Estimating COVID-19 Vaccination Effectiveness Using Electronic Health Records of an Academic Medical Center in Michigan

ImportanceSystematic characterization of the protective effect of vaccinations across time and at-risk populations is needed to inform public health guidelines and personalized interventions. ObjectiveTo evaluate the vaccine effectiveness (VE) over time and determine differences across demographic and clinical risk factors of COVID-19. Design, Setting, and ParticipantsThis test negative design consisted of adult patients who were tested or diagnosed for COVID-19 at Michigan Medicine in 2021. Variables extracted from Electronic Health Records included vaccination status, age, gender, race/ethnicity, comorbidities, body mass index, residential-level socioeconomic characteristics, past COVID-19 infection, being immunosuppressed, and health care worker status. ExposureThe primary exposure was vaccination status and was categorized into fully vaccinated with and without booster, partially vaccinated, or unvaccinated. Main Outcomes and MeasuresThe main outcomes were infection with COVID-19 (positive test or diagnosis) and having severe COVID-19, i.e., either being hospitalized or deceased. Based on these, VE was calculated by quarter, vaccine, and patient characteristics. ResultsOf 170,487 COVID-19 positive adult patients, 78,002 (45.8%) were unvaccinated, and 92,485 (54.2%) were vaccinated, among which 74,060 (80.1%) were fully vaccinated. COVID-19 positivity and severity rates were substantially higher among unvaccinated (12.1% and 1.4%, respectively) compared to fully vaccinated individuals (4.7% and 0.4%, respectively). Among 7,187 individuals with a booster, only 18 (0.3%) had a severe outcome. The covariate-adjusted VE against an infection was 62.1% (95%CI 60.3-63.8%), being highest in the Q2 of 2021 (90.9% [89.5-92.1%]), lowest in Q3 (60.1% [55.9-64.0%]), and rebounding in Q4 to 68.8% [66.3- 71.1%]). Similarly, VE against severe COVID-19 overall was 73.7% (69.6-77.3%) and remained high throughout 2021: 87.4% (58.1-96.3%), 92.2% (88.3-94.8%), 74.4% (64.8-81.5%) and 83.0% (78.8-86.4%), respectively. Data on fully vaccinated individuals from Q4 indicated additional protection against infection with an additional booster dose (VE-Susceptibility: 64.0% [61.1-66.7%] vs. 87.3% [85.0-89.2%]) and severe outcomes (VE-Severity: 78.8% [73.5-83.0%] vs. 94.0% [89.5-96.6%]). Comparisons between Pfizer-BioNTech and Moderna vaccines indicated similar protection against susceptibility (82.9% [80.7-84.9%] versus 88.1% [85.5- 90.2%]) and severity (87.1% [80.3-91.6%]) vs. (84.9% [76.2-90.5%]) after controlling for vaccination timing and other factors. There was no significant effect modification by all the factors we examined. Conclusions and RelevanceOur findings suggest that COVID-19 vaccines offered high protection against infection and severe COVID-19, and showed decreasing effectiveness over time and improved protection with a booster. Key PointsO_ST_ABSQuestionC_ST_ABSHow do the rates of COVID-19 outcomes (infections or mild/severe disease) compare across vaccination status and quarters of 2021, after adjusting for confounders? FindingsIn this cohort of 170,487 adult patients tested for or diagnosed with COVID-19 during 2021, both COVID-19 positivity and severity rates were substantially higher in unvaccinated compared to fully vaccinated individuals. Vaccine effectiveness estimation was adjusted for covariates potentially related to both being vaccinated and COVID-19 outcomes; this also allowed us to determine if effectiveness differed across patient subgroups. The estimated vaccine effectiveness across the four quarters of 2021 was 62.1% against infection and was 73.7% against severe COVID-19 (defined as hospitalization, ICU admission, or death). There was no significant effect modification by all the factors we examined. MeaningThese findings suggest COVID-19 vaccines had relatively high protection against infection and severe COVID-19 during 2021 for those who received two doses of an mRNA vaccine (Moderna or Pfizer-BioNTech) or one dose of the Janssen vaccine, of which the effectiveness decreased over time and improved with a booster.

Changes in COVID-19-related outcomes and the impacts of the potential risk factors over time: a follow-up analysis

ImportanceCharacteristics of COVID-19 patients changed over the course of the pandemic. Understanding how risk factors changed over time can enhance the coordination of healthcare resources and protect the vulnerable. ObjectiveTo investigate the overall trend of severe COVID-19-related outcomes over time since the start of the pandemic, and to evaluate whether the impacts of potential risk factors, such as race/ethnic groups, changed over time. DesignThis retrospective cohort study included patients tested or treated for COVID-19 at Michigan Medicine (MM) from March 10, 2020, to September 2, 2020. According to the quarter in which they first tested positive, the COVID-19-positive cohort were stratified into three groups: Q1, March 1, 2020 - March 31, 2020; Q2, April 1, 2020 - June 30, 2020; Q3, July 1, 2020 - September 2, 2020. SettingsLarge, academic medical center. ParticipantsIndividuals tested or treated for COVID-19. ExposureExamined potential risk factors included age, race/ethnicity, smoking status, alcohol consumption, comorbidities, body mass index (BMI), and residential-level socioeconomic characteristics. Main Outcomes and MeasuresThe main outcomes included COVID-19-related hospitalization, intensive care unit (ICU) admission, and mortality, which were identified from the electronic health records from MM. ResultsThe study cohort consisted of 53,853 patients tested or treated for COVID-19 at MM, with mean (SD) age of 44.8 (23.1), mean (SD) BMI of 29.1 (7.6), and 23,814 (44.2%) males. Among the 2,582 patients who tested positive, 719 (27.8%) were hospitalized, 377 (14.6%) were admitted to ICU, and 129 (5.0%) died. The overall COVID-positive hospitalization rate decreased from 41.5% in Q1 to 12.6% in Q3, and the overall ICU admission rate decreased from 24.5% to 5.3%. Black patients had significantly higher (unadjusted) overall hospitalization rate (265 [41.1%] vs 326 [23.2%]), ICU admission rate (139 [21.6%] vs 172 [12.2%]), and mortality rate (42 [6.5%] vs 56 [4.0%]) than White patients. Each quarter, the hospitalization rate remained higher for Black patients compared to White patients, but this difference was attenuated over time for the (unadjusted) odds ratios (Q1: OR=1.9, 95% CI [1.25, 2.90]; Q2: OR=1.42, 95% CI [1.02, 1.98]; Q3: OR=1.36, 95% CI [0.67, 2.65]). Similar decreasing patterns were observed for ICU admission and mortality. Adjusting for age, sex, socioeconomic status, and comorbidity score, the racial disparities in hospitalization between White and Black patients were not significant in each quarter of the year (Q1: OR=1.43, 95% CI [0.75, 2.71]; Q2: OR=1.25, 95% CI [0.79, 1.98]; Q3: OR=1.76 95% CI [0.81, 3.85]), in contrast to what was observed in the full cohort (OR=1.85, 95% CI [1.39, 2.47]). Additionally, significant association of hospitalization with living in densely populated area was identified in the first quarter (OR= 664, 95% CI [20.4, 21600]), but such association disappeared in the second and third quarters (Q2: OR= 1.72 95% CI [0.22, 13.5]; Q3: OR=3.69, 95% CI [0.103, 132]). Underlying liver diseases were positively associated with hospitalization in White patients (OR=1.60, 95% CI [1.01, 2.55], P=.046), but not in Black patients (OR=0.49, 95% CI [0.23, 1.06], P=.072, Pint=.013). Similar results were obtained for the effect of liver diseases on ICU admission in White and Black patients (White: OR=1.75, 95% CI [1.01, 3.05], P=.047; Black: OR=0.46, 95% CI [0.17, 1.26], P=.130, Pint=.030). Conclusions and RelevanceThese findings suggest that the COVID-19-related hospitalization, ICU admission, and mortality rates were decreasing over the course of the pandemic. Although racial disparities persisted, the magnitude of the differences in hospitalization and ICU admission rates diminished over time. Key PointsO_ST_ABSQuestionsC_ST_ABSHow did the overall hospitalization and intensive care unit (ICU) admission rates change over the course of the pandemic and how did they vary by race? FindingsIn this cohort study of 2,582 patients testing positive for COVID-19, the unadjusted hospitalization rate decreased from 50.5% in Q1 (March 10, 2020, to March 31, 2020) to 17.9% in Q3 (July 1, 2020, to September 2, 2020) for Black patients, and from 23.2% in Q1 to 13.8% in Q3 for White patients. After adjusting for age, sex, sociodemographic factors, and comorbidity conditions, the odds ratios of hospitalization between White and Black patients were not significant in each quarter of the year 2020. No significant associations between ICU admission and race/ethnic groups were identified in each quarter or the entire three quarters. MeaningThese findings suggests an appreciable decline in hospitalization and ICU admission rates among COVID-19 positive patients. The hospitalization and ICU admission rates across race/ethnic groups became closer over time.

Understanding the patterns of repeated testing for COVID-19: Association with patient characteristics and outcomes

ImportanceThe diagnostic tests for COVID-19 have a high false negative rate, but not everyone with an initial negative result is re-tested. Michigan Medicine, being one of the primary regional centers accepting COVID-19 cases, provided an ideal setting for studying COVID-19 repeated testing patterns during the first wave of the pandemic. ObjectiveTo identify the characteristics of patients who underwent repeated testing for COVID-19 and determine if repeated testing was associated with patient characteristics and with downstream outcomes among positive cases. DesignThis cross-sectional study described the pattern of testing for COVID-19 at Michigan Medicine. The main hypothesis under consideration is whether patient characteristics differed between those tested once and those who underwent multiple tests. We then restrict our attention to those that had at least one positive test and study repeated testing patterns in patients with severe COVID-19 related outcomes (testing positive, hospitalization and ICU care). SettingDemographic and clinical characteristics, test results, and health outcomes for 15,920 patients presenting to Michigan Medicine between March 10 and June 4, 2020 for a diagnostic test for COVID-19 were collected from their electronic medical records on June 24, 2020. Data on the number and types of tests administered to a given patient, as well as the sequences of patient-specific test results were derived from records of patient laboratory results. ParticipantsAnyone tested between March 10 and June 4, 2020 at Michigan Medicine with a diagnostic test for COVID-19 in their Electronic Health Records were included in our analysis. ExposuresComparison of repeated testing across patient demographics, clinical characteristics, and patient outcomes Main Outcomes and MeasuresWhether patients underwent repeated diagnostic testing for SARS CoV-2 in Michigan Medicine ResultsBetween March 10th and June 4th, 19,540 tests were ordered for 15,920 patients, with most patients only tested once (13596, 85.4%) and never testing positive (14753, 92.7%). There were 5 patients who got tested 10 or more times and there were substantial variations in test results within a patient. After fully adjusting for patient and neighborhood socioeconomic status (NSES) and demographic characteristics, patients with circulatory diseases (OR: 1.42; 95% CI: (1.18, 1.72)), any cancer (OR: 1.14; 95% CI: (1.01, 1.29)), Type 2 diabetes (OR: 1.22; 95% CI: (1.06, 1.39)), kidney diseases (OR: 1.95; 95% CI: (1.71, 2.23)), and liver diseases (OR: 1.30; 95% CI: (1.11, 1.50)) were found to have higher odds of undergoing repeated testing when compared to those without. Additionally, as compared to non-Hispanic whites, non-Hispanic blacks were found to have higher odds (OR: 1.21; 95% CI: (1.03, 1.43)) of receiving additional testing. Females were found to have lower odds (OR: 0.86; 95% CI: (0.76, 0.96)) of receiving additional testing than males. Neighborhood poverty level also affected whether to receive additional testing. For 1% increase in proportion of population with annual income below the federal poverty level, the odds ratio of receiving repeated testing is 1.01 (OR: 1.01; 95% CI: (1.00, 1.01)). Focusing on only those 1167 patients with at least one positive result in their full testing history, patient age in years (OR: 1.01; 95% CI: (1.00, 1.03)), prior history of kidney diseases (OR: 2.15; 95% CI: (1.36, 3.41)) remained significantly different between patients who underwent repeated testing and those who did not. After adjusting for both patient demographic factors and NSES, hospitalization (OR: 7.44; 95% CI: (4.92, 11.41)) and ICU-level care (OR: 6.97; 95% CI: (4.48, 10.98)) were significantly associated with repeated testing. Of these 1167 patients, 306 got repeated testing and 1118 tests were done on these 306 patients, of which 810 (72.5%) were done during inpatient stays, substantiating that most repeated tests for test positive patients were done during hospitalization or ICU care. Additionally, using repeated testing data we estimate the "real world" false negative rate of the RT-PCR diagnostic test was 23.8% (95% CI: (19.5%, 28.5%)). Conclusions and RelevanceThis study sought to quantify the pattern of repeated testing for COVID-19 at Michigan Medicine. While most patients were tested once and received a negative result, a meaningful subset of patients (2324, 14.6% of the population who got tested) underwent multiple rounds of testing (5,944 tests were done in total on these 2324 patients, with an average of 2.6 tests per person), with 10 or more tests for five patients. Both hospitalizations and ICU care differed significantly between patients who underwent repeated testing versus those only tested once as expected. These results shed light on testing patterns and have important implications for understanding the variation of repeated testing results within and between patients. Key PointsO_ST_ABSQuestionC_ST_ABSDoes having repeated diagnostic tests for the novel coronavirus (COVID-19) depend on patient characteristics and disease outcomes? FindingsThis cross-sectional study of testing patterns with 15,920 patients tested for SARS-CoV-2 virus at Michigan Medicine found significant differences in testing rates across patient age, body mass index, sex, race/ethnicity, neighborhood poverty level, prior history of circulatory diseases, any cancer, Type 2 diabetes, kidney, and liver diseases. Higher hospitalization rates and intensive care unit admissions were associated with repeated testing as expected. MeaningThe results of this study describe diagnostic testing patterns for the novel COVID-19 virus at Michigan Medicine, and how they relate to patient characteristics and COVID-19 outcomes.

A phenome-wide association study (PheWAS) of COVID-19 outcomes by race using the electronic health records data in Michigan Medicine

BackgroundWe perform a phenome-wide scan to identify pre-existing conditions related to COVID-19 susceptibility and prognosis across the medical phenome and how they vary by race. MethodsThe study is comprised of 53,853 patients who were tested/positive for COVID-19 between March 10 and September 2, 2020 at a large academic medical center. ResultsPre-existing conditions strongly associated with hospitalization were renal failure, pulmonary heart disease, and respiratory failure. Hematopoietic conditions were associated with ICU admission/mortality and mental disorders were associated with mortality in non-Hispanic Whites. Circulatory system and genitourinary conditions were associated with ICU admission/mortality in non-Hispanic Blacks. ConclusionsUnderstanding pre-existing clinical diagnoses related to COVID-19 outcomes informs the need for targeted screening to support specific vulnerable populations to improve disease prevention and healthcare delivery.

COVID-19 outcomes, risk factors and associations by race: a comprehensive analysis using electronic health records data in Michigan Medicine

Structured AbstractO_ST_ABSImportanceC_ST_ABSBlacks/African-Americans are overrepresented in the number of COVID-19 infections, hospitalizations and deaths. Reasons for this disparity have not been well-characterized but may be due to underlying comorbidities or sociodemographic factors. ObjectiveTo systematically determine patient characteristics associated with racial/ethnic disparities in COVID-19 outcomes. DesignA retrospective cohort study with comparative control groups. SettingPatients tested for COVID-19 at University of Michigan Medicine from March 10, 2020 to April 22, 2020. Participants5,698 tested patients and two sets of comparison groups who were not tested for COVID-19: randomly selected unmatched controls (n = 7,211) and frequency-matched controls by race, age, and sex (n = 13,351). Main Outcomes and MeasuresWe identified factors associated with testing and testing positive for COVID-19, being hospitalized, requiring intensive care unit (ICU) admission, and mortality (in/out-patient during the time frame). Factors included race/ethnicity, age, smoking, alcohol consumption, healthcare utilization, and residential-level socioeconomic characteristics (SES; i.e., education, unemployment, population density, and poverty rate). Medical comorbidities were defined from the International Classification of Diseases (ICD) codes, and were aggregated into a comorbidity score. ResultsOf 5,698 patients, (median age, 47 years; 38% male; mean BMI, 30.1), the majority were non-Hispanic Whites (NHW, 59.2%) and non-Hispanic Black/African-Americans (NHAA, 17.2%). Among 1,119 diagnosed, there were 41.2% NHW and 37.4% NHAA; 44.8% hospitalized, 20.6% admitted to ICU, and 3.8% died. Adjusting for age, sex, and SES, NHAA were 1.66 times more likely to be hospitalized (95% CI, 1.09-2.52; P=.02), 1.52 times more likely to enter ICU (95% CI, 0.92-2.52; P=.10). In addition to older age, male sex and obesity, high population density neighborhood (OR, 1.27 associated with one SD change [95% CI, 1.20-1.76]; P=.02) was associated with hospitalization. Pre-existing kidney disease led to 2.55 times higher risk of hospitalization (95% CI, 1.62-4.02; P<.001) in the overall population and 11.9 times higher mortality risk in NHAA (95% CI, 2.2-64.7, P=.004). Conclusions and RelevancePre-existing type II diabetes/kidney diseases and living in high population density areas were associated with high risk for COVID-19 susceptibility and poor prognosis. Association of risk factors with COVID-19 outcomes differed by race. NHAA patients were disproportionately affected by obesity and kidney disease. Key PointsO_ST_ABSQuestionC_ST_ABSWhat are the sociodemographic and pre-existing health conditions associated with COVID-19 outcomes and how do they differ by race/ethnicity? FindingsIn this retrospective cohort of 5,698 patients tested for COVID-19, high population density and comorbidities such as type II diabetes/kidney disease were associated with hospitalization, in addition to older age, male sex and obesity. Adjusting for covariates, non-Hispanic Blacks were 1.66 times more likely to be hospitalized and 1.52 times more likely to be admitted to ICUs than non-Hispanic Whites. MeaningTargeted interventions to support vulnerable populations are needed. Racial disparities existed in COVID-19 outcomes that cannot be explained after controlling for age, sex, and socioeconomic status.

History of Coronary Heart Disease Increases the Mortality Rate of Coronavirus Disease 2019 (COVID-19) Patients: A Nested Case-Control Study Based on Publicly Reported Confirmed Cases in Mainland China

BackgroundChina has experienced an outbreak of a novel human coronavirus (SARS-CoV-2) since December 2019, which quickly became a worldwide pandemic in early 2020. There is limited evidence on the mortality risk effect of pre-existing comorbidities for coronavirus disease 2019 (COVID-19), which has important implications for early treatment. ObjectiveEvaluate the risk of pre-existing comorbidities on COVID-19 mortality, and provide clinical suggestions accordingly. MethodThis study used a nested case-control design. A total of 94 publicly reported deaths in locations outside of Hubei Province, China, between December 18th, 2019 and March 8th, 2020 were included as cases. Each case was matched with up to three controls, based on gender and age {+/-} 1 year old (94 cases and 181 controls). The inverse probability weighted Cox proportional hazard model was performed. ResultsHistory of comorbidities significantly increased the death risk of COVID-19: one additional pre-existing comorbidity led to an estimated 40% higher risk of death (p<0.001). The estimated mortality risk in patients with CHD was three times of those without CHD (p<0.001). The estimated 30-day survival probability for a profile patient with pre-existing CHD (65-year-old female with no other comorbidities) was 0.53 (95% CI [0.34-0.82]), while it was 0.85 (95% CI [0.79-0.91]) for those without CHD. Older age was also associated with increased death risk: every 5-year increase in age was associated with a 20% increased risk of mortality (p<0.001). ConclusionExtra care and early medical intervention are needed for patients with pre-existing comorbidities, especially CHD.

Chronic dysfunction of Stromal interaction molecule by pulsed RNAi induction in fat tissue impairs organismal energy homeostasis in Drosophila.

Obesity is a progressive, chronic disease, which can be caused by long-term miscommunication between organs. It remains challenging to understand how chronic dysfunction in a particular tissue remotely impairs other organs to eventually imbalance organismal energy homeostasis. Here we introduce RNAi Pulse Induction (RiPI) mediated by short hairpin RNA (shRiPI) or double-stranded RNA (dsRiPI) to generate chronic, organ-specific gene knockdown in the adult Drosophila fat tissue. We show that organ-restricted RiPI targeting Stromal interaction molecule (Stim), an essential factor of store-operated calcium entry (SOCE), results in progressive fat accumulation in fly adipose tissue. Chronic SOCE-dependent adipose tissue dysfunction manifests in considerable changes of the fat cell transcriptome profile, and in resistance to the glucagon-like Adipokinetic hormone (Akh) signaling. Remotely, the adipose tissue dysfunction promotes hyperphagia likely via increased secretion of Akh from the neuroendocrine system. Collectively, our study presents a novel in vivo paradigm in the fly, which is widely applicable to model and functionally analyze inter-organ communication processes in chronic diseases.

VEGF-C Promotes Cervical Cancer Invasion via Regulation of microRNA-145/Smad Interacting Protein 1 / 中山大学学报(医学科学版)

[Objective]To investigate the role of microRNA-145/Smad interacting protein 1(SIP 1)in VEGF-C-enhanced cervical cancer metastasis.[Methods]Cervical cancer cell line SiHa cells were cultured and treated with VEGF-C to observe its effect on the expression of miR-145 and SIP1. After transfection with specific SIP1 siRNA,the invasion number of cultured cells were calculated by transwell chamber assay.[Results]Treatment with VEGF-C(100 ng/mL)for 12 h,24 h and 48 h all reduced miR-145 expression,with the expression abundance of(82.4±6.4)% (P<0.05),(72.5±7.2)%(P<0.01),and(60.6±9.6)%(P<0.001),respectively,when compared to control.Meanwhile, the same treatment with VEGF-C also increased SIP1 protein expression,with the expression abundance of(142.4 ± 16.5)%(P<0.05),(183.6 ± 11.4)%(P<0.01)and(220.8 ± 15.7)%(P<0.001),respectively. The transfection of miR-145 mimic significantly impaired VEGF-C effect on SIP1 expression. Finally,VEGF-C promoted SiHa cell invasion,which was largely inhibited by the tranfection of SIP siRNA with the inhibitory rate of(56.6±10.3)%(P<0.01).[Conclusion]VEGF-C downregulates miR-145,thus increases SIP1 expression and promotes cervical cancer cell invasion,which may contributes to cervical cancer malignant progression.

Treatment of depression using sleep electroencephalogram modulated repetitive transcranial magnetic stimulation / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>As a treatment of depression, the efficacy of conventional repetitive transcranial magnetic stimulation (rTMS) is limited, and symptoms recurrence is easy to occur after the treatment. This study aimed to examine the efficacy and safety of sleep electroencephalogram modulated repetitive rTMS (SEM-rTMS) in the treatment of depression.</p><p><b>METHODS</b>After 7 days without psychoactive medication, 164 patients with clinically defined depression were randomly divided into 3 groups: SEM-rTMS group (n = 57), conventional rTMS (C-rTMS, n = 55) group and sham-rTMS group (n = 52). Every patient was treated with the corresponding method for 30 minutes everyday for 10 days. Before and after scores on the 24-item Hamilton rating scale for depression (HAMD-24) and the clinical outcome on the 10th day of therapy for all subjects were analyzed.</p><p><b>RESULTS</b>Twenty-two cases in the SEM-rTMS group obtained improved mood as compared to 6 in the C-rTMS group and 2 in the sham-rTMS group (χ(2) = 15.89, P = 0.0004). After completion of the rTMS phase of the protocol, a (51 ± 5)% reduction of HAMD-24 scores from the baseline in the SEM-rTMS group was found compared with a (34 ± 4)% in the C-rTMS group (q = 26.09, P = 0.001) and a (14 ± 3)% in sham-rTMS group (q = 57.53, P = 0.000). The 88% total effective rate in the SEM-rTMS group was significantly higher than 68% in the C-rTMS group and 20% in the sham-rTMS group (χ(2) = 12.01, P = 0.0025). No significant side effects were noted.</p><p><b>CONCLUSION</b>SEM-rTMS is an effective and safe way for treating depression with repetitive transcranial magnetic stimulation (ChiCTR-TRC-00000438).</p>

[Molecular genetic analysis of mitochondrial DNA C1494T mutation in non-syndromic hearing loss of Chinese population].

OBJECTIVE: To conduct a molecular epidemiological survey on the mitochondrial DNA C1494T mutation in non-syndromic hearing loss patients in Chinese population. METHODS: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) were used to screen the mitochondrial DNA 12S rRNA C1494T mutation in 20 patients with aminoglycoside antibiotic induced hearing loss, 136 sporadic non-syndromic hearing loss patients and 50 probands of pedigrees with non-syndromic hearing loss. RESULTS: The C1494T mutation did not appear in all cases except for the positive control. CONCLUSION: Incidence of mitochondrial DNA C1494T mutation is much lower than that of mitochondrial DNA A1555G mutation in non-syndromic hearing loss of Chinese population. Mitochondrial DNA C1494T mutation may be a rare variation in non-syndromic hearing loss and is not the main cause of aminoglycoside antibiotic induced-deafness.

[Systematic studies on quality of main species of Herba epimedii].

OBJECTIVE: To achieve the quality control of Herba Epimedii, and to evaluate the quality of medical materials of the 8 official species including the 5 species recorded in 'Chinese Pharmacopoeia' including Epimedium brevicornum, E. sagittatum, E. pubescens, E. koreanum and E. wushanense, and the 3 other species (E. acuminatum, E. myrianthum, E. leptorrhizum) recorded in 'Guizhou Quality Criteria for Traditional Chinese Medical Material and Nationality Medical Material', and E. pseudowushanuse (new species) which is used as E. wushanense for a long time. METHOD: The contents of icariin and total flavonoids of 102 samples of 9 officinal species of Herba Epimedii were determined by HPLC and UV, respectively. RESULT AND CONCLUSION: The contents of icariin in about 30% of the samples of the 5 species recorded in 'Chinese Pharmacopoeia' were lower than 0.5%, which is acceptable quality recorded in 'Chinese Pharmacopoeia'. Refering the literatures, we suggested the total contents of epimedin A, B, C and icariin (epi-medium multi-glycosides, ABCI) should be established as a new standard instead of the content of icariin. The content of total flavonoids, not less than 5.0%, and ABCI, not less than 1.3%, could be used to evaluate the quality of the above medical materials efficiently.

Systematic studies on quality of main species of Herba epimedii / 中国中药杂志

<p><b>OBJECTIVE</b>To achieve the quality control of Herba Epimedii, and to evaluate the quality of medical materials of the 8 official species including the 5 species recorded in 'Chinese Pharmacopoeia' including Epimedium brevicornum, E. sagittatum, E. pubescens, E. koreanum and E. wushanense, and the 3 other species (E. acuminatum, E. myrianthum, E. leptorrhizum) recorded in 'Guizhou Quality Criteria for Traditional Chinese Medical Material and Nationality Medical Material', and E. pseudowushanuse (new species) which is used as E. wushanense for a long time.</p><p><b>METHOD</b>The contents of icariin and total flavonoids of 102 samples of 9 officinal species of Herba Epimedii were determined by HPLC and UV, respectively.</p><p><b>RESULT AND CONCLUSION</b>The contents of icariin in about 30% of the samples of the 5 species recorded in 'Chinese Pharmacopoeia' were lower than 0.5%, which is acceptable quality recorded in 'Chinese Pharmacopoeia'. Refering the literatures, we suggested the total contents of epimedin A, B, C and icariin (epi-medium multi-glycosides, ABCI) should be established as a new standard instead of the content of icariin. The content of total flavonoids, not less than 5.0%, and ABCI, not less than 1.3%, could be used to evaluate the quality of the above medical materials efficiently.</p>

Distribution behavior of lipophilic drugs in the oil-in-water microemulsions / 药学学报

Distribution behavior of lipophilic drugs in the oil-in-water (O/W) microemulsions was studied. Fluorescence spectra analysis was performed to investigate the effect of the compositions of microemulsions on the fluorescence spectra of armillarisin and ofloxacin which were used as the model drugs. The fluorescence spectra of the model drugs in the microemulsions with various amount of the compositions were compared. The results showed that the armillarisin were both localized in the interfacial film of microemulsion systems with both phenylmethanol and PEG 400 as the co-surfactants, separately. Ofloxacin was localized in the interfacial film of microemulsion systems with Gradamol GTCC as the oil phase, but in the oil pool of microemulsion systems with oleic acid/olive oil (OA/OO) (1:1) as the oil phase. Besides, it was found that the drug would have the tendency to locate in the microenvironment where the composition with the largest solubility to model drug is located, and its actual localized position would be dependent on the amount of this composition. The results indicate that the localized region of lipophilic drug in the O/W microemulsion systems is related with the solubility of the model drug in various compositions.

Ultrapure dialysate improves iron utilization and erythropoietin response in chronic hemodialysis patients - a prospective cross-over study.

BACKGROUND: The impact of ultrapure dialysis on dialysate-related chronic inflammatory status and anemia in uremic patients on maintenance hemodialysis (HD) remains uncertain. We evaluated ultrapure dialysate effects on erythropoietin (EPO) response and inflammatory status in a prospective, randomized, cross-over study. METHODS: Thirty-four HD patients were divided into two groups. One group was treated with conventional dialysate and the other group with ultrapure dialysate for 6 months and crossed over for another 6 months. Bacteria growth and dialysate endotoxin were examined. Parameters including C-reactive protein (CRP), recombinant human erythropoietin (rHuEPO) dose, ferritin, iron saturation and serum albumin were measured at the start, and at 6 and 12 months. RESULTS: The endotoxin levels reduced significantly in the ultrapure dialysate by adding a dialysate ultrafilter. After a 6-month treatment with ultrapure dialysate, there were statistically significant differences in the systemic inflammation markers between both groups. Changing from conventional to ultrapure dialysis fluid significantly reduced CRP (7.01 +/- 5.059 to 4.461 +/- 3.754 mg/L, p<0.05), and resulted in reduced rHuEPO doses (12500 +/- 7060 to 10440 +/- 7050 U/month, p<0.05). Continuous conventional dialysate use was not associated with significant alternations in CRP (from 5.849 +/- 7.744 to 6.187 +/- 7.997 mg/L, p=0.456) and rHuEPO dose (14060 +/- 6210 to 15060 +/- 7250U/month, p>0.05). The ferritin level reduced significantly (422 +/- 183 to 272 +/- 162 mcg/L, p<0.05) in the ultrapure dialysate group. After another 6-month cross-over, the study parameters were reversed among the two groups indicating the beneficial effect of ultrapure dialysis. CONCLUSIONS: Through endotoxin reduction in conventional dialysate, ultrapure dialysis in dialysis patients manifested a reduced inflammatory parameter, reduced rHuEPO dose and improved iron utilization; and therefore, could be beneficial in anemia treatment.