Publications

AIMS: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been shown to have benefit in patients with heart failure (HF). Multiple systematic reviews and meta-analyses (SRs and MAs) of randomized control trials (RCTs) comparing SGLT2i to placebo have been performed. However, there is uncertainty in the quality of the evidence and associated efficacy. We performed an overview of SRs and MAs of RCTs to summarize the evidence related to the efficacy of SGLT2i for the management of HF.

METHODS AND RESULTS: A comprehensive search of three databases (the Cochrane Library, EMBASE, and PubMed) was conducted until February 21, 2021. All SRs of RCTs evaluating the efficacy of SGLT2i in patients with HF were eligible for inclusion. The primary outcome was all-cause mortality. Methodological quality was evaluated using the AMSTAR-2 assessment tool. The overall quality of evidence was summarized using the Grading of Recommendations Assessment, Development, and Evaluation method. The initial search yielded 3431 references, of which, eight SRs and MAs met the inclusion criteria. The methodological quality ranged from critically low to high. The overall quality of evidence ranged from very low to moderate. Most of the SRs and MAs showed benefits in all-cause mortality, HF-related hospitalizations, and KCCQ score change.

CONCLUSIONS: SGLT2i are possibly beneficial in patients with HF, however, none of the SRs and MAs compared the efficacy between different types of SGLT2i. Furthermore, this paper emphasizes the need for consistent reproducible conduct and reporting of SRs to generate high-quality evidence and facilitate clinical decision-making.

Dysregulated anger can result in devastating health and interpersonal consequences for individuals, families, and communities. Compared to civilians, combat veterans and service members (C-V/SM) report higher levels of anger and often have risk factors for anger including posttraumatic stress disorder (PTSD), traumatic brain injury (TBI), pain, alcohol use, and impaired sleep. The current study examined the relative contributions of established variables associated with anger (e.g., combat exposure, current PTSD symptoms, history of TBI, pain interference, and hazardous alcohol use) in 1263 C-V/SM. Sleep impairments, represented by poor sleep quality and obstructive sleep apnea (OSA) risk, were also evaluated as potential mediators of the relationships between established risk factors and anger, and therefore potential modifiable treatment targets. Multiple regression model results revealed that PTSD symptoms (β = 0.517, p < .001), OSA risk (β = 0.057, p = .016), pain interference (β = 0.214, p < .001), and hazardous alcohol use (β = 0.054, p = .009) were significantly associated with anger. Results of the mediation models revealed that OSA risk accounted for the association between PTSD and anger, in addition to the association between pain interference and anger. The current study extends previous literature by simultaneously examining factors associated with anger using a multivariable model in a large sample of C-V/SM. Additionally, treating OSA may be a novel way to reduce anger in C-V/SM who have PTSD and/or pain interference.

Multiple clinical practice guidelines (CPGs) for heart failure management have been published to provide the best practices regarding the use of foundational therapies to reduce morbidity and mortality in this patient population. However, a critical appraisal of these heart failure guidelines has not been performed. This systematic review aimed to assess the methodological quality of current CPGs in the management of patients with heart failure. A comprehensive search of EMBASE and PubMed was conducted to identify CPGs published between January 1, 2021 and September 8, 2022. Any CPGs published in the last 2 years addressing the management of heart failure were eligible for inclusion. The methodological quality of the CPGs was assessed using the AGREE II (Appraisal of Guidelines for Research & Evaluate II) instrument. The initial search yielded 3,269 citations, of which, 6 CPGs were included. A total of 2 CPGs were each published by the cardiology associations in North America and Asia and 1 each in Europe and South America. The overall median score for the AGREE II domains were 100% for scope and purpose, 71% for stakeholder involvement, 71% for the rigor of development, 100% for clarity of presentation, 43% for applicability, 100% for editorial independence, and 64% for overall assessment. CPG developers would benefit from the use of a standardized approach to the development of CPGs and use the contents of the AGREE II tool to improve the methodological rigor, reporting, and applicability of CPGs.

BACKGROUND: Sepsis-associated encephalopathy (SAE) is characterized by a diffuse cerebral dysfunction that accompanies sepsis in the absence of direct central nervous system infection. The endothelial glycocalyx is a dynamic mesh containing heparan sulfate linked to proteoglycans and glycoproteins, including selectins and vascular/intercellular adhesion molecules (V/I-CAMs), which protects the endothelium while mediating mechano-signal transduction between the blood and vascular wall. During severe inflammatory states, components of the glycocalyx are shed into the circulation and can be detected in soluble forms. Currently, SAE remains a diagnosis of exclusion and limited information is available on the utility of glycocalyx-associated molecules as biomarkers for SAE. We set out to synthesize all available evidence on the association between circulating molecules released from the endothelial glycocalyx surface during sepsis and sepsis-associated encephalopathy.

METHODS: MEDLINE (PubMed) and EMBASE were searched since inception until May 2, 2022 to identify eligible studies. Any comparative observational study: i) evaluating the association between sepsis and cognitive decline and ii) providing information on level of circulating glycocalyx-associated molecules was eligible for inclusion.

RESULTS: Four case-control studies with 160 patients met the inclusion criteria. Meta-analysis of biomarkers ICAM-1 (SMD 0.41; 95% CI 0.05-0.76; p = 0.03; I2 = 50%) and VCAM-1 (SMD 0.55; 95% CI 0.12-0.98; p = 0.01; I2 = 82%) revealed higher pooled mean concentration in patients with SAE compared to the patients with sepsis alone. Single studies reported elevated levels of P-selectin (MD 0.80; 95% CI -17.77-19.37), E-selectin (MD 96.40; 95% Cl 37.90-154.90), heparan sulfate NS2S (MD 19.41; 95% CI 13.37-25.46), and heparan sulfate NS+NS2S+NS6S (MD 67.00; 95% CI 31.00-103.00) in patients with SAE compared to the patients with sepsis alone.

CONCLUSION: Plasma glycocalyx-associated molecules are elevated in SAE and may be useful for early identification of cognitive decline in sepsis patients.

OBJECTIVES: The policies regarding resident physician work hours are constantly being evaluated and changed. However, the results of randomised control trials (RCTs) are mixed. This systematic review of RCTs aims to synthesise the evidence associated with resident duty hour restrictions and its impact on resident- and patient-based outcomes.

METHODS: A comprehensive search of the Cochrane Library, EMBASE and PubMed was conducted from inception until 31 July 2020. Any RCT evaluating the impact of longer resident physician work hours compared to shorter resident physician work hours on resident- and patient-based outcomes was eligible for inclusion. Two reviewers extracted data independently. The primary outcome was the impact of resident duty hour restrictions on emotional exhaustion, depersonalisation and personal accomplishment, as defined by the Maslach Burnout Inventory. The secondary patient-related outcomes were patient hospital length of stay, serious medical errors and preventable adverse events. Data were pooled using a random-effects model.

RESULTS: Of the 873 references, nine RCTs met the inclusion criteria. A shorter shift length compared with longer shift length was associated with significantly less emotional exhaustion (standardised mean difference [SMD] = -0.11, 95% CI = -0.21, -0.00) and less dissatisfaction with overall well-being (OR = 0.61, 95% CI 0.38, 0.99) but not with hospital length of stay (SMD = -0.01, 95% CI = -0.05, 0.02, p = 0.45) and serious medical errors per 1000 patient hours (OR = 1.07, 95% CI = 0.52, 2.21; p = 0.86).

CONCLUSIONS: Shorter resident duty hours is possibly associated with improvement in resident-based outcomes, specifically, emotional exhaustion, dissatisfaction with overall well-being, sleep duration and sleepiness. These findings may inform the policy change in support of reduced shift hours resulting in overall well-being for the residents with possible reduction in burnout without adverse impact on patient-based outcomes.

BACKGROUND: There are various published clinical practice guidelines (CPGs) for the management of pancreatic cystic lesions. However, the quality of these guidelines has not been systematically appraised. This study aimed to evaluate the quality of CPGs published in the last 5 years for the management of pancreatic cysts.

METHODS: A systematic search of the PubMed database for eligible CPGs published between January 1, 2016 and November 17, 2021, using a sensitive filter. The quality of the CPGs was independently evaluated using the Appraisal of Guidelines for Research & Evaluation II instrument, with domain scores considered sufficient quality if >60% and good quality if >80%.

RESULTS: The search yielded 4 eligible CPGs out of 426 citations. The scores varied for different domains for each CPG, with the overall median score being 79% for scope and purpose, 26% for stakeholder involvement, 51% for rigor of development, 69% for clarity of presentation, 14% for applicability, and 75% for editorial independence.

CONCLUSIONS: The study revealed that the quality of the CPGs for pancreatic cyst management in adults remains moderate at best. Patient representatives were not involved in any of the CPG development process. There is a significant scope for improvement in methodological rigor and clarity of presentation.

BACKGROUND: Lifestyle changes and dietary intervention, including the use of probiotics, can modulate dysbiosis of gut microbiome and contribute to the management of type 2 diabetes mellitus (T2DM). This systematic review and meta-analysis aim to assess the efficacy of metformin plus probiotics versus metformin alone on outcomes in patients with T2DM.

METHODS: We searched MEDLINE and EMBASE from inception to February 2023 to identify all randomized controlled trials (RCTs), which compared the use of metformin plus probiotics versus metformin alone in adult patients with T2DM. Data were summarized as mean differences (MD) with 95 % confidence interval (CI) and pooled under the random effects model.

FINDINGS: Fourteen RCTs (17 comparisons, 1009 patients) were included in this systematic review. Pooled results show a significant decrease in fasting glucose (FG) (MD = -0.64, 95 % CI = -1.06, -0.22) and HbA1c (MD = -0.29, 95 % CI = -0.47, -0.10) levels in patients with T2DM treated with metformin plus probiotics versus metformin alone. The addition of probiotics to metformin resulted in lower odds of gastrointestinal adverse events (Odds ratio = 0.18, 95 % CI = 0.09, 0.3.8; I2 = 0 %).

CONCLUSIONS: The addition of probiotics to metformin therapy is associated with improvement in T2DM outcomes. However, high-quality and adequately reported RCTs are needed in the future to confirm our findings.

The American Diabetes Association's Standards of Medical Care in Diabetes emphasize the need for awareness regarding overbasalization (basal insulin doses >0.5 units/kg/day without bolus insulin) in the treatment of type 2 diabetes. However, outcomes data on the impact of overbasalization are limited. This post hoc analysis of a large randomized controlled trial suggests that an insulin therapy regimen involving overbasalization compared with a basal-bolus insulin regimen that avoids overbasalization is less effective at lowering A1C and may be associated with increased cardiovascular risk. Clinicians should consider alternative approaches to glycemic control before increasing basal insulin doses to >0.5 units/kg/day.

BACKGROUND: Anaphylaxis is an often under =diagnosed, severe allergic event for which epidemiological data are sporadic. Researchers have leveraged administrative and claims data algorithms to study large databases of anaphylactic events; however, little longitudinal data analysis is available after transition to the International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM).

OBJECTIVE: Study longitudinal trends in anaphylaxis incidence using direct and indirect query methods.

METHODS: Emergency department (ED) and inpatient data were analyzed from a large state health care administration database from 2011 to 2020. Incidence was calculated using direct queries of anaphylaxis ICD-9-CM and ICD-10-CM codes and indirect queries using a symptom-based ICD-9-CM algorithm and forward mapped ICD-10-CM version to identify undiagnosed anaphylaxis episodes and to assess algorithm performance at the population level.

RESULTS: An average of 2.4 million inpatient and 7.5 million ED observations/y were analyzed. Using the direct query method, annual ED anaphylaxis cases increased steadily from 1,454 (2011) to 4,029 (2019) then declined to 3,341 in 2020 during the coronavirus disease 2019 (COVID-19) pandemic. In contrast, inpatient cases remained relatively steady, with a slight decline after 2015 during the ICD version transition, until a significant drop occurred in 2020. Using the indirect queries, anaphylaxis cases increased markedly after the ICD transition year, especially involving drug-related anaphylaxis.

CONCLUSIONS: Nontypical drug associations with anaphylaxis episodes using the ICD-10-CM version of the algorithm suggest poor performance with drug-related codes. Further, the increased granularity of ICD-10-CM identified potential limitations of a previously validated symptom-based ICD-9-CM algorithm used to detect undiagnosed cases.

BACKGROUND: When treating potentially resectable pancreatic adenocarcinoma, therapeutic decisions are left to the sensibility of treating clinicians who, faced with a decision that post hoc can be proven wrong, may feel a sense of regret that they want to avoid. A regret-based decision model was applied to evaluate attitudes toward neoadjuvant therapy versus upfront surgery for potentially resectable pancreatic adenocarcinoma.

METHODS: Three clinical scenarios describing high-, intermediate-, and low-risk disease-specific mortality after upfront surgery were presented to 60 respondents (20 oncologists, 20 gastroenterologists, and 20 surgeons). Respondents were asked to report their regret of omission and commission regarding neoadjuvant chemotherapy on a scale between 0 (no regret) and 100 (maximum regret). The threshold model and a multilevel mixed regression were applied to analyze respondents' attitudes toward neoadjuvant therapy.

RESULTS: The lowest regret of omission was elicited in the low-risk scenario, and the highest regret in the high-risk scenario (P < .001). The regret of the commission was diametrically opposite to the regret of omission (P ≤ .001). The disease-specific threshold mortality at which upfront surgery is favored over the neoadjuvant therapy progressively decreased from the low-risk to the high-risk scenarios (P ≤ .001). The nonsurgeons working in or with lower surgical volume centers (P = .010) and surgeons (P = .018) accepted higher disease-specific mortality after upfront surgery, which resulted in the lower likelihood of adopting neoadjuvant therapy.

CONCLUSION: Regret drives decision making in the management of pancreatic adenocarcinoma. Being a surgeon or a specialist working in surgical centers with lower patient volumes reduces the likelihood of recommending neoadjuvant therapy.