Robert Gross

Background: The epidemiology of extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE) in low- and middle-income countries (LMICs) is poorly described. Identifying risk factors for ESCrE colonization is critical to inform antibiotic resistance reduction strategies because colonization is typically a precursor to infection. Methods: From 15 January 2020 to 4 September 2020, we surveyed a random sample of clinic patients at 6 sites in Botswana. We also invited each enrolled participant to refer up to 3 adults and children. All participants had rectal swabs collected that were inoculated onto chromogenic media followed by confirmatory testing. Data were collected on demographics, comorbidities, antibiotic use, healthcare exposures, travel, and farm and animal contact. Participants with ESCrE colonization (cases) were compared with noncolonized participants (controls) to identify risk factors for ESCrE colonization using bivariable, stratified, and multivariable analyses. Results: A total of 2000 participants were enrolled. There were 959 (48.0%) clinic participants, 477 (23.9%) adult community participants, and 564 (28.2%) child community participants. The median (interquartile range) age was 30 (12–41) and 1463 (73%) were women. There were 555 cases and 1445 controls (ie, 27.8% of participants were ESCrE colonized). Independent risk factors (adjusted odds ratio [95% confidence interval]) for ESCrE included healthcare exposure (1.37 [1.08–1.73]), foreign travel [1.98 (1.04–3.77]), tending livestock (1.34 [1.03–1.73]), and presence of an ESCrE-colonized household member (1.57 [1.08–2.27]). Conclusions: Our results suggest healthcare exposure may be important in driving ESCrE. The strong links to livestock exposure and household member ESCrE colonization highlight the potential role of common exposure or household transmission. These findings are critical to inform strategies to curb further emergence of ESCrE in LMICs.

Background: The epidemiology of extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE) in hospitalized patients in low- and middle-income countries (LMICs) is poorly described. Although risk factors for ESCrE clinical infection have been studied, little is known of the epidemiology of ESCrE colonization. Identifying risk factors for ESCrE colonization, which can predispose to infection, is therefore critical to inform antibiotic resistance reduction strategies. Methods: This study was conducted in 3 hospitals located in 3 districts in Botswana. In each hospital, we conducted ongoing surveillance in sequential units hospitalwide. All participants had rectal swabs collected which were inoculated onto chromogenic media followed by confirmatory testing using MALDI-TOF MS and VITEK-2. Data were collected via interview and review of the inpatient medical record on demographics, comorbidities, antibiotic use, healthcare exposures, invasive procedures, travel, animal contact, and food consumption. Participants with ESCrE colonization (cases) were compared to noncolonized participants (controls) using bivariable and multivariable analyses to identify risk factors for ESCrE colonization. Results: Enrollment occurred from January 15, 2020, to September 4, 2020, and 469 participants were enrolled. The median age was 42 years (IQR, 31–58) and 320 (68.2%) were female. The median time from hospital admission to date of sampling was 5 days (IQR, 3–12). There were 179 cases and 290 controls (ie, 38.2% of participants were ESCrE colonized). Independent risk factors for ESCrE colonization were a greater number of days on antibiotic, recent healthcare exposure, and tending swine prior to hospitalization. (Table). Conclusions: ESCrE colonization among hospitalized patients was common and was associated with several exposures. Our results suggest prior healthcare exposure may be important in driving ESCrE. The strong link to recent antibiotic use highlights the potential role of antibiotic stewardship interventions for prevention. The association with tending swine suggests that animal husbandry practices may play a role in community exposures, resulting in colonization detected at the time of hospital admission. These findings will help to inform future studies assessing strategies to curb further emergence of hospital ESCrE in LMICs. Disclosures: None

PURPOSE: Oral cancer is the sixth most common cancer worldwide and is the seventh most common in Botswana. Lack of improvement in oral cancer survival despite the availability of multiple treatment options may be due to the high prevalence of advanced stage at presentation. We identified risk factors for presenting with oral cancer at an advanced stage to facilitate interventions to reduce mortality from oral cancers.METHODS: A retrospective cohort analysis was conducted among individuals with biopsy-confirmed oral cancer at Princess Marina Hospital in Gaborone, Botswana, between 2010 and 2020. Data collected included age at diagnosis, sex, place of residence, HIV status, oral cancer stage, and oral subsite. Multivariable analyses were controlled for age, sex, district of residence, and oral subsite.RESULTS: Of the 218 records analyzed, 79% were male, 58% were HIV-positive, the median age was 56 years (interquartile range: 47-63), and 67% presented with advanced-stage disease. Cancers from hidden oral sites were more likely to present at an advanced stage with an adjusted odds ratio (OR) of 2.98 (95% CI, 1.29 to 6.89; P = .01). Residence in socioeconomically disadvantaged districts was associated with higher likelihood (OR, 2.36; 95% CI, 1.28 to 4.39; P = .01) of advanced stage presentation compared with other districts. HIV infection was not associated with risk of advanced lesion presentation (OR, 1; 95% CI, 0.61 to 1.61; P = .97).CONCLUSION: Hidden oral cancer sites and residence in districts with limited access to care were risk factors for advanced oral cancer at the time of diagnosis in Botswana. These findings support a need to increase efforts to improve access to care and increase oral cancer awareness to decrease the burden of advanced oral cancer.

PURPOSE: Patients who are HIV-positive and have breast cancer have worse overall survival (OS) compared with patients who are HIV-negative. Pathologic complete response (pCR) and relative dose intensity (RDI) of chemotherapy are associated with survival. We assessed whether pCR and RDI rates were lower for patients who are HIV-positive and received neoadjuvant chemotherapy (NACT). METHODS: This was a prospective cohort analysis of patients initiating NACT in Botswana (February 2017 to September 2019). Primary outcomes were pCR and RDI; secondary outcomes were OS and toxicity. HIV status and zidovudine (ZDV) treatment were stratification factors. Multivariable analysis was used to control for confounding. RESULTS: In total, 26 of 110 enrolled individuals were HIV-positive. In univariable analysis, HIV-positive (odds ratio [OR] = 0.2; P = .048) and RDI < 0.85 (OR = 0.30; P = .025) were associated with pCR. In multivariable analysis, the magnitude of association decreased for HIV-positive (OR = 0.28; P = .11), but RDI < 0.85 remained independently associated with pCR (OR = 0.32; P = .035). Patients who are HIV-positive had significantly lower mean RDI, and those on ZDV had significantly lower RDI. Ninety-one (83%) were stage III with 2-year OS significantly worse for patients who are HIV-positive (58% v 74%). Hazard ratio for all-cause mortality was 2.68 (95% CI, 1.17 to 6.13; P = .028) in patients who are HIV-positive compared with patients who are HIV-negative. Toxicity rates were similar despite patients who are HIV-positive receiving significantly lower dose intensity chemotherapy. CONCLUSION: Patients who are HIV-positive and have breast cancer in Botswana have lower pCR rates and also receive lower dose intensity therapy, which may contribute to worse OS. Patients who are HIV-positive on ZDV-containing regimens received even lower dose intensity of NACT. Administering optimal dose intensity in patients who are HIV-positive remains a challenge, and targeted interventions that address modifiable risk factors are needed to improve therapy delivery and outcomes.

Although CRE are a global threat, data in low- and middle-income countries are scarce. Colonization data are vital for informing antibiotic resistance strategies. We characterized the colonization prevalence of CRE in various settings in Botswana. This study was conducted in 3 districts in Botswana (1 hospital and 2 clinics per district). Adult inpatients and clinic patients were randomly selected for enrollment. Community subjects were enrolled by inviting each enrolled clinic subject to refer up to 3 adults. Each adult clinic or community subject was also asked to refer their children. All subjects had rectal swabs obtained and inoculated on selective chromogenic media for preliminary identification of CRE. Final identification and susceptibility testing were performed using MALDI-TOF MS and VITEK-2, respectively. CRE underwent genotyping for carbapenemase genes. Subjects were enrolled from 1/15/20-9/4/20 with a pause from 4/2/20-5/21/20 due to a countrywide COVID lockdown. Of 5,088 subjects approached, 2,469 (49%) participated. Enrollment by subject type was: hospital – 469 (19%); clinic – 959 (39%); community adult – 477 (19%); and community child – 564 (23%). Of 2,469 subjects, the median (interquartile range) age was 32 years (19-44) and 1,783 (72%) were female. 42 (1.7%) subjects were colonized with at least one CRE; 10 subjects were colonized with multiple strains. E. coli (n=17), K. pneumoniae (n=20), and E. cloacae complex (n=11) were most common. CRE colonization prevalence was 6.8% for hospital subjects, 0.7% for clinic subjects, 0.2% for adult community subjects, and 0.5% for child community subjects (p< 0.001)). CRE prevalence varied across regions (Figure 1) and was significantly higher pre- vs post-lockdown (Figure 2). VIM and NDM were the most common carbapenemase genes (Figure 3). Figure 1. CRE Colonization - Study Sites Figure 2. CRE Colonization - Temporal Trends FIgure 3. CRE Genotypic Analyses CRE colonization was significantly higher in hospital vs community settings in Botswana. CRE prevalence varied by region and decreased significantly following a countrywide lockdown. With CRE prevalence still modest, elucidating risk factors for CRE colonization holds promise in developing strategies to curb further emergence of CRE. Additional investigation of the CRE isolates without identified resistance genes is warranted. Robert Gross, MD, MSCE, Pfizer (Other Financial or Material Support, Serve on DSMB for drug unrelated to HIV) Ebbing Lautenbach, MD, MPH, MSCE, Merck (Other Financial or Material Support, Member of Data and Safety Monitoring Board (DSMB))

PURPOSE Multiple studies have demonstrated the negative impact of cancer care delays during the COVID-19 pandemic, and transmission mitigation techniques are imperative for continued cancer care delivery. We aimed to gauge the effectiveness of these measures at the University of Pennsylvania. METHODS We conducted a longitudinal study of SARS-CoV-2 antibody seropositivity and seroconversion in patients presenting to infusion centers for cancer-directed therapy between May 21, 2020, and October 8, 2020. Participants completed questionnaires and had up to five serial blood collections. RESULTS Of 124 enrolled patients, only two (1.6%) had detectable SARS-CoV-2 antibodies on initial blood draw, and no initially seronegative patients developed newly detectable antibodies on subsequent blood draw(s), corresponding to a seroconversion rate of 0% (95% CI, 0.0 TO 4.1%) over 14.8 person-years of follow up, with a median of 13 health care visits per patient. CONCLUSION These results suggest that patients with cancer receiving in-person care at a facility with aggressive mitigation efforts have an extremely low likelihood of COVID-19 infection. (C) 2021 by American Society of Clinical Oncology

We address a first step toward using social media data to supplement current efforts in monitoring population-level medication nonadherence: detecting changes to medication treatment. Medication treatment changes, like changes to dosage or to frequency of intake, that are not overseen by physicians are, by that, nonadherence to medication. Despite the consequences, including worsening health conditions or death, 50% of patients are estimated to not take medications as indicated. Current methods to identify nonadherence have major limitations. Direct observation may be intrusive or expensive, and indirect observation through patient surveys relies heavily on patients’ memory and candor. Using social media data in these studies may address these limitations. We annotated 9830 tweets mentioning medications and trained a convolutional neural network (CNN) to find mentions of medication treatment changes, regardless of whether the change was recommended by a physician. We used active and transfer learning from 12 972 reviews we annotated from WebMD to address the class imbalance of our Twitter corpus. To validate our CNN and explore future directions, we annotated 1956 positive tweets as to whether they reflect nonadherence and categorized the reasons given. Our CNN achieved 0.50 F₁-score on this new corpus. The manual analysis of positive tweets revealed that nonadherence is evident in a subset with 9 categories of reasons for nonadherence. We showed that social media users publicly discuss medication treatment changes and may explain their reasons including when it constitutes nonadherence. This approach may be useful to supplement current efforts in adherence monitoring.

Background: Diabetes mellitus is a major global public health issue where self-management is critical to reducing disease burden. Social media has been a powerful tool to understand public perceptions. Public perception of the drugs used for the treatment of diabetes may be useful for orienting interventions to increase adherence. Objective: The aim of this study was to explore the public perceptions of anti-diabetic drugs through the analysis of health-related tweets mentioning such medications. Methods: This study uses an infoveillance social listening approach to monitor public discourse using Twitter data. We coded 4000 tweets from January 1, 2019 to October 1, 2019 containing key terms related to anti-diabetic drugs by using qualitative content analysis. Tweets were coded for whether they were truly about an anti-diabetic drug and whether they were health-related. Health-related tweets were further coded based on who was tweeting, which anti-diabetic drug was being tweeted about, and the content discussed in the tweet. The main outcome of the analysis was the themes identified by analyzing the content of health-related tweets on anti-diabetic drugs. Results: We identified 1664 health-related tweets on 33 anti-diabetic drugs. A quarter (415/1664) of the tweets were confirmed to have been from people with diabetes, 17.9% (298/1664) from people posting about someone else, and 2.7% (45/1664) from health care professionals. However, the role of the tweeter was unidentifiable in two-thirds of the tweets. We identified 13 themes, with the health consequences of the cost of anti-diabetic drugs being the most extensively discussed, followed by the efficacy and availability. We also identified issues that patients may conceal from health care professionals, such as purchasing medications from unofficial sources. Conclusions: This study uses an infoveillance approach using Twitter data to explore public perceptions related to anti-diabetic drugs. This analysis gives an insight into the real-life issues that an individual faces when taking anti-diabetic drugs, and such findings may be incorporated into health policies to improve compliance and efficacy. This study suggests that there is a fear of not having access to anti-diabetic drugs due to cost or physical availability and highlights the impact of the sacrifices made to access anti-diabetic drugs. Along with screening for diabetes-related health issues, health care professionals should also ask their patients about any non–health-related concerns regarding their anti-diabetic drugs. The positive tweets about dietary changes indicate that people with type 2 diabetes may be more open to self-management than what the health care professionals believe.

BACKGROUND Diabetes mellitus is a major global public health issue where self-management is critical to reducing disease burden. Social media has been a powerful tool to understand public perceptions. Public perception of the drugs used for the treatment of diabetes may be useful for orienting interventions to increase adherence. OBJECTIVE The aim of this study was to explore the public perceptions of anti-diabetic drugs through the analysis of health-related tweets mentioning such medications. METHODS This study uses an infoveillance social listening approach to monitor public discourse using Twitter data. We coded 4000 tweets from January 1, 2019 to October 1, 2019 containing key terms related to anti-diabetic drugs by using qualitative content analysis. Tweets were coded for whether they were truly about an anti-diabetic drug and whether they were health-related. Health-related tweets were further coded based on who was tweeting, which anti-diabetic drug was being tweeted about, and the content discussed in the tweet. The main outcome of the analysis was the themes identified by analyzing the content of health-related tweets on anti-diabetic drugs. RESULTS We identified 1664 health-related tweets on 33 anti-diabetic drugs. A quarter (415/1664) of the tweets were confirmed to have been from people with diabetes, 17.9% (298/1664) from people posting about someone else, and 2.7% (45/1664) from health care professionals. However, the role of the tweeter was unidentifiable in two-thirds of the tweets. We identified 13 themes, with the health consequences of the cost of anti-diabetic drugs being the most extensively discussed, followed by the efficacy and availability. We also identified issues that patients may conceal from health care professionals, such as purchasing medications from unofficial sources. CONCLUSIONS This study uses an infoveillance approach using Twitter data to explore public perceptions related to anti-diabetic drugs. This analysis gives an insight into the real-life issues that an individual faces when taking anti-diabetic drugs, and such findings may be incorporated into health policies to improve compliance and efficacy. This study suggests that there is a fear of not having access to anti-diabetic drugs due to cost or physical availability and highlights the impact of the sacrifices made to access anti-diabetic drugs. Along with screening for diabetes-related health issues, health care professionals should also ask their patients about any non–health-related concerns regarding their anti-diabetic drugs. The positive tweets about dietary changes indicate that people with type 2 diabetes may be more open to self-management than what the health care professionals believe.