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Nevin Manimala Statistics

Impact of Post-Thaw Incubation Time of Frozen Embryos on Clinical Pregnancy Rate

J Hum Reprod Sci. 2023 Jan-Mar;16(1):64-69. doi: 10.4103/jhrs.jhrs_180_22.

ABSTRACT

BACKGROUND: Vitrification of embryos following a single-controlled ovarian stimulation has been the strategy practised now in many in vitro fertilisation clinics to minimise the risk of early ovarian hyper stimulation syndrome, to reduce multiple pregnancy rates and to improve cumulative pregnancy rates. In recent years, advances in vitrification techniques and improved culture conditions have led to good post-thaw embryo survival rates, thereby increasing pregnancy rates of frozen embryo transfer (FET) cycles.

AIM: The aim of this study was to analyse the effect of post-thaw incubation time of frozen embryos on the clinical pregnancy rates (CPRs) of frozen embryo transfer (FET) cycles.

SETTINGS AND DESIGN: This was a retrospective, comparative study done at a teaching hospital in assisted reproductive treatment.

MATERIALS AND METHODS: Three hundred and ten FET cycles were analysed, of which 125 had day 2 freezing and 185 had day 3 freezing. Depending upon the day of thawing and day of transfer, FET cycles were divided into six groups: Group 1 (day 2 thawing and day 3 transfer), Group 2 (day 2 thawing and day 4 transfer), Group 3 (day 2 thawing and day 5 transfer), Group 4 (day 3 thawing and day 3 transfer), Group 5 (day 3 thawing and day 4 transfer) and Group 6 (day 3 thawing and day 5 transfer).

STATISTICAL ANALYSIS USED: Statistical analysis was performed using version 14 R software version 4.0.1 (2020-06-06) (R foundation for Statistical Computing, Vienna, Austria). A P < 0.05 is taken as significant.

RESULTS: The CPR of Group 4 was 42.4% which was more than that of the other groups but it did not reach statistical significance.

CONCLUSIONS: Short incubation time of 2-4 h is as effective as an extended incubation time in terms of CPRs of FET cycles.

PMID:37305777 | PMC:PMC10256942 | DOI:10.4103/jhrs.jhrs_180_22

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Nevin Manimala Statistics

Investigating the effects of a blue-blocking software on the daily rhythm of sleep, melatonin, cortisol, positive and negative emotions

Chronobiol Int. 2023 Jun 11:1-7. doi: 10.1080/07420528.2023.2222816. Online ahead of print.

ABSTRACT

Since the use of light and electronic devices is inevitable, the use of blue light filters (in various light sources, electronic devices or optical devices including intraocular lenses) has been shown to improve sleep quality, especially in later hours of the day and during night time. In this study, we examine the effect of the blue light on sleep and wakefulness rhythms and positive and negative emotions. This randomized clinical trial was conducted with 80 AJA University of Medical Sciences employees who use computers at least 2 h a day. All subjects were employees of the discharge unit of Imam Reza Hospital, which is located next to AJA University. The subjects were divided into two groups of 40 people, blue light filter software intervention and sham treatment. Pittsburgh Sleep Quality Index (PSQI), Positive and Negative Affect Schedule (PANAS), Visual Function Questionnaire (VFQ), Epworth Sleepiness Scale (ESS) and salivary melatonin and cortisol levels were assessed for both groups before and 3 months after the intervention. Data analysis was performed using IBM SPSS statistics for windows, version 21.0 (Armonk, NY: IBM Corporation). P value ≤ 0.05 was considered as statistically significant. The results showed that the Pittsburgh sleep scale after the intervention was significantly lower in the intervention group than in the control group. After the intervention, the VFQ was significantly lower in the intervention group than in the control group (P = 0.018). There was no significant difference in the Epworth Sleepiness Scale (ESS) between the two study groups after the intervention (P = 0.370). There was no significant difference in Positive and Negative Affect Schedule (PANAS) in the two study groups after the intervention (P = 0.140). After the intervention, cortisol levels were significantly higher in the intervention group than in the control group (P = 0.006). Also, the amount of cortisol increased significantly in the intervention group (P = 0.028). The amount of melatonin decreased significantly in the intervention group (P = 0.034). The sleep quality score after the intervention was significantly lower in the intervention group than in the control group. This indicates better sleep quality in the intervention group. The results also show that the level of visual fatigue in the intervention group decreased significantly. However, no significant change was detected regarding positive and negative emotions. After the intervention, cortisol levels were significantly higher in the intervention group than the control group. In addition, cortisol levels increased significantly and melatonin levels decreased significantly in the intervention group during the course of study.

PMID:37302816 | DOI:10.1080/07420528.2023.2222816

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Nevin Manimala Statistics

Method for detecting rare differences between two LC-MS runs

Anal Biochem. 2023 Jun 9:115211. doi: 10.1016/j.ab.2023.115211. Online ahead of print.

ABSTRACT

LC-MS based multi-attribute methods (MAM) have drawn substantial attention due to their capability of simultaneously monitoring a large number of quality attributes of a biopharmaceutical product. For successful implementation of MAM, it is usually considered a requirement that the method is capable of detecting any new or missing peaks in the sample when compared to a control. Comparing a sample to a control for rare differences is also commonly practiced in many fields for investigational purpose. Because MS signal variability differs greatly between signals of different intensities, this type of comparison is often challenging, especially when the comparison is made without enough replicates. In this report we describe a statistical method for detecting rare differences between two very similar samples without replicate analyses. The method assumes that an overwhelming majority of components have equivalent abundance between the two samples, and signals with similar intensities have similar relative variability. By analyzing several monoclonal antibody peptide mapping datasets, we demonstrated that the method is suitable for new-peak detection for MAM as well as for other applications when rare differences between two samples need to be detected. The method greatly reduced false positive rate without a significant increase of false negative rate.

PMID:37302778 | DOI:10.1016/j.ab.2023.115211

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Nevin Manimala Statistics

Determining Optimal Combination Regimens for Patients with Multiple Myeloma

Eur J Pharm Sci. 2023 Jun 9:106492. doi: 10.1016/j.ejps.2023.106492. Online ahead of print.

ABSTRACT

While many novel therapies have been approved in recent years for treating patients with multiple myeloma, there is still no established curative regimen, especially for patients with high-risk disease. In this work, we use a mathematical modeling approach to determine combination therapy regimens that maximize healthy lifespan for patients with multiple myeloma. We start with a mathematical model for the underlying disease and immune dynamics, which was presented and analyzed previously. We add the effects of three therapies to the model: pomalidomide, dexamethasone, and elotuzumab. We consider multiple approaches to optimizing combinations of these therapies. We find that optimal control combined with approximation outperforms other methods, in that it can quickly produce a combination regimen that is clinically-feasible and near-optimal. Implications of this work can be used to optimize doses and advance the scheduling of drugs.

PMID:37302768 | DOI:10.1016/j.ejps.2023.106492

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Nevin Manimala Statistics

Association of HER2DX with pathological complete response and survival outcomes in HER2-positive breast cancer

Ann Oncol. 2023 Jun 9:S0923-7534(23)00721-4. doi: 10.1016/j.annonc.2023.05.012. Online ahead of print.

ABSTRACT

PURPOSE: The HER2DX genomic test predicts pathological complete response (pCR) and survival outcome in early-stage HER2+ breast cancer. Here, we evaluated the association of HER2DX scores with 1) pCR according to hormone receptor status and various treatment regimens, and 2) survival outcome according to pCR status.

METHODS: Seven neoadjuvant cohorts with HER2DX and clinical individual patient data were evaluated (DAPHNe, GOM-HGUGM-2018-05, CALGB-40601, ISPY-2, BiOnHER, NEOHER and PAMELA). All patients were treated with neoadjuvant trastuzumab (n=765) in combination with pertuzumab (n=328), lapatinib (n=187) or without a second anti-HER2 drug (n=250). Event-free survival (EFS) and overall survival (OS) outcomes were available in a combined series of 268 patients (i.e., NEOHER and PAMELA) with a pCR (n=118) and without a pCR (n=150). Cox models were adjusted to evaluate whether HER2DX can identify patients with low- or high-risk beyond pCR status.

RESULTS: HER2DX pCR score was significantly associated with pCR in all patients (odds-ratio [OR] per 10-unit increase=1.59, 95% CI 1.43-1.77; AUC=0.75), with or without dual HER2 blockade. A statistically significant increase in pCR rate due to dual HER2 blockade over trastuzumab-only was observed in HER2DX pCR-high tumors treated with chemotherapy (OR=2.56, 1.29-5.20). A statistically significant increase in pCR rate due to multi-agent chemotherapy over a single taxane was observed in HER2DX pCR-medium tumors treated with dual HER2 blockade (OR=3.11, 1.54-6.49). The pCR rates in HER2DX pCR-low tumors were ≤30.0% regardless of treatment administered. After adjusting by pCR status, patients identified as HER2DX low-risk had better EFS (p<0.001) and OS (p=0.006) compared to patients with HER2DX high-risk.

CONCLUSION: HER2DX pCR-score and risk-score might help identify ideal candidates to receive neoadjuvant dual HER2 blockade in combination with a single taxane in early-stage HER2+ breast cancer.

PMID:37302750 | DOI:10.1016/j.annonc.2023.05.012

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Association between Acid-Lowering Agents, Metformin, and Vitamin B12 among Boston-area Puerto Ricans

J Nutr. 2023 Jun 9:S0022-3166(23)72410-3. doi: 10.1016/j.tjnut.2023.05.031. Online ahead of print.

ABSTRACT

BACKGROUND: Vitamin B12 is involved in several physiological functions, and malabsorption is reported with medication use.

OBJECTIVE: Studies have reported an inverse association between use of metformin or acid lowering agents (ALAs) such as proton pump inhibitors (PPIs), histamine 2 receptor antagonists (H2RAs) and blood vitamin B12 concentration, due to malabsorption. The concomitant use of these medications is under reported. We sought to examine these associations in a cohort of Boston-area Puerto Rican adults.

METHODS: This analysis was conducted within the Boston Puerto Rican Health Study (BPRHS), an ongoing longitudinal cohort that enrolled 1499 Puerto Rican adults aged 45-75y at baseline. Our study comprised 1428, 1155 and 782 participants at baseline, wave2 (2.2y from baseline) and wave3 (6.2y from baseline), respectively. Covariate-adjusted linear and logistic regression were used to examine association between baseline medication use and vitamin B12 concentration or deficiency (vitamin B12 < 148 pmol/L or methylmalonic acid (MMA) > 271nmol/L), and long-term medication use (continuous use for ∼6.2y) and wave3 B12 concentration and deficiency. Sensitivity analyses were done to examine these associations in B12 supplement users.

RESULTS: At baseline, we observed an association between metformin use (β = -0.069, P = 0.03) and concomitant ALA and metformin use (β = -0.112, P = 0.02) and vitamin B12 concentration, but not deficiency. We did not observe associations between ALA, PPI, or H2RA, individually, with vitamin B12 concentration or deficiency.

CONCLUSIONS: These results suggest an inverse relationship between metformin and concomitant ALA and metformin use and serum vitamin B12 concentration.

PMID:37302714 | DOI:10.1016/j.tjnut.2023.05.031

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Nevin Manimala Statistics

Needs, Roles and Challenges of Young Asian Neurosurgeons

World Neurosurg. 2023 Jun 9:S1878-8750(23)00766-0. doi: 10.1016/j.wneu.2023.05.120. Online ahead of print.

ABSTRACT

BACKGROUND: Asia has a marked shortage of neurosurgical care, with approximately 2.5 million critical cases left untreated. The Young Neurosurgeons Forum (YNF) of the World Federation of Neurosurgical Societies (WFNS) surveyed Asian neurosurgeons to identify the of research, education, and practice.

METHODS: A cross-sectional study using a pilot-tested e-survey was circulated to the Asian neurosurgical community from April to November 2018. Descriptive statistics were used to summarize variables pertaining to demographics and neurosurgical practices. Chi square test was utilized to explore the relation between World Bank income level and variables on neurosurgical practices.

RESULTS: A total of 242 responses were analyzed. Respondents were mostly from the low- and middle-income countries (70%). Most represented institutions were teaching hospitals (53%). >50% of the hospitals had between 25-50 neurosurgical beds. Access to an operating microscope (p=0.038) or image guidance system (p=0.001) appeared to increase in correlation to a higher World Bank income level. Limited opportunities for conducting research (56%) and hands-on operating opportunities (45%) were leading challenges in daily academic practice. The leading challenges were limited numbers of intensive care unit beds (51%), inadequate or absent insurance coverage (45%), and lack of organized peri-hospital care (43%). Inadequate insurance coverage decreased with increasing World Bank income levels (p<0.001). Organized peri-hospital care (p=0.001), regular MRI access (p=0.032), and equipment necessary for microsurgery (p=0.007) increased with higher World Bank income levels.

CONCLUSION: Improving neurosurgical care hinges on regional and international collaboration and national policies to ensure universal access to essential neurosurgical care.

PMID:37302707 | DOI:10.1016/j.wneu.2023.05.120

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ACCURACY, PRECISION, AND RESIDUAL VOLUME OF COMMONLY USED SYRINGES FOR INTRAVITREAL INJECTIONS AND THE IMPACT ON INTRAOCULAR PRESSURE

Ophthalmol Retina. 2023 Jun 9:S2468-6530(23)00254-3. doi: 10.1016/j.oret.2023.06.003. Online ahead of print.

ABSTRACT

PURPOSE: To compare accuracy, precision, and residual volume of commonly used syringes for intravitreal injections (IVI), and to assess the intraocular pressure (IOP) rise by variations in volumes delivered.

DESIGN: Experimental lab study.

SUBJECTS: No subjects were involved in this study.

METHODS: We tested 8 syringe models with 2 different needle setups, with 2 different solutions (distilled water or glycerin) and target volumes (50 and 70 μL). To obtain the delivered and residual volumes, we weighed the syringe-needle setups with scale before liquid withdrawal, with liquid, and after liquid release. We also created an experimental eye model to determine the transient rise in IOP following stepwise 10-μL increases in injection volumes.

MAIN OUTCOME MEASURES: Delivered and residual volumes, IOP rise.

RESULTS: We tested a total of 600 syringe-needle setups. BD Ultra-Fine (0.34 ± 0.28 μL), Zero Residual (1.53 ± 1.15 μL) and Zero Residual Silicone Oil-free (1.40 ± 1.16 μL) syringes showed the lowest residual volume (p<0.001) in comparison to the others (range: 24.86 ± 1.78 μL for Injekt-F to 51.97 ± 3.37 μL for Omnifix-F). The most accurate setups were (percentage deviation from target volume): Zero Residual Silicone Oil-free (+0.70%), Zero Residual 0.3 mL (+4.49%), BD Ultra-Fine (+7.83%), Injekt-F (9.42%), Norm-Ject (+15.88%), Omnifix-F (+16.96%), BD Plastipak Brazil (+17.96%), and BD Plastipak Spain syringes (+19.41%). There was a statistically significant difference between the Zero Residual Silicone Oil-free syringe and all other syringes (p<0.0001), except for the Zero Residual 0.3 mL syringe (p=0.029). The coefficient of variation was low for all syringes. The modeled IOP rise ranged from 32.3 (SD 1.4) mmHg for 20-μL injection volume to 76.5 (SD 1.0) mmHg for 80-μL injection volume. For the standard 50-μL injection volume, the peak pressure was 50.7 (SD 0.1) mmHg, and the pressure rise duration was 28 (SD 2) minutes.

CONCLUSIONS: There were significant differences in accuracy and residual volume between syringes, whereas they showed a high precision. Volume excess results in a considerable increase in IOP rise following injection. These findings may provide a relevant overview to clinicians and to both device and drug manufacturers regarding pharmacoeconomic, safety and efficacy issues.

PMID:37302655 | DOI:10.1016/j.oret.2023.06.003

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Child care feeding programs associated with food security and health for young children from families with low incomes

J Acad Nutr Diet. 2023 Jun 9:S2212-2672(23)00301-5. doi: 10.1016/j.jand.2023.06.003. Online ahead of print.

ABSTRACT

BACKGROUND: The Child and Adult Care Food Program (CACFP) is the primary national program that enables child care settings to provide healthy meals for children. Associations between CACFP participation and child health and development and health care utilization are understudied.

OBJECTIVE: To assess associations between children’s health, development, health care utilization and food security by meal source (child care-provided versus parent-provided) among children from low-income families with a child care subsidy attending child care in settings likely eligible to participate in CACFP.

DESIGN: The study used repeat cross-sectional surveys (new sample at successive time-points) conducted year-round.

PARTICIPANTS: /Setting: Primary caregivers of 3,084 young children accessing emergency departments (EDs) or primary care in Baltimore, Boston, Little Rock, Minneapolis, and Philadelphia were interviewed between 2010-2020. The sample was limited to children aged 13-48 months, receiving a child care subsidy and attending child care centers or family child care homes >20 hours per week.

MAIN OUTCOME MEASURES: Outcomes included household and child food security; child health, growth, and developmental risk; and admission to the hospital on the day of the ED visit.

STATISTICAL ANALYSES: Meal source and participant characteristics were analyzed using chi-square; associations of outcomes with parent-provided meals were analyzed with adjusted logistic regression.

RESULTS: The majority of children had child care-provided meals (87.2% child care-provided vs. 12.8% parent-provided). Compared to children with parent-provided meals, children with child care-provided meals had lower adjusted odds of living in a food-insecure household (AOR 0.70, [95%CI 0.55, 0.88]), being in fair or poor health (AOR 0.61, [95%CI 0.46, 0.81]), or hospital admission from the ED (AOR 0.59, [95%CI 0.41, 0.83]), with no differences in growth or developmental risk.

CONCLUSIONS: Compared to meals provided from home, child care provided meals likely supported by the Child and Adult Care Food Program (CACFP) is related to food security, early childhood health, and reduced hospital admissions from the ED among low-income families with young children.

PMID:37302653 | DOI:10.1016/j.jand.2023.06.003

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Harmonized approach to estimate the burden of disease of dietary exposure to four chemical contaminants – A French study

Sci Total Environ. 2023 Jun 9:164804. doi: 10.1016/j.scitotenv.2023.164804. Online ahead of print.

ABSTRACT

Exposure to chemical contaminants found in foods has been associated with various adverse health effects. Burden of disease studies are increasingly used to estimate the public health impact of such exposures. The aims of this study were to estimate the burden of disease due to dietary exposure to four chemicals in France in 2019 (lead (Pb), cadmium (Cd), methylmercury (MeHg), and inorganic arsenic (i-As)), and to develop harmonized methods that can be applied for other chemicals and countries. We used national food consumption data from the third French national food consumption survey, chemical food monitoring data from the Second French Total Diet Study (TDS), dose-response data and disability weights from scientific literature, and disease incidence and demographics from national statistics. We adopted a risk assessment approach to estimate disease burden, incidence, mortality, and Disability-Adjusted Life Years (DALYs) attributable to dietary exposure to the chemicals. In all models, we harmonized food classification and exposure assessment. We propagated uncertainty through the calculations using Monte Carlo simulation. We estimated that, among these chemicals, i-As and Pb were responsible for the highest disease burden. i-As was estimated to cause 820 DALYs, or approximately 1.25 DALYs per 100,000 inhabitants. The estimated burden of Pb was 1834 to 5936 DALYs, or 2.7 (lower bound) to 8.96 (upper bound) DALYs/100,000. The burden of MeHg (192 DALYs), and Cd (0 DALY) was substantially lower. The foods contributing most to disease burden was drinks (30 %), “other foods” (mostly composite dishes) (19 %), and fish and seafood (7 %). Interpretation of estimates needs to consider all underlying uncertainties, linked with data and knowledge gaps. The harmonized models are the first to make use of data from TDS, which are available in several other countries. Thus, they can be applied to estimate the burden and to rank food-associated chemicals at national level.

PMID:37302596 | DOI:10.1016/j.scitotenv.2023.164804