scholarly journals Molnupiravir Extends COVID-19 Viral Phase, Evidenced by the High Frequency of Rare and Dangerous Mutations in SARS-COV-2

2021 ◽  
Author(s):  
Leo Goldstein
Keyword(s):  
Day Treatment ◽  
Random Variable ◽  
Worst Case ◽  
Virus Shedding ◽  
Viral Genomes ◽  
Number Of Patients ◽  
Safety Event ◽  
Heavy Tailed ◽  
Group 2 ◽  
Multiple Patients

This paper analyzes SARS-COV-2 mutations data from Merck’s Molnupiravir trials, in the larger context. •5-day treatment with Molnupiravir caused the appearance and selection (to a frequency >5%) of two of the most dangerous spike mutations – E484K and P681H – in multiple patients of a very small group (2/202 and 4/202, respectively).•Molnupiravir disproportionately increases the frequency of dangerous and unusual mutations•Molnupiravir worsens COVID-19 in patients, especially those who start treatment within 3 days of symptom onset. Some theoretically possible mechanisms causing this include acute bone marrow disorder and/or the generation of immune-evasive or even immunosuppressive viral genomes. •These mechanisms are likely to extend the virus shedding period in a substantial number of patients. The virus shed by these patients would be highly mutated and likely selected toward virulence.•Molnupiravir allows for virus diversification in the treated minority and purification in the untreated, a luxury rarely experienced by any virus in the nature. •Merck failed to collect enough data about Molnupiravir driven mutations. •For each important safety event, the collected data represents a few realizations of a random variable with unknown heavy tailed statistical distribution. Merck incorrectly treated this data as worst-case scenarios.

scholarly journals Geriatric Proximal Femur Fractures During the Covid-19 Pandemic - Fewer Cases, But More Comorbidities

2021 ◽  
Vol 12 ◽  
pp. 215145932110096
Author(s):  
Christina Polan ◽  
Heinz-Lothar Meyer ◽  
Manuel Burggraf ◽  
Monika Herten ◽  
Paula Beck ◽  
...  
Keyword(s):  
Nursing Home ◽  
Elderly Patients ◽  
Proximal Femur ◽  
Minor Trauma ◽  
Proximal Femur Fractures ◽  
Femur Fractures ◽  
Number Of Patients ◽  
Group 2 ◽  
The Impact ◽  
Group 1

Background: The COVID-19 pandemic is challenging healthcare systems worldwide. This study examines geriatric patients with proximal femur fractures during the COVID-19 pandemic, shifts in secondary disease profile, the impact of the pandemic on hospitalization and further treatment. Methods: In a retrospective monocentric study, geriatric proximal femur fractures treated in the first six months of 2020 were analyzed and compared with the same period of 2019. Pre-traumatic status (living in a care home, under supervision of a legal guardian), type of trauma, accident mechanism, geriatric risk factors, associated comorbidities, time between hospitalization and surgery, inpatient time and post-operative further treatment of 2 groups of patients, aged 65-80 years (Group 1) and 80+ years (Group 2) were investigated. Results: The total number of patients decreased (70 in 2019 vs. 58 in 2020), mostly in Group 1 (25 vs. 16) while the numbers in Group 2 remained almost constant (45 vs. 42). The percentage of patients with pre-existing neurological conditions rose in 2020. This corresponded to an increase in patients under legal supervision (29.3%) and receiving pre-traumatic care in a nursing home (14.7%). Fractures were mostly caused by minor trauma in a home environment. In 2020, total number of inpatient days for Group 2 was lower compared to Group 1 (p = 0.008). Further care differed between the years: fewer Group 1 patients were discharged to geriatric therapy (69.6% vs. 25.0%), whereas in Group 2 the number of patients discharged to a nursing home increased. Conclusions: Falling by elderly patients is correlated to geriatric comorbidities, consequently there was no change in the case numbers in this age group. Strategic measures to avoid COVID-19 infection in hospital setting could include reducing the length of hospital stays by transferring elderly patients to a nursing home as soon as possible and discharging independent, mobile patients to return home.

scholarly journals Interregional Transfers for Pandemic Surges

2020 ◽  
Author(s):  
Kenneth A Michelson ◽  
Chris A Rees ◽  
Jayshree Sarathy ◽  
Paige VonAchen ◽  
Michael Wornow ◽  
...  
Keyword(s):  
The United States ◽  
Upper Bounds ◽  
Hospital Inpatient ◽  
Worst Case ◽  
Icu Patients ◽  
Interregional Transfers ◽  
Number Of Patients ◽  
Bed Capacity ◽  
Model Scenarios ◽  
Do So

Abstract Background Hospital inpatient and intensive care unit (ICU) bed shortfalls may arise due to regional surges in volume. We sought to determine how interregional transfers could alleviate bed shortfalls during a pandemic. Methods We used estimates of past and projected inpatient and ICU cases of coronavirus disease 2019 (COVID-19) from 4 February 2020 to 1 October 2020. For regions with bed shortfalls (where the number of patients exceeded bed capacity), transfers to the nearest region with unused beds were simulated using an algorithm that minimized total interregional transfer distances across the United States. Model scenarios used a range of predicted COVID-19 volumes (lower, mean, and upper bounds) and non–COVID-19 volumes (20%, 50%, or 80% of baseline hospital volumes). Scenarios were created for each day of data, and worst-case scenarios were created treating all regions’ peak volumes as simultaneous. Mean per-patient transfer distances were calculated by scenario. Results For the worst-case scenarios, national bed shortfalls ranged from 669 to 58 562 inpatient beds and 3208 to 31 190 ICU beds, depending on model volume parameters. Mean transfer distances to alleviate daily bed shortfalls ranged from 23 to 352 miles for inpatient and 28 to 423 miles for ICU patients, depending on volume. Under all worst-case scenarios except the highest-volume ICU scenario, interregional transfers could fully resolve bed shortfalls. To do so, mean transfer distances would be 24 to 405 miles for inpatients and 73 to 476 miles for ICU patients. Conclusions Interregional transfers could mitigate regional bed shortfalls during pandemic hospital surges.

scholarly journals Effects of an Inactivated Porcine Circovirus Type 2 (PCV2) Vaccine on PCV2 Virus Shedding in Semen from Experimentally Infected Boars

2011 ◽  
Vol 18 (7) ◽  
pp. 1091-1096 ◽  
Author(s):  
Hwi Won Seo ◽  
Kiwon Han ◽  
Duyeol Kim ◽  
Yeonsu Oh ◽  
Ikjae Kang ◽  
...  
Keyword(s):  
Immunological Response ◽  
Porcine Circovirus Type ◽  
Porcine Circovirus Type 2 ◽  
Porcine Circovirus ◽  
Virus Shedding ◽  
Pcv2 Vaccine ◽  
Group 3 ◽  
Group 2 ◽  
Negative Controls

ABSTRACTThe objective of the present study was to determine the effect of an inactivated porcine circovirus type 2 (PCV2) vaccine on PCV2b virus shedding in the semen of experimentally infected boars by measuring the immunological response and the PCV2b DNA load in blood and semen. Twelve boars were randomly divided into three groups. The boars in group 1 (n= 4) were immunized with an inactivated PCV2 vaccine and were challenged with PCV2b. The boars in group 2 (n= 4) were only challenged with PCV2b. The boars in group 3 (n= 4) served as negative controls. The number of PCV2 genome copies of PCV2 in the serum and semen were significantly lower in vaccinated challenged boars than in nonvaccinated challenged boars at 7, 10, 14, 21, 32, 35, 42, 49, and 60 days postinoculation. The number of PCV2b genomes in the semen correlated with the number of PCV2b genomes in the blood in both vaccinated challenged (R= 0.714) and nonvaccinated challenged (R= 0.861) boars. The results of the present study demonstrate that the inactivated PCV2 vaccine significantly decreases the amount of PCV2b DNA shedding in semen from vaccinated boars after experimental infection with PCV2b.

Real-World Experience of Telbivudine and Lamivudine as Antiviral Prophylaxis for Chemotherapy-Related Hepatitis B Reactivation

2021 ◽  
Vol 15 (1) ◽  
pp. 11
Author(s):  
Lianda Siregar ◽  
Imelda Maria Loho ◽  
Agus Sudiro Waspodo ◽  
Siti Nadliroh ◽  
Rahmanandhika Swadari ◽  
...  
Keyword(s):  
Hepatitis B ◽  
Medical Records ◽  
Antiviral Treatment ◽  
Hbv Dna ◽  
Hbv Reactivation ◽  
Lamivudine Therapy ◽  
Number Of Patients ◽  
Group 2 ◽  
Good Treatment Option ◽  
Hbs Ag

Background: There is currently no data regarding the efficacy of prophylactic telbivudine in hepatitis B patients undergoing chemotherapy. This study aims to describe the results of preemptive telbivudine and lamivudine to prevent chemotherapy-related HBV reactivation.Methods: The medical records of all patients with HBsAg positive or HBs-Ag negative, anti-HBc positive, who were referred to the hepatology clinic between May 2014 and December 2016, were retrospectively reviewed. As this is a descriptive study, no statistical analysis was done.Results: A total of 52 patients with prophylactic telbivudine or lamivudine therapy were included, with 26 patients in each group. Rituximab-based treatment was given in nine and five patients in the telbivudine and lamivudine group, respectively. The number of patients who completed antiviral treatment up to six months after chemotherapy was 17 patients in each group. There was less incidence of HBV reactivation in the telbivudine group (2 of 17 patients, 11.8%) than in the lamivudine group (7 of 17 patients, 41.2%). Delayed reactivation was noticed in 1 of 2 patients in the telbivudine group and 3 of 7 patients in the lamivudine group. The median log10[HBV DNA] at reactivation was 4.52 (1.70 – 8.35) IU/mL. Severe hepatitis was observed in two patients in the lamivudine group and one patient in the telbivudine group. Of 34 patients who completed antiviral treatment, two patients died due to primary cancer. No interruption of chemotherapy or mortality due to hepatitis was noticed in both groups.Conclusions: Preemptive telbivudine or lamivudine in HBsAg positive or HBsAg negative, anti-HBc positive patients seems to be a good treatment option.

Experience of using heliox in the treatment of viral pneumonia in COVID-19

MedAlliance ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 8-14
Keyword(s):  
Lactate Dehydrogenase ◽  
Viral Pneumonia ◽  
P Value ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Number Of Patients ◽  
Helium Mixture ◽  
Ct Data ◽  
Group 2 ◽  
Group 1

SummaryIntroduction. With the ongoing COVID-19 pandemic, finding new treatments is an extremely important issue. The effectiveness of heliox was previously demonstrated in the complex treatment of patients with various bron-chopulmonary pathologies. Therefore, this method has been recommended for the treatment of pneumonia associated with COVID-19. Purpose. To study the safety and efficacy of inhaled heliox therapy in the treatment of pneumonia in COVID-19. Materials and methods. A sing-le-center prospective study was carried out for the period from 01.12.2020 to 15.02.2021. The study included 91 pa-tients. The patients were divided into two groups: group 1 (using heliox) included 46 people, and group 2 (con-trol) — 45. Inhalations of a heated oxygen-helium mixture heliox (70% helium, 30% oxygen) were carried out using “Ingalit-B2-01” inhaler. Objective (saturation, O2 flow) and laboratory parameters (lactate dehydrogenase, C-reactive protein), as well as chest organs CT data were studied. Differences between groups were determined using the χ2 test, as well as the Mann–Whitney U-test. The p value <0.05 was considered significant. Results. In group 1, side effects developed in 5 (11.3%) patients. These patients refused to further participate in the study. Final number of patients in group 1 — 41. Among patients of group 1, there was a tendency towards a more rapid normalization of lactate dehydrogenase and C-reactive protein, as well as a decrease in oxygen dependence. In group 1, according to CT data, no progression of pneumonia was recorded. In group 2, progression was observed in 6 (13.3%) patients. The overall effectiveness of treatment among patients in group 1 was 100%, among patients in group 2 — 86.7%. The differences between the groups are statistically sig-nificant (p=0.02). Conclusion. The use of inhalations with a heated oxygen-helium mixture heliox (30% oxygen, 70% helium) has shown its effectiveness and safety in the treatment of viral pneumonia (CT1- 2) associated with COVID-19.

scholarly journals The impact of postoperative percent change of parathormone level from baseline value on the rate of hypocalcemia after total thyroidectomy

2017 ◽  
Author(s):  
Ismail Cem Sormaz ◽  
Ahmet Yalin Iscan ◽  
Ilker Ozgur ◽  
Seyma Karakus ◽  
Fatih Tunca ◽  
...  
Keyword(s):  
Total Thyroidectomy ◽  
Albumin Concentration ◽  
Postoperative Hypocalcemia ◽  
Percent Change ◽  
Number Of Patients ◽  
Increased Risk ◽  
Symptomatic Hypocalcemia ◽  
Postoperative Serum ◽  
Group 2 ◽  
The Impact

Background: To investigate the impact of the percent change of postoperative parathormone (PoPTH) level from baseline value (∆PTH) on the rate of hypocalcemia after total thyroidectomy. Methods: Assays of serum PTH and calcium (Ca) were performed preoperatively and at 24 hours postoperatively in 222 consecutive patients who underwent total thyroidectomy. Postoperative hypocalcemia was defined as serum calcium level corrected for albumin concentration (cCa) &lt;8.5mg/dl. Patients with postoperative hypocalcemia were classified as group1 (n=100) and those with normal Ca levels as group 2 (n=122). The PoPTH levels and ∆PTH were compared between the two groups. ROC analysis was performed to determine the cut off values for PoPTH and ∆PTH. Results: The mean PoPTH level was significantly lower in group 1 compared to group 2 (18.6±15.3 pg/ml vs 32.3±15.6 pg/ml, respectively; P&lt;0.0001). PoPTH values were within normal range in 54% of the patients with hypocalcemia and 35% of those with symptomatic hypocalcemia. PoPTH &lt;28pg/ml or ∆PTH &gt;45 were significantly associated with increased risk of post-thyroidectomy hypocalcemia (P=0.0001). A ∆PTH &gt;70% ,PoPTH ≤ 15.5pg/ml and postoperative serum cCa concentrations&lt;8.0mg/dl significantly predicted symptomatic hypocalcemia(P=0.009;P=0.006;andP=0.0001;respevtively).The sensitivities of ∆PTH,PoPTH level and postoperative serum cCa concentration to predict symptomatic hypocalcemia were 67%,64% and100, respectively. Conclusion: Although, PTH decline significantly correlate with symptomatic hypocalcemia, a considerable number of patients may experience hypocalcemic symptoms in spite of normal PoPTH levels. Analysis of serum Ca concentrations at 24 hours postoperatively help to achieve a more precise prediction of patients who bear a high risk for developing hypocalcemic symptoms.

scholarly journals Improving the Asmussen–Kroese-Type Simulation Estimators

2012 ◽  
Vol 49 (4) ◽  
pp. 1188-1193 ◽  
Author(s):  
Samim Ghamami ◽  
Sheldon M. Ross
Keyword(s):  
Monte Carlo ◽  
Nonnegative Integer ◽  
Rare Event ◽  
Random Variables ◽  
Random Variable ◽  
Heavy Tailed ◽  
Independent Identically Distributed

The Asmussen–Kroese Monte Carlo estimators of P(Sn > u) and P(SN > u) are known to work well in rare event settings, where SN is the sum of independent, identically distributed heavy-tailed random variables X1,…,XN and N is a nonnegative, integer-valued random variable independent of the Xi. In this paper we show how to improve the Asmussen–Kroese estimators of both probabilities when the Xi are nonnegative. We also apply our ideas to estimate the quantity E[(SN-u)+].

scholarly journals Comparison of postoperative analgesic efficacy of preemptive USG-guided TAP block, USG-guided local infiltration and intravenous dexketoprofen in inguinal hernia repair

2020 ◽  
Author(s):  
Fikret Salık ◽  
Mustafa Bıçak ◽  
Hakan Akelma
Keyword(s):  
Inguinal Hernia ◽  
Postoperative Analgesia ◽  
Transversus Abdominis ◽  
Tap Block ◽  
Number Of Patients ◽  
Vas Scores ◽  
Group 3 ◽  
Group 2 ◽  
Local Anesthetic Infiltration ◽  
Group 1

Abstract Background Although regional techniques have been suggested more in order to provide postoperative analgesia in inguinal hernia repairs, the ideal method is still controversial. The aim of this study was to evaluate the effect of preemptive transversus abdominis plane (TAP) block, local anesthetic infiltration (LAI) and intravenous dexketoprofen (IVD) on postoperative pain in inguinal hernia repairs. Methods This prospective study included 120 patients with American Society of Anesthesiologists status 1-3 between 18-75 years of age who undergoing elective inguinal hernia surgery under spinal anesthesia. The patients were allocated into three groups: USG-guided TAP block (Group 1, n = 40), USG-guided LAI (Group 2, n = 40) and IVD (Group 3, n = 40) before surgical incision. The mean of tramadol consumption, number of patients in requiring rescue analgesics, duration of postoperative analgesia and complications were recorded for 24 hours postoperatively. VAS scores were evaluated at the 30 minute, 1, 2, 4, 8, 12, 16 and 24th hours. Results There was no significant difference between the postoperative mean tramadol consumption [Group 1: 22.5 mg; Group 2: 20 mg; Group 3: 27.5 (p 0.833)]. The number of patients requiring rescue analgesics was statistically similar (p 0.787). VAS scores at 30. min, 1, 2, 4, 8 and 12 hours were statistically lower in Group 1 than in the other groups (p 0.003, 007, 0013, 0049, 0015, 0021). VAS scores at 30. min and 2. h were lower in Group 1 than Group 2 (p 0.049, 0.037). İn addition, VAS scores at 30 min, 1, 2, 8 and 12 hours were lower in Group 1 than in Group 3 (p 0.003, 0.006, 0.021, 0.017, 0.016). VAS scores at all hours were statistically similar between Group 2 and Group 3. Conclusion This study demonsrated that preemptive transversus abdominis plane block, local anesthetic infiltration or iv dexketoprofen for postoperative analgesia in inguinal hernia repairs had similar effects on postoperative tramadol consumption and number of requiring rescue analgesic patients. However, TAP block provides lower VAS values and excellent analgesia in more patients in the first 24 hours postoperatively.

scholarly journals Long-term outcome of endocardial-only versus combined endocardial-epicardial homogenization of the scar for treatment of ventricular tachycardia in patients with ischemic cardiomyopathy

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
S Mohanty ◽  
C Trivedi ◽  
D G Della Rocca ◽  
C Gianni ◽  
B MacDonald ◽  
...  
Keyword(s):  
Ventricular Tachycardia ◽  
Ischemic Cardiomyopathy ◽  
Heart Surgery ◽  
Open Heart Surgery ◽  
Long Term Outcome ◽  
Obstructive Sleep ◽  
Number Of Patients ◽  
Group 2 ◽  
Group 1

Abstract Introduction We investigated the ablation success of scar homogenization with combined (epicardial + endocardial) versus endocardial-only approach for ventricular tachycardia (VT) in patients with ischemic cardiomyopathy (ICM) at 5 years of follow-up. Method Consecutive ICM patients undergoing VT ablation at our center were classified into group 1: endocardial scar homogenization and group 2: endocardial +epicardial scar homogenization. Patients with previous open heart surgery were excluded. All patients underwent bipolar substrate mapping with standard scar settings defined as normal tissue &gt;1.5 mV and severe scar &lt;0.5 mV. Non-inducibility of monomorphic VT was the procedural endpoint in both groups. Patients were followed up twice a year for 5 years with implantable device interrogations. Results A total of 361 (Group 1: 291 and group 2: 70) patients were included in the study (mean age: 67 years, male: 88.4%). At 5 years, significantly higher number of patients from group 2 remained arrhythmia-free (figure 1). Of those patients, 87 (45%) and 51 (89%) from group 1 and 2 respectively were off-anti-arrhythmic drugs (AAD) (p&lt;0.001). After adjusting for age, gender, hypertension, diabetes, and obstructive sleep apnea, scar homogenization using endo-epicardial approach was associated with 51% less recurrence compared to the endocardial ablation strategy (Hazard Ratio: 0.49, 95% CI: 0.27–0.89, p: 0.02). Conclusion In this series of patients with ischemic cardiomyopathy and VT, endo-epicardial scar homogenization was associated with a lower need for AAD and a significantly lower recurrence rate at 5-years of follow-up compared to the endocardial ablation alone. FUNDunding Acknowledgement Type of funding sources: None. Figure 1

scholarly journals The effect of hormonal disbalance on the aging rate change in the patients with arterial hypertension and comorbid endocrinopathies

2019 ◽  
Vol 23 (2) ◽  
pp. 277-282
Author(s):  
V. D. Nemtsova ◽  
I. A. Ilchenko ◽  
V. V. Zlatkina
Keyword(s):  
Arterial Hypertension ◽  
Premature Aging ◽  
Endocrine Disorders ◽  
Anthropometric Parameters ◽  
Aging Rate ◽  
Age Related ◽  
Number Of Patients ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Due to the growing number of patients with age-related diseases, the aim of the study was to investigate in the changes of aging rate (AR) in patients with comorbid course of arterial hypertension (H), type 2 diabetes mellitus (T2DM) and subclinical hypothyroidism (SH) and to study the features of these changes depending on hormonal imbalance. 118 patients (63 women and 55 men, average age — 53.6±4.3 years) were divided into 3 groups: group 1 (n=37) with isolated H; group 2 (n=42) — with H and T2DM; group 3 (n=39) — with H, T2DM and SH. The investigation program included: measurement of anthropometric parameters (blood pressure, height, body weight (BW), body mass index (BMI)), carbohydrate and thyroid metabolism using standard methods, biological age (BA) by V.P. Voitenko et al. Statistical processing was performed using the Statistica for Windows 8.0 software package. When evaluating AR, physiological aging was found in 8 patients (21.6%) of group 1, in 4 (9.5%) patients of group 2 and 3 (7.7%) of patients in group 3. In the overwhelming majority of the examined patients, premature aging (PA) was noted, however, the acceleration of PA between patients of groups 2 and 3 was not differ significantly (p>0.05). The increase in AR in group 2 patients was accompanied by an increase in BA by 7.2 years, in 3 group patients — by 7.3 years compared with their chronological age. A correlation analysis revealed a positive relationship between BMI and coefficient of aging rate (CAR) (r=0.679; p<0.05); BMI and BA (r=0.562; p<0.05) and CAR and the TSH level (r=0.050; p=0.388) in the 3rd group. Thus, the presence of hypertension and comorbid endocrinopathies — T2DM and SH significantly increases the AR and when assessing the effect of endocrine disorders, the presence of T2DM is more important than SH.

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