Publications

The combination of metformin and the peroxisome proliferator-activated receptors (PPAR) agonists offers a promising avenue for managing type 2 diabetes (T2D) through their potential complementary mechanisms of action. The results from randomized controlled trials (RCT) assessing the efficacy of PPAR agonists plus metformin versus metformin alone in T2D are inconsistent, which prompted the conduct of the systematic review and meta-analysis. We searched MEDLINE and EMBASE from inception (1966) to March 2023 to identify all RCTs comparing any PPAR agonists plus metformin versus metformin alone in T2D. Categorical variables were summarized as relative risk along with 95% confidence interval (CI). Twenty RCTs enrolling a total of 6058 patients met the inclusion criteria. The certainty of evidence ranged from moderate to very low. Pooled results show that using PPAR agonist plus metformin, as compared to metformin alone, results in lower concentrations of fasting glucose [MD = - 22.07 mg/dl (95% CI - 27.17, - 16.97), HbA1c [MD = - 0.53% (95% CI - 0.67, - 0.38)], HOMA-IR [MD = - 1.26 (95% CI - 2.16, - 0.37)], and fasting insulin [MD = - 19.83 pmol/L (95% CI - 29.54, - 10.13)] without significant increase in any adverse events. Thus, synthesized evidence from RCTs demonstrates the beneficial effects of PPAR agonist add-on treatment versus metformin alone in T2D patients. In particular, novel dual PPARα/γ agonist (tesaglitazar) demonstrate efficacy in improving glycaemic and lipid concentrations, so further RCTs should be performed to elucidate the long-term outcomes and safety profile of these novel combined and personalized therapeutic strategies in the management of T2D.PROSPERO registration no. CRD42023412603.

BACKGROUND: In nonpregnant individuals, the rate-pressure product, the product of heart rate and systolic blood pressure, is used as a noninvasive surrogate of myocardial O2 consumption during cardiac stress testing. Pregnancy is considered a physiological cardiovascular stress test. Evidence describing the impact of pregnancy on myocardial O2 demand, as assessed by the rate-pressure product, is limited.

OBJECTIVE: This study aimed to describe changes in the rate-pressure product for each pregnancy trimester, during labor and delivery, and the postpartum period among low-risk pregnancies.

STUDY DESIGN: This was a retrospective cohort study that assessed uncomplicated pregnancies delivered vaginally at term. We collected rate-pressure product (heart rate × systolic blood pressure) values preconception, during pregnancy for each trimester (at ≤13 weeks + 6/7 days, at 14 weeks + 0/7 days through 27 weeks + 6/7 days, and at ≥28 weeks + 0/7 days), during the labor and delivery encounter (hospital admission until complete cervical dilation, complete cervical dilation until placental delivery, and after placental delivery until hospital discharge), and during the outpatient postpartum visit at 2 to 6 weeks after delivery. We calculated the percentage change at each time point from the preconception rate-pressure product (delta rate-pressure product). We used a mixed-linear model to analyze differences in the mean delta rate-pressure product over time and the influence of prepregnancy age, prepregnancy body mass index, and neuraxial anesthesia status during labor and delivery on these estimates.

RESULTS: Our cohort comprised 316 patients. The mean rate-pressure product increased significantly from preconception starting at the third trimester of pregnancy and during labor and delivery (P≤.05). The mean delta rate-pressure product peaked at 12% and 38% in the third trimester and during labor and delivery, respectively. Prepregnancy body mass index was inversely correlated with the mean delta rate-pressure product changes (estimate, -0.308; 95% confidence interval, -0.536 to -0.80; P=.008). In contrast, neither the prepregnancy age, nor neuraxial anesthesia status during labor had a significant influence on this parameter.

CONCLUSION: This study validates the transient but significant increase in the rate-pressure product, a clinical estimate of myocardial O2 demand, during uncomplicated pregnancies delivered vaginally at term. Pregnant individuals with lower prepregnancy body mass index experienced a sharper increase in this parameter. Patients who receive neuraxial anesthesia during labor and delivery experience similar changes in the rate-pressure product as those who did not.

Despite therapeutic advances for acute promyelocytic leukemia (APL) with the emergence of all-trans retinoic acid, arsenic trioxide, and gemtuzumab-ozogamycin, approximately 10% of patients still experience disease relapse, typically occurring within 24 to 36 months following completion of front-line treatment. Traditionally, both allogeneic (allo) and autologous (auto) hematopoietic cell transplantation (HCT) have been considered reasonable treatment options for relapsed APL; however, no randomized controlled studies have been conducted comparing allo-HCT and auto-HCT in patients with relapsed APL. We performed a systematic review/meta-analysis to assess the totality of evidence pertaining to allo-HCT or auto-HCT in relapsed APL. Our search identified 1158 references, of which 23 met our inclusion criteria. While acknowledging the limitations of comparing these 2 treatment modalities indirectly, based on results from separate meta-analyses, it appears that pooled rates of event-free survival (71% versus 54%), progression-free survival (63% versus 43%), and overall survival (82% versus 58%) are higher after auto-HCT. This difference can be explained in part by the higher risk of pooled nonrelapse mortality (NRM) in patients undergoing allo-HCT (29% versus 5%), owing to inherent risks associated with this modality. In the absence of a randomized prospective clinical trial comparing allo-HCT and auto-HCT, our results show that both modalities are acceptable in patients with relapsed APL. The higher pooled NRM rate with allo-HCT is an important consideration when choosing this option. Additionally, the comparable pooled relapse rate for auto-HCT and allo-HCT (24% versus 23%) provides a rationale for evaluating post-HCT consolidative strategies to mitigate this risk.

BACKGROUND: The European Society of Cardiology (ESC) provided a focused update to the 2021 Guideline for the Management of Heart Failure, now providing a 1A recommendation for intravenous iron in patients with heart failure with reduced ejection fraction (HFrEF) and iron deficiency (ID). However, the findings from randomized controlled trials (RCT) are mixed. This systematic review of RCTs aims to provide an update and synthesize the evidence addressing the association of intravenous iron with patient-based outcomes in patients with HFrEF and ID.

METHODS: Any RCT evaluating the effect of intravenous iron in patients with HFrEF and ID was eligible for inclusion. A complete search of the EMBASE and PubMed databases was conducted from inception until 15 September 2023. The primary outcome was the composite of the quality of life (QoL) questionnaires, while the secondary outcomes included first heart failure (HF) hospitalizations and all-cause mortality. Data extraction was performed independently by two reviewers. Data were pooled using a random-effects model.

RESULTS: Of the 1035 references, 15 RCTs enrolling 6649 patients were included in this study. Intravenous iron was associated with significant improvement in the composite of QoL (standardized mean difference - 1.36, 95% confidence interval [CI] - 2.24 to - 0.48; p = 0.002), a significant reduction in first HF hospitalizations (hazard ratio [HR] 0.73, 95% CI 0.56-0.95; p = 0.02), and with no change in all-cause mortality (HR 0.90, 95% CI 0.79-1.03; p = 0.12). The certainty of the evidence ranged from moderate to very low.

CONCLUSION: Intravenous iron is possibly associated with improved QoL and reduced HF hospitalizations, without impacting all-cause mortality. These findings not only support the use of intravenous iron in patients with HFrEF but also emphasize the need for well-designed and executed RCTs with granular outcome reporting and powered sufficiently to address the impact of intravenous iron on mortality in patients with HFrEF and ID.

REGISTRATION: PROSPERO identifier number CRD42023389.

Although left ventricular assist device (LVAD) implantation can improve survival in patients with end-stage heart failure, it is not without risk. Numerous complications are possible, and durable support requires substantial lifestyle changes. The use of various knowledge-assessment tools may allow for more informed patient decisions. To synthesize the totality of the evidence, we conducted a systematic review and meta-analysis to summarize the efficacy of decision aid (DA) use in patients with advanced heart failure who are eligible for LVAD. Any randomized controlled trial (RCT) evaluating the efficacy of DAs in patients considering LVAD was eligible for inclusion. A complete search of EMBASE and PubMed was conducted from the start until June 8, 2023. The primary outcome was patients' LVAD knowledge. Data extraction was performed independently by 2 reviewers. Data were pooled using a random-effects model. Of the 575 references, 2 RCTs randomizing 490 patients were included in this study. DAs were associated with no significant change in LVAD knowledge (standardized mean difference 0.07, 95% confidence interval -0.24 to 0.39, p = 0.64) or decisional conflict (mean difference -1.48, 95% confidence interval -5.28 to 2.32, p = 0.45). The certainty of the evidence ranged from moderate to very low. The use of DAs in LVAD-eligible patients with advanced heart failure resulted in no difference in patients' knowledge of LVAD after LVAD education. The findings from this study will aid in the power analysis of a well-designed RCT to evaluate and encourage further investigation into the efficacy and relevance of DAs in preparing patients for a life with LVAD.

BACKGROUND AND AIM: The quality of clinical practice guidelines (CPGs) for the management of antithrombotic agents in patients undergoing gastrointestinal (GI) endoscopy has not been systematically appraised. The goal of this study was to evaluate the methodological quality of CPGs for the management of antithrombotic agents in periendoscopic period published within last 6 years.

METHODS: A systematic search of PubMed and Embase databases was performed to identify eligible CPGs published between January 1, 2016, and April 14, 2022, addressing the management of antithrombotic agents in the periendoscopic period. The quality of the CPG was independently assessed by six reviewers using the Appraisal of Guidelines for Research & Evaluation (AGREE) II instrument. Domain scores were considered of sufficient quality when > 60% and of good quality when > 80%.

RESULTS: The search yielded 343 citations, of which seven CPGs published by the gastroenterology associations in Asia (n = 3), Europe (n = 2), and North America (n = 2) were included for the critical appraisal. The overall median score for the AGREE II domains was 93% (interquartile range [IQR] 11%) for scope and purpose, 79% (IQR 61%) for stakeholder involvement, 79% (IQR 36%) for rigor of development, 100% (IQR 14%) for clarity of presentation, 32% (IQR 36%) for applicability, 93% (IQR 29%) for editorial independence, and 86% (IQR 29%) for overall assessment.

CONCLUSIONS: The findings show that the overall methodological quality of the CPGs for the management of antithrombotic agents in the periendoscopic period varies across the domains. There is significant scope for improvement in the methodological rigor and applicability of CPGs.

The combination of metformin and the peroxisome proliferator-activated receptors (PPAR) agonists offers a promising avenue for managing type 2 diabetes (T2D) through their potential complementary mechanisms of action. The results from randomized controlled trials (RCT) assessing the efficacy of PPAR agonists plus metformin versus metformin alone in T2D are inconsistent, which prompted the conduct of the systematic review and meta-analysis. We searched MEDLINE and EMBASE from inception (1966) to March 2023 to identify all RCTs comparing any PPAR agonists plus metformin versus metformin alone in T2D. Categorical variables were summarized as relative risk along with 95% confidence interval (CI). Twenty RCTs enrolling a total of 6058 patients met the inclusion criteria. The certainty of evidence ranged from moderate to very low. Pooled results show that using PPAR agonist plus metformin, as compared to metformin alone, results in lower concentrations of fasting glucose [MD = - 22.07 mg/dl (95% CI - 27.17, - 16.97), HbA1c [MD = - 0.53% (95% CI - 0.67, - 0.38)], HOMA-IR [MD = - 1.26 (95% CI - 2.16, - 0.37)], and fasting insulin [MD = - 19.83 pmol/L (95% CI - 29.54, - 10.13)] without significant increase in any adverse events. Thus, synthesized evidence from RCTs demonstrates the beneficial effects of PPAR agonist add-on treatment versus metformin alone in T2D patients. In particular, novel dual PPARα/γ agonist (tesaglitazar) demonstrate efficacy in improving glycaemic and lipid concentrations, so further RCTs should be performed to elucidate the long-term outcomes and safety profile of these novel combined and personalized therapeutic strategies in the management of T2D.PROSPERO registration no. CRD42023412603.

OBJECTIVE: To assess the cost-effectiveness of alternative approaches to diagnose and treat obstructive sleep apnea (OSA) in patients with traumatic brain injury (TBI) during inpatient rehabilitation.

SETTING: Data collected during the Comparison of Sleep Apnea Assessment Strategies to Maximize TBI Rehabilitation Participation and Outcome (C-SAS) clinical trial (NCT03033901) on an inpatient rehabilitation TBI cohort were used in this study.

STUDY DESIGN: Decision tree analysis was used to determine the cost-effectiveness of approaches to diagnosing and treating sleep apnea. Costs were determined using 2021 Centers for Medicare and Medicaid Services reimbursement codes. Effectiveness was defined in terms of the appropriateness of treatment. Costs averted were extracted from the literature. A sensitivity analysis was performed to account for uncertainty. Analyses were performed for all severity levels of OSA and a subgroup of those with moderate to severe OSA. Six inpatient approaches using various phases of screening, testing, and treatment that conform to usual care or guideline-endorsed interventions were evaluated: (1) usual care; (2) portable diagnostic testing followed by laboratory-quality testing; (3) screening with the snoring, tiredness, observed apnea, high BP, BMI, age, neck circumference, and male gender (STOP-Bang) questionnaire; (4) Multivariable Apnea Prediction Index (MAPI) followed by portable diagnostic testing and laboratory-quality testing; (5) laboratory-quality testing for all; and (6) treatment for all patients.

MAIN MEASURES: Cost, Effectiveness, and Incremental Cost-Effectiveness Ratio (ICER).

RESULTS: Phased approaches utilizing screening and diagnostic tools were more effective in diagnosing and allocating treatment for OSA than all alternatives in patients with mild to severe and moderate to severe OSA. Usual care was more costly and less effective than all other approaches for mild to severe and moderate to severe OSA.

CONCLUSIONS: Diagnosing and treating OSA in patients with TBI is a cost-effective strategy when compared with usual care.

OBJECTIVES: Missed appointments can lead to treatment delays and adverse outcomes. Telemedicine may improve appointment completion because it addresses barriers to in-person visits, such as childcare and transportation. This study compared appointment completion for appointments using telemedicine versus in-person care in a large cohort of patients at an urban academic health sciences center.

MATERIALS AND METHODS: We conducted a retrospective cohort study of electronic health record data to determine whether telemedicine appointments have higher odds of completion compared to in-person care appointments, January 1, 2021, and April 30, 2023. The data were obtained from the University of South Florida (USF), a large academic health sciences center serving Tampa, FL, and surrounding communities. We implemented 1:1 propensity score matching based on age, gender, race, visit type, and Charlson Comorbidity Index (CCI).

RESULTS: The matched cohort included 87 376 appointments, with diverse patient demographics. The percentage of completed telemedicine appointments exceeded that of completed in-person care appointments by 9.2 points (73.4% vs 64.2%, P < .001). The adjusted odds ratio for telemedicine versus in-person care in relation to appointment completion was 1.64 (95% CI, 1.59-1.69, P < .001), indicating that telemedicine appointments are associated with 64% higher odds of completion than in-person care appointments when controlling for other factors.

DISCUSSION: This cohort study indicated that telemedicine appointments are more likely to be completed than in-person care appointments, regardless of demographics, comorbidity, payment type, or distance.

CONCLUSION: Telemedicine appointments are more likely to be completed than in-person healthcare appointments.

Hepatosplenic T-cell lymphoma (HSTCL) is a rare and aggressive type of peripheral T-cell lymphoma with median overall survival (OS) of approximately 1 year. Data on the effectiveness of hematopoietic cell transplantation (HCT) is limited, as is the choice between autologous HCT (auto-HCT) and allogeneic HCT (allo-HCT) in the treatment of this disease. To evaluate the outcome of patients with HSTCL who underwent either auto-HCT or allo-HCT, we performed a multi-institutional retrospective cohort study to assess outcomes of HCT in HSTCL patients. Fifty-three patients with HSTCL were included in the study. Thirty-six patients received an allo-HCT and 17 received an auto-HCT. Thirty-five (66%) were males. Median age at diagnosis was 38 (range 2 to 64) years. Median follow-up for survivors was 75 months (range 8 to 204). The median number of prior lines of therapy was 1 (range 1 to 4). Median OS and progression-free survival (PFS) for the entire cohort were 78.5 months (95% CI: 25 to 79) and 54 months (95% CI: 18 to 75), respectively. There were no significant differences in OS (HR: 0.63, 95% CI: 0.28 to 1.45, P = .245) or PFS (HR: 0.7, 95% CI: 0.32 to 1.57, P = .365) between the allo-HCT and auto-HCT groups, respectively. In the allo-HCT group, the 3-year cumulative incidence of relapse was 35% (95% CI: 21 to 57), while 3-year cumulative incidence of NRM was 16% (95% CI: 7 to 35). In the auto-HCT group, the 3-year cumulative incidence of relapse and NRM were 43% (95% CI: 23 to 78) and 14% (95% CI: 4 to 52), respectively. Both Auto-HCT and Allo-HCT are effective consolidative strategies in patients with HSTCL, and patients should be promptly referred for HCT evaluation.