COVID-19 Drug Treatments Are Prone to Sequestration in Extracorporeal Membrane Oxygenation Circuits: An Ex Vivo Extracorporeal Membrane Oxygenation Study.

Drug treatments for coronavirus disease 2019 (COVID-19) dramatically improve patient outcomes, and although extracorporeal membrane oxygenation (ECMO) has significant use in these patients, it is unknown whether ECMO affects drug dosing. We used an ex vivo adult ECMO model to measure ECMO circuit effects on concentrations of specific COVID-19 drug treatments. Three identical ECMO circuits used in adult patients were set up. Circuits were primed with fresh human blood (temperature and pH maintained within normal limits). Three polystyrene jars with 75 ml fresh human blood were used as controls. Remdesivir, GS-441524, nafamostat, and tocilizumab were injected in the circuit and control jars at therapeutic concentrations. Samples were taken from circuit and control jars at predefined time points over 6 h and drug concentrations were measured using validated assays. Relative to baseline, mean (± standard deviation [SD]) study drug recoveries in both controls and circuits at 6 h were significantly lower for remdesivir (32.2% [±2.7] and 12.4% [±2.1], p < 0.001), nafamostat (21.4% [±5.0] and 0.0% [±0.0], p = 0.018). Reduced concentrations of COVID-19 drug treatments in ECMO circuits is a clinical concern. Remdesivir and nafamostat may need dose adjustments. Clinical pharmacokinetic studies are suggested to guide optimized COVID-19 drug treatment dosing during ECMO.

Effect of Alternatives to Opiates Program on Discharge Opioid Prescribing in Trauma Patients.

BACKGROUND: Opioid overdose deaths have increased over the last two decades, despite efforts to reduce prescribing. This study aimed to determine if a hospital-wide Alternatives to Opiates (ALTOSM) program reduced opioid prescribing in hospital and upon discharge after trauma. OBJECTIVES: The primary outcome was incidence of opioid prescribing at hospital discharge Pre- and Post-ALTO. Secondary outcomes were the percent of patients with in-hospital opioid, non-opioid and multimodal analgesia, and hospital and intensive care unit (ICU) length of stay (LOS). METHODS: This is a single-center, retrospective analysis of patients >/ = 18 years old admitted for >24 hours with the primary diagnosis of traumatic injury between August 2018 - October 2019. Patients with alcohol or polysubstance abuse, chronic opioid use, or in-hospital mortality were excluded. RESULTS: A total of 703 patients were included, 471 in Pre-ALTO and 232 in Post-ALTO groups. The mean age was 59 ± 22 years and most were male (58.7%). Mean initial Injury Severity Score (ISS) was 9.1 ± 7.7. Opioid prescribing at hospital discharge occurred more in the Post-ALTO group (132/332, 39.4% vs 90/203, 43.8%; P = .1237). Most patients were prescribed in-hospital opioid (332/471, 70.4% vs 203/232, 87.5%, P < .0001) and non-opioid (441/471, 93.6% vs 229/232, 98.7%; P = .0027) analgesics, or multimodal analgesia (397/471, 84.3% vs 203/232, 87.5%; P = .2591). Median hospital and ICU LOS were also similar between groups [5 (3-9) vs 4(3-7), P = .3427] and ICU [2(0-4) vs 3(2-5), P = .3461]. CONCLUSION: Opioids remain mainstay for trauma-related pain treatment. ALTOSM was not associated with less in-hospital or discharge opioid prescribing.

Haematological Trends and Transfusion during Adult Extracorporeal Membrane Oxygenation: A Single Centre Study.

The temporal trends in haematological parameters and their associations with blood product transfusion requirements in patients supported with extracorporeal membrane oxygenation (ECMO) are poorly understood. We performed a retrospective data analysis to better understand the behaviour of haematological and coagulation parameters and their associations with transfusion requirements during ECMO. METHODS: Patient demographics, haematological and coagulation parameters, plasma haemoglobin and fibrinogen concentrations, platelet count, the international normalised ratio (INR), the activated partial thromboplastin time (APTT), and blood product transfusion data from 138 patients who received ECMO in a single high-volume centre were analysed. RESULTS: Ninety-two patients received venoarterial (VA) ECMO and 46 patients received venovenous (VV) ECMO. The median (IQR) duration of VA, and VV ECMO was 8 (5-13) days and 13 (8-23) days, respectively. There were significant reductions in haemoglobin, the platelet count, and the fibrinogen concentration upon initiation of ECMO. On average, over time, patients on VV ECMO had platelet counts 44 × 109/L higher than those on VA ECMO (p ≤ 0.001). Fibrinogen and APTT did not vary significantly based on the mode of ECMO (p = 0.55 and p = 0.072, respectively). A platelet count < 50 × 109/L or a fibrinogen level < 1.8 g/L was associated with 50% chance of PRBC transfusion, regardless of the ECMO type, and packed red blood cell (PRBC) transfusion was more common with VA ECMO. APTT was predictive of the transfusion requirement, and the decrement in APTT was discriminatory between VVECMO survivors and nonsurvivors. CONCLUSION: ECMO support is associated with reductions in haemoglobin, platelet count, and fibrinogen. Patients supported with VA ECMO are more likely to receive a PRBC transfusion compared to those on VV ECMO. Thrombocytopaenia, hypofibrinogenaemia, and anticoagulation effect the likelihood of requiring PRBC transfusion. Further research is needed to define optimal blood management during ECMO, including appropriate transfusion triggers and the anticoagulation intensity.

Deployment of AMMI, GGE-biplot and MTSI to select elite genotypes of castor (Ricinus communis L.).

Castor (Ricinus communis L.) is an important industrial multipurpose non-edible oilseed C3 crop belongs to spurge family popularly known as Euphorbiaceae. Its oil has exceptional properties which provides an industrial importance to this crop. The present investigation is aimed to judge the stability and performance of yield and yield assigning traits and selection of suitable genotype for varied locality of western rainfed regions of India. During the study with 90 genotypes, the genotype × environment interaction was found to be significant for seed yield per plant as well as for plant height up to primary raceme, total length of primary raceme, effective length of primary raceme, capsules on main raceme and effective number of racemes per plant. E1 is the least interactive and highly representative site for seed yield. Which won where and what biplot decipher ANDCI 10-01 as vertex genotype for E3 while ANDCI 10-03 and P3141 for E1 and E2. Average Environment co-ordinate identify ANDCI 10-01, P3141, P3161, JI 357 and JI 418 as tremendously stable and high seed yielding genotypes. The study outlined the pertinency of Multi Trait Stability Index, that calculated based on the genotype-ideotype distance as the multiple interacting variables. MTSI evaluated all genotypes and sort ANDCI 12-01, JI 413, JI 434, JI 380, P3141, ANDCI 10-03, SKI 215, ANDCI 09, SI 04, JI 437, JI 440, RG 3570, JI 417 and GAC 11 with maximum stability and high mean performance of analyzed interacting traits.

Ulipristal acetate, a progesterone receptor modulator for emergency contraception.

Unwanted pregnancy is a global reproductive health problem. Emergency contraception is defined as the use of drug or device after unprotected or underprotected intercourse to prevent an unwanted pregnancy. 1.5 mg of levonorgestrel as a single dose or in two doses with 12 h apart taken within 72 h of unprotected intercourse is the current gold standard emergency contraception regimen. This method is only effective if used as soon as possible after sexual intercourse and before ovulation. A single dose of 30 mg ulipristal acetate, a novel selective progesterone receptor modulator, has recently been proposed for the emergency contraception use up to 120 h of unprotected intercourse with similar side effect profiles as levonorgestrel. Ulipristal acetate could possibly prevent pregnancy when administered in the advanced follicular phase, even if luteinizing hormone levels have already begun to rise, a time when levonorgestrel is no longer effective in inhibiting ovulation.

Effect of doxycycline in patients of moderate to severe chronic obstructive pulmonary disease with stable symptoms.

BACKGROUND: The protease-antiprotease hypothesis proposes that inflammatory cells and oxidative stress in chronic obstructive pulmonary disease (COPD) produce increased levels of proteolytic enzymes (neutrophil elastase, matrix metalloproteinases [MMP]) which contribute to destruction of parenchyma resulting in progressive decline in forced expiratory volume in one second. Doxycycline, a tetracycline analogue, possesses anti-inflammatory properties and inhibits MMP enzymes. OBJECTIVES: To assess the effect of 4 weeks doxycycline in a dose of 100 mg once a day in patients of moderate to severe COPD with stable symptoms. METHODS: In an interventional, randomized, observer-masked, parallel study design, the effect of doxycycline (100 mg once a day for 4 weeks) was assessed in patients of COPD having stable symptoms after a run-in period of 4 weeks. The study participants in reference group did not receive doxycycline. The parameters were pulmonary functions, systemic inflammation marker C-reactive protein (CRP), and medical research council (MRC) dyspnea scale. Use of systemic corticosteroids or antimicrobial agents was not allowed during the study period. RESULTS: A total of 61 patients completed the study (31 patients in doxycycline group and 30 patients in reference group). At 4 weeks, the pulmonary functions significantly improved in doxycycline group and the mean reduction in baseline serum CRP was significantly greater in doxycycline group as compared with reference group. There was no significant improvement in MRC dyspnea scale in both groups at 4 weeks. CONCLUSION: The anti-inflammatory and MMP-inhibiting property of doxycycline might have contributed to the improvement of parameters in this study.

Comparison of combinations of ciprofloxacin-metronidazole and ceftriaxone-metronidazole in controlling operative site infections in obstetrics and gynecological surgeries: A retrospective study.

OBJECTIVE: To compare the effectiveness of the ciprofloxacin-metronidazole (CIP-MET) regimen with the ceftriaxone-metronidazole (CEF-MET) regimen for operative site infection control in women undergoing obstetrical and gynecological surgeries. MATERIALS AND METHODS: One thousand and eighty-four case records of women who had undergone various obstetrical and gynecological surgeries who were given CIP-MET regimen and CEF-MET regimen were analyzed in predesigned and pretested proforma. Patients who were given CIP-MET regimen and CEF-MET regimen were classified as Group 1 and Group 2 respectively. The mode of administration of both the regimens was noted. Numbers of wound infections were recorded in the respective groups. Socioeconomic status and hemoglobin level of the patients were noted. Other data such as hospital stay, duration of operation were also noted. RESULTS: Out of a total of 1084 case records, 31 (5.8%) and eight (0.7%) patients contracted wound infections in Group 1 and Group 2 respectively (P = 0.0001). CONCLUSION: The CEF-MET regimen was found superior to the CIP-MET regimen to control operative site infection in obstetrical and gynecological surgeries.

Impact of proton pump inhibitors on efficacy of clopidogrel: Review of evidence.

Clopidogrel is a prodrug which requires cytochrome P450 2C19 (CYP 2C19) enzyme for its conversion to an active thiol metabolite. Proton pump inhibitors (PPIs) inhibits enzyme CYP 2C19 interfering with the conversion of clopidogrel into its active metabolite. Studies document the possible interaction of clopidogrel and PPIs leading to a decrease in the antiplatelet efficacy of clopidogrel. A PubMed/MEDLINE database literature search was carried out and the bibliographies of found articles were checked for other relevant literature. Most retrospective cohort studies and studies using platelet markers found a significant association between PPI use especially omeprazole and decreased efficacy of clopidogrel while few comparative trials using clinical outcomes found no association between the same. Pantoprazole was not associated with the decrease in the antiplatelet efficacy of clopidogrel. Patients on dual antiplatelet therapy and/or with a history of gastrointestinal bleed will require gastroprotection in the form of PPIs. In such cases, pantoprazole should be the preferred PPI. Rabeprazole can be used as an alternative.