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Altered profile of plasma phospholipids in woman with recurrent pregnancy loss and recurrent implantation failure treated with lipid emulsion therapy

Am J Reprod Immunol. 2022 Dec 31. doi: 10.1111/aji.13673. Online ahead of print.

ABSTRACT

BACKGROUND: Recurrent Pregnancy Loss (RPL) and Recurrent Implantation Failure (RIF) are highly heterogeneous condition and many of the mechanisms involved still require elucidation. The aim was to analyze the lipidomic profile in plasma of women with RPL and RIF before and after receiving the Lipid Emulsion Therapy (LET) containing 10% fish oil (SMOFlipid® 20%).

METHODS: This study included twenty-six women with RPL or RIF from immunological or inflammatory causes, with elevated natural killer cell levels and divided into a Pregnancy Loss or a Live Birth group according to the outcome. The women received intravenous LET and sample collecting was done before the first, third and fifth dose of LET in the pregnant women. Ultra-performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-QTOF MS) and multivariate statistical methods were performed to evaluate the profile of phospholipids present in the women’s plasma.

RESULTS: An increase of phosphatidylcholines (PC) 40:8 and 36:5 levels with predominance of n6 polyunsaturated fatty acids (PUFA) was observed in plasma lipids of the Pregnancy Loss Group compared to Live Birth Group. We also observed an increase in the relative abundance of n3 PUFA-PC species (42:10 and 36:6) and LysoPC 15:0 with the long term use of LET.

CONCLUSION: The greater availability of n3 PUFA in plasma of the pregnant women stemming from LET use can be considered advantageous regarding the alteration of the phospholipid profile and its postulated anti-inflammatory and immunomodulatory role. This article is protected by copyright. All rights reserved.

PMID:36585861 | DOI:10.1111/aji.13673

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Development and validation of an electronic health records-based opioid use disorder algorithm by expert clinical adjudication among patients with prescribed opioids

Pharmacoepidemiol Drug Saf. 2022 Dec 31. doi: 10.1002/pds.5591. Online ahead of print.

ABSTRACT

BACKGROUND: In the US, over 200 lives are lost from opioid overdoses each day. Accurate and prompt diagnosis of opioid use disorders (OUD) may help prevent overdose deaths. However, International Classification of Disease (ICD) codes for OUD are known to underestimate prevalence, and their specificity and sensitivity are unknown. We developed and validated algorithms to identify OUD in electronic health records (EHR) and examined the validity of OUD ICD codes.

METHODS: Through four iterations, we developed EHR-based OUD identification algorithms among patients who were prescribed opioids from 2014-2017. The algorithms and OUD ICD codes were validated against 169 independent “gold standard” EHR chart reviews conducted by an expert adjudication panel across four healthcare systems. After using 2014-2020 EHR for validating iteration 1, the experts were advised to use 2014-2017 EHR thereafter.

RESULTS: Of the 169 EHR charts, 81 (48%) were reviewed by more than one expert and exhibited 85% expert agreement. The experts identified 54 OUD cases. The experts endorsed all 11 OUD criteria from the Diagnostic and Statistical Manual of Mental Disorders-5, including craving (72%), tolerance (65%), withdrawal (56%), and recurrent use in physically hazardous conditions (50%). The OUD ICD codes had 10% sensitivity and 99% specificity, underscoring large underestimation. In comparison our algorithm identified OUD with 23% sensitivity and 98% specificity.

CONCLUSIONS AND RELEVANCE: This is the first study to estimate the validity of OUD ICD codes and develop validated EHR-based OUD identification algorithms. This work will inform future research on early intervention and prevention of OUD.

PMID:36585827 | DOI:10.1002/pds.5591

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Is anticholinergic and sedative drug burden associated with postdischarge institutionalization in community-dwelling older patients acutely admitted to hospital? A Norwegian registry-based study

Pharmacoepidemiol Drug Saf. 2022 Dec 30. doi: 10.1002/pds.5590. Online ahead of print.

ABSTRACT

PURPOSE: Investigate the association between anticholinergic (AC) and sedative (SED) drug burden before hospitalization and post-discharge institutionalization (PDI) in community-dwelling older patients acutely admitted to hospital.

METHODS: A cross-sectional study using data from the Norwegian Patient Registry and the Norwegian Prescription Database. We studied acutely hospitalized community-dwelling patients ≥70 years during 2013 (N=86,509). Patients acutely admitted to geriatric wards underwent subgroup analyses (n=1,715). We calculated drug burden by the Drug Burden Index (DBI), use of AC/SED drugs, and the number of AC/SED drugs. Piecewise linearity of DBI vs PDI and a knot point (DBI=2.45) was identified. Statistical analyses included an adjusted multivariable logistic regression model.

RESULTS: In the total population, 45.4% were exposed to at least one AC/SED drug, compared to 52.5% in the geriatric subgroup. AC/SED drugs were significantly associated with PDI. The DBI with Odds Ratios (ORs) of 1.11 (95% CI 1.07-1.15) for DBI<2.45 and 1.08 (95% CI 1.04-1.13) for DBI≥2.45. The number of AC/SED drugs with OR of 1.07 (95% CI 1.05-1.09). The AC component of DBI with OR 1.23 and the number of AC drugs with OR 1.13. In the subgroup, ORs were closer to 1 for AC drugs.

CONCLUSIONS: The use of AC/SED drugs was highly prevalent in older patients before acute hospital admissions, and significantly associated with PDI. The number, or just using AC/SED drugs, gave similar associations with PDI compared to applying the DBI. Using AC drugs showed higher sensitivity, indicating that to reduce the risk of PDI, a clinical approach could be to reduce the number of AC drugs.

PMID:36585814 | DOI:10.1002/pds.5590

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Design and characterization of lipid nanocarriers for oral delivery of immunotherapeutic peptides

J Biomed Mater Res A. 2022 Dec 30. doi: 10.1002/jbm.a.37477. Online ahead of print.

ABSTRACT

The use of therapeutic proteins and peptides is of great interest for the treatment of many diseases, and advances in nanotechnology offer a path toward their stable delivery via preferred routes of administration. In this study, we sought to design and formulate a nanostructured lipid carrier (NLC) containing a nominal antigen (insulin peptide) for oral delivery. We utilized the design of experiments (DOE) statistical method to determine the dependencies of formulation variables on physicochemical particle characteristics including particle size, polydispersity (PDI), melting point, and latent heat of melting. The particles were determined to be non-toxic in vitro, readily taken up by primary immune cells, and found to accumulate in regional lymph nodes following oral administration. We believe that this platform technology could be broadly useful for the treatment of autoimmune diseases by supporting the development of oral delivery-based antigen specific immunotherapies.

PMID:36585800 | DOI:10.1002/jbm.a.37477

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Health-related quality of life and productivity costs in breast cancer patients treated with tamoxifen in the Netherlands

Biomed Pharmacother. 2022 Dec 28;158:114158. doi: 10.1016/j.biopha.2022.114158. Online ahead of print.

ABSTRACT

The aim of this study was to describe health-related quality of life (HRQoL) and productivity in Dutch breast cancer patients treated with tamoxifen in an adjuvant setting. Patients who started treatment with a standard dose of tamoxifen and who gave written informed consent, were eligible for participation in this trial. A total of 145 patients were asked to complete a survey at 3 months (T1) and 6 months (T2) after initiation of tamoxifen. HRQoL was measured by the EQ-5D-5L and the FACT-B questionnaire, and productivity by using the iMTA Productivity Costs Questionnaire. At 3 months 137 (95%) and at 6 months 133 (92%) patients responded to the surveys. EQ-5D-5 L utility values for T1 and T2 were 0.81 ± 0.17 and 0.81 ± 0.18, respectively. FACT-B scores for T1 and T2 were 109 ± 17.9 and 108 ± 20.0, respectively. No differences in both EQ-5D-5 L utility and FACT-B scores were found between T1 and T2 (p > 0.05). Age and employment status were statistically significantly associated with FACT-B scores (p = 0.04 and p = 0.03, respectively), indicating that younger and unemployed respondents had lower FACT-B scores. Importantly, both short-term and long-term productivity improved during the first six months of tamoxifen treatment (p < 0.05). Here, short-term productivity losses (consisting of absenteeism, presenteeism and unpaid work) for T1 and T2 were estimated at € 855,- and € 396,-, respectively. Long-term productivity losses (consisting of absenteeism) for T1 and T2 were estimated at € 2876,- and € 1104,-, respectively. In conclusion, this study presents HRQoL scores using different instruments and detailed loss of productivity estimates for breast cancer patients treated with adjuvant endocrine therapy. The results presented here can be used to inform input parameters in health economic evaluations of interventions for patients with breast cancer in the Netherlands and other Western countries and ultimately support decision making.

PMID:36584427 | DOI:10.1016/j.biopha.2022.114158

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Octanol/Air Partition Coefficient─A General-Purpose Fragment Model to Predict Log Koa from Molecular Structure

Environ Sci Technol. 2022 Dec 30. doi: 10.1021/acs.est.2c06170. Online ahead of print.

ABSTRACT

The octanol/air partition coefficient Koa is important for assessing the bioconcentration of airborne xenobiotics in foliage and in air-breathing organisms. Moreover, Koa informs about compound partitioning to aerosols and indoor dust, and complements the octanol/water partition coefficient Kow and the air/water partition coefficient Kaw for multimedia fate modeling. Experimental log Koa at 25 °C has been collected from literature for 2161 compounds with molecular weights from 16 to 959 Da. The curated data set covers 18.2 log units (from -1.0 to 17.2). A newly developed fragment model for predicting log Koa from molecular structure outperforms COSMOtherm, EPI-Suite KOAWIN, OPERA, and linear solvation energy relationships (LSERs) regarding the root-mean-squared error (rms) and the maximum negative and positive errors (mne and mpe) (rms: 0.57 vs 0.86 vs 1.09 vs 1.19 vs 1.05-1.53, mne: -2.55 vs -3.95 vs -7.51 vs -7.54 vs (-5.63) – (-7.34), mpe: 2.91 vs 5.97 vs 7.54 vs 4.24 vs 6.89-10.2 log units). The prediction capability, statistical robustness, and sound mechanistic basis are demonstrated through initial separation into a training and prediction set (80:20%), mutual leave-50%-out validation, and target value scrambling in terms of temporarily wrong compound-Koa allocations. The new general-purpose model is implemented in a fully automatized form in the ChemProp software available to the public. Regarding Koa indirectly determined through Kow and Kaw, a new approach is developed to convert from wet to dry octanol, enabling higher consistency in experimental (and thus also predicted) Koa.

PMID:36584390 | DOI:10.1021/acs.est.2c06170

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Evaluation of health screening data for factors associated with peri-implant bone loss

J Periodontal Implant Sci. 2022 Dec;52(6):509-521. doi: 10.5051/jpis.2203620181.

ABSTRACT

PURPOSE: Systemic health has a profound effect on dental treatment. The aim of this study was to evaluate peri-implant bone loss and health screening data to discover factors that may influence peri-implant diseases.

METHODS: This study analyzed the panoramic X-rays of patients undergoing health screenings at the Health Promotion Center at Seoul St. Mary’s Hospital in 2018, to investigate the relationship between laboratory test results and dental data. The patients’ physical data, such as height, weight, blood pressure, hematological and urine analysis data, smoking habits, number of remaining teeth, alveolar bone level, number of implants, and degree of bone loss around the implant, were analyzed for correlations. Their associations with glycated hemoglobin, glucose, blood urea nitrogen (BUN), creatinine, and severity of periodontitis were evaluated using univariate and multivariate regression analysis.

RESULTS: In total, 2,264 patients opted in for dental health examinations, of whom 752 (33.2%) had undergone dental implant treatment. These 752 patients had a total of 2,658 implants, and 129 (17.1%) had 1 or more implants with peri-implant bone loss of 2 mm or more. The number of these implants was 204 (7%). Body mass index and smoking were not correlated with peri-implant bone loss. Stepwise multivariate regression analysis revealed that the severity of periodontal bone loss (moderate bone loss: odds ratio [OR], 3.154; 95% confidence interval [CI], 1.175-8.475 and severe bone loss: OR, 7.751; 95% CI, 3.003-20) and BUN (OR, 1.082; 95% CI, 1.027-1.141) showed statistically significant predictive value. The severity of periodontitis showed greater predictive value than the biochemical parameters of blood glucose, renal function, and liver function.

CONCLUSIONS: The results of this study showed that periodontal bone loss was a predictor of peri-implant bone loss, suggesting that periodontal disease should be controlled before dental treatment. Diligent maintenance care is recommended for patients with moderate to severe periodontal bone loss.

PMID:36584329 | DOI:10.5051/jpis.2203620181

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Outpatient Prosthetic Based Reconstruction During COVID-19 Pandemic Possible in Selected Patients Without Increased Complications

Plast Reconstr Surg. 2023 Jan 2. doi: 10.1097/PRS.0000000000010127. Online ahead of print.

ABSTRACT

BACKGROUND: Following the reopening of elective surgery, our division transitioned from inpatient admission to same-day discharge for immediate prosthetic breast reconstruction in an effort to decrease the hospital’s clinical burden and minimize potential COVID-19 exposure. This study aims to compare complication rates following this acute transition for patients who had inpatient and outpatient mastectomy with immediate alloplastic reconstruction.

METHODS: A retrospective chart review was performed on patients who underwent mastectomy with immediate prosthetic reconstruction. The outcome of interest was 30-day morbidity. Descriptive statistics were compared for patients with outpatient and inpatient surgeries. Odds ratios were calculated to determine whether any pre-operative factors increased odds of 30-day complications.

RESULTS: A total of 115 patients were included in this study. Twenty-six patients had outpatient surgery and 89 stayed inpatient postoperatively. Same-day discharge did not significantly impact the odds of having one or more 30-day complications (OR: 0.275, 95% CI: 0.047-1.618, p = 0.153). Patients with complications had significantly longer median operating times (5.0, IQR 4.0 – 6.0 vs. 4.0, IQR 3.0 – 5.0, p = 0.05), and there was a statistically significant association between length of surgery and odds of complication (OR: 1.596, 95% CI: 1.039-2.451, p = 0.033). Age was independently associated with increased risk of 30-day complication (OR: 1.062, 95% CI: 1.010-1.117, p = 0.020).

CONCLUSIONS: Our findings support a continuation of same-day discharge strategy which could decrease costs for patients and hospitals without increasing complications.

PMID:36584304 | DOI:10.1097/PRS.0000000000010127

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Association of eNOS gene 4a/4b VNTR and T786C polymorphism with Crimean-Congo hemorrhagic fever

Nucleosides Nucleotides Nucleic Acids. 2022 Dec 30:1-9. doi: 10.1080/15257770.2022.2162542. Online ahead of print.

ABSTRACT

The most common viral hemorrhagic fever is Crimean-Congo hemorrhagic fever (CCHF). Endothelial nitric oxide synthase (eNOS) gene polymorphisms have been linked to both hemorrhagic fevers and viral diseases. The study’s goal is to evaluate if the eNOS gene 4a/4b and T786C polymorphisms are related to CCHF. The study included 54 CCHF RNA-positive patients and 60 control subjects. The Bosphore CCHF virus Quantification Kit v1 was used to obtain CCHF RNA, and the Magnesia 16 isolation device was used to isolate DNA (Anatolia Gene works, Turkey). Polymerase chain reaction and restriction fragment length polymorphism were used to genotype the samples. The frequency of the eNOS 4a/4a, 4a/4b, and 4 b/4b genotypes in patients and the control was 6.6% versus 1.7%, 37.0% versus 43.3%, and 57.4% versus 55%, respectively. 4a: 24.07% of patients and 23.33% of controls; and 4 b: 75.92% of patients and 76.66% of controls. The frequency of the eNOS-786 T/C, T/T, T/C, and C/C genotypes in patients and the control group was 35.2% versus 68.3%; 51.9% versus 26.73%; and 13.0% versus 5.0%, respectively. The allele and genotype frequencies of the eNOS T786C variant differ statistically between patients and the control (p < 0.05). The eNOS T786C variant could be a genetic determinant for susceptibility to CCHF. To our knowledge, this is the first study to figure out the association between eNOS gene T786C polymorphisms and CCHF disease.

PMID:36584289 | DOI:10.1080/15257770.2022.2162542

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Catatonia and Delirium: Assessment of Comorbidity, Prevalence, and Therapeutic Response in Medically Ill Inpatients From a University Hospital

J Clin Psychopharmacol. 2023 Jan-Feb 01;43(1):55-59. doi: 10.1097/JCP.0000000000001621.

ABSTRACT

BACKGROUND: Catatonia is a cluster of motor features present in multiple psychiatric and clinical diseases. It may be confused with delirium because both entities are classified according to the type and degree of psychomotor activity. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria for catatonia secondary to medical conditions exclude comorbid catatonia and delirium; besides, there have been increasing reports about a comorbid presentation. This study aimed to describe the prevalence of comorbid catatonia and delirium, the therapeutic response to lorazepam, and the clinical characteristics of patients with an earlier diagnosis of delirium.

METHODS: A total of 120 consecutive patients at a university hospital with an earlier diagnosis of delirium were evaluated using the Delirium Scale (confusion assessment method for the intensive care unit) and the Bush-Francis Catatonia Rating Scale for catatonia. In cases of a positive diagnosis of catatonia or catatonia/delirium, a therapeutic trial with intramuscular lorazepam was performed.

FINDINGS: Thirty-one patients (26%) were positive for both catatonia and delirium, and 8 patients (7%) had catatonia. Sixty-six patients (55%) were positive only for delirium, and 5 patients (4%) were negative for delirium and catatonia. Lorazepam tests were applied on 22 patients. One in 9 patients with catatonia/delirium responded positively to lorazepam. Patients with catatonia had a 60% positive response rate.

CONCLUSIONS: This is the first study on lorazepam use in catatonia-delirium patients; however, further studies are needed to determine the safety and efficacy of lorazepam in these patients. Catatonia and catatonia/delirium are underdiagnosed in inpatient wards and should be routinely assessed in patients with an altered mental status.

PMID:36584250 | DOI:10.1097/JCP.0000000000001621