Patients’ experiences undergoing breast evaluation in Rwanda’s Women’s Cancer Early Detection Program (preprint)

Purpose There is urgent need for interventions to facilitate earlier diagnosis of breast cancer in low- and middle-income countries where mammography screening is not widely available. Understanding patients’ experiences with early detection efforts, whether they are ultimately diagnosed with cancer or benign disease, is critical to optimize interventions and maximize community engagement. We sought to understand the experiences of patients undergoing breast evaluation in Rwanda’s Women’s Cancer Early Detection Program (WCEDP).Methods We conducted in-person semi-structured interviews with 30 patients in two districts of Rwanda participating in the WCEDP. Patients represented a range of ages and both benign and malignant diagnoses. Interviews were recorded, transcribed, translated, and thematically analyzed.Results Participants identified facilitators and barriers of timely care along the breast evaluation pathway. Community awareness initiatives were facilitators to care-seeking, while persistent myths and stigma about cancer were barriers. Participants valued clear clinician-patient communication and emotional support from clinicians and peers. Poverty was a major barrier for participants who described difficulty paying for transport, insurance premiums, and other direct and indirect costs of hospital referrals in particular. COVID-19 lockdowns caused delays for referred patients. Although false-positive clinical breast exams conferred financial and emotional burdens, participants nonetheless voiced appreciation for their experience and felt empowered to monitor their own breast health and share knowledge with others.Conclusion Rwandan women experienced both benefits and burdens as they underwent breast evaluation. Enthusiasm for participation was not reduced by the experience of a false positive result. Reducing financial, logistical and emotional burdens of the breast diagnostic pathway through patient navigation, peer support and decentralization of diagnostic services could improve patients’ experience.

Vaccine effectiveness of BNT162b2 and CoronaVac against SARS-CoV-2 omicron infection and related hospital admission among people with substance use disorder in Hong Kong: a matched case-control study.

BACKGROUND: People with substance use disorder have a high risk of SARS-CoV-2 infection and subsequent poor outcomes. Few studies have evaluated COVID-19 vaccine effectiveness among people with substance use disorder. We aimed to estimate the vaccine effectiveness of BNT162b2 (Fosun-BioNTech) and CoronaVac (Sinovac) against SARS-CoV-2 omicron (B.1.1.529) infection and related hospital admission in this population. METHODS: We did a matched case-control study using electronic health databases in Hong Kong. Individuals diagnosed with substance use disorder between Jan 1, 2016, and Jan 1, 2022, were identified. People aged 18 years and older with SARS-CoV-2 infection from Jan 1 to May 31, 2022, and people with COVID-19-related hospital admission from Feb 16 to May 31, 2022, were included as cases and were matched by age, sex, and previous clinical history with controls from all individuals diagnosed with substance use disorder who attended the Hospital Authority health services: up to three controls for SARS-CoV-2 infection and up to ten controls for hospital admission. Conditional logistical regression was used to evaluate the association between vaccination status (ie, one, two, or three doses of BNT162b2 or CoronaVac) and the risk of SARS-CoV-2 infection and COVID-19-related hospital admission, adjusted for baseline comorbidities and medication use. FINDINGS: Among 57 674 individuals with substance use disorder, 9523 people with SARS-CoV-2 infections (mean age 61·00 years, SD 14·90; 8075 [84·8%] males and 1448 [15·2%] females) were identified and matched to 28 217 controls (mean age 60·99 years, 14·67; 24 006 [85·1%] males and 4211 [14·9%] females), and 843 people with COVID-19-related hospital admissions (mean age 70·48 years, SD 14·68; 754 [89·4%] males and 89 [10·6%] females) were identified and matched to 7459 controls (mean age 70·24 years, 13·87; 6837 [91·7%] males and 622 [8·3%] females). Data on ethnicity were not available. We observed significant vaccine effectiveness against SARS-CoV-2 infection for two-dose BNT162b2 vaccination (20·7%, 95% CI 14·0-27·0, p<0·0001) and three-dose vaccination (all BNT162b2 41·5%, 34·4-47·8, p<0·0001; all CoronaVac 13·6%, 5·4-21·0, p=0·0015; BNT162b2 booster after two-dose CoronaVac 31·3%, 19·8-41·1, p<0·0001), but not for one dose of either vaccine or two doses of CoronaVac. Significant vaccine effectiveness against COVID-19-related hospital admission was detected after one dose of BNT162b2 vaccination (35·7%, 3·8-57·1, p=0·032), two-dose vaccination (both BNT162b2 73·3%, 64·3 to 80·0, p<0·0001; both CoronaVac 59·9%, 50·2-67·7, p<0·0001), and three-dose vaccination (all BNT162b2 86·3%, 75·6-92·3, p<0·0001; all CoronaVac 73·5% 61·0-81·9, p<0·0001; BNT162b2 booster after two-dose CoronaVac 83·7%, 64·6-92·5, p<0·0001), but not after one dose of CoronaVac. INTERPRETATION: For both BNT162b2 and CoronaVac, two-dose or three-dose vaccination was protective against COVID-19-related hospital admission and the booster dose provided protection against SARS-CoV-2 infection among people with substance use disorder. Our findings confirm the importance of booster doses in this population during the period dominated by the omicron variant. FUNDING: Health Bureau, the Government of the Hong Kong Special Administrative Region.

Is Treating Post-Menopausal Women With Symptomatic Hand Osteoarthritis With Hormone Replacement Therapy Feasible?: Results From The Hope-E Randomised, Placebo-Controlled Feasibility Study

Purpose: Hand osteoarthritis (OA) is more common in women. Hand OA incidence increases further in females around the age of 50, the typical age of menopause. Estrogen-deficient states are associated with increased musculoskeletal pain and inflammation and with increased rates of symptomatic OA. Estrogen replacement and selective estrogen receptor modulators (SERMs) can improve pain and structure in some pre-clinical models of OA associated with estrogen loss, and in exploratory analysis from hormone replacement therapy (HRT) trials. However, no randomised clinical trials (RCTs) of HRT had been performed in symptomatic OA populations, specifically hand OA. By carrying out a RCT feasibility study of a form of HRT (conjugated estrogens (CE)-bazedoxifene) in post-menopausal women with painful hand OA, we set out to determine the feasibility and acceptability of this. We also aimed to generate proof-of concept data on likely outcomes, calculate a sample size and refine methods for a full trial. Method(s): We recruited females aged 40-65 years and 1-10 years after final menstrual period with definite hand OA and >=2 painful hand joints across three primary/secondary care sites and from the community. Medical exclusions included those typical for clinical HRT use. Design was parallel group, double-blind 1:1 randomisation of CE-bazedoxifene or placebo, taken orally once daily for 24 weeks, then tapering for 4 weeks before study end at Week 28. Primary feasibility outcomes were rates of eligible participant identification, recruitment, randomisation, retention, compliance, and likelihood of unblinding. Adverse events (AEs) were collected. Secondary clinical outcomes included the anticipated primary outcome in a full trial of mean hand pain over 14 days prior to each visit, scored on a 0-10 numerical rating scale (NRS) where 10 is worst pain possible, as well as hand function, appearance and menopause symptoms. Progression criteria to a full RCT were: (i) recruitment >=30 participants across all sites in 18 months (or proportionate to time open);(ii) a drop-out rate of <=30% of randomised individuals;and (iii) acceptability to the majority of participants, including acceptable AE rates. All clinical outcomes were analysed on an intention-to-treat basis. Though not powered to detect a treatment difference, change and treatment effects (the difference in the outcome between the two groups) were indicated with 95% CIs, with all models adjusted for clinical subtype of painful hand joint, study site, and baseline values. The sample size for a full trial was estimated using the standard deviation (SD) of week 24 mean hand pain. Result(s): Due to the COVID-19 pandemic, the recruitment window was reduced to 12-15 months. From May 2019 to December 2020, 434 enquiries/referrals were received. Of 96 telephone pre-screens, 35 individuals were potentially eligible and of these, 33 gave consent to participate. Of the remaining, 250/401 (62%) were ineligible, whilst 55/401 (14%) chose not to proceed, with the most common reason being not wanting to take HRT. 28/35 (80% (95%CI 63%,92%)) eligible participants were randomised to study medication. All 28 participants completed all follow-ups with high compliance (100% active, 13/14[93%] placebo) and outcome measure completeness (100%, mean hand pain). All three AE-related treatment withdrawals were on placebo when unblinded. No serious AEs occurred. Participants/investigators were well blinded (participant blinding index 0.50[95%CI 0.25 to 0.75]). All three prespecified progression criteria were therefore met for a full trial. The treatment effect difference over 24 weeks in mean hand pain between active and placebo was -0.71 (95% CI -2.20 to 0.78) (Fig 1A). During tapering/stopping medication, mean hand pain increased by 1.31 points in the active arm compared with 0.17 in the placebo arm, indicating a possible effect of cessation of medication (Fig 1A). Furthermore, 6/13 (46%) participants in the active group reported worsening pain at week 28 compared with week 24, but only 2/12 (17%) were worse on withdrawing placebo (Fig 1B). The sample size for a full trial was estimated as 296 (based on MCID 0.8 on NRS, SD 2.0, 90% power, 10% drop-out, alpha 5%). Conclusion(s): This first study of a RCT of HRT for painful hand OA met its progression criteria, indicating that a full trial of an HRT in this population is feasible and acceptable. Although not powered to detect an effect, there was a trend towards improvement in hand pain on treatment and worsening of hand pain on tapering in the active arm only. This adds to proof-of-concept data in this area, justifying more work.ISRCTN12196200. Funded by Research for Patient Benefit programme, National Institute for Health Research (UK) PB-PG-0416-20023 [Formula presented]Copyright © 2023

BNT162b2 or CoronaVac Vaccinations Are Associated With a Lower Risk of Myocardial Infarction and Stroke After SARS-CoV-2 Infection Among Patients With Cardiovascular Disease.

Background COVID-19 vaccines have demonstrated effectiveness against SARS-CoV-2 infection, hospitalization, and mortality. The association between vaccination and risk of cardiovascular complications shortly after SARS-CoV-2 infection among patients with cardiovascular disease remains unknown. Methods and Results A case-control study was conducted with cases defined as patients who had myocardial infarction or stroke within 28 days after SARS-CoV-2 infection between January 1, 2022 and August 15, 2022. Controls were defined as all other patients who attended any health services and were not cases. Individuals without history of cardiovascular disease were excluded. Each case was randomly matched with 10 controls according to sex, age, Charlson comorbidity index, and date of hospital admission. Adjusted odds ratio with 95% CI was estimated using conditional logistic regression. We identified 808 cases matched with 7771 controls among all patients with cardiovascular disease. Results showed that vaccination with BNT162b2 or CoronaVac was associated with a lower risk of myocardial infarction or stroke after SARS-CoV-2 infection with a dose-response relationship. For BNT162b2, risk decreased from 0.49 (95% CI, 0.29-0.84) to 0.30 (95% CI, 0.20-0.44) and 0.17 (95% CI, 0.08-0.34) from 1 to 3 doses, respectively. Similar trends were observed for CoronaVac, with risk decreased from 0.69 (95% CI, 0.57-0.85) to 0.42 (95% CI, 0.34-0.52) and 0.32 (95% CI, 0.21-0.49) from 1 to 3 doses, respectively. Conclusions Vaccination with BNT162b2 or CoronaVac is associated with a lower risk of myocardial infarction or stroke after SARS-CoV-2 infection among patients with cardiovascular disease.

Impact of facilitating continued accessibility to cancer care during COVID-19 lockdown on perceived wellbeing of cancer patients at a rural cancer center in Rwanda

During the COVID-19 pandemic in Rwanda, Partners In Health Inshuti Mu Buzima collaborated with the Butaro Cancer Center of Excellence (BCCOE) to mitigate disruptions to cancer care by providing patients with free transportation to treatment sites and medication delivery at patients' local health facilities. We assessed the relationship between facilitated access to care and self-reported wellbeing outcomes. This cross-sectional telephone survey included cancer patients enrolled at BCCOE in March 2020. We used linear regression to compare six dimensions of quality of life (EORTC QLQ-C30), depression (PHQ-9), anxiety (GAD-7), and financial toxicity (COST) among patients who did and did not receive facilitated access to care. We also assessed access to cancer care and whether patient wellbeing and its association with facilitated access to care differed by socioeconomic status. Of 214 respondents, 34.6% received facilitated access to care. Facilitated patients were more likely to have breast cancer and be on chemotherapy. Facilitation was significantly associated with more frequent in-person clinical encounters, improved perceived quality of cancer care, and reduced transportation-related barriers. Facilitated patients had significantly better global health status (β = 9.14, 95% CI: 2.3, 16.0, p <0.01) and less financial toxicity (β = 2.62, 95% CI: 0.2,5.0, p = 0.03). However, over half of patients reported missing or delaying appointment. Patient wellbeing was low overall and differed by patient socioeconomic status, with poor patients consistently showing worse outcomes. Socioeconomic status did not modify the association between facilitated access to care and wellbeing indicators. Further, facilitation did not lead to equitable wellbeing outcomes between richer and poorer patients. Facilitated access to care during COVID-19 pandemic was associated with some improvements in access to cancer care and patient wellbeing. However, cancer patients still experienced substantial disruptions to care and reported low overall levels of wellbeing, with socioeconomic disparities persisting despite facilitated access to care. Implementing more robust, equity-minded facilitation and better patient outreach programs during health emergencies may promote better care and strengthen patient care overall and effect better patients' outcomes.

Drug Repurposing for the Treatment of COVID-19: A Knowledge Graph Approach.

Identifying effective drug treatments for COVID-19 is essential to reduce morbidity and mortality. Although a number of existing drugs have been proposed as potential COVID-19 treatments, effective data platforms and algorithms to prioritize drug candidates for evaluation and application of knowledge graph for drug repurposing have not been adequately explored. A COVID-19 knowledge graph by integrating 14 public bioinformatic databases containing information on drugs, genes, proteins, viruses, diseases, symptoms and their linkages is developed. An algorithm is developed to extract hidden linkages connecting drugs and COVID-19 from the knowledge graph, to generate and rank proposed drug candidates for repurposing as treatments for COVID-19 by integrating three scores for each drug: motif scores, knowledge graph PageRank scores, and knowledge graph embedding scores. The knowledge graph contains over 48 000 nodes and 13 37 000 edges, including 13 563 molecules in the DrugBank database. From the 5624 molecules identified by the motif-discovery algorithms, ranking results show that 112 drug molecules had the top 2% scores, of which 50 existing drugs with other indications approved by health administrations reported. The proposed drug candidates serve to generate hypotheses for future evaluation in clinical trials and observational studies.

Sex-based differences in risk of ischemic stroke or systemic embolism after BNT162b2 or CoronaVac COVID-19 vaccination in patients with atrial fibrillation: A self-controlled case series and nested case-control study.

AIMS: Patients with atrial fibrillation (AF) have a higher risk of ischemic stroke or systemic embolism with a greater risk for female patients. This study aims to evaluate the risk of ischemic stroke or systemic embolism and bleeding following COVID-19 vaccination in patients with AF and the sex differences. METHODS AND RESULTS: Self-controlled case series (SCCS) analysis was conducted to evaluate the risk of ischemic stroke or systemic embolism and bleeding following BNT162b2 or CoronaVac in patients with AF, using the territory-wide electronic medical records from the Hospital Authority and vaccination records from the Department of Health in Hong Kong. Patients with a primary diagnosis of ischemic stroke or systemic embolism or bleeding in the inpatient setting between February 23, 2021 and March 31, 2022 were included. A nested case-control analysis was also conducted with each case randomly matched with ten controls according to sex, age, Charlson comorbidity index and date of hospital admission. Conditional Poisson regression was used in the SCCS analysis and conditional logistic regression was used in nested case-control analysis to assess the risks and all analyses were stratified by sex and type of vaccines. Among 51 158 patients with AF, we identified an increased risk of ischemic stroke or systemic embolism after the first dose of BNT162b2 in SCCS analysis during 0-13 days (incidence rate ratio 6.60[95% CI 1.51-28.77]) and 14-27 days (6.53[95% CI 1.31-32.51]), and nested case-control analysis during 0-13 days (adjusted odds ratio 6.21 [95% CI 1.14-33.91]) and 14-27 days (5.52 [95% CI 1.12-27.26]) only in female patients. The increased risk in female patients following the first dose of CoronaVac was only detected during 0-13 days (3.88 [95% CI 1.67-9.03]) in the nested case-control analysis. No increased risk of ischemic stroke or systemic embolism was identified in male patients and no increased risk of bleeding was detected in all patients with AF for both vaccines. An increased risk of ischemic stroke or systemic embolism after COVID-19 was also observed in both females (17.42 [95% CI 5.08-59.73]) and males (6.63 [95% CI 2.02-21.79]). CONCLUSIONS: The risk of ischemic stroke or systemic embolism after COVID-19 vaccination was only increased in female patients with AF. However, as the risk after COVID-19 was even higher, proactive uptake of COVID-19 vaccines is recommended to prevent the potential severe outcomes after infection.

The impact of COVID-19 and national pandemic responses on health service utilisation in seven low- and middle-income countries.

BACKGROUND: The COVID-19 pandemic has disrupted health services worldwide, which may have led to increased mortality and secondary disease outbreaks. Disruptions vary by patient population, geographic area, and service. While many reasons have been put forward to explain disruptions, few studies have empirically investigated their causes. OBJECTIVE: We quantify disruptions to outpatient services, facility-based deliveries, and family planning in seven low- and middle-income countries during the COVID-19 pandemic and quantify relationships between disruptions and the intensity of national pandemic responses. METHODS: We leveraged routine data from 104 Partners In Health-supported facilities from January 2016 to December 2021. We first quantified COVID-19-related disruptions in each country by month using negative binomial time series models. We then modelled the relationship between disruptions and the intensity of national pandemic responses, as measured by the stringency index from the Oxford COVID-19 Government Response Tracker. RESULTS: For all the studied countries, we observed at least one month with a significant decline in outpatient visits during the COVID-19 pandemic. We also observed significant cumulative drops in outpatient visits across all months in Lesotho, Liberia, Malawi, Rwanda, and Sierra Leone. A significant cumulative decrease in facility-based deliveries was observed in Haiti, Lesotho, Mexico, and Sierra Leone. No country had significant cumulative drops in family planning visits. For a 10-unit increase in the average monthly stringency index, the proportion deviation in monthly facility outpatient visits compared to expected fell by 3.9% (95% CI: -5.1%, -1.6%). No relationship between stringency of pandemic responses and utilisation was observed for facility-based deliveries or family planning. CONCLUSIONS: Context-specific strategies show the ability of health systems to sustain essential health services during the pandemic. The link between pandemic responses and healthcare utilisation can inform purposeful strategies to ensure communities have access to care and provide lessons for promoting the utilisation of health services elsewhere.

Impact of COVID-19 on access to cancer care in Rwanda: a retrospective time-series study using electronic medical records data.

INTRODUCTION: The COVID-19 pandemic has caused disruptions in access to routine healthcare services worldwide, with a particularly high impact on chronic care patients and low and middle-income countries. In this study, we used routinely collected electronic medical records data to assess the impact of the COVID-19 pandemic on access to cancer care at the Butaro Cancer Center of Excellence (BCCOE) in rural Rwanda. METHODS: We conducted a retrospective time-series study among all Rwandan patients who received cancer care at the BCCOE between 1 January 2016 and 31 July 2021. The primary outcomes of interest included a comparison of the number of patients who were predicted based on time-series models of pre-COVID-19 trends versus the actual number of patients who presented during the COVID-19 period (between March 2020 and July 2021) across four key indicators: the number of new patients, number of scheduled appointments, number of clinical visits attended and the proportion of scheduled appointments completed on time. RESULTS: In total, 8970 patients (7140 patients enrolled before COVID-19 and 1830 patients enrolled during COVID-19) were included in this study. During the COVID-19 period, enrolment of new patients dropped by 21.7% (95% prediction interval (PI): -31.3%, -11.7%) compared with the pre-COVID-19 period. Similarly, the number of clinical visits was 25.0% (95% PI: -31.1%, -19.1%) lower than expected and the proportion of scheduled visits completed on time was 27.9% (95% PI: -39.8%, -14.1%) lower than expected. However, the number of scheduled visits did not deviate significantly from expected. CONCLUSION: Although scheduling procedures for visits continued as expected, our findings reveal that the COVID-19 pandemic interrupted patients' ability to access cancer care and attend scheduled appointments at the BCCOE. This interruption in care suggests delayed diagnosis and loss to follow-up, potentially resulting in a higher rate of negative health outcomes among cancer patients in Rwanda.

Stressful experiences impact clinical symptoms in people with endometriosis

Endometriosis is a chronic condition that affects ~10% of women globally. Its symptoms include chronic pelvic pain, heavy periods and tiredness/fatigue, which have been associated with poorer quality of life and mental health. We aim to explore the impact of the COVID-19 pandemic on pain and fatigue symptoms and their interactions with the impact on mental health in people with endometriosis. This global cross-sectional online survey study collected data from 4717 adults with self-reported surgical/radiological diagnosis of endometriosis between May and June 2020. The survey included questions on the current status and changes of endometriosis symptoms (pelvic pain, tiredness/fatigue, and bleeding patterns), mental health, pain catastrophising, and the impact of the COVID-19 pandemic on the respondents’ lives. Compared to 6 months earlier, Respondents reported a marked worsening of their endometriosis symptoms (endometriosis-associated pain (39.3%;95% CI: 37.7, 40.5), tiredness/fatigue (49.9%;95% CI: 48.4, 51.2) and bleeding patterns (39.6%;95% CI: 38.2, 41)) and mental health (38.6%;95% CI: 37.2, 39.9). Those with a pre-existing mental health diagnosis (38.8%) were more likely to report their symptoms worsening. Worsening of pain and tiredness/fatigue was significantly correlated with worsening of mental health (P < 0.001). The relationship between changes in mental health and (a) change in pain and (b) change in fatigue was found to be weakly mediated by pain catastrophising scores (pain: B = 0.071, lower limit of confidence interval (LLCI) = 0.060, upper limit of confidence interval (ULCI) = 0.082, tiredness/fatigue: B = 0.050, LLCI = 0.040, ULCI = 0.060). This study demonstrates that stressful experiences impact the physical and mental health of people with endometriosis. The findings highlight the need to consider psychological approaches in the holistic management of people with endometriosis.Lay summary: Endometriosis is a chronic condition in which tissue similar to that of the lining of the womb grows outside it. It affects around 10% of women globally, and the symptoms often include persistent pelvic pain, heavy periods and tiredness/fatigue. These symptoms are associated with impaired mental health and life quality. This study used an online questionnaire to assess the experiences of people with endometriosis during the first months of the pandemic. Results from 4717 adults revealed that pelvic pain, tiredness/fatigue and bleeding worsened in more than 39% of the participants. Poor mental health was also exacerbated and associated with worsening in tiredness/fatigue. Further analysis revealed that this relationship could be partially explained by ‘pain catastrophising’, which measures how participants think about their pain. Our results suggest that stressful experiences like the pandemic negatively impact the already burdened mental health of people with endometriosis, who could benefit from psychological interventions.

Safety of BNT162b2 or CoronaVac COVID-19 vaccines in patients with heart failure: A self-controlled case series study

Summary Background COVID-19 vaccines are important for patients with heart failure (HF) to prevent severe outcomes but the safety concerns could lead to vaccine hesitancy. This study aimed to investigate the safety of two COVID-19 vaccines, BNT162b2 and CoronaVac, in patients with HF. Methods We conducted a self-controlled case series analysis using the data from the Hong Kong Hospital Authority and the Department of Health. The primary outcome was hospitalization for HF and the secondary outcomes were major adverse cardiovascular events (MACE) and all hospitalization. We identified patients with a history of HF before February 23, 2021 and developed the outcome event between February 23, 2021 and March 31, 2022 in Hong Kong. Incidence rate ratios (IRR) were estimated using conditional Poisson regression to evaluate the risks following the first three doses of BNT162b2 or CoronaVac. Findings We identified 32,490 patients with HF, of which 3035 were vaccinated and had a hospitalization for HF during the observation period (BNT162b2 = 755;CoronaVac = 2280). There were no increased risks during the 0–13 days (IRR 0.64 [95% confidence interval 0.33–1.26];0.94 [0.50–1.78];0.82 [0.17–3.98]) and 14–27 days (0.73 [0.35–1.52];0.95 [0.49–1.84];0.60 [0.06–5.76]) after the first, second and third doses of BNT162b2. No increased risks were observed for CoronaVac during the 0–13 days (IRR 0.60 [0.41–0.88];0.71 [0.45–1.12];1.64 [0.40–6.77]) and 14–27 days (0.91 [0.63–1.32];0.79 [0.46–1.35];1.71 [0.44–6.62]) after the first, second and third doses. We also found no increased risk of MACE or all hospitalization after vaccination. Interpretation Our results showed no increased risk of hospitalization for HF, MACE or all hospitalization after receiving BNT162b2 or CoronaVac vaccines in patients with HF. Funding The project was funded by a Research Grant from the Food and Health Bureau, The Government of the Hong Kong Special Administrative Region (Ref. No. COVID19F01). F.T.T.L. (Francisco T.T. Lai) and I.C.K.W. (Ian C.K. Wong)'s posts were partly funded by the D24H;hence this work was partly supported by AIR@InnoHK administered by Innovation and Technology Commission.

Food insecurity and level of depression among patients with chronic diseases, and associated factors during the COVID-19 lockdown: a cross-sectional study in rural Rwanda.

OBJECTIVES: We aimed to describe access to food and symptoms of depression among patients with chronic diseases or their caregivers, and assess associated factors during the COVID-19 lockdown in rural Rwanda. DESIGN: A cross-sectional study. SETTING AND PARTICIPANTS: A stratified random sampling technique was used to recruit 220 patients enrolled in the HIV, non-communicable diseases, mental health, paediatric development clinic and oncology programmes in three rural districts of Rwanda. OUTCOME MEASURES: Telephone-based interviews were conducted to collect data on the number of daily meals before and during the COVID-19, and depression was assessed using the Patient Health Questionnaire-9. We used logistic regression analysis to investigate factors associated with households reporting a reduction in daily meals and with the survey respondent reporting symptoms of depression. RESULTS: Of the participants, 19.1% reported a reduction in daily number of meals for either adults or children in their households during lockdown and 24.6% had depression. Reporting a reduction in daily meals was associated with the district of residence and estimated household's monthly income. Self-reported depression was significantly associated with negative experiences during lockdown, including reporting feeling depressed or fear (AOR 4.82; 95% CI 2.08 to 11.21), loneliness (AOR 4.33; 95% CI 1.32 to 14.13), reduction in daily meals (AOR 4.15; 95% CI 1.56 to 11.00) and lack of access to healthcare (OR 3.29; 95% CI 1.32 to 8.23). CONCLUSIONS: Our findings suggest that significant reduction in access to food affected rural Rwandans with chronic diseases during COVID-19 lockdown, and the lockdown effect varied by household's pre-pandemic level of vulnerability to food insecurity. Reduction in household meals, as well as other self-reported effects of the lockdown, were associated with worse psychological status of survey respondents. Economic and food support should be considered by governments and non-governmental organisations to protect those most vulnerable including patients with chronic diseases against the effects of pandemics and their associated containment measures.

A Multi-Site Survey Study of Patient Satisfaction with Teledermatology.

Introduction: Telemedicine has been of heightened focus due to spikes in usage during the COVID-19 pandemic. Disparities in health care may affect patient satisfaction with this resource depending on factors such as patient race, age, or socioeconomic background. The purpose of this study was to analyze patient satisfaction with teledermatology to identify any differences in satisfaction based on race, age, and income during the COVID-19 pandemic period. Methods: A 21-question, IRB-approved survey was administered to patients at two academic dermatology clinics in Kansas City. Patient satisfaction was measured using a five-point Likert scale. Results: A total of 64 completed surveys were analyzed (17.8% response rate). Most of the participants were female (n = 48, 75%), age 45 to 60 (n = 17, 26.6%), and reported White for race (n = 55, 85.9%). Overall, 73.4% (n = 47) of patients reported being satisfied with their visit. However, only 38.7% (n = 24) of participants were likely to choose a video over an in-person visit. Reasons for low patient satisfaction included concerns regarding ability to perform an accurate physical exam with a video visit (n = 9, 14.1%), receiving inadequate care (n = 4, 6.3%), protected privacy (n = 3, 4.7%), and provider understanding the patient (n = 2, 3.1%). Conclusions: Our findings were similar to prior studies stating no difference in patient satisfaction with regards to age, income, or race and patients reporting high satisfaction with teledermatology appointments despite a preference for in-person dermatology visits. Future studies with a larger diverse cohort of participants are needed to elucidate and address possible disparities associated with teledermatology use.

HAND OSTEOARTHRITIS: INVESTIGATING PAIN EFFECTS in A RANDOMISED PLACEBO-CONTROLLED FEASIBILITY STUDY of ESTROGEN-CONTAINING THERAPY (HOPE-E): REPORT on the PRIMARY FEASIBILITY OUTCOMES

Background: There is an unmet need for new treatments for hand osteoarthri-tis (OA). Symptomatic hand OA is more common in women and its incidence increases round the age of menopause. Pre-clinical, epidemiological and post hoc studies in Hormone Replacement Therapy (HRT) trials implicate estrogen defciency as of likely importance in OA aetiopathogenesis. No clinical trials of HRT have been carried out in hand OA to date. The licensed HRT Duavive (conjugated estrogens + SERM bazedoxifene) was selected on its potential for efficacy and tolerability. Objectives: We set out to determine the feasibility and acceptability of this form of HRT in post-menopausal women with hand OA, to generate proof of concept data and refne methods for a full study. Methods: ISRCTN12196200. Females aged 40-65 yrs and 1-10yrs after fnal menstrual period with hand OA fulflling ACR criteria and 2+ painful hand joints were recruited. Eligibility incorporated best practice for HRT prescription but did not require menopausal symptoms. Recruitment was at 3 sites in primary/secondary care, including directly from the community. Design was parallel group, double-blind 1:1 randomisation of Duavive or placebo, orally once daily for 24 weeks, then weaning for 4 weeks before stopping. Routes and rates of recruitment and the acceptability of randomisation, medication (compliance, retention), and proposed outcomes were measured, and the likelihood of unblinding. Measures related to hand pain and function, menopause symptoms and joint appearance. Patient and Public Involvement actively informed study rationale, design and materials. An end of study questionnaire and 2 participant focus groups provided further acceptability data. Results: Recruitment was for 12/possible 18 months, interrupted due to COVID-19. Some study procedures were modifed to allow reopening whilst collecting all primary outcomes. 434 enquiries/referrals were received, leading to 96 telephone pre-screens, of which 33 gave written informed consent and attended face to face screening. 28/33 screened (85%) were eligible and randomised. The highest number of randomisations was from study web presence (n=7) followed by SMS text from GP surgeries (n=5). Of 401 not proceeding, 250 (62%) were ineligible, most commonly due to contraindicated medication, followed by medical contraindication, whilst 55 (14%) decided not to take part, for reasons including not wanting to take a hormone-based drug or difficulty attending study visits. Retention and compliance were excellent. All 28 participants completed all study follow ups, with only 3 withdrawals from treatment due to AEs, 2 of these at week 24 and all in the placebo arm. There were no serious AEs. High levels of completeness of all study outcome measures were achieved. Bang's blinding index suggested that participants/investigators were well blinded. There were overall high/good levels of satisfaction with taking part in the study. 26/28 (92%) would recommend taking part to others with hand OA (irrespective of study arm). Many found the fexibility offered by a combination of remote and face to face visits (due to the pandemic) attractive. Additional insights from focus groups were to include hand stiffness as well as pain measures but to reduce the overall number of questions. Conclusion: Despite COVID-19 and a reduced recruitment period, this study recruited sufficient numbers to assess feasibility outcomes. Randomisation of eligible people and retention rates were high. A mixture of remote and face to face visits due to COVID-19 probably improved recruitment and retention and was supported by participants, who were generally satisfed with the study design and medication. The study provided useful insight and improvements that would be incorporated into a future study. Overall, this feasibility study showed that with clear messaging on eligibility and a defned recruitment strategy, recruitment and retention to a study testing this treatment is possible.

Safety of two-dose COVID-19 vaccination (BNT162b2 and CoronaVac) in adults with cancer: a territory-wide cohort study.

BACKGROUND: The World Health Organization has defined a list of adverse events of special interest (AESI) for safety surveillance of vaccines. AESI have not been adequately assessed following COVID-19 vaccination in patients with cancer contributing to vaccine hesitancy in this population. We aimed to evaluate the association between BNT162b2 and CoronaVac vaccines and the risk of AESI in adults with active cancer or a history of cancer. PATIENTS AND METHODS: We conducted a territory-wide cohort study using electronic health records managed by the Hong Kong Hospital Authority and vaccination records provided by the Department of Health. Patients with a cancer diagnosis between January 1, 2018, and September 30, 2021, were included and stratified into two cohorts: active cancer and history of cancer. Within each cohort, patients who received two doses of BNT162b2 or CoronaVac were 1:1 matched to unvaccinated patients using the propensity score. Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CIs) for AESI 28 days after the second vaccine dose. RESULTS: A total of 74,878 patients with cancer were included (vaccinated: 25,789 [34%]; unvaccinated: 49,089 [66%]). Among patients with active cancer, the incidence of AESI was 0.31 and 1.02 per 10,000 person-days with BNT162b2 versus unvaccinated patients and 0.13 and 0.88 per 10,000 person-days with CoronaVac versus unvaccinated patients. Among patients with history of cancer, the incidence was 0.55 and 0.89 per 10,000 person-days with BNT162b2 versus unvaccinated patients and 0.42 and 0.93 per 10,000 person-days with CoronaVac versus unvaccinated patients. Neither vaccine was associated with a higher risk of AESI for patients with active cancer (BNT162b2: HR 0.30, 95% CI 0.08-1.09; CoronaVac: 0.14, 95% CI 0.02-1.18) or patients with history of cancer (BNT162b2: 0.62, 95% CI 0.30-1.28; CoronaVac: 0.45, 95% CI 0.21-1.00). CONCLUSIONS: In this territory-wide cohort study of patients with cancer, the incidence of AESI following vaccination with two doses of either BNT162b2 or CoronaVac vaccines was low. The findings of this study can reassure clinicians and patients with cancer about the overall safety of BNT162b2 and CoronaVac in patients with cancer, which could increase the COVID-19 vaccination rate in this vulnerable group of patients.

Association between BNT162b2 or CoronaVac COVID-19 vaccines and major adverse cardiovascular events among individuals with cardiovascular disease.

AIMS: Concern about the cardiovascular safety of coronavirus disease 2019 (COVID-19) vaccines among individuals with cardiovascular disease (CVD) may lead to vaccine hesitancy. We sought to assess the association between two COVID-19 vaccines, BNT162b2 and CoronaVac, and the risk of major adverse cardiovascular events (MACE) in individuals with established CVD. METHODS AND RESULTS: We identified individuals with a history of CVD before 23 February 2021 and a diagnosis of MACE between 23 February 2021 and 31 January 2022 in Hong Kong. MACE was defined as a composite of myocardial infarction, stroke, revascularization, and cardiovascular death. Electronic health records from the Hong Kong Hospital Authority were linked to vaccination records from the Department of Health. A self-controlled case-series method was used to evaluate the risk of MACE for 0-13 and 14-27 days after two doses of COVID-19 vaccine. We estimated incidence rate ratios (IRRs) to compare the risk of MACE between each risk period and the baseline period. A total of 229 235 individuals with CVD were identified, of which 1764 were vaccinated and had a diagnosis of MACE during the observation period (BNT162b2 = 662; CoronaVac = 1102). For BNT162b2, IRRs were 0.48 [95% confidence interval (CI) 0.23-1.02] for the first dose and 0.87 (95% CI 0.50-1.52) for the second dose during the 0-13 days risk period, 0.40 (95% CI 0.18-0.93) for the first dose and 1.13 (95% CI 0.70-1.84) for the second dose during the 14-27 days risk period. For CoronaVac, the IRRs were 0.43 (95% CI 0.24-0.75) for the first dose and, 0.73 (95% CI 0.46-1.16) for the second dose during the 0-13 days risk period, 0.54 (95% CI 0.33-0.90) for the first dose and 0.83 (95% CI 0.54-1.29) for the second dose during the 14-27 days risk period. Consistent results were found in subgroup analyses for different sexes, age groups and different underlying cardiovascular conditions. CONCLUSION: Our findings showed no evidence of an increased risk of MACE after vaccination with BNT162b2 or CoronaVac in patients with CVD. Future research is required to monitor the risk after the third dose of each vaccine.

COVID-19 Vaccination Preferences of University Students and Staff in Hong Kong.

Importance: COVID-19 has required universities to rapidly develop vaccination policies for students and staff, yet little is known about the preferences of these individuals toward vaccination. Objective: To quantify student and staff preferences for COVID-19 vaccination at a university in Hong Kong. Design, Setting, and Participants: A cross-sectional online survey study was conducted from July 20 to September 21, 2021, before the announcement of a campus-wide vaccine mandate. A survey of 42 451 eligible university students and staff used discrete-choice experiment methods to quantify 7 attributes of COVID-19 vaccination: risk of a mild or moderate adverse event after vaccination, risk of a severe adverse event after vaccination, efficacy against COVID-19 infection, efficacy against severe manifestation of COVID-19 infection, duration of protection after vaccination, incentive for completing vaccination, and out-of-pocket costs. Main Outcomes and Measures: A mixed logit regression model was used to estimate the preferences of attributes for COVID-19 vaccines and marginal willingness to pay (mWTP) adjusted for background characteristics, role, vaccination, and COVID-19 infection status of family or friends, adverse event status after vaccination among family and friends of participants, and scenario block. Results: Among 42 451 eligible university students and staff invited, 3423 individuals completed the survey (mean [SD] age, 27.1 [9.9] years; 2053 [60.0%] women). Participants included 2506 students (73.2%) and 917 staff (26.8%), with a response rate of 8.1%. Quarantine-free travel was preferred (ß = 0.86; 95% CI, 0.72-0.99; mWTP: $235.9; 95% CI, $190.3-$294.2), followed by efficacy against any COVID-19 infection (ß = 0.30; 95% CI, 0.29-0.32; mWTP: $84.1; 95% CI, $71.8-$100.8), against severe manifestation of COVID-19 infection (ß = 0.25; 95% CI, 0.24-0.27; mWTP: $69.7; 95% CI, $465-$653), and risk of severe adverse events following vaccination (ß = -0.24; 95% CI, -0.27 to -0.21; mWTP: -$66.8; 95% CI, -$81.5 to -$55.3). Participants were less concerned about protection duration (ß = 0.17; 95% CI, 0.15-0.18; mWTP: $46.0; 95% CI, $38.6-$56.2) and risk of mild to moderate adverse events (ß = -0.12; 95% CI, -0.13 to -0.10; mWTP: -$32.7; 95% CI, -$41.2 to -$26.4). Conclusions and Relevance: Preference of all attributes were significant and were considered important by the participants for vaccine decision-making. Insights drawn could assist policy makers in future vaccination decisions, such as campus vaccine mandate and requirement of a third dose.

Rwanda's community health workers at the front line: a mixed-method study on perceived needs and challenges for community-based healthcare delivery during COVID-19 pandemic.

OBJECTIVE: During the COVID-19 pandemic, community health workers (CHWs) served as front-line workers in the COVID-19 response while maintaining community health services. We aimed to understand challenges faced by Rwanda's CHWs during a nationwide COVID-19 lockdown that occurred between March and May 2020 by assessing the availability of trainings, supplies and supervision while exploring perceived needs and challenges. DESIGN AND SETTING: This study was a mixed-method study conducted in three Rwandan districts: Burera, Kirehe and Kayonza. MAIN OUTCOME AND MEASURE: Using data collected via telephone, we assessed the availability of trainings, supplies and supervision during the first national lockdown, while exploring perceived needs and challenges of CHWs who were engaged in COVID-19 response, in addition to their existing duties of delivering health services in the community. RESULTS: Among the 292 quantitative survey participants, CHWs were responsible for a median of 55 households (IQR: 42-79) and visited a median of 30 households (IQR: 11-52) in the month prior to the survey (July 2020). In the previous 12 months, only 164 (56.2%) CHWs reported being trained on any health topic. Gaps in supply availability, particularly for commodities, existed at the start of the lockdown and worsened over the course of the lockdown. Supervision during the lockdown was low, with nearly 10% of CHWs never receiving supervision and only 24% receiving at least three supervision visits during the 3-month lockdown. In qualitative interviews, CHWs additionally described increases in workload, lack of personal protective equipment and COVID-specific training, fear of COVID-19, and difficult working conditions. CONCLUSION: Many challenges faced by CHWs during the lockdown predated COVID-19 and persisted or were exacerbated during the pandemic. To promote the resilience of Rwanda's CHW system, we recommend increased access to PPE; investment in training, supervision and supply chain management; and financial compensation for CHWs.

Erratum: Drug Repurposing for the Treatment of COVID-19: A Knowledge Graph Approach.

[This corrects the article DOI: 10.1002/adtp.202100055.].