Safety and efficacy of sofosbuvir‐containing regimens in hepatitis C‐infected patients with impaired renal function

BACKGROUND & AIMS: Renal clearance is the major elimination pathway for sofosbuvir (SOF). We assessed the safety and efficacy of SOF-containing regimens in patients with varying baseline estimated glomerular filtration rate (eGFR). METHODS: HCV-TARGET database is a multicentre, longitudinal 'real-world' treatment cohort. RESULTS: A total of 1789 patients [genotypes 1 (72%), 2 (17%) 3 (9%), 4-6 (2%)] had baseline eGFR determination: 73 with eGFR≤45 (18 with eGFR≤30, 5 on dialysis) were compared to 1716 with eGFR>45 ml/min/1.73 m(2) . Patients with baseline eGFR≤45 vs. >45 differed in being female (55% vs. 36%), age ≥65 years (24% vs. 16%), Black race (22% vs. 12%), having cirrhosis with decompensation (73% vs. 24%) and being post-transplant (49% vs. 10%), all P < 0.05. All patients with eGFR≤45 were treated with SOF 400 mg/day (including those on haemodialysis) and had median starting ribavirin (RBV) dose of 800 mg (IQR: 400-1200). Sustained virologic response (SVR) frequencies were similar across eGFR groups, ranging from 82-83%. Patients with eGFR ≤45 more frequently experienced anaemia, worsening renal function and serious AEs (all P < 0.05), and these associations persisted when limiting analysis to RBV-free regimens. Patients with baseline eGFR≤30 and eGFR 31-45 had similar frequencies of efficacy and safety outcomes. CONCLUSIONS: Sustained viral clearance was achieved in 83% of patients with renal impairment (eGFR ≤45 ml/min/1.73 m(2) ) treated with SOF-containing regimens. However, these patients had higher rates of anaemia, worsening renal dysfunction and serious adverse events regardless of use of RBV. Patient with renal impairment require close monitoring and should be treated by providers extensively experienced with SOF-containing regimens

Impacts of center and clinical factors in antihypertensive medication use after kidney transplantation

Hypertension guidelines recommend calcium channel blockers (CCBs), thiazide diuretics, and angiotensin‐converting‐enzyme inhibitors/angiotensin receptor blockers (ACEi/ARBs) as first‐line agents to treat hypertension. Hypertension is common among kidney transplant (KTx) recipients, but data are limited regarding patterns of antihypertensive medication (AHM) use in this population. We examined a novel database that links national registry data for adult KTx recipients (age > 18 years) with AHM fill records from a pharmaceutical claims warehouse (2007‐2016) to describe use and correlates of AHM use during months 7‐12 post‐transplant. For patients filling AHMs, individual agents used included: dihydropyridine (DHP) CCBs, 55.6%; beta‐blockers (BBs), 52.8%; diuretics, 30.0%; ACEi/ARBs, 21.1%; non‐DHP CCBs, 3.0%; and others, 20.1%. Both BB and ACEi/ARB use were significantly lower in the time period following the 2014 Eighth Joint National Committee (JNC‐8) guidelines (2014‐2016), compared with an earlier period (2007‐2013). The median odds ratios generated from case‐factor adjusted models supported variation in use of ACEi/ARBs (1.51) and BBs (1.55) across transplant centers. Contrary to hypertension guidelines for the general population, KTx recipients are prescribed relatively more BBs and fewer ACEi/ARBs. The clinical impact of this AHM prescribing pattern warrants further study.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154651/1/ctr13803.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154651/2/ctr13803_am.pd

Associations of obesity with antidiabetic medication use after living kidney donation: An analysis of linked national registry and pharmacy fill records

We examined a novel linkage of national US donor registry data with records from a pharmacy claims warehouse (2007‐2016) to examine associations (adjusted hazard ratio, LCLaHRUCL) of post‐donation fills of antidiabetic medications (ADM, insulin or non‐insulin agents) with body mass index (BMI) at donation and other demographic and clinical factors. In 28 515 living kidney donors (LKDs), incidence of ADM use at 9 years rose in a graded manner with higher baseline BMI: underweight, 0.9%; normal weight, 2.1%; overweight, 3.5%; obese, 8.5%. Obesity was associated with higher risk of ADM use compared with normal BMI (aHR, 3.364.596.27). Metformin was the most commonly used ADM and was filled more often by obese than by normal weight donors (9‐year incidence, 6.87% vs 1.85%, aHR, 3.555.007.04). Insulin use was uncommon and did not differ significantly by BMI. Among a subgroup with BMI data at the 1‐year post‐donation anniversary (n = 19 528), compared with stable BMI, BMI increase >0.5 kg/m2 by year 1 was associated with increased risk of subsequent ADM use (aHR, 1.031.482.14, P = .04). While this study did not assess the impact of donation on the development of obesity, these data support that among LKD, obesity is a strong correlate of ADM use.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152001/1/ctr13696_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152001/2/ctr13696.pd

Characterizing Long COVID: Deep Phenotype of a Complex Condition.

BACKGROUND: Numerous publications describe the clinical manifestations of post-acute sequelae of SARS-CoV-2 (PASC or long COVID ), but they are difficult to integrate because of heterogeneous methods and the lack of a standard for denoting the many phenotypic manifestations. Patient-led studies are of particular importance for understanding the natural history of COVID-19, but integration is hampered because they often use different terms to describe the same symptom or condition. This significant disparity in patient versus clinical characterization motivated the proposed ontological approach to specifying manifestations, which will improve capture and integration of future long COVID studies. METHODS: The Human Phenotype Ontology (HPO) is a widely used standard for exchange and analysis of phenotypic abnormalities in human disease but has not yet been applied to the analysis of COVID-19. FINDINGS: We identified 303 articles published before April 29, 2021, curated 59 relevant manuscripts that described clinical manifestations in 81 cohorts three weeks or more following acute COVID-19, and mapped 287 unique clinical findings to HPO terms. We present layperson synonyms and definitions that can be used to link patient self-report questionnaires to standard medical terminology. Long COVID clinical manifestations are not assessed consistently across studies, and most manifestations have been reported with a wide range of synonyms by different authors. Across at least 10 cohorts, authors reported 31 unique clinical features corresponding to HPO terms; the most commonly reported feature was Fatigue (median 45.1%) and the least commonly reported was Nausea (median 3.9%), but the reported percentages varied widely between studies. INTERPRETATION: Translating long COVID manifestations into computable HPO terms will improve analysis, data capture, and classification of long COVID patients. If researchers, clinicians, and patients share a common language, then studies can be compared/pooled more effectively. Furthermore, mapping lay terminology to HPO will help patients assist clinicians and researchers in creating phenotypic characterizations that are computationally accessible, thereby improving the stratification, diagnosis, and treatment of long COVID. FUNDING: U24TR002306; UL1TR001439; P30AG024832; GBMF4552; R01HG010067; UL1TR002535; K23HL128909; UL1TR002389; K99GM145411

Increased Incidence of Vestibular Disorders in Patients With SARS-CoV-2

OBJECTIVE: Determine the incidence of vestibular disorders in patients with SARS-CoV-2 compared to the control population. STUDY DESIGN: Retrospective. SETTING: Clinical data in the National COVID Cohort Collaborative database (N3C). METHODS: Deidentified patient data from the National COVID Cohort Collaborative database (N3C) were queried based on variant peak prevalence (untyped, alpha, delta, omicron 21K, and omicron 23A) from covariants.org to retrospectively analyze the incidence of vestibular disorders in patients with SARS-CoV-2 compared to control population, consisting of patients without documented evidence of COVID infection during the same period. RESULTS: Patients testing positive for COVID-19 were significantly more likely to have a vestibular disorder compared to the control population. Compared to control patients, the odds ratio of vestibular disorders was significantly elevated in patients with untyped (odds ratio [OR], 2.39; confidence intervals [CI], 2.29-2.50; CONCLUSIONS: The incidence of vestibular disorders differed between COVID-19 variants and was significantly elevated in COVID-19-positive patients compared to the control population. These findings have implications for patient counseling and further research is needed to discern the long-term effects of these findings

Minimal change disease associated with balsalazide therapy for ulcerative colitis

Introduction: 5-aminosalicylic acid (5-ASA) compounds have been used in the management of ulcerative colitis for decades. Nephrotoxicity has been previously described in patients treated with 5-ASA compounds and usually manifests as interstitial nephritis, however a few cases of nephrotic syndrome have been reported. Balsalazide is a pro-drug composed of 5-ASA linked to an inert carrier. Case Presentation: Here we report the case of a 74-year-old man with a history of ulcerative proctosigmoiditis treated with balsalazide who presented to our clinic with bilateral lower extremity edema three months after initiation of balsalazide. Laboratory workup showed nephrotic range proteinuria without an apparent secondary etiology. Given worsening proteinuria and renal function despite cessation of balsalazide, the patient underwent renal biopsy that revealed minimal change disease. High dose steroids were started and complete remission of proteinuria was achieved one month into therapy which was slowly tapered over the next five months. Eventual resolution of edema and return of creatinine back to patient’s baseline level was achieved. Conclusion: To our knowledge, this is the first report of nephrotic syndrome manifesting soon after initiation of balsalazide therapy. Our work highlights the importance of maintaining a high clinical suspicion for nephrotoxicity when using balsalazide

"Association of Severity of Posttraumatic Stress Disorder With Inflammation: Using Total White Blood Cell Count as a Marker".

Inflammation is known to be associated with posttraumatic stress disorder (PTSD). It is not known if total white blood cell (WBC) count, a routinely checked inflammatory marker, is associated with PTSD symptom trajectories using medical record data. We used latent class growth analysis to identify three-year PTSD symptom trajectories using PTSD Checklist (PCL) scores. The outcome for each patient was maximum WBC count from index PTSD diagnosis to last PCL. Using linear regression analysis, we then calculated and compared the average WBC count for each trajectory before and after controlling for age, gender, race, obesity, smoking, diabetes, hypertension, cardiovascular disease, depression and other co-morbid inflammatory conditions. Patients were 40.2 (SD±13.5) years of age, 83.7% male and 67.9% white. We identified three PCL trajectory groups based on symptom severity over time: 'moderate-large decrease', 'moderate severe-slight decrease', and 'severe-persistent'. In adjusted analyses, 'severe-persistent' vs. 'moderate-large decrease' had significantly higher WBC count (B=0.64; 95%CI=0.18, 1.09; p=.006). Although non-significant, 'moderate severe-slight decrease' vs. 'moderate-large decrease' also had a higher WBC count (B=0.42; 95% CI: -0.02, 0.86; p=.061). Persistently severe PTSD is associated with a higher WBC count than improving PTSD. WBC appears to have utility for measuring the association between psychiatric disorders and inflammation in retrospective cohort studies involving large administrative medical record data bases

"Association of Severity of Posttraumatic Stress Disorder With Inflammation: Using Total White Blood Cell Count as a Marker".

Background:Inflammation is known to be associated with posttraumatic stress disorder (PTSD). It is not known if total white blood cell (WBC) count, a routinely checked inflammatory marker, is associated with PTSD symptom trajectories using medical record data. Methods:We used latent class growth analysis to identify three-year PTSD symptom trajectories using PTSD Checklist (PCL) scores. The outcome for each patient was maximum WBC count from index PTSD diagnosis to last PCL. Using linear regression analysis, we then calculated and compared the average WBC count for each trajectory before and after controlling for age, gender, race, obesity, smoking, diabetes, hypertension, cardiovascular disease, depression and other co-morbid inflammatory conditions. Results:Patients were 40.2 (SD±13.5) years of age, 83.7% male and 67.9% white. We identified three PCL trajectory groups based on symptom severity over time: 'moderate-large decrease', 'moderate severe-slight decrease', and 'severe-persistent'. In adjusted analyses, 'severe-persistent' vs. 'moderate-large decrease' had significantly higher WBC count (B=0.64; 95%CI=0.18, 1.09; p=.006). Although non-significant, 'moderate severe-slight decrease' vs. 'moderate-large decrease' also had a higher WBC count (B=0.42; 95% CI: -0.02, 0.86; p=.061). Conclusion:Persistently severe PTSD is associated with a higher WBC count than improving PTSD. WBC appears to have utility for measuring the association between psychiatric disorders and inflammation in retrospective cohort studies involving large administrative medical record data bases