Heart Failure Spending Function: An Investment Framework for Sequencing and Intensification of Guideline-Directed Medical Therapies

Heart failure with reduced ejection fraction is managed with increasing numbers of guideline-directed medical therapies (GDMT). Benefits tend to be additive. Burdens can also be additive. We propose a heart failure spending function as a conceptual framework for tailored intensification of GDMT that maximizes therapeutic opportunity while limiting adverse events and patient burden. Each patient is conceptualized to have reserve in physiological and psychosocial domains, which can be spent for a future return on investment. Key domains are blood pressure, heart rate, serum creatinine, potassium, and out-of-pocket costs. For each patient, GDMT should be initiated and intensified in a sequence that prioritizes medications with the greatest expected cardiac benefit while drawing on areas where the patient has ample reserves. When reserve is underspent, patients fail to gain the full benefit of GDMT. Conversely, when a reserve is fully spent, addition of new drugs or higher doses that draw upon a domain will lead to patient harm. The benefit of multiple agents drawing upon varied physiological domains should be balanced against cost and complexity. Thresholds for overspending are explored, as are mechanisms for implementing these concepts into routine care, but further health care delivery research is needed to validate and refine clinical use of the spending function. The heart failure spending function also suggests how newer therapies may be considered in terms of relative value, prioritizing agents that draw on different spending domains from existing GDMT.

EFFORTS TO SURVIVE IN SCOTT NEUSTADTER’S AND MICHAEL H. WEBER’S MOVIE SCRIPT THE FAULT IN OUR STARS

This paper deals with the Effort to Survive in Scott Neustadter’s and Michael H. Weber’s movie script The Fault In Our Stars, and it refers to two topics of discussion i.e. pleasing herself and doing medication ; the protagonist’s effort to stay alive is due to suffering from stage 4 thyroid cancer. In analyzing the two topics, the descriptive qualitative method is taken as most appropriate method to process the data. The analysis indicates that the protagonist encouragingly makes some efforts for her healthy treatments as to please herself involving meeting her lover, going for a picnic, and meeting her favorite author; as to do medication by doing some therapies and joining support group. The results shows that the protagonist has attempted so hard to survive by doing things for her recovery; her cancer disease needs to have psychological treatment that can please herself and by doing medical treatment, medical therapies to cure a rare form of cancer. All of these are the protagonist’s efforts to live her life longer.

Recommendations for Standardizing Clinical Trial Design and Endoscopic Assessment in Postoperative Crohn’s Disease

Background The lack of standardized methods for clinical trial design and disease activity assessment has contributed to an absence of approved medical therapies for the prevention of postoperative Crohn’s disease (CD). We developed recommendations for regulatory trial design for this indication and for endoscopic assessment of postoperative CD activity. Methods An international panel of 19 gastroenterologists was assembled. Modified Research and Development/University of California Los Angeles methodology was used to rate the appropriateness of 196 statements using a 9-point Likert scale in 2 rounds of voting. Results were reviewed and discussed between rounds. Results Inclusion of patients with a history of completely resected ileocolonic CD in regulatory clinical trials for the prevention of postoperative recurrence was appropriate. Given the absence of approved medical therapies, a placebo-controlled design with a primary end point of endoscopic remission at 52 weeks was appropriate for drug development for this indication; however, there was uncertainty regarding the appropriateness of a coprimary end point of symptomatic and endoscopic remission and the use of currently available patient-reported outcome measures. The modified Rutgeerts Score, endoscopic assessment of the anastomosis, and a minimum of 5cm of neoterminal ileum were also appropriate; although the appropriateness of other indices including the Simple Endoscopic Score for CD for endoscopic assessment of postoperative CD activity was uncertain. Conclusions A framework for regulatory trial design for the prevention of postoperative CD recurrence and endoscopic assessment of disease activity has been developed. Research to empirically validate end points for these trials is needed.

Three Cases of Insomnia in Herniated Intervertebral Disk Patients Treated with Uhwangchungsim-won

Objective: This study examined a case in which insomnia and pain due to herniated intervertebral disks were improved by treatment with an oriental herbal and the administration of Uhwangchungsim-won.Case Summary: Three patients with insomnia diagnosed with herniated intervertebral disks were treated with a series of Korean medical therapies, including the herbal medication Uhwangchungsim-won, acupuncture, herbal acupuncture, and physical therapy. We used the Numerical Rating Scale (NRS) to measure subjective sleep states and the European Quality of Life Five Dimensions (EQ-5d) Scale to evaluate the therapeutic effect. Following treatment, subjective sleep states and the overall scores for pain had improved.Conclusion: The results indicate that Korean medical therapies with Uhwangchungsim-won have beneficial effects on insomnia for patients with herniated intervertebral disks.

Characteristics of Techirghiol Sludge and Different Methods of Peloid Therapy

The paper highlights the physical, chemical and biochemical composition of the sludge and systematizes the beneficial effects obtained by applying Techirghiol sludge through specific procedures. Techirghiol sludge is a well hydrated sapropelic sludge, with a high content of minerals and organic compounds. Following the application of sludge on the skin, a series of processes take place: stimulation of sensitive endings, energy and substance exchanges, general thermoregulation, vitamin D synthesis, regulation of homeostasis balance by immune, endocrine and neurovegetative mechanisms, better tissue oxygenation. The use of Techirghiol sludge in medical therapies is often alternative and complementary treatments in the treatment of diseases that can be good solutions for amelioration various diseases.

STAT1: a novel candidate biomarker and potential therapeutic target of the recurrent aphthous stomatitis

Background The recurrent aphthous stomatitis (RAS) frequently affects patient quality of life as a result of long lasting and recurrent episodes of burning pain. However, there were temporarily few available effective medical therapies currently. Drug target identification was the first step in drug discovery, was usually finding the best interaction mode between the potential target candidates and probe small molecules. Therefore, elucidating the molecular mechanism of RAS pathogenesis and exploring the potential molecular targets of medical therapies for RAS was of vital importance. Methods Bioinformatics data mining techniques were applied to explore potential novel targets, weighted gene co-expression network analysis (WGCNA) was used to construct a co-expression module of the gene chip data from GSE37265, and the hub genes were identified by the Molecular Complex Detection (MCODE) plugin. Results A total of 16 co-expression modules were identified, and 30 hub genes in the turquoise module were identified. In addition, functional analysis of Hub genes in modules of interest was performed, which indicated that such hub genes were mainly involved in pathways related to immune response, virus infection, epithelial cell, signal transduction. Two clusters (highly interconnected regions) were determined in the network, with score = 17.647 and 10, respectively, cluster 1 and cluster 2 are linked by STAT1 and ICAM1, it is speculated that STAT1 may be a primary gene of RAS. Finally, genistein, daidzein, kaempferol, resveratrol, rosmarinic acid, triptolide, quercetin and (-)-epigallocatechin-3-gallate were selected from the TCMSP database, and both of them is the STAT-1 inhibitor. The results of reverse molecular docking suggest that in addition to triptolide, (-)-Epigallocatechin-3-gallate and resveratrol, the other 5 compounds (flavonoids) with similar structures may bind to the same position of STAT1 protein with different docking score. Conclusions Our study identified STAT1 as the potential biomarkers that might contribute to the diagnosis and potential therapeutic target of RAS, and we can also screen RAS therapeutic drugs from STAT-1 inhibitors.

Impact of medical therapies for inflammatory bowel disease on the severity of COVID-19: a systematic review and meta-analysis

BackgroundDuring COVID-19 pandemic, the safety of medical therapies for inflammatory bowel disease (IBD) in relation to COVID-19 has emerged as an area of concern. This study aimed to evaluate the association between IBD therapies and severe COVID-19 outcomes.MethodWe performed a systematic review and meta-analysis of all published studies from December 2019 to August 2021 to identify studies that reported severe COVID-19 outcomes in patients on current IBD therapies including 5-aminosalicylic acid (5-ASA), immunomodulators, corticosteroids, biologics, combination therapy, or tofacitinib.ResultsTwenty-two studies were identified. Corticosteroids (risk ratio (RR) 1.91 (95% CI 1.25 to 2.91, p=0.003)) and 5-ASA (RR 1.50 (95% CI 1.17 to 1.93, p=0.001)) were associated with increased risk of severe COVID-19 outcomes in patients with IBD patients. However, possible confounders for 5-ASA use were not controlled for. Sub-analysis showed that corticosteroids increased the risk of intensive care unit (ICU) admission but not mortality. Immunomodulators alone (RR 1.18 (95% CI 0.87 to 1.59, p=0.28)) or in combination with anti-TNFs ((RR 0.96 (95% CI 0.80 to 1.15, p=0.63)), tofacitinib (RR 0.81 (95% CI 0.49 to 1.33, p=0.40)) and vedolizumab ((RR 1.02 (95% CI 0.79 to 1.31, p=0.89)) were not associated with severe disease. Anti-TNFs (RR 0.47 (95% CI 0.40 to 0.54, p<0.00001)) and ustekinumab (RR 0.55 (95% CI 0.43 to 0.72, p<0.00001)) were associated with decreased risk of severe COVID-19.ConclusionIn patients with IBD, the risk of severe COVID-19 is higher among patients receiving corticosteroids. Corticosteroid use was associated with ICU admission but not mortality. The risk is also higher among patients receiving 5-ASAs. However, patient-level data were lacking and insufficient data existed for meta-regression analyses to adjust for confounding. Vedolizumab, tofacitinib, and immunomodulators alone or in combination with anti-TNF were not associated with severe disease. Anti-TNFs, and ustekinumab were associated with favourable outcomes.