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Amino acids versus magnesium sulfate infusion for controlling postoperative shivering in patients undergoing percutaneous nephrolithotomy surgery: a randomized clinical trial

Minerva Anestesiol. 2022 Mar 22. doi: 10.23736/S0375-9393.22.16237-1. Online ahead of print.

ABSTRACT

BACKGROUND: General anesthetics disrupt the thermoregulatory mechanisms by reducing vasoconstriction and shivering thresholds. Postoperative shivering is a challenging anesthesia-related complication with an incidence range of 20%-70%. Amino acids that induce thermogenesis and magnesium sulfate are centrally acting mechanisms that could minimize shivering. Thus, this trial was designed to compare the effect of amino acid versus magnesium sulfate infusion on postoperative shivering in patients undergoing elective percutaneous nephrolithotomy (PCNL) surgery under general anesthesia.

METHODS: Eighty adults, American Society of Anesthesiologists I and II patients, were randomly assigned into one of two groups. Group A received general anesthesia and perioperative IV amino acid infusion. Group M received general anesthesia and perioperative IV magnesium sulfate infusion.

RESULTS: There was a statistically significant difference in shivering score, which was lower in group A than M (0.8 ± 1.1 versus 1.5 ± 1.3; P-value= 0.01). The incidence of postoperative shivering was lower in group A [4 (10%)] versus [11 (27.5%)] in group M. A less decrease in the core intraoperative temperature (Celsius) was observed in group A than in group M (35.5 ± 0.2 versus 35.1 ± 0.2; respectively, P < 0.001) and at the end of surgery (36.1 ± 0.3 versus 35.7 ± 0.3; respectively, P < 0.001).

CONCLUSIONS: Perioperative amino acids infusion is more effective and better tolerated than magnesium sulfate in preventing postoperative shivering in patients undergoing percutaneous nephrolithotomy surgery. Cost effectiveness should be kept in mind, and amino acids infusion should be reserved in high-risk surgeries for shivering.

PMID:35315622 | DOI:10.23736/S0375-9393.22.16237-1

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A Multi-Center, Double-Blind Randomized Controlled Phase III Clinical Trial to Evaluate the Antiviral Activity and Safety of DA-2802 (Tenofovir Disoproxil Orotate) and Viread (Tenofovir Disoproxil Fumarate) in Chronic Hepatitis B Patients

J Korean Med Sci. 2022 Mar 21;37(11):e92. doi: 10.3346/jkms.2022.37.e92.

ABSTRACT

BACKGROUND: Tenofovir disoproxil fumarate (TDF, Viread®) had been used as a standard treatment option of chronic hepatitis B (CHB). This clinical trial was conducted to evaluate the efficacy and safety of DA-2802 (tenofovir disoproxil orotate) compared to TDF.

METHODS: The present study was a double blind randomized controlled trial. Patients with CHB were recruited from 25 hospitals in Korea and given DA-2802 at a dose of 319 mg once daily or Viread® at a dose of 300 mg once daily for 48 weeks from March 2017 to January 2019. Change in hepatitis B virus (HBV) DNA level at week 48 after dosing compared to baseline was the primary efficacy endpoint. Secondary efficacy endpoints were proportions of subjects with undetectable HBV DNA, those with normal alanine aminotransferase (ALT) levels, and those with loss of hepatitis B envelop antigen (HBeAg), those with loss of hepatitis B surface antigen (HBsAg). Adverse events (AEs) were also investigated.

RESULTS: A total of 122 patients (DA-2802 group: n = 61, Viread® group: n = 61) were used as full analysis set for efficacy analysis. Mean age, proportion of males, laboratory results and virologic characteristics were not different between the two groups. The change in HBV DNA level at week 48 from baseline was -5.13 ± 1.40 in the DA-2802 group and -4.97 ± 1.40 log10 copies/mL in the Viread® group. The analysis of primary endpoint using the nonparametric analysis of covariance showed statistically significant results (P < 0.001), which confirmed non-inferiority of DA-2802 to Viread® by a prespecified noninferiority margin of 1. The proportion of undetectable HBV DNA was 78.7% in the DA-2802 group and 75.4% in the Viread® group (P = 0.698). The proportion of subjects who had normal ALT levels was 75.4% in the DA-2802 group and 73.3% in the Viread® group (P = 0.795). The proportion of those with HBeAg loss was 8.1% in the DA-2802 group and 10.8% in the Viread® group (P = 1.000). No subject showed HBsAg loss. The frequency of AEs during treatment was similar between the two groups. Most AEs were mild to moderate in severity.

CONCLUSION: DA-2802 is considered an effective and safe treatment for patients with CHB.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02967939.

PMID:35315603 | DOI:10.3346/jkms.2022.37.e92

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Understanding modulations of lipid mediators in cancer using a murine model of carcinomatous peritonitis

Cancer Med. 2022 Mar 22. doi: 10.1002/cam4.4699. Online ahead of print.

ABSTRACT

BACKGROUND: Numerous studies have investigated the possible involvement of eicosanoids, lysophospholipids, and sphingolipids in cancer. We considered that comprehensive measurement of these lipid mediators might provide a better understanding of their involvement in the pathogenesis of cancer. In the present study, we attempted to elucidate the modulations of sphingolipids, lysophospholipids, diacyl-phospholipids, eicosanoids, and related mediators in cancer by measuring their levels simultaneously by a liquid chromatography-mass spectrometry method in a mouse model of carcinomatous peritonitis.

METHODS: We investigated the modulations of these lipids in both ascitic fluid and plasma specimens obtained from Balb/c mice injected intraperitoneally with Colon-26 cells, as well as the modulations of the lipid contents in the cancer cells obtained from the tumor xenografts.

RESULTS: The results were as follows: the levels of sphingosine 1-phosphate were increased, while those of lysophosphatidic acid (LysoPA), especially unsaturated long-chain LysoPA, tended to be increased, in the ascitic fluid. Our findings suggested that ceramides, sphingomyelin, and phosphatidylcholine, their precursors, were supplied by both de novo synthesis and from elsewhere in the body. The levels of lysophosphatidylserine (LysoPS), lysophosphatidylinositol, lysophosphatidylglycerol, and lysophosphatidylethanolamine were also increased in the ascitic fluid, while those of phosphatidylserine (PS), a precursor of LysoPS, were markedly decreased. The levels of arachidonic acid derivatives, especially PGE2-related metabolites, were increased, while the plasma levels of eicosanoids and related mediators were decreased. Comprehensive statistical analyses mainly identified PS in the ascitic fluid and eicosanoids in the plasma as having highly negative predictive values for cancer.

CONCLUSIONS: The results proposed many unknown associations of lipid mediators with cancer, underscoring the need for further studies. In particular, the PS/LysoPS pathway could be a novel therapeutic target, and plasma eicosanoids could be useful biomarkers for cancer.

PMID:35315587 | DOI:10.1002/cam4.4699

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A polyphenol-rich diet increases the gut microbiota metabolite indole 3-propionic acid in older adults with preserved kidney function

Mol Nutr Food Res. 2022 Mar 22:e2100349. doi: 10.1002/mnfr.202100349. Online ahead of print.

ABSTRACT

SCOPE: Dietary polyphenols can alter the gut microbiota (GM) and promote the production of bioactive metabolites. Several indoles result of GM metabolism of dietary tryptophan have been associated with intestinal barrier integrity. Our aim was to study the changes in GM-derived indoles during a polyphenol-rich (PR) diet intervention in older adults.

METHODS AND RESULTS: Randomized, controlled, crossover trial in adults ≥60y living in a residential care facility during an 8-week PR versus control diet (n = 51). Seven GM-tryptophan metabolites were measured in serum, and metataxonomic analysis of GM was performed on fecal samples. Exploratory subgroup analyses were performed based on renal function (RF). The PR-diet significantly increased serum IPA in subjects with normal RF, but not in subjects with impaired RF. Other GM-tryptophan metabolites were not affected. Comparison of baseline GM composition showed shifts in Bacteroidales order members as well as higher abundance of Clostridiales in participants with normal RF. During the trial, variations of IPA were associated with changes in C-reactive protein (β = 0.32, p = 0.010) and GM, particularly with the Clostridiales (r = 0.35, p<0.001) and Enterobacteriales (r = -0.15, p<0.05) orders.

CONCLUSION: A PR diet increases the serum concentration of IPA in older adults with normal RF. Our findings may be important when defining appropriate dietary interventions for older adults.

TRIAL REGISTRATION NUMBER: ISRCTN10214981 (https://doi.org/10.1186/ISRCTN10214981). This article is protected by copyright. All rights reserved.

PMID:35315592 | DOI:10.1002/mnfr.202100349

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Violence against women and perceived health: An observational survey of patients treated in the multidisciplinary structure ‘The Women’s House’ and two Family Planning Centres in the metropolitan Paris area

Health Soc Care Community. 2022 Mar 22. doi: 10.1111/hsc.13797. Online ahead of print.

ABSTRACT

It is unknown how many women seeking care at French Family Planning Centres (FPCs) endure, or have endured intimate partner violence (IPV). To assess the prevalence of IPV, we surveyed women seeking care at three FPCs in the metropolitan Paris area (Seine-Saint-Denis). We examined the associations between IPV, socio-demographic characteristics and perceptions of health according to six indicators. Of the FPCs included in our survey, two are standalone facilities and one is located in The Women’s Home, a multidisciplinary structure dedicated to serving survivors of violence. We conducted an observational survey from December 2018 to February 2019. All women aged 18 years and older were eligible. We solicited data on socio-demographic factors, general stability and history of violence. We measured health status on a 10-point scale for six different symptoms. Of the 274 women who participated, 27% had experienced IPV. Women who reported experiencing, or having experienced IPV were more likely to be between 25 and 44 years old (than under 25), temporarily documented or undocumented, unemployed or seeking employment, and experiencing housing insecurity. Women seeking care at The Women’s House were more than twice as likely to report IPV (42%) than those visiting FPC-2 or FPC-3 (20% and 16%, respectively). Reports of violence increase among women with uncertain legal status, housing, employment and lower self-rated health. Results suggest that a FPC located in a structure specifically dedicated to serving women victims-survivors of violence like the Women’s House may be more attractive to survivors.

PMID:35315551 | DOI:10.1111/hsc.13797

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Training of deep cross-modality conversion models with a small dataset, and their application in megavoltage CT to kilovoltage CT conversion

Med Phys. 2022 Mar 22. doi: 10.1002/mp.15626. Online ahead of print.

ABSTRACT

PURPOSE: In recent years, deep-learning-based image processing has emerged as a valuable tool for medical imaging owing to its high performance. However, the quality of deep-learning-based methods heavily relies on the amount of training data; the high cost of acquiring a large dataset is a limitation to their utilization in medical fields. Herein, based on deep learning, we developed a computed tomography (CT) modality conversion method requiring only a few unsupervised images.

METHODS: The proposed method is based on CycleGAN with several extensions tailored for CT images, which aims at preserving the structure in the processed images and reducing the amount of training data. This method was applied to realize the conversion of megavoltage computed tomography (MVCT) to kilovoltage computed tomography (kVCT) images. Training was conducted using several datasets acquired from patients with head and neck cancer. The size of the datasets ranged from 16 slices (two patients) to 2745 slices (137 patients) for MVCT and 2824 slices (98 patients) for kVCT.

RESULTS: The required size of the training data was found to be as small as a few hundred slices. By statistical and visual evaluations, the quality improvement and structure preservation of the MVCT images converted by the proposed model were investigated. As a clinical benefit, it was observed by medical doctors that the converted images enhanced the precision of contouring.

CONCLUSIONS: We developed an MVCT to kVCT conversion model based on deep learning, which can be trained using only a few hundred unpaired images. The stability of the model against changes in data size was demonstrated. This study promotes the reliable use of deep learning in clinical medicine by partially answering commonly asked questions, such as “Is our data sufficient?” and “How much data should we acquire?” This article is protected by copyright. All rights reserved.

PMID:35315529 | DOI:10.1002/mp.15626

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Efficacy and Safety of Single-dose Antiviral Drugs for Influenza Treatment: A Systematic Review and Network Meta-analysis: Trial registration

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

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Temperature impacts the environmental suitability for malaria transmission by Anopheles gambiae and Anopheles stephensi

Ecology. 2022 Mar 22:e3685. doi: 10.1002/ecy.3685. Online ahead of print.

ABSTRACT

Extrinsic environmental factors influence the spatio-temporal dynamics of many organisms, including insects that transmit the pathogens responsible for vector-borne diseases (VBDs). Temperature is an especially important constraint on the fitness of a wide variety of ectothermic insects. A mechanistic understanding of how temperature impacts traits of ectotherms and thus the distribution of ectotherms and vector-borne infections is key to predicting the consequences of climate change on transmission of VBDs like malaria. However, the response of transmission to temperature and other drivers is complex, as thermal traits of ectotherms are typically non-linear, and they interact to determine transmission constraints. In this study, we assess and compare the effect of temperature on the transmission of two malaria parasites, Plasmodium falciparum and Plasmodium vivax, by two malaria vector species, Anopheles gambiae and Anopheles stephensi. We model the non-linear responses of temperature dependent mosquito and parasite traits (mosquito development rate, bite rate, fecundity, proportion of eggs surviving to adulthood, vector competence, mortality rate, and parasite development rate) and incorporate these traits into a suitability metric based on a model for the basic reproductive number across temperatures. Our model predicts that the optimum temperature for transmission suitability is similar for the four mosquito-parasite combinations assessed in this study, but may differ at the thermal limits. More specifically, we found significant differences in the upper thermal limit between parasites spread by the same mosquito (An. stephensi) and between mosquitoes carrying P. falciparum. In contrast, at the lower thermal limit the significant differences were primarily between the mosquito species that both carried the same pathogen (e.g., An. stephensi and An. gambiae both with P. falciparum). Using prevalence data, we show that the transmission suitability metric S(T) calculated from our mechanistic model is consistent with observed P. falciparum prevalence in Africa and Asia but is equivocal for P. vivax prevalence in Asia, and inconsistent with P. vivax prevalence in Africa. We mapped risk to illustrate the number of months various areas in Africa and Asia predicted to be suitable for malaria transmission based on this suitability metric. This mapping provides spatially explicit predictions for suitability and transmission risk.

PMID:35315521 | DOI:10.1002/ecy.3685

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Contrasting effects of nectar yeasts on the reproduction of Mediterranean plant species

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

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Evaluation of Oxidative Stress in Ectopic Pregnancies

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