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AIDS (London, England) Jun 2022The ability of antiretroviral drugs to penetrate and suppress viral replication in tissue reservoir sites is critical for HIV remission. We evaluated antiretroviral...
OBJECTIVE
The ability of antiretroviral drugs to penetrate and suppress viral replication in tissue reservoir sites is critical for HIV remission. We evaluated antiretroviral concentrations in lymph nodes and their impact on HIV transcription.
METHODS
Participants of the RV254/SEARCH010 Acute HIV Infection Cohort in Thailand were enrolled. Group 1 (n = 6) initiated and continued antiretrovirals with two nucleoside reverse transcriptase inhibitors (NRTIs), dolutegravir (DTG) and mar- aviroc (MVC). Group 2 (n = 12) initiated antiretrovirals with two NRTIs as well as efavirenz and were switched to two NRTIs as well as DTG. Antiretroviral concentrations were measured by mass spectroscopy. HIV RNA+ and DNA+ cells were measured by in-situ hybridization.
RESULTS
All participants were MSM. At lymph node biopsy, all had plasma HIV RNA less than 20 copies/ml. Group 2 had longer durations of antiretroviral and DTG use (medians of 135 and 63 weeks, respectively) compared with Group 1 (median 44 weeks for both). TFV-DP, 3TC-TP, DTG and MVC were quantifiable in all lymph node samples from participants receiving those drugs versus carbovir-triphosphate (CBV-TP) in four out of 14. Median ratios of lymph node to peripheral blood concentrations were DTG, 0.014; MVC, 6.9; CBV-TP, 0.38; 3TC-TP, 0.32; and TFV-DP, 3.78. Median inhibitory quotients [ratios of lymph node concentrations to in-vitro inhibitory levels (IC50-or-90)] were DTG, 0.8; MVC, 38.8; CBV-TP, 0.5; 3TC- TP, 4.1; and TFV-DP, 1.8. Ongoing viral transcription was detected in lymph node of all participants. Median lymph node RNA+ cells were 71 350 versus 99 750 cells/g for Groups 1 and 2, respectively (P = 0.111).
CONCLUSION
MVC has enhanced lymph node penetration and thereby may contribute to more complete viral suppression in the lymph node.
Topics: Anti-HIV Agents; Anti-Retroviral Agents; HIV Infections; Heterocyclic Compounds, 3-Ring; Humans; Lymph Nodes; Oxazines; Pyridones; RNA
PubMed: 35184069
DOI: 10.1097/QAD.0000000000003201 -
Health Economics May 2021Comparing median outcomes to gauge treatment effectiveness is widespread practice in clinical and other investigations. While common, such difference-in-median...
Comparing median outcomes to gauge treatment effectiveness is widespread practice in clinical and other investigations. While common, such difference-in-median characterizations of effectiveness are but one way to summarize how outcome distributions compare. This paper explores properties of median treatment effects (TEs) as indicators of treatment effectiveness. The paper's main focus is on decisionmaking based on median TEs and it proceeds by considering two paths a decisionmaker might follow. Along one, decisions are based on point-identified differences in medians alongside partially identified median differences; along the other decisions are based on point-identified differences in medians in conjunction with other point-identified parameters. On both paths familiar difference-in-median measures play some role yet in both the traditional standards are augmented with information that will often be relevant in assessing treatments' effectiveness. Implementing either approach is straightforward. In addition to its analytical results the paper considers several policy contexts in which such considerations arise. While the paper is framed by recently reported findings on treatments for COVID-19 and uses several such studies to explore empirically some properties of median-treatment-effect measures of effectiveness, its results should be broadly applicable.
Topics: COVID-19; Clinical Trials as Topic; Decision Making; Humans; Treatment Outcome
PubMed: 33667329
DOI: 10.1002/hec.4233 -
Tropical Medicine & International... Jun 2013To assess progress in improving use of medicines in developing and transitional countries by reviewing empirical evidence, 1990-2009, concerning patterns of primary care... (Review)
Review
OBJECTIVE
To assess progress in improving use of medicines in developing and transitional countries by reviewing empirical evidence, 1990-2009, concerning patterns of primary care medicine use and intervention effects.
METHODS
We extracted data on medicines use, study setting, methodology and interventions from published and unpublished studies on primary care medicine use. We calculated the medians of six medicines use indicators by study year, country income level, geographic region, facility ownership and prescriber type. To estimate intervention impacts, we calculated greatest positive (GES) and median effect sizes (MES) from studies meeting accepted design criteria.
RESULTS
Our review comprises 900 studies conducted in 104 countries, reporting data on 1033 study groups from public (62%), and private (mostly for profit) facilities (26%), and households. The proportion of treatment according to standard treatment guidelines was 40% in public and <30% in private-for-profit sector facilities. Most indicators showed suboptimal use and little progress over time: Average number of medicines prescribed per patient increased from 2.1 to 2.8 and the percentage of patients receiving antibiotics from 45% to 54%. Of 405 (39%) studies reporting on interventions, 110 (27%) used adequate study design and were further analysed. Multicomponent interventions had larger effects than single component ones. Median GES was 40% for provider and consumer education with supervision, 17% for provider education alone and 8% for distribution of printed education materials alone. Median MES showed more modest improvements.
CONCLUSIONS
Inappropriate medicine use remains a serious global problem.
Topics: Developing Countries; Humans; Inappropriate Prescribing; Pharmaceutical Preparations; Practice Patterns, Physicians'; Primary Health Care
PubMed: 23648177
DOI: 10.1111/tmi.12123 -
American Journal of Obstetrics and... Jan 2021US iodine intake, estimated from the median urinary iodine concentration of population representative data, has declined by half since the 1970s, which is problematic...
BACKGROUND
US iodine intake, estimated from the median urinary iodine concentration of population representative data, has declined by half since the 1970s, which is problematic because maternal iodine intake is critical for fetal neurodevelopment. Relying on median urinary concentrations to assess iodine intake of populations is standard practice but does not describe the number of individuals with insufficient intake. Prevalence estimates of inadequate and excessive intake are better for informing public health applications but require multiple urine samples per person; such estimates have been generated in pediatric populations but not yet among pregnant women.
OBJECTIVE
Our aims were as follows: (1) to assess median urinary iodine concentrations across pregnancy for comparison with national data and (2) to estimate the prevalence of inadequate and excessive iodine intake among pregnant women in mid-Michigan.
STUDY DESIGN
Data were collected from 2008 to 2015 as part of a prospective pregnancy cohort in which women were enrolled at their first prenatal clinic visit. Few exclusion criteria (<18 years or non-English speaking) resulted in a sample of women generally representative of the local community, unselected for any specific health conditions. Urine specimens were obtained as close as practicable to at least 1 specimen per trimester during routine prenatal care throughout pregnancy (n=1-6 specimens per woman) and stored at -80°C until urinary iodine was measured to estimate the iodine intake (n=1014 specimens from 464 women). We assessed urinary iodine across pregnancy by each gestational week of pregnancy and by trimester. We used multiple urine specimens per woman, accounted for within-person variability, performed data transformation to approximate normality, and estimated the prevalence of inadequate and excessive iodine intake using a method commonly employed for assessment of nutrient status.
RESULTS
Maternal characteristics reflected the local population in racial and ethnic diversity and socioeconomic status as follows: 53% non-Hispanic white, 22% non-Hispanic black, and 16% Hispanic; 48% had less than or equal to high school education and 71% had an annual income of <$25,000. Median urinary iodine concentrations in the first, second, and third trimester-including some women contributing more than 1 specimen per trimester-were 171 μg/L (n=305 specimens), 181 μg/L (n=366 specimens), and 179 μg/L (n=343 specimens), respectively, with no significant difference by trimester (P=.50, Kruskal-Wallis test for equality of medians). The estimated prevalence of inadequate and excessive iodine intake was 23% and <1%, respectively.
CONCLUSION
Median urinary iodine concentrations in each trimester were above the World Health Organization cutoff of 150 μg/L, indicating iodine sufficiency at the group level across pregnancy. However, the estimated prevalence of inadequate iodine intake was substantial at 23%, whereas prevalence of excessive intake was <1%, indicating a need for at least some women to increase consumption of iodine during pregnancy. The American Thyroid Association, the Endocrine Society, and the American Academy of Pediatrics recommend that all pregnant and lactating women receive a daily multivitamin or mineral supplement that contains 150 μg of iodine. The data presented here should encourage the collection of similar data from additional US population samples for the purpose of informing the American College of Obstetricians and Gynecologists' own potential recommendations for prenatal iodine supplementation.
Topics: Adult; Cohort Studies; Deficiency Diseases; Dietary Supplements; Female; Humans; Iodine; Michigan; Nutritional Requirements; Pregnancy; Pregnancy Complications; Pregnancy Trimesters; Prenatal Care; Prospective Studies; United States; Young Adult
PubMed: 32653458
DOI: 10.1016/j.ajog.2020.06.052 -
Clinical Therapeutics Apr 2014Erythropoiesis-stimulating agents (ESAs) increase red blood cell production in patients with chemotherapy-induced anemia (CIA). In Europe, short-acting ESAs (epoetin... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Erythropoiesis-stimulating agents (ESAs) increase red blood cell production in patients with chemotherapy-induced anemia (CIA). In Europe, short-acting ESAs (epoetin alfa, epoetin beta, epoetin zeta, and epoetin theta) and a long-acting ESA (darbepoetin alfa) are available to treat CIA.
OBJECTIVE
This systematic review aimed to determine potential dose efficiency associated with the use of different ESAs for the treatment of CIA according to European labeling.
METHODS
A systematic review of ESA studies with starting doses according to European labeling was conducted according to published methodology. Measures of dose efficiency were defined as mean weekly doses to achieve target hemoglobin level or final dose and dose adjustments (dose increase, decrease, or withheld). Electronic databases and grey literature sources were searched up to July 2012. Data were selected for analysis using an evidence hierarchy and quantitatively analyzed to assess statistical homogeneity. Where pooling of data was not appropriate, a narrative summary with descriptive statistics (medians and ranges) was reported.
RESULTS
Fifty-five studies met the inclusion criteria. Twenty-five studies considered to represent the highest level of evidence were extracted and included in the analysis. The analysis showed a high degree of statistical heterogeneity, often precluding meta-analysis. The patients included in the analysis were representative of those encountered in clinical practice, and patient characteristics were similar between the short-acting and the darbepoetin alfa groups. Mean weekly doses appeared ~30% lower with darbepoetin alfa versus short-acting ESAs (median, 136.5 μg or 27,300 IU [range, 21,560-38,260 IU] vs 38,230 IU [range, 31,634-42,714 IU], respectively), resulting in a mean weekly dose ratio of 1:280. Darbepoetin alfa patients appeared to need fewer dose increases compared with short-acting ESAs (pooled, 0.75%; I(2) = 21% vs median 26.6% [range, 7.6%-44.6%]) and more dose decreases (median, 74% [range, 57%-75%] vs 22% [range, 2.8%-59%]). A similar percentage of darbepoetin alfa and short-acting ESA patients required a dose to be withheld (20% and 33% [2 studies] vs median 33.2% [range, 12.6%-51.1%]).
CONCLUSIONS
Statistical heterogeneity between studies was high, although clinically the studies represented medical practice. Without randomized clinical trials directly comparing darbepoetin alfa and short-acting ESAs, these findings are tentative and future research is warranted. This review shows that good-quality, reliable data from head-to-head trials are lacking. The best available evidence comes from prospective ESA-arm data. Mean weekly doses, dose increases, and dose decreases suggest a dose efficiency for darbepoetin alfa compared with short-acting ESAs.
Topics: Anemia; Darbepoetin alfa; Databases, Factual; Epoetin Alfa; Erythropoiesis; Erythropoietin; Hematinics; Humans; Middle Aged; Prospective Studies; Recombinant Proteins
PubMed: 24656152
DOI: 10.1016/j.clinthera.2014.02.007 -
Journal of Applied Statistics 2020Deciding on the best statistical method to apply when the response variable is ordinal is essential because the way the categories are ordered in the data is relevant as...
Deciding on the best statistical method to apply when the response variable is ordinal is essential because the way the categories are ordered in the data is relevant as it could change the results of the analysis. Although the models for continuous variables have similarities to those for ordinal variables, this paper presents the advantages of the use of the ordering information on the outcomes with methods developed for modeling ordinal data such as the ordered stereotype model. The novelty of this article lies in showing the dangers of assigning equally spaced scores to ordered response categories in statistical analysis, which are illustrated with a simulation study and a case study. We propose a new way to use the score parameters, which incorporates the fitted spacing dictated by the data. Additionally, this article uses score parameter estimates in the ordered stereotype model to propose a new measure to calculate continuous medians in the raw data: the . It benefits the general audience who can easily understand the median as a summary statistic. Supplementary materials for this article are available online.
PubMed: 35707023
DOI: 10.1080/02664763.2019.1674790 -
Veterinary Clinical Pathology Jun 2017Previous reports reveal variation in the cellular composition of equine bronchoalveolar lavage fluid (BALF).
BACKGROUND
Previous reports reveal variation in the cellular composition of equine bronchoalveolar lavage fluid (BALF).
OBJECTIVES
The purpose of this study was to compare the profiles of BALF from horses to assess age-related differences. Serial BALF samples were collected from the same individuals over a one-year period to identify changes in individual animals as they aged.
METHODS
Collection of BALF was performed on horses aged one week and one, 2, 6, and 12 months. Total nucleated cell count (TNCC), protein concentration, and cytology were assessed. Longitudinal analysis was performed and compared to healthy adults.
RESULTS
Foals at one week and 6 months of age had significantly higher TNCC than adults (medians: 320/μL, 285/μL, and 90/μL, respectively); no differences in total protein were found. Foals at one month had the highest proportion of macrophages (median: 87.3%), differing significantly from both yearlings and adults (medians: 45.5% and 48.7%, respectively). Foals aged one week and one month had significantly lower proportions of lymphocytes than yearlings and adults (medians: 3.2% and 4.7% vs 43.2% and 45.8%, respectively). Eosinophil percentage was lowest in foals aged one week, one month, and 2 months (median: 0.0%) and highest in foals aged 6 months (median: 2.2%). Mast cell percentages were highest in yearlings and adults (medians: 2.2% and 3.3%, respectively) and neutrophil percentage was highest in foals aged one week (13.7%).
CONCLUSIONS
Cytologic profiles of BALF from foals and adult horses differed considerably. Significant changes in TNCC and percentages of lymphocytes, macrophages, and eosinophils occurred with age.
Topics: Age Factors; Aging; Animals; Bronchoalveolar Lavage Fluid; Female; Horses; Male
PubMed: 28346682
DOI: 10.1111/vcp.12473 -
Non-coding RNA Research Mar 2023Cerebrovascular stroke (CVS) is a potentially fatal disease. The most common risk factor for CVS is hypertension.
BACKGROUND
Cerebrovascular stroke (CVS) is a potentially fatal disease. The most common risk factor for CVS is hypertension.
AIM
While most studies in the field have focused on the functional roles of long noncoding RNAs (lncRNAs) NEAT1, GAS5, and HOTAIR in CVS, less attention has been paid to their clinical relevance to stroke incidence and prognosis. Also, a link has not yet been made between these lncRNAs and hypertension, our study aim was to investigate whether the expression of these lncRNAs differed between CVS with and without hypertension, as well as to compare each group to controls.
METHOD
In total, 181 CVS patients were enrolled, including 91 chronic hypertensive patients with stroke, 90 stroke patients without hypertension, and 51 control subjects. blood samples were collected on the day of recruitment from patients with CVS and controls. Real-time qRT-PCR was used to detect the expression of target lncRNAs in serum.
RESULTS
When compared to controls, there was a statistically higher level of lncNEAT1 in each case group (median (IQR) = 3.68 (1.35-7.35) and 3.05 (0.95-6.45) for the hypertensive and non-hypertensive groups, respectively, with a significantly higher level in the hypertensive group (P = 0.04). When compared to controls, lncHOTAIR was significantly downregulated in all case groups (medians in hypertensive and non-hypertensive patients were 0.13, and 0.34, respectively), with a significantly lower level in the hypertensive group (P = 0.05). LncGAS5 levels in patients were significantly lower (median (IQR) = 0.16 (0.02-0.55) and 0.25 (0.03-0.99) for the hypertensive and non-hypertensive groups, respectively) compared to controls, with a significantly lower level in the hypertensive group (P = 0.02). There was a significant positive correlation between NEAT1 and GAS5, but a significant negative correlation between each with HOTAIR in both patients' groups. We also detected a significant negative correlation between each NEAT1 or GAS5 and NIHSS score while a significant positive correlation between HOTAIR and NIHSS. ROC curve analysis for was able to differentiate patients with CVS hypertensive from patients with CVS non-hypertensive.
CONCLUSION
Patients in each case group had statistically higher levels of NEAT1 and lower levels of HOTAIR and GAS5 compared to control levels, with higher significant NEAT1 but lower significant HOTAIR and GAS5 in the hypertensive group. Therefore, lncRNAs NEAT1, HOTAIR, and GAS5 could be used as diagnostic and prognostic biomarkers of CVS that correlate with NIHSS score and could produce a novel target for CVS therapy.
PubMed: 36439973
DOI: 10.1016/j.ncrna.2022.10.004 -
Medicine Aug 2018To establish gestational age-specific and body weight-specific mid-trimester normal median equations for the prenatal serum markers α-fetoprotein (AFP), free β subunit...
To establish gestational age-specific and body weight-specific mid-trimester normal median equations for the prenatal serum markers α-fetoprotein (AFP), free β subunit human chorionic gonadotropin (fβHCG), and unconjugated oestriol (uE3) for a Chinese population; to compare and replace the median equations built in LifeCycle software; to evaluate the effect of equations used for gestation correction on estimating risk in Down's syndrome, Edward's syndrome, and neural tube defect (NTD).A total of 353,065 cases of prenatal screening data of pregnant women were screened by 13 prenatal screening institutions in China. The local median equations of each institution and the large data were fitted by the least square regression, and then the difference was compared between large data equations and local median equations. The applicability of the localized median equations was evaluated by the determination coefficient. Based on the established median equations, multiples of median (MoM) of each values were calculated and compared with the latest Down's syndrome quality assurance support service (DQASS).There is no significant difference between the local median equations of each institution and the large sample median equations, which are various from LifeCycle built-in median equations. Besides, the determination coefficient of localized median equations are >0.99. 97.0% MoM medians obtained by using local median equations are consistent with latest standard of DQASS.The median established by large sample data represents the median level of a Chinese population, and can be used to replace the software built-in median equations to achieve better screening results.
Topics: Adult; Biomarkers; China; Chorionic Gonadotropin, beta Subunit, Human; Diagnosis, Differential; Down Syndrome; Estriol; Female; Gestational Age; Humans; Neural Tube Defects; Pregnancy; Pregnancy Trimester, Second; Prenatal Diagnosis; Reference Values; Trisomy 18 Syndrome; alpha-Fetoproteins
PubMed: 30170416
DOI: 10.1097/MD.0000000000012045 -
Health Care Management Science Sep 2022Working with recent data and research findings, we estimate the probability that an air traveler in economy class would have contracted Covid-19 on a US domestic jet...
Working with recent data and research findings, we estimate the probability that an air traveler in economy class would have contracted Covid-19 on a US domestic jet flight over the nine-month period June 2020 to February 2021. The estimates take account of the rates of confirmed Covid-19 infections in the US, flight duration, fraction of seats occupied, and some demographic differences between US air travelers and US citizens as a whole. Based on point estimates, the risk of contracting Covid-19 in-flight exceeded 1 in 1000 on a fully-loaded two-hour flight at the height of the pandemic over the nine months, but was about 1 in 6000 on a half-full flight when the pandemic was at a low ebb. However, these estimates are subject to substantial uncertainty, with the 10th percentiles of various risk distributions only about 1/7 as large as the medians, and the 90th percentiles about four times as large. Based on seat-occupancy levels on US flights for each month over June 2020 to February 2021, the median risk estimate for that period is 1 in 2250, while the mean risk estimate is 1 in 1450. Indirect effects arose because those who contracted Covid-19 on US airplanes could in turn infect others.
Topics: Aircraft; COVID-19; Humans; Pandemics
PubMed: 35779143
DOI: 10.1007/s10729-022-09603-6