Significant Mortality Research Articles

Prescriber Adherence to Antihypertensive Prescription Guidelines and the Impact of Patient Socioeconomic Factors: A Cross-Sectional Study Using Data From the IrishLongitudinal Study on Ageing.

Uncontrolled hypertension causes significant morbidity and mortality worldwide. Several prescribing guidelines have been created to address this, however, prescriber adherence to guidelines is influenced by various sociodemographic patient factors. This study aims to determine the effects of these patient factors on prescriber adherence to antihypertensive prescription guidelines. A secondary analysis of data from the first wave of The Irish Longitudinal Study on Ageing (TILDA), was conducted. Participants were included if they reported previous hypertension diagnoses. Antihypertensive medication regimes were compared with the prescribing guidance in the 2011 NICE hypertension guidelines. The effects of patient sociodemographic factors on prescriber adherence to guidelines, and the effect of prescriber adherence on blood pressure control (≥ 140/90 mmHg), were determined using binomial logistic regression models. A total of 2992 participants were included in this analysis; 54.9% female with mean age 65.7 years (±9.23). Male sex and older age, and lower socioeconomic status were associated with increased prescriber guideline adherence. Prescribers were less likely to adhere to guidelines in female patients ≥ 55 years (Relative Risk [RR] 0.75 [0.62, 0.91]), and female patients across all age groups (RR 0.80 [0.67, 0.95]). Better blood pressure control was seen with medication regimes adherent to prescription guidelines (140.38 (±18.98)/83.09 (±11.02) mmHg adherent vs. 141.66 (±19.86)/84.77 (±11.71) mmHg non-adherent). This study highlights the effect of patient sex on prescriber adherence to antihypertensive prescription guidelines, emphasizing a larger issue of systemic undertreatment of females observed within healthcare. Further research is needed to determine the reasons for such differences in hypertensive care.

A prospective study of acute kidney injury in intensive care setting according to Rifle definition and its mortality predictors

Background: Acute Kidney Injury (AKI) in ICUs is associated with high morbidity, mortality, prolonged hospital stays, increased costs, and risk of progression to Chronic Kidney Disease (CKD). Early identification of AKI is essential. Aims and Objectives: To determine the incidence of AKI in ICU patients using the RIFLE criteria. · To identify etiological factors and comorbid conditions associated with AKI. · To assess the outcomes of AKI based on the RIFLE criteria. · To explore age, gender, serum creatinine, Fe Na, and urine spot Na as predictors of AKI mortality. Materials and Methods: A prospective observational study was conducted at Al-Ameen Medical College and Hospital, Vijayapura, with 83 patients over two years. ICU patients were monitored for AKI development using the RIFLE criteria. Results: Univariate logistic regression showed oliguria as a significant predictor of mortality (OR: 0.461). Among AKI survivors (n=51), the highest number (41.2%) were aged 50–59 years. In AKI deaths (n=32), most (40.6%) were over 60 years. Sepsis (39.2%) and shock (31.4%) were common in survivors, while sepsis (71.9%) dominated among deaths Conclusion: Early identification of high-risk AKI patients is crucial. Infections and hypotension drive significant mortality risk. Oliguric patients and those on ventilation require close monitoring. Timely diagnosis and management, especially of infections and multi-organ dysfunction, are key to improving outcomes. Haemodialysis was the preferred treatment.

Seabird and sea duck mortalities were lower during the second breeding season in eastern Canada following the introduction of highly pathogenic avian influenza A H5Nx viruses

ABSTRACT Capsule H5N1 clade 2.3.4.4b viruses have caused significant mortality events in various wild bird species across Europe, North America, South America, and Africa. In North America, the largest impacts on wild birds have been in eastern Canada, where at least 40,391 wild birds were reported to have died from highly pathogenic avian influenza (HPAI) between April and September 2022. Aims To apply previously established methods to collect and quantify the total reported wild bird mortality in eastern Canada from October 2022 to September 2023. Methods We documented the spatial, temporal, and taxonomic patterns of wild bird mortality in the 12 months that followed a mass mortality event in the summer of 2022, and then quantified the observed differences in mortality across the spring and summer (April to September) of 2022 and 2023. In eastern Canada, there was high uncertainty about whether 2023 would bring another year of devastating HPAI-linked mortalities. Results Mortalities in the spring and summer of 2023 were 93% lower than in 2022, but encompassed a wider diversity of species. Mortalities in the fall/autumn and winter (non-breeding season) were dominated by waterfowl, while mortalities during the spring and summer (breeding season) were dominated by seabirds. Due to a low prevalence of HPAI among a subset of tested birds, we cannot broadly attribute the reported mortalities in 2023 to HPAI. However, our analysis did identify three notable mortality events linked to HPAI, involving at least 1646 Greater Snow Geese Anser caerulescens atlanticus, 232 Canada Geese Branta canadensis, and 212 Northern Gannets Morus bassanus. The latter reflected the continuation of a mortality event from the Northern Gannet’s 2022 breeding season. Conclusions This study emphasizes the ongoing need for H5Nx surveillance and mortality assessments as the patterns of mortality in wild populations continue to change.

An evaluation of vilobelimab (anti-C5a) as a cost-effective option to treat severely ill mechanically ventilated patients with COVID-19.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. COVID-19 patients in intensive care units (ICUs) requiring invasive mechanical ventilation (IMV) have few available treatment options. PANAMO, a multicenter, double-blind, randomized, placebo-controlled phase 3 study of vilobelimab, which blocks the inflammatory process caused by complement component 5a, demonstrated a significant mortality benefit at 28 and 60 days in these patients. A cost-effectiveness analysis was conducted to assess the incremental cost per quality-adjusted life-year (QALY). A Markov model was used to estimate QALYs and the incremental cost-effectiveness ratio (ICER) of vilobelimab plus standard of care (SOC) versus SOC alone. The model simulated progression from severe COVID-19 to survival or death over a lifetime horizon. Outcomes data (COVID-19 all-cause mortality and renal replacement therapy) were incorporated from the PANAMO trial. COVID-19 mortality estimates were based on Centers for Disease Control and Prevention age-specific survival data. Utility values and hospital costs came from the literature. Vilobelimab cost was obtained from RED BOOK Online. For COVID-19 ICU patients, total costs of care were $103,414 (SOC) and $132,247 (SOC plus vilobelimab), respectively, resulting in an incremental cost of $28,833. SOC provided 6.70 QALYs versus 7.99 QALYs for vilobelimab, an additional 1.29 QALYs. The ICER for vilobelimab plus SOC versus SOC alone was $22,287/QALY. Probabilistic sensitivity analysis demonstrated the robustness of the cost-effectiveness result as vilobelimab plus SOC was favored at a willingness-to-pay threshold of $50,000 in over 81% of iterations. Vilobelimab provides a cost-effective option to treat ICU patients with severe COVID-19 receiving IMV compared to SOC, at well below the commonly accepted $50,000 US willingness-to-pay threshold.

Effects of two non-drug interventions on pain and anxiety in the nursing process of burn patients: a literature review with meta-analysis

BackgroundBurns are a global health issue causing significant mortality and high medical costs. Non-pharmacological interventions such as music therapy and virtual reality (VR) therapy have shown potential in alleviating pain and anxiety in burn patients. This study systematically evaluates the impact of these interventions using a network meta-analysis.MethodsA systematic review and network meta-analysis were conducted according to PRISMA 2020 guidelines and registered in PROSPERO (CRD42024566536). Searches in PubMed, Cochrane Library, Web of Science, and Embase up to November 22, 2023, identified randomized controlled trials (RCTs) involving music therapy or VR therapy in burn patients. The Cochrane Risk of Bias Tool (2.0) assessed study quality. Data were analyzed using StataMP-64 software.ResultsSeventeen RCTs with 1,119 burn patients were included. Both music therapy and VR therapy significantly reduced pain and anxiety compared to control groups. Music therapy was more effective for pain reduction (SUCRA: 85.4%), while VR therapy was superior for anxiety relief (SUCRA: 79.5%).ConclusionMusic therapy and VR therapy effectively reduce pain and anxiety in burn patients. Integrating these interventions into burn care can enhance patient outcomes. Further research is needed to confirm these findings and optimize individualized treatment plans.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, PROSPERO (CRD42024566536).

Significance of Initial Chest CT Severity Score (CTSS) and Patient Characteristics in Predicting Outcomes in Hospitalized COVID-19 Patients: A Single Center Study

The aim of this study is to examine the prognostic role of initial chest computed tomography severity score index (CTSS) and its association with demographic, socio-epidemiological, and clinical parameters in COVID-19 hospitalized patients. A retrospective study included patients who were hospitalized in the COVID Hospital of the Clinical Hospital Center Kosovska Mitrovica from July 2020 to March 2022. We compared patient characteristics and outcome of their hospital stay with values of CT severity score (mild, moderate, and severe form of the disease). Patients with severe disease were statistically significantly older, they treated more days, and they presented statistically significant highest mortality rate compared to mild and moderate forms. Smokers and obese were significantly more frequent among patients with higher CT, while vaccinated patients were more common among those with a mild form. Biochemical parameters at admission also showed statistical significance between the examined groups. We can conclude that by employing the initial CT severity score as the strongest predictor of mortality, it is possible to predict the outcome in hospitalized patients. A comprehensive examination of the patient upon admission, including determining the extent of inflammatory changes in the lungs using computed tomography, the levels of oxygen saturation, and other laboratory parameters, can assist doctors in making an adequate clinical evaluation and apply appropriate therapeutic protocols in the treatment of COVID-19.

Determining the Accuracy of Two Pelvic Ring Classification Systems: AO Tile and Young Burgess- A Systematic Review

Pelvic ring fractures (PRF) are high energy fractures with an incidence of 20/100,000 among all fractures and significant associated morbidity and mortality. PRF are often classified using Young-Burgess classification, and Tile AO classification. This project aims to review the literature comparing the two classification systems for reliability, clinical implications and guide for treatment plan. Google Scholar search was performed with the following words: “Young”, “Burgess”, “Tile”, “presentation”, “treatment”, “pelvic ring” in the Title/Abstract. After review of 828 results, 11 articles are included in this systematic review. Reliability of the classification systems positively correlated with an increase in years of experience. When comparing the reliability, Young-Burgess is shown to have moderate-to-substantial level of agreement for classifying pelvic fractures when accounting for expertise level, while Tile showed substantial agreement between specialists only. Young-Burgess better predicted mortality as compared to Tile, while another study found no significant difference. Tile B and LC fractures are found to have higher frequency of hemodynamic instability and undergo laparotomies more frequently. When comparing treatment options, there is a moderate level of agreement for the treatment option solely based on images. However, the question of how the classifications guide treatment outcomes remains unanswered. After review of current literature, it appears that Young-Burgess classification has slightly higher reliability and better prediction for mortality than Tile. However, there is a need for further research on how the classification systems can determine the treatment and outcomes to improve morbidity and mortality.

The spectrum of congenital heart defects among children at federal medical centre, Asaba, Nigeria

Background: Congenital heart disease (CHD) is a common problem in the pediatric age group with significant morbidity and mortality when early diagnosis and prompt treatment are not instituted. Recent reports have shown an increasing burden of this disease. This study was aimed at documenting the prevalence and patter of CHD among children at Federal Medical Centre (FMC), Asaba. Methods: This was a hospital based retrospective observational study. The records of all children seen at the department of pediatrics FMC Asaba who did cardiac echo-cardiogram between 2019 and 2022 were reviewed. The clinical, demographic and echocardiogram details were retrieved, descriptive analysis was done using Statistical Package for Social Science (SPSS), version 21. Results: A total of 324 children were identified to have CHD of which 178 (54.9%) were male and 146 (45.1%) were female given a male to female ration of 1.2:1. Ventricular septal defect (27.7%) was the most common congenital heart disease seen while tetralogy of fallot 25 (7.7%) was the most prevalent cyanotic congenital heart disease. Trisomy 21 (5.5%) was the most frequently identified chromosomal abnormality identified among the subjects. A total of 61 (18.8%) of the subject died. Conclusions: The spectrum of CHD in our study was largely similar to previous documentation in the literatures. The mortality rate among children with CHD in our environment is still high largely due to non-availability of surgical intervention.

Outcomes of odontoid fractures with associated cardiac arrest: retrospective bi-center case series and systematic literature review

BackgroundOdontoid fractures from high-energy trauma are associated with significant morbidity and mortality, including spinal cord injury, neurological damage, and cardiac arrest. The literature on odontoid fractures leading to cardiac arrest is limited to isolated case reports. This study aims to conduct a retrospective bi-center case series and a systematic review of existing literature.MethodsWe conducted a retrospective bi-center case series on patients with odontoid fractures from high-energy trauma who experienced post-traumatic cardiac arrest with return of spontaneous circulation (ROSC) after CPR from two Level 1 Trauma Centers (2008–2024). The primary outcome was in-hospital mortality; secondary outcomes included epidemiological, pre-hospital, and in-hospital data, and CT and MRI findings. Additionally, we performed a systematic literature review to summarize existing evidence.ResultsThe study included 25 patients (mean age 71.1 ± 12.3 years, SD; 8 females). The mortality rate was 92% (23 patients). Median downtime before CPR was 5.0 min (IQR: 7.0), with CPR lasting 17.0 min (IQR: 13.0), primarily initiated by professionals (60%). All patients were quadriplegic. Type II Anderson d’Alonzo fractures were most common (88%), with all patients showing myelopathy on MRI. Only three patients (12%) underwent surgical intervention due to favorable prognosis. Our literature review identified seven case reports, with two patients surviving and one achieving full recovery.ConclusionsIn this case series, patients experiencing cardiac arrest after odontoid fractures exhibited high mortality rates despite comprehensive management at Level 1 trauma centers. Survivors faced significant and enduring morbidity.

Clinical Management and Pathophysiology of Infective Endocarditis: An Updated Review of Diagnostic Challenges and Therapeutic Approaches

Infective endocarditis (IE) is a severe and life-threatening condition characterized by infection of the endocardial surface of the heart, primarily affecting the heart valves. Despite advances in diagnostic techniques and antimicrobial therapies, IE remains associated with significant morbidity and mortality due to its complex pathogenesis and clinical variability. This article reviews the most recent developments in the pathophysiology, diagnostic criteria, and management strategies of infective endocarditis. Key issues such as microbial etiology, including common pathogens like Staphylococcus aureus and Streptococcus species, are discussed alongside less frequent organisms and their association with specific patient populations. The article emphasizes the importance of early diagnosis using advanced imaging modalities, such as echocardiography and PET-CT, and laboratory findings, particularly blood cultures. We explore both medical and surgical management strategies, highlighting the role of antibiotic therapy and the indications for valve surgery. A focus is given to the management of complex cases, including prosthetic valve endocarditis and infections in immunocompromised patients. The article aims to provide clinicians with a comprehensive understanding of the evolving landscape of infective endocarditis and its implications for patient outcomes.

Targeted hematopoietic stem cell depletion through SCF-blockade

BackgroundHematopoietic stem cell transplantation (HSCT) is a curative treatment for many diverse blood and immune diseases. However, HSCT regimens currently commonly utilize genotoxic chemotherapy and/or total body irradiation (TBI) conditioning which causes significant morbidity and mortality through inducing broad tissue damage triggering infections, graft vs. host disease, infertility, and secondary cancers. We previously demonstrated that targeted monoclonal antibody (mAb)-based HSC depletion with anti(α)-CD117 mAbs could be an effective alternative conditioning approach for HSCT without toxicity in severe combined immunodeficiency (SCID) mouse models, which has prompted parallel clinical αCD117 mAbs to be developed and tested as conditioning agents in clinical trials starting with treatment of patients with SCID. Subsequent efforts have built upon this work to develop various combination approaches, though none are optimal and how any of these mAbs fully function is unknown.MethodsTo improve efficacy of mAb-based conditioning as a stand-alone conditioning approach for all HSCT settings, it is critical to understand the mechanistic action of αCD117 mAbs on HSCs. Here, we compare the antagonistic properties of αCD117 mAb clones including ACK2, 2B8, and 3C11 as well as ACK2 fragments in vitro and in vivo in both SCID and wildtype (WT) mouse models. Further, to augment efficacy, combination regimens were also explored.ResultsWe confirm that only ACK2 inhibits SCF binding fully and prevents HSC proliferation in vitro. Further, we verify that this corresponds to HSC depletion in vivo and donor engraftment post HSCT in SCID mice. We also show that SCF-blocking αCD117 mAb fragment derivatives retain similar HSC depletion capacity with enhanced engraftment post HSCT in SCID settings, but only full αCD117 mAb ACK2 in combination with αCD47 mAb enables enhanced donor HSC engraftment in WT settings, highlighting that the Fc region is not required for single-agent efficacy in SCID settings but is required in immunocompetent settings. This combination was the only non-genotoxic conditioning approach that enabled robust donor engraftment post HSCT in WT mice.ConclusionThese findings shed new insights into the mechanism of αCD117 mAb-mediated HSC depletion. Further, they highlight multiple approaches for efficacy in SCID settings and optimal combinations for WT settings. This work is likely to aid in the development of clinical non-genotoxic HSCT conditioning approaches that could benefit millions of people world-wide.

Epidemiological, clinical, paraclinical, evolutionary, and therapeutic aspects of hypertensive patients infected by COVID-19: about 702 patients in our city

Abstract Introduction Hypertension (HT) is a major cardiovascular risk factor frequently observed in COVID-19 patients. This study aimed to determine the frequency of hypertensive patients infected with COVID-19 at a national hospital, describe their epidemiological, clinical, paraclinical, and therapeutic profile, their disease progression, and identify factors associated with death. Methodology A retrospective, descriptive, and analytical study was conducted over 24 months and 4 days, from 27 March 2020 to 30 March 2022, at national hospital. Included were hospitalized patients at a hospital with a confirmed COVID-19 diagnosis, known hypertensives, regardless of gender, and with a hospitalization record. COVID-19 diagnosis was based on a positive SARS-CoV-2 RT-PCR or a positive COVID Rapid Diagnostic Test. Data were collected using a survey form, with a p-value less than 0.05 considered statistically significant for bivariate analysis. Results The study enrolled 702 patients, a hospital frequency of 23.95%. The average age was 65.14 ± 12.24 years with a sex ratio of 0.81. Comorbidities were predominantly diabetes (40.5%) and dyslipidemia (4.8%). Common symptoms included cough (65%), dyspnea (42.3%), fever (47.4%), and asthenia (35.9%). Blood pressure was normal in 15.2%, high-normal in 16.8% of patients. HT was Grade I in 12.1%, Grade II in 10%, and Grade III in 6.8% of the population, with blood pressure unmeasurable in 0.3% of known hypertensive patients. SARSCOV2 infection was mild in 34.2% and moderate in 42.8% of cases. CT scans showed extensive (31.8%), severe (25.9%), moderate (25.6%), critical (8.5%), and minimal (7.9%) lung damage. Treatment mainly consisted of ACE inhibitors (29%), ACE inhibitors in combination with another antihypertensive (8.4%), and ARBs in combination with an antihypertensive (). The average hospital stay was 12.85 days with a favorable outcome in 81% and a mortality rate of 15.5%. Factors associated with death included not being vaccinated against COVID-19 (HR: 11.70; 95% CI: 1.324-103.519), critical clinical form (HR: 11.70; 95% CI: 1.324-103.519), pulmonary consolidation (HR: 8.87; 95% CI: 7.539-24.207), high creatinine (HR: 4.69; 95% CI: 1.360-16.181), critical CT thoracic level (HR: 2.42; 95% CI: 1.020-5.745), and not taking ARBs (HR: 6.02; 95% CI: 2.812-12.889). Conclusion HT can be associated with COVID-19, impacting the disease's prognosis with significant mortality. Preventing its incidence and morbidity/mortality is crucial.

Scleroderma renal crisis, an increasingly rare but persistently challenging condition: a retrospective cohort study

Abstract Objective Scleroderma renal crisis (SRC) is associated with high morbidity and mortality and there remain unmet needs regarding early identification and treatment. We aimed to assess risk factors for and the outcomes of SRC at a large Australian tertiary hospital. Methods Seventeen incident SRC cases were diagnosed between 2012–2022. Demographic, systemic sclerosis (SSc) manifestations, and treatment data were extracted. Using data from the Australian Scleroderma Cohort Study (ASCS) (n = 483), logistic regression analysis was performed to identify risk factors for SRC. Results The prevalence of SRC was 3.52%. The median SSc disease duration at SRC onset was 2 (IQR 1–4) years. Peak creatinine occurred at a median of 11 (IQR 5–14) days post-SRC diagnosis with a median peak creatinine of 144 (IQR 86–306) µmol/l. Nine (52.94%) SRC patients had evidence of acute neurologic and/or cardiac complications. Acute hemofiltration was required in 3 (17.65%) patients. Over the follow-up period, 7 (41.18%) SRC patients died 2.75 (IQR 0.74–7.25) years after SRC onset. Patients with SRC were more likely to be male (OR 9.73, 95%CI 3.57–26.56), have diffuse disease (OR 23.16, 95%CI 5.22–102.80), and have antibodies to Scl70 (OR 3.34, 95%CI 1.24–9.04) or RNA polymerase III (RNAPIII) (OR 5.15, 95%CI 1.91–13.89). Conclusion SRC is an uncommon manifestation, but outcomes remain poor. A significant proportion of patients presenting with SRC in Australia are positive for Scl70 or RNAPIII antibody. Despite relatively low peak serum creatinine and rates of renal replacement therapy, SRC was still associated with significant mortality.

The incidence of death and risk factors for mortality following major bleeding in patients anticoagulated with factor Xa inhibitors: an observational study in the UK clinical setting (AXIOM UK)

Abstract Background Major bleeding (MB) in association with anticoagulant use results in significant mortality. Mortality can be directly attributed to bleeding, or may follow bleeding complications such acute kidney injury, myocardial infarction, stroke and other cardiovascular events. Most real-world data relating to bleeding mortality is derived from cohorts receiving vitamin-K antagonists. We investigated all-cause mortality (ACM) after MB in a large cohort anticoagulated with Factor Xa inhibitors (FXai), e.g. direct oral anticoagulants (DOAC) rivaroxaban, apixaban and low-molecular-weight heparins (LMWH). Purpose To describe incidence rates of and risk factors for ACM following MB in patients receiving FXai. To investigate MB related ACM by bleeding site, treatment indication, treatment subgroups and individual and cumulative time periods. Methods Retrospective cohort analysis of new users of FXai, between 2012-2020, for therapeutic indications including atrial fibrillation (AF), venous thromboembolism, bioprosthetic cardiac valves or adult congenital heart disease was conducted. MB was defined by the International Society on Thrombosis and Haemostasis (ISTH) criteria. Incidence rates were reported per 100 person-years. Sub-distribution hazard ratios with 95% confidence intervals (95% CI) were estimated from Fine and Gray regression models accounting for competing risks. Results In 240,357 new users of FXai, 88% used an oral FXai. The most common FXai indication was AF (72%). There were 10,163 patients (4.2%) hospitalised for bleeding events during FXai use. Of these, 3,873 MB events (38%) fulfilled the ISTH definition of MB and 1312 died during 3,542 person years of follow-up (Table 1). ACM incidence rates varied by time, indication, bleeding subtype, and drug type. ACM occurred in 926 patients (23.9%) in the first month. Mortality rates were highest in the first month 607 (95% CI 568-647) per 100 person years, the rates then decreased over the year but remained elevated throughout the first year compared with subsequent years. Those receiving LMWH had higher ACM than those receiving a DOAC, but this was not significant in the adjusted risk factor analysis. Risk factors for ACM following bleeding included age ≥80, and a history of current smoking, myocardial infarction, congestive heart failure, peripheral artery disease, Stage 4 or 5 kidney disease, metastatic cancer, and intracranial haemorrhage. Age<60, bleeding following major trauma, and a history of anaemia were associated with lower risk of ACM (Table 2). Conclusions There is a significant incidence of ACM following MB among FXai users. The incidence rate of ACM in patients treated with FXai was highest in the first month after FXai initiation, declined during the first year and then plateaued. Multiple risk factors associated with ACM have been recognised and these could guide urgent therapies such as antidotes.

Adherence to anti-hypertensive therapy with perindopril-based single-pill versus free-pill combinations: a 10-year real-world analysis in Italy

Abstract Background/Introduction Despite the growing availability of blood pressure-lowering drugs, hypertension remains poorly controlled and a significant mortality cause worldwide. The silent course of the disease, suboptimal adherence, and complexity of therapeutic schedules are important factors in reducing the effectiveness of anti-hypertensive treatments at the population level. With the purpose of simplifying patients’ medication self-management, guidelines have strongly endorsed the use of anti-hypertensive therapy with single-pill combinations (SPCs). Perindopril (PER)-based SPCs, including both two- and three-drug combinations, have been available since 2008. Purpose We explored treatment adherence over 10 years in patients receiving PER-based regimens (SPC or free-pill combination) in Italy. Methods A retrospective real-world analysis was conducted on administrative databases covering 6.7 million Italian health-assisted residents. Among adults with hospitalization discharge diagnosis or exemption code for hypertension between 2010 and 2021, those with PER-based prescriptions were identified, considering combinations with amlodipine (AML) and/or indapamide (IND), either as SPC or free-pill or mixed (SPC+separate pill). The index-date (ID) was that of the first prescription of a PER-based regimen throughout the inclusion period. All patients with at least 12 months of available data before and after the ID were included. A cross-sectional analysis evaluated the yearly adherence for the period 2012-2021, calculating the proportion of days covered (PDC) by drug prescriptions on 1-year follow-up (PDC≥80% indicated high-adherence). Results Over 2012-2021, of 121,397 patients on a PER-based therapy, those treated with SPC ranged from 87% (during 2012) to 94.4% (during 2021), while free-pill and SPC+separate pill cohorts represented, respectively, 10.6-3.5% and 2.4-2.1% of all hypertensive patients. Over the decade, the proportion of adherent patients in SPC users was markedly higher than in free-pill and SPC+separate pill cohorts (Fig. 1). The sudden reduction of adherent patients during 2018-2019 was possibly due to a temporary shortage of PER/AML/IND as SPC in Italy from Nov-2018 to Mar-2019. Multivariate analysis showed that over 2012-2021 decade, free-pill and SPC+separate pill regimens resulted in significantly lower adherence (more than 80% reduction) than SPC formulation, while male gender and older age were predictive of better adherence (Table 1). Conclusions These findings from real clinical practice in Italy highlighted a growing attitude from clinicians to prescribe more manageable anti-hypertensive schemes based on SPC formulations, in line with current guidelines. The higher proportion of adherent patients among the users of PER-based SPCs corroborates the importance of alleviating pill burden, that is a key component in blood pressure control, and so in the reduction of hypertensive complications and cardiovascular risk.

Transthyretin stabiliser therapy in patients with transthyretin amyloid cardiomyopathy: a systematic review and meta-analysis

Abstract Introduction The safety and efficacy of transthyretin (TTR) stabilisers in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) remains unclear. Objectives We aimed to assess whether TTR stabilisers are effective and safe to promote medical optimisation in patients with ATTR-CM. Methods We systematically searched PubMed, Embase and Cochrane for studies comparing the use of TTR stabilisers with placebo or no TTR stabilisers in patients with ATTR-CM. Statistical analyses were performed using RevMan 5.1.7. Heterogeneity was examined with the Cochran Q test and I2 statistics. Risk ratios (RR) and hazard ratios (HR) with 95% confidence intervals (CI) were computed with a random-effects model for binary endpoints. Results We included 2 randomised controlled trials (RCT) and 12 observational studies, comprising 3324 patients, of whom 1563 (47,02%) received TTR stabilisers. Follow-up ranged from 7 to 36 months. TTR stabilisers were significantly associated with lower all-cause mortality (RR 0.32; 95% CI 0.18-0.57; p<0.01) and cardiovascular hospitalisation (RR 0.67; 95% CI 0.52-0.86; p=0.02) as compared with control group. In a sub analysis of RCTs and multivariate-adjusted data, the composite endpoint of all-cause mortality, heart transplant, and cardiac assist device implantation yielded significant lower rates in the TTR stabiliser group (HR 0.46; 95% CI 0.28-0.73; p=0.01). Conclusion In patients with ATTR-CM, TTR stabilisers were associated with significant lower rates of all-cause mortality and cardiovascular hospitalisations as compared with control group.

Diastolic shock index: a novel prognostic parameter unveiling insights into vasodilatory cardiogenic shock

Abstract Introduction Systemic vasodilation is an increasingly acknowledged feature in cardiogenic shock (CS), defining a subset of patients with low systemic vascular resistances and higher vasopressor requirements. While a diastolic shock index (DSI) above 2.0 predicts vasoplegia and mortality in septic shock, its cut-off and prognostic significance in CS remain unclear. Our study aimed to characterize vasoplegia in CS using the DSI and assess its impact on prognosis. Methods Single-center retrospective cohort study on Cardiac Intensive Care Unit (CICU) admissions for CS from January 2017 to October 2023. Data included patient variables, CS features, vasoactive drugs, mechanical circulatory support, and 30-day mortality. DSI (heart rate (HR) to invasive diastolic blood pressure (DBP) ratio) impact on 30-day all-cause mortality was assessed with univariate Cox regression. Optimal DSI cut-off for adverse outcomes was determined through ROC curve analysis, and survival based on this cut-off was analyzed using Kaplan-Meier curves. Results 185 patients (mean age 59 ± 12 years, 63% male) were included. Acute myocardial infarction-related CS (47%) and heart failure-related CS (29%) were predominant. According to SCAI classification, 86% were class C, 22% class D, and 4% class E, with 26% experiencing previous cardiac arrest. Median Vasoactive-Inotropic Score (VIS) was 48 (IQR 21-85), and 25% used mechanical circulatory support. At admission, median HR was 105 bpm (IQR 90-125), DBP was 60 mmHg (IQR 55-65), and DSI was 1.71 (IQR 1.31-2.18). Thirty-day all-cause mortality was 36% (n=67), with median time to death of 4 days (IQR 1-10). DSI at 30 days predicted mortality (OR 1.42, 95%CI 1.06-1.91, p=0.020). DSI showed fair discriminative power for 30-day mortality (C-Statistic 0.60, 95% CI 0.51-0.68, p=0.031) with a cut-off of 2.2. Patients with DSI >2.2 exhibited heightened likelihood of prior cardiac arrest (38% vs. 20%, p=0.032), and higher serum lactate (5.5 vs. 3.9 mmol/L, p=0.008), and serum creatinine (2.64 vs. 1.88 mg/dL, p=0.003) at admission. Despite higher VIS at 48 hours (120±136 vs. 65±93.9, p=0.04), MCS need did not significantly differ. This group had superior 30-day mortality risk (log-rank p=0.011). Conclusion In our cohort, the admission Diastolic Shock Index (DSI) emerged as a promising identifier for CS vasoplegic patients and was a predictor of a higher risk for mortality. A DSI above 2.2 identified a subset of patients with previous cardiac arrest and higher lactate levels, enlightening possible risk factors associated with vasoplegia. Further studies are warranted to establish the robustness of this novel prognostic parameter in CS patients and its therapeutic implications.

Efficacies of different treatment strategies for infants hospitalized with acute bronchiolitis.

: Acute bronchiolitis is a common cause of hospitalization during infancy that carries significant morbidity and mortality rates. : This study compared the efficacy of different treatment modalities for infants with bronchiolitis in terms of hospital stay and clinical severity scores. : The PubMed database was searched for re- levant studies. Eligibility criteria included double-blind randomized controlled trial design, assessment of the effect of treatment on bronchiolitis in infants under 2 years of age, and publication in English from inception through July 31, 2020. The primary efficacy outcome was the length of hospital stay, while the secondary outcome was the clinical severity score. The standardized treatment effect and standard error of the effect size were calculated. : We identified 45 randomized controlled trials of 24 pairwise comparisons. These 45 trials included 5,061 participants and investigated 13 types of interventions (12 active, 1 placebo). Inhalation therapy with epinephrine (standard mean difference [SMD], -0.41; 95% confidence interval [CI], -0.8 to -0.03) and hypertonic saline (SMD, -0.29; 95% CI, -0.55 to -0.03) reduced the length of hospital stay compared with normal saline. Hypertonic saline was the most effective at improving the clinical severity score (SMD, -0.52; 95% CI, -0.95 to -0.10). : Inhalation therapy with epinephrine and hypertonic saline reduced the length of hospital stay and the clinical severity of bronchiolitis among infants under 2 years of age.

Agroecological importance of smooth brome in managing wheat stem sawfly (Hymenoptera: Cephidae) via associated braconid parasitoids.

Wheat stem sawfly (WSS), Cephus cinctus Norton (Hymenoptera: Cephidae), is a major pest of cereal crops throughout the Northern Great Plains of North America. Native parasitoids, Bracon cephi (Gahan) and B. lissogaster Muesebeck (Hymenoptera: Braconidae), play a key role in suppressing WSS populations and limiting associated damage. Smooth brome grass (Bromus inermis Leyss.) serves as a potential trap reservoir for WSS when grown in areas surrounding wheat (Triticum aestivum L.) fields in Montana. Its unique biology allows it to support high WSS infestation while promoting significant larval mortality throughout the growing season. Late-season WSS survivors can then serve as hosts for WSS parasitoids. Our study investigated smooth brome as a host refuge for WSS parasitoids. We measured WSS larval infestation and survival rate inside smooth brome grown within WSS-inclusion cages, finding a maximum infestation of 66.5% and an end-of-year WSS survival of 5.7%. In addition, we collected stems from sites in central and north-central Montana to measure the WSS infestation and parasitoid prevalence in wheat and adjacent smooth brome. WSS infestation was high in both Big Sandy (64.5% smooth brome, 65.7% adjacent wheat) and Moccasin, MT (50.6%, 38.6%). Year-end WSS larval mortality was 43.6% greater in smooth brome compared to adjacent wheat at both field sites, but both hosted similar numbers of WSS parasitoids. This research underscores the importance of smooth brome in providing a sustainable host refuge for WSS parasitoids and highlights its significant role in supporting the economics of wheat cultivation.

Intra, short and long-term results of mitral VIV for the degenerated surgical mitral prosthesis from italian VIV registry (MIVIV registry)

Abstract Background/Introduction Reoperation of failed bioprosthetic mitral valves is associated with significant morbidity and mortality. Transcatheter mitral valve-in-valve (MViV) replacement was explored early in the development of THVs with transseptal/transfemoral (TS/TF) and transapical (TA) approaches. Purpose This is the first Italian Registry on mitral VIV and it was designed to explore contemporary MViV outcomes with all types of balloon expandable valves. The present study out of the registry aims to asses the >10 years follow-up outcomes in terms of mortality, gender diversity, and perioperative result. Methods Participating centers used standardized definitions to collect clinical information, including patient demographic characteristics, comorbidities, functional status, quality of life indexes, procedural details, and patient outcomes from consecutive MViV cases. Cohort of 265 patients was available for the primary analysis and follow-up too.The patients were grouped by 11 hospitals in Italy performing VIV for degenerated biological mitral prostheses. Results A total of 265 pts underwent mitral VIV due to bioprosthesis degeneration between January 2010 and January 2023. They have been subdivided by transfemoral (TF) with 117 (44%) pts and transapical (TA) with 148 (55,8%) pts. Most of the patients were of female sex (59,2%) and EuroScore II for surgical re-operation was 16.1%. Mixed disease (48%) was more common than mitral regurgitation (29%) and stenosis (22%). 69,8% of the total cohort was in class NYHA III and the mean LVEF was 54%.Otherwise, there were no significant demographic differences between patients undergoing TS and TA. In TF there was more severe PVL (5%)(p-value: 0,001) and much more cases of severe grade of stenosis (54,7%) and regurgitation (57%)(p-value< 0,0001). Considering intraoperative outcomes, technical success has been established in around 97,7% of the total cohort without difference btw groups. Only 3,3% died during hospitalization without difference between groups (P-value=0,735). LVOT obstruction has been seen in 3,4% in the case of TA and 0 for TF. Only 1,5% of the total cohort underwent surgical conversion as well as embolization in only 1,1%. Overall survival from the total cohort was 91,3% at >10 years, Figure 1. Concerning the freedom from cardiac death (CV death) was 96,6% in the total cohort at 13 years. Concerning the difference between access, the general survival is established at 97,4% in TF while 86,3% in TA (p-value =0,050)(Figure 2). Freedom from CV death was 99,1% in TF and 94,5 in TA (p-value=0,209). In gender analysis differentiation, the general survival in females was 98,5% in TF and 85,6% in TA at 13 years (p-value=0,056). Conclusion(s) Transcatheter MViV using a balloon-expandable valve is associated with high technical success, a low complication rate, and a solid long-term benefit in terms of survival. Transseptal access was associated with lower mortality compared with TA access.Figure 1Figure 2