Major Outcomes Research Articles

What happens when private general practitioners receive incentivisation offers from pharmaceutical sales representatives? A qualitative study in Pakistan.

Pharmaceutical incentivisation of physicians for profit maximisation is a well-documented health system challenge. This study examined general practitioners' (GPs) reactions to pharmaceutical incentivisation offers in one region in Pakistan. We used the Standardised Pharmaceutical Sales Representative (SPSR) method and qualitative interviews with GPs. SPSRs were field researchers representing mock pharmaceutical companies who recorded their observations of 267 GPs' responses to pharmaceutical incentivisation offers. We triangulated SPSR data using qualitative interviews with a subset of the same GPs to gather information about how they interpreted different interaction outcomes. We found four major outcomes for GPs being offered incentives by pharmaceutical companies for prescribing medications. GPs might agree to make incentivisation deals, reject incentivisation offers, disallow PSRs to access them, or remain indeterminate with no clear indication of acceptance or rejection of incentivisation offers. GPs rejecting SPSRs' incentivisation offers indicated having active commitments to other pharmaceutical companies, not being able to work with unheard-of companies, and asking SPSRs to return later. The GP-pharmaceutical sales representative interaction that centres on profit-maximisation is complex as offers to engage in prescribing for mutual financial benefit are not taken up immediately. The SPSR method helps understand the extent of distortion of practices impacted by incentivisation. Such an understanding can support the development of strategies to control unethical behaviours.

Outcomes of "a new modification of Jensen technique combined with medial rectus recession" in patients with complete sixth cranial nerve palsy.

To report the outcomes of "our modified Jensen technique" for treating esotropia in cases with complete sixth cranial nerve (CN VI) palsy. This study is a 30-year case series of isolated complete CN VI palsy who underwent combined medial rectus recession and our modified Jensen operation. We modified the original technique by anchoring the muscle-unifying sutures to the sclera near the equator using a non-absorbable suture. Major outcomes such as postoperative diplopia, face turn, horizontal and vertical eye deviations, and abduction limitation were assessed. Successful surgery was defined as orthotropia or esotropia equal to or less than 8 prism diopters (PD) and the absence of any vertical deviation. Fifty-three cases with a mean age of 28 years old were included in this study. The male-to-female ratio was 3 to 1. Forty-five cases (85%) presented with unilateral palsy, whereas 8 patients (15%) had bilateral palsy. Trauma was the most common etiology (85%). Diplopia or face turn, presented in 42 patients before the operation, remained in seven cases after the operation. Primary position esotropia, which was the main complaint in all patients, decreased from 49 PD to 4 PD in unilateral palsy and from 101 PD to 10 PD in bilateral palsy. The mean reduction of abduction deficit was 1.78 in unilateral and 1.75 in bilateral palsy. The success rate was 76% in unilateral and 62% in bilateral palsy. Our modified Jensen operation was effective in treating patients with complete CN VI palsy, producing no significant permanent complications.

Use of ACEi/ARBs, SGLT2 inhibitors and MRAs can help us reach the therapeutic ceiling in CKD

ABSTRACT Chronic kidney disease (CKD) is increasing in prevalence worldwide, posing major implications for public health such as kidney failure requiring dialysis, and increased risk of cardiovascular and all-cause mortality. Diabetic and hypertensive kidney disease represent the two most common causes of CKD. Until a few years ago, lifestyle modifications, blood pressure, glycaemic and lipid control, along with angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker monotherapy were the only measures for retarding these two diseases and were the cornerstone of treatment for CKD of any aetiology. Effective application of all these measures could reduce the estimated glomerular filtration rate (eGFR) decline in proteinuric CKD roughly from 10–12 to 5–6 mL/min/1.73 m2/year, hence leaving a large unmet need in CKD treatment. In recent years, major kidney outcome trials showed that the addition of sodium–glucose cotransporter-2 inhibitors (SGLT2i) in patients with CKD with or without type 2 diabetes (T2D) and of the non-steroidal mineralocorticoid receptor antagonist finerenone in patients with CKD with T2D can largely improve kidney and cardiovascular outcomes. Elegant analyses of these trials shed further light on these effects, showing that SGLT2i or finerenone use on top of standard-of-care treatment in patients with albuminuric CKD can further reduce chronic eGFR annual loss to 2–2.5 mL/min/1.73 m2, while SGLT2is in normoalbuminuric CKD can reduce this loss <0.5 mL/min/1.73 m2, i.e. well below the aging-related GFR loss. Therefore, current evidence suggests that available treatments, if properly implemented, can help us reach the therapeutic ceiling in the majority of CKD patients.

Direct oral anticoagulants versus vitamin K antagonists in patients with atrial fibrillation and stage 5 chronic kidney disease under dialysis: A systematic review and meta-analysis of randomized controlled trials.

In patients with atrial fibrillation (AF) and normal or slightly impaired renal function, the use of direct oral anticoagulants (DOACs) is preferable to vitamin K antagonists (VKAs). However, in patients undergoing hemodialysis, the efficacy, and safety of DOACs compared with VKAs are still unknown. To review current evidence about the safety and efficacy of DOACs compared to VKAs, in patients with AF and chronic kidney disease under hemodialysis. We systematically searched PubMed, Scopus, and Cochrane databases for RCTs comparing DOACs with VKAs for anticoagulation in patients with AF on dialysis therapy. Outcomes of interest were: (1) stroke; (2) major bleeding; (3) cardiovascular mortality; and (4) all-cause mortality. Statistical analysis was performed using RevMan 5.1.7 and heterogeneity was assessed by I2 statistics. Three randomized controlled trials were included, comprising a total of 383 patients. Of these, 218 received DOACs (130 received apixaban; 88 received rivaroxaban), and 165 were treated with VKAs (116 received warfarin; 49 received phenprocoumon). The incidence of stroke was significantly lower in patients treated with DOACs (4.7%) compared with those using VKAs (9.5%) (RR 0.42; 95% CI 0.18-0.97; p = 0.04; I2 = 0%). However, the difference was not statistically significant in the case of ischemic stroke specifically (RR 0.42; 95% CI 0.17-1.04; p = 0.06; I2 = 0%). As for the major bleeding outcome, the DOAC group (11%) had fewer events than the VKA group (13.9%) but without statistical significance (RR 0.75; 95% CI 0.45-1.28; p = 0.29; I2 = 0%). There was no significant difference between groups regarding cardiovascular mortality (RR 1.23; 95% CI 0.66-2.29; p = 0.52; I2 = 13%) and all-cause mortality (RR 0.98; 95% CI 0.77-1.24; p = 0.84; I2 = 16%). This meta-analysis suggests that in patients with AF on dialysis, the use of DOACs was associated with a significant reduction in stroke, and a numerical trend of less incidence of major bleeding compared with VKAs, but in this case with no statistical significance. Results may be limited by a small sample size or insufficient statistical power.

Efficacy and safety of 40 mg osimertinib administered every other day for non-small cell lung cancer harboring an epidermal growth factor receptor mutation: A single-center retrospective cohort study.

Osimertinib is a first-line or adjuvant therapy for non-small cell lung cancer (NSCLC) harboring an epidermal growth factor receptor (EGFR) mutation. However, owing to the adverse events associated with treatment, certain patients cannot maintain a daily regimen of 80 or 40 mg. In this study, we examined the efficacy of 40 mg of osimertinib administered every other day. In this single-center, retrospective study, we evaluated patients with NSCLC harboring an EGFR mutation in whom treatment was initiated with 40 mg osimertinib every other day at our institution between May 2016 and June 2023. The major outcome was the duration of administering 40 mg osimertinib every other day. Six patients with NSCLC were evaluated. The median duration of 40 mg osimertinib intake every other day was 12.6 months. Four of the six patients weighed below 50 kg, and four experienced weight loss. Additionally, four of the six patients had severe renal impairment upon receiving 40 mg osimertinib every other day. Thus, our findings suggest the efficacy of administering 40 mg osimertinib every other day in patients with low bodyweight, weight loss, or severe renal impairment.

3D flow of variable properties viscoelastic nanofluids with impacts of Arrhenius energy and Cattaneo–Christov double-diffusion

In several situations, particularly, flow of viscoelastic nanofluids, the dynamic viscosity and thermal conductivity should be considered as variables due to their roles in various practical applications. Therefore, this article aims applying the Cattaneo–Christov double-diffusion theory to investigate the three-dimensional (3D) forced flow of second-grade viscoelastic nanofluids over a permeable stretching surface. The properties of the mixture are considered to be variables where the dynamic viscosity is exponentially varied with temperature and the thermal conductivity and Brownian motion are linearly dependent on temperature and concentration, respectively. The included medium is isotropic porous, and both heat generation and thermal radiation impacts are assumed. At the surface, the nanoparticles are either active or passively controlled, and the convective boundary conditions are considered for the surface temperature. The solution methodology is based on similarity transformations, and the numerical technique is based on 4th-order Runge-Kutta method. The major outcomes revealed that the growth in thermal relaxation time δ e and viscoelastic parameter K causes gradually decreases in temperature and nanoparticles features. Also, constant dynamic viscosity gives higher velocity features compared to the variable case. Furthermore, the considered range of thermal conductivity coefficient ε 1 gives an enhancement in rate of the heat transfer by 5.26%.

Major clinical outcomes of the regulation of metainflammation in patients with obesity in the light of nutrology: a systematic review

Introduction: Obesity stands out as a multifactorial disease that can cause several public health problems. There are 2.0 billion overweight and obese people in the world, and Brazil is in fifth place in the world ranking. A healthy nutritional status promotes immune function and can prevent the onset of a serious inflammatory process and severe infections, especially in times of pandemics such as COVID-19. Objective: It was to highlight the main clinical outcomes of the regulation of meta-inflammation in patients with obesity in the light of nutrology. Methods: The systematic review rules of the PRISMA Platform were followed. The research was carried out from August to September 2023 in Scopus, PubMed, Science Direct, Scielo, and Google Scholar databases. The quality of the studies was based on the GRADE instrument and the risk of bias was analyzed according to the Cochrane instrument. Results and Conclusion: A total of 130 articles were found. A total of 42 articles were fully evaluated and 29 were included and developed in the present systematic review study. Considering the Cochrane tool for risk of bias, the overall assessment resulted in 29 studies at high risk of bias and 21 studies that did not meet the GRADE. Most studies showed homogeneity in their results, with X2=71.7%>50%. Research has shown that unbalanced eating patterns, such as the Western diet, rich in simple sugars, refined carbohydrates, and saturated and trans fatty acids, lead to chronic inflammatory responses, increased adipose deposition, and future comorbidities associated with overweight and obesity. Calorie restriction decreased CRP in obese patients and diet administration over 12 weeks had a beneficial effect. Furthermore, obese patients with antioxidant supplementation had lower values of BMI, waist circumference, fasting blood glucose level, and assessment of the homeostasis model of insulin resistance when compared to the placebo group, as well as having lower levels of total cholesterol, triglycerides, LDL, malondialdehyde and tumor necrosis factor-alpha. n-3 PUFA supplementation can significantly reduce serum C-reactive protein (CRP), tumor necrosis factor α (TNFα), and interleukin 6 (IL-6) concentrations.

Impact of untreated chronic obstructive coronary artery disease on outcomes after transcatheter aortic valve replacement.

In transcatheter aortic valve replacement (TAVR) recipients, the optimal management of concomitant chronic obstructive coronary artery disease (CAD) remains unknown. Some advocate for pre-TAVR percutaneous coronary intervention, while others manage it expectantly. The aim of this study was to assess the impact of varying degrees and extent of untreated chronic obstructive CAD on TAVR and longer-term outcomes. The authors conducted a retrospective cohort study of TAVR recipients from January 2015 to November 2021, separating patients into stable non-obstructive or varying degrees of obstructive CAD. The major outcomes of interest were procedural all-cause mortality and complications, major adverse cardiovascular events, and post-TAVR unplanned coronary revascularization. Of the 1911 patients meeting inclusion, 75%, 6%, 10%, and 9% had non-obstructive, intermediate-risk, high-risk, and extreme-risk CAD, respectively. Procedural complication rates overall were low (death 0.4%, shock 0.1%, extracorporeal membrane oxygenation 0.1%), with no difference across groups. At a median follow-up of 21 months, rates of acute coronary syndrome and unplanned coronary revascularization were 0.7% and 0.5%, respectively, in the non-obstructive population, rising in incidence with increasing severity of CAD (P < .001 for acute coronary syndrome/unplanned coronary revascularization). Multivariable analysis did not yield a significantly greater risk of all-cause mortality or major adverse cardiovascular events across groups. One-year acute coronary syndrome and unplanned coronary revascularization rates in time-to-event analyses were significantly greater in the non-obstructive (98%) vs. obstructive (94%) subsets (Plog-rank< .001). Transcatheter aortic valve replacement can be performed safely in patients with untreated chronic obstructive CAD, without portending higher procedural complication rates and with relatively low rates of unplanned coronary revascularization and acute coronary syndrome at 1 year.

P846 Impact of 5-ASA discontinuation in children with ulcerative colitis under biological therapy

Abstract Background Mesalamine (5-ASA) is recommended as a first-line medication for inducing and maintaining remission in mild to moderate ulcerative colitis (UC), but indications regarding its use in children with moderate to severe disease treated with biologics are lacking. We aimed to evaluate whether discontinuing 5-ASA might impact the outcomes of children with UC treated with anti-TNFα. Methods Retrospective, single-center, case-control study of children with UC receiving anti-TNFα therapy between January 2018 and January 2023 and with a minimum follow of 6 months. Children who discontinued 5-ASA within six months from the biological therapy initiation were compared to those who continued mesalamine as maintenance therapy. Every 6 months, during a 2-year follow-up, major outcomes defined as disease flares, IBD-related hospitalization, surgery, need for step-up treatment were recorded. Results Ninety-eight children were included in the final analysis, 51 (52%) maintained 5-ASA and 47 (48%) discontinued 5-ASA. The 2 groups were comparable for all the baseline clinical and demographic characteristics. At 6 months, the cumulative incidence of major outcomes, acute severe colitis and need for step up treatment was significantly higher in children who discontinued 5-ASA (p &amp;lt; 0.05). Throughout the follow-up period, children who discontinued 5-ASA were at significant higher risk of hospitalization (Log Rank p=0.02), need for step up treatment (Log Rank p=0.02) and acute severe colitis (Log Rank p=0.003). Conclusion Our data suggest that 5-ASA discontinuation might have a negative impact on the clinical course of children with UC treated with anti-TNFα in terms of major outcomes. However, conclusive evidence regarding this matter requires prospective randomized trials.

Comparison of two single-pill dual combination antihypertensive therapies in Chinese patients: a randomized, controlled trial

BackgroundCurrent hypertension guidelines recommend combination of an angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker with a calcium-channel blocker or thiazide diuretic as initial antihypertensive therapy in patients with monotherapy uncontrolled hypertension. However, to what extent these two different combinations are comparable in blood pressure (BP)-lowering efficacy and safety remains under investigation, especially in the Chinese population. We investigated the BP-lowering efficacy and safety of the amlodipine/benazepril and benazepril/hydrochlorothiazide dual therapies in Chinese patients.MethodsIn a multi-center, randomized, actively controlled, parallel-group trial, we enrolled patients with stage 1 or 2 hypertension from July 2018 to June 2021 in 20 hospitals and community health centers across China. Of the 894 screened patients, 560 eligible patients were randomly assigned to amlodipine/benazepril 5/10 mg (n = 282) or benazepril/hydrochlorothiazide 10/12.5 mg (n = 278), with 213 and 212 patients, respectively, who completed the study and had a valid repeat ambulatory BP recording during follow-up and were included in the efficacy analysis. The primary outcome was the change from baseline to 24 weeks of treatment in 24-h ambulatory systolic BP. Adverse events including symptoms and clinically significant changes in physical examinations and laboratory findings were recorded for safety analysis.ResultsIn the efficacy analysis (n = 425), the primary outcome, 24-h ambulatory systolic BP reduction, was − 13.8 ± 1.2 mmHg in the amlodipine/benazepril group and − 12.3 ± 1.2 mmHg in the benazepril/hydrochlorothiazide group, with a between-group difference of − 1.51 (p = 0.36) mmHg. The between-group differences for major secondary outcomes were − 1.47 (p = 0.18) in 24-h diastolic BP, − 2.86 (p = 0.13) and − 2.74 (p = 0.03) in daytime systolic and diastolic BP, and − 0.45 (p = 0.82) and − 0.93 (p = 0.44) in nighttime systolic and diastolic BP. In the safety analysis (n = 560), the incidence rate of dry cough was significantly lower in the amlodipine/benazepril group than in the benazepril/hydrochlorothiazide group (5.3% vs 10.1%, p = 0.04).ConclusionsThe amlodipine/benazepril and benazepril/hydrochlorothiazide dual therapies were comparable in ambulatory systolic BP lowering. The former combination, compared with the latter, had a greater BP-lowering effect in the daytime and a lower incidence rate of dry cough.Trial registrationClinicalTrials.gov, NCT03682692. Registered on 18 September 2018.

Nomogram for predicting major bleeding after off-pump coronary artery bypass grafting

ObjectiveThe purpose of this investigation is to develop a novel nomogram for predicting major bleeding following off-pump coronary artery bypass grafting (CABG).MethodsBetween January 2012 and December 2022, 541 patients who underwent off-pump isolated primary CABG were included in a retrospective analysis. The primary outcome measure after off-pump CABG was major bleeding. Based on the outcomes of a multivariate analysis, nomograms were constructed. Using receiver operating characteristic analysis and calibration, the predictive accuracy of the nomograms was assessed. Using decision curve analysis (DCA), the clinical benefit of the nomograms was determined.ResultsWe categorized 399 and 142 patients in the “no major bleeding group” and “major bleeding group”, respectively. Age (odds ratio (OR) 1.038; 95% confidence interval (CI) 1.009–1.068; p = 0.009), body mass index (OR 0.913; 95% CI 0.849–0.982; p = 0.014), hemoglobin (OR 0.958; 95% CI 0.945–0.971; p < 0.001), sodium (OR 0.873; 95% CI 0.807–0.945; p = 0.001), blood urea nitrogen (OR 1.198; 95% CI 1.073–1.338; p = 0.001), and operation time (OR 1.012; 95% CI 1.008–1.017; p < 0.001) were independent predictors for major bleeding after off-pump CABG. The model based on independent predictors exhibited excellent discrimination and calibration, with good agreement between actual and nomogram-estimated probabilities of generalization. DCA demonstrated that nomogram-assisted decisions have a greater positive benefit than treating all patients or none.ConclusionsThe plotted nomogram accurately predicted major bleeding outcomes following off-pump CABG and may therefore contribute to clinical decision-making, patient treatment, and consultation services.

Glucagon-like peptide-1 receptor agonists and risk of major adverse liver outcomes in patients with chronic liver disease and type 2 diabetes

ObjectivePhase II trials suggest glucagon-like peptide-1 receptor (GLP1) agonists resolve metabolic dysfunction-associated steatohepatitis but do not affect fibrosis regression. We aimed to determine the long-term causal effect of GLP1 agonists...

Financial burden of tuberculosis diagnosis and treatment for patients in Ethiopia: a systematic review and meta-analysis

BackgroundDespite the diagnosis and treatment of tuberculosis (TB) given free of charge in many high-burden countries, the costs that patients face in the cascade of care remain a major concern. Here, we aimed to investigate the financial burden of TB diagnosis and treatment for people with TB in Ethiopia.MethodFor this systematic review and meta-analysis, we searched PubMed/MEDLINE, Embase, and Cochrane Center for Clinical Trials from December 1 2022 to 31 June 2023 for articles reporting the cost of diagnosis and treatment for patients regardless of their age with all forms of TB in Ethiopia. Major study outcomes were catastrophic costs, direct (out-of-pocket) pre-diagnosis, medical cost, and post-diagnosis costs, indirect (income loss) costs, coping costs, and total costs. We have used a threshold of 20% to define catastrophic costs. We used random-effects meta-analyses to calculate summary estimates of costs. R-studio software was used for analysis. The study is registered with PROSPERO: CRD42023387687.ResultTwelve studies, with a total of 4792 patients with TB, were included in our analysis. At the 20% threshold of total expenses, 51% of patients (2301 participants from 5 studies, 95% CI: 36-65%, I2 = 97%) faced catastrophic costs due to bacteriologically confirmed drug-sensitive pulmonary TB. Private facility diagnosis, drug-resistance TB, TB-HIV co-infection, hospitalization, and occupation were found to be associated with catastrophic costs. Reduction in the total cost spent by the patients was associated with digital adherence interventions, community-based direct observed therapy, short-course MDR-TB treatment regimens, and active case-finding. Pre-diagnosis costs had a positive correlation with diagnosis delays and the number of facilities visited until diagnosis. Post-diagnosis costs had a positive correlation with rural residence and inpatient treatments.ConclusionIrrespective of a national policy of free TB service, more than half of TB patients are suffering catastrophic costs due to drug-sensitive pulmonary TB in Ethiopia and most of the patients spend a lot of money during the pre-diagnosis period and intensive phase, but declined drastically over time. Active case-finding, digital adherence interventions, community-based treatment, and comprehensive health insurance coverage have the potential to minimize the financial burden of TB diagnosis and treatment.

Long-term follow-up of balloon-expandable valves according to the implantation strategy: insight from the DIRECTAVI trial

BackgroundSafety and feasibility of transcatheter aortic valve replacement (TAVR) without balloon aortic valvuloplasty (BAV) using the SAPIEN 3 balloon-expandable device has been previously demonstrated. The impact on long-term valve hemodynamic performances and outcomes remains however unknown. We evaluate long-term clinical and hemodynamic results according to the implant strategy (direct TAVR versus BAV pre TAVR) in patients included in the DIRECTAVI randomized trial (NCT02729519). MethodsClinical and echocardiographic follow-up until January 2023 was performed for all patients included in the DIRECTAVI trial since 2016 (n=228). The primary endpoint was incidence of moderate/severe hemodynamic valve deterioration (HVD), according to the Valve Academic Research defined Consortium-3 criteria (increase in mean gradient ≥10 mmHg resulting in a final mean gradient ≥20 mmHg, or new/worsening aortic regurgitation of 1 grade resulting in ≥ moderate aortic regurgitation). ResultsMedian follow-up was 3.8 (2.2-4.7) years. Mean age at follow-up was 87 ±6.7 years. No difference in incidence of HVD in the direct implantation group compared to the BAV group was found (incidence of 1.97 per 100 person-years and 1.45 per 100 person-years, respectively, p=0.6). Prevalence of predicted prothesis-patient mismatch was low (n=13 [11.4%] in the direct TAVR group versus n=15 [13.2%] in BAV group) and similar between both groups (p=0.7). Major outcomes including death, stroke, hospitalization for heart failure and pacemaker implantation were similar between both groups, (p=0.4, p=0.7, p=0.3 and p=0.3 respectively). ConclusionDirect implantation of the balloon-expandable device in TAVR was not associated with an increased risk of moderate/severe HVD or major outcomes up to 6-year follow-up. These results guarantee wide use of direct balloon-expandable valve implantation, when feasible. Clinical Trials Registration numberNCT05140317

Communication Strategies of Transplant Hematologists in High-Risk Decision-Making Conversations.

Shared decision making (SDM) is essential to empower patients with blood cancers to make goal-concordant decisions about allogeneic hematopoietic cell transplantation. This study characterizes communication strategies used by hematologists to discuss treatment options and facilitate SDM with patients in this high-risk, high-reward setting. We recruited US hematologists who routinely perform allogeneic hematopoietic cell transplant through email. Participants conducted up to an hour-long video-recorded encounter with an actor portraying a 67-year-old man with recently diagnosed high-risk myelodysplastic syndrome. We transcribed and qualitatively analyzed video-recorded data. The mean age of participants (N = 37) was 44 years, 65% male, and 68% White. Many hematologists included similar key points in this initial consultation, although varied in how much detail they provided. Their discussion of treatment options included transplant and chemotherapy and less commonly supportive care or clinical trials. They often emphasized transplant's potential for cure, discussed transplant chronologically from pretransplant considerations through the post-transplant course, and outlined risks, complications, and major outcomes. Hematologists referred to several elements that formed the basis of treatment decision making. The strength of their treatment recommendations ranged from strong recommendations for transplant or chemotherapy to deferrals pending more information. Hematologists also varied in the extent to which they indicated the decision was physician-driven, patient-led, or shared. The transplant decision-making discussion is complex. Identification of similar content areas used by hematologists can be used as the basis for a communication tool to help hematologists discuss allogeneic hematopoietic cell transplant with patients.

Misclassified Alcohol-related Liver Disease is Common in Presumed Metabolic Dysfunction-associated Steatotic Liver Disease and Highly Increases Risk for Future Cirrhosis

Background and aimsAlcohol overconsumption is a risk factor for disease progression in patients with presumed metabolic dysfunction-associated steatotic liver disease (MASLD). How commonly this occurs and how it affects progression to major adverse liver outcomes (MALO) is not well known. MethodsWe did a register-based cohort study, including all patients with a diagnosis of MASLD in Sweden between 1987 and 2020. Patients were stratified on co-occurrence of diagnoses of alcohol-related liver disease (ALD) or alcohol use disorder (AUD) prior to MASLD diagnosis. Incident MALO:s were derived from national registers. Cox regression was used to calculate hazard ratios for incident MALO. ResultsA total of 15,107 patients with MASLD were identified. Median age was 55 years and 52% were female. 1,843 (12%) had a prior diagnosis of ALD or AUD. During follow-up, a further 787 (5.2%) received a diagnosis of ALD or AUD. Patients with previous ALD or AUD diagnoses at or before baseline had considerably higher rates of MALO compared to patients without (19.5% vs 7.8%, aHR=3.12, 95%CI=2.74-3.55). Acquiring an ALD or AUD diagnosis after MASLD diagnosis was associated with higher rates of MALO (aHR=5.81, 95%CI=4.90-6.88). ConclusionsALD or AUD is commonly diagnosed prior to or after MASLD diagnosis. Such patients have considerably higher rates of progression to MALO. Correctly separating between MASLD and ALD is vital to assess prognosis.

An Endovascular- Versus a Surgery-First Revascularization Strategy for Chronic Limb-Threatening Ischemia: A Meta-Analysis of Randomized Controlled Trials

Timely revascularization is essential for limb salvage and to reduce mortality in patients with chronic limb-threatening ischemia (CLTI). In patients who are candidates for endovascular therapy and surgical bypass, the optimal revascularization strategy remains uncertain. Recently published randomized controlled trials (RCTs) have presented conflicting results. We conducted a trial-level meta-analysis to compare the outcomes between endovascular-first and surgery-first strategies for revascularization. PubMed, Web of Science, and the Cochrane Library were searched to identify RCTs comparing the outcomes of endovascular-first versus surgery-first strategies for revascularization in patients with CLTI. Data were pooled for major outcomes and their aggregate risk ratios (RRs) with 95% confidence intervals were calculated using a random-effects model. Kaplan-Meier curves for amputation-free survival and overall survival time were plotted using the pooled aggregated data from published curves, with their corresponding hazard ratios (HRs) and 95% confidence intervals reported for up to 5 years of follow-up. A total of 3 RCTs with 2,627 patients (1,312 endovascular-first and 1,315 surgery-first) were included in the meta-analysis. Of these, 1,864 patients (70.9%) were men and 347 (13.2%) were older than 80 years. Comparing the endovascular-first and surgery-first approaches, there was no significant difference in the overall (HR 0.92 [0.83 to 1.01], p = 0.09) or amputation-free survival (HR 0.98 [0.92 to 1.03], p = 0.42), reintervention (RR 1.24 [0.74 to 2.07], p = 0.41), major amputation, (RR 1.16 [0.87 to 1.54], p = 0.31), or therapeutic crossover (RR 0.92 [0.37 to 2.26], p = 0.85). In conclusion, data from available RCTs suggest that there is no difference in clinical outcomes between endovascular-first and surgery-first revascularization strategies for CLTI. A planned patient-level meta-analysis may provide further insight.

Vitamin D and human health: evidence from Mendelian randomization studies.

We summarized the current evidence on vitamin D and major health outcomes from Mendelian randomization (MR) studies. PubMed and Embase were searched for original MR studies on vitamin D in relation to any health outcome from inception to September 1, 2022. Nonlinear MR findings were excluded due to concerns about the validity of the statistical methods used. A meta-analysis was preformed to synthesize study-specific estimates after excluding overlapping samples, where applicable. The methodological quality of the included studies was evaluated according to the STROBE-MR checklist. A total of 133 MR publications were eligible for inclusion in the analyses. The causal association between vitamin D status and 275 individual outcomes was examined. Linear MR analyses showed genetically high 25-hydroxyvitamin D (25(OH)D) concentrations were associated with reduced risk of multiple sclerosis incidence and relapse, non-infectious uveitis and scleritis, psoriasis, femur fracture, leg fracture, amyotrophic lateral sclerosis, anorexia nervosa, delirium, heart failure, ovarian cancer, non-alcoholic fatty liver disease, dyslipidemia, and bacterial pneumonia, but increased risk of Behçet's disease, Graves' disease, kidney stone disease, fracture of radium/ulna, basal cell carcinoma, and overall cataracts. Stratified analyses showed that the inverse association between genetically predisposed 25(OH)D concentrations and multiple sclerosis risk was significant and consistent regardless of the genetic instruments GIs selected. However, the associations with most of the other outcomes were only pronounced when using genetic variants not limited to those in the vitamin D pathway as GIs. The methodological quality of the included MR studies was substantially heterogeneous. Current evidence from linear MR studies strongly supports a causal role of vitamin D in the development of multiple sclerosis. Suggestive support for a number of other health conditions could help prioritize conditions where vitamin D may be beneficial or harmful.

Utility of Cardiac POCUS in the Evaluation of Pediatric Chest Pain in the Emergency Department

Background/Objective:Chest pain in children is rarely caused by a life-threatening pathology. Despite the rarity of potentially life-threatening disease, most children presenting to EDs are evaluated with chest radiographs and laboratory tests without yielding helpful information that significantly changes immediate management. While the utilization of cardiac Point-of-Care Ultrasound (POCUS) by adult emergency physicians has become standard of practice, the data in pediatric emergency departments (PED) is not as robust. This study aims to describe practice patterns in the evaluation of pediatric chest pain presenting in a PED and determine clinical outcomes.&#x0D; Methods:We reviewed charts of previously healthy children aged &lt;18 years old who presented to Riley Children’s Hospital from January 2019 to July 2020 with a chief complaint of chest pain. Patients with known medical history, prior evaluations by a pediatric cardiologist, transfers from other hospital with existing workup were excluded. Patient demographics, laboratory tests and imaging ordered while in the ED, electrocardiography (EKG), consults with subspecialties, disposition and follow up plans were analyzed. We categorized clinical significance of PED interventions as minor, moderate, or major.&#x0D; Results:Out of three hundred and nineteen patients included in the study, 79.6% (254) received chest radiographs, 93.4% (298) underwent EKG, and 4.1% (13) received cardiac POCUS. The findings of these orders prompted minor interventions in 92.8% (296) of patients, moderateintervention in 4.7% (15) of patients, and major intervention in 2.5% (8) of patients.&#x0D; Conclusion and Implications:These results show a lack of use for POCUS in pediatric patients presenting with chest pain while chest radiography is preferred in the ED. Additionally, POCUS did not result in any moderate or major significant clinical outcomes.

New Insights into Rate Control: Time in Target Range of Resting Heart Rate and Major Adverse Outcomes in Atrial Fibrillation.

Few studies have examined the relationship between the fluctuation of heart rate control over time and cardiovascular outcomes in patients with atrial fibrillation. Our study sought to evaluate the independent association between time in target range (TIR) of resting heart rate and cardiovascular outcomes in the AFFIRM (Atrial Fibrillation Follow-Up Investigation of Rhythm Management) study. Target range of resting heart was defined as less than 80 beats per minute (bpm) for both rate and rhythm control groups. Time in target range was estimated over the first 8 months of follow-up using Rosendaal interpolation method. The association between TIR of resting heart rate and cardiovascular outcomes was estimated using adjusted Cox proportional hazards regression models. Time in target range of resting heart rate (months 0 through 8) was 71 ± 34% in the rate control group and 83 ± 27% in the rhythm control group. Each 1-SD increase in TIR of resting heart rate was significantly associated with lower risk of major adverse cardiovascular events after full adjustment for demographics, medical history and history of prior heart surgery, as well as all-cause mortality. Time in target range of resting heart rate independently predicts the risk of cardiovascular outcomes in patients with atrial fibrillation. Long-term maintenance of heart rate on target is of great importance for patients with atrial fibrillation.