Assessing the clinical validity and cost-effectiveness of human papillomavirus testing using self-collected specimens for cervical cancer screening in Kenya

Invasive cervical cancer (ICC) is the leading cause of cancer-related deaths among women in sub-Saharan Africa (SSA). Through the implementation of organized cytology-based screening programs, high-income countries have reduced ICC incidence and mortality by 80%. However, challenges remain in screening program implementation and coverage in SSA due to relatively weak healthcare infrastructure, poorly equipped health facilities, and limited skilled healthcare providers. In Kenya, the estimated screening coverage is only 3.5% among women aged 25 - 64years, compared to the global coverage of 40%. To improve access and effectiveness of cervical cancer prevention programs in low-resource settings, screening methods that are cost-effective, simple to implement, and incorporate effective linkage to treatment are needed. From 2013 to 2018, a total of 399 female sex workers participated in this cross-sectional study. Participants provided two self-collected specimens: one stored dry(sc-DRY) using a Viba brush (Rovers), and one stored wet (sc-WET) with Aptima media (Hologic) using an Evalyn brush (Rovers). Two physician-collected specimens for HPV mRNA testing (APTIMA) and conventional cytology were collected. We estimated test characteristics for each hr-HPV screening method using conventional cytology as the gold standard. We also examined participant preference for sc-DRY and sc-WET. HR-HPV mRNA positivity was higher in sc-WET (36.8%) than sc-DRY samples (31.8%). Prevalence of ≥HSIL was 6.9% (n = 27). Sensitivity of hr-HPV mRNA testing for detecting ≥HSIL was similar in sc-WET (85%, 95% CI: 66-96), and sc-DRY specimens (78%, 95% CI: 58-91). Specificity was 65% (95% CI: 61-71) in sc-WET and 70%, (95% CI: 65-75) in sc-DRY specimens. Women preferred sc-DRY specimen collection (46%) compared to sc-WET (31%). However, more women preferred physician-collection (64%) than self-collection (36%), which should be further evaluated. Sc-DRY specimens appeared to perform similarly to sc-WET for the detection of ≥HSIL. To evaluate cost-effectiveness of cervical cancer screening delivery using self-collection, we assessed the outcomes, costs, and cost-effectiveness of four cervical cancer screening scenarios in Kenya, each using community health campaign (CHC) based HPV self-screening: (1) followed by VIA to assess appropriateness of cryotherapy (“HPV & Treat”), with standard linkage to treatment and (2) “HPV & Treat” with enhanced linkage to treatment; and (3) followed by VIA screening for triage to treatment (“HPV+VIA & Treat”), with standard linkage to treatment and (4) “HPV+VIA & Treat” with enhanced linkage to treatment. Compared to “HPV+VIA & treat,” we found that “HPV & Treat” led to better health outcomes, as measured in DALYs and was more cost-effective due to fewer missed cases of CIN2+ eligible for treatment. More specifically, we found that compared to no screening, HPV& Treat with enhanced linkage to treatment was the most cost-effective option at $5492.62 I$/DALY averted. Deterministic sensitivity analyses showed that the proportion of women successfully linked to treatment significantly impacted the cost-effectiveness of “HPV& treat” options. Future studies to assess programmatic costs from the perspective of the Kenyan Ministry of Health to inform national scale-up of CHCs are needed.Doctor of Philosoph

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Evaluating Mental Health–Related Symptoms Among Cancer Survivors During the COVID-19 Pandemic: An Analysis of the COVID Impact Survey

PURPOSE: The COVID-19 pandemic has affected the mental health of adults in the United States because of recommended preventive behaviors such as physical distancing. Our objective was to evaluate mental health symptoms and identify associated determinants among cancer survivors during the COVID-19 pandemic in the United States. METHODS: We used nationally representative data of 10,760 US adults from the COVID-19 Impact Survey. We defined cancer survivors as adults with a self-reported diagnosis of cancer (n = 854, 7.6%). We estimated associations of mental health symptoms among cancer survivors using multinomial logistic regression. We estimated determinants of reporting at least one mental health symptom 3-7 times in the 7 days before survey administration among cancer survivors using multivariable Poisson regression. RESULTS: Cancer survivors were more likely to report feeling nervous, anxious, or on edge (adjusted odds ratio [aOR], 1.42; 95% CI, 1.07 to 1.90); depressed (aOR, 1.57; 95% CI, 1.18 to 2.09); lonely (aOR, 1.42; 95% CI, 1.05 to 1.91); and hopeless (aOR, 1.51; 95% CI, 1.11 to 2.06) 3-7 days per week in the last 7 days when compared with adults without cancer. Among cancer survivors, adults of age 30-44 years (adjusted prevalence ratio [aPR], 1.87; 95% CI, 1.18 to 2.95), females (aPR, 1.55, 95% CI, 1.12 to 2.13), adults without a high school degree (aPR, 1.79; 95% CI, 1.05 to 3.04), and adults with limited social interaction (aPR, 1.40, 95% CI, 1.01 to 1.95) were more likely to report at least one mental health–related symptom in the last 7 days (3-7 days/week). CONCLUSION: Cancer survivors are reporting mental health symptoms during the COVID-19 pandemic, particularly young adults, adults without a high school degree, women, and survivors with limited social support

Racial/ethnic differences in knowledge and attitudes towards clinical trials among adults in the United States: An analysis of the 2020 U.S. HINTS

e18573 Background: Despite the use of clinical trials to provide gold-standard evidence of treatment and intervention effectiveness, racial/ethnic minorities are frequently underrepresented participants. Our objective was to evaluate racial/ethnic differences in knowledge and attitudes towards clinical trials among adults in the U.S. Methods: We leveraged Health Informational National Trends Survey (HINTS) data, which is a weighted, nationally representative survey of 3865 adults (≥18 years). Data were collected between February-June 2020, and included age, race/ethnicity, sex, cancer history, and comorbidities. Participants were asked questions focused on clinical trials, including their knowledge, influential factors to participate, trusted sources of information, and if they were ever invited or participated in a clinical trial. Among adults who self-reported to have heard of clinical trials (n = 2366), we used multivariable logistic regression to evaluate racial/ethnic differences in self-reported invitation and participation in clinical trials after adjustment for cancer history, age, sex, comorbidities, and insurance status. Results: Overall, the sample included 64% non-Hispanic (NH) White, 11% NH-Black, 17% Hispanic, and 5% NH-Asian respondents. Nine percent were cancer survivors. Almost 60% self-reported to at least have some knowledge about clinical trials. When asked about factors that would influence their decision to participate in clinical trials “A lot”, participants across racial groups most frequently chose “I would want to get better” and “If the standard care was not covered by my insurance.” Cancer survivors also frequently reported their decision would be influenced “A lot” or “Somewhat” if “My doctor encouraged me to participate.” NH-White (76%), NH-Black (78%), and Hispanic (77%) cancer survivors reported their trusted source of information about clinical trials was their health care provider; NH-Asian cancer survivors reported their health care provider (51%) as well as government health agencies (30%). Compared to NH-White adults, NH-Black adults were more likely to be invited to participate in a clinical trial (OR: 2.60, 95% CI: 1.53-4.43). However, compared to NH-White adults, our data suggest NH-Black adults were less likely to participate in the clinical trial (OR: 0.76, 95% CI: 0.39-1.49) although not statistically significant. Compared to NH-White adults, NH-Asian adults were less likely to participate in clinical trials (OR: 0.10, 95% CI: 0.06-0.18). Conclusions: Health care providers are a trusted source of clinical trial information. Although NH-Black adults are more likely to be invited, they are less likely to participate in a clinical trial; as well as Asian adults. Efforts to leverage insights gained on factors of influence and sources of trusted information on clinical trials should be prioritized

Attitudes Toward Using COVID-19 mHealth Tools Among Adults With Chronic Health Conditions: Secondary Data Analysis of the COVID-19 Impact Survey

Adults with chronic conditions are disproportionately burdened by COVID-19 morbidity and mortality. Although COVID-19 mobile health (mHealth) apps have emerged, research on attitudes toward using COVID-19 mHealth tools among those with chronic conditions is scarce. This study aimed to examine attitudes toward COVID-19, identify determinants of COVID-19 mHealth tool use across demographic and health-related characteristics, and evaluate associations between chronic health conditions and attitudes toward using COVID-19 mHealth tools (eg, mHealth or web-based methods for tracking COVID-19 exposures, symptoms, and recommendations). We used nationally representative data from the COVID-19 Impact Survey collected from April to June 2020 (n=10,760). Primary exposure was a history of chronic conditions, which were defined as self-reported diagnoses of cardiometabolic, respiratory, immune-related, and mental health conditions and overweight/obesity. Primary outcomes were attitudes toward COVID-19 mHealth tools, including the likelihood of using (1) a mobile phone app to track COVID-19 symptoms and receive recommendations; (2) a website to track COVID-19 symptoms, track location, and receive recommendations; and (3) an app using location data to track potential COVID-19 exposure. Outcome response options for COVID-19 mHealth tool use were extremely/very likely, moderately likely, or not too likely/not likely at all. Multinomial logistic regression was used to compare the likelihood of COVID-19 mHealth tool use between people with different chronic health conditions, with not too likely/not likely at all responses used as the reference category for each outcome. We evaluated the determinants of each COVID-19 mHealth intervention using Poisson regression. Of the 10,760 respondents, 21.8% of respondents were extremely/very likely to use a mobile phone app or a website to track their COVID-19 symptoms and receive recommendations. Additionally, 24.1% of respondents were extremely/very likely to use a mobile phone app to track their location and receive push notifications about whether they have been exposed to COVID-19. After adjusting for age, race/ethnicity, sex, socioeconomic status, and residence, adults with mental health conditions were the most likely to report being extremely/very or moderately likely to use each mHealth intervention compared to those without such conditions. Adults with respiratory-related chronic diseases were extremely/very (conditional odds ratio 1.16, 95% CI 1.00-1.35) and moderately likely (conditional odds ratio 1.23, 95% CI 1.04-1.45) to use a mobile phone app to track their location and receive push notifications about whether they have been exposed to COVID-19. Our study demonstrates that attitudes toward using COVID-19 mHealth tools vary widely across modalities (eg, web-based method vs app) and chronic health conditions. These findings may inform the adoption of long-term engagement with COVID-19 apps, which is crucial for determining their potential in reducing disparities in COVID-19 morbidity and mortality among individuals with chronic health conditions

Preventive Behaviors and Mental Health-Related Symptoms Among Immunocompromised Adults During the COVID-19 Pandemic: An Analysis of the COVID Impact Survey

The COVID-19 pandemic has disrupted the continuity of care of U.S. adults living with chronic diseases, including immunocompromised adults. Disruption in care may be a barrier to identifying COVID-19 associated sequelae, such as mental health symptoms, among the immunocompromised. Our objectives were to evaluate COVID-19-related preventive behaviors, with a focus on canceling doctor's appointments as a proxy for continuity of care, and to compare COVID-19-related mental health symptoms among the immunocompromised with the general population. We used nationally-representative data of 10,760 U.S. adults from the publicly-available COVID-19 Household Impact Survey. We defined immunocompromised as adults with a self-reported diagnosis of "a compromised immune system" (  = 854, 7.6%). We adherence to self-reported COVID-19 preventive behaviors among immunocompromised adults to others using -tests. We focused on continuity of care and estimated determinants of canceling doctor's appointments among the immunocompromised using multivariable Poisson regression to estimate adjusted prevalence ratios (aPRs) with 95% confidence intervals (95% CIs). We evaluated associations of mental health symptoms with being immunocompromised using multinomial logistic regression and estimated conditional odds ratios (cOR) with 95% CIs. Immunocompromised adults were more likely to adhere to recommended COVID-19 preventive behaviors, including washing or sanitizing hands (96.3% vs. 89.8%, <0.001), maintaining social distance (91.9% vs. 83.7%, <0.001), and canceling a doctor's appointment (47.1% vs. 29.7%, <0.001). Hispanic immunocompromised adults (aPR: 1.47, 95% CI: 1.12-1.92) and immunocompromised women (aPR: 1.25, 95% CI: 1.00-1.56) were more likely to cancel doctor's appointments compared to non-Hispanic White immunocompromised adults and men, respectively. Immunocompromised adults reported higher odds of feeling nervous/anxious/on edge (cOR: 1.89, 95% CI: 1.44-2.51), depressed (cOR: 2.81, 95% CI: 2.17-3.64), lonely (cOR: 2.28, 95% CI: 1.74-2.98), and hopeless (cOR: 2.86, 95% CI: 2.21-3.69) 3-7 days in the last week. Immunocompromised adults were more likely to cancel their doctor's appointments and report COVID19-related mental health symptoms. The continuity of care of immunocompromised adults should be prioritized through alternative interventions, such as telehealth

Prevalence and Risk Factors of COVID-19 Symptoms among U.S. Adults with Allergies

Background: This study sought to evaluate COVID-19 associated physical and mental health symptoms among adults with allergies compared to the general U.S. adult population. Methods: Data for these analyses were obtained from the publicly available COVID-19 Household Impact Survey, which provides national and regional statistics about physical health, mental health, economic security, and social dynamics among U.S. adults (ages 18 and older). Data from 20–26 April 2020; 4–10 May 2020; and 30 May–8 June 2020 were included. Our primary outcomes for this analysis were physical and mental health symptoms experienced in the last seven days. The primary predictor was participants’ self-report of a physician diagnosis of an allergy. Results/Discussion: This study included 10,760 participants, of whom 44% self-reported having allergies. Adults with allergies were more likely to report physical symptoms compared to adults without allergies including fever (aOR 1.7, 95% CI 1.44–1.99), cough (aOR 1.9, 95% CI 1.60–2.26), shortness of breath (aOR 2.04, 95% CI 1.71–2.43), and loss of taste or sense of smell (aOR 1.9, 95% CI 1.58–2.28). Adults with allergies were more likely to report feeling nervous (cOR 1.34, 95% CI 1.13, 1.60), depressed (cOR 1.32, 95% CI 1.11–1.57), lonely (cOR 1.23, 95% CI 1.04–1.47), hopeless (cOR 1.44, 95% CI 1.21–1.72), or having physical reactions when thinking about COVID-19 pandemic (cOR 2.01, 95% CI 1.44–2.82), compared to those without allergies. During the COVID-19 pandemic, adults with allergies are more likely to report physical and mental health symptoms compared to individuals without allergies. These findings have important implications for diagnostic and treatment challenges for allergy physicians

Prevalence and Risk Factors of COVID-19 Symptoms among U.S. Adults with Allergies

Background: This study sought to evaluate COVID-19 associated physical and mental health symptoms among adults with allergies compared to the general U.S. adult population. Methods: Data for these analyses were obtained from the publicly available COVID-19 Household Impact Survey, which provides national and regional statistics about physical health, mental health, economic security, and social dynamics among U.S. adults (ages 18 and older). Data from 20–26 April 2020; 4–10 May 2020; and 30 May–8 June 2020 were included. Our primary outcomes for this analysis were physical and mental health symptoms experienced in the last seven days. The primary predictor was participants’ self-report of a physician diagnosis of an allergy. Results/Discussion: This study included 10,760 participants, of whom 44% self-reported having allergies. Adults with allergies were more likely to report physical symptoms compared to adults without allergies including fever (aOR 1.7, 95% CI 1.44–1.99), cough (aOR 1.9, 95% CI 1.60–2.26), shortness of breath (aOR 2.04, 95% CI 1.71–2.43), and loss of taste or sense of smell (aOR 1.9, 95% CI 1.58–2.28). Adults with allergies were more likely to report feeling nervous (cOR 1.34, 95% CI 1.13, 1.60), depressed (cOR 1.32, 95% CI 1.11–1.57), lonely (cOR 1.23, 95% CI 1.04–1.47), hopeless (cOR 1.44, 95% CI 1.21–1.72), or having physical reactions when thinking about COVID-19 pandemic (cOR 2.01, 95% CI 1.44–2.82), compared to those without allergies. During the COVID-19 pandemic, adults with allergies are more likely to report physical and mental health symptoms compared to individuals without allergies. These findings have important implications for diagnostic and treatment challenges for allergy physicians