Routine in-hospital interventions during acute exacerbation of COPD are associated with improved 30-day care.

BACKGROUND: Implementing standard of care therapy for chronic obstructive pulmonary disease (COPD) has barriers. Hospitalization with an acute exacerbation of COPD (AECOPD) is a major adverse event that could also be an opportunity to improve patients' long-term care. OBJECTIVES: To evaluate which in-hospital interventions during AECOPD are associated with improved 30-day care. METHODS: This was a prospective study that included patients from 10 medical centers across Israel, hospitalized with AECOPD between 2017 and 2019. Patients were approached during hospitalization in internal medicine departments. A semi-structured follow-up call was performed 30 days after discharge, and six COPD areas of care were assessed. Multivariate analyses were used to analyze predictors for each area of care. RESULTS: 234 patients were included (mean age 69 years and 34% females). A lower 30-day readmission rate was independently associated with smoking cessation and prescription of renin-angiotensin blockers. Initiating or continuing long acting bronchodilators (LABD) during admission was an independent predictor for their 30-day use. Among patients with prior LABD treatment, only 38% continued at 30-days if it was not prescribed during admission (OR 4, 95% CI 1.98-8.08, p<0.01). In-hospital daily respiratory physiotherapy was an independent predictor for smoking cessation (AOR 5.1, 95% CI 1.1-23, p=0.04), while smoking cessation recommendation was not (p=0.28). Initiating a smoking cessation program (5%) or pulmonary rehabilitation (1%) after discharge was performed only by patients with a written referral. CONCLUSION: Routine procedures during hospitalization for AECOPD could impact patients' long-term care in areas with proven effects on disease outcomes.

Management of acute exacerbations of COPD in the emergency department and its associations with clinical variables.

Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a common cause for emergency department (ED) visits. Still, large scale studies that assess the management of AECOPD in the ED are limited. Our aim was to evaluate treatment characteristics of AE-COPD in the ED on a national scale. A prospective study as part of the COPD Israeli survey, conducted between 2017 and 2019, in 13 medical centers. Patients hospitalized with AECOPD were included and interviewed. Clinical data related to their ED and hospital stay were collected. 344 patients were included, 38% females, mean age of 70 ± 11 years. Median (IQR) time to first ED treatment was 59 (23-125) minutes and to admission 293 (173-490) minutes. Delayed ED treatment (> 1 h) was associated with older age (p = 0.01) and lack of a coded diagnosis of COPD in hospital records (p = 0.01). Long ED length-of-stay (> 5 h) was linked with longer hospitalizations (p = 0.01). Routine ED care included inhalations of short-acting bronchodilators (246 patients, 72%) and systemic steroids (188 patients, 55%). Receiving routine ED care was associated with its continuation during hospitalization (p < 0.001). In multivariate analysis, predictors for patients not receiving routine care were obesity (adjusted odds ratio 0.5, 95% CI 0.3-0.8, p = 0.01) and fever (AOR 0.3, 95% CI 0.1-0.6, p < 0.01), while oxygen saturation < 91% was an independent predictor for ED routine treatment (AOR 3.6, 95% CI 2.1-6.3, p < 0.01). Our findings highlight gaps in the treatment of AECOPD in the ED on a national scale, with specific predictors for their occurrence.

Anti PCSK9 Monoclonal Antibody Treatment in Elderly Patients: A Real-world Clinical Experience.

BACKGROUND: The use of proprotein convertase subtilisin/kexin type 9 monoclonal antibodies (PCSK9 mAbs) is emerging for lowering low-density lipoprotein cholesterol (LDL-C). However, real-world data is lacking for their use among elderly patients. OBJECTIVES: To define the characteristics of elderly patients treated with PCSK9 mAbs and to evaluate the efficacy and tolerability compared with younger patients. METHODS: We conducted a retrospective cohort study of elderly patients (≥ 75 years at enrollment) treated with PCSK9 mAbs for primary and secondary cardiovascular prevention. Data were retrieved for demographic and clinical characteristics; indications for treatment; agents and dosages; concomitant lipid lowering treatment; LDL-C levels at baseline, 6, 12 months, and at the end of follow up. Data also included achieving LDL-C target levels and adverse effects. RESULTS: The cohort included 91 elderly patients and 92 younger patients, mean age 75.2 ± 3.76 and 58.9 ± 7.4 years (P < 0.0001). Most patients (82%, 80%) were in high/very high-risk categories. For almost all (98%, 99%), the indication was statin intolerance, with PCSK9 mAb monotherapy the most prevalent regimen. The average follow-up was 38.1 ± 20.5 and 30.9 ± 15.8 months (P = 0.0258). Within 6 months the LDL-C levels were reduced by 57% in the elderly group and by 59% in the control group (P = 0.2371). Only 53% and 57% reached their LDL-C target levels. No clinically significant side effects were documented. CONCLUSIONS: PCSK9 mAbs have similar effects and are well tolerated among elderly patients as in younger patients.

Challenges in Implementing Guideline on Integrative Oncology and Pain: The Israeli Perspective.

CONTEXT AND OBJECTIVES: To explore the feasibility of implementing the joint guideline on integrative medicine for pain management in oncology, published by the Society for Integrative Oncology (SIO) and the American Society of Clinical Oncology (ASCO), for integrative oncology (IO) services in supportive and palliative care. METHODS: A qualitative research methodology was co-designed by the SIO-ASCO guideline committee, with the Society for Complementary Medicine, Israel Medical Association (IMA). A questionnaire with five open-ended questions exploring barriers and enablers to implementing the guideline was distributed to chairs and board members of nine IMA-affiliated medical societies; four deans of Israeli medical schools; and nurses from the Israeli Society for Oncology Nursing. Respondent narratives were qualitatively analyzed using ATLAS.Ti software for systematic coding. RESULTS: Questionnaires were completed by 52 physicians and nurses from medical oncology, hematology, gynecological oncology, pediatric oncology, palliative medicine, pain, family medicine, internal medicine, and integrative medicine. The SIO-ASCO guidelines were endorsed by nine IMA-affiliated societies. The domains identified included the importance of guideline implementation in clinical practice; barriers and facilitators to implementation; practical aspects required for this implementation (e.g., IO training); clinical indications for referral; budget-related issues; and clinical and administrative models enabling practical implementation of the guideline. CONCLUSION: We found across-the-board consensus among the nine IMA-affiliated societies supporting the current guideline. This, while identifying potential facilitators and barriers in order to address the implementation of the SIO-ASCO guideline recommendations.

The Treatment of Venous Thromboembolism in the Emergency Department in the DOACs Era.

BACKGROUND: Low-risk venous thromboembolism (VTE) patients are advised to be discharged from the emergency department (ED) on direct oral anticoagulants (DOACs) treatment. There is no data on whether this recommendation is followed in Israel. OBJECTIVES: To characterize newly diagnosed VTE patients who were discharged from the ED, their anticoagulation treatment at the ED, the recommended discharge protocol, and patient adherence. METHODS: We conducted a retrospective cohort study, which included all newly diagnosed VTE patients who were discharged from the ED. Collected data included demographic and clinical background; anticoagulation treatment at the ED, recommended discharge protocol and its subsequent adherence, patient subsequent, recommended hematological evaluation, and adverse events. RESULTS: The study group included 443 patients, 89% with deep vein thrombosis (DVT). Approximately three-quarters were treated with anticoagulants in the ED, 98% with enoxaparin. At discharge, anticoagulants were recommended for all; 49% continued enoxaparin, 47% DOACs, and 4% warfarin. After 4 weeks, 67% were treated with DOACs, 22% with enoxaparin, 5% with warfarin. Approximately 6% discontinued all treatment. After 12 weeks, 90% of the patients who were taking DOACs adhered to the protocol, whereas only 70% and 50% among the enoxaparin and warfarin users, respectively, did. Only 56% were referred for hematological evaluation. The 12-week rate of adverse reactions was approximately 2%. The use of DOACs and the recommendation for further hematological evaluation increased over time. CONCLUSIONS: Clinician training regarding discharge of VTE patients from the ED should continue.

Clinical Outcomes of Hospitalized Patients with SARS-CoV-2 Omicron Variant vs. Influenza A During Influenza Season 2021 to 2022: A Retrospective Observational Study.

BACKGROUND: Influenza and coronavirus disease 2019 (COVID-19) are respiratory diseases with similar modes of transmission. In December 2021, influenza re-emerged after it had been undetected since March 2020 and the Omicron variant replaced the Delta variant. Data directly comparing the two diseases are scarce. OBJECTIVES: To compare the outcomes of patients with both the Omicron variant and influenza during 2021-2022. METHODS: We performed a retrospective study conducted in Beilinson hospital, Israel, from December 2021 to January 2022. We included all hospitalized patients with either laboratory-confirmed COVID-19 or influenza. The primary outcome was 30-day mortality. RESULTS: We identified 167 patients diagnosed with Omicron and 221 diagnosed with Influenza A. The median age was 71 years for Omicron and 65 years for influenza. Patients with Omicron had a significantly higher Charlson Comorbidity Index score (4 vs. 3, P < 0.001). Patients with Omicron developed more respiratory failure that needed mechanical ventilation (7% vs. 2%, P = 0.05) and vasopressors (14% vs. 2%, P < 0.001) than patients with influenza. In a multivariate model, 30-day mortality was lower in patients diagnosed with influenza than in patients diagnosed with Omicron (19/221 [9%] vs. 44/167 [26%], hazard ratio 0.45, 95% confidence interval 0.25-0.81). CONCLUSIONS: Patients diagnosed with Omicron had higher mortality than patients diagnosed with seasonal influenza. This finding could be due to differences in co-morbidities, the virus pathogenicity, and host responses to infection.

Congestive Heart Failure at the Department of Medicine: Demographic and Clinical Characteristics.

BACKGROUND: Congestive heart failure (CHF) with reduced ejection fraction (HFrEF) or with preserved ejection fraction (HFpEF) is a common diagnosis in patients hospitalized in the department of internal medicine. Recently, the therapeutic regimens were updated, as the sodium-glucose cotransporter-2 (SGLT2) inhibitors became an integral part of the therapeutic regimen for either HFrEF or HFpEF. OBJECTIVES: To define the demographic and clinical characteristics of CHF patients hospitalized in the department of medicine. METHODS: We conducted a retrospective cohort study that included all patients hospitalized in the departments of medicine at the Rabin Medical Center, Israel, between 2016 and 2019. Demographic and clinical background, in-hospital procedures, discharge regimens, and outcome parameters were evaluated according to HFrEF/HFpEF. RESULTS: The cohort included 4458 patients. The majority (97%) presented with a preexisting diagnosis, whereas HF was an active condition in only half of them. The rates of HFrEF/HFpEF were equal. In most cases, the trigger of the exacerbation could not be determined; however, infection was the most common cause. There were basic differences in the demography, clinical aspects, and therapeutic regimens at discharge between HFrEF and HFpEF. Both conditions were associated with high in hospital mortality (8%) and re-admissions rates (30 days [20%], 90 days [35%]) without any difference between them. CONCLUSIONS: HFrEF/HFpEF patients differed by demographics and co-morbidities. They were equally represented among patients admitted to medical wards and had similar prognosis. For both diagnoses, hospitalization should be considered for updating therapeutic regimens, especially with SGLT2 inhibitors.

Management of acute COPD exacerbations in the internal medicine departments in Israel-a national survey.

Background: Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality. Acute exacerbations of COPD (AECOPD) drastically affect the clinical course of the disease. We aimed to evaluate the treatment of AECOPD in the internal medicine departments in Israel, nationwide. Methods: The COPD Israeli survey (COPDIS) is the first national survey of patients admitted with AECOPD to internal medicine departments between 2017 and 2019. The survey includes prospective (n = 344) and retrospective (n = 1,166) data from 13 medical centers. We analyzed the pre-hospital, in-hospital, and pre-discharge care. Hospital evaluation, outcomes and discharge recommendations were assessed as well. Results: The mean (±SD) age was 74 (±8) years, and 54% were males. 74% had comorbidities, and 88% had a diagnosis of COPD in their history. 70% of the patients received systemic steroids and antibiotics during their hospitalization, yet upon discharge, a lower rate of antibiotics prescription (10%) was found. Treatment with most long-acting bronchodilators dramatically dropped during admission, compared with their pre-hospital use. Overall, a long-acting bronchodilator (LABD) was used by 47% before admission, 28% in-hospital, and was prescribed to 54% at discharge. The discharge plan included a referral to pulmonary rehabilitation in only 11% and a smoking cessation recommendation in 43% of active smokers. The in-hospital mortality was 3% and the 1-year mortality rate was 25%. In multivariate analysis, performing a chest X-ray (adjusted OR 0.64, 95% CI 0.46-0.90) and prescribing LABD at discharge (AOR 0.73, 95% CI 0.57-0.95) were independent predictors for lower 1-year mortality. Conclusion: Our results demonstrate AECOPD characteristics in Israel, and highlight several important gaps in AECOPD healthcare, which must be addressed to improve patient care.

Community versus health care-associated Clostridioides difficile infection: A comparison between clinical characteristics and outcomes in hospitalized patients.

BACKGROUND: Clostridioides difficile infection (CDI) can be divided according to its acquisition site, health care (HC) or community (CA) associated CDI. Studies showed severe disease, higher recurrence, and mortality among HC-CDI patients, while others reported the opposite. We aimed to compare the outcomes according to the CDI acquisition site. METHODS: The study analyzed medical records and laboratory computerized system data to identify patients (≥18 years old) who were hospitalized with the first CDI from January 2013 to March 2021. Patients were divided into HC-CDI and CA-CDI groups. The primary outcome was 30-day mortality. Other outcomes: CDI severity, colectomy, intensive care unit (ICU) admission, length of hospitalization, 30 and 90-day recurrence, and 90 days all-cause mortality. RESULTS: Of 867 patients, 375 were defined as CA-CDI and 492 as HC-CDI. CA-CDI patients had more underlying malignancy (26% vs 21% P = .04) and inflammatory bowel disease (7% vs 1%, P < .001). The 30 days mortality was similar (10% CA-CDI and 12% HC-CDI, P = .5), and the acquisition site was not found to be a risk factor. There was no difference in severity nor in complications, but the recurrence rate was higher among those with CA-CDI (4% vs 2%, P = .055). CONCLUSIONS: There were no differences between the CA-CDI and HC-CDI groups regarding rates, in-hospital complications, short-term mortality, and 90-day recurrence rates. However, the CA-CDI patients had a higher recurrence rate at 30 days.

Real-World Use of Alirocumab: Experience from a Large Healthcare Provider.

With the emerging use of anti-PCSK9 monoclonal antibodies for lowering low-density lipoprotein cholesterol (LDL-C) levels, real-world evidence (RWE) is needed to evaluate drug effectiveness. This study aimed to characterize new users of alirocumab and evaluate its effectiveness in achieving LDL-C target levels. Included were patients initiating treatment with alirocumab from 1 August 2016 to 1 May 2020, with blood lipids evaluations during baseline (180 days prior to therapy initiation) and after 120 (±60) days of follow-up. Patients with treatment intensification during the follow-up period were excluded. LDL-C change from baseline and reaching LDL-C target levels, according to 2019 ESC/EAS guidelines, were evaluated. Among 623 included patients, 50.2% were men, the mean age was 65 years (±9 y), 62% were classified as very-high risk, and 76% had statin intolerance. During the follow-up, 65% (n = 407) were treated only with alirocumab. In 90% the initiation dose was 75 mg, and 21% were up-titrated. Alirocumab was associated with a 31.7% reduction in LDL-C, with 20.5% of patients reaching target levels. In this RWE study, alirocumab was used primarily as a single agent for eligible patients. Suboptimal use and adherence to therapy may have led to a lower LDL-C reduction compared to previous RCTs and most reported real-world studies.

Current and future options in cholesterol lowering treatments.

The relative risk reduction of cardiovascular events is proportional to the absolute reduction in LDL-C levels, the primary target of therapy, no matter the way of reduction. During the last decades, the therapeutic regimens for reducing the LDL-C levels have been immerged and improved, with favorable effects on the atherosclerotic process and clinical benefits of various cardiovascular outcomes. From a practical view of point, this review is focusing only on the current available lipid lowering agents: statins, ezetimibe, anti PCSK9 monoclonal antibodies, the small interfering RNA (siRNA) agent, Inclisiran, and Bempedoic acid. The recent changes in lipid lowering regimens, including the early combination of lipid lowering agents and "Low LDL-C" levels <30 mg/dL for high/very high cardiovascular risk patients will also be discussed.

Treatment with Anti-PCSK9 Monoclonal Ab: Experience from a Lipid Clinic in Israel.

BACKGROUND: There is an increasing use of anti-protein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies (mAbs); however, real-world data is lacking. OBJECTIVES: To define the demographic and clinical characteristics of patients treated with anti-PCSK9 mAbs. To evaluate efficacy, tolerability, and differences between the approved agents. METHODS: A retrospective cohort study was conducted of patients treated at the lipid clinic at Rabin Medical Center (Beilinson Campus), Israel, from January 2016 to December 2019. Data from electronic records were evaluated for demographic and clinical characteristics, indication for use, response of lowering low-density lipoprotein cholesterol (LDL-C)/non-high-density lipoprotein cholesterol (non-HDL-C) levels and reaching target levels, side effects, tolerability, differences between the agents, and doses. RESULTS: The study cohort included 115 patients. Two-thirds (n=75) were at high cardiovascular risk, the rest at very high risk (n=40). The major indication for treatment was statin intolerance (n=97, 84%). Most patients (n=102, 88%) were treated by anti-PCSK9 mAbs agents only. LDL-C and non-HDL-C levels were decreased by 47% and 39%, respectively (156 + 49 to 81 + 39 and 192 + 53 to 116 + 42 mg/dl), within 6 months and remained stable. Two-thirds (n=76) of the patients reached their lipid target levels. No clinically significant differences were observed between the agents in efficacy or tolerability. CONCLUSIONS: In a real-world setting, anti-PCSK9 mAbs are used primarily as a single agent in high-risk and very high-risk cardiovascular populations with statin intolerance. They are well tolerated and effective in reduction of LDL-C levels. Further studies are needed to clarify comparisons between agents and doses.

The Association between Low Levels of Low Density Lipoprotein Cholesterol and Intracerebral Hemorrhage: Cause for Concern?

Excessive levels of low-density lipoprotein cholesterol (LDL-C) in the blood are a known risk factor for atherosclerosis, and a common target of treatment for primary and secondary prevention of cerebrocardiovascular disease. As lipid lowering agents including statins, ezetimibe and anti-proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have shown good therapeutic results, the guidelines are constantly lowering the "optimal" LDL-C goals. However, old and new data point towards an association between low LDL-C and total cholesterol and intracerebral hemorrhage (ICH). In this review we aimed to shed light on this troubling association and identify the potential risk factors of such a potential adverse reaction. With respect to the data presented, we concluded that in patients with high risk of ICH, a cautious approach and individualized therapy strategy are advised when considering aggressive LDL reduction.

Comparison of Low and Full Dose Apixaban Versus Warfarin in Patients With Atrial Fibrillation and Renal Dysfunction (from a National Registry).

The use of direct oral anticoagulants for stroke prevention in patients with non-valvular atrial fibrillation (NVAF) is robust. However, the efficacy and safety of different dosage in patients with renal dysfunction is still a clinical challenge. We aimed to evaluate the clinical characteristics and outcomes of patients treated with apixaban in its different doses. A multicenter prospective cohort study, where consecutive eligible apixaban or warfarin treated patients with NVAF and renal impairment, were registered. Patients were followed-up for clinical events over a mean period of 1 year. Analyses were performed according to the dose of apixaban given, with consideration to the standard indications for dose reduction. Primary outcome was a composite of 1-year mortality, stroke or systemic embolism, major bleeding and myocardial infarction, while secondary outcomes included those components separated. Among the study population (n = 2,140), risk of composite outcome was significantly lower in the high dose apixaban group (10%, n = 491) than the low dose group (18%, n = 673) and the warfarin group (18%, n = 976) p <0.001. Results of 1-year mortality were similar. Apixaban dosing analysis revealed 65% of patients were appropriately dosed, while 31% were under-dosed and 4% were over-dosed. Furthermore, 53% of patients treated with low dose apixaban were under-dosed. Propensity score analysis revealed that patients who were appropriately treated with low-dose apixaban had a trend towards better composite outcome and mortality than 1:1 matched warfarin treated patients (18% vs 24%, p = 0.09 and 16% vs 23%, p = 0.06, respectively). Overall, appropriately dosed apixaban treated patients at any dose had significantly better outcomes than matched warfarin treated patients (composite outcome probability of 13.1% vs 18.6%, p = 0.007). In conclusion, apixaban at any dose is a reasonable alternative to warfarin in patients with renal impairment, possibly associated with improved outcomes.

[RESEARCH AND CLINICAL PRACTICE- THE SOUL AND BREATH OF INTERNAL MEDICINE].

BACKGROUND: We welcome the readers of Harefuah to the following issue that deals with the research and clinical practice that was carried out in this challenging year of the COVID-19 pandemic. Despite the high hospitalization rates throughout the country in these times, our clinicians found the spirit to continue and conduct their research activities. The following issue presents the essence of the good clinical practice along with interesting research outcomes.

Multidisciplinary team led by internists improves diabetic foot ulceration outcomes a before-after retrospective study.

STUDY OBJECTIVE: Diabetic foot ulceration (DFU) is associated with high mortality and morbidity. A multidisciplinary approach has been suggested, but as these patients usually present with various comorbidities, leadership of a multidisciplinary team by internists was initiated. Our aim was to evaluate the impact of the leadership of the multidisciplinary team by internists on the outcomes of patients with DFU. METHODS: Outcomes of patients with salvable DFU admitted pre and post introduction of the multidisciplinary team were compared, i.e., a major amputation (above or below the knee), blood stream infection, major medical complications, 30 day mortality, vascular interventions, diabetes control, medication regiments and laboratory results. RESULTS: The cohort included 315 patients, 207 - multidisciplinary pre-period and 108 - multidisciplinary period. During the multidisciplinary period, the rates of major amputations, blood stream infections were found significantly lower than the pre-multidisciplinary period (10% vs. 14%; p = 0.01 and 2% vs. 13%, p = 0.04, respectively). The 30 day mortality rates tended to be lower (5% vs. 11%, p = 0.08). Vascular interventions increased significantly (18% vs. 1%, p<0.01). The diabetes control significantly improved (median glucose levels 163 vs. 185 mg/dl, p = 0.03). Treatment consisting of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, statins) were updated and laboratory results at discharge (albumin, CRP) showed improved disease control. CONCLUSION: The treatment of hospitalized DFU patients by a multidisciplinary team led by internists using a holistic therapeutic approach demonstrated improved clinical outcomes.

Apixaban in Patients with Atrial Fibrillation and Severe Renal Dysfunction: Findings from a National Registry.

BACKGROUND: Real-world information regarding the use of direct oral anticoagulants therapy and the outcome in patients with renal dysfunction is limited. OBJECTIVES: To evaluate the clinical characteristics and outcomes of patients with atrial fibrillation (AF) and severe renal dysfunction who are treated with apixaban. METHODS: A sub-analysis was conducted within a multicenter prospective cohort study. The study included consecutive eligible apixaban- or warfarin-treated patients with non-valvular AF and renal impairment (estimated glomerular filtration rate [eGFR] modification of diet in renal disease [MDRD] < 60 ml/min/BSA) were registered. All patients were prospectively followed for clinical events and over a mean period of 1 year. Our sub-analysis included the patients with 15 < eGFR MDRD < 30 ml/min/BSA. The primary outcomes at 1 year were recorded. They included mortality, stroke or systemic embolism, major bleeding, and myocardial infarction as well as their composite occurrence. RESULTS: The sub-analysis included 155 warfarin-treated patients and 97 apixaban-treated ones. All had 15 < eGFR MDRD < 30 ml/min/BSA. When comparing outcomes for propensity matched groups (n=76 per group) of patients treated by reduced dose apixaban or warfarin, the rates of the 1-year composite endpoint as well as mortality alone were higher among the warfarin group (30 [39.5%] vs. 14 [18.4%], P = 0.007 and 28 [36.8%] vs.12 [15.8%], P = 0.006), respectively. There was no significant difference in the rates of stroke, systemic embolism, or major bleeding. CONCLUSIONS: Apixaban might be a reasonable alternative to warfarin in patients with severe renal impairment.