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The healthcare industry across the globe provides adequate access to save and extend patients' life expectancy with the motto "to get people healthy.” The entire world has understood the significance and necessity of the healthcare industry during the Covid-19 pandemics. Starting from age-old healthcare 1.0, the healthcare industry is now transformed to the current scenario healthcare 4.0. Earlier, in the first generation, the interaction between the doctor and the patient was limited and the private information of the patient was completely confidential. But, as the technology evolved, fourth generation healthcare industry (healthcare 4.0) adopted a lot of technologically advanced concepts such as Internet of Things (IoT), Fog and Cloud Computing, Telemedicine, etc., which naturally added up a lot of stakeholders, thereby increasing the risk of leaking private information to attackers or hackers. This particular chapter, "Evolution of Healthcare Sector and Evolving Cyberattacks, " briefly introduces the readers to the distributed system across computer systems and discusses its specific role in the healthcare sector. Though there are several cyber threat targets in the market, the healthcare industry at any scale was the prime target for cyber attackers. The major cause and effect of all these recurrent security threats are discussed in this chapter with a detailed infographic representation of the cyberattacks imposed on the healthcare industry. This chapter further helps to understand various forms and types of these cyberattacks in the healthcare sector. With a focus on curbing cyberattacks, this chapter also focuses on contemporary research trends with multiple insights into the healthcare sector to safeguard the patients' health records from any further attacks or data breaches. Finally, this chapter concludes by describing simple precautionary steps that healthcare industries can practice to defend themselves from cyberattacks. © 2023 selection and editorial matter, Preeti Nagrath, Jafar A. Alzubi, Bhawna Singla, Joel J. P. C. Rodrigues and A. K. Verma;individual chapters, the contributors.
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Background: Long COVID, also known as post-acute sequelae of COVID (PASC), affects more than 144 million people globally. While there is no broadly accepted consensus on a definition for the term "long COVID," studies have found symptoms persist or begin weeks or months after the end of SARS-CoV-2 infection. This study assessed the incidence of codes found in medical claims and hospital chargemasters that were consistent with long COVID symptoms commonly found in the literature. Method(s): Using the HealthVerity database, which provides closed claims and linked hospital chargemaster data on more than 25 million US patients, we examined patients aged 12 and above hospitalized between May 1, 2020 and September 30, 2021 with a diagnosis of COVID-19 who had at least 365 days of closed medical claims enrollment prior to index hospitalization admission and 90 days after admission, and did not have a long COVID diagnosis (ICD-10- CM U09.9) prior to the index hospitalization. Patients were allowed to have symptoms prior to hospitalization. The assessment period for the outcomes, which included 10 symptoms, was 90 days to 270 days after the date of hospitalization. Incidence rate per 100 person-years was calculated as the number of patients with the outcome divided by total person-time contributed (90 days after admission to the minimum of the following: outcome, inpatient death, disenrollment, end of data (April 30, 2022), or 270 days after admission). Result(s): The dataset included 3,661,303 patients with an inpatient hospitalization during the study period. The final study cohort included 44,922 patients hospitalized with COVID-19, 20,627 of whom experienced at least one of the long COVID symptoms. Anosmia and dysgeusia were the rarest events captured in medical claims. More commonly found symptoms were joint pain, fatigue and breathlessness (see table). Conclusion(s): This study examined diagnosed symptoms commonly found posthospitalization among COVID-19 patients and reported the incidence of these symptoms in a representative population. The start period of long COVID used in this study (90 days post hospitalization) is consistent with the WHO definition of long COVID. In the absence of an understanding of the pathophysiology of long COVID, the use of diagnosed symptoms to define long COVID has the advantage of ease of use and availability of data. Further studies of additional symptoms and predictors of long COVID are needed. (Figure Presented).
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Over the past two years, COVID-19 has spread over 200 countries, leading to pandemic proportions. Still, the virus is rapidly changing, the variants spreading through direct and indirect contact in places irrespective of the vaccine distribution. Many infectious diseases spread through droplets, and micro-droplets require face masks and other social distancing measures. This article proposed for pandemic circumstances called real-time face mask with health screening (RTFMHS) with two screening methods: (i) Internet of Things (IoT) node monitors a real-time intelligent face mask detection using multi-level high-speed augmented convolution neural network (MLHS-CNN), (ii) Individuals health indicators such as non-contact body temper-ature sensor and blood oxygen saturation are sending to fog cloud to manipulate and display the user health status. A face mask detection technique based on MLHS-CNN is proposed to determine whether a person is wearing a mask properly. User health is computed in real-time by an RNN running on the fog server to estimate the risk of infection spreading. The proposed method uses a lightweight IoT node and fog-based Deep Learning (DL) tools for data analysis and diagnosis. The experimental results outperformed previous research in terms of detection accuracy, precision, recall, and time complexity. © 2022 IEEE.
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Background: Remdesivir (RDV), a direct-acting nucleotide pro-drug inhibitor of viral RNA-dependent RNA polymerases, was approved by the FDA for the treatment of hospitalized patients (pts) with COVID-19 infection and has been shown to shorten time to recovery and improve clinical outcomes in randomized clinical trials. We present the final Day 28 (D28) analysis of RDV vs standard of care (SOC) (interim Day 14 [D14] analysis published [Olender et al. Clin Infect Dis 2020]). Methods: Final comparative analysis from two studies: a prospective phase 3, randomized study of RDV (RDV cohort) and a real-world retrospective cohort study of SOC (non-RDV cohort). Both studies enrolled pts with SARS-CoV-2 infection confirmed by polymerase chain reaction, who had oxygen saturation ≤94% on room air or required supplemental oxygen and had pulmonary infiltrates. Pts in the RDV cohort were randomized 1:1 to receive IV RDV for 5 or 10 days (200 mg on Day 1 followed by 100 mg/day on Days 2-5 or 2-10), plus SOC;the two randomized dose-groups were combined for analysis. Pts in the non-RDV cohort received SOC as determined by local treatment practices (excluding RDV). Analysis populations were balanced using propensity score (PS) matching. The coprimary endpoints were D14 clinical recovery (determined using a 7-point ordinal scale) and D28 all-cause mortality. Factors associated with D28 mortality were assessed using a multivariable logistic regression model. Results: After PS matching, baseline characteristics were generally similar in the RDV and non-RDV cohorts;median age 61 years, 63% male, 42% obese, 12% Black, 71% no/low-flow oxygen use, 25% high-flow oxygen, 3% ventilated. Pts in the RDV cohort had significantly higher D14 clinical recovery rates (65% vs 57%) and significantly lower D28 mortality rates (12% vs 16%) compared with the non-RDV cohort (Table). In the multivariable analysis, in addition to RDV use, a lower risk of death at D28 was associated with: younger age;being female;being White (versus being Black/African American);receiving an HIV protease inhibitor prior to baseline;not having cardiovascular disease or COPD;more days of symptoms prior to baseline;and being on room air or low-flow oxygen at baseline (versus being on invasive mechanical ventilation). Conclusion: RDV was associated with significantly higher rates of clinical recovery at Day 14 and lower Day 28 mortality compared with SOC in hospitalized pts with severe SARS-CoV-2 infection.
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Background: Remdesivir (RDV), an RNA-dependent RNA polymerase inhibitor of SARS-CoV-2, and its intravenous formulation excipient, cyclodextrin, are renally cleared. We sought to characterize whether RDV was associated with worsening renal function in hospitalized patients with moderate COVID-19. Methods: We conducted an open-label, phase 3 trial (NCT04252664) involving hospitalized patients with confirmed SARS-CoV-2 infection, evidence of pulmonary infiltrates, oxygen saturation >94% on room air and eGFR ≥50 mL/ min/1.73m2. Patients were randomly assigned 1:1:1 to receive up to 5d or 10d of RDV with standard of care (SoC), or SoC alone. Also included in this analysis were patients who enrolled in an extension phase of the trial, receiving 10d of RDV. RDV was dosed intravenously at 200 mg on d1 and 100 mg daily thereafter. Acute kidney injury (AKI) was defined as an increase in serum creatinine from baseline and classified as Stage 1 (increase > 0.3 and % change ≤25%, or % change >25% and ≤ 100%), Stage 2 (% change >100% and ≤200%), Stage 3 (% change >200%). For AKI development (ever/never for stage 1 or greater), age-adjusted risk ratios (RR) and 95% Wald confidence intervals (CI) were reported. Results: 1005 patients (822 [83%] RDV, 183 [17%] SoC) with creatinine values collected through d14 were evaluated. Baseline patient demographics, creatinine, and eGFR were mostly similar between RDV vs SoC arms. Worsening renal function was observed less frequently in patients receiving RDV vs SOC (7% vs 10%, p=0.03, Table). After adjustment for age, there was no significant association of RDV with risk of AKI relative to SoC (RR=0.66;95% CI 0.40, 1.09). Most AKI events were observed in patients with baseline eGFR >90 mL/min, with few events occurring in patients with a baseline eGFR 50-59 mL/min. In patients who developed Stage 3 AKI, those treated with RDV (n=2, 0.2%) returned to baseline creatinine values while those on SOC (n=4, 2%) remained elevated to d14. No difference in AKI between treatment arms was observed in patients with a history of chronic kidney disease (CKD;RDV: n=6 [12%] vs SOC: n=2 [40%] p=0.14). Older age, history of CKD, and eGFR status at baseline were independently associated with worsening renal function. Conclusion: AKI events were observed less frequently in patients with moderately severe COVID-19 patients treated with RDV compared to SoC.
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Background: Remdesivir (RDV) has been shown to shorten recovery time and was well tolerated in patients with severe COVID-19. Here we report safety of RDV in patients with moderate COVID-19. Methods: We conducted an open-label, phase 3 trial (NCT04252664) in hospitalized patients with confirmed SARS-CoV-2 infection, evidence of pulmonary infiltrates, and oxygen saturation >94% on room air. Patients were randomly assigned to receive RDV (5 or 10 days) or standard of care (SOC). RDV was dosed intravenously at 200 mg on day 1, 100 mg daily thereafter. Adverse events (AEs) and laboratory abnormalities were evaluated through the day 11 data cut;safety data through day 28 will be presented at the meeting. Results: 584 patients were randomized and treated (5d RDV: n=191;10d RDV, n=193;SOC: n=200). Baseline characteristics were balanced among groups;median (range) age was 57y (12-95y), 39% were female and 19% Black, 39% had arterial hypertension, 15% hyperlipidemia, 11% asthma. Briefly, across both the 5d and 10d arms, RDV was well tolerated with a similar rate of Grade 3 or 4 AEs and fewer SAEs compared to SOC (Table). AEs more common with RDV vs SOC included nausea, headache, and hypokalemia. Overall, across the 3 arms, incidence of AEs leading to discontinuation and death were low and no clinically relevant changes in laboratory parameters were observed. In addition, median changes in renal and liver function tests from baseline were not statistically significant between the RDV 5d and RDV 10d groups compared to the SOC only group at d14 (Table 1). Conclusion: RDV given for 5d or 10d was well tolerated in patients with moderate COVID-19. No clinically significant safety signals were observed with RDV vs SOC. (Figure Presented).
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Background: Remdesivir (RDV) has been shown to shorten recovery time and was well tolerated in patients with severe COVID-19. Hydroxychloroquine (HQN) is an experimental treatment for COVID-19. Effects of coadministration of HQN with RDV have not been studied and are relevant given the long half-life (∼22 days) of HQN. We report the impact of concomitant HQN and RDV use on clinical outcomes and safety in patients with moderate COVID-19. Methods: We enrolled hospitalized patients with confirmed SARS-CoV-2 infection, oxygen saturation >94% on room air, and radiological evidence of pneumonia. Patients were randomized 1:1:1 to receive 5d or 10d of intravenous RDV once daily plus standard of care (SoC), or SoC only. We compared patients on concomitant HQN (HQNpos) vs not (HQNneg). Clinical recovery was evaluated using Cox proportional hazards. Covariate adjustment included age, sex, race, region, symptom duration, oxygen support status and obesity. Recovery and adverse events (AEs) were assessed through death, discharge, or d14. Results: Of 584 patients, 199 (34%) received HQN (5d RDV: n=57 [30%];10d RDV, n=49 [25%];SoC: n=93 [47%]). Through median follow-up of 13d (range 1-41d), HQNpos patients on 5d or 10d RDV had a lower recovery rate (adjusted HR [95% CI] 0.78 [0.59, 1.03], p=0.09) with longer median time to recovery (8 vs 6 days) compared to HQNneg. HQNpos compared to HQNneg patients in 5d RDV showed a trend of reduced recovery rate (HR: 0.69 [0.45,1.04], p=0.080);such an effect was not observed in 10d RDV or SoC (Table 1). More HQNpos than HQNneg patients had AEs in RDV (5/10d) or SoC arms evaluated separately, and all arms combined. This difference was significant for AEs and SAEs for all arms combined after covariate adjustment (Table 2). Conclusion: In moderate COVID-19 patients, concomitant HQN may delay recovery on RDV and showed no impact on recovery with SoC alone. The AE profile of HQNpos patients was worse than that observed for HQNneg patients, regardless of RDV treatment.
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Background: Remdesivir (RDV) has been shown to shorten recovery time and was well tolerated in patients with severe COVID-19. Here we report baseline characteristics associated with clinical improvement at day (d) 14. Methods: We enrolled hospitalized patients with confirmed SARS-CoV-2 infection, oxygen saturation >94% on room air, and radiological evidence of pneumonia. Patients were randomized 1:1:1 to receive 5d or 10d of intravenous RDV once daily plus standard of care (SoC), or SoC only. For this analysis, patients were followed through discharge, d14, or death. Baseline demographic and disease characteristics associated with clinical improvement in oxygen support (≥2-point improvement on a 7-category ordinal scale ranging from discharge to death) were evaluated using multivariable logistic regression methods. Results: 584 patients were randomized and treated (5/10d RDV, n=384;SoC: n=200). 159 (27%) were ≥65y, 227 (39%) female, 328 (61%) white, 102 (19%) Asian, and 99 (19%) Black. 252 participants (43%) were enrolled in Europe, 260 (45%) North America (NA), and 72 (12%) in Asia. Most patients (483 [83%]) were not on supplemental oxygen but required medical care at baseline. In a multivariable model, 5/10d RDV was significantly positively associated with clinical improvement (adjusted odds ratio [OR] 1.69, 95% CI: 1.08, 2.65;p=0.0226). Significant covariables positively associated with clinical improvement included age < 65y (p< 0.0001) and region of treatment (Europe and NA vs Asia, p< 0.0001 each;Table);other examined factors were not significantly associated with clinical improvement, including gender, race, ethnicity, baseline oxygen support, duration of symptoms and hospitalization, obesity, and baseline transaminase levels. Conclusion: In moderate COVID-19 patients, after adjusting for treatment arm, age < 65y and region (NA vs Asia;Europe vs Asia) were associated with higher rates of clinical improvement. These observations recapitulate younger age as positive prognostic factor, and highlight the differences in the impact of the pandemic globally.
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Background: COVID-19 has spread rapidly: from the first case in Dec 2019, the declaration of a global pandemic in Mar 2020, to Jun 18, 2020 with >8 M confirmed cases and >400,000 deaths worldwide. Throughout this rapid spread, Gilead has focused on contributing antiviral expertise and resources to help patients (pts) and communities fighting COVID-19 Methods: Gilead is supporting the efforts of governments, partnering with professionals, and community-based org., and collaborating with healthcare providers to accelerate research and access to remdesivir (RDV), the first medicine with demonstrated efficacy in treatment of COVID-19. This is a review of the programs initiated in RDV research, access, research grants and collaborative education Results: In Jan 2020 Gilead began working with government and regulatory authorities to make RDV accessible to pts globally through the compassionate use and expanded access programs. These programs has treated >2000 COVID-19 pts. By Feb 2020, several phase 3 randomized trials on RDV were initiated. Based on trials completed and published data (n= >2000), RDV was granted emergency use authorization in the US on May 1, 2020 with full approval in 5 countries thereafter and several under review elsewhere. Collectively there will be >12,000 pts enrolled in RDV clinical programs by Dec 2020. Increasing manufacturing of RDV began at-risk in Jan 2020. By May 2020 Gilead has decreased production time, increased supply and committed to donating all its 1.5 M doses. Under the licensing agreements with generic drug manufacturers, RDV will be available in 127 countries upon approval. Gilead has committed to supporting research grants to enhance the understanding of the clinical course and outcomes in vulnerable population, long-term sequelae, and evaluate real world safety and effectiveness of COVID-19 therapies. Finally, Gilead has provided corporate grants to support the efforts of community-based orgs and public health entities to expand education on COVID-19 Conclusion: Gilead has initiated a global, multifaceted rapid response that reflects the unprecedented emergency posed by SARS-COV-2. This includes increasing RDV production, access, timely initiation of phase 3 RDV trials, and establishment of grants programs for community projects, research and education.
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Background: Remdesivir (RDV), a RNA polymerase inhibitor with potent in vitro activity against SARS-CoV-2, is the only treatment with demonstrated efficacy in shortening the duration of COVID-19. Here we report regional differences in clinical outcomes of severe COVID-19 patients treated with RDV, as part of an open-label, randomized phase-3 trial establishing RDV treatment duration. Methods: Hospitalized patients with oxygen saturation ≤94%, a positive SARS-CoV-2 PCR in the past 4 days and radiographic evidence of pneumonia were randomized 1:1 to receive 5d or 10d of intravenous RDV. We compared d14 clinical outcomes of patients from different geographical areas, as measured by mortality rates, change in clinical status from baseline (BL) on a 7-point ordinal scale and change in O2 requirements from BL. Based on previous analyses in compassionate use data showing region as an important predictor of outcome, Italy was examined separately from other regions. Results: 397 patients were treated with RDV, of which 229 (58%) were in the US, 77 (19%) Italy, 61 (15% in Spain), 12 (3%) Republic of Korea, 9 (2%) Singapore, 4 (1%) Germany, 4 (1%) Hong Kong and 1 (< 1%) Taiwan. BL clinical status was worse in Italy compared to other regions (72% vs 17% requiring high-flow oxygen delivery or higher), and Italian patients were more likely to be male than patients from other regions (69% vs 63%). Overall results showed 5d RDV was as effective as 10d. Mortality at d14 was higher in Italy (18%) compared to all other countries except Italy (7%). Similarly, clinical improvement at d14, measured as ≥2-point increase in the ordinal scale, was lower in Italian patients (39%) compared to all other countries combined (64%). (Fig.1). Conclusion: Overall, our results demonstrate significant geographical differences in the clinical course of severe COVID-19 patients treated with RDV. We observed worse outcomes, such as increased mortality and lower rate of clinical improvement, in patients from Italy compared to other regions. (Table Presented).
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Background: Remdesivir (RDV) shortens time to recovery time in patients with severe COVID-19. Its effect in patients with moderate COVID-19 remains unclear. Methods: We conducted an open-label, phase 3 trial (NCT04252664) involving hospitalized patients with confirmed SARS-CoV-2 infection, evidence of pulmonary infiltrates, and oxygen saturation >94% on room air. Patients were randomly assigned 1:1:1 to receive up to 5d or 10d of RDV with standard of care (SoC), or SoC alone;patients could be discharged prior to completing per-protocol assigned treatment duration. RDV was dosed intravenously at 200 mg on d1, 100 mg daily thereafter. Patients were evaluated daily while hospitalized, and via telephone if discharged. The primary endpoint was clinical status on d11 assessed on a 7-point ordinal scale. Results regarding the primary endpoint are expected to be published before IDWeek 2020;we plan to present d28 results at the meeting. Results: In total, 584 patients underwent randomization and started their assigned treatment (191, 5d RDV;193, 10d RDV;200, SoC). By d11, 3 2 point improvement on the ordinal scale occurred in 70% of patients in the 5d arm, 65% in the 10d arm, and 61% in the SoC arm. Patients in the 5d RDV arm were significantly more likely to have an improvement in clinical status than those receiving SoC (odds ratio [OR], 1.65;95% confidence interval [CI], 1.09-2.48;P=0.017);OR of improvement for the 10d RDV arm compared to SoC was 1.31 (95% CI, 0.88-1.95];p=0.183). This improvement in the 5-day arm over the SOC arm was noted from d6 through d11. We observed a peak of discharges corresponding with the assigned treatment duration of RDV, with increased discharges at d6 in the 5-day arm and at d11 in the 10-day arm. A worsening of clinical status of ≥ 1 point in the ordinal scale was observed more commonly in the SoC am (n=19, 10%) versus the 5d RDV (n=7, 4%) and 10d RDV (n=9, 5%). Conclusion: RDV for up to 5 days was superior to SoC in improving the clinical status of patients with moderate COVID-19 by d11. We will report d28 outcomes at the meeting. (Table Presented).
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Background: Remdesivir (RDV), a nucleotide analogue prodrug that inhibits viral RNA polymerases, has demonstrated potent in vitro and in vivo activity against SAR-CoV-2 and favorable clinical efficacy and tolerability in patients with moderate and severe COVID-19 Elevated transaminase levels are commonly seen in patients with severe COVID-19 prior to treatment Here we report safety and clinical outcomes after RDV treatment in patients with normal versus elevated baseline alanine aminotransferase (ALT) levels Methods: We conducted a randomized, open-label, phase 3 trial, involving hospitalized patients with confirmed COVID-19 pneumonia with Sat<94% Patients with screening ALT or AST> 5x the upper limit of normal (ULN) were excluded from the study Patients were randomized 1:1 to receive either 5 or 10 days of intravenous RDV once daily We compared patients with baseline ALT below and above the ULN based on AASLD criteria (ALT 35 U/L for males and 25 U/L for females) Covariates for adjustment included age, sex, race and baseline oxygen support Clinical recovery and all-cause mortality were evaluated using logistic regression Clinical outcomes and adverse events (AEs) were assessed through day 28 Results: Of 397 patients treated with RDV, 215 (54%) had elevated baseline ALT Median ALT was 53 U/L (IQR: 40 - 78 U/L) in the high ALT group Patients with high ALT at time of RDV initiation were younger (median 58 vs 65 years, p<0 001), required less oxygen (p=0 02), and had longer symptom duration (median 10 vs 8 days, p<0.001) prior to first dose of RDV. Incidence of serious AEs, grade ≥3 AEs, and AE leading to discontinuation were similar between groups (Table1). Grade ≥3 hepatobiliary adverse events, particularly transaminase elevations, were not common but numerically higher in the high ALT group (8 8% vs 3 3%, p=0 068) Time to clinical recovery, 2-point clinical improvement, 1-point clinical improvement, room air, and death were similar between groups Conclusion: In severe COVID-19 patients, adverse events and clinical outcomes after RDV initiation were similar among patients with baseline normal ALT and those with elevated ALT (1-5x ULN)(Table Presented).