ABSTRACT
BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RA) have cardiovascular benefits in type 2 diabetes, but none of the cardiovascular trials studied atrial fibrillation/atrial flutter (AF) as a primary endpoint. Data from post-marketing surveillance studies remains sparse. OBJECTIVE: To examine the real-world risk of AF comparing GLP-1RA with other non-insulin glucose-lowering agents. DESIGN: Cohort study using de-identified electronic health record data from the Optum Labs Data Warehouse. PARTICIPANTS: Adult patients with diabetes who were newly prescribed add-on non-insulin glucose-lowering agents and were on metformin between 2005-2020. EXPOSURES: New users of GLP-1RA were separately compared with new users of dipeptidyl peptidase-4 inhibitors (DPP4i) and sodium-glucose cotransporter 2 inhibitors (SGLT2i), using 1:1 propensity score matching to adjust for differences in patient characteristics. MAIN MEASURES: The primary outcome was incident AF, defined and captured by diagnosis code for AF. Incidence rate difference (IRD) and hazard ratio (HR) were estimated in the matched cohorts. KEY RESULTS: In the matched cohort of 14,566 pairs of GLP-1RA and DPP4i followed for a median of 3.8 years, GLP-1RA use was associated with a lower risk of AF (IRD, -1.0; 95% CI, -1.8 to -0.2 per 1000 person-years; HR, 0.82; 95% CI, 0.70 to 0.96). In the matched cohort of 9,424 pairs of patients on GLP-1RA and SGLT2i with a median follow-up of 2.9 years, there was no difference in the risk for AF (IRD, 0.4; 95% CI -0.7 to 1.5 per 1000 person-years; HR, 1.12; 95% CI, 0.89 to 1.42). CONCLUSIONS: In this real-word study, GLP-1RA was associated with a lower risk of AF compared with DPP4i, but no difference compared with SGLT2i, suggesting that cardiovascular benefits of GLP-1RA use may extend to prevention for AF in patients with diabetes. Our findings call for future randomized controlled trials to focus on the effects of GLP-1RA on AF prevention.
Subject(s)
Atrial Fibrillation , Diabetes Mellitus, Type 2 , Dipeptidyl-Peptidase IV Inhibitors , Glucagon-Like Peptide-1 Receptor , Hypoglycemic Agents , Humans , Atrial Fibrillation/epidemiology , Atrial Fibrillation/drug therapy , Male , Female , Glucagon-Like Peptide-1 Receptor/agonists , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/drug therapy , Middle Aged , Aged , Hypoglycemic Agents/therapeutic use , Hypoglycemic Agents/adverse effects , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Dipeptidyl-Peptidase IV Inhibitors/adverse effects , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Cohort Studies , Risk Factors , Adult , Incidence , Glucagon-Like Peptide-1 Receptor AgonistsABSTRACT
AIMS: We aimed to examine trends in overall prescription medication use among patients with type 2 diabetes in the United States to provide insights for patient care. MATERIALS AND METHODS: We used nationally representative data from the National Health and Nutrition Examination Survey from 1999 to 2020 and included adult patients with type 2 diabetes. We examined the use of prescription drugs, overall and by drug class, polypharmacy (use of ≥5 medications), and number of medications attributed to specific classes. RESULTS: In the period 2015-2020, the mean patient age was 59.6 (51.0-70.0) years, with 46.8% (43.6-49.9) being female and 57.8% (52.8-62.8) being non-Hispanic White. Among 9489 adults with type 2 diabetes, the prevalence of polypharmacy was high and increased from 35.1% (31.6-38.6) in 1999-2002 to 47.2% (43.7-50.7) in 2003-2006, and further to 51.1% (48.3-53.9) in 2015-2020 (p for trend <0.001). Increasing trends of polypharmacy were found across all population subgroups and across the majority of therapeutic classes. Use of non-cardiometabolic medications was common. Among them, the most common were antidepressants (19.8%), proton pump inhibitors (19.0%) and analgesics (16.2%). Among patients with polypharmacy, approximately 40% of medication use was attributed to non-cardiometabolic medications. CONCLUSIONS: Prescription medication burden and complexity increased substantially among patients with type 2 diabetes, with more than 50% of patients with polypharmacy. Attention should be paid to this escalating medication use and regimen complexity, which requires multidisciplinary and coordinated care.
Subject(s)
Diabetes Mellitus, Type 2 , Nutrition Surveys , Polypharmacy , Prescription Drugs , Humans , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/epidemiology , Female , Male , United States/epidemiology , Middle Aged , Aged , Prescription Drugs/therapeutic use , Hypoglycemic Agents/therapeutic use , Drug Utilization/trends , Drug Utilization/statistics & numerical data , Prevalence , AdultABSTRACT
BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1RA) are increasingly recommended in type 2 diabetes. Hypoglycemia is a serious adverse effect of glucose-lowering agents. Real-world comparison of hypoglycemic risks among SGLT2i, GLP1RA, dipeptidyl peptidase-4 inhibitor (DPP4i), and sulfonylureas is limited. OBJECTIVE: Quantify the risk of hypoglycemia associated with SGLT2i, GLP1RA, DPP4i, and sulfonylureas (the primary reference group). DESIGN: Retrospective cohort study conducted using electronic health records from Geisinger Health, Pennsylvania (2015-2019). PARTICIPANTS: A total of 10,713 patients with type 2 diabetes who newly received SGLT2i (n=1487), GLP1RA (n=1241), DPP4i (n=2938), or sulfonylureas (n=5047). Propensity score-based inverse probability of treatment weighting was used to balance patient characteristics across four treatment groups simultaneously. MAIN MEASURES: Hypoglycemia was defined as capillary blood glucose <70 mg/dL; severe hypoglycemia was defined as capillary blood glucose <54 mg/dL. A weighted Cox proportional hazards regression model was used to estimate the risk of outcomes for pairwise comparisons of SGTL2i, GLP1RA, DPP4i, and sulfonylureas. KEY RESULTS: Median follow-up was 21.3 months. Compared with sulfonylureas, the risk of hypoglycemia was lower with SGLT2i (hazard ratio 0.60 [95% confidence interval 0.48-0.75]), GLP1RA (0.49 [0.34-0.69]), and DPP4i (0.60 [0.48-0.78]). The risk of severe hypoglycemia was also lower with SGLT2i (0.43 [0.35-0.74]), GLP1RA (0.50 [0.28-0.87]), and DPP4i (0.64 [0.46-0.90]) compared to sulfonylureas. The risks of hypoglycemia and severe hypoglycemia were similar across the SGLT2i, GLP1RA, and DPP4i groups (SGLT2i vs. DPP4i: 0.95 [0.67-1.34]; GLP1RA vs. DPP4i: 0.81 [0.55-1.19]; SGLT2i vs. GLP1RA: 1.17 [0.76-1.82] for hypoglycemia). CONCLUSION: SGLT2i and GLP1RA confer a lower risk of hypoglycemia compared with sulfonylureas and similar risk compared with DPP4i. Given the known cardiovascular benefits associated with SGLT2i and GL1PRA, our results suggesting the safety of SGLT2i and GL1PRA further support their use.
Subject(s)
Diabetes Mellitus, Type 2 , Dipeptidyl-Peptidase IV Inhibitors , Hypoglycemia , Sodium-Glucose Transporter 2 Inhibitors , Humans , Diabetes Mellitus, Type 2/drug therapy , Glucose , Blood Glucose , Retrospective Studies , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Hypoglycemic Agents/adverse effects , Dipeptidyl-Peptidase IV Inhibitors/adverse effects , Hypoglycemia/chemically induced , Hypoglycemia/epidemiology , Sulfonylurea Compounds/adverse effectsABSTRACT
Differential diagnosis of erythroderma is challenging in dermatology, especially in differentiating erythrodermic cutaneous T-cell lymphoma from erythrodermic inflammatory dermatoses. This study retrospectively reviewed the peripheral blood flow cytometric results of 73 patients diagnosed with erythroderma at Peking University First Hospital from 2014 to 2019. The flow cytometry antibody panel included white blood cell markers, T-cell markers, B-cell markers, T-cell activation markers, and T helper cell differentiation markers. Features of the cell surface antigens were compared between 34 patients with erythrodermic cutaneous T-cell lymphoma and 39 patients with erythrodermic inflammatory dermatoses. The percentage of HLA-DR+/CD4+T cells was the most pronounced marker to distinguish erythrodermic cutaneous T-cell lymphoma from erythrodermic inflammatory dermatoses, with a threshold of 20.85% (sensitivity 96.77%, specificity 70.37%, p = 0.000, area under the curve (AUC) 0.882), suggesting its potential capability in the differential diagnosis of erythrodermic cutaneous T-cell lymphoma from erythrodermic inflammatory dermatoses. Moreover, in contrast to erythrodermic inflammatory dermatoses, the percentage of Th17 cells was significantly downregulated in erythrodermic cutaneous T-cell lymphoma (p = 0.001), demonstrating a dysregulated immune environment in erythrodermic cutaneous T-cell lymphoma.
Subject(s)
Dermatitis, Exfoliative , Lymphoma, T-Cell, Cutaneous , Mycosis Fungoides , Skin Neoplasms , Humans , Dermatitis, Exfoliative/pathology , Retrospective Studies , Flow Cytometry , CD4 Antigens , Skin Neoplasms/pathology , HLA-DR Antigens , Lymphoma, T-Cell, Cutaneous/diagnosis , Lymphoma, T-Cell, Cutaneous/pathologyABSTRACT
RATIONALE & OBJECTIVE: Evidence is mixed regarding the optimal choice of the first permanent vascular access for elderly patients receiving hemodialysis (HD). Lacking data from randomized controlled trials, we used a target trial emulation approach to compare arteriovenous fistula (AVF) versus arteriovenous graft (AVG) creation among elderly patients receiving HD. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Elderly patients included in the US Renal Data System who initiated HD with a catheter and had an AVF or AVG created within 6 months of starting HD. EXPOSURE: Creation of an AVF versus an AVG as the incident arteriovenous access. OUTCOMES: All-cause mortality, all-cause and cause-specific hospitalization, and sepsis. ANALYTICAL APPROACH: Target trial emulation approach, high-dimensional propensity score and inverse probability of treatment weighting, and instrumental variable analysis using the proclivity of the operating physician to create a fistula as the instrumental variable. RESULTS: A total of 19,867 patients were included, with 80.1% receiving an AVF and 19.9% an AVG. In unweighted analysis, AVF creation was associated with significantly lower risks of mortality and hospitalization, especially within 6 months after vascular access creation. In inverse probability of treatment weighting analysis, AVF creation was associated with lower incidences of mortality and hospitalization within 6 months after creation (hazard ratios of 0.82 [95% CI, 0.75-0.91] and 0.82 [95% CI, 0.78-0.87] for mortality and all-cause hospitalization, respectively), but not between 6 months and 3 years after access creation. No association between AVF creation and mortality, sepsis, or all-cause, cardiovascular disease-related, or infection-related hospitalization was found in instrumental variable analyses. However, AVF creation was associated with a lower risk of access-related hospitalization not due to infection. LIMITATIONS: Potential for unmeasured confounding, analyses limited to elderly patients, and absence of data on actual access use during follow-up. CONCLUSIONS: Using observational data to emulate a target randomized controlled trial, the type of initial arteriovenous access created was not associated with the risks of mortality, sepsis, or all-cause, cardiovascular disease-related, or infection-related hospitalization among elderly patients who initiated HD with a catheter.
Subject(s)
Arteriovenous Shunt, Surgical , Kidney Failure, Chronic , Sepsis , Aged , Arteriovenous Shunt, Surgical/adverse effects , Hospitalization , Humans , Kidney Failure, Chronic/therapy , Renal Dialysis/adverse effects , Retrospective Studies , Sepsis/therapyABSTRACT
RATIONALE & OBJECTIVE: Creation of an arteriovenous fistula (AVF), compared with an arteriovenous graft (AVG), is associated with longer initial catheter dependence after starting hemodialysis (HD) but longer access survival and lower long-term catheter dependence. The extent of these potential long-term benefits in elderly patients is unknown. We assessed catheter dependence after AVF or AVG placement among elderly patients who initiated HD without a permanent access in place. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Patients≥67 years of age identified in the US Renal Data System who had a first AVF (n=14,532) or AVG (n=3,391) placed within 1 year after HD initiation between May 2012 and May 2017. EXPOSURE: AVF versus AVG placement in the first year of HD. OUTCOME: Catheter dependence after AVF or AVG placement assessed using CROWNWeb data. ANALYTICAL APPROACH: Generalized estimating equations and negative binomial regression for catheter use over time and Cox proportional hazards models for mortality. RESULTS: Creation of an AVF versus AVG placement was associated with greater catheter dependence at 1 month (95.6% vs 92.5%) and 3 months (82.8% vs 41.2%), but lower catheter dependence at 12 months (14.2% vs 15.8%) and 36 months (8.2% vs 15.0%). Creation of an AVF, however, remained significantly associated with greater cumulative catheter-dependent days (80.1 vs 54.6 days per person-year) and a lower proportion of catheter-free survival time (78.1% vs 85.1%) after 3 years of follow-up. LIMITATIONS: Potential for unmeasured confounding and analyses limited to elderly patients. CONCLUSIONS: Creation of an AVF was associated with significantly greater cumulative catheter dependence than placement of an AVG in an elderly population initiating HD without a permanent access. As the long-term benefits in terms of catheter dependence of an AVF are not realized in many elderly patients, specific patient characteristics should be considered when making decisions regarding vascular access.
Subject(s)
Arteriovenous Shunt, Surgical/adverse effects , Catheters , Graft Occlusion, Vascular/epidemiology , Kidney Failure, Chronic/therapy , Renal Dialysis/adverse effects , Risk Assessment/methods , Age Factors , Aged , Female , Follow-Up Studies , Graft Occlusion, Vascular/etiology , Humans , Incidence , Male , Retrospective Studies , Risk Factors , Survival Rate/trends , Time Factors , Treatment Outcome , United States/epidemiologyABSTRACT
Hypomagnesemia is common in kidney transplant recipients (KTRs). We sought to explore the relationship between Mg and outcomes in KTRs, which may be associated with mortality and thus may be a potential intervention target to improve outcomes. We followed KTRs performed between 01/2000 and 6/2016 at a large US transplant center from 6 months post-transplant to graft failure, death, or loss to follow-up. Using Mg as a time-dependent variable, associations between Mg and outcomes any time after 6 months post-transplant were evaluated. 3680 KTRs with 50 413 Mg measurements met inclusion criteria. 657 deaths occurred over a median follow-up of 5.1 years. Compared to Mg of 1.5-1.8 mg/dl, both lower (HR 1.17, 95% confidence interval (CI): 1.07-1.28) and higher (HR 1.16, 95% CI: 1.09-1.23) Mg levels were associated with greater risk of mortality. Similar U-shaped associations were observed for Mg and cardiovascular disease-related mortality (HR for Mg ≤1.5 mg/dl: 1.31; CI: 1.03-1.68) and infection-related mortality (HR for Mg ≤1.5 mg/dl: 1.28; CI: 1.09-1.51), although relationships for Mg >1.8 mg/dl were not statistically significant. Mg exhibits a U-shaped association with mortality in KTRs, with levels between 1.5 and 1.8 mg/dl associated with the lowest risk.
Subject(s)
Kidney Transplantation , Magnesium , Cohort Studies , Humans , Risk Factors , Transplant RecipientsABSTRACT
BACKGROUND: In the general population, use of proton pump inhibitor (PPI) has been linked to higher risk of osteoporotic fractures. PPI is commonly prescribed in kidney transplant recipients (KTRs). However, the effect of PPI on osteoporosis in KTRs is largely unstudied. METHODS: A total of 1,774 adult KTRs in the Wisconsin Allograft Recipient Database with at least one eligible bone mineral density (BMD) measurement at least 3 months after transplantation were included in the analyses. Associations between use of PPI and histamine-2 receptor antagonist (H2RA) at 3 months after transplantation and subsequent slope of T-score were assessed. RESULTS: A total of 1,478 (83.3%) participants were using a PPI at 3 months after transplantation. Compared to the use of H2RA, use of PPI was not significantly associated with annualized slope of hip T-score (ß = -0.0039, 95% CI -0.00497 to 0.0021) or annualized slope of spine T-score (ß = -0.017, 95% CI -0.049 to 0.083) after adjustment for potential confounders. Similarly, no significant association between use of PPI and slope of T-score was observed when defining PPI/H2RA exposure as use within 6 months of the initial BMD measurement, or only including participants with at least 2 BMD measurements, or stratified by different age and sex. CONCLUSIONS: Use of PPI was not associated with an increased rate of BMD loss in KTRs. Our results support previous findings that PPI use does not have a significant effect on bone mineral loss.
Subject(s)
Bone Density/drug effects , Histamine H2 Antagonists/administration & dosage , Kidney Transplantation/adverse effects , Peptic Ulcer/prevention & control , Proton Pump Inhibitors/administration & dosage , Absorptiometry, Photon , Adult , Female , Hip/diagnostic imaging , Histamine H2 Antagonists/adverse effects , Humans , Kidney Failure, Chronic/surgery , Male , Middle Aged , Osteoporosis/chemically induced , Osteoporosis/diagnosis , Osteoporosis/epidemiology , Osteoporosis/prevention & control , Peptic Ulcer/etiology , Proton Pump Inhibitors/adverse effects , Risk Assessment/statistics & numerical data , Risk Factors , Spine/diagnostic imagingABSTRACT
The risk of subsequent cytomegalovirus infection (CMV) in kidney transplant recipients (KTR) after diagnosis of BK polyomavirus viremia (BKV) is unclear, and current evidence is conflicting. We reviewed all KTR transplanted at our institution between 1/1/2005 and 12/31/2015. Follow-up began 3 months after transplantation to avoid confounding effects of prophylaxis. Clinically significant BKV, defined as detectable BK viremia >1000 copies/mL via molecular diagnostic testing (PCR), was treated as a time-varying exposure with 1-year follow-up. This viral load cutoff was chosen to ensure a more homogenous population that would be considered to have clinically significant BK viremia that necessitated management via immunosuppressive modification. Patients were then screened for subsequent CMV infection. 2435 RTX recipients met inclusion criteria; of these, 314 developed BKV during follow-up (BK+). Lymphocyte depletion, tacrolimus maintenance, and biopsy-proven rejection were significantly higher in the BK+ group. BK+ was associated with lower risk of subsequent CMV infection (BK+ HR 0.45, 95% CI 0.22-0.94, P = .03, relative risk reduction 55%). When adjusted for significant confounding factors, CMV incidence remained reduced in the BK+ population (HR 0.47, 95% CI 0.22-0.98, P = .04). This large series of KTR demonstrates that BKV is associated with lower risk of subsequent CMV infection.
Subject(s)
BK Virus , Cytomegalovirus Infections , Kidney Transplantation , Polyomavirus Infections , Tumor Virus Infections , Cytomegalovirus Infections/diagnosis , Cytomegalovirus Infections/drug therapy , Cytomegalovirus Infections/epidemiology , Humans , Kidney Transplantation/adverse effects , Polyomavirus Infections/diagnosis , Polyomavirus Infections/drug therapy , Polyomavirus Infections/epidemiology , Risk , Risk Factors , Transplant Recipients , Tumor Virus Infections/diagnosis , Tumor Virus Infections/drug therapy , Tumor Virus Infections/epidemiology , Viremia/diagnosis , Viremia/drug therapy , Viremia/epidemiologyABSTRACT
Obstructive sleep apnea (OSA) is common but underdiagnosed among patients with kidney disease. This study examines whether the diagnosis of OSA in kidney transplant recipients (KTR) affected death, death-censored graft failure (DCGF), and acute rejection (AR). We analyzed the records of KTR who underwent transplant between 2000 and 2015. A total of 4014 kidney transplants were performed during the study period. Of these, 415 (10.3%) had a diagnosis of pretransplant OSA. Pretransplant OSA was associated with a higher risk of death in unadjusted analyses. After adjustment for potential confounders, pretransplant OSA was not associated with risk of death (HR = 1.04, 95% CI: 0.80-1.36). Similarly, pretransplant OSA was associated with a slightly higher incidence of DCGF or AR but neither associations were significant (HR: 1.23, 95% CI: 0.85-1.47 for DCGF; HR 1.10, 95% CI: 0.90-1.36 for AR). A total of 117 (3.3%) were diagnosed with de novo OSA after transplant. Similar to the pretransplant OSA, unadjusted HR for death was significantly higher in the de novo OSA group (HR: 1.48, 95% CI: 1.19-1.84); however, after adjustment, de novo OSA was not significantly associated with risk of death (HR: 1.15, 95% CI: 0.92-1.45). Similarly, DCGF and AR rates were not significantly associated with de novo OSA (HR: 1.10, 95% CI: 0.84-1.44 for DCGF; HR 1.10, 95% CI: 0.90-1.33 for AR). Our work did not detect significant associations between OSA and risk of death, graft failure, and rejection but the estimates might be underestimated due to underdiagnosis of OSA.
Subject(s)
Graft Rejection/mortality , Graft Survival , Kidney Transplantation/mortality , Sleep Apnea, Obstructive/mortality , Female , Graft Rejection/etiology , Graft Rejection/pathology , Humans , Male , Middle Aged , Prognosis , Risk Factors , Sleep Apnea, Obstructive/etiology , Sleep Apnea, Obstructive/pathologyABSTRACT
The risk of cytomegalovirus infection (CMV) after rejection treatment is poorly understood. To investigate this, we conducted a case/control (1:2) analysis of adult renal transplant recipients between January 1, 2005 and December 31, 2015, via incidence density sampling and survival analysis. Our objective was to evaluate the association of prior acute rejection with subsequent CMV, including epidemiology and outcomes. There were 2481 eligible renal transplants within the study period and 251 distinct CMV infections. Despite the use of antiviral prophylaxis rejection was a significant risk factor for CMV on unadjusted (HR 1.73 [1.34, 2.24] P < 0.05) and adjusted analysis (HR 1.46 [1.06, 2.04] P < 0.05). When matching cases to controls patients with CMV had significantly more rejection prior to CMV diagnosis (26.7% vs 14.2%, P < 0.01). CMV was associated with a twofold increased risk of prior rejection on unadjusted (OR 1.94, 95%CI: 1.28-2.96, P < 0.01) and adjusted analysis (OR 2.16, 95% CI: 1.31-3.58, P < 0.01). Patients with rejection preceding CMV had significantly increased graft loss (HR 2.89, 95% CI: 1.65-5.09, P < 0.01) and mortality (HR 1.82, 95% CI: 1.12-4.24, P = 0.03) as compared to those CMV cases without rejection. In conclusion, rejection is a risk factor for CMV infection that appears to persist for 1 year. Preceding rejection events increased risk of graft loss and mortality in CMV patients. Given this, prolonged surveillance monitoring for CMV after rejection may be warranted. Studies are needed investigating optimal monitoring strategies.
Subject(s)
Cytomegalovirus Infections/epidemiology , Cytomegalovirus/isolation & purification , Graft Rejection/etiology , Kidney Failure, Chronic/mortality , Kidney Transplantation/mortality , Transplant Recipients/statistics & numerical data , Antiviral Agents/therapeutic use , Case-Control Studies , Cytomegalovirus Infections/drug therapy , Cytomegalovirus Infections/virology , Female , Follow-Up Studies , Graft Rejection/pathology , Graft Survival , Humans , Incidence , Kidney Failure, Chronic/surgery , Kidney Failure, Chronic/virology , Kidney Transplantation/adverse effects , Male , Middle Aged , Prognosis , Risk Factors , Survival Rate , Wisconsin/epidemiologyABSTRACT
BACKGROUND: Cytomegalovirus (CMV) infection in kidney transplant recipients has been anecdotally observed with concomitant or subsequent opportunistic infections (OI), but this association has yet to be defined or quantified. METHODS: Patients who received a renal transplant between 1/1/2005 and 6/30/2014 and developed CMV infection were matched to controls in a ratio of 1:2 and the rates of opportunistic co-infection were calculated within pre-specified time frames (-30 days to +90 days and -30 days to +180 days). The primary outcome was composite OI rate, and secondary outcomes included time to OI and patient and graft outcomes. CMV-OI association rates were estimated via conditional logistic regression. RESULTS: There were 2405 patients who received a renal transplant during the study period; 394 cases of CMV infection were identified. These cases were matched to 783 controls for a total of 805 participants. OI occurred in 14 patients in the CMV case group (CMV+) and in 5 patients in the control group (CMV-) in the -30 to +90 day time period (3.55% vs 0.64%, OR = 5.60, 95% CI: 2.02-12.55). When considering 180-day follow-up, OI occurred in 17 CMV+ patients and 8 CMV- patients (4.3% vs 1%, OR = 4.25, 95% CI: 1.83-9.85). Mean time from CMV diagnosis to OI was 33 ± 64 days (median 7 days). Mortality was 3 times more likely in the group with concomitant OI (CMV+/OI+) as compared to a matched cohort of patients with CMV infection without OI (CMV+/OI-) (unadjusted HR 3.02, 1.64-5.55, Tables 6 and 7). Cumulative survival for CMV+/OI+ patients was significantly worse than CMV+/OI- patients (P < 0.01). CONCLUSIONS: CMV is associated with a significantly increased risk of co-infection with OI, particularly fungal infections. Clinical suspicion for concomitant OI should drive further workup after a CMV diagnosis. Future studies are needed to better define those patients at highest risk to elucidate subpopulations where the benefits of prophylaxis outweigh the potential risks associated with these therapies.
Subject(s)
Cytomegalovirus Infections/complications , Kidney Transplantation/adverse effects , Opportunistic Infections/complications , Adult , Aged , Antiviral Agents/therapeutic use , Cohort Studies , Coinfection/complications , Cytomegalovirus/drug effects , Cytomegalovirus/isolation & purification , Cytomegalovirus Infections/drug therapy , Electronic Health Records , Female , Ganciclovir/therapeutic use , Graft Rejection , Humans , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , Risk Factors , Transplant RecipientsABSTRACT
Despite advancements in symptom management for heart failure (HF), this devastating clinical syndrome remains the leading cause of death in the developed world. Studies using animal models have greatly advanced our understanding of the molecular mechanisms underlying HF; however, differences in cardiac physiology and the manifestation of HF between animals, particularly rodents, and humans necessitates the direct interrogation of human heart tissue samples. Nevertheless, an ever-present concern when examining human heart tissue samples is the potential for artefactual changes related to temperature changes during tissue shipment or sample processing. Herein, we examined the effects of temperature on the post-translational modifications (PTMs) of sarcomeric proteins, the proteins responsible for muscle contraction, under conditions mimicking those that might occur during tissue shipment or sample processing. Using a powerful top-down proteomics method, we found that sarcomeric protein PTMs were differentially affected by temperature. Specifically, cardiac troponin I and enigma homolog isoform 2 showed robust increases in phosphorylation when tissue was incubated at either 4⯰C or 22⯰C. The observed increase is likely due to increased cyclic AMP levels and activation of protein kinase A in the tissue. On the contrary, cardiac troponin T and myosin regulatory light chain phosphorylation decreased when tissue was incubated at 4⯰C or 22⯰C. Furthermore, significant protein degradation was also observed after incubation at 4⯰C or 22⯰C. Overall, these results indicate that temperature exerts various effects on sarcomeric protein PTMs and careful tissue handling is critical for studies involving human heart samples. Moreover, these findings highlight the power of top-down proteomics for examining the integrity of cardiac tissue samples.
Subject(s)
Myocardium/metabolism , Protein Processing, Post-Translational , Proteomics/methods , Sarcomeres/metabolism , Temperature , Adaptor Proteins, Signal Transducing , Analysis of Variance , Chromatography, Reverse-Phase , Cyclic AMP/analysis , Cyclic AMP-Dependent Protein Kinases/metabolism , Heart Failure/metabolism , Humans , LIM Domain Proteins , Myosin Light Chains/metabolism , Phosphorylation , Protein Isoforms/metabolism , Proteolysis , Specimen Handling/adverse effects , Tandem Mass Spectrometry , Troponin I/metabolism , Troponin T/metabolismABSTRACT
BACKGROUND: Arteriovenous (AV) access dysfunction is a common complication in hemodialysis patients. Markers of vascular calcification are associated with cardiovascular outcomes and mortality in this population, but their association with vascular access outcomes is unknown. In this study, we aimed to evaluate the association between selected vascular calcification makers and vascular access complications in a cohort of hemodialysis patients. METHOD: Fetuin-A, osteopontin (OPN), osteoprotegerin (OPG), and bone morphogenetic protein-7 (BMP-7) were measured in blood samples from 219 dialysis patients in the Choice for Healthy Outcomes in Caring for end-stage renal disease study; these patients were using a permanent vascular access. Participants were followed for up to 1 year or until the occurrence of a vascular access intervention or replacement. Associations with AV fistula (AVF) and AV graft (AVG) intervention-free survival were assessed in models adjusted for demographic characteristics, comorbidities, and inflammation. RESULTS: A total of 24 out 103 participants with an AVF and 43 out of 116 participants with an AVG had an intervention during follow-up. Lower fetuin-A, higher OPN, and higher BMP-7 were associated with a higher risk of AVF intervention (adjusted hazard ratios [aHR] for highest versus lowest tertile = 0.30 [95% CI 0.10-0.94]) for fetuin-A, 3.84 (95% CI 1.16-12.74) for OPN, and 3.49 (95% CI 1.16-10.52) for BMP-7. OPG was not significantly associated with the risk of AVF intervention. The associations of OPN and BMP-7 with AVF intervention appeared stronger among participants without diabetes (aHR 8.06; 95% CI 1.11-58.57 for OPN and aHR 2.55; 95% CI 1.08-6.08 for BMP-7, respectively) than among their counterparts with diabetes (p interaction = 0.06). None of the markers studied were significantly associated with AVG interventions. CONCLUSION: Lower fetuin-A and higher OPN and BMP-7 are associated with complications in AVF but not in AVG, suggesting a role for calcification in the pathogenesis AVF failure.
Subject(s)
Arteriovenous Shunt, Surgical/adverse effects , Kidney Failure, Chronic/therapy , Renal Dialysis/adverse effects , Vascular Calcification/diagnosis , Vascular Grafting/adverse effects , Adult , Aged , Biomarkers/blood , Female , Follow-Up Studies , Graft Survival , Humans , Kidney Failure, Chronic/blood , Male , Middle Aged , Prospective Studies , Renal Dialysis/instrumentation , Risk Factors , Vascular Calcification/blood , Vascular Calcification/etiology , Vascular PatencyABSTRACT
Objective: Culture and eating habits, which vary greatly across different ethnic groups, have a substantial impact on drinking behavior. This study aimed to examine whether the drinking patterns and reasons differ by ethnic groups, and provide useful insights for multi-ethnic areas that seek to cut down alcohol intake. Methods: We recruited excessive drinkers and collected the drinking patterns and motivations by questionnaire in a multi-ethnic society. Multiple linear regressions were used to evaluate the variations in drinking characteristics among different ethnic groups. Results: We recruited 1287 participants through convenience sampling (a non-probability sampling technique used in research where the researcher selects participants or units for a study based on their accessibility and proximity), among whom 439 excessive drinkers were eligible. The mean age was 38 years for the 439 participants, 92.9% were men, 36.0% were Han, and 64.0% were minorities mainly composed of the Yi. The majority of the participants were married (75.9%) and did physical work (58.1%). Ethnic minorities consumed more alcohol on a single occasion than Han people did (47.3 vs 41.8g/session) while drinking less frequently. For the minority and Han participants, 67% and 42% were not used to drinking with food, respectively. Peer pressure and fostering a good atmosphere were the most common drinking reasons for the minority and Han, respectively. Conclusion: We found substantial differences in drinking patterns and reasons between ethnic minorities and Han ethnicity, attributable to their culture and customs. Findings highlight the importance of drinking habits and motivations in exploring alcohol control education strategies in the context of ethnic integration and population immigration.
ABSTRACT
BACKGROUND: Contemporary data on the quantity and quality of medication use among older adults are lacking. This study examined recent trends in the number and appropriateness of prescription medication use among older adults in the United States. METHODS: Data from the National Health and Nutrition Examination Survey (NHANES) between 2011 and March 2020 were used, and 6 336 adult participants aged 65 and older were included. We examined the number of prescription medication, prevalence of polypharmacy (≥5 prescription drugs), use of potentially inappropriate medication (PIM), and use of recommended medications (angiotensin-converting enzyme inhibitor [ACEI]/angiotensin receptor blockers [ARBs] plus beta-blockers among patients with heart failure and ACEI/ARBs among patients with albuminuria). RESULTS: There has been a slight increase in the prevalence of polypharmacy (39.3% in 2011-2012 to 43.8% in 2017-2020, p for trendâ =â .32). Antihypertensive, antihyperlipidemic, antidiabetic medications, and antidepressants are the most commonly used medications. There was no substantial change in the use of PIM (17.0% to 14.7%). Less than 50% of older adults with heart failure received ACEI/ARBs plus beta-blockers (44.3% in 2017-2020) and approximately 50% of patients with albuminuria received ACEI/ARBs (54.0% in 2017-2020), with no improvement over the study period. Polypharmacy, older age, female, and lower socioeconomic status were generally associated with greater use of PIM but lower use of recommended medications. CONCLUSIONS: The medication burden remained high among older adults in the United States and the appropriate utilization of medications did not improve in the recent decade. Our results underscore the need for greater attentions and interventions to the quality of medication use among older adults.
Subject(s)
Inappropriate Prescribing , Nutrition Surveys , Polypharmacy , Humans , Aged , Male , Female , United States , Inappropriate Prescribing/trends , Inappropriate Prescribing/statistics & numerical data , Independent Living , Potentially Inappropriate Medication List/statistics & numerical data , Potentially Inappropriate Medication List/trends , Aged, 80 and over , Drug Utilization/trends , Drug Utilization/statistics & numerical data , Prescription Drugs/therapeutic use , Adrenergic beta-Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Angiotensin Receptor Antagonists/therapeutic useABSTRACT
BACKGROUND: Potentially inappropriate medication (PIM) use is an important public health problem, particularly among older adults who may need multiple pharmacologic therapies for various chronic conditions. As socioeconomic status (SES) affects the quality of healthcare that individuals receive, SES may be associated with the use of PIM in older adults. This study aimed to determine whether low SES is associated with increased use of PIM. METHODS: We studied 4927 participants (aged 66-90 years) who were on at least one medication at visit five (2011-2013) of the Atherosclerosis Risk in Communities Study. We created a cumulative SES score categorized as high (7-9), middle (3-6), and low (0-2) based on education, income, and area deprivation index. We use multivariable logistic regression to examine the associations between SES and use of two or more PIM for older adults, defined by the 2019 Beers Criteria. RESULTS: A total of 31.0% and 6.9% of the participants used one or more PIM and two or more PIM, respectively. After adjusting for demographic characteristics and insurance type, low cumulative SES score was associated with significantly greater use of two or more PIM (odds ratio [OR] = 1.83 [95% confidence interval (CI) 1.18-2.86]), as was middle cumulative SES score (OR = 1.40 [95% CI 1.06-1.83]), compared to high cumulative SES score. The results remained significant after further adjusting for comorbidities and medication burden for low cumulative SES score (OR = 1.66 [95%CI 1.02-2.71]). CONCLUSIONS: We found that lower SES was associated with greater use of PIM among older adults independent of their medication burden and comorbidities, suggesting socioeconomic disparities in quality of medication management. Focused efforts targeting older adults with low SES to reduce PIM use may be needed to prevent adverse drug events.
Subject(s)
Inappropriate Prescribing , Potentially Inappropriate Medication List , Humans , Aged , Inappropriate Prescribing/prevention & control , Comorbidity , Social Class , IncomeABSTRACT
Clinical trials have demonstrated cardiovascular benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA). However, their impact on all-cause and cause-specific hospitalization in real-world practice remains unclear. We identified patients with diabetes who initiated SGLT2i (n = 2,492), GLP-1RA (n = 1,982), or dipeptidyl peptidase-4 inhibitors (DPP4i, n = 2,492) between 2015 and 2018 in Geisinger Health System. We examined all-cause hospitalization (net benefit indicator) and cardiovascular disease (CVD) hospitalization (CV benefit indicator), as well as non-CVD hospitalization (harm indicator), using Cox proportional hazards regression. During a median follow-up of 16 months, SGLT2i and GLP-1RA were associated with lower risk of all-cause hospitalization (hazard ratio [HR] 0.85, 95% CI 0.75 to 0.95 for SGLT2i; HR 0.89, 95% CI 0.78 to 0.98 for GLP-1RA), as well as CVD hospitalization (HR 0.61, 95% CI 0.47 to 0.79) for SGLT2i; HR 0.77, 95% CI 0.60 to 0.99 for GLP-1RA) compared with DPP4i. The risks of all-cause and CVD hospitalization were similar between SGLT2i and GLP-1RA. SGLT2i was associated with substantially lower risk of myocardial infarction and heart failure hospitalization compared with DPP4i and lower risk of heart failure hospitalization compared with GLP-1RA. The risk of non-CVD hospitalization did not differ among the treatment groups. These results from real-world comparison further encourage SGLT2i and GLP-1RA use in routine diabetes care, particularly among patients at high risk of cardiovascular events.