Nevin Manimala

J Med Virol. 2022 Mar 22. doi: 10.1002/jmv.27729. Online ahead of print.

ABSTRACT

OBJECTIVE: To conduct network meta-analysis (NMA) of clinical efficacy and safety of single-dose antiviral drugs, grouped by dosage, in treatment of influenza.

METHODS: Systematic retrievals were conducted in databases, including Pubmed, Embase, Web of Science, the Cochrane Register of Clinical Trials and from the website ClinicalTrials.gov, for clinical trials recorded between the interception of the databases and March 31, 2021. Randomized controlled trials (RCTs) of influenza treatment in which single-dose antiviral drugs were administered were selected according to pre-set inclusion and exclusion criteria by two researchers who screened the literature independently from each other. The quality of the included studies was assessed using the Cochrane bias risk assessment tool. Software such as Stata 16.0 and Review Manager 5.3 was adopted for statistical analysis. Pairwise meta-analysis and NMA were carried out under the random-effects model. For both binary and continuous variables, odds ratio (OR), mean difference (MD) and their 95% confidence intervals (CI) were used to rank treatment efficiencies and analyze the differences.

RESULTS: A total of 12 RCTs involving 7,296 participants were included in the analysis. According to the NMA results, peramivir 300 mg [MD = -17.68, 95% CI (-34.05, -1.32)], peramivir 600 mg [MD = -16.15, 95% CI (-29.35, -2.95)], baloxavir [MD = -14.67, 95% CI (-26.75, -2.58)] and laninamivir 40 mg [MD = -12.42, 95% CI (-22.53, -2.31)] remarkably outperformed laninamivir 20 mg in time to alleviation of symptoms (TTAS). However, no intervention statistically outperform others in antipyretic time, virus titer variations against the baseline 24 h and 48 h after medication and adverse events (AEs). The efficacy rankings were: peramivir 300 mg (SUCRA, the surface under the cumulative ranking curve = 80.3%) > peramivir 600 mg (SUCRA = 76.2%) > baloxavir (SUCRA = 68.4%) > laninamivir 40 mg (SUCRA = 55.0%) > laninamivir 20 mg (SUCRA = 16.6%) for TTAS; baloxavir (SUCRA = 76.3%) > peramivir 600 mg (SUCRA = 67.8%) > laninamivir 40 mg (SUCRA = 47.2%) > laninamivir 20 mg (SUCRA = 40.0%) for antipyretic time; baloxavir (SUCRA = 96.7%)＞peramivir 300 mg (SUCRA = 64.5%) ≈ peramivir 600 mg (SUCRA = 63.2%), baloxavir (SUCRA = 93.2%) > peramivir 600 mg (SUCRA = 64.0%) ≈ peramivir 300 mg (SUCRA = 55.0%), for virus titer variations against the baseline 24h and 48h after medication, respectively; and baloxavir (SUCRA = 83.4%) > peramivir 300 mg (SUCRA = 71.4%) > laninamivir 20 mg (SUCRA = 62.4%) > peramivir 600 mg (SUCRA = 56.2%) > laninamivir 40 mg (SUCRA = 36.8%) for adverse events.

CONCLUSIONS: Among the single-dose anti-influenza virus drugs compared, peramivir is superior to baloxavir and laninamivir in TTAS, whereas baloxavir has the best efficacy in antipyretic time, virus titer variations against the baseline 24 h and 48 h after medication and AEs. This article is protected by copyright. All rights reserved.

PMID:35315516 | DOI:10.1002/jmv.27729

Am J Bot. 2022 Mar 22. doi: 10.1002/ajb2.1834. Online ahead of print.

ABSTRACT

PREMISE: Yeasts are often present in floral nectar and can influence plant fitness directly (independently of pollinators) or indirectly by influencing pollinator visitation and behavior. However, few studies have assessed the effect of nectar yeasts on plant reproductive success or compared effects across different plant species, limiting our understanding of the relative impact of direct vs. indirect effects.

METHODS: We inoculated the nectar of six plant species in the field with the cosmopolitan yeast Metschnikowia reukaufii to analyze the direct and indirect effects on female reproductive success over 2 years. The pollinator assemblage for each species was recorded during both flowering years.

RESULTS: Direct yeast effects on female fecundity were statistically nonsignificant for all plant species. There were significant indirect, pollinator-mediated effects on fruit production and seed mass for the two species pollinated almost exclusively by bumblebees or hawkmoths, with the direction of the effects differing for the quantity- and quality-related fitness components. There were no consistent effects of the yeast on maternal fecundity for any of the species with diverse pollinator assemblages.

CONCLUSIONS: Effects of M. reukaufii on plant reproduction ranged from negative to neutral or positive depending on the plant species. The among-species variation in the indirect effects of nectar yeasts on plant pollination could reflect variation in the pollinator community, the specific microbes colonizing the nectar, and the order of microbial infection (priority effects), determining potential species interactions. Elucidating the nature of these multitrophic plant-pollinator-microbe interactions is important to understand complex processes underlying plant pollination.

PMID:35315515 | DOI:10.1002/ajb2.1834

Acta Biomed. 2022 Mar 14;93(1):e2022025. doi: 10.23750/abm.v93i1.11097.

ABSTRACT

PURPOSE: The aim of the study is to show the relationship between oxidative stress and ectopic pregnancy.

MATERIALS AND METHODS: A total of 62 patients, 31 in the ectopic pregnancy group (study group) and 31 in the first-trimester pregnancy (control group) were included in the study. Patients between 18-45 years of age who had tubal ectopic pregnancy diagnosed by transvaginal ultrasonography and serum β-HCG values were included in the study group. Serum thiol- disulfide hemostasis were measured from venous blood.

RESULTS: Between the control group and the ectopic pregnant group; there was no statistically significant difference in terms of age, total thiol, albumin, disulfide, index 1 (disulfide / total thiol), index 2 (disulfide / native thiol), and index 3 levels (p> 0.05). The area under the ROC curve for native thiol measurements was statistically significant in distinguishing the control group and the ectopic pregnant group [AUC = 0.657, 95% CI: 0.521-0.793, p = 0.034] Conclusion: This study shows that ectopic pregnancies may be associated with the presence of high oxidative stress. Especially in early stage suspected patients, demonstrating the presence of oxidative stress together with serial β-HCG follow-up may be helpful in diagnosis.

PMID:35315421 | DOI:10.23750/abm.v93i1.11097

Acta Biomed. 2022 Mar 14;93(1):e2022033. doi: 10.23750/abm.v93i1.11887.

ABSTRACT

Qatar Biobank (QBB) is actively acquiring data on the range of short- and long-term health impacts associated with COVID-19. This is performed through the COVID-19 biorepository National project. In this report, we describe the most common indications for the referral to Qatar’s healthcare system of COVID-19 biorepository participants in comparison with the Qatar Biobank (QBB) general population study. Methods Patients with a laboratory diagnosis of COVID-19, who were Qatar residents that could communicate in Arabic, English, Hindi and Urdu were eligible to participate in the COVID-19 biorepository project. Biological samples of Consented participants were collected on a weekly basis until recovery, and then monthly for a year. Participants were also offered a bone density scan three months after recovery and non-contrast MRI brain and whole-body scan six months after recovery. Number of participants requiring referral for medical follow up after recovery for any abnormal clinically significant findings were recorded and statistically compared to general population referred participants Results: The majority of referrals for the general population study was for osteopenia versus diabetes for the COVID-19 biorepository project Conclusion Descriptive analysis of the referral data of the COVID-19 participants and QBB general population (not previously affected by the virus) shows a clear difference between the two populations’ reasons for referrals. Diabetes for COVID 19 recovered participants versus osteopenia for general population Keywords: COVID19, Reason for Referrals, Diabetes, Qatar biobank.

PMID:35315407 | DOI:10.23750/abm.v93i1.11887

Acta Biomed. 2022 Mar 14;93(1):e2022032. doi: 10.23750/abm.v93i1.11989.

ABSTRACT

BACKGROUND: The aim of this study is to establish the value of PETCO2 in COVID-19 patients intubated in emergency department, and its effects on mortality. Objectives: Between May 15, 2020 and January 15, 2021, The patients aged ≥18 years and diagnosed COVID-19, scheduled for urgent intubation in the emergency department were included.

METHOD: Single-center, prospective and observational study. Age, gender, vital signs, laboratory findings are recorded. Immediately after intubation as measured by the capnography, the initial PETCO2_1 and at post-ventilation 15 min, PETCO2_2 and first, second arterial blood gas analysis are recorded.

RESULTS: The mean age of the 48 patients was 74 years. The PETCO2_1 and PETCO2_2 measurements were statistically significantly different between the patients who survived and those who died (p=0.014, p=0.015). The patients with a high first PETCO2_1 value and a decrease to the normal level survived, but those with a low PETCO2_1 value that could not increase to a normal value died (p=0.038, p=0.031). Increased levels of SpO2, PETCO2_1, PETCO2_2 and PaCO2_2 decreased the risk of mortality, while an increased level of PaO2_2 increased the risk of mortality.

CONCLUSION: Capnography is non-invasive and provides continuous measurement. Assessment of changes in PETCO2 value would contribute to patient survival.

PMID:35315404 | DOI:10.23750/abm.v93i1.11989

Acta Biomed. 2022 Mar 14;93(1):e2022014. doi: 10.23750/abm.v93i1.12208.

ABSTRACT

OBJECTIVE: We performed a systematic review and meta-analysis for exploring clinical benefits and safety of tocilizumab in addition to standard of care (SOC) in treating patients with coronavirus disease 2019 (COVID-19).

METHODS: An electronic search was carried out in PubMed, EMBASE, Cochrane Library, and Science Direct, as well as in medRxiv preprint server, to identify eligible studies. Only randomized Controlled Trials (RCTs) that compared mortality events and/or adverse events between a tocilizumab + SOC group and a SOC-only control group were included. The primary outcome was 28-day mortality. Secondary outcomes include progression to severe disease, defined as need for mechanical ventilation (MV) or intensive care unit (ICU) admission, and adverse events (AE).

RESULTS: A total of nine studies (6,490 participants) could be included in this meta-analysis, with 3,358 participants in the tocilizumab + SOC group and 3,132 participants in the SOC-only group. The overall mortality rate was lower in the tocilizumab group compared to the SOC-only group, though the difference was not statistically significant (odds ratio [OR], 0.87; 95% CI, 0.73-1.04; I2, 15%). This finding was unaffected by subgroup analyses based on initial use of steroids or mechanical ventilation at baseline. Patients receiving tocilizumab were 26% less likely to progress to MV, and this difference was statistically significant (OR, 0.74; 95% CI, 0.64-0.86; I2, 0%). Among patients who were not in ICU at randomization, the tocilizumab group had 34 % lower rate of ICU admission compared to the SOC-only group (OR, 0.66; 95% CI, 0.40-2.14; I2, 29%). The occurrence of serious infections was lower in the tocilizumab group (OR, 0.57; 95% CI, 0.36-0.89; I2, 21%).

CONCLUSION: Tocilizumab is generally well-tolerated in COVID-19. Although this drug does not appear to have a significant benefits on survival, it may have a role in preventing progression to intensive care and MV.

PMID:35315395 | DOI:10.23750/abm.v93i1.12208

Med Care. 2022 Mar 22. doi: 10.1097/MLR.0000000000001707. Online ahead of print.

ABSTRACT

BACKGROUND: The Centers for Medicare and Medicaid Services (CMS) implemented the Medicare durable medical equipment (DME) Competitive Bidding Program (CBP) in 2011. Since then, concerns have been raised regarding access to equipment and adverse health outcomes.

OBJECTIVES: The aim was to evaluate whether the CBP was associated with changes in spending, utilization, and adverse health events (emergency department visits, hospitalizations, and falls).

RESEARCH DESIGN: A comparative interrupted time series over 8 years was used to compare Round1 and Round2 bidding to nonbidding areas. Medicare fee for services claims were aggregated at the quarterly Metropolitan Statistical Area (MSA) level from 2009 to 2016.

RESULTS: For the 3 evaluated DME (continuous positive airway pressure machines, oxygen supplies, and walkers), we found that implementation of the Medicare CBP was associated with reductions in per capita spending without changes in DME utilization or adverse health outcomes in CBP areas compared with nonbidding areas. For example, the slope change in the proportion of oxygen supplies purchasers in Round1 areas after implementation of Round1 was similar to the slope change in nonbidding areas (-0.0002; 95% CI: -0.0004, 0.0001; P=0.189). The difference in slope changes of emergency department visits and hospitalization in Round1 areas for oxygen supplies were (-0.0004; 95% CI: -0.0016, 0.0008; P=0.514) and (0.0002; 95% CI: -0.0010, 0.0014; P=0.757), respectively. Findings in Round2 areas after implementation of Round2 were similar to findings in Round1 areas.

CONCLUSIONS: The Medicare DME CBP lowered Medicare expenditures while not reducing beneficiary access or increasing adverse outcomes.

PMID:35315377 | DOI:10.1097/MLR.0000000000001707

Med Care. 2022 Mar 22. doi: 10.1097/MLR.0000000000001711. Online ahead of print.

ABSTRACT

BACKGROUND: Access to health care continues to be a challenge, especially in remote areas. Since 2013, 70 rural hospitals have closed in the United States further exacerbating barriers to health care access in rural areas.

OBJECTIVE: The objective of this study is to identify the impact of rural hospital closures on total medical spending and utilization among the commercially insured rural population.

RESEARCH DESIGN: We use a pre-post study design with a comparison group. Individual-level Texas commercial claims data in 2014-2019 were linked to the Centers for Medicare & Medicaid Services (CMS) Provider of Services Current Files, Area Health Resource File, and Census American Community Survey. We performed an event study to test for pre-trends.

SUBJECTS: Analysis sample included commercially insured individuals 19-64 years of age residing in Texas.

MEASURES: Total medical spending and counts of health care encounters.

RESULTS: Individuals residing in rural Texas areas affected by a hospital closure experienced decreases in outpatient and emergency department (ED) utilization and no statistically significant changes in total medical spending relative to the unaffected individuals. Outpatient and ED utilization decreased by 0.133 (<0.1) and 0.015 (7<0.05) visits, respectively. Heterogeneity analysis showed that individuals residing in urban Texas experienced increases in total medical spending by $12.2 per month (<0.01) as well as individual spending subcategories.

CONCLUSIONS: Rural hospital closures led to significant decreases in outpatient and ED utilization while having no effect on health care spending. Close attention must be paid to rural hospital closures to ensure equitable health care access, especially for underserved populations.

PMID:35315376 | DOI:10.1097/MLR.0000000000001711

Am J Dermatopathol. 2022 Mar 22. doi: 10.1097/DAD.0000000000002185. Online ahead of print.

ABSTRACT

Juvenile xanthogranuloma is a group C and L non-Langerhans cell histiocytosis, and its cell of origin is still debatable. The expression of CD11c, a more recently described macrophage marker, and CD4 have not been studied comprehensively. This study aimed to expand immunophenotypic profile and hence our understanding of the origin of these lesions. The surgical pathology archive was searched for the cases with the pathologic diagnosis of “xanthogranuloma” from 1995 to 2019. Immunohistochemical (IHC) stains were performed for factor XIIIa, CD11c, and CD4. Morphologically, each lesion was classified into early classic, classic, or transitional subtypes. Seventy-seven cases were included with the median age of 7.8 years (male:female 1.3:1). Uniform positivity was noticed for CD4 (n = 77), CD68 (n = 37), CD163 (n = 5), and vimentin (n = 4) stains. Other stains included CD11c 75/77 (97.4%), factor XIIIa 71/76 (93.4%), S-100 protein 4/23 (17.4%), and CD1a 0/18 (0%). Despite insignificant association between morphologic subtype and main studied IHC stains, factor XIIIa reactivity was highest in transitional lesions and CD11c showed higher reactivity in early classic lesions. CD11c and CD4 are sensitive markers and showed promising results in the diagnosis of juvenile xanthogranuloma compared with factor XIIIa. Despite different reactivity of factor XIIIa and CD11c in various morphologic subtypes, such association was statistically insignificant.

PMID:35315372 | DOI:10.1097/DAD.0000000000002185

J Pharmacol Toxicol Methods. 2022 Mar 18:107168. doi: 10.1016/j.vascn.2022.107168. Online ahead of print.

ABSTRACT

INTRODUCTION: Porcine animal models are used in biomedical research due to anatomical and physiological similarities with human patients. The study aimed to validate telemetric systemic blood pressure (BP) and heart rate (HR) monitoring in Göttingen Minipigs, and in addition to study the effects of three different anaesthesia protocols on telemetric BP and HR measurements.

METHODS: Eight female Göttingen Minipigs had telemetry transmitters implanted in the right carotid artery. Over ten weeks, systemic 24-h BP and HR monitoring were repeated four times, each ending with an angiotensin II stimulation test. In addition, systemic BP and HR evaluated by telemetry, intra-arterial catheter (IAC) and oscillometric tail-cuff were compared before and after the 10-weeks period. Furthermore, changes in telemetric systemic BP and HR were monitored during anaesthesia in a cross-over design using three different protocols of general anaesthesia: Midazolam/ketamine (MK), propofol, and a combination of tiletamine, zolazepam, xylazine, ketamine and butorphanol (Zoletil-mix).

RESULTS: One minipig was excluded and some data were missing due to central-venous catheter issues. The coefficient of variation was below 10% for the 24-h BP and HR measurements, but higher during angiotensin II stimulation. There was a disagreement between the tail-cuff measurement and telemetry/IAC, however the differences were independent of the BP and HR level. All anaesthesia protocols numerically influenced BP and HR, but only propofol statistically significantly decreased the BP.

CONCLUSION: The study showed acceptable reproducibility of telemetric measurement of BP and HR over ten weeks in freely moving Göttingen Minipigs. There was a disagreement between direct and indirect BP measurement, and BP and HR were influenced by all anaesthesia protocols.

PMID:35315338 | DOI:10.1016/j.vascn.2022.107168