Clinical Outcomes of Ustekinumab in Inflammatory Bowel Disease.

Inflammatory bowel diseases including Crohn's disease (CD) and ulcerative colitis (UC) are characterized by abdominal pain, diarrhea, blood in stools, weight loss, and fatigue. It presents in patients with varying severity from mild to severe depending on the inflammation. Detailed analysis and guidelines are required for the safe usage of biological therapies in the treatment of inflammatory bowel diseases as surgery is reserved for more complex cases. There is also geographical variation in inflammatory bowel disease (IBD) incidence and prevalence based on environmental and climate changes, and socio-demographics. Studies also show that there is more hospitalization and reduced health-related quality of life in IBD patients when compared to normal people. We conducted an extensive literature database search for articles with keywords within the last 10 years on adults >18 years of age with IBD and its treatment, especially with ustekinumab. Ustekinumab is a human immunoglobulin G1 (IgG1) kappa monoclonal antibody, that blocks IL-12 and IL-23 and was approved by the FDA for the treatment of moderate to severe IBD, especially in patients who are intolerant to immunomodulators or corticosteroids treatment. There are several retrospective studies that show the effectiveness of ustekinumab dosage escalation every four weeks in IBD patients. This escalation of dose not only improved the clinical outcome but also reduced the worsening of the disease. Previous studies also show the importance of considering dosage escalation before switching biological agents in the IBD treatment. Ustekinumab has also demonstrated both efficacy and safety in the induction and maintenance of the treatment of this disease. There are certain challenges and opportunities associated with ustekinumab usage in IBD patients that require further research. Ustekinumab seems to be more cost-effective in the tumor necrosis factor (TNF)-alpha-inhibitor failure population when compared to previously used biological treatment regimes.

Immunomodulatory effect of different statin regimens on regulatory T-cells in patients with acute coronary syndrome: a systematic review and network meta-analysis of randomized clinical trials.

AIMS: We conducted a network meta-analysis (NMA) to determine the effects of low-dose (20 mg/day or less) conventional statin therapy (CST) and high-dose (40 mg/day or more) intensive statin therapy (IST) on the frequency of Tregs and their associated cytokines (IFN-γ, IL-10, TGF-ß) compared with control. METHODS AND RESULTS: PubMed, Cochrane Library, and EMBASE databases were searched for randomized clinical trials (RCTs) to identify relevant articles published until June 2021. We pooled data extracted from the included studies using the standardized mean difference (SMD). A random-effects model was used to conduct this NMA. Heterogeneity was evaluated using Cochran's Q test and the I2 test. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) was used to assess the quality of the study. Data analysis was conducted using R software.A total of 505 patients were enrolled in the five RCTs. NMA indicated a significant increase in Treg frequency in the CST group compared with the control group (SMD 1.77; 95% CI: 0.77-2.76; P = 0.0005) and a larger increase in the Treg frequency associated with the IST group compared with the control group (SMD 2.12; 95% CI: 1.15-3.10; P-value < 0.0001). However, there was significant heterogeneity and inconsistency among the included studies [τ2 = 0.6096; τ = 0.7808; I2 = 91.2% (80.5%; 96.0%)]. When compared with control, both CST and IST increased the levels of secreted IL-10 (SMD 2.69; 95% CI: 2.07-3.31; P-value < 0.0001 and SMD 2.14; 95% CI: 1.76-2.52; P-value < 0.0001). Compared with the control group, CST was associated with increased levels of TGF-ß (SMD 3.83; 95% CI: 0.63-7.0; P-value = 0.0189); this association was not seen in the IST group. IFN-γ levels decreased significantly in both the IST and CST groups (SMD -1.52; 95% CI: -1.94-1.10; P-value < 0.0001 and SMD -2.34; 95% CI: -2.73-1.95; P-value < 0.0001, respectively). CONCLUSION: The findings of our study indicated that both high- and low-dose statin groups increased Treg frequency compared with the control group. IST demonstrated greater benefits than CST. Furthermore, statin therapy increased IL-10 and TGF-ß levels and decreased IFN-γ levels. Overall, these results have significant implications for patients with ACS who would benefit from Treg-induced immunomodulatory balance.

Hospice vs Palliative care: A comprehensive review for primary care physician.

End-of-life medical services in the form of Hospice or Palliative care were initiated in the middle of 1900 in order to comfort the dying patients and support their families. There are a lot of similarities and differences between the two services. Many healthcare providers, including physicians, physician assistants, and nurses, are not fully trained or have comprehensive knowledge of these two types of end-of-life medical care. Through this paper, we aim to provide a thorough review of Hospice and Palliative care for internist and primary care physicians both in terms of indications or eligibility criteria; the similarities and differences between the two types of care; factors that disqualify an enrolled patient; and lastly, the role or use of Hospice and palliative care during COVID-19 pandemic.

Patient-Reported Outcome Measures of Breast Cancer Surgery: Evidence Review and Tool Adaptation.

The objective of this scoping review was to review survey instruments for Patient-Reported Outcome Measures (PROMs) and provide recommendations to construct a tool for PROMs specifically for breast cancer patients who have undergone surgery, to overcome the limitations of existing validated tools. A total of 924 articles were screened. Nine articles were selected based on the eligibility criteria. We found that PROMs' data collection along with advancements in the treatment of breast cancer and the resultant improved clinical outcomes, there is a growing appreciation and focus on improving patients' quality of life (QoL). Previous studies have shown that the assessment of PROMs is linked to a positive effect on patients' symptoms of distress, quality of life, acceptance, and satisfaction. Several PROMs tools have been validated for use in cancer survivors. However, it is unclear whether existing tools are appropriate for use in breast cancer patients who have undergone surgical treatment. Hence, we conducted a scoping review. Following a review of the current PROM related to breast cancer and the necessity to build specialized PROMs related to the outcomes of breast cancer surgery, we provide recommendations for the development of a comprehensive tool to overcome the limitations of existing PROMs tools.

Impact of Patient Engagement on Healthcare Quality: A Scoping Review.

Patient engagement (PE) is a well-known strategy introduced and implemented by pharmaceutical and medical device companies for patient compliance and adherence to treatment protocols during clinical trials and care processes. This can affect a wider range of outcomes such as the quality of treatment decisions and quality of care outcomes. Few studies have paid attention to it. The involvement of patient is one of the crucial stakeholders of health care in their treatment that makes controversial opinions about the potential outcomes of their engagement in various aspects of healthcare. This scoping review was conducted in 2022 to collect the results of PE. The search was performed in the MEDLINE and Web of Sciences databases. The selected documents were categorized and reported by the direct content analysis method. Out of 3974 published documents, 17 articles were selected. Findings are categorized into 4 groups: (1) Health outcome, (2) patient compliance, (3) self-efficiency, and (4) return on investment. PE can improve both treatment outcomes and consequently patient satisfaction and health, as well as the productivity of the service provider. However, increasing self-care and patient adherence are among the positive effects of this engagement on the patient, and return on investment is still a challenge for PE.

Cardiac Implications of COVID-19 in Deceased and Recovered Patients: A Systematic Review.

Background: Patients infected with coronavirus disease 2019 (COVID-19) present with various clinical presentations with majority of them developing pulmonary complications. This study focuses on cardiac implications of COVID-19 which are less discussed and thus will help to address cardiac implications of COVID-19. Methods: PubMed, PubMed Central, and Google Scholar were screened for articles which mentioned cardiac implications of COVID-19. NHLBI Study Quality Assessment Tools for the observational cohort and cross-sectional studies was used for assessing the risk of bias of our studies. Results: All 14 studies selected were good and had score of ≥9 by NHLBI Study Quality Assessment Tools. Cardiac complications of COVID-19 are common. They are associated with significant mortality. Also, people infected with COVID-19 with premorbid conditions such as cardiovascular diseases and diabetes mellitus have poor prognosis as compared to those without premorbid conditions. Cardiac biomarkers such as highly sensitive troponin I, creatinine, and creatinine kinase-MB on admission are good prognostic markers. Conclusions: Cardiac complications such as heart failure, myocardial injury, and arrhythmias are common among patients infected with COVID-19. Elevated cardiac markers and patients with cardiac complications require utmost care and continuous cardiac monitoring.

The association of COVID-19 severity and susceptibility and genetic risk factors: A systematic review of the literature.

BACKGROUND: COVID-19 is associated with several risk factors such as distinct ethnicities (genetic ancestry), races, sexes, age, pre-existing comorbidities, smoking, and genetics. The authors aim to evaluate the correlation between variability in the host genetics and the severity and susceptibility towards COVID-19 in this study. METHODS: Following the PRISMA guidelines, we retrieved all the relevant articles published until September 15, 2021, from two online databases: PubMed and Scopus. FINDINGS: High-risk HLA haplotypes, higher expression of ACE polymorphisms, and several genes of cellular proteases such as TMPRSS2, FURIN, TLL-1 increase the risk of susceptibility and severity of COVID-19. In addition, upregulation of several genes encoding for both innate and acquired immune systems proteins, mainly CCR5, IFNs, TLR, DPPs, and TNF, positively correlate with COVID-19 severity. However, reduced expression or polymorphisms in genes affecting TLR and IFNλ increase COVID-19 severity. CONCLUSION: Higher expression, polymorphisms, mutations, and deletions of several genes are linked with the susceptibility, severity, and clinical outcomes of COVID-19. Early treatment and vaccination of individuals with genetic predisposition could help minimize the severity and mortality associated with COVID-19.

Mesenchymal stromal cells (MSCs) and their exosome in acute liver failure (ALF): a comprehensive review.

Recently, mesenchymal stromal cells (MSCs) and their derivative exosome have become a promising approach in the context of liver diseases therapy, in particular, acute liver failure (ALF). In addition to their differentiation into hepatocytes in vivo, which is partially involved in liver regeneration, MSCs support liver regeneration as a result of their appreciated competencies, such as antiapoptotic, immunomodulatory, antifibrotic, and also antioxidant attributes. Further, MSCs-secreted molecules inspire hepatocyte proliferation in vivo, facilitating damaged tissue recovery in ALF. Given these properties, various MSCs-based approaches have evolved and resulted in encouraging outcomes in ALF animal models and also displayed safety and also modest efficacy in human studies, providing a new avenue for ALF therapy. Irrespective of MSCs-derived exosome, MSCs-based strategies in ALF include administration of native MSCs, genetically modified MSCs, pretreated MSCs, MSCs delivery using biomaterials, and also MSCs in combination with and other therapeutic molecules or modalities. Herein, we will deliver an overview regarding the therapeutic effects of the MSCs and their exosomes in ALF. As well, we will discuss recent progress in preclinical and clinical studies and current challenges in MSCs-based therapies in ALF, with a special focus on in vivo reports.

Post-COVID-19 Pulmonary Fibrosis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected millions worldwide with a high mortality rate due to a lack of definitive treatment. Despite having a wide range of clinical features, acute respiratory distress syndrome (ARDS) has emerged as the primary cause of mortality in these patients. Risk factors and comorbidities like advanced age with limited lung function, pre-existing diabetes, hypertension, cardiovascular diseases, and obesity have increased the risk for severe COVID-19 infection. Rise in inflammatory markers like transforming growth factor ß (TGF-ß), interleukin-6 (IL-6), and expression of matrix metalloproteinase 1 and 7 (MMP-1, MMP-7), along with collagen deposition at the site of lung injury, results in extensive lung scarring and fibrosis. Anti-fibrotic drugs, such as Pirfenidone and Nintedanib, have emerged as potential treatment options for post-COVID-19 pulmonary fibrosis. A lung transplant might be the only life-saving treatment. Despite the current advances in the management of COVID-19, there is still a considerable knowledge gap in the management of long-term sequelae in such patients, especially concerning pulmonary fibrosis. Follow up on the current clinical trials and research to test the efficacy of various anti-inflammatory drugs is needed to prevent long-term sequelae early mortality in these patients.

Use of Epoprostenol in the Treatment of Pulmonary Arterial Hypertension.

Pulmonary Hypertension (PH) is defined as a disorder in which the mean Pulmonary Arterial Pressure (mPAP) is greater than 20 mmHg at rest. Pulmonary Arterial Hypertension (PAH) is considered when mPAP is > 20 mmHg and pulmonary vascular resistance (PVR) is ⩾ 3 WU. PAH is a chronic progressive disease resulting in right heart failure and premature death. It is postulated to be due to an inactivating mutation of a gene named bone morphogenetic protein receptor type 2 (BMPR2), whose predominant function is halting vascular proliferation. It has a lamentable prognosis if not rapidly diagnosed and adequately treated. Treatment of PAH has evolved in the past few decades since many related pathways and potential therapeutic targets have been explored. Parenteral prostanoids are the most effective therapeutic options for PAH. Epoprostenol is a synthetic analog of prostacyclin and a potent vasodilator that was Food and Drug Administration (FDA)-approved in December 1995 for intravenous use to treat PAH. It has also been used to treat different PAH subtypes, including connective tissue-related PAH like lupus and systemic sclerosis, congenital heart disease, and drug-induced PAH. It is effective in reducing mortality rates and improving survival rates. Although the use of Epoprostenol for PAH is challenging, it has been one of the most successful therapies used. In this manuscript, we review the pathophysiology of PAH and the risk stratification tool. We also discuss the mechanism of action of PAH-targeted therapies while focusing on the role of epoprostenol that has been investigated in many clinical trials. Finally, we discuss two ongoing clinical trials which highlight some potential therapeutic options.

Assessing hospital quality management systems: evidence from Iran.

PURPOSE: A quality management system (QMS) is defined as interacting activities, methods and procedures used to monitor, control and improve service quality. The purpose of this paper is to describe the QMS status using the Quality Management System Index (QMSI) in hospitals affiliated to Shahid Beheshti Medical Sciences University in Tehran, Iran. DESIGN/METHODOLOGY/APPROACH: In this cross-sectional study, 28 hospitals were investigated. A validated 46-item questionnaire was used for data collection. Data were analyzed using descriptive statistics, Pearson correlation, independent student's t-test and regression analysis. FINDINGS: The mean QMSI score was 18.4: 15.3 for public and 20.9 for non-public hospitals ( p=0.001). The lowest (1.96) and the highest (2.14) scores related to "Quality policy documents" and "Quality monitoring by the board," respectively. The difference between public and non-public hospitals was significant in all nine QMSI dimensions ( p=0.001). The QMSI score was higher in non-public and small hospitals than in public and large ones ( p=0.05). ORIGINALITY/VALUE: Most QMS studies come from developed countries, and there is no systematic information about the mechanisms and processes involved in implementing QMS in developing countries like Iran. This is the first study on Iranian hospital QMS using a newly developed tool (QMSI), and results showed that QMS maturity in these hospitals was relatively good, but the non-public hospitals status (private and charity) was far better than public hospitals.

Cost of Tuberculosis Treatment: Evidence from Iran's Health System.

OBJECTIVES: This study aimed to estimate the cost of smear-positive drug-susceptible pulmonary tuberculosis (TB) treatment of the patients in the Azadshahr district, Golestan Province, Iran. METHODS: In this retrospective study, all new smear positive pulmonary TB patients who had been registered at the district's health network between April, 2013 and December, 2015 and had successfully completed their treatment were entered into the study (45 patients). Treatment costs were estimated from the provider's perspective using an activity-based costing (ABC) method. RESULTS: The cost of treating a new smear-positive pulmonary TB patient was US dollar (USD) 1,409.00 (Iranian Rial, 39,438,260), which can be divided into direct and indirect costs (USD 1,226.00 [87%] and USD 183.00 [13%], respectively). The highest cost (58.1%) was related to care and management of TB patients (including 46.1% human resources costs and 12% directly-observed treatment, short course implementation) and then respectively related to hospitalization (12.1%), supportive activity centers (11.4%), transportation (6.5%), medicines (5.3%), and laboratory tests and radiography (3.2%). CONCLUSION: Using disease-specific cost studies can help the healthcare system management to have correct insight into the financial burden created by the disease. This can subsequently be used in prioritization, planning, operational budgeting, economic evaluation of programs, interventions, and ultimately in disease management.

Study of Out-of-Pocket Expenditures for Outpatient Imaging Services in Imam-Khomeini Hospital in 2014.

BACKGROUND: Direct out-of-pocket (OOP) payment is the most inequitable way to pay for healthcare services, and this trend exposes patients and their families to backbreaking financial risks. The aim of this study was to estimate the out-of-pocket expenditures for outpatient imaging services in Imam-Khomeini Hospital in Tehran. METHODS: This cross-sectional study was conducted in 2014 on 100 users of outpatient imaging services (radiology, ultrasonography, CT-scan, and MRI) in Imam-Khomeini Hospital in Tehran. Structured interviews and the analysis of related documents were used to acquire the pertinent data. The percentage of out-of-pocket expenditures was obtained by dividing the out-of-pocket expenditures by the total expenditures paid to the service provider, i.e., the sum of out-of-pocket expenditures and insurance payments. To analyze the data, we used descriptive-analytic statistics, distribution indices, the t-test, and the Pearson product-moment correlation coefficient. RESULTS: Health insurance covered 84% of costs incurred by users of outpatient imaging services. There was no significant relationship between the user's age and the amount of out-of-pocket expense (p = 0.01). The relationship between the user's gender and out-of-pocket expense was significant (p = 0.05). The average payment for males was greater than the average payment for females. The highest percentage of the total payment the users incurred was 41% for a CT-scan, and the lowest percentage the users incurred was 30% for radiology services. CONCLUSION: It is suggested that expensive diagnostic tests, such as CT-scans, be prescribed according to the actual needs of patients to make the financial burden of diagnostic services reasonable for all patients.

An empirical study of the impact of service quality on patient satisfaction in private hospitals, Iran.

OBJECTIVE: Perceived service quality is the most important predictor of patient satisfaction. The purpose of this study was to investigate the impact of the service quality on the overall satisfaction of patients in private hospitals of Tehran, Iran. METHOD: This cross-sectional study was conducted in the year 2010. The study's sample consisted of 969 patients who were recruited from eight private general hospitals in Tehran, Iran using consecutive sampling. A questionnaire was used for data collection; contacting 21 items (17 items about service quality and 4 items about overall satisfaction) and its validity and reliability were confirmed. Data analysis was performed using t-test, ANOVA and multivariate regression. RESULT: this study found a strong relationship between service quality and patient satisfaction. About 45% of the variance in overall satisfaction was explained by four dimensions of perceived service quality. The cost of services, the quality of the process and the quality of interaction had the greatest effects on the overall satisfaction of patients, but not found a significant effect on the quality of the physical environment on patient satisfaction. CONCLUSIONS: Constructs related to costs, delivery of service and interpersonal aspect of care had the most positive impact on overall satisfaction of patients. Managers and owners of private hospitals should set reasonable prices compared to the quality of service. In terms of process quality, waiting time for visits, admissions, and surgeries must be declined and services provided at the fastest possible time. It should be emphasized to strengthen of interpersonal aspects of care and communication skills of care providers.