Fertility and pregnancy outcomes in primary hyperparathyroidism: Observations from a large insured population.

CONTEXT: Primary hyperparathyroidism (PHPT) has initially been implicated in adverse maternal and neonatal outcomes, while subsequent population studies have failed to show an association. OBJECTIVE: To compare maternal, pregnancy, and neonatal outcomes in patients with and without PHPT. DESIGN: Retrospective matched-cohort study (2005-2020). SETTING: An integrated healthcare delivery system in Southern California. PATIENTS: Women aged 18-44 years were included. Patients with biochemical diagnosis of PHPT were matched 1:3 with eucalcemic controls (non-PHPT). MAIN OUTCOME MEASURES: Achievement of pregnancy, pregnancy outcomes (including rates of abortion, maternal complications), and neonatal outcomes (including hypocalcemia, need for intensive care). RESULTS: The cohort comprised 386 women with PHPT and 1158 age-matched controls. Pregnancy rates between PHPT and control groups were similar (10.6% vs 12.8%). The adjusted rate ratio of pregnancy was 0.89 (95% CI: 0.64-1.24) (PHPT vs non-PHPT). Twenty-nine pregnancies occurred in women with co-existing PHPT and 191 pregnancies occurred in controls, resulting in 23 (79.3%) and 168 (88.0%) live births, respectively (p=0.023). Neonatal outcomes were similar. Live birth rates were similar (86.4%, 80%, 79.2%) for those undergoing parathyroidectomy prior (n=22), during (n=5), or after pregnancy/never (n=24). Among patients who underwent parathyroidectomy during pregnancy, no spontaneous abortions occurred in women entering pregnancy with peak calcium <11.5 mg/dL [2.9 mmol/L]. CONCLUSIONS: We observed no difference in pregnancy rates between women with or without PHPT. Performing parathyroidectomy before pregnancy or during the second trimester appears to be a safe and successful strategy, and adherence to this strategy may be most critical for patients with higher calcium levels (≥11.5 mg/dL [2.9 mmol/L]).

Sleep stage continuity is associated with objective daytime sleepiness in patients with suspected obstructive sleep apnea.

STUDY OBJECTIVES: Excessive daytime sleepiness (EDS) in patients with obstructive sleep apnea (OSA) is poorly explained by standard clinical sleep architecture metrics. We hypothesized that reduced sleep stage continuity mediates this connection independently from standard sleep architecture metrics. METHODS: 1,907 patients with suspected OSA with daytime sleepiness complaints underwent in-lab diagnostic polysomnography and next-day Multiple Sleep Latency Test (MSLT). Sleep architecture was evaluated with novel sleep-stage continuity quantifications (mean sleep stage duration and probability of remaining in each sleep stage), and conventional metrics (total N1, N2, N3 and REM times; and sleep onset latency). Multivariate analyses were utilized to identify variables associated with moderate EDS (5 ≤ mean daytime sleep latency (MSL) ≤ 10 minutes) and severe EDS (MSL < 5 minutes). RESULTS: Compared to those without EDS, participants with severe EDS had lower N3 sleep continuity (mean N3 period duration 10.4 vs 13.7 minutes, p<0.05), less N3 time (53.8 vs 76.5 minutes, p<0.05); greater total sleep time (374.0 vs 352.5 minutes, p<0.05) and greater N2 time (227.5 vs 186.8 minutes, p<0.05). After adjusting for standard sleep architecture metrics using multivariate logistic regression, decreased mean wake and N3 period duration, and the decreased probability of remaining in N2 and N3 sleep remained significantly associated with severe EDS, while the decreased probability of remaining in wake and N2 sleep were associated with moderate EDS. CONCLUSIONS: Patients with OSA with EDS experience lower sleep continuity, noticeable especially during N3 sleep and wake. Sleep-stage continuity quantifications assist in characterizing the sleep architecture and are associated with objective daytime sleepiness highlighting the need for more detailed evaluations of sleep quality.

Flow Limitation Is Associated with Excessive Daytime Sleepiness in Individuals without Moderate or Severe Obstructive Sleep Apnea.

Rationale: Moderate-Severe Obstructive Sleep Apnea (OSA, AHI>15) disturbs sleep through frequent bouts of apnea and is associated with daytime sleepiness. However, many individuals without moderate-severe OSA (i.e., AHI<15) also report sleepiness. Objective: To test the hypothesis that sleepiness in the AHI<15 group is a consequence of substantial flow limitation, in the absence of overt reductions in airflow (i.e., apnea/hypopnea). Methods: N=1886 participants from the MESA sleep cohort were analyzed for frequency of flow limitation from polysomnogram recorded nasal airflow signal. Excessive daytime sleepiness (EDS) was defined by Epworth Sleepiness Scale ≥11. Covariate-adjusted logistic regression assessed the association between EDS (binary dependent variable) and frequency of flow limitation (continuous) in individuals with an AHI<15. Results: N=772 individuals with an AHI<15 were included in primary analysis. Flow limitation was associated with EDS (odds ratio of 2.04, CI95% [1.17-3.54], per 2 standard deviation (2SD) increase in flow limitation frequency) after adjusting for age, sex, BMI, race/ethnicity, and sleep duration. This effect size did not appreciably change after additionally adjusting for AHI. Conclusions: In individuals with an AHI<15, increasing flow limitation frequency by 2SD is associated with a 2-fold increase in risk of EDS. Future studies should investigate addressing flow limitation in low AHI individuals as a potential mechanism for ameliorating sleepiness.

Real-World Experience in the Use of Immunosuppression for the Management of Inflammatory Eye Disease.

PURPOSE: Patients with sight-threatening inflammatory eye disease (IED) are maintained on systemic immunosuppression whilst in long-term clinical remission. There are no clear guidelines on the duration of remission before implementing treatment withdrawal. We present a real-world analysis on the use of immunosuppression in IED in long-term remission and consider strategies for withdrawal. METHODS: Adult IED patients on systemic immunosuppression were categorised into four disease groups: Corneal Transplant Survival Strategies (CTSS), Ocular Surface Disease (OSD), Non-infectious Uveitis (NIU) and Scleritis. Patients with Behçet's disease were excluded. Data on systemic immunosuppressants and biologics used; duration of treatment; reasons for drug discontinuation; disease activity/remission status; duration of clinical remission with an emphasis on patients who had been in remission for a minimum of 24 months were captured. RESULTS: Out of a total of 303 IED patients, 128 were on systemic immunosuppression with a clinical remission of their ocular disease for ≥24 months. The median duration of remission was 4-5 years with the longest duration of remission 22 years, and some patients on immunosuppression for up to 23 years. Sixty patients stopped at least one immunosuppressive agent without prior discussion with a health-care practitioner. CONCLUSION: Progressive conditions, such as cicatrising conjunctivitis may require lifelong immunosuppression, but patients with NIU and Scleritis and those on CTSS, immunosuppression withdrawal should be considered if they remain in remission for 2 years. Any patient stopping a medication should be contacted immediately for counselling. These data will better inform patients, encourage adherence and aide formal guideline development.

Investigating psychological mechanisms linking pain severity to depression symptoms in women cancer survivors at a cancer center with a rural catchment area.

PURPOSE: Women cancer survivors, especially those in rural areas, with high levels of depression may be acutely susceptible to pain due to the ways they think, feel, and behave. The current study seeks to elucidate the relationship between symptoms of depression and pain severity in women cancer survivors, by examining the putative mediators involved in this relationship, specifically their self-efficacy for managing their health, how overwhelmed they were from life's responsibilities, and relational burden. METHODS: Self-report data were collected from 183 cancer survivors of breast, cervical, ovarian, or endometrial/uterine cancer, who were between 6 months and 3 years post-active therapy. RESULTS: Women cancer survivors with higher (vs. lower) symptoms of depression had more severe pain. Individual mediation analyses revealed that survivors with higher levels of depression felt more overwhelmed by life's responsibilities and had lower self-efficacy about managing their health, which was associated with greater pain severity. When all mediators were simultaneously entered into the same model, feeling overwhelmed by life's responsibilities significantly mediated the link between survivors' symptoms of depression and their pain severity. CONCLUSIONS: The relationship between symptoms of depression and pain severity in women cancer survivors may be attributed in part to their self-efficacy and feeling overwhelmed by life's responsibilities. Early and frequent assessment of psychosocial factors involved in pain severity for women cancer survivors may be important for managing their pain throughout the phases of cancer survivorship.

Multicentre sleep-stage scoring agreement in the Sleep Revolution project.

Determining sleep stages accurately is an important part of the diagnostic process for numerous sleep disorders. However, as the sleep stage scoring is done manually following visual scoring rules there can be considerable variation in the sleep staging between different scorers. Thus, this study aimed to comprehensively evaluate the inter-rater agreement in sleep staging. A total of 50 polysomnography recordings were manually scored by 10 independent scorers from seven different sleep centres. We used the 10 scorings to calculate a majority score by taking the sleep stage that was the most scored stage for each epoch. The overall agreement for sleep staging was κ = 0.71 and the mean agreement with the majority score was 0.86. The scorers were in perfect agreement in 48% of all scored epochs. The agreement was highest in rapid eye movement sleep (κ = 0.86) and lowest in N1 sleep (κ = 0.41). The agreement with the majority scoring varied between the scorers from 81% to 91%, with large variations between the scorers in sleep stage-specific agreements. Scorers from the same sleep centres had the highest pairwise agreements at κ = 0.79, κ = 0.85, and κ = 0.78, while the lowest pairwise agreement between the scorers was κ = 0.58. We also found a moderate negative correlation between sleep staging agreement and the apnea-hypopnea index, as well as the rate of sleep stage transitions. In conclusion, although the overall agreement was high, several areas of low agreement were also found, mainly between non-rapid eye movement stages.

Review and perspective on sleep-disordered breathing research and translation to clinics.

Sleep-disordered breathing, ranging from habitual snoring to severe obstructive sleep apnea, is a prevalent public health issue. Despite rising interest in sleep and awareness of sleep disorders, sleep research and diagnostic practices still rely on outdated metrics and laborious methods reducing the diagnostic capacity and preventing timely diagnosis and treatment. Consequently, a significant portion of individuals affected by sleep-disordered breathing remain undiagnosed or are misdiagnosed. Taking advantage of state-of-the-art scientific, technological, and computational advances could be an effective way to optimize the diagnostic and treatment pathways. We discuss state-of-the-art multidisciplinary research, review the shortcomings in the current practices of SDB diagnosis and management in adult populations, and provide possible future directions. We critically review the opportunities for modern data analysis methods and machine learning to combine multimodal information, provide a perspective on the pitfalls of big data analysis, and discuss approaches for developing analysis strategies that overcome current limitations. We argue that large-scale and multidisciplinary collaborative efforts based on clinical, scientific, and technical knowledge and rigorous clinical validation and implementation of the outcomes in practice are needed to move the research of sleep-disordered breathing forward, thus increasing the quality of diagnostics and treatment.

Increased Flow Limitation During Sleep Is Associated With Increased Psychomotor Vigilance Task Lapses in Individuals With Suspected OSA.

BACKGROUND: Impaired daytime vigilance is an important consequence of OSA, but several studies have reported no association between objective measurements of vigilance and the apnea-hypopnea index (AHI). Notably, the AHI does not quantify the degree of flow limitation, that is, the extent to which ventilation fails to meet intended ventilation (ventilatory drive). RESEARCH QUESTION: Is flow limitation during sleep associated with daytime vigilance in OSA? STUDY DESIGN AND METHODS: Nine hundred ninety-eight participants with suspected OSA completed a 10-min psychomotor vigilance task (PVT) before same-night in-laboratory polysomnography. Flow limitation frequency (percent of flow-limited breaths) during sleep was quantified using airflow shapes (eg, fluttering and scooping) from nasal pressure airflow. Multivariable regression assessed the association between flow limitation frequency and the number of lapses (response times > 500 ms, primary outcome), adjusting for age, sex, BMI, total sleep time, depression, and smoking status. RESULTS: Increased flow limitation frequency was associated with decreased vigilance: a 1-SD (35.3%) increase was associated with 2.1 additional PVT lapses (95% CI, 0.7-3.7; P = .003). This magnitude was similar to that for age, where a 1-SD increase (13.5 years) was associated with 1.9 additional lapses. Results were similar after adjusting for AHI, hypoxemia severity, and arousal severity. The AHI was not associated with PVT lapses (P = .20). In secondary exploratory analysis, flow limitation frequency was associated with mean response speed (P = .012), median response time (P = .029), fastest 10% response time (P = .041), slowest 10% response time (P = .018), and slowest 10% response speed (P = .005). INTERPRETATION: Increased flow limitation during sleep was associated with decreased daytime vigilance in individuals with suspected OSA, independent of the AHI. Flow limitation may complement standard clinical metrics in identifying individuals whose vigilance impairment most likely is explained by OSA.

Nasal Pressure Derived Airflow Limitation and Ventilation Measurements are Resilient to Reduced Signal Quality.

Obstructive sleep apnea is a disorder characterized by partial or complete airway obstructions during sleep. Our previously published algorithms use the minimally invasive nasal pressure signal routinely collected during diagnostic polysomnography (PSG) to segment breaths and estimate airflow limitation (using flow:drive) and minute ventilation for each breath. The first aim of this study was to investigate the effect of airflow signal quality on these algorithms, which can be influenced by oronasal breathing and signal-to-noise ratio (SNR). It was hypothesized that these algorithms would make inaccurate estimates when the expiratory portion of breaths is attenuated to simulate oronasal breathing, and pink noise is added to the airflow signal to reduce SNR. At maximum SNR and 0% expiratory amplitude, the average error was 2.7% for flow:drive, -0.5% eupnea for ventilation, and 19.7 milliseconds for breath duration (n = 257,131 breaths). At 20 dB and 0% expiratory amplitude, the average error was -15.1% for flow:drive, 0.1% eupnea for ventilation, and 28.4 milliseconds for breath duration (n = 247,160 breaths). Unexpectedly, simulated oronasal breathing had a negligible effect on flow:drive, ventilation, and breath segmentation algorithms across all SNRs. Airflow SNR ≥ 20 dB had a negligible effect on ventilation and breath segmentation, whereas airflow SNR ≥ 30 dB had a negligible effect on flow:drive. The second aim of this study was to explore the possibility of correcting these algorithms to compensate for airflow signal asymmetry and low SNR. An offset based on estimated SNR applied to individual breath flow:drive estimates reduced the average error to ≤ 1.3% across all SNRs at patient and breath levels, thereby facilitating for flow:drive to be more accurately estimated from PSGs with low airflow SNR.Clinical Relevance- This study demonstrates that our airflow limitation, ventilation, and breath segmentation algorithms are robust to reduced airflow signal quality.

Mobile sensing to advance tumor modeling in cancer patients: A conceptual framework.

As mobile and wearable devices continue to grow in popularity, there is strong yet unrealized potential to harness people's mobile sensing data to improve our understanding of their cellular and biologically-based diseases. Breakthrough technical innovations in tumor modeling, such as the three dimensional tumor microenvironment system (TMES), allow researchers to study the behavior of tumor cells in a controlled environment that closely mimics the human body. Although patients' health behaviors are known to impact their tumor growth through circulating hormones (cortisol, melatonin), capturing this process is a challenge to rendering realistic tumor models in the TMES or similar tumor modeling systems. The goal of this paper is to propose a conceptual framework that unifies researchers from digital health, data science, oncology, and cellular signaling, in a common cause to improve cancer patients' treatment outcomes through mobile sensing. In support of our framework, existing studies indicate that it is feasible to use people's mobile sensing data to approximate their underlying hormone levels. Further, it was found that when cortisol is cycled through the TMES based on actual patients' cortisol levels, there is a significant increase in pancreatic tumor cell growth compared to when cortisol levels are at normal healthy levels. Taken together, findings from these studies indicate that continuous monitoring of people's hormone levels through mobile sensing may improve experimentation in the TMES, by informing how hormones should be introduced. We hope our framework inspires digital health researchers in the psychosocial sciences to consider how their expertise can be applied to advancing outcomes across levels of inquiry, from behavioral to cellular.

Healthcare professionals' views on the most important outcomes for non-infectious uveitis of the posterior segment: A qualitative study.

BACKGROUND: Uveitis comprises a range of conditions that result in intraocular inflammation. Most sight-threatening uveitis falls into the broad category known as Non-infectious Posterior Segment-Involving Uveitis (PSIU). To evaluate treatments, trialists and clinicians must select outcome measures. The aim of this study was to understand healthcare professionals' perspectives on what outcomes are important to adult patients with PSIU and their carers. METHODS: Twelve semi-structured telephone interviews were undertaken to understand the perspectives of healthcare professionals. Interviews were audio recorded, transcribed and thematically analysed. Findings were compared with the views of patients and carers and outcomes abstracted from a previously published systematic review. RESULTS: Eleven core domains were identified as important to healthcare professionals: (1) visual function, (2) symptoms, (3) functional ability, (4) impact on relationships, (5) financial impact, (6) psychological morbidity and emotional well-being (7) psychosocial adjustment to uveitis, (8) doctor / patient / interprofessional relationships and access to health care, (9) treatment burden, (10) treatment side effects, (11) disease control. Healthcare professionals recognised a similar range of domains to patients and carers but placed more emphasis on certain outcomes, particularly in the disease control domain. In contrast the range of outcomes identified via the systematic review was limited. CONCLUSION: Healthcare professionals recognise all of the published outcome domains as patients/carers in the previous publication but with subtly differing emphasis within some domains and with a priority for certain types of measures. Healthcare professionals discussed the disease control and side effects/complications to a greater degree than patients and carers in the focus groups.

A multi-dimensional assessment of financial hardship of cancer patients using existing health system data.

BACKGROUND: Existing financial hardship screening does not capture the multifaceted and dynamic nature of the problem. The use of existing health system data is a promising way to enable scalable and sustainable financial hardship screening. METHODS: We used existing data from 303 adult patients with cancer at the University of Virginia Comprehensive Cancer Center (2016-2018). All received distress screening and had a valid financial assistance screening based solely on household size-adjusted income. We constructed a composite index that integrates multiple existing health system data (Epic, distress screening, and cancer registry) to assess comprehensive financial hardship (e.g., material conditions, psychological responses, and coping behaviors). We examined differences of at-risk patients identified by our composite index and by existing single-dimension criterion. Dynamics of financial hardship over time, by age, and cancer type, were examined by fractional probit models. RESULTS: At-risk patients identified by the composite index were generally younger, better educated, and had a higher annual household income, though they had lower health insurance coverage. Identified periods to intervene for most patients are before formal diagnosis, 2 years, and 6 years after diagnosis. Within 2 years of diagnosis and more than 4 years after diagnosis appear critical for subgroups of patients who may suffer from financial hardship disparities. CONCLUSION: Existing health system data provides opportunities to systematically measure and track financial hardship in a systematic, scalable and sustainable way. We find that the dimensions of financial hardship can exhibit different patterns over time and across patient subgroups, which can guide targeted interventions. The scalability of the algorithm is limited by existing data availability.

Pancreatoscopy-guided laser lithotripsy to manage obstructing intraductal pancreatic calculi.

Video 1Pancreatoscopy-guided laser lithotripsy to manage obstructing intraductal pancreatic calculi.

How to recognise a Behçet's ulcer from other types of oral ulceration? Defining Behçet's ulceration by an International Delphi Consultation.

OBJECTIVES: To define the clinical characteristics of oral ulceration (OU) in Behçet's disease (BD), to allow differentiation from other causes of OU, including aphthous ulcers, by an International Delphi consultation. To develop a clinical guideline on how to recognise BD ulcers. METHODS: Round 1. 40 clinical images of OU in BD, recurrent aphthous stomatitis (RAS), inflammatory bowel disease (IBD) and mucous membrane pemphigoid (MMP) were shown. Participants answered, independently, which images would be consistent with a BD ulcer. Round 2. The results from marking independently were shown. The panel remarked the questions through iteration process. The images not agreed to be a possible BD ulcer were discarded. Round 3. 10 clinical descriptors that may define BD ulcers were suggested. Participants ranked the level of importance for each descriptor on each image presented. Round 4. Participants re-ranked their level of agreement for each descriptor through iteration process. Whether the clinical pictures would be different from RAS was also explored. A final agreement was reached. RESULTS: This study has shown clear differentiation between BD, IBD and MMP ulcers when defining them by phenotype through clinical images only. On the other hand, no differentiation between RAS and BD ulcers was found. The most important clinical descriptors that define BD ulcers have been agreed. CONCLUSIONS: New clinical guidance for Health Care Professionals (HCP) on how to recognise a BD ulcer has been proposed. This should elucidate an earlier diagnosis, quicker access to treatment and control of the disease enhancing patient's quality of life.

Associations between context and affect within the daily lives of cancer caregivers.

PURPOSE: This study used ecological momentary assessment (EMA) to test the association between activity, location, and social company contexts with cancer caregivers' in-the-moment affect to identify precisely when and where to deliver psychological interventions for caregivers. METHODS: Current cancer caregivers (N = 25) received 8 EMA prompts per day for 7 consecutive days. At each prompt, caregivers reported their current positive affect and negative affect, as well as what they were doing, where they were located, and who they were with. Multilevel logistic regressions tested the associations between caregivers' contexts with their own person-mean-centered state (concurrent momentary level) and trait (overall weekly average) positive or negative affect. RESULTS: Caregivers reported lower state negative affect, as well as higher state positive affect, when socializing (ps < .001), when at a public location (ps < .03), and when around their friends, family, spouse/partner, or care recipient (i.e., person with cancer, ps < .02), relative to when not endorsing the context. Caregivers also reported lower state negative affect when eating/drinking or engaging in leisure (ps < .01; but no parallel effects for state positive affect). Caregivers reported higher state negative affect while working, when at their workplace, or when around work colleagues (ps < .001) and lower state positive affect when at home or alone (ps < .03). CONCLUSIONS: Results suggest the pertinence of a behavioral activation framework to mitigate the emotional strain of caregiving. Interventions that facilitate caregivers' ability to socialize with a range of friends and family, including their loved one with cancer, outside of the home may have the strongest positive emotional impact.

Mortality associated with third-generation cephalosporin resistance in Enterobacterales bloodstream infections at eight sub-Saharan African hospitals (MBIRA): a prospective cohort study.

BACKGROUND: Bacteria of the order Enterobacterales are common pathogens causing bloodstream infections in sub-Saharan Africa and are frequently resistant to third-generation cephalosporin antibiotics. Although third-generation cephalosporin resistance is believed to lead to adverse outcomes, this relationship is difficult to quantify and has rarely been studied in this region. We aimed to measure the effects associated with resistance to third-generation cephalosporins in hospitalised patients with Enterobacterales bloodstream infection in Africa. METHODS: We conducted a prospective, matched, parallel cohort study at eight hospitals across sub-Saharan Africa. We recruited consecutive patients of all age groups with laboratory-confirmed Enterobacterales bloodstream infection and matched them to at least one patient without bloodstream infection on the basis of age group, hospital ward, and admission date. Date of infection onset (and enrolment) was defined as the day of blood sample collection for culturing. Patients infected with bacteria with a cefotaxime minimum inhibitory concentration of 1 mg/L or lower were included in the third-generation cephalosporin-susceptible (3GC-S) cohort, and the remainder were included in the third-generation cephalosporin-resistant (3GC-R) cohort. The primary outcomes were in-hospital death and death within 30 days of enrolment. We used adjusted multivariable regression models to first compare patients with bloodstream infection against matched patients within the 3GC-S and 3GC-R cohorts, then compared estimates between cohorts. FINDINGS: Between Nov 1, 2020, and Jan 31, 2022, we recruited 878 patients with Enterobacterales bloodstream infection (221 [25·2%] to the 3GC-S cohort and 657 [74·8%] to the 3GC-R cohort) and 1634 matched patients (420 [25·7%] and 1214 [74·3%], respectively). 502 (57·2%) bloodstream infections occurred in neonates and infants (age 0-364 days). Klebsiella pneumoniae (393 [44·8%] infections) and Escherichia coli (224 [25·5%] infections) were the most common Enterobacterales species identified. The proportion of patients who died in hospital was higher in patients with bloodstream infection than in matched controls in the 3GC-S cohort (62 [28·1%] of 221 vs 22 [5·2%] of 420; cause-specific hazard ratio 6·79 [95% CI 4·06-11·37] from Cox model) and the 3GC-R cohort (244 [37·1%] of 657 vs 115 [9·5%] of 1214; 5·01 [3·96-6·32]). The ratio of these cause-specific hazard ratios showed no significant difference in risk of in-hospital death in the 3GC-R cohort versus the 3GC-S cohort (0·74 [0·42-1·30]). The ratio of relative risk of death within 30 days (0·82 [95% CI 0·53-1·27]) also indicated no difference between the cohorts. INTERPRETATION: Patients with bloodstream infections with Enterobacterales bacteria either resistant or susceptible to third-generation cephalosporins had increased mortality compared with uninfected matched patients, with no differential effect related to third-generation cephalosporin-resistance status. However, this finding does not account for time to appropriate antibiotic treatment, which remains clinically important to optimise. Measures to prevent transmission of Enterobacterales could reduce bloodstream infection-associated mortality from both drug-resistant and drug-susceptible bacterial strains in Africa. FUNDING: Bill & Melinda Gates Foundation.