospective cohort study of a large, US commercial managed care plan claims database with pharmacy coverage from 2008 to 2018. Singleton pregnancies with at least one prior spontaneous preterm birth (sPTB) were included. Regional and state-based differences in 17-OHP use were compared. Data were analyzed using t-tests and Fisher's exact tests. RESULTS: Of the 4,514 individuals with an indication for 17-OHP, 580 (12.8%) were prescribed 17-OHP. Regional and state-based differences in 17-OHP utilization were identified; Northeast 15.7%, Midwest 13.7%, South 12.0%, and West 10.4% (p=0.003). CONCLUSIONS: While significant regional differences in 17-OHP utilization were demonstrated, 17-OHP utilization remained low despite this cohort having insurance through a US commercial managed care plan. Suboptimal utilization demonstrates a disconnect between research and uptake in clinical practice. This underscores a need for implementation science in obstetrics to translate updated recommendations more effectively and efficiently into clinical practice.

Effectiveness of 17-OHP for Prevention of Recurrent Preterm Birth: A Retrospective Cohort Study.

OBJECTIVE: 17-α-hydroxyprogesterone caproate (17-OHP) has been recommended by professional societies for the prevention of recurrent preterm birth, but subsequent clinical studies have reported conflicting efficacy results. This study aimed to contribute to the evidence base regarding the effectiveness of 17-OHP in clinical practice using real-world data. STUDY DESIGN: A total of 4,422 individuals meeting inclusion criteria representing recurrent spontaneous preterm birth (sPTB) were identified in a database of insurance claims, and 568 (12.8%) received 17-OHP. Crude and propensity score-matched recurrence rates and risk ratios (RRs) for the association of receiving 17-OHP on recurrent sPTB were calculated. RESULTS: Raw sPTB recurrence rates were higher among those treated versus not treated; after propensity score matching, no association was detected (26.3 vs. 23.8%, RR = 1.1, 95% CI: 0.9-1.4). CONCLUSION: We failed to identify a beneficial effect of 17-OHP for the prevention of spontaneous recurrent preterm birth in our observational, U.S. based cohort. KEY POINTS: · •We observed higher risk for sPTB in the group receiving 17-OHP in the unmatched analysis. · •After propensity-score matching, we still failed to identify a beneficial effect of 17-OHP on sPTB. · •Sensitivity analyses demonstrated robustness to the inclusion criteria and modeling assumptions..

Attachment and thought problems in an adolescent inpatient sample: The mediational role of theory of mind.

BACKGROUND: Previous research has documented increased incidence of insecure attachment and theory of mind (ToM) deficits in individuals experiencing psychotic disorders. ToM has been theorized as a possible mediator of the relation between attachment and psychosis (Korver-Nieberg et al., 2014). The current study sought to extend this area of research to adolescents for the first time by examining adolescent-parent attachment and ToM in inpatient adolescents. METHODS: Participants were 362 inpatient adolescents and their parents; participants completed the Child Attachment Interview, Movie for the Assessment of Social Cognition, Youth Self Report, and Child Behavior Checklist. RESULTS: Bivariate correlations indicated that attachment coherence (a marker of security) was significantly and positively correlated with ToM abilities, and that low attachment coherence and poor ToM performance were each associated with increased youth- and parent-reported thought problems. Mediational models indicated that ToM mediated the relation between insecure attachment and thought problems according to both parent- and self-report. CONCLUSIONS: The results of the current study provide support for a model in which impairments in ToM contribute to the frequently documented association between insecure attachment and emerging psychotic symptoms. Theoretical and clinical implications of these results are discussed, including the potential support for ToM-based interventions for early psychotic symptoms.

Development and evaluation of a writing retreat program to build community and promote productivity in academic hospital medicine.

BACKGROUND: Scientific writing is a core component of academic hospital medicine, and yet finding time to engage in deeply focused writing is difficult in part due to the highly clinical, 24/7 nature of the specialty that can limit opportunities for writing-focused collaboration and mentorship. OBJECTIVE: Our objective was to develop and evaluate an academic writing retreat program. METHODS: We drafted a set of key retreat features to guide implementation of a 3-day, 2-night retreat program held within a 2 h radius of our hospital. Agendas included writing blocks ranging from 45 to 90 min interspersed with breaks and opportunities for feedback, exercise, and preparing meals together. After each retreat, we distributed an evaluation with multiple choice and free text response options to characterize retreat helpfulness and later gathered data on the status of each paper and grant worked on. RESULTS: We held 4 retreats between September 2022 and October 2023, engaging 18 faculty and fellows at a cost of $296 per attendee per retreat. In evaluations, nearly 80% reported that the retreat was extremely helpful, and comments praised the highly mentored environment, enriching community of colleagues, and release from commitments that get in the way of writing. Of the 24 papers attendees worked on, 12 have been accepted and 6 are under review. Of the 4 grant proposals, 2 are under review. CONCLUSIONS: We implemented a low-cost, productive writing retreat program that attendees reported was helpful in supporting deep work and represented a meaningful step toward building a community centered around academic writing.

What the COVID-19 Pandemic Teaches Us About Pediatric Iatrogenic Risk.

Iatrogenic morbidity and mortality are pediatric public health risks. This article considers how the COVID-19 pandemic illuminates these risks, as clinicians have been forced to navigate increased diagnostic uncertainty and changes to pediatric health care systems, including closures, limited staffing, and new infection control guidelines.

Clinical pathways and diagnostic reasoning: A qualitative study of pediatric residents' and hospitalists' perceptions.

BACKGROUND: Clinical pathways are evidence-based guidelines adapted to local settings. They have been shown to improve patient outcomes and reduce resource utilization. However, it is unknown how physicians integrate clinical pathways into their clinical reasoning. METHODS: We conducted a single-center qualitative study involving one-on-one semi-structured interviews of pediatric residents and pediatric hospitalist attendings between August 2021 and March 2022. Interviews were audio-recorded and professionally transcribed. We utilized a qualitative descriptive framework to code data and identify themes. RESULTS: We interviewed 15 pediatric residents and 12 pediatric hospitalists. Thematic analysis of interview transcripts revealed four themes related to physician utilization of and experience with clinical pathways: (1) utility as a tool, (2) means of standardizing care, (3) reflection of institutional culture, and (4) element of the dynamic relationship with the clinician diagnostic process. These themes were generally common to both residents and attending physicians; however, some differences existed and are noted when they occurred. CONCLUSIONS: Clinical pathways are part of many clinicians' diagnostic processes. Pathways can standardize care, influence the diagnostic process, and express local institutional culture. Further research is required to ascertain the optimal clinical pathway design to augment and not inhibit the clinician's diagnostic process.

Medication Rounds: A Tool to Promote Medication Safety for Children with Medical Complexity.

Children with medical complexity (CMC) often have lengthy medication lists and are at risk of experiencing suboptimal medication management. This tool tutorial describes a novel and pragmatic strategy for the development and implementation of medication rounds, a model that promotes medication safety for hospitalized CMC. An interprofessional group designed and implemented a pharmacy-led medication rounding care model, in which clinicians and pharmacists partner weekly to conduct reviews of all patient medications on a general pediatrics CMC team using a comprehensive checklist. This approach fosters medication safety for hospitalized CMC and could be adapted to other complex inpatient populations.

Nonsteroidal anti-inflammatory drugs sensitize epithelial cells to Clostridioides difficile toxin-mediated mitochondrial damage.

Clostridioides difficile damages the colonic mucosa through the action of two potent exotoxins. Factors shaping C. difficile pathogenesis are incompletely understood but are likely due to the ecological factors in the gastrointestinal ecosystem, mucosal immune responses, and environmental factors. Little is known about the role of pharmaceutical drugs during C. difficile infection (CDI), but recent studies have demonstrated that nonsteroidal anti-inflammatory drugs (NSAIDs) worsen CDI. The mechanism underlying this phenomenon remains unclear. Here, we show that NSAIDs exacerbate CDI by disrupting colonic epithelial cells (CECs) and sensitizing cells to C. difficile toxin-mediated damage independent of their canonical role of inhibiting cyclooxygenase (COX) enzymes. Notably, we find that NSAIDs and C. difficile toxins target the mitochondria of CECs and enhance C. difficile toxin-mediated damage. Our results demonstrate that NSAIDs exacerbate CDI by synergizing with C. difficile toxins to damage host cell mitochondria. Together, this work highlights a role for NSAIDs in exacerbating microbial infection in the colon.

Resident Communication With Patients and Families Preferring Languages Other Than English.

OBJECTIVES: Patients and families preferring languages other than English (LOE) often experience inequitable communication with their health care providers, including the underutilization of professional interpretation. This study had 2 aims: to characterize resident-perceived communication with families preferring LOE and to evaluate the impact of language preference on frequency of resident interactions with hospitalized patients and families. METHODS: This was a cross-sectional study at a quaternary care children's hospital. We developed a questionnaire for residents regarding their interactions with patients preferring LOE. We concurrently developed a communication tracking tool to measure the frequency of resident communication events with hospitalized patients. Data were analyzed with logistic and Poisson regression models. RESULTS: Questionnaire results demonstrated a high level of resident comfort with interpretation, though more than 30% of residents reported "sometimes" or "usually" communicating with families preferring LOE without appropriate interpretation (response rate, 47%). The communication tracking tool was completed by 36 unique residents regarding 151 patients, with a 95% completion rate. Results demonstrated that patients and families preferring LOE were less likely to be present on rounds compared with their counterparts preferring English (adjusted odds ratio, 0.17; 95% confidence interval [CI], 0.07-0.39). Similarly, patients and families preferring LOE were less likely to receive a resident update after rounds (adjusted odds ratio, 0.29; 95% CI, 0.13-0.62) and received fewer resident updates overall (incidence rate ratio, 0.45; 95% CI, 0.30-0.69). CONCLUSIONS: Hospitalized patients and families preferring LOE experience significant communication-related inequities. Ongoing efforts are needed to promote equitable communication with this population and should consider the unique role of residents.

Opportunities for Diagnostic Improvement Among Pediatric Hospital Readmissions.

OBJECTIVES: Diagnostic errors, termed "missed opportunities for improving diagnosis" (MOIDs), are known sources of harm in children but have not been well characterized in pediatric hospital medicine. Our objectives were to systematically identify and describe MOIDs among general pediatric patients who experienced hospital readmission, outline improvement opportunities, and explore factors associated with increased risk of MOID. PATIENTS AND METHODS: Our retrospective cohort study included unplanned readmissions within 15 days of discharge from a freestanding children's hospital (October 2018-September 2020). Health records from index admissions and readmissions were independently reviewed and discussed by practicing inpatient physicians to identify MOIDs using an established instrument, SaferDx. MOIDs were evaluated using a diagnostic-specific tool to identify improvement opportunities within the diagnostic process. RESULTS: MOIDs were identified in 22 (6.3%) of 348 readmissions. Opportunities for improvement included: delay in considering the correct diagnosis (n = 11, 50%) and failure to order needed test(s) (n = 10, 45%). Patients with MOIDs were older (median age: 3.8 [interquartile range 1.5-11.2] vs 1.0 [0.3-4.9] years) than patients without MOIDs but similar in sex, primary language, race, ethnicity, and insurance type. We did not identify conditions associated with higher risk of MOID. Lower respiratory tract infections accounted for 26% of admission diagnoses but only 1 (4.5%) case of MOID. CONCLUSIONS: Standardized review of pediatric readmissions identified MOIDs and opportunities for improvement within the diagnostic process, particularly in clinician decision-making. We identified conditions with low incidence of MOID. Further work is needed to better understand pediatric populations at highest risk for MOID.

A Trainee-Led Quality Improvement Project Using Change Management Theory to Improve Bedside Rounding.

OBJECTIVE: The coronavirus disease 2019 pandemic disrupted the practice of family-centered rounds. After the height of the pandemic, a trainee-led team identified a low percentage of bedside rounds on general pediatrics resident teams and combined a quality improvement framework and change management theory to increase bedside rounds. Initial efforts focused on a single general pediatrics team with the aim to increase bedside rounds from 18% to 50% within 6 months and sustain improvement for 12 months. A second aim was to increase bedside rounds from 7% to 50% for all general pediatrics resident teams within 6 months of spread. METHODS: The Model for Improvement informed the identification of 3 primary drivers of bedside rounds: knowledge, culture, and logistics. Twelve plan-do-study-act (PDSA) cycles were implemented. Measures included the percentage of bedside rounds (primary outcome), caregiver attendance (secondary outcome), and nurse attendance and rounding time (balancing measures). RESULTS: For the initial team, 13 522 patient days were analyzed for the primary outcome with the average percentage of weekly bedside rounds increasing from 18% to 89% with 12 months of sustained improvement. The spread of the intervention to all teams revealed an increase in bedside rounding from 7% to 54%. The most significant improvements occurred after PDSA cycle 2, a communication bundle, and PDSA cycle 5, when the project was spread to all teams. CONCLUSIONS: This trainee-led initiative reveals the strength of the incorporation of change management theory within a quality improvement framework, resulting in rapid and sustainable increase in bedside rounds.

Spontaneous version after preterm prelabor rupture of membranes.

BACKGROUND: Preterm prelabor rupture of membranes (PPROM), defined as rupture of membranes before the onset of labor at < 37 weeks' gestation, affects approximately 3% of all pregnancies. For PPROM prior to 34 weeks' gestation, in the absence of contraindications to expectant management, antibiotics are administered to increase the latency period and reduce the incidence of maternal and neonatal infection. The latency period additionally provides an opportunity for fetal presentation to change, which impacts the mode of delivery. It is important to better understand the incidence of spontaneous version after PPROM to enhance patient counseling with regard to the mode of delivery. OBJECTIVE: To determine the incidence of discordant fetal presentation, resulting from spontaneous version, between admission for PPROM and time of delivery for cephalic and non-cephalic fetuses among patients diagnosed with PPROM prior to 34 weeks' gestation and to compare characteristics of those with and without discordant fetal presentation. STUDY DESIGN: We performed a retrospective cohort study of singleton pregnancies diagnosed with PPROM identified using ICD-9/10-CM codes, < 34 weeks' gestation, admitted to a tertiary care center's antepartum service from 2011-2018. Patients were included if the fetal presentation was documented by ultrasound within 48 h of admission and PPROM, and delivery occurred >24 h after PPROM. Data are presented as proportions, median (interquartile range) or risk ratio and 95% confidence interval. RESULTS: We included 209 patients. Patient age, body mass index, parity, and race/ethnicity were similar among patients with cephalic and non-cephalic fetal presentations at admission. Patients with cephalic presentation at time of PPROM presented at a later gestational age than patients with a non-cephalic presentation. Among patients with a cephalic presentation at admission, the incidence of non-cephalic presentation at delivery was 11.7% (19/162), whereas with non-cephalic presentation at admission, the incidence of cephalic presentation at delivery was 21.3% (10/47). While there was an increased risk of spontaneous version resulting in a discordant presentation at delivery with non-cephalic presentation, this relationship was attenuated and not significant when adjusted for gestational age at time of PPROM.​ Patients with discordant presentation presented with PPROM at an earlier gestational age and had a longer latency period compared to patients with a concordant presentation. Patient age, body mass index, amniotic fluid assessment at admission, and infant birth weight were similar in those with and without a change in fetal presentation. CONCLUSION: Discordant fetal presentation resulting from spontaneous version from cephalic to non-cephalic presentation after PPROM occurred in 11.7% (19/162) of patients, while discordant presentation from non-cephalic to cephalic presentation occurred in 21.3% (10/47) of patients. Given the limited published data on spontaneous version after PPROM these results may impact patient counseling.

A Quality Improvement Initiative to Improve Patient Safety Event Reporting by Residents.

INTRODUCTION: Residents play a key role in patient care at academic medical centers and have unique insights into safety improvement opportunities. At our institution, <1% of safety events were reported by resident trainees. The primary objective of this quality improvement (QI) initiative was to increase the monthly incidence of event reporting by pediatric residents by 20% from baseline within 12 months. METHODS: A QI team used the model for improvement to identify barriers to submitting safety event reports. The team used multiple intervention cycles to increase knowledge and promote engagement in event reporting. Interventions included educational tip sheets, a hospital-wide Morbidity and Mortality (M&M) conference, peer recognition and acknowledgment by senior leadership for report submission, and an interactive reporting activity. The outcome measure was monthly number of reports filed by residents. The process measure was the number of unique residents submitting a report each month. Time to complete a report was a balancing measure. RESULTS: The number of reports placed by residents increased significantly, with a centerline shift from 15 to 29 reports per month (statistical process control chart-Fig. 3). The number of unique residents submitting reports increased from 10 to 22 per month. The time to complete a report was unchanged. CONCLUSIONS: Engaging residents in patient safety initiatives through education, experiential learning, and recognition can increase safety event reporting by residents. Future planned interventions include enhancing safety event reporting technology, developing patient safety faculty and resident champions, and increasing transparency regarding outcomes of safety event reports.

Geographic variation in management of patients with placenta accreta spectrum: An international survey of experts (GPASS).

OBJECTIVE: To describe global geographic variations in the diagnosis and management of placenta accreta spectrum (PAS). METHODS: An international cross-sectional study was conducted among PAS experts practicing at medical institutions in member states of the United Nations. Survey questions focused on diagnostic evaluation and management strategies for PAS. RESULTS: A total of 134 centers participated. Participating centers represented each of the United Nations' designated regions. Of those, 118 (88%) reported practicing in a medium-volume or high-volume center. First-trimester PAS screen was reported in 35 (26.1%) centers. Respondents consistently implement guideline-supported care practices, including utilization of ultrasound as the primary diagnostic modality (134, 100%) and implementation of multidisciplinary care teams (115, 85.8%). Less than 10% of respondents reported routinely managing PAS without hysterectomy; these centers were predominantly located in Europe and Africa. Antepartum management and availability of mental health support for PAS patients varied widely. CONCLUSION: Worldwide, there is a strong adherence to PAS care guidelines; however, regional variations do exist. Comparing variations in care to outcomes will provide insight into the clinically significant practice variability.

Iron deficiency linked to altered bile acid metabolism promotes Helicobacter pylori-induced inflammation-driven gastric carcinogenesis.

Gastric carcinogenesis is mediated by complex interactions among Helicobacter pylori, host, and environmental factors. Here, we demonstrate that H. pylori augmented gastric injury in INS-GAS mice under iron-deficient conditions. Mechanistically, these phenotypes were not driven by alterations in the gastric microbiota; however, discovery-based and targeted metabolomics revealed that bile acids were significantly altered in H. pylori-infected mice with iron deficiency, with significant upregulation of deoxycholic acid (DCA), a carcinogenic bile acid. The severity of gastric injury was further augmented when H. pylori-infected mice were treated with DCA, and, in vitro, DCA increased translocation of the H. pylori oncoprotein CagA into host cells. Conversely, bile acid sequestration attenuated H. pylori-induced injury under conditions of iron deficiency. To translate these findings to human populations, we evaluated the association between bile acid sequestrant use and gastric cancer risk in a large human cohort. Among 416,885 individuals, a significant dose-dependent reduction in risk was associated with cumulative bile acid sequestrant use. Further, expression of the bile acid receptor transmembrane G protein-coupled bile acid receptor 5 (TGR5) paralleled the severity of carcinogenic lesions in humans. These data demonstrate that increased H. pylori-induced injury within the context of iron deficiency is tightly linked to altered bile acid metabolism, which may promote gastric carcinogenesis.

The impact of diabetes on tuberculosis treatment outcomes: a systematic review.

BACKGROUND: Multiple studies of tuberculosis treatment have indicated that patients with diabetes mellitus may experience poor outcomes.We performed a systematic review and meta-analysis to quantitatively summarize evidence for the impact of diabetes on tuberculosis outcomes. METHODS: We searched PubMed, EMBASE and the World Health Organization Regional Indexes from 1 January 1980 to 31 December 2010 and references of relevant articles for reports of observational studies that included people with diabetes treated for tuberculosis. We reviewed the full text of 742 papers and included 33 studies of which 9 reported culture conversion at two to three months, 12 reported the combined outcome of failure and death, 23 reported death, 4 reported death adjusted for age and other potential confounding factors, 5 reported relapse, and 4 reported drug resistant recurrent tuberculosis. RESULTS: Diabetes is associated with an increased risk of failure and death during tuberculosis treatment. Patients with diabetes have a risk ratio (RR) for the combined outcome of failure and death of 1.69 (95% CI, 1.36 to 2.12). The RR of death during tuberculosis treatment among the 23 unadjusted studies is 1.89 (95% CI, 1.52 to 2.36), and this increased to an effect estimate of 4.95 (95% CI, 2.69 to 9.10) among the 4 studies that adjusted for age and other potential confounding factors. Diabetes is also associated with an increased risk of relapse (RR, 3.89; 95% CI, 2.43 to 6.23). We did not find evidence for an increased risk of tuberculosis recurrence with drug resistant strains among people with diabetes. The studies assessing sputum culture conversion after two to three months of tuberculosis therapy were heterogeneous with relative risks that ranged from 0.79 to 3.25. CONCLUSIONS: Diabetes increases the risk of failure and death combined, death, and relapse among patients with tuberculosis. This study highlights a need for increased attention to treatment of tuberculosis in people with diabetes, which may include testing for suspected diabetes, improved glucose control, and increased clinical and therapeutic monitoring.

Naloxone Prescribing and Education in Outpatient Pain Management and Palliative Care.

Over the past two decades, opioid use and overdose have increased substantially. Naloxone, an opioid overdose reversal agent, has been one of many risk mitigation strategies for preventing mortality due to overdose. Most literature describing naloxone utilization has been about populations of illicit drug users and patients in hospitals, primary care, and pharmacies. There is limited information regarding naloxone prescribing and training for opioid users in specialty pain management clinics. Furthermore, there are no known publications concerning patients receiving palliative care services and overdose prevention. Pain and palliative care patients are commonly at risk of opioid overdose. In an interdisciplinary outpatient pain and palliative care clinic, pharmacists implemented naloxone prescribing and education. Eleven patients at increased risk for overdose were prescribed naloxone and educated on overdose risk factors, recognition, and management. Seven patients reported picking up their naloxone prescription from the pharmacy, and none reported using it within two weeks of the initial education. This intervention was deemed successful within the clinic, but small sample size and the pharmacist role may not be replicable within other pain and palliative care settings. It encourages further research of overdose risk and prevention in pain management and palliative care.