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  1. Article ; Online: Use of Tenofovir Alafenamide Fumarate for HIV Pre-Exposure Prophylaxis and Incidence of Hypertension and Initiation of Statins.

    Rivera, Adovich S / Pak, Katherine J / Mefford, Matthew T / Hechter, Rulin C

    JAMA network open

    2023  Volume 6, Issue 9, Page(s) e2332968

    Abstract: Importance: Pre-exposure prophylaxis (PrEP) is an important tool for preventing HIV infection. However, PrEP's impact on cardiometabolic health is understudied.: Objective: To examine the risk of incident hypertension and statin initiation among ... ...

    Abstract Importance: Pre-exposure prophylaxis (PrEP) is an important tool for preventing HIV infection. However, PrEP's impact on cardiometabolic health is understudied.
    Objective: To examine the risk of incident hypertension and statin initiation among adult (age ≥18 years) health plan members starting PrEP with tenofovir alafenamide fumarate (TAF) compared with propensity score-matched adults taking tenofovir disoproxil fumarate (TDF).
    Design, setting, and participants: This retrospective cohort study used electronic health records (EHRs) from Kaiser Permanente Southern California. Adult members starting PrEP in Kaiser Permanente Southern California between October 2019 and May 2022 were included. Propensity score matching with multiple imputation (50 matched data sets) was conducted to generate 1 TAF:4 TDF matched data sets with balanced baseline covariates.
    Exposures: PrEP initiation with either TAF or TDF during the study period.
    Main outcomes and measures: Incident hypertension and statin initiation within 2 years of PrEP initiation were ascertained through blood pressure and outpatient pharmacy records, respectively. Risk differences and odds ratios (ORs) were estimated using logistic regression and g-computation.
    Results: A total of 6824 eligible individuals were identified (mean [SD] age, 33.9 [10.3] years; 6618 [97%] male). This pool was used to generate 2 cohorts without baseline hypertension or statin use for matching (hypertension: n = 5523; statin: n = 6149) In both cohorts, those starting PrEP with TAF were older and were more likely to be non-Hispanic White compared with those starting with TDF. In matched analysis adjusting for baseline covariates, TAF use was associated with elevated risk of incident hypertension (TAF: n = 371; risk difference, 0.81 [95% CI, 0.12-1.50]; OR, 1.64 [95% CI, 1.05-2.56]). TAF use was also associated with elevated risk of statin initiation (TAF: n = 382; risk difference, 0.85 [95% CI, 0.37-1.33]; OR, 2.33 [95% CI, 1.41-3.85]). Subgroup analyses restricted to individuals 40 years and older at PrEP initiation showed similar results with larger risk difference in statin initiation (risk difference, 4.24 [95% CI, 1.82-6.26]; OR, 3.05 [95% CI, 1.64-5.67]).
    Conclusions and relevance: In this study of people taking PrEP, TAF use was found to be associated with higher incident hypertension and statin initiation compared with TDF use, especially in those 40 years or older. Continued monitoring of blood pressure and lipids for TAF users is warranted.
    MeSH term(s) Adult ; Male ; Humans ; Adolescent ; Female ; HIV Infections/epidemiology ; HIV Infections/prevention & control ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use ; Pre-Exposure Prophylaxis ; Incidence ; Retrospective Studies ; Adenine ; Tenofovir/adverse effects ; Hypertension/epidemiology ; Hypertension/prevention & control ; Fumarates
    Chemical Substances Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Adenine (JAC85A2161) ; Tenofovir (99YXE507IL) ; Fumarates
    Language English
    Publishing date 2023-09-05
    Publishing country United States
    Document type Journal Article
    ISSN 2574-3805
    ISSN (online) 2574-3805
    DOI 10.1001/jamanetworkopen.2023.32968
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  2. Article: Changes in Glomerular Filtration Rate After Switching From Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide Fumarate for Human Immunodeficiency Virus Preexposure Prophylaxis.

    Rivera, Adovich S / Pak, Katherine / Mefford, Matthew T / Hechter, Rulin C

    Open forum infectious diseases

    2023  Volume 11, Issue 2, Page(s) ofad695

    Abstract: Background: Tenofovir alafenamide fumarate (TAF) was promoted as a safer alternative to tenofovir disoproxil fumarate (TDF) for human immunodeficiency virus oral preexposure prophylaxis (PrEP). It is unknown if switching from TDF to TAF translates to ... ...

    Abstract Background: Tenofovir alafenamide fumarate (TAF) was promoted as a safer alternative to tenofovir disoproxil fumarate (TDF) for human immunodeficiency virus oral preexposure prophylaxis (PrEP). It is unknown if switching from TDF to TAF translates to improved renal function. We used electronic health record (EHR) data to assess changes in creatinine-estimated glomerular filtration rate (eGFR) after switching from TDF to TAF.
    Methods: We conducted a retrospective cohort study using EHR data from Kaiser Permanente Southern California. We identified individuals who switched from TDF to TAF between October 2019 and May 2022 and used time-varying propensity score matching to identify controls who were on TDF ("nonswitchers"). We then used Bayesian longitudinal modeling to compare differences in eGFR between switching and nonswitching scenarios.
    Results: Among 5246 eligible individuals, we included 118 TDF to TAF switchers and 114 nonswitchers. Compared to nonswitchers, switchers had older age of starting TDF but similar body weights at index date. A higher proportion of switchers were White, on Medicare or Medicaid, and had dyslipidemia at index date. Switching to TAF was associated with a higher eGFR compared to staying on TDF in 3-15 months post-switch, but the differences were not statistically significant (eg, month 9 difference: 1.27 [95% credible interval, -1.35 to 3.89]). While most of the estimated changes showed eGFR increase associated with switching, most were <2 eGFR units. Sensitivity analyses to address missingness or nonadherence showed similar results.
    Conclusions: Switching from TDF to TAF for PrEP was associated with a nonsignificant increase in eGFR. Findings need to be confirmed using larger cohorts.
    Language English
    Publishing date 2023-12-29
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2757767-3
    ISSN 2328-8957
    ISSN 2328-8957
    DOI 10.1093/ofid/ofad695
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  3. Article ; Online: Understanding Barriers and Facilitators of Pre-exposure Prophylaxis (PrEP) Among Transgender and Gender Diverse Adults in an Integrated Health Care System.

    Bruxvoort, Katia / Portugal, Cecilia / Munis, Mercedes / Pak, Katherine / Hechter, Rulin

    AIDS and behavior

    2023  Volume 27, Issue 8, Page(s) 2579–2591

    Abstract: Transgender and gender diverse individuals face health disparities such as higher HIV prevalence, but limited studies have found low PrEP uptake among these populations. To understand both patient and provider perspectives regarding PrEP care for ... ...

    Abstract Transgender and gender diverse individuals face health disparities such as higher HIV prevalence, but limited studies have found low PrEP uptake among these populations. To understand both patient and provider perspectives regarding PrEP care for transgender and gender diverse individuals, we conducted a mixed-methods study at Kaiser Permanente Southern California from September 2020 to October 2021. Transgender and gender diverse adults (N = 396) participated in a web-based survey, and qualitative interviews were subsequently conducted with a subset of survey respondents (N = 32) and healthcare providers (N = 8). Among survey respondents, > 75% were familiar with PrEP, and > 40% reported at least one HIV risk factor, but < 5% had taken PrEP. Interview themes included increasing providers' inclusivity in primary care for transgender and gender diverse patients, and reducing logistical barriers and costs associated with PrEP-related visits. To improve PrEP uptake among transgender and gender diverse individuals, barriers across patient, provider, and health system levels must be addressed.
    MeSH term(s) Humans ; Adult ; Transgender Persons ; Pre-Exposure Prophylaxis/methods ; Qualitative Research ; Anti-HIV Agents/therapeutic use ; HIV Infections/epidemiology ; HIV Infections/prevention & control ; HIV Infections/drug therapy ; Delivery of Health Care, Integrated
    Chemical Substances Anti-HIV Agents
    Language English
    Publishing date 2023-01-17
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1339885-4
    ISSN 1573-3254 ; 1090-7165
    ISSN (online) 1573-3254
    ISSN 1090-7165
    DOI 10.1007/s10461-023-03983-8
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  4. Article ; Online: All-Cause and Cardiovascular-Related Mortality in CKD Patients With and Without Heart Failure: A Population-Based Cohort Study in Kaiser Permanente Southern California.

    Yu, Albert S / Pak, Katherine J / Zhou, Hui / Shaw, Sally F / Shi, Jiaxiao / Broder, Benjamin I / Sim, John J

    Kidney medicine

    2023  Volume 5, Issue 5, Page(s) 100624

    Abstract: Rationale & objective: Heart failure and chronic kidney disease (CKD) frequently coexist reflective of the strong interplay between these organ systems. A better understanding of the prevalence of different types of heart failure (preserved and reduced ... ...

    Abstract Rationale & objective: Heart failure and chronic kidney disease (CKD) frequently coexist reflective of the strong interplay between these organ systems. A better understanding of the prevalence of different types of heart failure (preserved and reduced ejection fraction) and their subsequent mortality risks among advanced CKD patients would provide important epidemiologic insights and may pave the way for more focused and proactive management strategies.
    Study design: Retrospective cohort study.
    Setting & population: Patients aged ≥18 years with incident CKD (estimated glomerular filtration rate ≤45 mL/min/1.73 m
    Exposure: Heart failure, heart failure with preserved ejection fraction (HFpEF), heart failure with reduced ejection fraction (HFrEF).
    Outcomes: All-cause and cardiovascular-related mortality within one year of CKD identification.
    Analytical approach: HRs were estimated using Cox proportional-hazards model for risk of all-cause mortality and Fine-Gray subdistribution hazard model for risk of cardiovascular-related mortality within 1 year.
    Results: The study cohort included 76,688 patients with incident CKD between 2007 and 2017, of which 14,249 (18.6%) had prevalent heart failure. Among these patients, 8,436 (59.2%) had HFpEF and 3,328 (23.3%) had HFrEF. Compared with patients without heart failure, the HR for 1-year all-cause mortality was 1.70 (95% CI, 1.60-1.80) among patients with heart failure. The HRs were 1.59 (95% CI, 1.48-1.70) for patients with HFpEF and 2.43 (95% CI, 2.23-2.65) for patients with HFrEF. Compared with patients without heart failure, the 1-year cardiovascular-related mortality HR for patients with heart failure was 6.69 (95% CI, 5.93-7.54). Cardiovascular-related mortality HR was even higher among those with HFrEF (HR, 11.47; 95% CI, 9.90-13.28).
    Limitations: Retrospective design with a short 1-year follow-up period. Additional variables including medication adherence, medication changes, and time-varying variables were not accounted for in this intention-to-treat analysis.
    Conclusions: Among patients with incident CKD, heart failure was highly prevalent with HFpEF accounting for over 70% among patients with known ejection fraction. Although the presence of heart failure was associated with higher 1-year all-cause and cardiovascular-related mortality, patients with HFrEF were the most vulnerable.
    Language English
    Publishing date 2023-03-09
    Publishing country United States
    Document type Journal Article
    ISSN 2590-0595
    ISSN (online) 2590-0595
    DOI 10.1016/j.xkme.2023.100624
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  5. Article ; Online: Autoantibodies Recognizing Specificity Protein 4 Co-occur With Anti-Transcription Intermediary Factor 1 and Are Associated With Distinct Clinical Features and Immunogenetic Risk Factors in Juvenile Myositis.

    Sherman, Matthew A / Pak, Katherine / Pinal-Fernandez, Iago / Flegel, Willy A / Targoff, Ira N / Miller, Frederick W / Rider, Lisa G / Mammen, Andrew L

    Arthritis & rheumatology (Hoboken, N.J.)

    2023  Volume 75, Issue 9, Page(s) 1668–1677

    Abstract: Objective: Autoantibodies recognizing specificity protein 4 (Sp4) were recently discovered in adults with idiopathic inflammatory myopathies (IIM). Anti-Sp4 autoantibodies co-occurred in patients with anti-transcription intermediary factor 1 (anti-TIF1) ...

    Abstract Objective: Autoantibodies recognizing specificity protein 4 (Sp4) were recently discovered in adults with idiopathic inflammatory myopathies (IIM). Anti-Sp4 autoantibodies co-occurred in patients with anti-transcription intermediary factor 1 (anti-TIF1) autoantibody-positive dermatomyositis (DM) and were associated with a reduced risk of cancer. In the present study, the prevalence and clinical features associated with anti-Sp4 autoantibodies in juvenile-onset IIM were investigated.
    Methods: Serum samples from 336 patients with juvenile myositis in a cross-sectional cohort and 91 healthy controls were screened for anti-Sp4 autoantibodies using enzyme-linked immunosorbent assay. Clinical characteristics, outcomes, and HLA alleles of those with and those without anti-Sp4 autoantibodies were compared.
    Results: Anti-Sp4 autoantibodies were present in 23 patients (7%) with juvenile myositis and were not present in any of the controls. Anti-Sp4 autoantibodies were found among each clinical myositis subgroup. The frequency of TIF1 autoantibody positivity was significantly higher among those with anti-Sp4 autoantibodies (21 [91%] versus 92 [30%], P < 0.001). In the anti-TIF1 autoantibody-positive subgroup, Raynaud's phenomenon (8 [38%] versus 2 [2%], P < 0.001) was more common and peak aspartate aminotransferase was significantly lower in those with anti-Sp4 autoantibodies. None of the patients with anti-Sp4 autoantibodies required a wheelchair. Among White patients, DQA1*04 and DRB1*08 were associated with anti-Sp4 autoantibodies.
    Conclusion: Anti-Sp4 autoantibodies were found in patients with juvenile-onset IIM, predominantly those with coexisting anti-TIF1 autoantibodies. Patients with anti-Sp4 autoantibodies represent a phenotypic subset of anti-TIF1 autoantibody-positive myositis characterized by frequent Raynaud's phenomenon and less pronounced muscle involvement, similar to adults with these autoantibodies. Novel immunogenetic risk factors for White patients with IIM were identified among juveniles with anti-Sp4 autoantibodies.
    MeSH term(s) Adult ; Humans ; Dermatomyositis ; Autoantibodies ; Cross-Sectional Studies ; Immunogenetics ; Mediation Analysis ; Myositis ; Risk Factors
    Chemical Substances Autoantibodies
    Language English
    Publishing date 2023-07-19
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Intramural
    ZDB-ID 2756371-6
    ISSN 2326-5205 ; 2326-5191
    ISSN (online) 2326-5205
    ISSN 2326-5191
    DOI 10.1002/art.42512
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  6. Article ; Online: Clinical Features and Immunogenetic Risk Factors Associated With Additional Autoantibodies in Anti-Transcriptional Intermediary Factor 1γ Juvenile-Onset Dermatomyositis.

    Sherman, Matthew A / Yang, Qingyuan / Gutierrez-Alamillo, Laura / Pak, Katherine / Flegel, Willy A / Mammen, Andrew L / Rider, Lisa G / Casciola-Rosen, Livia A

    Arthritis & rheumatology (Hoboken, N.J.)

    2024  Volume 76, Issue 4, Page(s) 631–637

    Abstract: Objective: Novel autoantibody specificities including anti-CCAR1 were recently discovered in adult patients with anti-transcriptional intermediary factor (TIF1)-positive dermatomyositis (DM) and were associated with attenuated cancer emergence. The aims ...

    Abstract Objective: Novel autoantibody specificities including anti-CCAR1 were recently discovered in adult patients with anti-transcriptional intermediary factor (TIF1)-positive dermatomyositis (DM) and were associated with attenuated cancer emergence. The aims of the present study were to examine whether these autoantibodies occur in patients with juvenile-onset DM (JDM) and to determine their associated features.
    Methods: Sera from 150 patients with anti-TIF1γ autoantibody-positive JDM in a cross-sectional cohort and 90 juvenile healthy controls were assayed for anti-CCAR1, anti-C1Z1, anti-IMMT, anti-TBL1XR1, and anti-Sp4 autoantibodies. Demographics, myositis autoantibodies, clinical features, medications, outcomes, and HLA-DRB1 and HLA-DQA1 alleles were compared between those with and without these autoantibodies.
    Results: Any one of the anti-TIF1γ-associated autoantibodies was present in 44 patients (29%) overall, including 25 (17%) with anti-Sp4, 22 (15%) with anti-TBL1XR1, 14 (9%) with anti-CCAR1, 2 (1%) with anti-C1Z1, and 2 (1%) with anti-IMMT autoantibodies. These anti-TIF1γ-associated autoantibodies frequently co-occurred. Patients with any of the anti-TIF1γ-associated autoantibodies had less frequent falling (34% [15] vs. 53% [56], P = 0.032) and lower peak muscle enzymes. None of the patients had cancer. Among White patients, HLA-DRB1*03 was protective against an anti-TIF1γ-associated autoantibody (odds ratio 0.20, 95% confidence interval 0.07-0.52).
    Conclusion: Autoantibodies associated with anti-TIF1γ were found in isolation and in combination among a subset of patients with JDM. Patients with these autoantibodies had less severe muscle disease and were not enriched for HLA-DRB1*03. Additional autoantibodies among patients with positive anti-TIF1γ with JDM likely contribute to the heterogeneity of the anti-TIF1γ serologic subgroup.
    MeSH term(s) Adult ; Humans ; Dermatomyositis ; Mediation Analysis ; HLA-DRB1 Chains ; Autoantibodies ; Cross-Sectional Studies ; Immunogenetics ; Risk Factors ; Neoplasms
    Chemical Substances HLA-DRB1 Chains ; Autoantibodies
    Language English
    Publishing date 2024-01-30
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2756371-6
    ISSN 2326-5205 ; 2326-5191
    ISSN (online) 2326-5205
    ISSN 2326-5191
    DOI 10.1002/art.42768
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    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  7. Article ; Online: Myositis-Associated Autoantibodies in Patients With Juvenile Myositis Are Associated With Refractory Disease and Mortality.

    Sherman, Matthew A / Noroozi Farhadi, Payam / Pak, Katherine / Trieu, Edward P / Sarkar, Kakali / Targoff, Ira N / Neely, Megan L / Mammen, Andrew L / Rider, Lisa G

    Arthritis & rheumatology (Hoboken, N.J.)

    2024  

    Abstract: Objective: Myositis-associated autoantibodies (MAAs) have been associated with overlap myositis, certain disease manifestations such as interstitial lung disease (ILD), and worse prognosis in the idiopathic inflammatory myopathies. MAAs overall remain ... ...

    Abstract Objective: Myositis-associated autoantibodies (MAAs) have been associated with overlap myositis, certain disease manifestations such as interstitial lung disease (ILD), and worse prognosis in the idiopathic inflammatory myopathies. MAAs overall remain largely uncharacterized in patients with juvenile-onset myositis. Moreover, it is unknown whether the number of MAAs is associated with disease severity.
    Methods: Patients with juvenile myositis in cross-sectional natural history studies who underwent testing for myositis autoantibodies were included. Demographics, myositis autoantibodies, clinical characteristics, medications received, and outcomes of those with and without MAAs were compared. Multivariable logistic regression was performed to determine whether the number of MAAs detected was associated with severe disease features.
    Results: Among 551 patients, 36% had an MAA and 13% had more than one MAA. Among those who were MAA positive, there was a higher frequency of overlap myositis (18% vs 5.9%, P < 0.001). MAA positivity was associated with certain clinical features, including Raynaud phenomenon (odds ratio [OR] 2.44, 95% confidence interval [CI] 1.41-4.28) and ILD (OR 3.43, 95% CI 1.75-6.96), as well as a chronic disease course (OR 1.72, 95% CI 1.10-2.72) and mortality (OR 3.76, 95% CI 1.72-8.43). The number of MAAs was also associated with mortality (OR 1.83, 95% CI 1.16-2.86).
    Conclusion: MAAs were prevalent in a large cohort of patients with juvenile myositis. ILD, refractory disease, and mortality were associated with MAA positivity. Prospective studies are needed to determine whether early detection of MAAs may lead to improved outcomes for patients with juvenile myositis.
    Language English
    Publishing date 2024-01-25
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2756371-6
    ISSN 2326-5205 ; 2326-5191
    ISSN (online) 2326-5205
    ISSN 2326-5191
    DOI 10.1002/art.42813
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  8. Article ; Online: Chronic and Sustained High-Dose Opioid Use in an Integrated Health System.

    Hechter, Rulin C / Pak, Katherine J / Chang, Craig K / Xie, Fagen / Gray, Patricia L / Ling Grant, Deborah S / Barreras, Joanna L / Zhou, Hui

    American journal of preventive medicine

    2022  Volume 64, Issue 2, Page(s) 167–174

    Abstract: Introduction: The Centers for Disease Control and Prevention Guideline for Prescribing Opioids for Chronic Pain released in 2016 had led to decreases in opioid prescribing. This study sought to examine chronic and sustained high-dose prescription opioid ...

    Abstract Introduction: The Centers for Disease Control and Prevention Guideline for Prescribing Opioids for Chronic Pain released in 2016 had led to decreases in opioid prescribing. This study sought to examine chronic and sustained high-dose prescription opioid use in an integrated health system.
    Methods: A serial cross-sectional study was conducted in 2021 to estimate the annual age-adjusted prevalence and incidence of chronic and high-dose opioid use among demographically diverse noncancer adults in an integrated health system in Southern California during 2013-2020. Interrupted time-series analysis with segmented regression was conducted to estimate changes in the trends in annual rates before (2013-2015) and after (2017-2020) the 2016 guideline, treating 2016 as a wash-out period.
    Results: Prevalence and incidence of chronic use and sustained high-dose use had started to decrease after a health system intervention program before the 2016 Centers for Disease Control and Prevention guideline release and continued to decline after the guideline. Among those with sustained high-dose use, there was a substantial decrease in persons with an average daily dosage ≥90 morphine milligram equivalent and concurrent benzodiazepine use. An accelerated decrease in prevalent chronic use after the guideline was observed (slope change: -11.1 [95% CI= -20.3, -1.9] users/10,000 person-years, p=0.03). The incidence of chronic use and sustained high-dose use continued to decrease after the guideline release but at a slower pace.
    Conclusions: Implementing evidence-based prescribing guidelines was associated with a decrease in chronic and sustained high-dose prescription opioid use.
    MeSH term(s) Adult ; Humans ; Analgesics, Opioid/therapeutic use ; Cross-Sectional Studies ; Practice Patterns, Physicians' ; Opioid-Related Disorders/epidemiology ; Chronic Pain/drug therapy ; Delivery of Health Care, Integrated ; Drug Prescriptions
    Chemical Substances Analgesics, Opioid
    Language English
    Publishing date 2022-12-15
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 632646-8
    ISSN 1873-2607 ; 0749-3797
    ISSN (online) 1873-2607
    ISSN 0749-3797
    DOI 10.1016/j.amepre.2022.09.013
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  9. Article: Nailfold capillaroscopy findings of a multicentric multi-ethnic cohort of patients with idiopathic inflammatory myopathies.

    Torres-Ruiz, Jiram / Pinal-Fernandez, Iago / Selva-O'Callaghan, Albert / Campbell, Bianca / Muñoz-Braceras, Sandra / Mejía-Domínguez, Nancy R / Núñez-Álvarez, Carlos / Milisenda, José / Casal-Domínguez, Maria / Pak, Katherine / Guillén-Del-Castillo, Alfredo / Trallero-Araguas, Ernesto / Gil-Vila, Albert / Mammen, Andrew Lee

    Clinical and experimental rheumatology

    2024  Volume 42, Issue 2, Page(s) 367–376

    Abstract: Objectives: To assess nailfold video capillaroscopic (NVC) abnormalities and their association with clinical features, myositis-specific autoantibodies (MSA), and myositis-associated antibodies (MAA) in a large multi-ethnic cohort of patients with ... ...

    Abstract Objectives: To assess nailfold video capillaroscopic (NVC) abnormalities and their association with clinical features, myositis-specific autoantibodies (MSA), and myositis-associated antibodies (MAA) in a large multi-ethnic cohort of patients with idiopathic inflammatory myopathies (IIM).
    Methods: We recruited 155 IIM patients from three centres in Mexico, Spain, and the USA. We evaluated the clinical and laboratory features of the patients and performed semiquantitative and quantitative analyses of the NVC. Each NVC study was defined as having a normal, non-specific, early systemic sclerosis (SSc), active SSc, or late SSc pattern. Twenty-three patients had at least one follow-up NVC when disease control was achieved. Quantitative variables were expressed as medians and interquartile range (IQR) and were compared with the Kruskal-Wallis, the Mann-Whitney U-test, and the Wilcoxon test for paired medians. Associations between qualitative variables were assessed with the χ2 test.
    Results: Most patients were women (68.3%), Hispanic (73.5%), and had dermatomyositis (DM) (61.2%). Fourteen patients (9%) had a normal NVC. A non-specific abnormality pattern was the most frequent (53.9%), and was associated with joint involvement, interstitial lung disease, Jo1 autoantibodies, anti-synthetase syndrome, and immune-mediated necrotising myopathy. The SSc pattern was observed mostly in DM and overlap myositis and was associated with cutaneous features and anti-TIF-1g autoantibodies. After treatment, there was a decrease in the capillaroscopic score, the capillary diameter, and the number of avascular areas, and an increase in capillary density and bushy capillary number.
    Conclusions: NVC abnormalities are related to the diagnosis, clinical features, disease activity, and autoantibodies of patients with IIM.
    MeSH term(s) Humans ; Female ; Male ; Microscopic Angioscopy ; Nails/blood supply ; Myositis/complications ; Capillaries ; Autoantibodies ; Scleroderma, Systemic/diagnosis
    Chemical Substances Autoantibodies
    Language English
    Publishing date 2024-03-14
    Publishing country Italy
    Document type Journal Article
    ZDB-ID 605886-3
    ISSN 1593-098X ; 0392-856X
    ISSN (online) 1593-098X
    ISSN 0392-856X
    DOI 10.55563/clinexprheumatol/l9gudh
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Trim33 (Tif1γ) is not required for skeletal muscle development or regeneration but suppresses cholecystokinin expression.

    Parks, Cassie A / Pak, Katherine / Pinal-Fernandez, Iago / Huang, Wilson / Derfoul, Assia / Mammen, Andrew L

    Scientific reports

    2019  Volume 9, Issue 1, Page(s) 18507

    Abstract: The expression of Trim33 (Tif1γ) increases in skeletal muscles during regeneration and decreases upon maturation. Although Trim33 is required for the normal development of other tissues, its role in skeletal muscle is unknown. The current study aimed to ... ...

    Abstract The expression of Trim33 (Tif1γ) increases in skeletal muscles during regeneration and decreases upon maturation. Although Trim33 is required for the normal development of other tissues, its role in skeletal muscle is unknown. The current study aimed to define the role of Trim33 in muscle development and regeneration. We generated mice with muscle-specific conditional knockout of Trim33 by combining floxed Trim33 and Cre recombinase under the Pax7 promoter. Muscle regeneration was induced by injuring mouse muscles with cardiotoxin. We studied the consequences of Trim33 knockdown on viability, body weight, skeletal muscle histology, muscle regeneration, and gene expression. We also studied the effect of Trim33 silencing in satellite cells and the C2C12 mouse muscle cell line. Although Trim33 knockdown mice weighed less than control mice, their skeletal muscles were histologically unremarkable and regenerated normally following injury. Unexpectedly, RNAseq analysis revealed dramatically increased expression of cholecystokinin (CCK) in regenerating muscle from Trim33 knockout mice, satellite cells from Trim33 knockout mice, and C2C12 cells treated with Trim33 siRNA. Trim33 knockdown had no demonstrable effect on muscle differentiation or regeneration. However, Trim33 knockdown induced CCK expression in muscle, suggesting that suppression of CCK expression requires Trim33.
    MeSH term(s) Animals ; Body Weight ; Cardiotoxins ; Cell Survival ; Cholecystokinin/metabolism ; Exons ; Female ; Genotype ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Muscle, Skeletal/metabolism ; RNA-Seq ; Regeneration ; Satellite Cells, Skeletal Muscle/metabolism ; Transcription Factors/metabolism ; Transcriptome
    Chemical Substances Cardiotoxins ; Transcription Factors ; Trim33 protein, mouse ; Cholecystokinin (9011-97-6)
    Language English
    Publishing date 2019-12-06
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Intramural
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-019-54651-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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