Characteristics and outcomes of pregnancies in the Maternal Outcomes Masterset real-world database.

PURPOSE: Describe patient characteristics and pregnancy outcomes among all pregnant patients, and additionally describe infant outcomes among the subset with linked infants in the Maternal Outcomes Masterset (MOM). METHODS: We used closed claims within the MOM data to identify publicly and privately insured patients at the first record of pregnancy January 1, 2018-December 1, 2021, with ≥180 days baseline enrollment. We described characteristics during baseline and follow-up (until an observed pregnancy endpoint, disenrollment, or 42-week maximum). We described maternal and infant characteristics overall and by infant linkage and contextualized them within national statistics. RESULTS: Among the 1 438 861 pregnant patients meeting the study criteria, the most common pregnancy endpoint recorded was live birth (42%) followed by spontaneous abortion (14%). Among 602 721 patients with a live birth, 99% had a week-specific gestational age recorded and 35% had at least one linked infant. Patients with infant linkage and sufficient follow-up (N = 155 621) had similar baseline comorbidities, pregnancy complications, and gestational age at delivery as those without any linkage. However, more patients with linkage had commercial coverage (70% vs. 31%), and were therefore older (50% vs. 31% aged ≥30 years) and more likely to have an unknown race (57% vs. 34%). CONCLUSIONS: In this large sample of pregnant patients, maternal and infant characteristics generally align with national statistics, providing confidence in the use of this data source for pregnancy research. Further, confirmation that the subset of patients with infant linkage is similar to the overall pregnancy cohort provides assurance that this subset can be considered representative.

The influence of SARS-CoV-2 on male reproduction and men's health.

BACKGROUND: SARS-CoV-2, the virus responsible for COVID-19, primarily affects the respiratory system by targeting the Angiotensin-converting enzyme 2 (ACE2) receptor and TMPRSS2. However, these receptors are also present in other organs, including the testes, where a higher concentration of ACE2 receptors has been observed. This raises concerns about the potential impact of the virus on male fertility. AIMS: In this study, we aimed to assess the effects of SARS-CoV-2 on semen parameters by comparing samples during and after infection in the same patients. MATERIALS & METHOD: The study enrolled 51 individuals who had contracted COVID-19 and analysed various parameters related to sperm quality and quantity, including C-reactive protein, testosterone levels, total sperm concentration, motility and morphology. A comparison was made between these parameters during the initial infection with SARS-CoV-2 and after a 2- and 5-month recovery period. RESULTS: The results indicated that all of the mentioned parameters were significantly affected during COVID-19 infection (PCR-ct, CRP, WBCs LH, FSH and testosterone levels, p-value = .0001). Furthermore, the study assessed TC, TM and sperm morphology in patients infected with SARS-CoV-2 and found that these parameters were also significantly influenced during the infection, (p-value = .0001; Morphology, p-value = .0004). We observed significant alterations in sperm count and morphology during infection, suggesting a potential negative impact on sperm quality. Additionally, lower hormone levels were observed during COVID-19 infection, possibly due to increased inflammatory cytokines. However, both hormones and inflammation markers returned to normal following recovery. Our findings indicate a statistically significant change in total sperm count, motility and morphology post-infection, which aligns with previous studies. Discussion, COVID-19 have a transient impact on sperm parameters and fertility, emphasizing the importance of further investigation into the long-term implications.

Comparing effects of beetroot juice and Mediterranean diet on liver enzymes and sonographic appearance in patients with non-alcoholic fatty liver disease: a randomized control trials.

Background: In both developed and developing countries, non-alcoholic fatty liver disease (NAFLD) has lately risen to the top of the list of chronic liver illnesses. Although there is no permanent cure, early management, diagnosis, and treatment might lessen its effects. The purpose of conducting the current study is to compare the effects of beetroot juice and the Mediterranean diet on the lipid profile, level of liver enzymes, and liver sonography in patients with NAFLD. Methods: In this randomized controlled trial, 180 people with a mean age of (45.19 ± 14.94) years participated. Participants ranged in age from 19 to 73. The mean weight before intervention was (82.46 ± 5.97) kg, while the mean weight after intervention was roughly (77.88 ± 6.26) kg. The trial lasted for 12 weeks. The participants were split into four groups: control, a Mediterranean diet with beet juice (BJ + MeD), Mediterranean diet alone (MeD), and beetroot juice (BJ). The Mediterranean diet included fruits, vegetables, fish, poultry, and other lean meats (without skin), sources of omega-3 fatty acids, nuts, and legumes. Beetroot juice had 250 mg of beetroot. Data analysis was done using SPSS software (version 26.0). p < 0.05 is the statistical significance level. Results: Following the intervention, Serum Bilirubin, alkaline phosphatase (ALP), alanine transaminase (ALT), serum cholesterol (CHOL), triglyceride (TG), and low-density lipoprotein (LDL) levels were significantly decreased in the BJ + MeD, BJ, and MeD groups (p = 0.001). Also, high-density lipoprotein (HDL) significantly increased in the BJ + MeD, BJ, and MeD groups (p = 0.001), while decreasing in the Control group (p = 0.001). Conclusion: The research findings indicate a significant reduction in hepatic steatosis among the groups receiving beetroot juice (BJ) and beetroot juice combined with the Mediterranean diet (BJ + MeD). This suggests that beetroot juice holds potential as an effective treatment for non-alcoholic fatty liver disease (NAFLD) in adults. Furthermore, the combination of beetroot juice with the Mediterranean diet showed enhanced efficacy in addressing NAFLD.Clinical trial registration: ClinicalTrials.gov, identifier NCT05909631.

Molecular and clinical significance of FLT3, NPM1, DNMT3A and TP53 mutations in acute myeloid leukemia patients.

BACKGROUND: Acute myeloid leukemia (AML) is a type of blood cancer that affects the bone marrow and blood cells. AML is characterized by the rapid growth and accumulation of abnormal white blood cells, known as myeloblasts, which interfere with the production of normal blood cells. AIMS: The main aim was to determine the relationship between these genetic alterations and the clinico-haematological parameters and prognostic factors with therapy for Iraqi patients with AML. METHODS: We used Sanger Sequencing to detect the mutations in 76 AML patients. Clinical data of AML patients were retrospectively analysed to compare the prognosis of each gene mutation group. RESULTS: Somatic mutations were identified in 47.4% of the enrolled patients in a core set of pathogenic genes, including FLT3 (18 patients, 23.7%), DNMT3A (14, 18.4%), NPM1 (11, 14.5%) and TP53 (5, 6.8%). As multiple mutations frequently coexisted in the same patient, we classified patients into 10 further groups. Two novel mutations were detected in FLT3-ITD, with new accession numbers deposited into NCBI GenBank (OP807465 and OP807466). These two novel mutations were computationally analysed and predicted as disease-causing mutations. We found significant differences between patients with and without the detected mutations in disease progression after induction therapy (remission, failure and death; pv = < 0.001) and statistically significant differences were reported in total leukocyte count (pv = < 0.0001). CONCLUSION: These genes are among the most frequently mutated genes in AML patients. Understanding the molecular and clinical significance of these mutations is important for guiding treatment decisions and predicting patient outcomes.

Heterogeneity in the definition of chronic rhinosinusitis disease control: a systematic review of the scientific literature.

PURPOSE: Disease control is conceptually recognized to be an important outcome measure for chronic rhinosinusitis (CRS). However, inconsistent usage is a significant factor in disadoption of important concepts and it is presently unclear how consistently the construct of CRS 'control' is being defined/applied. The objective of this study was to determine the heterogeneity of CRS disease control definitions in the scientific literature. METHODS: Systematic review of PubMed and Web of Science databases from inception through December 31, 2022. Included studies used CRS disease control as an explicitly stated outcome measure. The definitions of CRS disease control were collected. RESULTS: Thirty-one studies were identified with more than half published in 2021 or later. Definitions of CRS control were variable, although 48.4% of studies used the EPOS (2012 or 2020) criteria to define control, 14 other unique definitions of CRS disease control were also implemented. Most studies included the burden CRS symptoms (80.6%), need for antibiotics or systemic corticosteroids (77.4%) or nasal endoscopy findings (61.3%) as criteria in their definitions of CRS disease control. However, the specific combination of these criteria and prior time periods over which they were assessed were highly variable. CONCLUSION: CRS disease control is not consistently defined in the scientific literature. Although many studies conceptually treated 'control' as the goal of CRS treatment, 15 different criteria were used to define CRS disease control, representing significant heterogeneity. Scientific derivation of criteria and collaborative consensus building are needed for the development of a widely-accepted and -applied definition of CRS disease control.

Determinants of impact factor and Eigenfactor score in otolaryngology journals.

Objective: This study aims to identify determinants of high impact, measured by Impact Factor (IF) and Eigenfactor score, among otolaryngology journals. Methods: Bibliometric data of "otorhinolaryngology" journals were collected from the Journal Citation Reports (JCR) database. For the years 2009-2020, we collected normalized Eigenfactor score, 5-year IF, immediacy index, fraction of IF from journal-self citation, proportion and magnitude of published citable articles, and total citation counts. High-IF and -Eigenfactor journals were considered those within the top-quartile of that metric each respective year. Results: High-IF and -Eigenfactor otolaryngology journals displayed higher 5-year IFs, immediacy indexes, and IF without self-citation (p < .05 for all years) including total citations counts and citable articles when ranked by Eigenfactor (p < .05 for all years). Otolaryngology IF correlated with 5-year IF and immediacy index within the same year (p < .05 for all years) and from previous years (p < .05 for all years; p < .05 for 2017-2018; p > .05 for 2009-2016). Eigenfactor correlated with 5-year IF, total citation counts, and citable articles within the same year (p < .05 for all years) and previous years (p < .05 for 2013-2018). Multilinear regression revealed that 5-year IF (p < .05 for 2009-2018) and immediacy index from the prior 2 years (p < .05 for 2017-2018; p > .05 for 2009-2016) predicted 2019 IF. Similarly, 5-year IF, total citation counts, and citable articles (p < .05 for 2013-2018) predicted 2019 Eigenfactor score. Conclusion: Sustained publication of impactful articles is the dominant driver of high IF and Eigenfactor score. Eigenfactor score reflects a unique evaluation of otolaryngology journals; ranking otolaryngology journals by their Eigenfactor scores significantly alters journal ranking compared to ranking by IF. Level of evidence: NA.

Clinical outcomes and phylogenetic analysis in reflection with three predominant clades of SARS-CoV-2 variants.

BACKGROUND: The pandemic of coronavirus disease 2019 (COVID-19) has a broad spectrum of clinical manifestations. The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) undergoes continuous evolution, resulting in the emergence of several variants. Each variant has a different severity and mortality rate. MATERIALS AND METHODS: In this study, 1174 COVID-19 patients were studied for mortality and severity over three SARS-CoV-2 predominating variant periods in 2021 and 2022 in Sulaimani Province, Iraq. In each period, a representative, variant virus was subjected to phylogenetic and molecular and clinical analysis. RESULTS: Phylogenetic analysis revealed three SARS-CoV-2 variants, belonging to: Delta B.1.617.2, Omicron BA.1.17.2, and Omicron BA.5.6. The Delta variants showed more severe symptoms and a lower PCR-Ct value than Omicron variants regardless of gender, and only 4.3% of the cases were asymptomatic. The mortality rate was lower with Omicron (.5% for BA.5.2 and 1.3% for BA.1.17.2) compared with Delta variants (2.5%). The higher mortality rate with Delta variants was in males (2.84%), while that with Omicron BA1.17.2 and BA.5.2 was in females, 1.05% and .0%, respectively. Age group (≥70) years had the highest mortality rate; however, it was (.0%) in the age group (30-49) years with Omicron variants, compared with (.96%) in Delta variants. CONCLUSIONS: There has been a surge in COVID-19 infection in the city due to the predominant lineages of SARS-CoV-2, B.1.617, Omicron BA.1.17.2 and Omicron BA.5.6, respectively. A higher PCR-Ct value and severity of the Delta variant over Omicron BA.1.17.2 and/or BA.5.2 variants were significantly correlated with a higher death rate in the same order.

Using primary care data to assess comparative effectiveness and safety of apixaban and rivaroxaban in patients with nonvalvular atrial fibrillation in the UK: an observational cohort study.

OBJECTIVE: To compare real-world effectiveness and safety of direct oral anticoagulants (DOACs) in patients with nonvalvular atrial fibrillation (AFib) for prevention of stroke. STUDY DESIGN AND SETTING: A comparative cohort study in UK general practice data from The Health Improvement Network database. PARTICIPANTS AND INTERVENTIONS: Before matching, 5655 patients ≥18 years with nonvalvular AFib who initiated at least one DOAC between 1 July 2014 and 31 December 2020 were included. DOACs of interest included apixaban, rivaroxaban, edoxaban and dabigatran, with the primary comparison between apixaban and rivaroxaban. Initiators of DOACs were defined as new users with no record of prescription for any DOAC during 12 months before index date. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was stroke (ischaemic or haemorrhagic). Secondary outcomes included the occurrence of all-cause mortality, myocardial infarction (MI), transient ischaemic attacks (TIA), major bleeding events and a composite angina/MI/stroke (AMS) endpoint. RESULTS: Compared with rivaroxaban, patients initiating apixaban showed similar rates of stroke (HR: 0.93; 95% CI 0.64 to 1.34), all-cause mortality (HR: 1.03; 95% CI 0.87 to 1.22), MI (HR: 0.95; 95% CI 0.54 to 1.68), TIA (HR: 1.03; 95% CI 0.61 to 1.72) and AMS (HR: 0.96; 95% CI 0.72 to 1.27). Apixaban initiators showed lower rates of major bleeding events (HR: 0.60; 95% CI 0.47 to 0.75). CONCLUSIONS: Among patients with nonvalvular AFib, apixaban was as effective as rivaroxaban in reducing rate of stroke and safer in terms of major bleeding episodes. This head-to-head comparison supports conclusions drawn from indirect comparisons of DOAC trials against warfarin and demonstrates the potential for real-world evidence to fill evidence gaps and reduce uncertainty in both health technology assessment decision-making and clinical guideline development.

Identification of three novel DNMT3A mutations with compromising methylation capacity in human acute myeloid leukaemia.

BACKGROUND: Acute myeloid leukaemia (AML) is a complex and heterogeneous hematopoietic stem and progenitor cell malignancy characterised by the accumulation of immature blast cells in the bone marrow, blood, and other organs linked to environmental, genetic, and epigenetic factors. Somatic mutations in the gene DNA (cytosine-5)-methyltransferase 3A (DNMT3A; NM_022552.4) are common in AML patients. METHODS: In this study, we used Sanger sequencing to detect the mutations in the DNMT3A gene in 61 Iraqi AML patients, Hence, the protein function and stability within alterations were identified and analyzed using a variety of computational tools with the goal of determining how these changes affect total protein stability, and then the capacity of methylation was analyzed by methylation specific PCR MSP status at CpG islands. RESULTS: Three novel mutations in exon 23 of DNMT3A were identified in 14 patients (22.9%; V877I, N879delA, and L888Q). The V877I and L888Q substitutions are caused by heterozygous C2629G > A and C2663T > A mutations, respectively, while frameshift mutation C2635delA caused protein truncation with stop codon N879T*. Methylation was detected in the DNMT3A promoter region in 9 patients carrying DNMT3A mutations (64.28%) by MSP, and we found significant correlations between DNMT3A mutations and promoter methylation (p = 8.52 × 105). In addition, we found a significant overrepresentation of DNMT3A methylation status in patients ≥ 50 years old (p = 0.025). CONCLUSION: Our findings highlight the importance of studying the effects of DNMT3A methylation alteration in Iraqi populations beyond R882 substitutions in the leukemogenic pathway so that patient treatment can be tailored to prevent therapeutic resistance and relapse.

Disease severity and efficacy of homologous vaccination among patients infected with SARS-CoV-2 Delta or Omicron VOCs, compared to unvaccinated using main biomarkers.

From March 2021, various countries including Iraq issued prompted recommendations for increased COVID-19 vaccine protection in individuals especially those at risk of catching the virus (i.e., lifestyle, health sector workers, and chronic diseases). It is critically important to understand the impact of COVID-19 vaccinations with the most commonly used vaccines (Pfizer and AstraZeneca) among populations either on the severity of the disease or the transmissibility of SARS-CoV-2 variants of concern (VOCs) and in sequential waves. This study was conducted to establish the clinical severity of COVID-19 caused by Delta and Omicron SARS-CoV-2 variants among patients who either attended or were admitted to hospitals and to compare the effectiveness of Pfizer and AstraZeneca COVID-19 vaccines (single or double doses) at least to prevent hospitalizations if not eradicating the pandemic. A case-control study was done of 570 hospitalized patients; including 328 COVID-19 confirmed patients (166 males, 160 females) who received homologous vaccinations and 242 unvaccinated patients (128 males, 114 females) during the studied waves. The study showed that unvaccinated COVID-19 patients in both waves had expressed significantly a higher number and longer periods of symptoms than vaccinated ones. Additionally, there was no significant effect of vaccine types, Pfizer and AstraZeneca or vaccine shot numbers on the PCR-Ct in the last (Omicron) wave of the pandemic. However, in the previous (Delta) wave of the pandemic, fully vaccinated (double doses) COVID-19 patients had higher PCR-Ct values. Whether among vaccinated or unvaccinated patients, lower CRP levels recorded during the Omicron wave than that of the Delta wave, and regardless of the vaccine type or shot numbers, there were no significant differences between the two waves. Lower WBCs were observed in patients (vaccinated and unvaccinated) infected with the Delta variant in comparison to those infected with the Omicron variant and without any remarkable effect of the vaccine type or shot numbers. This is the first molecular and investigational study of the Delta variant and circulated Omicron in Iraq, regarding the severity of these two waves of SARS-CoV-2 pandemic and the efficacy of homologous vaccination, indicating the insufficiency of two doses and the demand for booster dose(s) as the most effective way of keeping on the safe-side against SARS-CoV-2.

Clinical laboratory parameters and comorbidities associated with severity of coronavirus disease 2019 (COVID-19) in Kurdistan Region of Iraq.

Background: The pandemic coronavirus disease (COVID-19) dramatically spread worldwide. Considering several laboratory parameters and comorbidities may facilitate the assessment of disease severity. Early recognition of disease progression associated with severe cases of COVID-19 is essential for timely patient triaging. Our study investigated the characteristics and role of laboratory results and comorbidities in the progression and severity of COVID-19 cases. Methods: The study was conducted from early-June to mid-August 2020. Blood samples and clinical data were taken from 322 patients diagnosed with COVID-19 at Qala Hospital, Kalar, Kurdistan Region of Iraq. Biological markers used in this study include complete blood count (CBC), D-dimer, erythrocyte sedimentation rate (ESR), serum ferritin, blood sugar, C-reactive protein (CRP) and SpO2. Results: The sample included 154 males (47.8%) and 168 females (52.2%). Most females were in the mild and moderate symptom groups, while males developed more severe symptoms. Regarding comorbidities, diabetes mellitus was considered the greatest risk factor for increasing the severity of COVID-19 symptoms. As for biological parameters, WBC, granulocytes, ESR, Ferritin, CRP and D-Dimer were elevated significantly corresponding to the severity of the disease, while lymphocytes and SpO2 showed the opposite pattern. Higher RBC was significantly associated with COVID-19 severity, especially in females. Conclusion: Gender, age and diabetes mellitus are important prognostic risk factors associated with severity and mortality of COVID-19. Relative to non-severe COVID-19, severe cases are characterized by an increase of most biological markers. These markers could be used to recognize severe cases and to monitor the clinical course of COVID-19.

Serum troponin, D-dimer, and CRP level in severe coronavirus (COVID-19) patients.

BACKGROUND: Abnormal inflammation coagulation biomarker levels of troponin, C-reactive protein (CRP), and D-dimer levels in serum have been demonstrated to be associated and involved in the disease progression of coronavirus disease 2019 (COVID-19). METHODS: First: the study aimed to investigate the correlation of troponin, CRP, d-dimer, white blood cell (WBC) and polymerase chain reaction-cycle threshold (PCR-Ct) within COVID-19 survivors (143 patients; 79 males, 64 females) and in deceased (30 patients; 12 males, 18 females) group. Also, assessing any differences between both groups in studied parameters. Second: a correlation study of studied parameters' level has been conducted within families (41 patients; 23 males [seven deaths] and 18 females [eight deaths]) that lost more than one member due to the severity of the disease. Also, differences between these family and control group (132 patients; 69 males and 63 females) group in studied parameters have been assessed. RESULTS: In the first week of hospitalization, there were significant differences in D-dimer, CRP and troponin level between survived and deceased patient groups. In the second week of the admission, both groups had significant differences in the level of all studied parameters; troponin I, D-dimer, CRP, and WBCs. WBC levels positively correlated to CRP in male survivors (r = 0.75, p < 0.0001), and to troponin in deceased male patients (r = 0.74, p = 0.007). The second week of patient admission was critical in the group of families who lost more than one person, when troponin was correlated positively with D-dimer, CRP, and WBCs. CONCLUSION: Troponin, D-dimer, CRP, and WBCs level were significantly higher in COVID-19 patients who died than in COVID-19 survivors. High troponin and WBC levels, were considerably associated with families that lost more than one member, when compared with the unrelated COVID-19 patient control.

Natural killer cell immunosuppressive function requires CXCR3-dependent redistribution within lymphoid tissues.

NK cell suppression of T cells is a key determinant of viral pathogenesis and vaccine efficacy. This process involves perforin-dependent elimination of activated CD4+ T cells during the first 3 days of infection. Although this mechanism requires cell-cell contact, NK cells and T cells typically reside in different compartments of lymphoid tissues at steady state. Here, we showed that NK cell suppression of T cells is associated with transient accumulation of NK cells within T cell-rich sites of the spleen during lymphocytic choriomeningitis virus infection. The chemokine receptor CXCR3 was required for this relocation and suppression of antiviral T cells. Accordingly, NK cell migration was mediated by type I IFN-dependent promotion of CXCR3 ligand expression. In contrast, adenoviral vectors that weakly induced type I IFN and did not stimulate NK cell inhibition of T cells also did not promote measurable redistribution of NK cells to T cell zones. Exogenous IFN rescued NK cell migration during adenoviral vector immunization. Thus, type I IFN and CXCR3 were critical for properly positioning NK cells to constrain antiviral T cell responses. Development of strategies to curtail migration of NK cells between lymphoid compartments may enhance vaccine-elicited immune responses.

Hypoalbuminemia in patients following their recovery from severe coronavirus disease 2019.

Coronavirus disease 2019 (COVID-19) is caused by a contagious virus that has spread to more than 200 countries, territories, and regions. Thousands of studies to date have examined all aspects of this disease, yet little is known about the postrecovery status of patients, especially in the long term. Here, we examined erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and serum albumin biomarkers in patients with a history of severe and mild-to-moderate COVID-19 following their recovery. In patients with severe COVID-19 serum albumin had a strong negative correlation with both ESR and CRP levels (R2 = - 0.861 and R2 = - 0.711), respectively. Also, there was a positive correlation between ESR and CRP level (R2 = 0.85) in the same group. However, there was no correlation between these biomarkers among mild-to-moderate COVID-19 patients. In addition, no correlation was recorded between the severe and mild-to-moderate COVID-19 groups. This finding highlights the sustained elevation of ESR and CRP level and reduced serum albumin level that may persist postrecovery in patients with a history of severe COVID-19.

Health care resource utilization and cost of severe hypoglycemia treatment in insulin-treated patients with diabetes in the United States.

BACKGROUND: Hypoglycemia is a major limiting factor in achieving glycemic control in persons with diabetes. In some instances, recovery from a severe hypoglycemia event may require health care resource utilization (HCRU), including the use of emergency medical services (EMS), visits to the emergency department (ED), and inpatient hospitalization. OBJECTIVES: To (a) describe the profiles of patients who experience severe hypoglycemic events and (b) characterize HCRU and the associated cost related to severe hypoglycemia treatment. METHODS: This retrospective, observational cohort study used administrative claims data from IBM MarketScan Research Databases. The study examined a cohort of subjects who experienced severe hypoglycemic events that involved HCRU during the 1-year index period. Baseline patient demographic data were collected according to patient profiles, such as payer type, type of diabetes, age, and type of insulin. HCRU and the associated cost data categorized by the patient profiles and care progression scenarios were described. RESULTS: 9,563 patients from the IBM MarketScan Research Databases experienced a severe hypoglycemic event during the index period and were included in the study; approximately 75% of those patients did not experience a severe hypoglycemic event in the previous year. Of the 9,563 patients in the cohort, the largest patient profile (n = 1,767, 18.5%) consisted of those who were on Medicaid, had type 2 diabetes, and used basal/bolus or premixed-only insulins. Overall, more than 90% of the index severe hypoglycemic events involved visits to the ED. EMS claims in the 24 hours before the ED visit were found for half of the severe hypoglycemic events (51.5%). CONCLUSIONS: Differences in HCRU and the associated costs for the treatment of severe hypoglycemia were observed among patients based on insurance, diabetes, and insulin types. Clinicians need to be aware of these differences. Optimizing treatment of severe hypoglycemia, specifically EMS care, and examining patient profiles to develop targeted interventions could potentially provide benefits to patients and reduce cost and resource utilization. DISCLOSURES: This study was funded by Eli Lilly and Company. All authors are employees and shareholders of Eli Lilly and Company. The data presented here have been presented in poster form at AMCP Nexus 2020 Virtual, October 19-23, 2020; ADCES Virtual Conference 2020, August 13-16, 2020; and Virtual ISPOR 2020, May 18-20, 2020.

Reasons for discontinuing insulin and factors associated with insulin discontinuation in patients with type 2 diabetes mellitus: a real-world evidence study.

BACKGROUND: Evidence suggests that insulin therapy of patients with type 2 diabetes mellitus (T2DM) is frequently discontinued. However, the reasons for discontinuing insulin and factors associated with insulin discontinuation in this patient population are not well understood. METHODS: We conducted a retrospective cohort study of adults with T2DM prescribed insulin between 2010 and 2017 at Partners HealthCare. Reasons for discontinuing insulin and factors associated with insulin discontinuation were studied using electronic medical records (EMR) data. Natural language processing (NLP) was applied to identify reasons from unstructured clinical notes. Factors associated with insulin discontinuation were extracted from structured EMR data and evaluated using multivariable logistic regression. RESULTS: Among 7009 study patients, 2957 (42.2%) discontinued insulin within 12 months after study entry. Most patients who discontinued insulin (2121 / 71.7%) had reasons for discontinuation documented. The most common reasons were improving blood glucose control (33.2%), achieved weight loss (18.5%) and initiation of non-insulin diabetes medications (16.7%). In multivariable analysis adjusted for demographics and comorbidities, patients were more likely to discontinue either basal or bolus insulin if they were on a basal-bolus regimen (OR 1.6, 95% CI 1.3 to 1.8; p <  0.001) or were being seen by an endocrinologist (OR 2.6; 95% CI 2.2 to 3.0; p <  0.001). CONCLUSIONS: In this large real-world evidence study conducted in an area with a high penetration of health insurance, insulin discontinuation countenanced by healthcare providers was common. In most cases it was linked to achievement of glycemic control, achieved weight loss and initiation of other diabetes medications. Factors associated with and stated reasons for insulin discontinuation were different from those previously described for non-adherence to insulin therapy, identifying it as a distinct clinical phenomenon.

Immunomodulatory effects of cytokine-induced expansion of cytotoxic lymphocytes in a mouse model of lupus-like disease.

BACKGROUND AIMS: Certain therapies (e.g., daclizumab) that promote expansion of natural killer (NK) cells are associated with clinical amelioration of disease in the context of multiple sclerosis and associated mouse models. The clinical benefits are putatively attributable to an enhanced capacity of NK cells to kill activated pathogenic T cells. Whether a parallel approach will also be effective in systemic lupus erythematosus (lupus), a multi-organ autoimmune disease driven by aberrant responses of self-reactive T and B cells, is unclear. METHODS: In the present study, the authors assess the therapeutic impact of IL-2- and IL-15-based strategies for expanding NK cells on measures of lupus-like disease in a mouse model. RESULTS: Unexpectedly, cytokine-mediated expansion of cytotoxic lymphocytes aggravated immunological measures of lupus-like disease. Depletion studies revealed that the negative effects of these cytokine-based regimens can largely be attributed to expansion of CD8 T cells rather than NK cells. CONCLUSIONS: These results provoke caution in the use of cytokine-based therapeutics to treat co-morbid cancers in patients with lupus and highlight the need for new methods to selectively expand NK cells to further assess their clinical value in autoimmune disease.