Citations

Abstract Background: Hypertension is a widely prevalent condition associated with significant morbidity and premature mortality, primarily because it is a risk factor for CVDs. The aim of this study was to estimate the trend of the burden of hypertension in Saudi Arabia in the last three decades. Methods: We conducted a systematic analysis of secondary data obtained from the Global Burden of Disease Study (GBD). We estimated sex-stratified, age-standardised and age-specific rates (per 100,000) of prevalence, deaths, and disability-adjusted years (DALYs) associated with hypertension in adults aged 20-94 years in Saudi Arabia between 1990 and 2019. Results: In Saudi Arabia, the age-standardised prevalence of hypertension increased from 87.7 cases per 100,000 in 1990 to 94.9 per 100,000 in 2019. More women than men had hypertension throughout the past three decades. The death and DALYs rate, however, decreased during this time. In 1990, 9.2 deaths per 100,000 in women and 3.0 deaths per 100,000 in men were due to hypertension; the respective rates declined to 6.5 and 2.8 in 2019. While the rates of DALYs in women declined steadily from 211.7 to 151.8 per 100,000 DALYs between 1990 and 2019, the rate in males did not decline considerably. The burden of hypertension–prevalence, deaths, and DALYs–were greater in older people. Conclusion: The prevalence of hypertension has increased in Saudi Arabia during the last 30 years; however, death rates and DALY related to hypertension has decreased during this time. Age- and sex-specific strategies are needed to decrease the prevalence of hypertension in Saudi Arabia.

Background: Despite the well-established potent benefit of mechanical thrombectomy (MT) for large vessel occlusion (LVO) stroke, access to MT has not been studied globally. We conducted a worldwide survey of countries on 6 continents to define MT access (MTA), the disparities in MTA, and its determinants on a global scale. Methods: Our survey was conducted in 75 countries through the Mission Thrombectomy 2020+ global network between November 22, 2020, and February 28, 2021. The primary end points were the current annual MTA, MT operator availability, and MT center availability. MTA was defined as the estimated proportion of patients with LVO receiving MT in a given region annually. The availability metrics were defined as ([current MT operators×50/current annual number of estimated thrombectomy-eligible LVOs]×100 = MT operator availability) and ([current MT centers×150/current annual number of estimated thrombectomy-eligible LVOs]×100= MT center availability). The metrics used optimal MT volume per operator as 50 and an optimal MT volume per center as 150. Multivariable-adjusted generalized linear models were used to evaluate factors associated with MTA. Results: We received 887 responses from 67 countries. The median global MTA was 2.79% (interquartile range, 0.70–11.74). MTA was <1.0% for 18 (27%) countries and 0 for 7 (10%) countries. There was a 460-fold disparity between the highest and lowest nonzero MTA regions and low-income countries had 88% lower MTA compared with high-income countries. The global MT operator availability was 16.5% of optimal and the MT center availability was 20.8% of optimal. On multivariable regression, country income level (low or lower–middle versus high: odds ratio, 0.08 [95% CI, 0.04–0.12]), MT operator availability (odds ratio, 3.35 [95% CI, 2.07–5.42]), MT center availability (odds ratio, 2.86 [95% CI, 1.84–4.48]), and presence of prehospital acute stroke bypass protocol (odds ratio, 4.00 [95% CI, 1.70–9.42]) were significantly associated with increased odds of MTA. Conclusions: Access to MT on a global level is extremely low, with enormous disparities between countries by income level. The significant determinants of MT access are the country’s per capita gross national income, prehospital LVO triage policy, and MT operator and center availability.

499 Background: The impact of socioeconomic status on gastrointestinal (GI) cancer mortality in the United States (US) is not well-established. We hypothesized that socially vulnerable populations have disproportionately higher mortality rates. Hence, we assessed the association of the social vulnerability index (SVI) with GI cancer mortality across US counties. Methods: Social vulnerability indices were obtained from the agency for toxic substances and disease registry (ATSDR) from 2014-2018 to compute percentile ranking scores (PRS: ranging from 0-1) for each US county. PRS were further categorized into quartiles (Q: 1st: 0-0.25 [least vulnerable]; 4th:0.75-1.00 [most vulnerable]). The wide-ranging online data for epidemiological research (WONDER) database was queried to abstract county-level age-adjusted mortality rates (AAMR) per 100,000 person-years (PY) for populations diagnosed with GI cancers. AAMRs were then linked with quartile rankings. Rate ratios (RR) of AAMRs between 4th and 1st Q were subsequently estimated with 95% confidence intervals using population-weighted, Poisson regression. Results: A total of 3142 counties were included in this analysis. The AAMR for overall deaths (OD) and premature deaths (PD; defined as death at age <65) in the GI cancer population was 53.8 and 17.7 per 100,000 PY. A gradient increase in GI cancer-related mortality was observed from 1st Q to 4th Q (OD: 49.2 vs 59.3; PD: 14.1 vs 21.3). This stepwise increase in AAMR over the quartiles was consistent across gender, different racial/ethnic subgroups, and rural/urban categories of counties. The AAMRs for OD were significantly higher in the 4th Q as compared to the 1st Q for gastric (RR: 1.67 [95% CI, 1.51-1.86]), hepatocellular including intrahepatic biliary (1.52 [1.45-1.61]), colorectal (1.21 [1.16-1.26]) and biliary (1.17 [1.06-1.28]) cancer. Similarly, significantly higher AAMRs for PD were observed in 4th Q vs1st Q for gastric (1.81 [1.60-2.05]), hepatocellular including intrahepatic biliary (1.78 [1.58-2.00]), biliary (1.64 [1.35-1.99]), colorectal (1.29 [1.21-1.39]) and pancreatic (1.16 [1.07-1.25]) cancer. However, no significant differences were observed for esophageal and small intestinal cancers. Men with gastric (1.58 [1.41-1.78]) and hepatocellular cancer (1.54 [1.43-1.66]), non-Hispanic Black population (1.54 [1.31-1.80]) with hepatocellular cancer, and Hispanic population with colorectal cancer (1.50 [1.31-1.72]) were observed to have higher overall mortality in the 4th Q compared to the 1st Q. The findings were similar for premature mortality. Conclusions: Population-level data suggests that the US counties with higher socio-economic adversities may be at an increased risk of GI cancer-related mortality. Investigations using patient-level data are required to probe the impact of socioeconomic vulnerabilities on cancer-related mortality.

23 Background: Identification of factors associated with enrollment disparities in clinical trials can narrow cancer care inequities. Funding source can influence minority representation in clinical trials. Therefore, we aimed to assess the impact of funding sources on enrollment disparities in colorectal (CRC) clinical trials. Methods: CRC phase II/III randomized controlled trial (RCTs) identified through MEDLINE and EMBASE from each database’s inception through 2022 were considered eligible. Trial level enrollment incidence ratios (EIR) were computed; defined as the ratio of trial proportions of a gender, age, or racial/ethnic subgroup category and the global incidence in the corresponding gender/age subgroup (from the global burden of disease database), or the US-population-based incidence in the corresponding racial/ethnic subgroup (from SEER 21 database). EIRs were then meta-analyzed using a random-effects model for each funding source category (US- government, industry, others). Temporal trends were analyzed using a univariate meta-regression. Results: Using data from 287 RCTs, women were significantly under-represented in the industry sponsored trials (EIR: 0.85 [95% CI: 0.83 - 0.88]) but not in US-government sponsored trials (0.92 [0.84-1.00]). A total of 87 RCTs reported age proportions; older adults (above 65 years) were significantly under-represented in the industry sponsored (0.84 [0.74-0.96]) and as well as in US-government sponsored CRC trials (0.52 [0.44-0.61]). Only 56 and 15 trials reported race and ethnicity, respectively. Limited data on racial/ethnic enrollment revealed significant under-representation of Black (0.45 [0.36 -0.57]) and Hispanic (0.45 [0.31-0.66]) patients across industry sponsored CRC trials. In contrast, no significant disparity was observed in the inclusion of Asian race in the industry sponsored trials. The number of US-government sponsored trials reporting racial/ethnic subgroups were small ( < 10) which precluded any meaningful statistics. Trends show that the representation of women has improved ( P: 0.02) while the representation of Black ( P: 0.007) and Hispanic patients ( P: 0.04) has worsened over the last three decades in industry sponsored CRC trials. Conclusions: The reporting of race/ethnicity is suboptimal in CRC trials especially in those sponsored by US government. Older adults may be under-represented regardless of funding source. Women, Blacks and Hispanics may be under-represented in industry sponsored CRC clinical trials. While representation of women appears to be improving, representation of Black and Hispanic patients has worsened in industry sponsored CRC clinical trials over the last three decades.

Abstract Modern medicine has developed a myriad of therapeutic drugs against a wide range of human diseases leading to increased life expectancy and better quality of life for millions of people. Despite the undeniable benefit of medical advancements in pharmaceutical technology, many of the most effective drugs currently in use have serious limitations such as off target side effects as a result of systemic toxicity. New generations of specialized drug constructs will enhance targeted therapeutic efficacy of existing and new drugs leading to safer and more effective treatment options for a variety of human ailments. As one of the most efficient drugs known for the treatment of cardiac arrhythmia, Amiodarone presents the same conundrum of serious systemic side effects associated with long term treatment. In this article we present the synthesis of a next generation prodrug construct of amiodarone for the purpose of advanced targeting of cardiac arrhythmias by delivering the drug to cardiomyocytes using a novel cardiac targeting peptide, a cardiomyocyte-specific cell penetrating peptide. Our in vivo studies in guinea pigs indicate that cardiac targeting peptide-amiodarone conjugate is able to have similar effects on calcium handling as amiodarone at 1/15th the total molar dose of amiodarone. Further studies are warranted in animal models of atrial fibrillation to show efficacy of this conjugate.

ImportanceProstate cancer (PCa) is marked by disparities in clinical outcomes by race, ethnicity, and age. Equitable enrollment in clinical trials is fundamental to promoting health equity.ObjectiveTo evaluate disparities in the inclusion of racial and ethnic minority groups and older adults across PCa clinical trials.Data SourcesMEDLINE, Embase, and ClinicalTrials.gov were searched to identify primary trial reports from each database's inception through February 2021. Global incidence in age subgroups and US population-based incidence in racial and ethnic subgroups were acquired from the Global Burden of Disease and Surveillance, Epidemiology, and End Results 21 incidence databases respectively.Study SelectionAll phase 2/3 randomized PCa clinical trials were eligible for age disparity analyses. Trials recruiting exclusively from the US were eligible for primary racial and ethnic disparity analyses.Data Extraction and SynthesisThis study was reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. Data were pooled using a random-effects model.Main Outcomes and MeasuresEnrollment incidence ratios (EIRs), trial proportions (TPs) of participants 65 years or older or members of a racial and ethnic subgroup divided by global incidence in the corresponding age group, or US population–based incidence in the corresponding racial and ethnic subgroup, were calculated. Meta-regression was used to explore associations between trial characteristics and EIRs and trends in EIRs during the past 3 decades.ResultsOf 9552 participants among trials reporting race, 954 (10.8%) were African American/Black, 80 (1.5%) were Asian/Pacific Islander, and 8518 (78.5) were White. Of 65 US trials, 45 (69.2%) reported race and only 9 (13.8%) reported data on all 5 US racial categories. Of 286 global trials, 75 (26.2%) reported the enrollment proportion of older adults. Outcomes by race and age were reported in 2 (3.1%) and 41 (15.0%) trials, respectively. Black (EIR, 0.70; 95% CI, 0.59-0.83) and Hispanic (EIR, 0.70; 95% CI, 0.59-0.83) patients were significantly underrepresented in US trials. There was no disparity in older adult representation (TP, 21 143 [71.1%]; EIR, 1.00; 95% CI, 0.95-1.05). The representation of Black patients was lower in larger trials (meta-regression coefficient, −0.06; 95% CI, −0.10 to −0.02; P = .002).Conclusions and RelevanceThe results of this meta-analysis suggest that Black and Hispanic men are underrepresented in trials compared with their share of PCa incidence. The representation of Black patients has consistently remained low during the past 2 decades.

AbstractHealthcare workers (HCWs) have faced an increased amount of mental health struggles amidst the COVID‐19 pandemic. However, those in conflict‐based settings with fragile healthcare systems meet additional challenges. This study reviews violence, conflict and mental health among HCWs in five countries: Syria, Palestine, Yemen, Afghanistan and Lebanon. Our study reports that HCWs are targeted by violence, bombings, mistreatment and different forms of abuse, including verbal and physical. With the additional burdens of the pandemic including prolonged working hours, limited resources and insufficient humanitarian aid, the healthcare workers fall victim to increased levels of burnout and mental illnesses. The situation leads to dire consequences on their personal lives and professional development, compelling them to quit their job or country all together. Although healthcare workers remain resilient in these conflict‐based settings, immediate interventions are required to prevent violence against them and cater to their rapidly declining mental health.

ImportanceCytokine storm due to COVID-19 can cause high morbidity and mortality and may be more common in patients with cancer treated with immunotherapy (IO) due to immune system activation.ObjectiveTo determine the association of baseline immunosuppression and/or IO-based therapies with COVID-19 severity and cytokine storm in patients with cancer.Design, Setting, and ParticipantsThis registry-based retrospective cohort study included 12 046 patients reported to the COVID-19 and Cancer Consortium (CCC19) registry from March 2020 to May 2022. The CCC19 registry is a centralized international multi-institutional registry of patients with COVID-19 with a current or past diagnosis of cancer. Records analyzed included patients with active or previous cancer who had a laboratory-confirmed infection with SARS-CoV-2 by polymerase chain reaction and/or serologic findings.ExposuresImmunosuppression due to therapy; systemic anticancer therapy (IO or non-IO).Main Outcomes and MeasuresThe primary outcome was a 5-level ordinal scale of COVID-19 severity: no complications; hospitalized without requiring oxygen; hospitalized and required oxygen; intensive care unit admission and/or mechanical ventilation; death. The secondary outcome was the occurrence of cytokine storm.ResultsThe median age of the entire cohort was 65 years (interquartile range [IQR], 54-74) years and 6359 patients were female (52.8%) and 6598 (54.8%) were non-Hispanic White. A total of 599 (5.0%) patients received IO, whereas 4327 (35.9%) received non-IO systemic anticancer therapies, and 7120 (59.1%) did not receive any antineoplastic regimen within 3 months prior to COVID-19 diagnosis. Although no difference in COVID-19 severity and cytokine storm was found in the IO group compared with the untreated group in the total cohort (adjusted odds ratio [aOR], 0.80; 95% CI, 0.56-1.13, and aOR, 0.89; 95% CI, 0.41-1.93, respectively), patients with baseline immunosuppression treated with IO (vs untreated) had worse COVID-19 severity and cytokine storm (aOR, 3.33; 95% CI, 1.38-8.01, and aOR, 4.41; 95% CI, 1.71-11.38, respectively). Patients with immunosuppression receiving non-IO therapies (vs untreated) also had worse COVID-19 severity (aOR, 1.79; 95% CI, 1.36-2.35) and cytokine storm (aOR, 2.32; 95% CI, 1.42-3.79).Conclusions and RelevanceThis cohort study found that in patients with cancer and COVID-19, administration of systemic anticancer therapies, especially IO, in the context of baseline immunosuppression was associated with severe clinical outcomes and the development of cytokine storm.Trial RegistrationClinicalTrials.gov Identifier: NCT04354701